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Sample records for gonadotropin ovarian stimulation

  1. Total renin after gonadotropin stimulation in polycystic ovarian disease.

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    Matinlauri, I; Anttila, L; Jaatinen, T A; Koskinen, P; Aalto, M; Irjala, K; Nikkanen, V

    1995-02-01

    To examine the influence of polycystic ovarian disease (PCOD) on the levels of total renin in plasma and follicular fluid (FF) after stimulation with hMG. Comparative study of the plasma and FF concentrations of total renin in women with and without PCOD after stimulation with hMG. In vitro fertilization-embryo transfer program at the Department of Obstetrics and Gynecology, the University Central Hospital of Turku, Finland. Thirty-six women undergoing IVF-ET for infertility with (n = 10) or without (n = 26) ultrasonographically diagnosed PCOD. Of the latter group, 15 women had tubal infertility, and the rest suffered from an anovulatory infertility and reacted with PCO-like ovarian response to stimulation. The concentrations of total renin in plasma and FF, serum E2, and protein in FF. The concentrations of plasma total renin after the gonadotropin stimulation were significantly higher in the PCOD and PCO-like groups when compared with the tubal group. The concentration of total renin in FF and the ratio of total renin per protein in FF were higher in the PCOD and PCO-like groups than in the tubal group, but the differences did not reach statistical significance. Positive correlations were found between the plasma total renin and serum E2 concentrations in the PCO-like and in the tubal group and between plasma total renin concentrations and the number of mature follicles in all groups. Follicular fluid total renin did not correlate with FF protein in any group. All findings were independent of the total hMG dosage used and the body mass index of the patients. In the present study the concentrations of total renin in plasma were enhanced markedly after gonadotropin stimulation in women with PCOD compared with women having tubal infertility. The pattern of the hormonal secretions revealed a group of infertile patients reacting biochemically like women with PCOD.

  2. Laparoscopic ovarian cystectomy of endometriomas does not affect the ovarian response to gonadotropin stimulation.

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    Marconi, Guillermo; Vilela, Martín; Quintana, Ramiro; Sueldo, Carlos

    2002-10-01

    To evaluate the ovarian response cycles of IVF-ET in patients who previously underwent laparoscopic cystectomy for endometriomas. Retrospective study with prospective selection of participants and controls. Instituto de Ginecología y Fertilidad Buenos Aires, Argentina. Thirty-nine patients underwent an operation for ovarian endometriomas by atraumatic removal of the pseudocapsule with minimal bipolar cauterization of small bleeders and an IVF-ET cycle (group A) and 39 control patients of similar age underwent an IVF-ET cycle for tubal factor infertility (group B). Laparoscopic endometrioma cystectomy, IVF-ET cycle. E(2) levels, number of gonadotropin ampoules, follicles, oocytes retrieved, number and quality of embryos transferred, and clinical pregnancy rate. There were no differences in all the parameters studied (E(2) levels, number of follicles, oocytes retrieved, number and quality of embryos transferred, and clinical pregnancy rate) except for the number of gonadotropin ampoules needed for ovarian hyperstimulation, which was significantly higher in group A than in group B. Our results indicate that laparoscopic cystectomy for endometriomas is an appropriate treatment since it did not negatively affect the ovarian response for IVF-ET.

  3. Gonadotropin-releasing hormone antagonist use in controlled ovarian stimulation and intrauterine insemination cycles in women with polycystic ovary syndrome.

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    Ertunc, Devrim; Tok, Ekrem C; Savas, Aysun; Ozturk, Ilay; Dilek, Saffet

    2010-03-01

    To observe the effects of ganirelix on controlled ovarian stimulation and intrauterine insemination (COS/IUI) cycles in women with polycystic ovary syndrome (PCOS). Prospective, randomized, controlled clinical study. An academic clinical research center. Women with PCOS and anovulatory infertility undergoing COS/IUI. Recombinant FSH therapy was started on day 3. In women assigned to the control group (n = 47), treatment was continued up to the day of hCG administration. In patients assigned to receive GnRH antagonist (n = 42), ganirelix was added when the leading follicle was > or =14 mm. Pregnancy rates, serum E(2), P, and LH levels, and follicle numbers at hCG day, prevalence of premature luteinization, and cost of stimulation. Serum E(2), P, and LH levels were significantly lower in the ganirelix group. Although premature luteinization and cycle cancellation was encountered less in the ganirelix group, the pregnancy rates per cycle were similar (15.4% vs. 10.7%). Patients would pay 6,153 dollars more for each pregnancy when using ganirelix. Gonadotropin-releasing hormone antagonist resulted in more monofollicular development, less premature luteinization, and less cycle cancellation in IUI cycles of patients with PCOS; however, the cost of stimulation increased without an improvement in pregnancy rates. Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  4. OVULATION INDUCTION IN PREMATURE OVARIAN FAILURE - A PLACEBO-CONTROLLED RANDOMIZED TRIAL COMBINING PITUITARY SUPPRESSION WITH GONADOTROPIN STIMULATION

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    VANKASTEREN, YM; HOEK, A; SCHOEMAKER, J

    Objectives: To determine the effect of pituitary suppression with a GnRH agonist (GnRH-a) on the success of ovulation induction with exogenous gonadotropins in patients with premature ovarian failure (POF). Design: Placebo-controlled, randomized, double-blind study. The data were analyzed with a

  5. Evaluating the ovarian cancer gonadotropin hypothesis

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    Lee, Alice W; Tyrer, Jonathan P; Doherty, Jennifer A

    2015-01-01

    OBJECTIVE: Ovarian cancer is a hormone-related disease with a strong genetic basis. However, none of its high-penetrance susceptibility genes and GWAS-identified variants to date are known to be involved in hormonal pathways. Given the hypothesized etiologic role of gonadotropins, an assessment...... of how variability in genes involved in the gonadotropin signaling pathway impacts disease risk is warranted. METHODS: Genetic data from 41 ovarian cancer study sites were pooled and unconditional logistic regression was used to evaluate whether any of the 2185 SNPs from 11 gonadotropin signaling pathway...... genes was associated with ovarian cancer risk. A burden test using the admixture likelihood (AML) method was also used to evaluate gene-level associations. RESULTS: We did not find any genome-wide significant associations between individual SNPs and ovarian cancer risk. However, there was some...

  6. The gonadotropin-releasing hormone antagonist protocol--the protocol of choice for the polycystic ovary syndrome patient undergoing controlled ovarian stimulation

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    Kol, Shahar; Homburg, Roy; Alsbjerg, Birgit

    2012-01-01

    Polycystic ovary syndrome (PCOS) patients are prone to develop ovarian hyperstimulation syndrome (OHSS), a condition which can be minimized or completely eliminated by the use of a gonadotropin-releasing hormone agonist (GnRHa) trigger. In this commentary paper, we maintain that the gonadotropin-...... ongoing pregnancy rates in the subsequent frozen-thawed transfer cycles....

  7. Differential gene expression in human granulosa cells from recombinant FSH versus human menopausal gonadotropin ovarian stimulation protocols

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    Bietz Mandi G

    2010-03-01

    Full Text Available Abstract Background The study was designed to test the hypothesis that granulosa cell (GC gene expression response differs between recombinant FSH and human menopausal gonadotropin (hMG stimulation regimens. Methods Females Results After exclusions, 1736 genes exhibited differential expression between groups. Over 400 were categorized as signal transduction genes, ~180 as transcriptional regulators, and ~175 as enzymes/metabolic genes. Expression of selected genes was confirmed by RT-PCR. Differentially expressed genes included A kinase anchor protein 11 (AKAP11, bone morphogenetic protein receptor II (BMPR2, epidermal growth factor (EGF, insulin-like growth factor binding protein (IGFBP-4, IGFBP-5, and hypoxia-inducible factor (HIF-1 alpha. Conclusions Results suggest that major differences exist in the mechanism by which pure FSH alone versus FSH/LH regulate gene expression in preovulatory GC that could impact oocyte maturity and developmental competence.

  8. Low dosing of gonadotropins in in vitro fertilization cycles for women with poor ovarian reserve: systematic review and meta-analysis

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    Youssef, Mohamed Abdel-Fattah; van Wely, Madelon; Mochtar, Monique; Fouda, Usama Mohamed; Eldaly, Ashraf; El Abidin, Eman Zein; Elhalwagy, Ahmed; Mageed Abdallah, Ahmed Abdel; Zaki, Sherif Sameh; Abdel Ghafar, Mohamed Sayed; Mohesen, Mohamed Nagi; van der Veen, Fulco

    2018-01-01

    Objective: To evaluate the effectiveness of low doses of gonadotropins and gonadotropins combined with oral compounds compared with high doses of gonadotropins in ovarian stimulation regimens in terms of ongoing pregnancy per fresh IVF attempt in women with poor ovarian reserve undergoing

  9. Localization of gonadotropin binding sites in human ovarian neoplasms

    International Nuclear Information System (INIS)

    Nakano, R.; Kitayama, S.; Yamoto, M.; Shima, K.; Ooshima, A.

    1989-01-01

    The binding of human luteinizing hormone and human follicle-stimulating hormone to ovarian tumor biopsy specimens from 29 patients was analyzed. The binding sites for human luteinizing hormone were demonstrated in one tumor of epithelial origin (mucinous cystadenoma) and in one of sex cord-stromal origin (theca cell tumor). The binding sites for human follicle-stimulating hormone were found in three tumors of epithelial origin (serous cystadenoma and mucinous cystadenoma) and in two of sex cord-stromal origin (theca cell tumor and theca-granulosa cell tumor). The surface-binding autoradiographic study revealed that the binding sites for gonadotropins were localized in the stromal tissue. The results suggest that gonadotropic hormones may play a role in the growth and differentiation of a certain type of human ovarian neoplasms

  10. Supplementation with a recombinant human chorionic gonadotropin microdose leads to similar outcomes in ovarian stimulation with recombinant follicle-stimulating hormone using either a gonadotropin-releasing hormone agonist or antagonist for pituitary suppression.

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    Cavagna, Mario; Maldonado, Luiz Guilherme Louzada; de Souza Bonetti, Tatiana Carvalho; de Almeida Ferreira Braga, Daniela Paes; Iaconelli, Assumpto; Borges, Edson

    2010-06-01

    To compare the outcomes of protocols for ovarian stimulation with recombinant hCG microdose, with GnRH agonists and antagonists for pituitary suppression. Prospective nonrandomized clinical trial. A private assisted reproduction center. We studied 182 patients undergoing intracytoplasmic sperm injection (ICSI) cycles, allocated into two groups: GnRH agonist group, in which patients received a GnRH agonist (n = 73), and a GnRH antagonist group, in which patients were administered a GnRH antagonist for pituitary suppression (n = 109). Pituitary suppression with GnRH agonist or GnRH antagonist. Ovarian stimulation carried out with recombinant FSH and supplemented with recombinant hCG microdose. Total dose of recombinant FSH and recombinant hCG administered; E(2) concentrations and endometrial width on the day of hCG trigger; number of follicles aspirated, oocytes and mature oocytes retrieved; fertilization, pregnancy (PR), implantation, and miscarriage rates. The total dose of recombinant FSH and recombinant hCG administered were similar between groups, as were the E(2) concentrations and endometrial width. The number of follicles aspirated, oocytes, and metaphase II oocytes collected were also comparable. There were no statistically significant differences in fertilization, PR, implantation, and miscarriage rates in the GnRH agonist and GnRH antagonist groups. When using recombinant hCG microdose supplementation for controlled ovarian stimulation (COS), there are no differences in laboratory or clinical outcomes with the use of either GnRH antagonist or agonist for pituitary suppression. Copyright (c) 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  11. A Proof-of-Concept Clinical Trial of A Single Luteal Use of Long-Acting Gonadotropin-Releasing Hormone Antagonist Degarelix in Controlled Ovarian Stimulation for In Vitro Fertilization: Long Antagonist Protocol

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    Evangelos G. Papanikolaou

    2018-03-01

    Full Text Available IntroductionA drawback of gonadotropin-releasing hormone (GnRH antagonist protocols in in vitro fertilization (IVF is that they have limited flexibility in cycle programming. This proof of concept study explored the efficacy of a single-dose, long-acting GnRH antagonist IVF protocol. Trial registration number is NCT03240159, retrospectively registered on March 08, 2017.Materials and methodsThe efficacy of a single-dose long-acting antagonist, degarelix, was explored initially in healthy donors and subsequently in infertile patients. In the first part, five healthy oocyte donors underwent ovarian stimulation with this new protocol: in the late luteal phase, at day 24, a bolus injection of degarelix was administered subcutaneously to control the LH surge in the follicular phase. Ovarian stimulation with gonadotropins was initiated subsequently from day 7 to day 10. End points were first to inhibit the LH surge later in the follicular phase and, second, to retrieve mature oocytes for IVF. In the second part, five infertile women received the same bolus injection of degarelix administered during the luteal phase at day 24. Different gonadotropin starting days (day 2 through day 8 were tested in order to observe possible differences in ovarian stimulation. In these infertile patients, fresh embryo transfers were performed to assess the pregnancy efficacy of this protocol on pregnancy outcomes and to address any possible negative effects on endometrium receptivity.ResultsIn the first part of the study, all donors were effectively downregulated with a single luteal dose of 0.5 ml of degarelix for up to 22 days until the final oocyte maturation triggering day. Mature oocytes were retrieved after 36 h from all patients and all produced 2–7 blastocysts. In the second part, all five infertile patients achieved sufficient LH downregulation and completed ovarian stimulation without any LH surge. All patients (except one with freeze all strategy had

  12. Low dosing of gonadotropins in in vitro fertilization cycles for women with poor ovarian reserve: systematic review and meta-analysis.

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    Youssef, Mohamed Abdel-Fattah; van Wely, Madelon; Mochtar, Monique; Fouda, Usama Mohamed; Eldaly, Ashraf; El Abidin, Eman Zein; Elhalwagy, Ahmed; Mageed Abdallah, Ahmed Abdel; Zaki, Sherif Sameh; Abdel Ghafar, Mohamed Sayed; Mohesen, Mohamed Nagi; van der Veen, Fulco

    2018-02-01

    To evaluate the effectiveness of low doses of gonadotropins and gonadotropins combined with oral compounds compared with high doses of gonadotropins in ovarian stimulation regimens in terms of ongoing pregnancy per fresh IVF attempt in women with poor ovarian reserve undergoing IVF/intracytoplasmic sperm injection (ICSI) treatment. A systematic review and meta-analysis of randomized controlled studies that evaluate the effectiveness of low dosing of gonadotropins alone or combined with oral compounds compared with high doses of gonadotropins in women with poor ovarian reserve undergoing IVF/ICSI treatment. Not applicable. Subfertile women with poor ovarian reserve undergoing IVF/ICSI treatment. We searched the PubMed, EMBASE, Web of Science, the Cochrane Library, and the Clinical Trials Registry using medical subject headings and free text terms up to June 2016, without language or year restrictions. We included randomized controlled studies (RCTs) enrolling subfertile women with poor ovarian reserve undergoing IVF/ICSI treatment and comparing low doses of gonadotropins and gonadotropins combined with oral compounds versus high doses of gonadotropins. We assessed the risk of bias using the criteria recommended by the Cochrane Collaboration. We pooled the results by meta-analysis using the fixed and random effects model. The primary outcome was ongoing pregnancy rate (PR) per woman randomized. We retrieved 787 records. Fourteen RCTs (N = 2,104 women) were included in the analysis. Five studies (N = 717 women) compared low doses of gonadotropins versus high doses of gonadotropins. There was no evidence of a difference in ongoing PR (2 RCTs: risk rate 0.98, 95% confidence interval 0.62-1.57, I 2 = 0). Nine studies (N = 1,387 women) compared ovarian stimulation using gonadotropins combined with the oral compounds letrozole (n = 6) or clomiphene citrate (CC) (n = 3) versus high doses of gonadotropins. There was no evidence of a difference in ongoing PR (3 RCTs: risk

  13. Ovarian hyperstimulation syndrome in gonadotropin-treated laboratory South African clawed frogs (Xenopus laevis).

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    Green, Sherril L; Parker, John; Davis, Corrine; Bouley, Donna M

    2007-05-01

    Ovarian hyperstimulation syndrome (OHS) is a rare but sometimes fatal iatrogenic complication of ovarian stimulation associated with the administration of exogenous gonadotropins to women undergoing treatment for infertility. Laboratory Xenopus spp are commonly treated with human chorionic gonadotropin (hCG) to stimulate ovulation and optimize the number of oocytes harvested for use in biomedical research. Here we report cases of OHS in 2 gonadotropin-treated laboratory Xenopus laevis. After receiving hCG, the frogs developed severe subcutaneous accumulation of fluid, coelomic distention, and whole-body edema and were unable to dive, although they continued to eat and swim. At postmortem examination, extensive subcutaneous edema was present; ascites and massive numbers of free-floating eggs were found in the coelomic cavity and in aberrant locations: around the heart-sac and adhered to the liver capsule. Whole-body edema, gross enlargement of the ovaries, ascites, and abdominal distention are findings comparable to those observed in women with OHS. The pathophysiology of OHS is thought to be related to hormonally induced disturbances of vasoactive mediators, one of which may be vascular endothelial growth factor secreted by theca and granulosa cells. We know of no other report describing OHSlike symptoms in gonadotropin-treated frogs, and the cases described here are 2 of the 3 we have observed at our respective institutions over the last 6 y. According to these results, OHS appears to be rare in gonadotropin-treated laboratory Xenopus. However, the condition should be included in the differential diagnosis for the bloated frog.

  14. Peritoneal Adhesion and Angiogenesis in Ovarian Carcinoma Are Inversely Regulated by Hyaluronan: The Role of Gonadotropins

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    Yael Chagit Tzuman

    2010-01-01

    Full Text Available Ovarian carcinoma is the leading cause of death among gynecologic cancers. Although transformation of the outer ovarian epithelium was linked with ovulation, the disease is significantly more prevalent and severe in postmenopausal women. We postulated that menopause could augment ovarian cancer progression through the effects of gonadotropins on multifocal seeding to the mesothelial layer lining the peritoneum. This seeding is mediated by integrins as well as by CD44 interaction with hyaluronan (HA. Here, we report the effect of gonadotropins on HA synthesis and degradation and on peritoneal adhesion. A significant concentration- and time-dependent induction in expression levels of HA synthases (HASs and hyaluronidases (Hyals was observed in vitro on stimulation of human epithelial ovarian carcinoma cells by gonadotropins. Hormonal regulation of HA-mediated adhesion was manifested in vivo as well, by fluorescence microscopy of stained MLS multicellular tumor spheroids. The number of spheroids adhered to the mesothelium of ovariectomized CD-1 nude mice 9.5 hours after intraperitoneal insertion was significantly higher than in nonovariectomized mice. Inhibition of HA synthesis by 6-diazo-5-oxo-1-norleucine (DON both in spheroids and ovariectomized mice significantly reduced the number of adhered spheroids. Thus, the change in the hormonal environment during menopause assists in HA-dependent adherence of ovarian cancer spheroids onto the peritoneum. However, HA is antiangiogenic and it can significantly suppress tumor progression. Accordingly, angiogenesis of the adhered spheroids was significantly elevated in DON-treated tumors. These results can explain the selective pressure that can lead to simultaneously increased tumor expression of both HASs and Hyals.

  15. Does the time interval between antimüllerian hormone serum sampling and initiation of ovarian stimulation affect its predictive ability in in vitro fertilization-intracytoplasmic sperm injection cycles with a gonadotropin-releasing hormone antagonist?

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    Polyzos, Nikolaos P; Nelson, Scott M; Stoop, Dominic

    2013-01-01

    To investigate whether the time interval between serum antimüllerian hormone (AMH) sampling and initiation of ovarian stimulation for in vitro fertilization-intracytoplasmic sperm injection (IVF-ICSI) may affect the predictive ability of the marker for low and excessive ovarian response.......To investigate whether the time interval between serum antimüllerian hormone (AMH) sampling and initiation of ovarian stimulation for in vitro fertilization-intracytoplasmic sperm injection (IVF-ICSI) may affect the predictive ability of the marker for low and excessive ovarian response....

  16. Gonadotropin binding sites in human ovarian follicles and corpora lutea during the menstrual cycle

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    Shima, K.; Kitayama, S.; Nakano, R.

    1987-05-01

    Gonadotropin binding sites were localized by autoradiography after incubation of human ovarian sections with /sup 125/I-labeled gonadotropins. The binding sites for /sup 125/I-labeled human follicle-stimulating hormone (/sup 125/I-hFSH) were identified in the granulosa cells and in the newly formed corpora lutea. The /sup 125/I-labeled human luteinizing hormone (/sup 125/I-hLH) binding to the thecal cells increased during follicular maturation, and a dramatic increase was preferentially observed in the granulosa cells of the large preovulatory follicle. In the corpora lutea, the binding of /sup 125/I-hLH increased from the early luteal phase and decreased toward the late luteal phase. The changes in 3 beta-hydroxysteroid dehydrogenase activity in the corpora lutea corresponded to the /sup 125/I-hLH binding. Thus, the changes in gonadotropin binding sites in the follicles and corpora lutea during the menstrual cycle may help in some important way to regulate human ovarian function.

  17. A mild ovarian stimulation strategy in women with poor ovarian reserve undergoing IVF: a multicenter randomized non-inferiority trial.

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    Youssef, M A; van Wely, M; Al-Inany, H; Madani, T; Jahangiri, N; Khodabakhshi, S; Alhalabi, M; Akhondi, M; Ansaripour, S; Tokhmechy, R; Zarandi, L; Rizk, A; El-Mohamedy, M; Shaeer, E; Khattab, M; Mochtar, M H; van der Veen, F

    2017-01-01

    In subfertile women with poor ovarian reserve undergoing IVF does a mild ovarian stimulation strategy lead to comparable ongoing pregnancy rates in comparison to a conventional ovarian stimulation strategy? A mild ovarian stimulation strategy in women with poor ovarian reserve undergoing IVF leads to similar ongoing pregnancy rates as a conventional ovarian stimulation strategy. Women diagnosed with poor ovarian reserve are treated with a conventional ovarian stimulation strategy consisting of high-dose gonadotropins and pituitary downregulation with a long mid-luteal start GnRH-agonist protocol. Previous studies comparing a conventional strategy with a mild ovarian stimulation strategy consisting of low-dose gonadotropins and pituitary downregulation with a GnRH-antagonist have been under powered and their effectiveness is inconclusive. This open label multicenter randomized trial was designed to compare one cycle of a mild ovarian stimulation strategy consisting of low-dose gonadotropins (150 IU FSH) and pituitary downregulation with a GnRH-antagonist to one cycle of a conventional ovarian stimulation strategy consisting of high-dose gonadotropins (450 IU HMG) and pituitary downregulation with a long mid-luteal GnRH-agonist in women of advanced maternal age and/or women with poor ovarian reserve undergoing IVF between May 2011 and April 2014. Couples seeking infertility treatment were eligible if they fulfilled the following inclusion criteria: female age ≥35 years, a raised basal FSH level >10 IU/ml irrespective of age, a low antral follicular count of ≤5 follicles or poor ovarian response or cycle cancellation during a previous IVF cycle irrespective of age. The primary outcome was ongoing pregnancy rate per woman randomized. Analyses were on an intention-to-treat basis. We randomly assigned 195 women to the mild ovarian stimulation strategy and 199 women to the conventional ovarian stimulation strategy. Ongoing pregnancy rate was 12.8% (25/195) for mild

  18. Reference values in ovarian response to controlled ovarian stimulation throughout the reproductive period.

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    La Marca, Antonio; Grisendi, Valentina; Spada, Elena; Argento, Cindy; Milani, Silvano; Plebani, Maddalena; Seracchioli, Renato; Volpe, Annibale

    2014-01-01

    Abstract The age-related decline in ovarian response to gonadotropins has been well known since the beginning of ovarian stimulation in IVF cycles and has been considered secondary to the age-related decline in ovarian reserve. The objective of this study was to establish reference values and to construct nomograms of ovarian response for any specific age to gonadotropins in IVF/ICSI cycles. We analyzed our database containing information on IVF cycles. According to inclusion and exclusion criteria, a total of 703 patients were selected. Among inclusion criteria, there were regular menstrual cycle, treatment with a long GnRH agonist protocol and starting follicle-stimulating hormone (FSH) dose of at least 200 IU per day. To estimate the reference values of ovarian response, the CG-LMS method was used. A linear decline in the parameters of ovarian response with age was observed: the median number of oocytes decreases approximately by one every three years, and the median number of follicles >16 mm by one every eight years. The number of oocytes and growing follicles corresponding to the 5th, 25th, 50th, 75th and 95th centiles has been calculated. This study confirmed the well known negative relationship between ovarian response to FSH and female ageing and permitted the construction of nomograms of ovarian response.

  19. Nonsupplemented luteal phase characteristics after the administration of recombinant human chorionic gonadotropin, recombinant luteinizing hormone, or gonadotropin-releasing hormone (GnRH) agonist to induce final oocyte maturation in in vitro fertilization patients after ovarian stimulation with recombinant follicle-stimulating hormone and GnRH antagonist cotreatment

    NARCIS (Netherlands)

    N.S. Macklon (Nick); M.J.C. Eijkemans (René); M. Ludwig (Michael); R.E. Felberbaum; K. Diedrich; S. Bustion; E. Loumaye; B.C.J.M. Fauser (Bart); N.G.M. Beckers (Nicole)

    2003-01-01

    textabstractReplacing GnRH agonist cotreatment for the prevention of a premature rise in LH during ovarian stimulation for in vitro fertilization (IVF) by the late follicular phase administration of GnRH antagonist may render supplementation of the luteal phase redundant, because

  20. Luteal-phase ovarian stimulation increases the number of mature oocytes in older women with severe diminished ovarian reserve.

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    Rashtian, Justin; Zhang, John

    2018-03-22

    In older women with severe diminished ovarian response (DOR), in vitro fertilization (IVF) treatment is much less successful due to the low number of mature oocytes collected. The objective of this study was to assess whether follicular-phase stimulation (FPS) and luteal-phase stimulation (LPS) in the same menstrual cycle (double ovarian stimulation) in older women with severe DOR will produce a higher number of oocytes compared to FPS alone. Women with DOR (n = 69; mean age = 42.4) who underwent double ovarian stimulation for IVF were included. Women underwent ovarian stimulation in FPS using clomiphene citrate, letrozole, and gonadotropins followed by oocyte retrieval. The next day following oocyte retrieval, women underwent a second ovarian stimulation (LPS) using the same medications followed by a second oocyte retrieval. T-test was performed in order to compare the clinical characteristics and outcome in the same participant between FPS and LPS. Although antral follicle count at the start of FPS tended to be higher than at the start of the LPS cycle, there was no statistically significant difference between the duration of ovarian stimulation, peak estradiol levels, number of small (FPS alone. The addition of LPS to the conventional FPS increases the number of mature oocytes retrieved in the same IVF cycle, thus potentially increasing the chances of pregnancy in older women with severe DOR. AFC: antral follicle count; BMI: body mass index; DOR: diminished ovarian reserve; E2: estradiol; FPS: follicular-phase stimulation; FSH: follicle stimulating hormone; GnRH: gonadotropin-releasing hormone; HCG: human chorionic gonadotropin; IRB: institutional review board; IVF: in vitro fertilization; LH: luteinizing hormone; LPS: luteal-phase stimulation; MII: metaphase II.

  1. Ovarian stimulation and embryo quality

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    Baart, Esther; Macklon, Nick S.; Fauser, Bart J. C. M.

    To Study the effects of different ovarian stimulation approaches on oocyte and embryo quality, it is imperative to assess embryo quality with a reliable and objective method. Embryos rated as high quality by standardized morphological assessment are associated with higher implantation and pregnancy

  2. Clomiphene citrate versus high doses of gonadotropins for in vitro fertilisation in women with compromised ovarian reserve: a randomised controlled non-inferiority trial

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    Ragni Guido

    2012-12-01

    Full Text Available Abstract Background The aim of the present randomised controlled non-inferiority trial is to test whether in women with compromised ovarian reserve requiring in vitro fertilisation, a protocol of ovarian stimulation using exclusively clomiphene citrate performs similarly to a regimen with high doses of gonadotropins. Methods Women with day 3 serum FSH > 12 IU/ml on at least two occasions or previous poor response to hyper-stimulation were recruited at four Italian infertility units. Selected women were allocated to clomiphene citrate 150 mg/day from day 3 to day 7 of the cycle (n=145 or to a short protocol with GnRH agonist 0.1 mg and recombinant FSH 450 IU daily (n=146. They were randomised by means of a computer-generated list into two groups. The study was not blinded. The main outcome of the study was the delivery rate per started cycle. Results The study was interrupted after the scheduled two years of recruitment before reaching the sample size. 148 women were allocated to clomiphene citrate and 156 to the short protocol with high doses of gonadotropins; 124 and 125 participants were analysed in the groups, respectively. Women allocated to high doses of gonadotropins retrieved more oocytes and had a higher probability to perform embryo-transfer. However, the chances of success were similar. The delivery rate per started cycle in women receiving clomiphene citrate and high-dose gonadotropins was 3% (n=5 and 5% (n=7, respectively (p=0.77. The mean estimated cost per delivery in the two groups was 81,294 and 113,107 Euros, respectively. No side-effects or adverse events were observed. Conclusions In women with compromised ovarian reserve selected for in vitro fertilisation, ovarian stimulation with clomiphene citrate or high-dose gonadotropins led to similar chances of pregnancy but the former is less expensive. Trial registration Trial registered on http://www.clinicaltrials.gov (NCT01389713

  3. Individualized controlled ovarian stimulation in expected poor-responders: an update.

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    Haahr, Thor; Esteves, Sandro C; Humaidan, Peter

    2018-03-09

    Controlled ovarian stimulation with subsequent multi-follicular development continues to be a keystone in ART. Evidence supports an individualized approach to ovarian stimulation, usually involving combinations of ovarian reserve tests, body mass index and age to tailor the exogenous gonadotropin dose, and potentially adjuvant treatment aiming for high safety and a shortening of time to live birth. While stimulation and trigger concepts have been developed successfully in normo- and hyperresponder patients, the poor responder patient remains difficult to manage. However, recent advances in definition and classification of the expected poor ovarian responder patient might enable a more accurate and clinically useful interpretation of new treatment concepts in a more homogenous study population. In the present review, we discuss the classification of the expected poor ovarian responder patient as well as clinically useful measurements of efficacy for controlled ovarian stimulation, and finally, we discuss the evidence for clinical management of patients with expected poor ovarian response, including adjuvant treatments such as growth hormone, androgens, and LH activity.In conclusion, the best available evidence supports that the treatment of the expected poor ovarian response patient should be individualized in all steps of ART, including the choice of GnRH analogue, the gonadotropin type and dose, ovulation trigger, and the possible use of adjuvant therapies.

  4. Revisiting ovarian hyper stimulation syndrome: Towards OHSS free clinic

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    Manish Banker

    2015-01-01

    Full Text Available A rapid development and application of assisted reproductive technologies (ARTs and ovulation-induction drugs may lead to ovarian hyper stimulation syndrome (OHSS. Young age, low body mass index (BMI, polycystic ovarian syndrome (PCOS, previous OHSS, high follicle count, and elevated serum estradiol (E2 are the certain factors that predispose women to OHSS. Many strategies have been used to reduce or avoid OHSS. Use of human chorionic gonadotropin (hCG increases ovarian vascular permeability and is responsible for activating the vascular endothelial growth factors (VEGF pathway and thus the entire cascade, leading to symptomatic OHSS. Gonadotropin-releasing hormone (GnRH agonists are used as a replacement for hCG for final oocyte maturation in antagonist cycles. Reducing or eliminating the use of hCG and use of GnRH agonist triggered GnRH antagonist cycles and cryopreservation of oocytes or embryos is the most promising approach in making OHSS free clinic a reality.

  5. Association of luteinizing hormone chorionic gonadotropin receptor gene polymorphism (rs2293275) with polycystic ovarian syndrome.

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    Thathapudi, Sujatha; Kodati, Vijayalakshmi; Erukkambattu, Jayashankar; Addepally, Uma; Qurratulain, Hasan

    2015-03-01

    Polycystic ovaries and irregular menstruation/anovulation are important diagnostic criteria along with hyperandrogenism as per the Androgen Excess Society-2006 criteria for polycystic ovarian syndrome (PCOS). In the etiopathogenesis of PCOS, one of the candidate genes causing ovarian failure is the luteinizing hormone (LH) chorionic gonadotropin hormone receptor (LHCGR). Our aim was to study the association of LHCGR polymorphism (rs2293275) with PCOS in our study population. Genetic case-control study from multiple gynecological centers from Hyderabad, a cosmopolitan city in South India. The study involved 204 women with PCOS and 204 healthy, sex-, and age-matched controls. Anthropometric and biochemical profiles were taken in a well-designed pro forma. Isolation of deoxyribonucleic acid (DNA) and genotype analysis were done for the entire study population using the polymerase chain reaction-restriction fragment length polymorphism method followed by 12% polyacrylamide gel electrophoresis. In this study, we have demonstrated an association between LHCGR (rs2293275) polymorphism and PCOS. The frequency of the G allele was 0.60 in PCOS and 0.49 in controls (odds ratio [OR] 1.531, confidence interval [CI] 1.16-2.01, and p-value=0.0026), which indicates that the G allele is associated with PCOS in our population. The GG genotype conferred a significant risk of developing PCOS (OR 3.36, CI 1.96-5.75, and p-value<0.0001). We found a significant association of the GG allele with body-mass index, waist to hip ratio, insulin resistance, LH, and LH/follicle-stimulating hormone (FSH) ratio in PCOS when compared with controls. The AA allele showed high basal FSH levels. This study suggests that LHCGR (rs2293275) polymorphism is associated with PCOS and could be used as a relevant molecular marker to identify women with the risk of developing PCOS in our population and may provide an understanding about the etiology of PCOS.

  6. Increased Progesterone/Estradiol Ratio on the Day of hCG Administration Adversely Affects Success of In Vitro Fertilization–Embryo Transfer in Patients Stimulated with Gonadotropin-releasing Hormone Agonist and Recombinant Follicle-stimulating Hormone

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    Yu-Che Ou

    2008-06-01

    Conclusion: Premature luteinization, defined as late follicular P/E2 ratio of > 1 in long GnRHa cycles with rFSH stimulation, adversely affected ovarian responses and clinical outcomes. It seems unrelated to preovulatory luteinizing hormone (LH elevation and LH/hCG content of gonadotropins and could be associated with poor ovarian response and the presence of dysmature follicles. [Taiwan J Obstet Cynecol 2008;47(2:1 68-1 74

  7. Elevated progesterone during ovarian stimulation for IVF

    DEFF Research Database (Denmark)

    Al-Azemi, M; Kyrou, D; Kolibianakis, E M

    2012-01-01

    of Medline and PubMed were searched to identify relevant publications. Good-quality evidence supports the negative impact on endometrial receptivity of elevated progesterone concentrations at the end of the follicular phase in ovarian stimulation. Future trials should document the cause and origin...... phase in ovarian stimulation. The databases of Medline and PubMed were searched to identify relevant publications. Good-quality evidence supports the negative impact on endometrial receptivity of elevated progesterone concentrations at the end of follicular phase in ovarian stimulation. Future trials...

  8. Pituitary Gonadotropins, Prolactin and Growth Hormone Differentially Regulate AQP1 Expression in the Porcine Ovarian Follicular Cells

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    Mariusz T. Skowronski

    2017-12-01

    Full Text Available The present in vitro study analyzed whether the hormones that affect the ovarian follicular steroidogenesis process also participate in the regulation of AQP1 mRNA and protein expression. Granulosa (Gc and theca cells (Tc of medium and large porcine ovarian follicles were exposed to follicle-stimulating hormone (FSH, luteinizing hormone (LH, prolactin (PRL and growth hormone (GH for 24 h in separated cells and co-cultures of these cells. Real-time PCR, Western blotting, immunofluorescence and volumetric analysis were then performed. Gonadotropins, PRL and GH had a stimulatory impact on AQP1 mRNA and protein expression in Gc and Tc of medium and large ovarian cells. Moreover, swelling assays, in response to a hypotonic environment, demonstrated the functional presence of AQPs in porcine Gc and Tc. Immunofluorescence analysis showed that AQP1 protein was mainly localized in the perinuclear region of the cytoplasm, endosomes and cell membranes of Gc and Tc from medium and large follicles. It seems possible that AQP1 present in Gc and Tc cells may be implicated not only in the regulation of water homeostasis required for follicle development but also in cell proliferation and migration.

  9. Antimüllerian hormone in gonadotropin releasing-hormone antagonist cycles

    DEFF Research Database (Denmark)

    Arce, Joan-Carles; La Marca, Antonio; Mirner Klein, Bjarke

    2013-01-01

    To assess the relationships between serum antimüllerian hormone (AMH) and ovarian response and treatment outcomes in good-prognosis patients undergoing controlled ovarian stimulation using a gonadotropin-releasing hormone (GnRH) antagonist protocol....

  10. [Which ovarian stimulation to which women: The polycystic ovary syndrome (PCOS)].

    Science.gov (United States)

    Merviel, P; Bouée, S; Ménard, M; Le Martelot, M-T; Roche, S; Lelièvre, C; Chabaud, J-J; Jacq, C; Drapier, H; Beauvillard, D

    2017-11-01

    Polycystic ovarian syndrome (PCOS) is a frequent pathology in the young woman, linking infertility to a metabolic disease. Initial support will include a plan (in the case of overweight or obesity) to lose at least 5 to 10% of the weight. Subsequently, clomiphene citrate is the first treatment for ovulation induction with pregnancy rates of 40 to 80% after 6 cycles. If there is resistance to clomiphene citrate, the choice will be between the ovarian drilling (50-60% of pregnancy in the year following, including the half spontaneous) or ovarian stimulation with gonadotropins. The risk of ovarian stimulation in these women is hyperstimulation and multiple pregnancies. We also discuss the place of the GnRH pulsatile administration, insulin-sensitizers, in vitro fertilization and in vitro maturation in these women. Once infertility support, these women should be long-term followed because of the neoplasic and cardiovascular risks they present. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  11. Effects of a gonadotropin-releasing hormone vaccine on ovarian cyclicity and uterine morphology of an Asian elephant (Elephas maximus).

    Science.gov (United States)

    Boedeker, Nancy C; Hayek, Lee-Ann C; Murray, Suzan; de Avila, David M; Brown, Janine L

    2012-09-01

    This report describes the successful use of a gonadotropin-releasing hormone (GnRH) vaccine to suppress ovarian steroidogenic activity and to treat hemorrhage and anemia associated with reproductive tract pathology in a 59-year-old Asian elephant (Elephas maximus). The Repro-BLOC GnRH vaccine was administered subcutaneously as a series of 4 boosters of increasing dose from 3 to 30 mg of recombinant ovalbumin-GnRH fusion protein given at variable intervals after initial vaccination with 3 mg protein. Efficacy was confirmed over a year after initial vaccination based on complete ovarian cycle suppression determined by serum progestagen analyses. Estrous cycle suppression was associated with a significant increase in GnRH antibody binding and subsequent decrease in serum luteinizing hormone and follicle-stimulating hormone concentrations. Ultrasonographic examinations of the reproductive tract documented a reduction in uterine size and vascularity after immunization. The hematocrit level normalized soon after the initial intrauterine hemorrhage, and no recurrence of anemia has been detected. No substantive adverse effects were associated with GnRH vaccination. The results indicate that GnRH vaccination in elephants shows potential for contraception and management of uterine pathology in older elephants.

  12. Outcomes and Recommendations of an Indian Expert Panel for Improved Practice in Controlled Ovarian Stimulation for Assisted Reproductive Technology

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    Baiju Ahemmed

    2017-01-01

    Full Text Available Purpose. To improve success of in vitro fertilization (IVF, assisted reproductive technology (ART experts addressed four questions. What is optimum oocytes number leading to highest live birth rate (LBR? Are cohort size and embryo quality correlated? Does gonadotropin type affect oocyte yield? Should “freeze-all” policy be adopted in cycles with progesterone >1.5 ng/mL on day of human chorionic gonadotropin (hCG administration? Methods. Electronic database search included ten studies on which panel gave opinions for improving current practice in controlled ovarian stimulation for ART. Results. Strong association existed between retrieved oocytes number (RON and LBRs. RON impacted likelihood of ovarian hyperstimulation syndrome (OHSS. Embryo euploidy decreased with age, not with cohort size. Progesterone > 1.5 ng/dL did not impair cycle outcomes in patients with high cohorts and showed disparate results on day of hCG administration. Conclusions. Ovarian stimulation should be designed to retrieve 10–15 oocytes/treatment. Accurate dosage, gonadotropin type, should be selected as per prediction markers of ovarian response. Gonadotropin-releasing hormone (GnRH antagonist based protocols are advised to avoid OHSS. Cumulative pregnancy rate was most relevant pregnancy endpoint in ART. Cycles with serum progesterone ≥1.5 ng/dL on day of hCG administration should not adopt “freeze-all” policy. Further research is needed due to lack of data availability on progesterone threshold or index.

  13. Outcomes and Recommendations of an Indian Expert Panel for Improved Practice in Controlled Ovarian Stimulation for Assisted Reproductive Technology

    Science.gov (United States)

    Ahemmed, Baiju; Sundarapandian, Vani; Gutgutia, Rohit; Balasubramanyam, Sathya; Jagtap, Richa; Biliangady, Reeta; Gupta, Priti; Jadhav, Sachin; Satwik, Ruma; Thakor, Priti

    2017-01-01

    Purpose. To improve success of in vitro fertilization (IVF), assisted reproductive technology (ART) experts addressed four questions. What is optimum oocytes number leading to highest live birth rate (LBR)? Are cohort size and embryo quality correlated? Does gonadotropin type affect oocyte yield? Should “freeze-all” policy be adopted in cycles with progesterone >1.5 ng/mL on day of human chorionic gonadotropin (hCG) administration? Methods. Electronic database search included ten studies on which panel gave opinions for improving current practice in controlled ovarian stimulation for ART. Results. Strong association existed between retrieved oocytes number (RON) and LBRs. RON impacted likelihood of ovarian hyperstimulation syndrome (OHSS). Embryo euploidy decreased with age, not with cohort size. Progesterone > 1.5 ng/dL did not impair cycle outcomes in patients with high cohorts and showed disparate results on day of hCG administration. Conclusions. Ovarian stimulation should be designed to retrieve 10–15 oocytes/treatment. Accurate dosage, gonadotropin type, should be selected as per prediction markers of ovarian response. Gonadotropin-releasing hormone (GnRH) antagonist based protocols are advised to avoid OHSS. Cumulative pregnancy rate was most relevant pregnancy endpoint in ART. Cycles with serum progesterone ≥1.5 ng/dL on day of hCG administration should not adopt “freeze-all” policy. Further research is needed due to lack of data availability on progesterone threshold or index. PMID:28246628

  14. Comparative Gene Expression Profiling in Human Cumulus Cells according to Ovarian Gonadotropin Treatments

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    Said Assou

    2013-01-01

    Full Text Available In in vitro fertilization cycles, both HP-hMG and rFSH gonadotropin treatments are widely used to control human follicle development. The objectives of this study are (i to characterize and compare gene expression profiles in cumulus cells (CCs of periovulatory follicles obtained from patients stimulated with HP-hMG or rFSH in a GnRH antagonist cycle and (ii to examine their relationship with in vitro embryo development, using Human Genome U133 Plus 2.0 microarrays. Genes that were upregulated in HP-hMG-treated CCs are involved in lipid metabolism (GM2A and cell-to-cell interactions (GJA5. Conversely, genes upregulated in rFSH-treated CCs are implicated in cell assembly and organization (COL1A1 and COL3A1. Interestingly, some genes specific to each gonadotropin treatment (NPY1R and GM2A for HP-hMG; GREM1 and OSBPL6 for rFSH were associated with day 3 embryo quality and blastocyst grade at day 5, while others (STC2 and PTX3 were related to in vitro embryo quality in both gonadotropin treatments. These genes may prove valuable as biomarkers of in vitro embryo quality.

  15. Random Start Ovarian Stimulation for Oocyte or Embryo Cryopreservation in Women Desiring Fertility Preservation Prior to Gonadotoxic Cancer Therapy.

    Science.gov (United States)

    Danis, Rachel B; Pereira, Nigel; Elias, Rony T

    2017-11-10

    Women of reproductive age diagnosed with cancer are often interested in preserving gametes or reproductive tissue that would allow for future genetic parenthood. Preservation of fertility is often accomplished in young cancer patients via ovarian stimulation followed by oocyte or embryo cryopreservation. Conventional stimulation protocols, however, require 2-4 weeks to complete ovarian stimulation, oocyte retrieval and possible fertilization. Such a strategy may not be feasible in patients requiring urgent cancer treatment. Recent studies have highlighted that random start ovarian stimulation can be initiated irrespective of the phase of the menstrual cycle and is an attractive alternative to conventional ovarian stimulation. The primary aim of the current review is to discuss the feasibility and success of random start ovarian stimulation for oocyte or embryo cryopreservation in women desiring fertility preservation prior to gonadotoxic cancer therapy. We performed a systematic review of medical literature published between January 2000 to June 2017 reporting the utility of random start ovarian stimulation for fertility preservation. Search terms included "fertility preservation," "cancer," "ovarian stimulation," "random-start ovarian stimulation," "embryo cryopreservation, and" "oocyte cryopreservation." Publications were included in this review only if patients underwent random start ovarian stimulation prior to cancer therapy. Nineteen publications were identified and perused by the authors. Most publications described the utility of random start ovarian stimulation in the setting of breast cancer. Radom-start stimulation was associated with a reduced time interval between ovarian stimulation initiation and oocyte or embryo cryopreservation. The yield of mature oocytes and their developmental potential into embryos was comparable between conventional and random-start protocols, albeit with higher gonadotropin doses in the latter. The current review suggests

  16. Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation (AMIGOS) Trial: Baseline Characteristics

    Science.gov (United States)

    Diamond, Michael P.; Legro, Richard S.; Coutifaris, Christos; Alvero, Ruben; Robinson, Randal D.; Casson, Peter; Christman, Gregory M.; Ager, Joel; Huang, Hao; Hansen, Karl R.; Baker, Valerie; Usadi, Rebecca; Seungdamrong, Aimee; Bates, G. Wright; Rosen, R. Mitchell; Haisonleder, Daniell; Krawetz, Stephen A.; Barnhart, Kurt; Trussell, J.C.; Jin, Yufeng; Santoro, Nanette; Eisenberg, Esther; Zhang, Heping

    2015-01-01

    Objective To identify baseline characteristics of women with unexplained infertility to determine whether treatment with an aromatase inhibitor will result in a lower rate of multiple gestations than current standard ovulation induction medications. Design Randomized, prospective clinical trial Patients 900 couples with unexplained infertility Interventions: Ovarian stimulation with gonadotropins, clomiphene citrate, or letrozole in conjunction with intrauterine insemination. Setting Multicenter University based clinical practices. Main Outcome Measures Demographic, laboratory, imaging, and survey characteristics. Interventions Collection of baseline demographics, blood samples, and ultrasonographic assessments. Results Demographic characteristics of women receiving clomiphene citrate, letrozole, or gonadotropins for ovarian stimulation were very consistent. Their mean age was 32.2 ± 4.4 years and infertility duration was 34.7± 25.7 months, with 59% primary infertility. More than 1/3 of the women were current or past smokers. The mean BMI was 27 and mean AMH level was 2.6; only 11 women (1.3%) had antral follicle counts of less than 5. Similar observations were identified for hormonal profiles, ultrasound characterization of the ovaries, semen parameters, and quality of life assessments in both male and female partners. Conclusion The cause of infertility in the couples recruited to this treatment trial is elusive, as the women were regularly ovulating and had evidence of good ovarian reserve both by basal FSH, AMH levels, and antral follicle counts; the male partners had normal semen parameters. The three treatment subgroups have common baseline characteristics, thereby providing comparable patient populations for testing the hypothesis that use of letrozole for ovarian stimulation can reduce the rates of multiples from that observed with gonadotropin and clomiphene citrate treatment. PMID:25707331

  17. Avoiding OHSS: Controlled Ovarian Low-Dose Stimulation in Women with PCOS.

    Science.gov (United States)

    Fischer, D; Reisenbüchler, C; Rösner, S; Haussmann, J; Wimberger, P; Goeckenjan, M

    2016-06-01

    The polycystic ovary syndrome is a common endocrine disorder which influences outcome and potential risks involved with controlled ovarian stimulation for artificial reproductive techniques (ART). Concrete practical recommendations for the dosage of gonadotropins, the preferred protocol and preventive methods to avoid ovarian hyperstimulation syndrome (OHSS) are lacking. We present retrospective data of 235 individually calculated gonadotropin low-dose stimulations for ART in a single center from 2012 to 2014. Clinical data and outcome parameter of patients diagnosed with PCOS according to Rotterdam criteria (n = 39) were compared with patients without PCOS (n = 196). The starting dose of gonadotropins was individually calculated depending on patients' age, BMI, ovarian reserve, ovarian response in previous cycles, and diagnostic criteria of PCOS. Mean age and duration of infertility did not differ between the groups, whereas mean BMI (p = 0.007) and AMH (p PCOS-group. A lower mean FSH-starting and maximum dose was administered to women with PCOS (p PCOS-patients did not differ from those of the control group (42.2 % and 34.4 % respectively). Neither mild, nor moderate or severe manifestation of OHSS occurred significantly more often in patients with PCOS. Our study supports the use of a calculated low-dose FSH-stimulation strategy in ART for patients with PCOS. Further randomized clinical trials should confirm this strategy and lead to define individual risk factors for OHSS, which can be used for recommendation of safer ART-techniques like in vitro maturation.

  18. The laparoscopic ovarian electrocautery versus gonadotropin therapy in infertile women with clomiphene citrate-resistant polycystic ovary syndrome; a randomized controlled trial.

    Science.gov (United States)

    Mehrabian, Ferdous; Eessaei, Fatemeh

    2012-03-01

    This study aimed to compare two methods of treatment of infertility with gonadotropin with laparoscopic ovarian electrocauterization in patients with clomiphene citrate-resistant polycystic ovary syndrome (PCOS). A number of 104 nulipara patients with polycystic ovary syndrome, who were resistant to clomiphene citrate were randomly assigned to two groups. One group received gonadotropin; after the bleeding withdrawal and from the third day of the cycle, the injection of human menopausal gonadotropin (HMG) was started with 10 mg medroxy progesterone. The patients were followed with serial trans-vaginal sonographies. When the diameter of follicles reached to 18 mm, human chorionic gonadotropin (HCG) was prescribed. The other group was treated with laparoscopic ovarian electrocauterization under general anesthesia. If after 3 cycles, the anovulation was established with progesterone measurement, the clomiphene citrate was prescribed. Gonadotropin was administered, if the lack of ovulation persisted. No significant difference was documented between the two groups in terms of the obesity indexes, duration of infertility, age, sonographic and laboratory findings. In the gonadotropin group, 37 cases (71%) of pregnancy occurred. The rate of pregnancy was the same in the other group consisting of 18 cases treated by electrocautery, 9 cases with cautery + clomiphene, and 10 cases with clomiphene + cautery + gonadotropin. In the group treated with gonadotropin, there were 1 triple and 4 twins pregnancies. In the group treated with ovarian electrocautery, one twin pregnancy was observed. In the group treated with gonadotropin, 2 cases of ovarian hyperstimulation syndrome, 1 case of ectopic pregnancy and 6 cases of miscarriage occurred; the corresponding figure in the ovarian electrocautery group consisted of 5 cases of miscarriage. Our findings suggest that ovarian electrocauterization is an appropriate method with good efficacy and low complication rate for infertility

  19. Ovarian reaction and estrus manifestation in delayed puberty gilts after treatment with equine chorionic gonadotropin

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    Stančić Ivan B

    2012-08-01

    Full Text Available Abstract Background Prolonged pre-insemination anestrus (i.e. delayed puberty is a major contributing factor for culling up to 30% of the replacement gilts at large breeding farm units in Vojvodina. It is imperative to determine if these gilts are acyclic (prepubertal or cyclic, but just fail to exhibit behavioural estrus. Recent investigations demonstrate that treatment with equine chorionic gonadotropin (eCG can increase the diestrous phase duration in sexually mature gilts. Based on these finding, the aim of the present studies was to determine the reproductive status of delayed puberty gilts following injection with eCG. Methods Two experiments were conducted on a swine breeding farm in Vojvodina. In Exp. 1, 20 prepubertal (acyclic gilts, and 120 sexually mature (cyclic gilts were injected with a single injection of 400 IU eCG + 200 IU human chorionic gonadotropin (hCG or with 1000 IU eCG (cyclic gilts, at d5, d11 or d17 after spontaneous estrus detection, to determine their ovarian reaction and induced estrus manifestation. In Exp. 2, sixty delayed puberty gilts (estrus not detected until 8 month of age, av. 258 days were culled from breeding herd and slaughtered to determine their reproductive status based on ovarian anatomical features. The second group of gilts (n = 60 was treated with a single 1000 IU eCG injection to determine their reproductive status, based on the interval between eCG injection to estrus detection and duration. The data were analyzed by descriptive statistics, t-test, analysis of variance and Duncan’s test in the software package Statistics 10th. Results Ovulations were induced in 90% of acyclic (sexually immature and, on average, 93.3% of cyclic (sexually mature gilts after the eCG injection. On average, 4 days after the eCG injection, estrus was detected in 85% of the treated acyclic (sexually immature gilts and in 95% (19/20 of the cyclic (sexually mature gilts, treated with eCG on day 17

  20. Obesity, serum steroid levels, and pulsatile gonadotropin secretion in polycystic ovarian disease.

    Science.gov (United States)

    Laatikainen, T; Tulenheimo, A; Andersson, B; Kärkkäinen, J

    1983-04-01

    Serum binding capacity of sex-hormone binding globulin (SHBG-BC), steroid concentrations, and secretion patterns of LH and FSH were compared between groups of seven nonobese and seven obese patients with polycystic ovarian disease (PCOD). Obese patients with PCOD differed from those with normal weight in having very low SHBG-BC and elevated serum levels of free and albumin bound testosterone. Compared to healthy women in the follicular phase, both nonobese and obese patients with PCOD showed equally elevated serum levels of androstenedione, estrone, and albumin-bound and free estradiol. Pattern of gonadotropin secretion was studied from blood samples taken at 15 min intervals for 6 h. In 6 patients of both groups low pulses of FSH were found coincidently with pulses of LH. Serum level of LH showed a clear pulsatile pattern in all patients with PCOD, varying from 4.5 to 7.5 pulses per 6 h. The mean pulse rate in the groups of nonobese and obese patients with PCOD was similar, 5.9 pulses per 6 h. In the obese patients the mean LH levels were, however, less elevated and the pulse amplitudes were smaller than those in the nonobese patients. We suggest that this difference is due to high levels of biologically active testosterone in obese patients with PCOD.

  1. Preconception folic acid use modulates estradiol and follicular responses to ovarian stimulation.

    Science.gov (United States)

    Twigt, John M; Hammiche, Fatima; Sinclair, Kevin D; Beckers, Nicole G; Visser, Jenny A; Lindemans, Jan; de Jong, Frank H; Laven, Joop S E; Steegers-Theunissen, Régine P

    2011-02-01

    Folate is a methyl donor. Availability of folate affects DNA methylation profiles and thereby gene expression profiles. We investigated the effects of low-dose folic acid use (0.4 mg/d) on the ovarian response to mild and conventional ovarian stimulation in women. In a randomized trial among subfertile women, 24 and 26 subjects received conventional and mild ovarian stimulation, respectively. Blood samples were taken during the early follicular phase of the cycle prior to treatment and on the day of human chorionic gonadotropin administration for determination of serum total homocysteine, anti-Müllerian hormone (AMH), estradiol, and folate. Folic acid use was validated by questionnaire and serum folate levels. Preovulatory follicles were visualized, counted, and diameters recorded using transvaginal ultrasound. The relation between folic acid use and ovarian response was assessed using linear regression analysis. Folic acid use modified the ovarian response to ovarian stimulation treatment. The estradiol response was higher in nonfolic acid users receiving conventional treatment [β(interaction) = 0.52 (0.07-0.97); P = 0.03], and this effect was independent of serum AMH levels and the preovulatory follicle count. In the conventional treatment, the mean follicle number was also greater in nonusers compared with the users group (14.1 vs. 8.9, P = 0.03). Low-dose folic acid use attenuates follicular and endocrine responses to conventional stimulation, independent of AMH and follicle count. The nature of this observation suggests that the effect of folic acid is most prominent during early follicle development, affecting immature follicles. Deleterious effects of folate deficiency, like DNA hypomethylation and oxidative stress, can help to explain our observations.

  2. Resurgence of Minimal Stimulation In Vitro Fertilization with A Protocol Consisting of Gonadotropin Releasing Hormone-Agonist Trigger and Vitrified-Thawed Embryo Transfer

    Directory of Open Access Journals (Sweden)

    Zhang John

    2016-07-01

    Full Text Available Minimal stimulation in vitro fertilization (mini-IVF consists of a gentle controlled ovarian stimulation that aims to produce a maximum of five to six oocytes. There is a misbelief that mini-IVF severely compromises pregnancy and live birth rates. An appraisal of the literature pertaining to studies on mini-IVF protocols was performed. The advantages of minimal stimulation protocols are reported here with a focus on the use of clomiphene citrate (CC, gonadotropin releasing hormone (GnRH ago- nist trigger for oocyte maturation, and freeze-all embryo strategy. Literature review and the author’s own center data suggest that minimal ovarian stimulation protocols with GnRH agonist trigger and freeze-all embryo strategy along with single embryo transfer produce a reasonable clinical pregnancy and live birth rates in both good and poor responders. Additionally, mini-IVF offers numerous advantages such as: i. Reduction in cost and stress with fewer office visits, needle sticks, and ultrasounds, and ii. Reduction in the incidence of ovarian hyperstimulation syndrome (OHSS. Mini-IVF is re-emerging as a solution for some of the problems associated with conventional IVF, such as OHSS, cost, and patient discomfort.

  3. Comparison Pregnancy Outcomes Between Minimal Stimulation Protocol and Conventional GnRH Antagonist Protocols in Poor Ovarian Responders

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    Shamim Pilehvari

    2016-05-01

    Full Text Available Objective: To compare the pregnancy outcomes achieved by in vitro fertilization (IVF between minimal stimulation and conventional antagonist protocols in poor ovarian responders (PORs.Materials and methods: In this randomized controlled trial, 77 PORs undergoing IVF were selected and divided into two groups. First group was the minimal stimulation group (n = 42 receiving 100 mg/day clomiphene citrate on day 2of the cycle for 5 day that was followed by150IU/day human menopausal gonadotropin (hMG on day 5 of the cycle. Second group was the conventional group (n = 35 receiving at least 300 IU/daygonadotropin on day 2 of the cycle. Gonadotropin-releasing hormone (GnRH antagonist protocol was applied for both groups according to flexible protocol. Number of retrieved oocytes and chemical pregnancy rate were the main outcomes.Results: There was no difference in number ofretrieved oocyte and pregnancy rate (2.79 ± 1.96 vs. 2.20 ± 1.71 and 5.6% vs. 4.1%; p > 0.05 between both groups. The gonadotropin dose used in the minimal stimulation group was lower than conventional group (1046 ± 596 vs. 2806 ± 583.Conclusion: Minimal stimulation protocol with lower gonadotropin used is likely to be considered as a patient- friendly and cost-effective substitute for PORs. 

  4. Gonadotropin-dependent oocyte maturational competence requires activation of the protein kinase A pathway and synthesis of RNA and protein in ovarian follicles of Nibe, Nibea mitsukurii (Teleostei, Sciaenidae)

    Science.gov (United States)

    Yoshizaki, G.; Shusa, M.; Takeuchi, T.; Patino, R.

    2002-01-01

    Luteinizing hormone- (LH)-dependent ovarian follicle maturation has been recently described in two stages for teleost fishes. The oocyte's ability to respond to the steroidal maturation-inducing hormone (MIH), also known as oocyte maturational competence (OMC), is acquired during the first stage; whereas the MIH-dependent resumption of meiosis occurs during the second stage. However, studies directly addressing OMC have been performed with a limited number of species and therefore the general relevance of the two-stage model and its mechanisms remain uncertain. In this study, we examined the hormonal regulation of OMC and its basic transduction mechanisms in ovarian follicles of the sciaenid teleost, Nibe (Nibea mitsukurii). Exposure to MIH [17,20??-dihydroxy-4-pregnen-3-one or 17,20??,21-trihydroxy-4-pregnen-3-one] stimulated germinal vesicle breakdown (index of meiotic resumption) in full-grown follicles primed with human chorionic gonadotropin (HCG, an LH-like gonadotropin) but not in those pre-cultured in plain incubation medium. The induction of OMC by HCG was mimicked by protein kinase A (PKA) activators (forskolin and dibutyryl cyclic AMP), and blocked by specific inhibitors of PKA (H89 and H8) as well as inhibitors of RNA (actinomycin D) and protein (cycloheximide) synthesis. Forskolin-induced OMC was also inhibited by actinomycin D and cycloheximide. A strong activator of protein kinase C, PMA, inhibited HCG-dependent OMC. In conclusion, OMC in Nibe ovarian follicles is gonadotropin-dependent and requires activation of the PKA pathway followed by gene transcription and translation events. These observations are consistent with the two-stage model of ovarian follicle maturation proposed for other teleosts, and suggest that Nibe can be used as new model species for mechanistic studies of ovarian follicle differentiation and maturation in fishes.

  5. How to personalize ovarian stimulation in clinical practice.

    Science.gov (United States)

    Sighinolfi, Giovanna; Grisendi, Valentina; La Marca, Antonio

    2017-09-01

    Controlled ovarian stimulation (COS) in in vitro fertilization (IVF) cycles is the starting point from which couple's prognosis depends. Individualization in follicle-stimulating hormone (FSH) starting dose and protocol used is based on ovarian response prediction, which depends on ovarian reserve. Anti-Müllerian hormone levels and the antral follicle count are considered the most accurate and reliable markers of ovarian reserve. A literature search was performed for studies that addressed the ability of ovarian reserve markers to predict poor and high ovarian response in assisted reproductive technology cycles. According to the predicted response to ovarian stimulation (poor- normal- or high- response), it is possible to counsel couples before treatment about the prognosis, and also to individualize ovarian stimulation protocols, choosing among GnRH-agonists or antagonists for endogenous FSH suppression, and the FSH starting dose in order to decrease the risk of cycle cancellation and ovarian hyperstimulation syndrome. In this review we discuss how to choose the best COS therapy, based on ovarian reserve markers, in order to enhance chances in IVF.

  6. Circulating gonadotropins and ovarian adiponectin system are modulated by acupuncture independently of sex steroid or β-adrenergic action in a female hyperandrogenic rat model of polycystic ovary syndrome.

    Science.gov (United States)

    Maliqueo, Manuel; Benrick, Anna; Alvi, Asif; Johansson, Julia; Sun, Miao; Labrie, Fernand; Ohlsson, Claes; Stener-Victorin, Elisabet

    2015-09-05

    Acupuncture with combined manual and low-frequency electrical stimulation, or electroacupuncture (EA), reduces endocrine and reproductive dysfunction in women with polycystic ovary syndrome (PCOS), likely by modulating sympathetic nerve activity or sex steroid synthesis. To test this hypothesis, we induced PCOS in rats by prepubertal implantation of continuous-release letrozole pellets (200 µg/day) or vehicle. Six weeks later, rats were treated for 5-6 weeks with low-frequency EA 5 days/week, subcutaneous injection of 17β-estradiol (2.0 µg) every fourth day, or a β-adrenergic blocker (propranolol hydrochloride, 0.1 mg/kg) 5 days/week. Letrozole controls were handled without needle insertion or injected with sesame oil every fourth day. Estrous cyclicity, ovarian morphology, sex steroids, gonadotropins, insulin-like growth factor I, bone mineral density, and gene and protein expression in ovarian tissue were measured. Low-frequency EA induced estrous-cycle changes, decreased high levels of circulating luteinizing hormone (LH) and the LH/follicle-stimulating hormone (FSH) ratio, decreased high ovarian gene expression of adiponectin receptor 2, and increased expression of adiponectin receptor 2 protein and phosphorylation of ERK1/2. EA also increased cortical bone mineral density. Propranolol decreased ovarian expression of Foxo3, Srd5a1, and Hif1a. Estradiol decreased circulating LH, induced estrous cycle changes, and decreased ovarian expression of Adipor1, Foxo3, and Pik3r1. Further, total bone mineral density was higher in the letrozole-estradiol group. Thus, EA modulates the circulating gonadotropin levels independently of sex steroids or β-adrenergic action and affects the expression of ovarian adiponectin system. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  7. The rate of high ovarian response in women identified at risk by a high serum AMH level is influenced by the type of gonadotropin.

    Science.gov (United States)

    Arce, Joan-Carles; Klein, Bjarke M; La Marca, Antonio

    2014-06-01

    The aim was to compare ovarian response and clinical outcome of potential high-responders after stimulation with highly purified menotropin (HP-hMG) or recombinant follicle-stimulating hormone (rFSH) for in vitro fertilisation/intracytoplasmic sperm injection. Retrospective analysis was performed on data collected in two randomized controlled trials, one conducted following a long GnRH agonist protocol and the other with an antagonist protocol. Potential high-responders (n = 155 and n = 188 in the agonist and antagonist protocol, respectively) were defined as having an initial anti-Müllerian hormone (AMH) value >75th percentile (5.2 ng/ml). In both protocols, HP-hMG stimulation in women in the high AMH category was associated with a significantly lower occurrence of high response (≥15 oocytes retrieved) than rFSH stimulation; 33% versus 51% (p = 0.025) and 31% versus 49% (p = 0.015) in the long agonist and antagonist protocol, respectively. In the potential high-responder women, trends for improved live birth rate were observed with HP-hMG compared with rFSH (long agonist protocol: 33% versus 20%, p = 0.074; antagonist protocol: 34% versus 23%, p = 0.075; overall population: 34% versus 22%, p = 0.012). In conclusion, the type of gonadotropin used for ovarian stimulation influences high-response rates and potentially clinical outcome in women identified as potential high-responders.

  8. Evaluation of puberty by verifying spontaneous and stimulated gonadotropin values in girls.

    Science.gov (United States)

    Chin, Vivian L; Cai, Ziyong; Lam, Leslie; Shah, Bina; Zhou, Ping

    2015-03-01

    Changes in pharmacological agents and advancements in laboratory assays have changed the gonadotropin-releasing hormone analog stimulation test. To determine the best predictive model for detecting puberty in girls. Thirty-five girls, aged 2 years 7 months to 9 years 3 months, with central precocious puberty (CPP) (n=20) or premature thelarche/premature adrenarche (n=15). Diagnoses were based on clinical information, baseline hormones, bone age, and pelvic sonogram. Gonadotropins and E2 were analyzed using immunochemiluminometric assay. Logistic regression for CPP was performed. The best predictor of CPP is the E2-change model based on 3- to 24-h values, providing 80% sensitivity and 87% specificity. Three-hour luteinizing hormone (LH) provided 75% sensitivity and 87% specificity. Basal LH lowered sensitivity to 65% and specificity to 53%. The E2-change model provided the best predictive power; however, 3-h LH was more practical and convenient when evaluating puberty in girls.

  9. Calcium-independent phosphatidylinositol response in gonadotropin-releasing-hormone-stimulated pituitary cells.

    OpenAIRE

    Naor, Z; Molcho, J; Zakut, H; Yavin, E

    1985-01-01

    This paper describes the effect of gonadotropin-releasing hormone (GnRH, gonadoliberin) on phospholipid metabolism in cultured rat pituitary cells. The cells were incubated with [32P]Pi to label endogenous phospholipids (10-60 min) and then stimulated with GnRH for up to 60 min. Cellular phospholipids were separated by two-dimensional t.l.c. and the radioactivity was determined. Phosphatidylinositol (PI), a minor constituent of cellular phospholipids (7.7%), was the major labelled phospholipi...

  10. Gonadotropin-Releasing Hormone Stimulate Aldosterone Production in a Subset of Aldosterone-Producing Adenoma

    Science.gov (United States)

    Kishimoto, Rui; Oki, Kenji; Yoneda, Masayasu; Gomez-Sanchez, Celso E.; Ohno, Haruya; Kobuke, Kazuhiro; Itcho, Kiyotaka; Kohno, Nobuoki

    2016-01-01

    Abstract We aimed to detect novel genes associated with G protein-coupled receptors (GPCRs) in aldosterone-producing adenoma (APA) and elucidate the mechanisms underlying aldosterone production. Microarray analysis targeting GPCR-associated genes was conducted using APA without known mutations (APA-WT) samples (n = 3) and APA with the KCNJ5 mutation (APA-KCNJ5; n = 3). Since gonadotropin-releasing hormone receptor (GNRHR) was the highest expression in APA-WT by microarray analysis, we investigated the effect of gonadotropin-releasing hormone (GnRH) stimulation on aldosterone production. The quantitative polymerase chain reaction assay results revealed higher GNRHR expression levels in APA-WT samples those in APA-KCNJ5 samples (P APA-WT samples, and there was a significant and positive correlation between GNRHR and LHCGR expression in all APA samples (r = 0.476, P APA-WT (n = 9), which showed higher GNRHR and LHCGR levels, had significantly higher GnRH-stimulated aldosterone response than those with APA-KCNJ5 (n = 13) (P APA-WT, and the molecular analysis including the receptor expression associated with clinical findings of GnRH stimulation. PMID:27196470

  11. The role of corifollitropin alfa in controlled ovarian stimulation for IVF in combination with GnRH antagonist

    Directory of Open Access Journals (Sweden)

    Seyhan A

    2011-08-01

    Full Text Available Ayse Seyhan, Baris AtaDivision of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, McGill University, Montreal, QC, CanadaAbstract: Corifollitropin alfa is a synthetic recombinant follicle-stimulating hormone (rFSH molecule containing a hybrid beta subunit, which provides a plasma half-life of ∼65 hours while maintaining its pharmocodynamic activity. A single injection of corifollitropin alfa can replace daily FSH injections for the first week of ovarian stimulation for in vitro fertilization. Stimulation can be continued with daily FSH injections if the need arises. To date, more than 2500 anticipated normoresponder women have participated in clinical trials with corifollitropin alfa. It is noteworthy that one-third of women did not require additional gonadotropin injections and reached human chorionic gonadotropin criterion on day 8. The optimal corifollitropin dose has been calculated to be 100 µg for women with a body weight ≤ 60 kg and 150 µg for women with a body weight >60 kg, respectively. Combination of corifollitropin with daily gonadotropin-releasing hormone antagonist injections starting on stimulation day 5 seems to yield similar or significantly higher numbers of oocytes and good quality embryos, as well as similar ongoing pregnancy rates compared with women stimulated with daily rFSH injections. Stimulation characteristics, embryology, and clinical outcomes seem consistent with repeated corifollitropin-stimulated assisted reproductive technologies cycles. Multiple pregnancy or ovarian hyperstimulation syndrome rates with corifollitropin were not increased over daily FSH regimen. The corifollitropin alfa molecule does not seem to be immunogenic and does not induce neutralizing antibody formation. Drug hypersensitivity and injection-site reactions are not increased. Incidence and nature of adverse events and serious adverse events are similar to daily FSH injections. Current trials do not

  12. Individualization of controlled ovarian stimulation in vitro fertilization using ovarian reserve markers.

    Science.gov (United States)

    Grisendi, Valentina; La Marca, Antonio

    2017-06-01

    In assisted reproduction technologies (ART) the controlled ovarian stimulation (COS) therapy is the starting point from which a good oocytes retrieval depends. Treatment individualization is based on ovarian response prediction, which largely depends on a woman's ovarian reserve. Anti-Müllerian hormone (AMH) and antral follicle count (AFC) are considered the most accurate and reliable markers of ovarian reserve. A literature search was carried out for studies that addressed the ability of AMH and AFC to predict poor and/or excessive ovarian response in IVF cycles. According to the predicted response to ovarian stimulation (poor- normal- or high-response) is today possible not only to personalize pre-treatment counseling with the couple, but also to individualize the ovarian stimulation protocol, choosing among GnRH-agonists or antagonists for endogenous follicle-stimulating hormone (FSH) suppression and formulating the FSH starting dose most adequate for the single patients. In this review we discuss how to choose the best COS therapy for the single patient, on the basis of the markers-guided ovarian response prediction.

  13. Triggering ovulation with gonadotropin-releasing hormone agonist versus human chorionic gonadotropin in polycystic ovarian syndrome. A randomized trial

    Directory of Open Access Journals (Sweden)

    Amr Hassaan Farag

    2015-12-01

    Full Text Available Objectives: To compare GnRH agonist to hCG for triggering ovulation in polycystic ovarian syndrome treated with clomiphene citrate. Study design: Prospective randomized study. Materials & methods: Eighty five infertile women with PCOS participated in a randomized allocation concealed prospective trial and had induction of ovulation with clomiphene citrate. GnRH agonist 0.2 mg subcutaneously (group 1 or hCG 10,000 IU intramuscularly (group 2 was given to trigger ovulation. Primary outcome was mid-luteal serum progesterone, while secondary outcomes were ovulation rates and clinical pregnancy rates along 3 cycles. Results: No difference was found between group 1 and group 2 regarding mean serum progesterone and clinical pregnancy rates in each cycle. Cumulative pregnancy rates were similar (17.14% versus 20% respectively; P = 0.332. Ovulation rates were 80% versus 68.6% (P = 0.413; 94.3% versus 90.9% (P = 0.669; 97.1% versus 93.7% (P = 0.603 in the two groups respectively. However, a significant rise in number of patients with mid-luteal serum progesterone >10 ng/mL was noted in the 3rd cycle between both groups, (P < 0.0001 for group 1 while P = 0.007 for group 2. Conclusion: Triggering ovulation with GnRH-a after treatment with clomiphene citrate in PCOS, in view of its known protective effect against OHSS, may be an effective physiological alternative to conventional hCG without compromising luteal function and pregnancy rates after repeated cycles of treatment.

  14. Can anti-Mullerian hormone (AMH) predict the outcome of intrauterine insemination with controlled ovarian stimulation?

    Science.gov (United States)

    Bakas, Panagiotis; Boutas, Ioannis; Creatsa, Maria; Vlahos, Nicos; Gregoriou, Odysseas; Creatsas, George; Hassiakos, Dimitrios

    2015-10-01

    To assess whether the levels of anti-Mullerian hormone (AMH) are related to outcome of intrauterine insemination (IUI) in patients treated with gonadotropins. A total of 195 patients underwent controlled ovarian stimulation (COS) with recombinant follicle stimulating hormone (rFSH) (50-150 IU/d). All patients were submitted upto three cycles of IUI. Primary outcome was the ability of AMH levels to predict clinical pregnancy at first attempt and the cumulative clinical pregnancy probability of upto three IUI cycles. Secondary outcomes were the relation of AMH, LH, FSH, BMI, age, parity and basic estradiol levels with each other and the outcome of IUI. The area under the receiver operating characteristic (ROC) curve in predicting clinical pregnancy for AMH at first attempt was 0.53 and for cumulative clinical pregnancy was 0.76. AMH levels were positively correlated with clinical pregnancy rate at first attempt and with cumulative clinical pregnancy rate, but negatively correlated with patient's age and FSH levels. Patient's FSH, LH levels were negatively correlated with cumulative clinical pregnancy rate. AMH levels seem to have a positive correlation and patient's age and LH levels had a negative correlation with the outcome of IUI and COS with gonadotropins. AMH concentration was significantly higher and LH was significantly lower in patients with a clinical pregnancy after three cycles of IUI treatment compared with those who did not achieve pregnancy.

  15. Mild ovarian stimulation for IVF: 10 years later

    DEFF Research Database (Denmark)

    Fauser, Bart C J M; Nargund, Geeta; Andersen, Anders Nyboe

    2010-01-01

    Ovarian stimulation to achieve multiple follicle development has been an integral part of IVF treatment. In the context of improved laboratory performance, the need for a large number of oocytes as an integral part of a successful IVF programme may be questioned. The aim of the current debate...... is to summarize the studies performed during the last decade to develop the concept of mild stimulation aiming to obtain fewer than eight oocytes. Here we examine the balance between IVF success and patient discomfort, and complications and cost, and how these might improve by simpler ovarian stimulation...

  16. The ISMAAR proposal on terminology for ovarian stimulation for IVF

    NARCIS (Netherlands)

    Nargund, G.; Fauser, B. C. J. M.; Macklon, N. S.; Ombelet, W.; Nygren, K.; Frydman, R.

    IVF is performed with oocytes collected in natural and stimulated cycles. Different approaches to ovarian stimulation have been employed worldwide. Following the introduction of GnRH antagonists and strategies to reduce multiple births such as single embryo transfer, there is a genuine scientific

  17. The ISMAAR proposal on terminology for ovarian stimulation for IVF

    NARCIS (Netherlands)

    Nargund, G.; Fauser, B. C. J. M.; Macklon, N. S.; Ombelet, W.; Nygren, K.; Frydman, R.

    2007-01-01

    IVF is performed with oocytes collected in natural and stimulated cycles. Different approaches to ovarian stimulation have been employed worldwide. Following the introduction of GnRH antagonists and strategies to reduce multiple births such as single embryo transfer, there is a genuine scientific

  18. Overriding follicle selection in controlled ovarian stimulation protocols: Quality vs quantity

    Directory of Open Access Journals (Sweden)

    Zelinski-Wooten Mary B

    2004-06-01

    Full Text Available Abstract Selection of the species-specific number of follicles that will develop and ovulate during the ovarian cycle can be overridden by increasing the levels of pituitary gonadotropin hormones, FSH and LH. During controlled ovarian stimulation (COS in nonhuman primates for assisted reproductive technology (ART protocols, the method of choice (but not the only method has been the administration of exogenous gonadotropins, either of nonprimate or primate origin. Due to species-specificity of the primate LH (but not FSH receptor, COS with nonprimate (e.g., PMSG hormones can be attributed to their FSH activity. Elevated levels of FSH alone will produce large antral follicles containing oocytes capable of fertilization in vitro (IVF. However, there is evidence that LH, probably in lesser amounts, increases the rate of follicular development, reduces heterogeneity of the antral follicle pool, and improves the viability and rate of pre-implantation development of IVF-produced embryos. Since an endogenous LH surge typically does not occur during COS cycles (especially when a GnRH antagonist is added, a large dose of an LH-like hormone (i.e., hCG may be given to reinitiate meiosis and produce fertilizable oocytes. Alternate approaches using exogenous LH (or FSH, or GnRH agonist to induce an endogenous LH surge, have received lesser attention. Current protocols will routinely yield dozens of large follicles with fertilizable eggs. However, limitations include non/poor-responding animals, heterogeneity of follicles (and presumably oocytes and subsequent short luteal phases (limiting embryo transfer in COS cycles. However, the most serious limitation to further improvements and expanded use of COS protocols for ART is the lack of availability of nonhuman primate gonadotropins. Human, and even more so, nonprimate gonadotropins are antigenic in monkeys, which limits the number of COS cycles to as few as 1 (PMSG or 3 (recombinant hCG protocols in macaques

  19. Oral contraceptive therapy for polycystic ovary disease after chronic gonadotropin-releasing agonist administration. Predictors of continued ovarian suppression.

    Science.gov (United States)

    Elkind-Hirsch, K E; Anania, C; Malinak, R

    1996-09-01

    To study the beneficial effects of oral contraceptive (OC) therapy following gonadotropin-releasing hormone agonist (GnRH-a) administration in women with polycystic ovary disease (PCOD). Twenty-three hyperandrogenic women (aged 15-39) were randomized into two groups; GnRH-a (depot every 28 days) for six months or combination therapy (GnRH-a plus OC "addback") for six months. Following six months of treatment with either therapy, all patients received OC therapy for at least six months. The hormonal state was evaluated at three-month intervals. Hormone levels of luteinizing hormone (LH), testosterone (T) and free T remained suppressed within the normal range in 11 of 17 patients (65%) during the six months of OC only therapy, while the other six patients showed "escape" from suppression, with the LH, T and free T concentrations rising to pre-GnRH-a treatment levels. Use of OC addback therapy did not potentiate the long-acting therapeutic effect of GnRH-a pretreatment; three of six patients in the escape group were pretreated with combination therapy and three with GnRH-a only. In the majority of women with PCOD, OC therapy following GnRH-a administration was effective in maintaining ovarian androgen suppression. Failure to maintain ovarian suppression in this patient population was associated with higher elevations of baseline free T concentrations.

  20. A regulator of G Protein signaling, RGS3, inhibits gonadotropin-releasing hormone (GnRH-stimulated luteinizing hormone (LH secretion

    Directory of Open Access Journals (Sweden)

    Musgrove Lois C

    2001-11-01

    Full Text Available Abstract Background Luteinizing hormone secreted by the anterior pituitary gland regulates gonadal function. Luteinizing hormone secretion is regulated both by alterations in gonadotrope responsiveness to hypothalamic gonadotropin releasing hormone and by alterations in gonadotropin releasing hormone secretion. The mechanisms that determine gonadotrope responsiveness are unknown but may involve regulators of G protein signaling (RGSs. These proteins act by antagonizing or abbreviating interaction of Gα proteins with effectors such as phospholipase Cβ. Previously, we reported that gonadotropin releasing hormone-stimulated second messenger inositol trisphosphate production was inhibited when RGS3 and gonadotropin releasing hormone receptor cDNAs were co-transfected into the COS cell line. Here, we present evidence for RGS3 inhibition of gonadotropin releasing hormone-induced luteinizing hormone secretion from cultured rat pituitary cells. Results A truncated version of RGS3 (RGS3T = RGS3 314–519 inhibited gonadotropin releasing hormone-stimulated inositol trisphosphate production more potently than did RSG3 in gonadotropin releasing hormone receptor-bearing COS cells. An RSG3/glutathione-S-transferase fusion protein bound more 35S-Gqα than any other member of the G protein family tested. Adenoviral-mediated RGS3 gene transfer in pituitary gonadotropes inhibited gonadotropin releasing hormone-stimulated luteinizing hormone secretion in a dose-related fashion. Adeno-RGS3 also inhibited gonadotropin releasing hormone stimulated 3H-inositol phosphate accumulation, consistent with a molecular site of action at the Gqα protein. Conclusions RGS3 inhibits gonadotropin releasing hormone-stimulated second messenger production (inositol trisphosphate as well as luteinizing hormone secretion from rat pituitary gonadotropes apparently by binding and suppressing the transduction properties of Gqα protein function. A version of RGS3 that is amino

  1. Effects of human chorionic gonadotropin combined with clomiphene on Serum E2, FSH, LH and PRL levels in patients with polycystic ovarian syndrome.

    Science.gov (United States)

    Yonggang, Huang; Xiaosheng, Lu; Zhaoxia, Huang; Yilu, Chen; Jiqiang, Lv; Huina, Zhang

    2017-02-01

    Effects of human chorionic gonadotropin combined with clomiphene on serum E 2 , FSH, LH and PRL levels in patients with polycystic ovarian syndrome were analyzed. 90 patients with polycystic ovarian syndrome treated from January 2015 to March 2016 were randomly and evenly divided into control group and observation group. Patients in the control group were only treated with clomiphene. On the basis of the treatment in control group, human chorionic gonadotropin was added in the treatment of observation group. The changes of E 2 , FSH, LH, PRL levels were compared between two groups before and after the treatment. Clinical curative effects of patients in the two groups was evaluated. Adverse reactions during treatment in two groups were observed and recorded. The incidence of adverse reactions was calculated. Serum E 2 , FSH, LH and PRL levels in the two groups decreased significantly after treatment compared with that before treatment. The difference is statistical significant ( P   0.05). Combined use of human chorionic gonadotropin can significantly reduce serum E 2 , FSH, LH and PRL levels, improve clinical curative effects and reduce the incidence of adverse reactions. Human chorionic gonadotropin has high application value on the treatment of polycystic ovary syndrome.

  2. Comparison between pulsatile GnRH therapy and gonadotropins for ovulation induction in women with both functional hypothalamic amenorrhea and polycystic ovarian morphology.

    Science.gov (United States)

    Dumont, Agathe; Dewailly, Didier; Plouvier, Pauline; Catteau-Jonard, Sophie; Robin, Geoffroy

    2016-12-01

    Ovulation induction in patients having both functional hypothalamic amenorrhea (FHA) and polycystic ovarian morphology (PCOM) has been less studied in the literature. As results remain contradictory, no recommendations have yet been established. To compare pulsatile GnRH therapy versus gonadotropins for ovulation induction in "FHA-PCOM" patients and to determine if one treatment strikes as superior to the other. A 12-year retrospective study, comparing 55 "FHA-PCOM" patients, treated either with GnRH therapy (38 patients, 93 cycles) or with gonadotropins (17 patients, 53 cycles). Both groups were similar, defined by low serum LH and E2 levels, low BMI, excessive follicle number per ovary and/or high serum AMH level. Ovulation rates were significantly lower with gonadotropins (56.6% versus 78.6%, p = 0.005), with more cancellation and ovarian hyper-responses (14% versus 34% per initiated cycle, p < 0.005). Pregnancy rates were significantly higher with GnRH therapy, whether per initiated cycle (26.9% versus 7.6%, p = 0.005) or per patient (65.8% versus 23.5%, p = 0.007). In our study, GnRH therapy was more successful and safer than gonadotropins, for ovulation induction in "FHA-PCOM" patients. If results were confirmed by prospective studies, it could become a first-line treatment for this population, just as it is for FHA women without PCOM.

  3. Subcutaneous injection of kisspeptin-54 acutely stimulates gonadotropin secretion in women with hypothalamic amenorrhea, but chronic administration causes tachyphylaxis.

    Science.gov (United States)

    Jayasena, Channa N; Nijher, Gurjinder M K; Chaudhri, Owais B; Murphy, Kevin G; Ranger, Amita; Lim, Adrian; Patel, Daksha; Mehta, Amrish; Todd, Catriona; Ramachandran, Radha; Salem, Victoria; Stamp, Gordon W; Donaldson, Mandy; Ghatei, Mohammad A; Bloom, Stephen R; Dhillo, Waljit S

    2009-11-01

    Kisspeptin is a critical regulator of normal reproductive function. A single injection of kisspeptin in healthy human volunteers potently stimulates gonadotropin release. However, the effects of kisspeptin on gonadotropin release in women with hypothalamic amenorrhea (HA) and the effects of repeated administration of kisspeptin to humans are unknown. The aim of this study was to determine the effects of acute and chronic kisspeptin administration on gonadotropin release in women with HA. We performed a prospective, randomized, double-blinded, parallel design study. Women with HA received twice-daily sc injections of kisspeptin (6.4 nmol/kg) or 0.9% saline (n = 5 per group) for 2 wk. Changes in serum gonadotropin and estradiol levels, LH pulsatility, and ultrasound measurements of reproductive activity were assessed. On the first injection day, potent increases in serum LH and FSH were observed after sc kisspeptin injection in women with HA (mean maximal increment from baseline within 4 h after injection: LH, 24.0 +/- 3.5 IU/liter; FSH, 9.1 +/- 2.5 IU/liter). These responses were significantly reduced on the 14th injection day (mean maximal increment from baseline within 4 h postinjection: LH, 2.5 +/- 2.2 IU/liter, P < 0.05; FSH, 0.5 +/- 0.5 IU/liter, P < 0.05). Subjects remained responsive to GnRH after kisspeptin treatment. No significant changes in LH pulsatility or ultrasound measurements of reproductive activity were observed. Acute administration of kisspeptin to women with infertility due to HA potently stimulates gonadotropin release, but chronic administration of kisspeptin results in desensitization to its effects on gonadotropin release. These data have important implications for the development of kisspeptin as a novel therapy for reproductive disorders in humans.

  4. Mild ovarian stimulation for IVF: 10 years later

    DEFF Research Database (Denmark)

    Fauser, Bart C J M; Nargund, Geeta; Andersen, Anders Nyboe

    2010-01-01

    Ovarian stimulation to achieve multiple follicle development has been an integral part of IVF treatment. In the context of improved laboratory performance, the need for a large number of oocytes as an integral part of a successful IVF programme may be questioned. The aim of the current debate is ...

  5. Does the Ovarian Stimulation Phase Length Predict In vitro Fertilization Outcomes?

    Directory of Open Access Journals (Sweden)

    Angela Baerwald

    2011-01-01

    Full Text Available Background: Bi-directional communication between the follicle and oocyte is necessary toregulate follicle and oocyte development. Currently, it is not practical to monitor the serial growthof individual follicles during assisted reproduction. The ovarian stimulation phase length (SPLis an indirect measure of mean follicular growth rate. The objective of this study was to test thehypothesis that a short or long SPL would be associated with suboptimal outcomes in womenundergoing in vitro fertilization (IVF.Materials and Methods: A retrospective cohort study was conducted in 140 women who underwentIVF. Follicle development was monitored every 2-3 days during ovarian stimulation usingtransvaginal ultrasonography. Once > 3 follicles reached ≥ 17 mm, human chorionic gonadotropin(hCG was administered. Oocyte retrieval was performed approximately 35 hours after hCG.Oocytes underwent IVF on the day of collection and were evaluated daily thereafter. Embryos weretransferred on days 3 or 5, depending on the number and quality of embryos available. Associationsbetween SPL, age, follicle, oocyte, embryo and pregnancy outcomes were evaluated (SPSS version17.0; SPSS Inc., Chicago, IL, USA.Results: A SPL of 11 days was associated with an optimal number of follicles that developed to≥ 6 mm, ≥ 10 mm and ≥ 15 mm; serum estradiol concentrations; and number of oocytes collected(p0.05. Associations betweenSPL and outcomes were not influenced by age (p>0.05.Conclusion: The ovarian SPL can be used to predict the number of follicles that develop, oocytescollected and serum estradiol concentrations, but not embryo or pregnancy outcomes.

  6. Environmental impacts on the gonadotropic system in female Atlantic salmon (Salmo salar) during vitellogenesis: Photothermal effects on pituitary gonadotropins, ovarian gonadotropin receptor expression, plasma sex steroids and oocyte growth.

    Science.gov (United States)

    Taranger, Geir Lasse; Muncaster, Simon; Norberg, Birgitta; Thorsen, Anders; Andersson, Eva

    2015-09-15

    The gonadotropic system and ovarian growth and development were studied during vitellogenesis in female Atlantic salmon subjected to either simulated natural photoperiod and ambient water temperature (NL-amb), or an accelerating photoperiod (short day of LD8:16 from May 10) combined with either warmed (ca 2°C above ambient; 8L-warm) or cooled water (ca 2°C below ambient; 8L-cold) from May to September. Monthly samples were collected from 10 females/group for determination of transcript levels of pituitary gonadotropin subunits (fshb and lhb) and ovarian gonadotropin receptors (fshr and lhr), plasma sex steroids (testosterone: T and estradiol-17β: E2), gonadosomatic index (GSI) and oocyte size. Short day in combination with either warmed or cooled water induced an earlier increase in pituitary fshb and lhb levels compared with NL-amb controls, and advanced ovarian growth and the seasonal profiles of T, E2. By contrast only minor effects were seen of the photothermal treatments on ovarian fshr and lhr. The 8L-cold had earlier increase in fshb, lhb and E2, but similar oocyte and gonadal growth as 8L-warm, suggesting that the 8L-cold group tried to compensate for the lower water temperature during the period of rapid gonadal growth by increasing fshb and E2 production. Both the 8L-warm and 8L-cold groups showed incomplete ovulation in a proportion of the females, possibly due to the photoperiod advancement resulting in earlier readiness of spawning occurring at a higher ambient temperature, or due to some reproductive dysfunction caused by photothermal interference with normal neuroendocrine regulation of oocyte development and maturation. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Follicular fluid placental growth factor is increased in polycystic ovarian syndrome: correlation with ovarian stimulation.

    Science.gov (United States)

    Tal, Reshef; Seifer, David B; Grazi, Richard V; Malter, Henry E

    2014-08-20

    Polycystic ovarian syndrome (PCOS) is characterized by increased ovarian angiogenesis and vascularity. Accumulating evidence indicates that vascular endothelial growth factor (VEGF) is increased in PCOS and may play an important role in these vascular changes and the pathogenesis of this disease. Placental growth factor (PlGF), a VEGF family member, has not been previously characterized in PCOS women. We investigated levels and temporal expression patterns of PlGF and its soluble receptor sFlt-1 (soluble Fms-like tyrosine kinase) in serum and follicular fluid (FF) of women with PCOS during controlled ovarian stimulation. This was a prospective cohort study of 14 PCOS women (Rotterdam criteria) and 14 matched controls undergoing controlled ovarian stimulation. Serum was collected on day 3, day of hCG and day of oocyte retrieval. FF was collected on retrieval day. PlGF, sFlt-1 and anti-mullerian hormone (AMH) protein concentrations were measured using ELISA. Since sFlt-1 binds free PlGF, preventing its signal transduction, we calculated PlGF bioavailability as PlGF/sFlt-1 ratio. Serum PlGF and sFlt-1 levels were constant throughout controlled ovarian stimulation, and no significant differences were observed in either factor in PCOS women compared with non-PCOS controls at all three measured time points. However, FF PlGF levels were increased 1.5-fold in PCOS women compared with controls (p ovarian reserve marker anti-mullerian hormone (AMH) and negatively with age. In addition, FF sFlt-1 levels were decreased 1.4-fold in PCOS women compared to controls (p = 0.04). PlGF bioavailability in FF was significantly greater (2-fold) in PCOS women compared with non-PCOS controls (p ovarian stimulation and that its bioavailability is increased in women with PCOS undergoing controlled ovarian stimulation. This suggests that PlGF may play a role in PCOS pathogenesis and its angiogenic dysregulation.

  8. Individualization of controlled ovarian stimulation in IVF using ovarian reserve markers: from theory to practice.

    Science.gov (United States)

    La Marca, Antonio; Sunkara, Sesh Kamal

    2014-01-01

    The main objective of individualization of treatment in IVF is to offer every single woman the best treatment tailored to her own unique characteristics, thus maximizing the chances of pregnancy and eliminating the iatrogenic and avoidable risks resulting from ovarian stimulation. Personalization of treatment in IVF should be based on the prediction of ovarian response for every individual. The starting point is to identify if a woman is likely to have a normal, poor or a hyper response and choose the ideal treatment protocol tailored to this prediction. The objective of this review is to summarize the predictive ability of ovarian reserve markers, such as antral follicle count (AFC) and anti-Mullerian hormone (AMH), and the therapeutic strategies that have been proposed in IVF after this prediction. A systematic review of the existing literature was performed by searching Medline, EMBASE, Cochrane library and Web of Science for publications in the English language related to AFC, AMH and their incorporation into controlled ovarian stimulation (COS) protocols in IVF. Literature available to May 2013 was included. The search generated 305 citations of which 41 and 25 studies, respectively, reporting the ability of AMH and AFC to predict response to COS were included in this review. The literature review demonstrated that AFC and AMH, the most sensitive markers of ovarian reserve identified to date, are ideal in planning personalized COS protocols. These sensitive markers permit prediction of the whole spectrum of ovarian response with reliable accuracy and clinicians may use either of the two markers as they can be considered interchangeable. Following the categorization of expected ovarian response to stimulation clinicians can adopt tailored therapeutic strategies for each patient. Current scientific trend suggests the elective use of the GnRH antagonist based regimen for hyper-responders, and probably also poor responders, as likely to be beneficial. The

  9. Clinical and hormonal effects of chronic gonadotropin-releasing hormone agonist treatment in polycystic ovarian disease.

    Science.gov (United States)

    Steingold, K; De Ziegler, D; Cedars, M; Meldrum, D R; Lu, J K; Judd, H L; Chang, R J

    1987-10-01

    Previously, we reported that short term administration of a highly potent GnRH agonist (GnRHa) for 1 month to patients with polycystic ovarian disease (PCO) resulted in complete suppression of ovarian steroidogenesis without measurable effects on adrenal steroid production. This new study was designed to evaluate the effects of long term GnRHa administration in PCO patients with respect to their hormone secretion patterns and clinical responses. Eight PCO patients and 10 ovulatory women with endometriosis were treated daily with sc injections of [D-His6-(imBzl]),Pro9-NEt]GnRH (GnRHa; 100 micrograms) for 6 months. Their results were compared to hormone values in 8 women who had undergone bilateral oophorectomies. In response to GnRHa, PCO and ovulatory women had rises of serum LH at 1 month, after which it gradually declined to baseline. In both groups FSH secretion was suppressed throughout treatment. Serum estradiol, estrone, progesterone, 17-hydroxyprogesterone, androstenedione, and testosterone levels markedly decreased to values found in oophorectomized women by 1 month and remained low thereafter. In contrast, serum pregnenolone and 17-hydroxypregnenolone were partially suppressed, and dehydroepiandrosterone, dehydroepiandrosterone sulfate, and cortisol levels did not change. Clinically, hyperplastic endometrial histology in three PCO patients reverted to an inactive pattern, and proliferative endometrium in two other PCO patients became inactive in one and did not change in the other. Regression of proliferative endometrial histology occurred in all ovulatory women. Vaginal bleeding occurred in all women studied during the first month of GnRHa administration, after which all but one PCO patient became amenorrheic. Hot flashes were noted by all ovulatory women and by four of eight PCO patients. All PCO patients noted subjective reduction of skin oiliness, and five had decreased hair growth. We conclude that in premenopausal women: 1) chronic Gn

  10. Role of Gonadotropin-releasing Hormone Stimulation Test in Diagnosing Gonadotropin Deficiency in Both Males and Females with Delayed Puberty

    Directory of Open Access Journals (Sweden)

    Qi-Hong Sun

    2015-01-01

    Conclusions: Our data suggest that isolated use of the gonadorelin stimulation test is almost sufficient to discriminate between HH and CDP in males, but unnecessary in females. The most useful predictor is serum basal or peak LH to differentiate these two disorders in males, but serum basal LH or FSH in females.

  11. Quality of common marmoset (Callithrix jacchus) oocytes collected after ovarian stimulation.

    Science.gov (United States)

    Kanda, Akifumi; Nobukiyo, Asako; Yoshioka, Miyuki; Hatakeyama, Teruhiko; Sotomaru, Yusuke

    2018-01-15

    The common marmoset (Callithrix jacchus) is an experimental animal that is considered suitable for the creation of next-generation human disease models. It has recently been used in the reproductive technology field. Oocytes can be effectively collected from female marmosets via ovarian stimulation with injections of follicle-stimulating hormone (FSH) and human chorionic gonadotropin (hCG). The oocytes, collected about 28 h after the hCG injection, include both premature oocytes and postmature (in vivo matured; IVO) oocytes, and the premature oocytes can be matured by in vitro culture (in vitro matured; IVM). Although IVM and IVO oocytes are equivalent in appearance at the MII stage, it remains unclear whether there are differences in their properties. Therefore, we investigated their in vitro fertilization and developmental capacities and cytoskeletal statuses. Our findings revealed that the IVM and IVO oocytes had similar fertilization rates but that no IVO oocytes could develop to the blastocyst stage. Additionally, IVO oocytes showed abnormal cytoskeletal formation. It is concluded that IVM oocytes maintain normal function, whereas IVO oocytes would be affected by aging and other factors when they remain for a long time in the ovary. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. The camp analogue, dbcAMP can stimulate rabbit reproductive functions: I. Effect on ovarian folliculogenesis, ovulation and embryo production

    Directory of Open Access Journals (Sweden)

    Chrenek P.

    2012-01-01

    Full Text Available The aim of our study was to examine the influence of administration of N6,2’-dibutyryladenosine 3’5’-cyclic monophosphate (dbcAMP, a cAMP agonist, on ovarian folliculogenesis and atresia, as well as on reproductive efficiency in rabbits, whose ovarian cycle and ovulation was induced by gonadotropins. Ovarian cycle and ovulation of control rabbits were induced by 20 IU/kg PMSG followed by 35 IU/kg hCG administration. Experimental animals received PMSG and hCG together with dbcAMP (at 5, 25 or 50 μg/animal. After ovulation and insemination, the animals were sacrificed. Ovaries were weighted, histological sections of ovaries were prepared, and the presence of ovulated and not ovulated follicles and different stages of atresia was evaluated by light microscopy. The eggs were flushed from the oviducts after insemination and cultured up to blastocyst cell stage. Numbers of ovarian Corpora lutea, ovulated oocytes and oocyte-derived zygotes and embryos reaching hatched blastocyst stage were determined. Administration of dbcAMP (at doses 25 or 50 μg/animal, but not at 5 μg/animal was able to increase the proportion of follicles with cystic and luteinization-related atresia. Furthermore, dbcAMP (50 μg/animal, but not lower doses increased the ovarian mass, number of Corpora lutea, number of harvested oocytes, zygotes and embryos at blastocyst stage derived from these zygotes after culture. These data demonstrate that dbcAMP can stimulate rabbit ovarian follicle atresia, ovulation, oocyte, zygote and embryo yield and development. Furthermore, they confirm in the involvement of cyclic nucleotide-dependent intracellular mechanisms in the control of rabbit reproductive functions and potential practical usefulness of dbcAMP in improving animal reproduction and fertility.

  13. Enhancement of a robust arcuate GABAergic input to gonadotropin-releasing hormone neurons in a model of polycystic ovarian syndrome.

    Science.gov (United States)

    Moore, Aleisha M; Prescott, Mel; Marshall, Christopher J; Yip, Siew Hoong; Campbell, Rebecca E

    2015-01-13

    Polycystic ovarian syndrome (PCOS), the leading cause of female infertility, is associated with an increase in luteinizing hormone (LH) pulse frequency, implicating abnormal steroid hormone feedback to gonadotropin-releasing hormone (GnRH) neurons. This study investigated whether modifications in the synaptically connected neuronal network of GnRH neurons could account for this pathology. The PCOS phenotype was induced in mice following prenatal androgen (PNA) exposure. Serial blood sampling confirmed that PNA elicits increased LH pulse frequency and impaired progesterone negative feedback in adult females, mimicking the neuroendocrine abnormalities of the clinical syndrome. Imaging of GnRH neurons revealed greater dendritic spine density that correlated with increased putative GABAergic but not glutamatergic inputs in PNA mice. Mapping of steroid hormone receptor expression revealed that PNA mice had 59% fewer progesterone receptor-expressing cells in the arcuate nucleus of the hypothalamus (ARN). To address whether increased GABA innervation to GnRH neurons originates in the ARN, a viral-mediated Cre-lox approach was taken to trace the projections of ARN GABA neurons in vivo. Remarkably, projections from ARN GABAergic neurons heavily contacted and even bundled with GnRH neuron dendrites, and the density of fibers apposing GnRH neurons was even greater in PNA mice (56%). Additionally, this ARN GABA population showed significantly less colocalization with progesterone receptor in PNA animals compared with controls. Together, these data describe a robust GABAergic circuit originating in the ARN that is enhanced in a model of PCOS and may underpin the neuroendocrine pathophysiology of the syndrome.

  14. Potential role of follicle-stimulating hormone (FSH) and transforming growth factor (TGFβ1) in the regulation of ovarian angiogenesis.

    Science.gov (United States)

    Kuo, Shih-Wei; Ke, Ferng-Chun; Chang, Geen-Dong; Lee, Ming-Ting; Hwang, Jiuan-Jiuan

    2011-06-01

    Angiogenesis occurs during ovarian follicle development and luteinization. Pituitary secreted FSH was reported to stimulate the expression of endothelial mitogen VEGF in granulosa cells. And, intraovarian cytokine transforming growth factor (TGF)β1 is known to facilitate FSH-induced differentiation of ovarian granulosa cells. This intrigues us to investigate the potential role of FSH and TGFβ1 regulation of granulosa cell function in relation to ovarian angiogenesis. Granulosa cells were isolated from gonadotropin-primed immature rats and treated once with FSH and/or TGFβ1 for 48 h, and the angiogenic potential of conditioned media (granulosa cell culture conditioned media; GCCM) was determined using an in vitro assay with aortic ring embedded in collagen gel and immunoblotting. FSH and TGFβ1 increased the secreted angiogenic activity in granulosa cells (FSH + TGFβ1 > FSH ≈ TGFβ1 >control) that was partly attributed to the increased secretion of pro-angiogenic factors VEGF and PDGF-B. This is further supported by the evidence that pre-treatment with inhibitor of VEGF receptor-2 (Ki8751) or PDGF receptor (AG1296) throughout or only during the first 2-day aortic ring culture period suppressed microvessel growth in GCCM-treated groups, and also inhibited the FSH + TGFβ1-GCCM-stimulated release of matrix remodeling-associated gelatinase activities. Interestingly, pre-treatment of AG1296 at late stage suppressed GCCM-induced microvessel growth and stability with demise of endothelial and mural cells. Together, we provide original findings that both FSH and TGFβ1 increased the secretion of VEGF and PDGF-B, and that in turn up-regulated the angiogenic activity in rat ovarian granulosa cells. This implicates that FSH and TGFβ1 play important roles in regulation of ovarian angiogenesis during follicle development. Copyright © 2010 Wiley-Liss, Inc.

  15. Optimal cutoff value of basal anti-mullerian hormone in iranian infertile women for prediction of ovarian hyper-stimulation syndrome and poor response to stimulation.

    Science.gov (United States)

    Aghssa, Malek Mansour; Tarafdari, Azam Manshadi; Tehraninejad, Ensieh Shahrokh; Ezzati, Mohammad; Bagheri, Maryam; Panahi, Zahra; Mahdavi, Saeed; Abbasi, Mehrshad

    2015-09-10

    We intended to establish the threshold of Anti-Mullerian Hormone (AMH) for detection of Ovarian Hyper-Stimulation Syndrome (OHSS) and poor response to treatment in Iranian infertile women. Pre-stimulation menstrual cycle day-3 hormonal indices including basal AMH values were measured in 105 infertile women aged 32.5 ± 4.3 years. Patients underwent long GnRH agonist Controlled Ovarian Hyperstimulation (COH) in a referral infertility center (Tehran, Iran). The gonadotropin dose was determined based on the age and basal serum Follicular Stimulating Hormone (FSH) level. The IVF/ICSI cycles were followed and the clinical and sonographic data were recorded. Sixteen cases developed OHSS. The prevalence of PCOS was higher in subjects with OHSS [62.5 % (38.8-86.2) vs. 17 % (9.2-24.9)]. The patients with OHSS had higher ovarian follicular count [23.7 (3.2) vs. 9.1 (0.5); p Basal AMH level and oocyte yields (but not age, BMI, and PCOS) correlated with occurrence of OHSS; and only the AMH levels were associated with poor ovarian response (oocytes yield ≤ 4). The optimal cutoff value for the prediction of OHSS was 6.95 ng/ml (area under the receiver operating characteristics curve: 0.86; CI: 0.78-0.95; sensitivity: 75 %; specificity: 84 %; odds ratio for occurrence of OHSS: 9 and p basal AMH level > 6.95 ng/ml are at high risk of developing OHSS and those with AMH level < 1.65 ng/ml are poor responders.

  16. Improving the luteal phase after ovarian stimulation

    DEFF Research Database (Denmark)

    Andersen, Claus Yding; Vilbour Andersen, K

    2014-01-01

    The human chorionic gonadotrophin (HCG) trigger used for final follicular maturation in connection with assisted reproduction treatment combines ovulation induction and early luteal-phase stimulation of the corpora lutea. The use of a gonadotrophin-releasing hormone agonist (GnRHa) for final...... follicular maturation has, however, for the first time allowed a separation of the ovulatory signal from the early luteal-phase support. This has generated new information that may improve the currently employed luteal-phase support. Thus, combined results from a number of randomized controlled trials using...

  17. Response to ovarian stimulation in patients facing gonadotoxic therapy.

    Science.gov (United States)

    Johnson, Lauren N C; Dillon, Katherine E; Sammel, Mary D; Efymow, Brenda L; Mainigi, Monica A; Dokras, Anuja; Gracia, Clarisa R

    2013-04-01

    Chemotherapy naïve patients undergoing embryo/oocyte banking for fertility preservation (FP) were assessed for response to ovarian stimulation. Fifty FP patients facing gonadotoxic therapy were matched by age, race, cycle number, date of stimulation and fertilization method to patients undergoing IVF for infertility or oocyte donation. There were no differences in baseline FSH, anti-Müllerian hormone, antral follicle count and total gonadotrophin dose. FP patients had more immature oocytes (2.2 versus 1.1; P=0.03) and lower fertilization rates per oocyte retrieved (52% versus 70%; P=0.002). There were no differences in numbers of oocytes retrieved, mature oocytes or fertilized embryos. Subgroup analysis revealed that FP patients taking letrozole required higher gonadotrophin doses (3077IU versus 2259IU; P=0.0477) and had more immature oocytes (3.4 versus 1.2; P=0.03) than matched controls. There were no differences in gonadotrophin dose or oocyte immaturity among FP patients not taking letrozole. Overall, chemotherapy naïve FP patients had similar ovarian reserve, response to stimulation and oocyte and embryo yield compared to controls. Patients who received letrozole required higher gonadotrophin doses and produced more immature oocytes, suggesting that response to ovarian stimulation may be impaired in patients with hormone-sensitive cancers receiving letrozole. With improvement in cancer survival rates, there has been a shift in attention toward management of long-term consequences of cancer therapy, including infertility. Many young women with cancer, particularly those who will be treated with chemotherapy, pursue fertility preservation (FP) strategies for the purpose of banking oocytes or embryos for future use. We examined patients with no prior exposure to chemotherapy who underwent IVF to freeze embryos or oocytes for FP. Fifty FP patients were identified and matched to healthy controls by age, race, cycle number, date of stimulation and fertilization

  18. Risk of borderline and invasive ovarian tumours after ovarian stimulation for in vitro fertilization in a large Dutch cohort

    NARCIS (Netherlands)

    F.E. van Leeuwen; H. Klip; T.M. Mooij (Thea); A.M.G. van de Swaluw; C.B. Lambalk (Cornelius); M. Kortman; J.S.E. Laven (Joop); C.A.M. Jansen; F.M. Helmerhorst; B.J. Cohlen; W.N.P. Willemsen (Wim); J.M.J. Smeenk; A.H.M. Simons; F. van der Veen; J.L.H. Evers (Johannes); P.A. van Dop; N.S. Macklon (Nick); C.W. Burger (Curt)

    2011-01-01

    textabstractBackground: Long-term effects of ovarian stimulation for IVF on the risk of ovarian malignancies are unknown.Methods: We identified a nationwide historic cohort of 19 146 women who received IVF treatment in the Netherlands between 1983 and 1995, and a comparison group of 6006 subfertile

  19. Risk of borderline and invasive ovarian tumours after ovarian stimulation for in vitro fertilization in a large Dutch cohort

    NARCIS (Netherlands)

    van Leeuwen, F. E.; Klip, H.; Mooij, T. M.; de Swaluw, A. M. G. van; Lambalk, C. B.; Kortman, M.; Laven, J. S. E.; Jansen, C. A. M.; Helmerhorst, F. M.; Cohlen, B. J.; Willemsen, W. N. P.; Smeenk, J. M. J.; Simons, A. H. M.; van der Veen, F.; Evers, J. L. H.; van Dop, P. A.; Macklon, N. S.; Burger, C. W.

    2011-01-01

    BACKGROUND: Long-term effects of ovarian stimulation for IVF on the risk of ovarian malignancies are unknown. METHODS: We identified a nationwide historic cohort of 19 146 women who received IVF treatment in the Netherlands between 1983 and 1995, and a comparison group of 6006 subfertile women not

  20. Microdose Flare-up Gonadotropin-releasing Hormone (GnRH) Agonist Versus GnRH Antagonist Protocols in Poor Ovarian Responders Undergoing Intracytoplasmic Sperm Injection.

    Science.gov (United States)

    Boza, Aysen; Cakar, Erbil; Boza, Barıs; Api, Murat; Kayatas, Semra; Sofuoglu, Kenan

    2016-01-01

    Microdose flare-up GnRH agonist and GnRH antagonist have become more popular in the management of poor ovarian responders (POR) in recent years; however, the optimal protocol for POR patients undergoing in vitro fertilization has still been a challenge. In this observational study design, two hundred forty four poor ovarian responders were retrospectively evaluated for their response to GnRH agonist protocol (group-1, n=135) or GnRH antagonist protocol (group-2, n=109). Clinical pregnancy rate was the primary end point and was compared between the groups. Student t-test, Mann Whitney U test and χ (2)-test were used to compare the groups. The pmicrodose flare-up protocol has favorable outcomes with respect to the number of oocytes retrieved and implantation rate; nevertheless, the clinical pregnancy rate was found to be similar in comparison to GnRH antagonist protocol in poor ovarian responders. GnRH antagonist protocol appears to be promising with significantly lower gonadotropin requirement and lower treatment cost in poor ovarian responders.

  1. Corifollitropin alfa compared to daily rFSH or HP-HMG in GnRH antagonist controlled ovarian stimulation protocol for patients undergoing assisted reproduction.

    Science.gov (United States)

    Souza, Priscila Morais Galvão; Carvalho, Bruno Ramalho de; Nakagawa, Hitomi Miura; Rassi, Thalita Reis Esselin; Barbosa, Antônio César Paes; Silva, Adelino Amaral

    2017-06-01

    This study aimed to compare the outcomes of controlled ovarian stimulation (COS) with corifollitropin alfa versus daily recombinant follicle-stimulating hormone (rRFSH) or highly purified human menopausal gonadotropin (HP-HMG) in patients undergoing in vitro fertilization (IVF) cycles based on gonadotropin-releasing hormone (GnRH) antagonist protocols. The primary endpoints were total number of oocytes and mature oocytes. This retrospective study looked into 132 controlled ovarian stimulation cycles from IVF or oocyte cryopreservation performed in a private human reproduction center between January 1 and December 31, 2014. Enrollment criteria: women aged 0.05). There were no significant differences in fertilization (76.9% vs. 76.8%, p=1.0), biochemical pregnancy (66.7% vs. 47.2%, p=0.1561) or embryo implantation rates (68.7% vs. 50%, p=0.2588) between the groups using corifollitropin alfa and rFSH or HMG, respectively. Corifollitropin alfa seems to be as effective as rFSH or HP-HMG when used in the first seven days of ovulation induction for patients undergoing assisted reproduction in GnRH antagonist protocols.

  2. Microdose gonadotropin-releasing hormone agonist in the absence of exogenous gonadotropins is not sufficient to induce multiple follicle development.

    Science.gov (United States)

    Chung, Karine; Fogle, Robin; Bendikson, Kristin; Christenson, Kamilee; Paulson, Richard

    2011-01-01

    Because the effectiveness of the "microdose flare" stimulation protocol often is attributed to the dramatic endogenous gonadotropin release induced by the GnRH agonist, the aim of this study was to determine whether use of microdose GnRH agonist alone could induce multiple ovarian follicle development in normal responders. Based on these data, the duration of gonadotropin rise is approximately 24 to 48 hours and is too brief to sustain continued multiple follicle growth. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  3. The duration of gonadotropin stimulation does not alter the clinical pregnancy rate in IVF or ICSI cycles.

    Science.gov (United States)

    Purandare, N; Emerson, G; Kirkham, C; Harrity, C; Walsh, D; Mocanu, E

    2017-08-01

    Ovarian stimulation is an essential part of assisted reproduction treatments. Research on whether the duration of stimulation alters the success in assisted reproduction has not been conclusive. The purpose of the study was to establish whether the duration of ovarian stimulation alters the success in assisted reproduction treatments. All fresh (non-donor) stimulation cycles performed in an academic tertiary referral ART centre over a period of 18 years, between 1st January 1997 and 31st December 2014, were identified. Data were prospectively and electronically collected. IVF and ICSI cycles were analysed independently. Each category was then subdivided into assisted reproduction cycles where the antagonist, long (down regulation) and flare protocol were used. Clinical pregnancy was the main outcome measured. A total of 10,478 stimulation cycles (6011 fresh IVF and 4467 fresh ICSI) reaching egg collection were included. We showed no significant difference in CP rates in IVF cycles for the long (p = 0.082), antagonist (p = 0.217) or flare (p = 0.741) protocol cycles or in ICSI cycles with the long (p = 0.223), antagonist (p = 0.766) or the flare (p = 0.690) protocol with regards the duration of stimulation. The duration of stimulation does not alter the CP rate in ICSI or IVF cycles using the long, antagonist or flare stimulation protocol.

  4. Effect of simultaneously started clomiphene citrate and gonadotropins in antagonist regimes, on cumulative live births, fresh-cycle live births and cost of stimulation in IVF cycles.

    Science.gov (United States)

    Satwik, Ruma; Kochhar, Mohinder

    2018-04-11

    The aim of the study was to compare simultaneously started clomiphene citrate (CC) and gonadotropins (Gn) with gonadotropins alone in conventional antagonist regimes with respect to fresh-cycle live births, cumulative live births and cost of ovarian stimulation per started cycle. This was a single-center prospective cohort study conducted over 1 year. Women undergoing autologous in vitro fertilization (IVF) treatment in antagonist protocols and who consented to participate in the study were divided into two cohorts. The CC cohort (n = 86) received 50 mg CC for 5 days and individualized Gn daily until the hCG trigger, both starting from day 2 and antagonist daily from day 8 of menstrual cycle. The Gn-only cohort (n = 349) received individualized Gn from day 2 and the antagonist from day 7 of menstrual cycle. IVF outcomes and cost of stimulation were compared between two cohorts across expected ovarian response categories. The CC cohort used a mean lower dose of Gn (1741.38 ± 604.46 vs 1980.54 ± 686.42; MD = -239.16; 95%CI = -348.03 to -189.24; P = 0.003) over fewer days (8.54 ± 1.86 vs 9.25 ± 1.97; MD =-0.71;95% CI = -1.17 to -0.25; P = 0.0026) to achieve similar retrieved oocytes, (9.19 ± 5.92 vs 9.36 ± 6.96; MD = -0.17; 95%CI -1.77 to + 1.43; P = 0.83), positive bhCG rates (40% vs 29.6%, MD = 10.4%; OR = 1.65, 95%CI = 0.95-2.86; P = 0.078) and live births in fresh cycles (32.31% vs 21.30%; MD = 11.01%; OR = 1.76; 95%CI = 0.97-3.19; P = 0.06) and cumulative live births per initiated cycle (30.23% vs 20.34%; MD = 9.89%; OR = 1.697; 95%CI = 0.99-2.88; P = 0.0501). The dose lowering achieved a 28-40% reduction in the cost of stimulation, which was most noticeable in the hyper-responder category for both hMG cycles, (Rs.11 602.3 ± 3365.9 vs 19615 ± 2677.1; MD = -8012.7; %age reduction: 40.8%; P = 0.0007) and recombinant FSH cycles (Rs. 22

  5. Letrozole+ GnRH antagonist stimulation protocol in poor ovarian responders undergoing intracytoplasmic sperm injection cycles: An RCT

    Directory of Open Access Journals (Sweden)

    Mahbod Ebrahimi

    2017-08-01

    Full Text Available Background: Gonadotropin-releasing hormone (GnRH antagonist protocol has been proposed as a potentially proper option for the patients with limited ovarian reserve. Nevertheless, there is no significant difference in terms of clinical pregnancy between the GnRH antagonist and agonist cycles. The use of aromatase inhibitors such as letrozole was suggested by some studies. Objective: The object of this study was to evaluate the efficacy of letrozole cotreatment with GnRH-antagonist protocol in ovarian stimulation of poor responder patients undergoing intracytoplasmic sperm injection. Materials and Methods: A double-blinded randomized control trial was conducted on 70 infertile women with poor ovarian response based on Bologna criteria in two groups: letrozole+GnRH-antagonist (LA group and placebo+GnRH-antagonist (PA group (n=35/each. The LA group involved at letrozole 2.5 mg daily over 5 days and recombinant human follicle stimulating hormone 225 IU/daily. The PA group received placebo over 5 days and recombinant human follicle stimulating hormone at the same starting day and dose, similar to LA group. GnRH-antagonist was introduced once one or more follicle reached ≥14 mm. The main outcome measures were the number of oocytes retrieved, fertilization rate, implantation rate, cycle cancellation rate, and clinical pregnancy rate. Results: There were no significant differences in demographic characteristics between groups. There were no significant differences between groups regarding the number of oocytes retrieved (p=0.81, number of embryos transferred (p=0.82, fertilization rate (p=0.225, implantation rate (p=0.72, total cycle cancelation rate (p=0.08, and clinical pregnancy rate (p=0.12. Conclusion: The use of letrozole in GnRH-antagonist cycles does not improve clinical outcomes in poor responder patients undergoing intracytoplasmic sperm injection.

  6. Random-start ovarian stimulation in women desiring elective cryopreservation of oocytes.

    Science.gov (United States)

    Pereira, Nigel; Voskuilen-Gonzalez, Anna; Hancock, Kolbe; Lekovich, Jovana P; Schattman, Glenn L; Rosenwaks, Zev

    2017-10-01

    The current study investigates the utility of random-start ovarian stimulation in women desiring elective oocyte cryopreservation. Women in the study cohort underwent random-start ovarian stimulation, and were subdivided based on the phase of the menstrual cycle that ovarian stimulation began, i.e. early follicular, late follicular or luteal phase. Women undergoing conventional cycle day (CD) 2/3 ovarian stimulation start were controls. A total of 1302 women were included - 859 (66.0%) conventional CD 2/3, 342 (26.3%) early follicular, 42 (3.2%) late follicular and 59 (4.5%) luteal ovarian stimulation starts. There was no difference in the demographics or baseline ovarian stimulation characteristics. The duration of ovarian stimulation (11 versus 9 days; P start group. The number of total and MII oocytes in the control and random-start groups was similar. A non-significant trend towards increased cycle cancellation was noted in the late follicular start group (7.1%). Study findings indicate the number of total and MII oocytes derived from random-start protocols initiated during any phase of the menstrual cycle is similar to conventional CD 2/3 ovarian stimulation start protocols in women desiring elective oocyte cryopreservation. Copyright © 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

  7. Dietary lipid and cholesterol induce ovarian dysfunction and abnormal LH response to stimulation in rabbits.

    Directory of Open Access Journals (Sweden)

    Anne-Gaël Cordier

    Full Text Available BACKGROUND/AIM: Excess of fat intake is dramatically increasing in women of childbearing age and results in numerous health complications, including reproductive disorders. Using rabbit does as a biomedical model, the aim of this study was to evaluate onset of puberty, endocrine responses to stimulation and ovarian follicular maturation in females fed a high fat high cholesterol diet (HH diet from 10 weeks of age (i.e., 2 weeks before normal onset of puberty or a control diet (C diet. METHODOLOGY/PRINCIPAL FINDINGS: Three experiments were performed, each including 8 treated (HH group and 8 control (C group does. In experiment 1, the endocrine response to Gonadotropin releasing hormone (GnRH was evaluated at 13, 18 and 22 weeks of age. In experiment 2, the follicular population was counted in ovaries of adult females (18 weeks of age. In experiment 3, the LH response to mating and steroid profiles throughout gestation were evaluated at 18 weeks of age. Fetal growth was monitored by ultrasound and offspring birth weight was recorded. Data showed a significantly higher Luteinizing hormone (LH response after induction of ovulation at 13 weeks of age in the HH group. There was no difference at 18 weeks, but at 22 weeks, the LH response to GnRH was significantly reduced in the HH group. The number of atretic follicles was significantly increased and the number of antral follicles significantly reduced in HH does vs. controls. During gestation, the HH diet induced intra-uterine growth retardation (IUGR. CONCLUSION: The HH diet administered from before puberty onwards affected onset of puberty, follicular growth, hormonal responses to breeding and GnRH stimulation in relation to age and lead to fetal IUGR.

  8. New trends in combined use of gonadotropin-releasing hormone antagonists with gonadotropins or pulsatile gonadotropin-releasing hormone in ovulation induction and assisted reproductive technologies.

    Science.gov (United States)

    Gordon, K; Danforth, D R; Williams, R F; Hodgen, G D

    1992-10-01

    The use of gonadotropin-releasing hormone agonists as adjunctive therapy with gonadotropins for ovulation induction in in vitro fertilization and other assisted reproductive technologies has become common clinical practice. With the recent advent of potent gonadotropin-releasing hormone antagonists free from the marked histamine-release effects that stymied earlier compounds, an attractive alternative method may be available. We have established the feasibility of combining gonadotropin-releasing hormone antagonist-induced inhibition of endogenous gonadotropins with exogenous gonadotropin therapy for ovulation induction in a nonhuman primate model. Here, the principal benefits to be gained from using the gonadotropin-releasing hormone antagonist rather than the gonadotropin-releasing hormone agonist are the immediate inhibition of pituitary gonadotropin secretion without the "flare effect," which brings greater safety and convenience for patients and the medical team and saves time and money. We have also recently demonstrated the feasibility of combining gonadotropin-releasing hormone antagonist with pulsatile gonadotropin-releasing hormone therapy for the controlled restoration of gonadotropin secretion and gonadal steroidogenesis culminating in apparently normal (singleton) ovulatory cycles. This is feasible only with gonadotropin-releasing hormone antagonists because, unlike gonadotropin-releasing hormone agonists, they achieve control of the pituitary-ovarian axis without down regulation of the gonadotropin-releasing hormone receptor system. This capacity to override gonadotropin-releasing hormone antagonist-induced suppression of pituitary-ovarian function may allow new treatment modalities to be employed for women who suffer from chronic hyperandrogenemia with polycystic ovarian disease.

  9. Physical-chemical and biological characterization of different preparations of equine chorionic gonadotropin

    OpenAIRE

    Alvarez, Rafael Herrera; Natal, Fabio Luis Nogueira; Ribela, Maria Teresa Carvalho Pinto; de Almeida, Beatriz Elane; de Oliveira, Jo?o Ezequiel; Bartolini, Paolo

    2016-01-01

    Ovarian stimulation with commercial preparations of equine chorionic gonadotropin (eCG) produces extremely variable responses in domestic animals, ranging from excessive stimulation to practically no stimulation, when applied on the basis of their declared unitage. This study was conducted to analyze four commercial preparations from different manufacturers via reversed-phase HPLC (RP-HPLC) in comparison with a reference preparation and an official International Standard from the World Health...

  10. Induction of puberty with human chorionic gonadotropin and follicle-stimulating hormone in adolescent males with hypogonadotropic hypogonadism.

    Science.gov (United States)

    Barrio, R; de Luis, D; Alonso, M; Lamas, A; Moreno, J C

    1999-02-01

    To evaluate the clinical and hormonal responses of adolescent males with hypogonadotropic hypogonadism (HH) in response to gonadotropin replacement with the use of long-term combined hCG and FSH therapy. Prospective clinical study. Clinical pediatric department providing tertiary care. Seven prepubertal males with isolated HH with a mean (+/-SD) age of 15.44+/-1.97 years and seven prepubertal males with panhypopituitarism-associated HH with a mean (+/-SD) age of 18.1+/-3.24 years were studied. Human chorionic gonadotropin (1,000-1,500 IU IM) and FSH (75-100 IU SC) were administered every alternate day of the week until the total induction of puberty and spermatogenesis was achieved. Serum testosterone levels, testicular volume, penis length, and sperm count were evaluated after the administration of hCG and FSH. All patients achieved normal sexual maturation and normal or nearly normal adult male levels of testosterone. The increase in testicular size was significant in both groups. Positive sperm production was assessed in four of five patients with isolated HH and in three of three patients with panhypopituitarism-associated HH. Long-term combined hCG and FSH therapy is effective in inducing puberty, increasing testicular volume, and stimulating spermatogenesis in adolescent males with isolated HH and panhypopituitarism-associated HH.

  11. No Evidence for the Benefit of Gonadotropin-Releasing Hormone Agonist in Preserving Ovarian Function and Fertility in Lymphoma Survivors Treated With Chemotherapy: Final Long-Term Report of a Prospective Randomized Trial.

    Science.gov (United States)

    Demeestere, Isabelle; Brice, Pauline; Peccatori, Fedro A; Kentos, Alain; Dupuis, Jehan; Zachee, Pierre; Casasnovas, Olivier; Van Den Neste, Eric; Dechene, Julie; De Maertelaer, Viviane; Bron, Dominique; Englert, Yvon

    2016-08-01

    We have reported previously that after 1-year follow up, gonadotropin-releasing hormone agonist (GnRHa) did not prevent chemotherapy-induced premature ovarian failure (POF) in patients with lymphoma, but may provide protection of the ovarian reserve. Here, we report the final analysis of the cohort after 5 years of follow up. A total of 129 patients with lymphoma were randomly assigned to receive either triptorelin plus norethisterone (GnRHa group) or norethisterone alone (control group) during chemotherapy. Ovarian function and fertility were reported after 2, 3, 4, and 5 to 7 years of follow up. The primary end point was POF, defined as at least one follicle-stimulating hormone value of > 40 IU/L after 2 years of follow up. Sixty-seven patients 26.21 ± 0.64 years of age had available data after a median follow-up time of 5.33 years in the GnRHa group and 5.58 years in the control group (P = .452). Multivariate logistic regression analysis showed a significantly increased risk of POF in patients according to age (P = .047), the conditioning regimen for hematopoietic stem cell transplant (P = .002), and the cumulative dose of cyclophosphamide > 5 g/m(2) (P = .019), but not to the coadministration of GnRHa during chemotherapy (odds ratio, 0.702; P = .651). The ovarian reserve, evaluated using anti-Müllerian hormone and follicle-stimulating hormone levels, was similar in both groups. Fifty-three percent and 43% achieved pregnancy in the GnRHa and control groups, respectively (P = .467). To the best of our knowledge, this is the first long-term analysis confirming that GnRHa is not efficient in preventing chemotherapy-induced POF in young patients with lymphoma and did not influence future pregnancy rate. These results reopen the debate about the drug's benefit in that it should not be recommended as standard for fertility preservation in patients with lymphoma. © 2016 by American Society of Clinical Oncology.

  12. Gonadotropin stimulates oocyte translation by increasing magnesium activity through intracellular potassium-magnesium exchange

    International Nuclear Information System (INIS)

    Horowitz, S.B.; Tluczek, L.J.

    1989-01-01

    We previously showed that gonadotropin increases the K + activity in Xenopus oocytes and that this is a signal for increased translation. However, K + need not act to control synthesis directly but may act through an unidentified downstream effector. Using microinjection to vary the salt content of oocytes and concomitantly measuring [ 3 H]leucine incorporation, we found that small changes in Mg 2+ greatly affect translation rates. (Ca 2+ had little influence.) By measuring intracellular ion activities, we found that oocyte cations existed in a buffer-like (ion-exchange) equilibrium in which K + and Mg 2+ are the preponderant monovalent and divalent cations. Hence, increasing cellular K + activity might increase translation by causing Mg 2+ activity to rise. If so, the increased translation rates produced by hormone treatment or K + injection would be prevented by EDTA, a Mg 2+ chelating agent. This prediction was tested and confirmed. We conclude that, when gonadotropin increases K + activity, the cell's internal ion-exchange equilibrium is altered thereby increasing Mg 2+ activity and this up-regulates translation

  13. Follicular aspiration versus coasting for ovarian hyper-stimulation syndrome prevention

    Science.gov (United States)

    Bushaqer, Nayla J.; Dayoub, Nawal M.; AlHattali, Khalsa K.; Ayyoub, Hisham A.; AlFaraj, Samaher S.; Hassan, Samar N.

    2018-01-01

    Objectives: To compare follicular reduction prior to human chorionic gonadotropin (HCG) trigger and coasting in terms of ovarian hyper-stimulation syndrome (OHSS) reduction, pregnancy, and cancellation rates in in vitro fertilization/ intracytoplasmic sperm injection (IVF/ICSI) cycles. Methods: This study was designed as a prospective study. The setting was the IVF unit at King Abdulaziz Medical City, Riyadh, Kingdom of Saudi Arabia. A total of 39 patients undergoing IVF/ICSI cycles, who were at risk of OHSS, 20 were put into a coasting group and 19 had follicular reduction instead. This occurred between October 2010 and January 2011. Our main outcome was OHSS reduction. Results: Six (30%) women developed OHSS in the coasting group and 2 (10.5%) women developed OHSS in the follicular group (p-value=0.235). The pregnancy rates in the cycles were similar for both groups: 4/20 (20%) in the coasting group and 3/19 (15.8%) in the follicular group (p-value=1.000). The cancellation rate of the cycles was similar for both groups, 6/20 (30%) in the coasting group and 1/19 (5.3%) in the follicular group (p-value=0.09). The median number of punctured follicles was significantly lower in the follicular group (16 follicles, interquartile range (IQR)=21-12) compared to the coasting group (29 follicles, IQR=37.8-19.8, p-value=0.001). The retrieved, fertilized, and cleaved oocytes, as well as the number of embryos transferred, were similar amongst both groups. Conclusion: There was no difference between follicular reduction prior to HCG and coasting, in terms of OHSS reduction, pregnancy, and cancellation rates in both the IVF and ICSI cycles. PMID:29543308

  14. Diagnosis and management of an immature teratoma during ovarian stimulation: a case report

    Directory of Open Access Journals (Sweden)

    Douay-Hauser Nathalie

    2011-11-01

    Full Text Available Abstract Introduction The discovery of a mature teratoma (dermoid cyst of the ovary during ovarian stimulation is not a rare event. Conversely, we could not find any reported cases of immature teratoma in such a situation. Clinical and ultrasound arguments for this immature form are scarcely or poorly evaluated. Case Presentation We describe the case of a 31-year-old Caucasian woman with primary infertility, who developed an immature teratoma during an in vitro fertilization ovarian stimulation cycle. Conclusions Ultrasound signs of an atypical cyst during ovarian stimulation allowed us to adopt a careful medical attitude and to adapt the required surgical oncological treatment.

  15. Comparison of luteal estradiol patch and gonadotropin-releasing hormone antagonist suppression protocol before gonadotropin stimulation versus microdose gonadotropin-releasing hormone agonist protocol for patients with a history of poor in vitro fertilization outcomes.

    Science.gov (United States)

    Weitzman, Vanessa N; Engmann, Lawrence; DiLuigi, Andrea; Maier, Donald; Nulsen, John; Benadiva, Claudio

    2009-07-01

    To compare IVF outcomes in poor-responder patients undergoing stimulation after luteal phase E(2) patch/GnRH antagonist (LPG) protocol versus microdose GnRH agonist protocol. Retrospective analysis. University-based IVF center. Forty-five women undergoing ovarian stimulation for IVF using the LPG protocol were compared with 76 women stimulated with the microdose GnRH agonist protocol from May 2005 to April 2006. Cancellation rate, number of oocytes retrieved, and clinical pregnancy rates. The mean number of oocytes (9.1 +/- 4.1 vs. 8.9 +/- 4.3) and mature oocytes (6.7 +/- 3.5 vs. 6.8 +/- 3.1) retrieved were similar, as were the fertilization rates (70.0% +/- 24.2% vs. 69.9% +/- 21.5%) and the number of embryos transferred (2.5 +/- 1.1 vs. 2.7 +/- 1.3). The cancellation rate was not significantly different between the groups (13/45, 28.9% vs. 23/76, 30.3%). Likewise, there were no significant differences among the implantation rate (15.0% vs. 12.5%), clinical pregnancy rate (43.3% vs. 45.1%), and ongoing pregnancy rate per transfer (33.3% vs. 26.0%) between both groups. This study demonstrates that the use of an E(2) patch and a GnRH antagonist during the preceding luteal phase in patients with a history of failed cycles can provide similar IVF outcomes when compared with the microdose GnRH agonist protocol.

  16. Factors that predict a positive response on gonadotropin-releasing hormone stimulation test for diagnosing central precocious puberty in girls

    Directory of Open Access Journals (Sweden)

    Junghwan Suh

    2013-12-01

    Full Text Available PurposeThe rapid increase in the incidence of precocious puberty in Korea has clinical and social significance. Gonadotropin-releasing hormone (GnRH stimulation test is required to diagnose central precocious puberty (CPP, however this test is expensive and time-consuming. This study aimed to identify factors that can predict a positive response to the GnRH stimulation test.MethodsClinical and laboratory parameters, including basal serum luteinizing hormone (LH, follicle-stimulating hormone (FSH, and estradiol (E2, were measured in 540 girls with clinical signs of CPP.ResultsTwo hundred twenty-nine of 540 girls with suspected CPP had a peak serum LH level higher than 5 IU/L (the CPP group. The CPP group had advanced bone age (P<0.001, accelerated yearly growth rate (P<0.001, increased basal levels of LH (P=0.02, FSH (P<0.001, E2 (P=0.001, and insulin-like growth factor-I levels (P<0.001 compared to the non-CPP group. In contrast, body weight (P<0.001 and body mass index (P<0.001 were lower in the CPP group. Although basal LH was significantly elevated in the CPP group compared to the non-CPP group, there was considerable overlap between the 2 groups. Cutoff values of basal LH (0.22 IU/L detected CPP with 87.8% sensitivity and 20.9% specificity.ConclusionNo single parameter can predict a positive response on the GnRH stimulation test with both high sensitivity and specificity. Therefore, multiple factors should be considered in evaluation of sexual precocity when deciding the timing of the GnRH stimulation test.

  17. Comparing the effect of aqueous extract of green tea and catechin on gonadotropins, β-estradiol, Progesterone, testosterone and ovarian follicle in polycystic ovarian syndrome rat model

    Directory of Open Access Journals (Sweden)

    Sayed Damoon Sadoughi

    2017-09-01

    Conclusion: Compared with green tea, catechin has a more favorable effect on improving hormonal parameters, especially FSH hormone and increasing the number of ovarian follicles in rats with polycystic ovary syndrome.

  18. Standardization of androstenedione and estrone radioimmunoassay and profile of sex steroids, gonadotropins and prolactin - in patients with chronic anovulation due to inappropriate feedback (polycystic ovarian syndrome)

    International Nuclear Information System (INIS)

    Vilanova, Maria do Socorro Veras

    1992-01-01

    Full text. In order to evaluate the profile of the sex steroids gonadotropin and prolactin in polycystic ovarian syndrome (POS), 24 patients with POS were studied and compared with 20 normal women during the early follicular phase of the menstrual cycle. Radioimmunoassay techniques for androstenedione (A) and estrone (E 1 ) were standardized for the purpose of the study. Androstenedione and estrone were extracted from plasma with ethyl ether. The assays were maintained in equilibrium and the labelled hormone-antibody complex was then separated from the free hormone using dextran charcoal. The sensitivity of the method was 6.8 pg/tube for A and 3.7 pg/tube for E 1 . Nonspecific binding ws 3.4 for A and 3.3 for E 1 . The interessay error at the D50 level was 15.6 for A and 8.6 for E 1 . Patients with POS had significantly higher basal levels of LH, A, T E 1 and PRL and similar FSH and DHEA-S levels when compared with normal women. The LH/FSH ratio was significantly elevated and the A/T ratio was significantly decreased. The A/E 1 and T/E 2 ratios were elevated and the E 1 /E 2 was decreased, although the differences were not statistically significant. A positive correlation between A and E 1 was observed in patients with POS. In view of the above data, it was concluded that: the quality control parameters of the radioimmunoassay for A and E 1 standardized in the present study are considered satisfactory, and the assay could be used for diagnosis and research; the patients with POS have a different sex steroid and gonadotropin profile when compared normal women during the early follicular phase of the menstrual cycle

  19. Useful predictors of ovarian stimulation response in women undergoing in vitro fertilization

    NARCIS (Netherlands)

    van der Stege, JG; van der Linden, PJQ

    2001-01-01

    Eighty-seven patients undergoing in vitro fertilization were studied to evaluate the prognostic value of different tests in predicting ovarian stimulation response. We studied basal follicle-stimulating hormone (FSH) value on cycle day 3, the clomiphene citrate (CC) challenge test and serum

  20. New stimulation regimens: endogenous and exogenous progesterone use to block the LH surge during ovarian stimulation for IVF.

    Science.gov (United States)

    Massin, Nathalie

    2017-03-01

    The advent of embryo and oocyte vitrification today gives reproductive specialists an opportunity to consider new strategies for improving the practice and results of IVF attempts. As the freezing of entire cohorts does not compromise, and may even improve, the results of IVF attempts, it is possible to break away from the standard sequence of stimulation-retrieval-transfer. The constraints associated with ovarian stimulation in relation to the potential harmful effects of the hormonal environment on endometrial receptivity can be avoided. This review will look at the new stimulation protocols where progesterone is used to block the LH surge. Thanks to 'freeze all' strategies, the increase in progesterone could actually be no longer a cause for concern. There are two ways of using progesterone, whether it be endogenous, as in luteal phase stimulation, or exogenous, as in the use of progesterone in the follicular phase i.e. progestin primed ovarian stimulation. A literature search was carried out (until September 2016) on MEDLINE. The following text words were utilized to generate the list of citations: progestin primed ovarian stimulation, luteal phase stimulation, luteal stimulation, duostim, double stimulation, random start. Articles and their references were then examined in order to identify other potential studies. All of the articles are reported in this review. The use of progesterone during ovarian stimulation is effective in blocking the LH surge, whether endogenous or exogenous, and it does not affect the number of oocytes collected or the quality of the embryos obtained. Its main constraint is that it requires total freezing and delayed transfer. A variety of stimulation protocols can be derived from these two methods, and their implications are discussed, from fertility preservation to ovarian response profiles to organization for the patients and clincs. These new regimens enable more flexibility and are of emerging interest in daily practice. However

  1. Controlled ovarian stimulation with r-FSH plus r-LH vs. HMG plus r-FSH in patients candidate for IVF/ICSI cycles: An RCT

    Directory of Open Access Journals (Sweden)

    Ensieh Shahrokh Tehraninejad

    2017-08-01

    Full Text Available Background: Different combination of gonadotropin preparation has been introduced with no definite superiority of one over others in in vitro fertilization (IVF, but individualized regimens for each patient are needed. Objective: The aim of the present study was to investigate the effect of controlled ovarian stimulation with recombinant- follicle stimulating hormone (r-FSH plus recombinant-luteinizing hormone (rLH versus human menopausal gonadotropin (HMG plus r-FSH on fertility outcomes in IVF patients. Materials and Methods: This is a randomized clinical trial study that was performed from October 2014-April 2016 on 140 infertile patients with a set of inclusion criteria that referred to infertility clinics in Vali- asr and Gandhi Hospital in Tehran. The women were randomly divided into two treatment groups. The first group (n=70 received rFSH from the second day of cycle and was added HMG in 6th day and the 2nd group (n=70, received rFSH from the second day of cycle and was added recombinant-LH in 6th day. Then ovum Pick-Up and embryo transfer were performed. In this study, we assessed the outcomes such as; chemical and clinical pregnancy rate, live birth and abortion rate. Results: Number of follicles in ovaries, total number of oocytes or M2 oocytes and quality of fetuses has no significant differences between two groups (p>0.05. Total number of fetuses were significantly higher in patients who received rFSH + HMG (p=0.02. Fertility outcomes consisted of: live birth rate, chemical pregnancy and clinical pregnancy rate were higher in rFSH + HMG group in comparison to rFSH +r-LH group (p<0.05. Conclusion: It seems that in IVF patients, HMG + rFSH used for controlled ovarian hyperstimulation have better effects on fertility outcomes, but in order to verify the results, it is recommended to implement studies on more patients.

  2. Minimal stimulation protocol using letrozole versus microdose flare up GnRH agonist protocol in women with poor ovarian response undergoing ICSI.

    Science.gov (United States)

    Mohsen, Iman Abdel; El Din, Rasha Ezz

    2013-02-01

    To compare the IVF outcomes of letrozole/antagonist and microdose GnRH agonist flare up protocols in poor ovarian responders undergoing intracytoplasmic sperm injection. A randomized controlled trial was performed in patients with one or more previous failed IVF cycles in which four or less oocytes were retrieved when the gonadotrophin starting dose was at least 300 IU/day. Sixty patients were randomized by computer-generated list to receive either letrozole/antagonist (mild stimulation) n = 30 or GnRH-a protocol (microdose flare) n = 30. Both groups were similar with respect to background and hormonal characteristics (age, duration of infertility, BMI, FSH, LH and E2). The clinical pregnancy rate per cycle was similar in both groups (13.3 vs. 16.6%; OR = 0.769; 95% CI = 0.185, 3.198). The doses of used gonadotropins and the number of stimulation days were significantly lower in the letrozole/antagonist protocol. The peak E2 level on the day of hCG, the endometrial thickness, the retrieved oocytes, the number of fertilized oocytes, the number of transferred embryos and the cancellation rate were statistically similar in both groups. The letrozole/antagonist protocol is a cost-effective and patient-friendly protocol that may be used in poor ovarian responders for IVF/ICSI.

  3. alpha-difluoromethylornithine modifies gonadotropin-releasing hormone release and follicle-stimulating hormone secretion in the immature female rat.

    Science.gov (United States)

    Thyssen, S M; Becú-Villalobos, D; Lacau-Mengido, I M; Libertun, C

    1997-06-01

    Polyamines play an essential role in tissue growth and differentiation, in body weight increment, in brain organization, and in the molecular mechanisms of hormonal action, intracellular signaling, and cell-to-cell communication. In a previous study, inhibition of their synthesis by alpha-difluoromethylornithine (DFMO), a specific and irreversible inhibitor of ornithine decarboxylase, during development in female rats, was followed by prolonged high follicle-stimulating hormone (FSH) serum level and a delayed puberty onset. Those changes were relatively independent of body mass and did not impair posterior fertility. The present work studies the mechanisms and site of action of polyamine participation in FSH secretion during development. DFMO was injected in female rats between Days 1 and 9 on alternate days. At 10 days of age, hypothalami from control and DFMO rats were perifused in vitro, and basal and potassium-induced gonadotropin-releasing hormone (GnRH) release were measured. The response to membrane depolarization was altered in DFMO hypothalami. Increased GnRH release in response to a low K+ concentration was evidenced. Adenohypophyses of the same treated prepubertal rats were perifused in vitro and the response to GnRH pulses was checked. In DFMO-treated rats, higher FSH release was observed, with no changes in LH or PRL secretion. Finally, pituitary GnRH receptor number in adenohypophyseal membranes from treated and control groups was quantified. A significant reduction in specific binding was evident in hypophyses from DFMO-treated rats when compared with binding in the control group. In summary, DFMO treatment in a critical developmental period in the female rat impacts the immature GnRH neuronal network and immature gonadotropes. A delay in maturation is evidenced by a higher sensitivity to secretagogs in both pituitary glands and hypothalamic explants. These events could explain the prolonged high FSH serum levels and delayed puberty onset seen in

  4. Aromatase inhibitors in stimulated IVF cycles

    DEFF Research Database (Denmark)

    Papanikolaou, Evangelos G; Polyzos, Nikolaos P; Al Humaidan, Peter Samir Heskjær

    2011-01-01

    are available regarding their efficacy in IVF stimulated cycles. Current available evidence support that letrozole may have a promising role in stimulated IVF cycles, either when administered during the follicular phase for ovarian stimulation. Especially for women with poor ovarian response, letrozole appears...... to have the potential to increase clinical pregnancy rates when combined with gonadotropins, whereas at the same time reduces the total gonadotropin dose required for ovarian stimulation. However, given that in all of the trials letrozole has been administered in GnRH antagonist cycles, it is intriguing...... to test in the future how it may perform when used in GnRH agonist cycles. Finally administration of letrozole during luteal phase in IVF cycles offers another treatment modality for patients at high risk for OHSS taking into account that it drastically reduces estradiol levels....

  5. Sequential versus simultaneous use of chemotherapy and gonadotropin-releasing hormone agonist (GnRHa) among estrogen receptor (ER)-positive premenopausal breast cancer patients: effects on ovarian function, disease-free survival, and overall survival.

    Science.gov (United States)

    Zhang, Ying; Ji, Yajie; Li, Jianwei; Lei, Li; Wu, Siyu; Zuo, Wenjia; Jia, Xiaoqing; Wang, Yujie; Mo, Miao; Zhang, Na; Shen, Zhenzhou; Wu, Jiong; Shao, Zhimin; Liu, Guangyu

    2018-04-01

    To investigate ovarian function and therapeutic efficacy among estrogen receptor (ER)-positive, premenopausal breast cancer patients treated with gonadotropin-releasing hormone agonist (GnRHa) and chemotherapy simultaneously or sequentially. This study was a phase 3, open-label, parallel, randomized controlled trial (NCT01712893). Two hundred sixteen premenopausal patients (under 45 years) diagnosed with invasive ER-positive breast cancer were enrolled from July 2009 to May 2013 and randomized at a 1:1 ratio to receive (neo)adjuvant chemotherapy combined with sequential or simultaneous GnRHa treatment. All patients were advised to receive GnRHa for at least 2 years. The primary outcome was the incidence of early menopause, defined as amenorrhea lasting longer than 12 months after the last chemotherapy or GnRHa dose, with postmenopausal or unknown follicle-stimulating hormone and estradiol levels. The menstrual resumption period and survivals were the secondary endpoints. The median follow-up time was 56.9 months (IQR 49.5-72.4 months). One hundred and eight patients were enrolled in each group. Among them, 92 and 78 patients had complete primary endpoint data in the sequential and simultaneous groups, respectively. The rates of early menopause were 22.8% (21/92) in the sequential group and 23.1% (18/78) in the simultaneous group [simultaneous vs. sequential: OR 1.01 (95% CI 0.50-2.08); p = 0.969; age-adjusted OR 1.13; (95% CI 0.54-2.37); p = 0.737]. The median menstruation resumption period was 12.0 (95% CI 9.3-14.7) months and 10.3 (95% CI 8.2-12.4) months for the sequential and simultaneous groups, respectively [HR 0.83 (95% CI 0.59-1.16); p = 0.274; age-adjusted HR 0.90 (95%CI 0.64-1.27); p = 0.567]. No significant differences were evident for disease-free survival (p = 0.290) or overall survival (p = 0.514) between the two groups. For ER-positive premenopausal patients, the sequential use of GnRHa and chemotherapy showed ovarian preservation

  6. Ovarian response to recombinant human follicle-stimulating hormone

    DEFF Research Database (Denmark)

    Arce, Joan-Carles; Andersen, Anders Nyboe; Fernández-Sánchez, Manuel

    2014-01-01

    OBJECTIVE: To evaluate the dose-response relationship of a novel recombinant human FSH (rhFSH; FE 999049) with respect to ovarian response in patients undergoing IVF/intracytoplasmic sperm injection treatment; and prospectively study the influence of initial antimüllerian hormone (AMH) concentrat......OBJECTIVE: To evaluate the dose-response relationship of a novel recombinant human FSH (rhFSH; FE 999049) with respect to ovarian response in patients undergoing IVF/intracytoplasmic sperm injection treatment; and prospectively study the influence of initial antimüllerian hormone (AMH...

  7. Using the ovarian sensitivity index to define poor, normal, and high response after controlled ovarian hyperstimulation in the long gonadotropin-releasing hormone-agonist protocol: suggestions for a new principle to solve an old problem.

    Science.gov (United States)

    Huber, Malin; Hadziosmanovic, Nermin; Berglund, Lars; Holte, Jan

    2013-11-01

    To explore the utility of using the ratio between oocyte yield and total dose of FSH, i.e., the ovarian sensitivity index (OSI), to define ovarian response patterns. Retrospective cross-sectional study. University-affiliated private center. The entire unselected cohort of 7,520 IVF/intracytoplasmic sperm injection treatments (oocyte pick-ups [OPUs]) during an 8-year period (long GnRH agonist-recombinant FSH protocol). None. The distribution of the OSI (oocytes recovered × 1,000/total dose of FSH), the cutoff levels for poor and high response, set at ±1 SD, and the relationship between OSI and treatment outcome. OSI showed a log-normal distribution with cutoff levels for poor and high response at 1.697/IU and 10.07/IU, respectively. A nomogram is presented. Live-birth rates per OPU were 10.5 ± 0.1%, 26.9 ± 0.6%, and 36.0 ± 1.4% for poor, normal, and high response treatments, respectively. The predictive power (C-statistic) for OSI to predict live birth was superior to that of oocyte yield. The OSI improves the definition of ovarian response patterns because it takes into account the degree of stimulation. The nomogram presents evidence-based cutoff levels for poor, normal, and high response and could be used for unifying study designs involving ovarian response patterns. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  8. Ovarian and Adrenal Androgens and Their Link to High Human Chorionic Gonadotropin Levels: A Prospective Controlled Study

    Directory of Open Access Journals (Sweden)

    René Rodríguez-Gutiérrez

    2014-01-01

    Full Text Available Background. Although the association between human chorionic gonadotropin (hCG and hyperandrogenism was identified more than 40 years ago, relevant questions remain unanswered. Design and Methods. We conducted a prospective, longitudinal, and controlled study in 23 women with a diagnosis of a complete hydatidiform mole (HM. Results. All participants completed the study. Before HM evacuation mean hCG was markedly higher in the cases than in the control group (P≤0.001. Free testosterone (T and dehydroepiandrosterone sulfate (DHEA-S were found to be higher in the cases (2.78 ± 1.24 pg/mL and 231.50 ± 127.20 μ/dL when compared to the control group (1.50 ± 0.75 pg/mL and 133.59 ± 60.69 μ/dL (P=0.0001 and 0.001, respectively. There was a strong correlation between hCG and free T/total T/DHEA-S concentrations (r=0.78; P≤0.001, r=0.74;  P≤0.001, and r=0.71;  P≤0.001, respectively. In the cases group 48 hours after HM evacuation, hCG levels were found to be significantly lower when compared to initial levels (P=0.001 and free T and DHEA-S declined significantly (P=0.0002 and 0.009. Conclusion. Before uterus evacuation, hCG, free T, and DHEA-S levels were significantly higher when compared with controls finding a strong correlation between hCG and free T/DHEA-S levels. Forty-eight hours after HM treatment hCG levels declined and the difference was lost. A novel finding of our study is that in cases, besides free T, DHEA-S was also found to be significantly higher and both the ovaries and adrenal glands appear to be the sites of this androgen overproduction.

  9. Oocyte mitochondrial deletions and heteroplasmy in a bovine model of ageing and ovarian stimulation.

    Science.gov (United States)

    Hammond, Elizabeth R; Green, Mark P; Shelling, Andrew N; Berg, Martin C; Peek, John C; Cree, Lynsey M

    2016-04-01

    Maternal ageing and ovarian stimulation result in the accumulation of mitochondrial DNA (mtDNA) deletions and heteroplasmy in individual oocytes from a novel bovine model for human assisted reproductive technology (ART). The levels of mtDNA deletions detected in oocytes increased with ovarian ageing. Low levels of mtDNA heteroplasmy were apparent across oocytes and no relationship was identified with respect to ovarian ageing or ovarian stimulation. Oocyte quality decreases with ovarian ageing and it is postulated that the mtDNA may have a role in this decline. The impact of ovarian stimulation on oocyte quality is poorly understood. Human studies investigating these effects are often limited by the use of low quality oocytes and embryos, variation in age and ovarian stimulation regimens within the patients studied, as well as genetic and environmental variability. Further, no study has investigated mtDNA heteroplasmy in individual oocytes using next-generation sequencing (NGS), and little is known about whether the oocyte accumulates heteroplasmic mtDNA mutations following ageing or ovarian stimulation. A novel bovine model for the effect of stimulation and age in human ART was undertaken using cows generated by somatic cell nuclear transfer (SCNT) from one founder, to produce a homogeneous population with reduced genetic and environmental variability. Oocytes and somatic tissues were collected from young (3 years of age; n = 4 females) and old (10 years of age; n = 5 females) cow clones following multiple natural ovarian cycles, as well as oocytes following multiple mild (FSH only) and standard (based on human a long GnRH agonist protocol) ovarian stimulation cycles. In addition, oocytes were recovered in a natural cycle from naturally conceived cows aged 4-13.5 years (n = 10) to provide a heterogeneous cohort for mtDNA deletion studies. The presence or absence of mtDNA deletions were investigated using long-range PCR in individual oocytes (n = 62). To determine

  10. Follicular development and hormonal levels following highly purified or recombinant follicle-stimulating hormone administration in ovulatory women undergoing ovarian stimulation after pituitary suppression for in vitro fertilization: implications for implantation potential.

    Science.gov (United States)

    Balasch, J; Fábregues, F; Creus, M; Peñarrubia, J; Vidal, E; Carmona, F; Puerto, B; Vanrell, J A

    2000-01-01

    The main goal in the present study was to compare follicular development and estradiol levels after ovarian stimulation in pituitary suppressed normally ovulating women undergoing IVF, using highly purified urinary follicle stimulating hormone (FSH) (u-FSH-HP) and recombinant FSH (rec-FSH). A secondary variable in our study was embryo implantation potential, which is closely related to appropriate follicular development and oocyte competence. For the main purpose of this study, 30 IVF patients (group 1) were treated during IVF consecutive cycles, using the same stimulation protocol, with u-FSH-HP in the first treatment study cycle and rec-FSH in the second one. As a control group (group 2) for implantation rates obtained in cycles treated with rec-FSH, 30 additional IVF patients were included who underwent a second IVF attempt again with u-FSH-HP. The total dose of FSH used and ovarian response obtained in terms of estradiol plasma levels and the total number of growing follicles on the day of human chronic gonadotropin (HCG) injection were similar in both treatment cycles in group 1 but better follicular dynamics and oocyte maturity were obtained with rec-FSH. The implantation rate was significantly higher in rec-FSH treated cycles in patients in group 1 than in control women (group 2). rec-FSH is more efficacious than u-FSH-HP when used in the same patient in inducing multiple follicular development in down-regulated cycles as indicated by ovarian performance and oocyte maturity. In addition, rec-FSH yields significantly higher implantation rates than u-FSH-HP when used in patients undergoing their second IVF attempt.

  11. FROM THE CONVENTIONAL TO THE MILDER APPROACHES TO OVARIAN STIMULATION FOR IN VITRO FERTILIZATION

    Directory of Open Access Journals (Sweden)

    Eda Vrtačnik-Bokal

    2018-02-01

    Full Text Available Background: In-vitro fertilization (IVF is performed with oocytes collected in natural and stimulated cycles. Different approaches to ovarian stimulation have been employed worldwide. Fol- lowing the introduction of gonadotrophin realising hormone (GnRH antagonists and strategies to reduce multiple birth such as single embryo transfer, there is an interest in the revival of natural and mild approaches to ovarian stimulation in IVF. Particulary mild ovarian stimulation aims to achieve cost-effective, patient-friendly regimens which optimize the balance between outcomes and risks of treatment. Methods: Pubmed was searched up to 2009 for papers on natural, modified natural, mild and con- ventional IVF cycles. Results: Data discussed in this review do not allow any conclusions to be drawn regarding the most optimal mild ovarian stimulation protocol. However, it is absolutelly clear that introduction of GnRH antagonists into clinical practice has allowed for the introduction of milder stimulation approaches for IVF treatment because of preventing premature luteinising hor- mone (LH rise by competitive blockade of the GnRH receptors. Studies also show that mild exogenous gonadotrophins interference with the decrease in follicle-stimulating hormone ((FSH levels in the mid-folicular phase was sufficient to override the selection of a single dominant follicle and enhance the most mature follicles to growth due to their increased sensitivity for FSH and acquired responsiveness to LH. Conclusions: The implementation of mild stimulation and modified natural cycle into standard clinical practise appears to be justified, although more prospective studies are needed to find the most appropriate mild stimulation approaches.

  12. Does methotrexate administration for ectopic pregnancy after in vitro fertilization impact ovarian reserve or ovarian responsiveness?

    Science.gov (United States)

    Boots, Christina E; Gustofson, Robert L; Feinberg, Eve C

    2013-12-01

    To evaluate the effects of methotrexate (MTX) on the future fertility of women undergoing IVF by comparing ovarian reserve and ovarian responsiveness in the IVF cycle before and after an ectopic pregnancy (EP) treated with MTX. Retrospective cohort study. Private reproductive endocrinology and infertility practice. Sixty-six women undergoing IVF before and after receiving MTX for an EP. Methotrexate administration and ovarian stimulation. Markers of ovarian reserve (day 3 FSH, antral follicle count), measures of ovarian responsiveness (duration of stimulation, peak E2 level, total dose of gonadotropins, number of oocytes retrieved, fertilization rate), and time from MTX administration to subsequent IVF cycle. There were no differences after MTX administration in body mass index (BMI), FSH, or antral follicle count. A greater dose of gonadotropins was used in the cycle after MTX, but there were no differences in numbers of oocytes retrieved or high quality embryos transferred. As expected, there was a slight increase in age in the subsequent IVF cycle. The pregnancy rates (PR) were comparable to the average PRs within the practice when combining all age groups. Methotrexate remains the first line of therapy for medical management of asymptomatic EP and does not compromise ovarian reserve, ovarian responsiveness, or IVF success in subsequent cycles. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  13. Follicle-stimulating hormone to substitute equine chorionic gonadotropin in the synchronization of ovulation in Santa Inês ewes

    Directory of Open Access Journals (Sweden)

    Bianor Matias Cardoso Neto

    2012-03-01

    Full Text Available The substitution of equine chorionic gonadotropin (eCG by follicle-stimulating hormone (FSH in protocols for synchronization of ovulation in Santa Inês ewes was assessed. Ten females were submitted to the insertion of intravaginal sponges containing 60 mg medroxyprogesterone acetate for 10 days; after this period sponges were withdrawn and the animals were randomly divided into two groups. Group 1 (n = 5: intramuscular injection of 0.5 mL d-cloprostenol and 300 UI eCG; Group 2 (n = 5: intramuscular injection of 0.5 mL d-cloprostenol and 20 mg FSH. Interval between sponge withdrawal and estrus beginning was 27.7 h and 35.9 h for eCG and FSH, respectively. Interval between sponge withdrawal and the end of estrus was 55.8 h for eCG treatment and 55.6 h for FSH treatment. Estrus length was 29.3 h and 19.6 h, for eCG and FSH treatments, respectively. The biggest follicle and the second in size measured 0.74 cm and 0.54 cm for eCG treatment, whereas for the FSH treatment they measured 0.73 and 0.50 cm. The interval between the beginning of estrus and ovulation was similar within all groups: 21.0 h for eCG treated ewes and 25.2 h for the ones treated with FSH. Ewes treated with eCG presented an interval of 47.5 h between sponge withdrawal and ovulation, while the ones treated with FSH presented a 61.1 h interval. Ovulation occurred 8.3 h before the end of estrus in the eCG group. On the other hand, ewes treated with FSH ovulated 5.5 h after the end of estrus. Estrus and ovulation were efficiently synchronized in Santa Inês ewes by using long-term progestogen protocol associated to the administration of 20 mg FSH, along with Prostaglandin F2α (PGF2α at the moment of sponge withdrawal, thus substituting the use of eCG.

  14. Perinatal outcome in singletons after modified natural cycle IVF and standard IVF with ovarian stimulation

    NARCIS (Netherlands)

    Pelinck, Marie-Jose; Keizer, Marjan H.; Hoek, Annemieke; Simons, Arnold H. M.; Schelling, Karin; Middelburg, Karin; Heineman, Maas Jan

    Objective: Singletons born after IVF treatment are at risk for adverse pregnancy outcome, the cause of which is unknown. The aim of the present study was to investigate the influence of ovarian stimulation on perinatal outcome. Study design: In this single-centre retrospective study, perinatal

  15. Perinatal outcome in singletons after modified natural cycle IVF and standard IVF with ovarian stimulation

    NARCIS (Netherlands)

    Pelinck, Marie-José; Keizer, Marjan H.; Hoek, Annemieke; Simons, Arnold H. M.; Schelling, Karin; Middelburg, Karin; Heineman, Maas Jan

    2010-01-01

    Objective: Singletons born after IVF treatment are at risk for adverse pregnancy outcome, the cause of which is unknown. The aim of the present study was to investigate the influence of ovarian stimulation on perinatal outcome. Study design: In this single-centre retrospective study, perinatal

  16. Risk of Colorectal Cancer After Ovarian Stimulation for In Vitro Fertilization

    NARCIS (Netherlands)

    Spaan, M.; Belt-Dusebout, A.W. van den; Burger, C.W.; Leeuwen, F.E. van; Schats, R.; Lambalk, C.B.; Kortman, M.; Laven, J.S.E.; Jansen, C.A.; Westerlaken, L.A. van der; Cohlen, B.J.; Braat, D.D.M.; Smeenk, J.M.; Land, J.A.; Veen, F. van der; Evers, J.L.; Rumste, M.M. van

    2016-01-01

    BACKGROUND & AIMS: Apart from lifestyle factors, sex hormones also seem to have a role in the etiology of colorectal cancer. This raises interest in the possible effects of fertility drugs, especially because the use of ovarian stimulation for in vitro fertilization (IVF) has strongly increased over

  17. Risk of Colorectal Cancer After Ovarian Stimulation for In Vitro Fertilization

    NARCIS (Netherlands)

    Spaan, Mandy; van den Belt-Dusebout, Alexandra W.; Burger, Curt W.; van Leeuwen, Flora E.; Land, Jolande A.

    BACKGROUND & AIMS: Apart from lifestyle factors, sex hormones also seem to have a role in the etiology of colorectal cancer. This raises interest in the possible effects of fertility drugs, especially because the use of ovarian stimulation for in vitro fertilization (IVF) has strongly increased over

  18. Selective use of corifollitropin for controlled ovarian stimulation for IVF in patients with low anti-Müllerian hormone

    DEFF Research Database (Denmark)

    Nielsen, Anna Pors; Korsholm, Anne-Sofie; Lemmen, Josephine G.

    2016-01-01

    Corifollitropin, a long-acting follicle-stimulating hormone (FSH) analogue used for in vitro fertilization (IVF), does not allow individualization of dosage, and the ovarian response is similar to around 300 IU of daily recombinant FSH. This has raised concerns about the risk of ovarian hyperstim......Corifollitropin, a long-acting follicle-stimulating hormone (FSH) analogue used for in vitro fertilization (IVF), does not allow individualization of dosage, and the ovarian response is similar to around 300 IU of daily recombinant FSH. This has raised concerns about the risk of ovarian...

  19. Effects on steroid hormones secretion resulting from the acute stimulation of sectioning the superior ovarian nerve to pre-pubertal rats

    Directory of Open Access Journals (Sweden)

    Morales-Ledesma Leticia

    2012-10-01

    Full Text Available Abstract In the adult rat, neural signals arriving to the ovary via the superior ovarian nerve (SON modulate progesterone (P4, testosterone (T and estradiol (E2 secretion. The aims of the present study were to analyze if the SON in the pre-pubertal rat also modulates ovarian hormone secretion and the release of follicle stimulating hormone (FSH and luteinizing (LH hormone. P4, T, E2, FSH and LH serum levels were measured 30 or 60 minutes after sectioning the SON of pre-pubertal female rats. Our results indicate that the effects on hormone levels resulting from unilaterally or bilaterally sectioning the SON depends on the analyzed hormone, and the time lapse between surgery and autopsy, and that the treatment yielded asymmetric results. The results also suggest that in the pre-pubertal rat the neural signals arriving to the ovaries via the SON regulate the enzymes participating in P4, T and E2 synthesis in a non-parallel way, indicating that the mechanisms regulating the synthesis of each hormone are not regulated by the same signals. Also, that the changes in the steroids hormones are not explained exclusively by the modifications in gonadotropins secretion. The observed differences in hormone levels between rats sacrificed 30 and 60 min after surgery reflect the onset of the compensatory systems regulating hormones secretion.

  20. The pregnancy outcome of progestin-primed ovarian stimulation using 4 versus 10 mg of medroxyprogesterone acetate per day in infertile women undergoing in vitro fertilisation: a randomised controlled trial.

    Science.gov (United States)

    Dong, J; Wang, Y; Chai, W R; Hong, Q Q; Wang, N L; Sun, L H; Long, H; Wang, L; Tian, H; Lyu, Q F; Lu, X F; Chen, Q J; Kuang, Y P

    2017-06-01

    To investigate the clinical outcome and endocrinological characteristics of progestin-primed ovarian stimulation (PPOS) using 4 versus 10 mg of medroxyprogesterone acetate (MPA) per day in infertile women with normal ovary reserve. A randomised parallel controlled trial. Tertiary-care academic medical centre. A cohort of 300 infertile women undergoing in vitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI) treatment. Human menopausal gonadotropin (hMG; 225 iu per day) and MPA (group A, 10 mg per day; group B, 4 mg per day) were started simultaneously from cycle day 3 onwards. Ovulation was co-triggered by human chorionic gonadotropin (hCG; 1000 iu) and gonadotropin-releasing hormone agonist (GnRH agonist; 0.1 mg) when dominant follicles matured. Viable embryos were cryopreserved for later frozen embryo transfer (FET) in both groups. The primary outcome measure was the number of oocytes retrieved. Secondary outcomes included the incidence of a premature surge in luteinising hormone (LH), the number of viable embryos, and clinical pregnancy outcomes. The number of oocytes retrieved and viable embryos were similar between two groups (9.8 ± 6.3 versus 9.6 ± 5.9; 4.2 ± 2.6 versus 3.7 ± 3.0; P > 0.05). No significant difference was found in clinical pregnancy rate (58.0 versus 48.7%) and live birth rate per participant (48.7 versus 42.0%; P > 0.05). No premature LH surge and ovarian hyperstimulation syndrome (OHSS) occurred in either group. Progestin-primed ovarian stimulation (PPOS) using 4 or 10 mg of MPA per day was comparable in terms of the number of oocytes retrieved and pregnancy outcome after FET. The administration of 4 mg of MPA per day was sufficient to prevent an untimely LH rise in women undergoing IVF/ICSI treatment. An RCT confirmed similar pregnancy outcome in P-primed ovarian stimulation with a daily dose of 4 or 10 mg MPA. © 2017 Royal College of Obstetricians and Gynaecologists.

  1. Investigating the association between polymorphism of follicle-stimulating hormone receptor gene and ovarian response in controlled ovarian hyperstimulation

    Directory of Open Access Journals (Sweden)

    Mohammad Hasan Sheikhha

    2011-01-01

    Full Text Available Aim : The aim of the study was to investigate the association between follicle-stimulating hormone receptor (FSHR gene polymorphism at Position 680 and the outcomes of controlled ovarian hyperstimulation for in vitro fertilization and embryo transfer (IVF-ET in infertile women. Materials and Methods : One hundred and eight patients under 35 years of age who underwent IVF-ET procedures were included in this study. The hormonal profile and treatment of all patients were analyzed and FSHR polymorphism was examined by polymerase chain reaction-restriction fragment length polymorphism. Women from all groups were classified based on polymorphisms at Position 680, occupied either by asparagines (Asn or serine (Ser as Asn/Asn, Asn/Ser, and Ser/Ser genotype. Result : Our study showed that all patients in the Asn/Asn group were normal responders and in the Asn/Ser group 64.8% were normal responders and 21.1% and 14.1% were poor and hyper responders respectively. In the Ser/Ser group we did not have normal responders and 46.7% of these patients were poor responders and 53.3% were hyper responders. Conclusion : FSH receptor polymorphism is correlated with response to ovarian stimulation.

  2. Repeat dose of gonadotropin-releasing hormone agonist trigger in polycystic ovarian syndrome undergoing In Vitro fertilization cycles provides a better cycle outcome - a proof-of-concept study

    Directory of Open Access Journals (Sweden)

    Krishna Deepika

    2017-01-01

    Full Text Available Objective: Is a single dose of gonadotropin-releasing hormone agonist (GnRHa trigger to induce final oocyte maturation in polycystic ovarian syndrome (PCOS undergoing in vitro fertilization (IVF cycles with GnRH antagonist protocol sufficient to provide optimal oocyte maturity? Design: This is a prospective, randomized, double-blind, proof-of-concept study. Setting: This study was carried out at a tertiary care center. Material and Methods: A total of 125 patients diagnosed with PCOS defined as per the ESHRE/ASRM Rotterdam criteria (2003 undergoing IVF in antagonist protocol were randomized into two groups. Group A: single dose of GnRHa 0.2 mg, 35 h prior to oocyte retrieval, and Group B: 0.2 mg GnRHa 35 h prior to oocyte retrieval + repeat dose of 0.1 mg 12 h following the 1st dose. 12 h post-trigger, luteinizing hormone (LH, progesterone (P4, and follicle-stimulating hormone (FSH values were estimated. Statistical Analysis: Continuous variables were expressed as mean ± standard deviation and categorical variables as proportions where applicable. Independent sample t-test was used for continuous variables which were normally distributed and Mann–Whitney U-test for data not normally distributed. Chi-square test or Fisher's exact test was used for categorical variables where appropriate. Odds ratio (OR with 95% confidence intervals (CIs was calculated. In addition, receiver operating characteristic curve was used to evaluate the post-trigger LH, P4, and FSH values at 12 h as predictors of oocyte maturity. Main Outcome Measures: Primary outcome: maturity rate of the oocytes. Secondary outcomes: oocyte yield, fertilization rate, availability of good quality embryos on day 3, blastocyst conversion, OHSS rates, post-trigger serum LH (IU/L, FSH (IU/L, and P4 (ng/mL levels implantation rate and clinical pregnancy rate. Results: A higher number of mature (metaphase II oocytes were obtained in Group B compared to Group A (OR of 0.47; CI: 0.38–0

  3. Hepatocyte growth factor secreted by ovarian cancer cells stimulates peritoneal implantation via the mesothelial-mesenchymal transition of the peritoneum.

    Science.gov (United States)

    Nakamura, Michihiko; Ono, Yoshihiro J; Kanemura, Masanori; Tanaka, Tomohito; Hayashi, Masami; Terai, Yoshito; Ohmichi, Masahide

    2015-11-01

    A current working model for the metastatic process of ovarian carcinoma suggests that cancer cells are shed from the ovarian tumor into the peritoneal cavity and attach to the layer of mesothelial cells that line the inner surface of the peritoneum, and several studies suggest that hepatocyte growth factor (HGF) plays an important role in the dissemination of ovarian cancer. Our objectives were to evaluate the HGF expression of ovarian cancer using clinical data and assess the effect of HGF secreted from human ovarian cancer cells to human mesothelial cells. HGF expression was immunohistochemically evaluated in 165 epithelial ovarian cancer patients arranged as tissue microarrays. HGF expression in four ovarian cancer cell lines was evaluated by using semi-quantitative polymerase chain reaction, Western blotting and enzyme-linked immunosorbent assay. The effect of ovarian cancer cell derived HGF to the human mesothelial cells was assessed by using morphologic analysis, Western blotting and cell invasion assay. The effect of HGF on ovarian cancer metastasis was assessed by using in vivo experimental model. The clinical data showed a significantly high correlation between the HGF expression and the cancer stage. The in vivo and in vitro experimental models revealed that HGF secreted by ovarian cancer cells induces the mesothelial-to-mesenchymal transition and stimulates the invasion of mesothelial cells. Furthermore, manipulating the HGF activity affected the degree of dissemination and ascite formation. We demonstrated that HGF secreted by ovarian cancer cells plays an important role in cancer peritoneal implantation. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Highly purified HMG versus recombinant FSH for ovarian stimulation in IVF cycles

    DEFF Research Database (Denmark)

    Platteau, P.; Nyboe, Andersen A.; Loft, A.

    2008-01-01

    The objective of this study was to compare the live birth rates resulting from ovarian stimulation with highly purified human menopausal gonadotrophin (HP-HMG), which combines FSH and human chorionic gonadotrophin-driven LH activities, or recombinant FSH (rFSH) alone in women undergoing IVF cycles....... An integrated analysis was performed of the raw data from two randomized controlled trials that were highly comparable in terms of eligibility criteria and post-randomization treatment regimens with either HP-HMG or rFSH for ovarian stimulation in IVF, following a long down-regulation protocol. All randomized...... subjects who received at least one dose of gonadotrophin in an IVF cycle (HP-HMG, n = 491; rFSH, n = 495) were included in the analysis. Subjects who underwent intracytoplasmic sperm injection cycles were excluded. The superiority of one gonadotrophin preparation over the other was tested using...

  5. Effect of endometrial biopsy on intrauterine insemination outcome in controlled ovarian stimulation cycle

    OpenAIRE

    Wadhwa, Leena; Pritam, Amrita; Gupta, Taru; Gupta, Sangeeta; Arora, Sarika; Chandoke, Rajkumar

    2015-01-01

    OBJECTIVE: The objective was to evaluate the effect of endometrial biopsy (EB) on intrauterine insemination (IUI) outcome in controlled ovarian stimulation (COS) cycle. DESIGN: Prospective randomized control study. SETTING: Tertiary care center. MATERIALS AND METHODS: A total of 251 subjects were enrolled in the study. Subjects undergoing COS with IUI were randomly allocated into three groups. Group A: EB was taken between D19 and 24 of the spontaneous menstrual cycles that precedes the ferti...

  6. Promotion of ovarian follicle growth following mTOR activation: synergistic effects of AKT stimulators.

    Directory of Open Access Journals (Sweden)

    Yuan Cheng

    Full Text Available Mammalian target of rapamycin (mTOR is a serine/threonine kinase and mTOR signaling is important in regulating cell growth and proliferation. Recent studies using oocyte- and granulosa cell-specific deletion of mTOR inhibitor genes TSC1 or TSC2 demonstrated the important role of mTOR signaling in the promotion of ovarian follicle development. We now report that treatment of ovaries from juvenile mice with an mTOR activator MHY1485 stimulated mTOR, S6K1 and rpS6 phosphorylation. Culturing ovaries for 4 days with MHY1485 increased ovarian explant weights and follicle development. In vivo studies further demonstrated that pre-incubation of these ovaries with MHY1485 for 2 days, followed by allo-grafting into kidney capsules of adult ovariectomized hosts for 5 days, led to marked increases in graft weights and promotion of follicle development. Mature oocytes derived from MHY1485-activated ovarian grafts could be successfully fertilized, leading the delivery of healthy pups. We further treated ovaries with the mTOR activator together with AKT activators (PTEN inhibitor and phosphoinositol-3-kinase stimulator before grafting and found additive enhancement of follicle growth. Our studies demonstrate the ability of an mTOR activator in promoting follicle growth, leading to a potential strategy to stimulate preantral follicle growth in infertile patients.

  7. Overnight Levels of Luteinizing Hormone, Follicle-Stimulating Hormone and Growth Hormone before and during Gonadotropin-Releasing Hormone Analogue Treatment in Short Boys Born Small for Gestational Age

    NARCIS (Netherlands)

    van der Kaay, Danielle C. M.; de Jong, Frank H.; Rose, Susan R.; Odink, Roelof J. H.; Bakker-van Waarde, Willie M.; Sulkers, Eric J.; Hokken-Koelega, Anita C. S.

    2009-01-01

    Aims: To evaluate if 3 months of gonadotropin-releasing hormone analogue (GnRHa) treatment results in sufficient suppression of pubertal luteinizing hormone (LH) and follicle-stimulating hormone (FSH) profile patterns in short pubertal small for gestational age (SGA) boys. To compare growth hormone

  8. Effect of chronic exposure to gamma radiation and of hormonal stimulation with serum gonadotropin on catecholamine levels in hypothalamus, epiphysis and adrenals of ewes

    International Nuclear Information System (INIS)

    Pastorova, B.; Arendarcik, J.

    1989-01-01

    The effects were studied of exposure to whole body continuous irradiation and of the administration of serum gonadotropin (SG) on the concentration of catecholamines (epinephrine and norepinephrine) in the hypothalamus, epiphysis and adrenal glands of ewes during the anestric period with synchronized estrus. The first group (young barren ewes) and second group (older ewes) were exposed to continuous radiation of 60 Co for five days. The radiation was applied at a rate of 0.020 Gy per hour. After the termination of irradiation the ewes were subjected to hormonal stimulation by fractionated administration of 1500 I.U. SG. The third and fourth experimental groups of ewes were stimulated with 1500 I.U. SG without irradiation. Catecholamines were separated from the tissue supernatants by adsorption chromatography and the catecholamine contents in the eluates were determined spectrofluorometrically. Chronic exposure to gamma radiation and hormonal stimulation with SG reduced the concentration of norepinephrine in the whole hypothalamus of the sheep. A statistically significant decrease (P<0.001) was recorded in the medial and caudal hypothalamus of the adult ewes and in the rostral and caudal hypothalamus regions of the young ewes. A decrease in norepinephrine concentration, statistically significant in the caudal (P<0.01) and medial hypothalamus was recorded in the group of adult ewes after hormonal stimulation with SG without irradiation. The experimental group of young ewes responded to hormonal stimulation by a greater reduction of norepinephrine contents as compared with combined exposure to radiation and hormonal stimulation. It is assumed that the decrease in catecholamine concentration after hormonal stimulation with SG is associated with the increase in the contents of estrogens which act on the adrenergic receptors of the hypothalamus. (author). 4 figs., 21 refs

  9. Increase of antitumor activity of cisplatin using agonist of gonadotropin-realising hormone and inhibitor of aromatase on the model of ascites ovarian tumor.

    Science.gov (United States)

    Tkalia, I G; Vorobyova, L I; Grabovoy, A N; Svintsitsky, V S; Tarasova, T O; Lukyanova, N Y; Todor, I N; Chekhun, V F

    2014-09-01

    To study antitumor activity of triptorelin - agonist of gonadotropin-releasing hormone and exemestane - inhibitor of aromatase in monotherapy and in combination with cisplatin on the model of receptor-positive for estrogens and progesterone malignant ascites transplantable ovarian tumor (TOT), to assess therapeutic pathomorphosis and level of VEGF expression in tumor cells using diffe-rent combinations of cytostatics and hormonal drugs. 72 female Wistar rats, which underwent intraperitoneal transplantation of ascitic TOT, by 5·10(6) cells per animal, have been involved in the study. Rats were divided into 8 groups, 9 rats in each group. Histological study with assessment of therapeutic pathomorphosis in TOT and immunohistochemical study has been carried out. Survival of animals in the studied groups has been evaluated. Among animals treated in regimen of monotherapy, the most pronounced antiangiogenic activity in TOT has been observed on application of hormonal drugs (triptorelin - 39.4 ± 1.9 and exemestane - 33.9 ± 1.4%; р = 0.003), the highest grade of treatment pathomorphosis in TOT has been observed at treatment with cisplatin (11.7%; р = 0.001). Combination of triptorelin and exemestane has amplified antiangiogenic activity in TOT (12.2 ± 0.9%; р = 0.001), but has not significantly changed rates of pathomorphosis (22.1 ± 0.4%; р=0.005) and survival of animals (32.2%; р = 0.007) as compared with the same rates in rats treated with hormonal drugs in monotherapy. Significant correlation between VEGF expression and pathomorphosis has been established (relative part of viable tumor tissue (RPVTT)) in TOT (r = 0.712; р = 0.001), as well as between RPVTT and life-span of animals (r = -0.320; р = 0.007). However, lack of correlation between VEGF expression in cells of TOT and survival of rats has been determined (r = -0.194; р = 0.11). Combination of cytostatic agent with triptorelin or exemestane has demonstrated significantly high rates of therapeutic

  10. Mechanisms and Chemoprevention of Ovarian Carcinogenesis

    National Research Council Canada - National Science Library

    Cvetkovic, Dusica

    2008-01-01

    .... We have demonstrated that DMBAinduced mutagenesis in the rat ovary, combined with gonadotropin hormone-mediated enhanced mitogenesis of the ovarian surface epithelium, produces lesions ranging...

  11. South Asian women with polycystic ovary syndrome exhibit greater sensitivity to gonadotropin stimulation with reduced fertilization and ongoing pregnancy rates than their Caucasian counterparts.

    Science.gov (United States)

    Palep-Singh, M; Picton, H M; Vrotsou, K; Maruthini, D; Balen, A H

    2007-10-01

    Polycystic ovary syndrome (PCOS) is a heterogeneous syndrome. In vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) is required for PCOS cases that are refractory to standard ovulation induction or have co-existing infertility factors in women with PCOS and Tubal factor subfertility. Assess ethnic variations in response to IVF/ICSI treatment. Observational Comparative study in a University hospital fertility clinic in women with PCOS and Tubal factor subfertility. Women with PCOS (Asians: AP=104; Caucasians: CP=220) and those with tubal factor infertility seeking fertility treatment were assessed (Asians: AC=84; Caucasians: CC=200). Six hundred and eight fresh IVF or ICSI cycles using long protocol of GnRHa suppression and resulting in a fresh embryo transfer were compared. The primary endpoint was to assess the dose of gonadotropins used in the cycles. The secondary outcomes were: total number of oocytes retrieved, fertilization and ongoing clinical pregnancy rates. We found that the South Asian women presented at a younger age for the management of sub-fertility. An extended stimulation phase and Caucasian ethnicity showed an inverse correlation with the number of oocytes retrieved in the PCOS subgroup. Caucasian ethnicity was associated with a higher fertilization rate however increase in body mass index (BMI) and the laboratory technique of IVF appeared to have a negative impact on fertilization rates in the PCOS subgroup. Commencing down regulation on day 1 of the cycles was negatively associated with fertilization rates in the tubal group. In terms of clinical pregnancy rates, the Caucasian PCOS had a 2.5 times (95% CI: 1.25-5) higher chance of an ongoing clinical pregnancy as compared with their Asian counterpart. Also, a unit increase in the basal FSH concentration reduced the odds of pregnancy by 18.6% (95% CI: 1.8-32.6%) in the PCOS group. The Asian PCOS have a greater sensitivity to gonadotropin stimulation with lower fertilization and

  12. Comparison of letrazole and Clomiphene Citrate in Women with Polycystic Ovaries Undergoing Ovarian Stimulation

    International Nuclear Information System (INIS)

    Sharief, M.; Nafee, N. R.

    2015-01-01

    Objective: To compare the efficacy of letrazole in the induction of ovulation with clomiphene citrate in patients with polycystic ovary syndrome and primary infertility. Methods: The prospective clinical trial was conducted at Basrah Maternity and Child Hospital, Basrah, Iraq, between January 2012 and April 2013, and comprised women with polycystic ovarian syndrome and primary infertility who were randomised into 2 groups. Group A received 100-200mg clomiphene citrate daily while group 2 received letrazole (2.5-5mg) daily. Both groups were followed by ultrasound until the dominant follicle reached a diameter >18mm, human chorionic gonadotropin10.000 U/L was given and timed intercourse was advised. Results: Of the 75 subjects in the study, 40(53.3 percent) were in group A and 35(46.6 percent) in group B. The mean age in group A was 25.3+2.1 years versus 26.1+1.3 years in group B (p=0.05). The number of mature follicles was significantly lower, but the endometrial thickness and ovulation were significantly higher in group B than in group A (p<0.05 each). There was no significant difference in pregnancy rate between the two groups (p>0.05). Conclusion: Letrazole may have a role as the first-line treatment for unovulatory patients with polycystic ovary syndrome. (author)

  13. IVF with planned single-embryo transfer versus IUI with ovarian stimulation in couples with unexplained subfertility: an economic analysis.

    Science.gov (United States)

    van Rumste, Minouche M E; Custers, Inge M; van Wely, Madelon; Koks, Carolien A; van Weering, Hans G I; Beckers, Nicole G M; Scheffer, Gabrielle J; Broekmans, Frank J M; Hompes, Peter G A; Mochtar, Monique H; van der Veen, Fulco; Mol, Ben W J

    2014-03-01

    Couples with unexplained subfertility are often treated with intrauterine insemination (IUI) with ovarian stimulation, which carries the risk of multiple pregnancies. An explorative randomized controlled trial was performed comparing one cycle of IVF with elective single-embryo transfer (eSET) versus three cycles of IUI-ovarian stimulation in couples with unexplained subfertility and a poor prognosis for natural conception, to assess the economic burden of the treatment modalities. The main outcome measures were ongoing pregnancy rates and costs. This study randomly assigned 58 couples to IVF-eSET and 58 couples to IUI-ovarian stimulation. The ongoing pregnancy rates were 24% in with IVF-eSET versus 21% with IUI-ovarian stimulation, with two and three multiple pregnancies, respectively. The mean cost per included couple was significantly different: €2781 with IVF-eSET and €1876 with IUI-ovarian stimulation (Pcosts per ongoing pregnancy were €2456 for IVF-eSET. In couples with unexplained subfertility, one cycle of IVF-eSET cost an additional €900 per couple compared with three cycles of IUI-ovarian stimulation, for no increase in ongoing pregnancy rates or decrease in multiple pregnancies. When IVF-eSET results in higher ongoing pregnancy rates, IVF would be the preferred treatment. Couples that have been trying to conceive unsuccessfully are often treated with intrauterine insemination (IUI) and medication to improve egg production (ovarian stimulation). This treatment carries the risk of multiple pregnancies like twins. We performed an explorative study among those couples that had a poor prognosis for natural conception. One cycle of IVF with transfer of one selected embryo (elective single-embryo transfer, eSET) was compared with three cycles of IUI-ovarian stimulation. The aim of this study was to assess the economic burden of both treatments. The Main outcome measures were number of good pregnancies above 12weeks and costs. We randomly assigned 58

  14. Circulating basal anti-Müllerian hormone levels as predictor of ovarian response in women undergoing ovarian stimulation for in vitro fertilization.

    Science.gov (United States)

    Nardo, Luciano G; Gelbaya, Tarek A; Wilkinson, Hannah; Roberts, Stephen A; Yates, Allen; Pemberton, Phil; Laing, Ian

    2009-11-01

    To evaluate the clinical value of basal anti-Müllerian hormone (AMH) measurements compared with other available determinants, apart from chronologic age, in the prediction of ovarian response to gonadotrophin stimulation. Prospective cohort study. Tertiary referral center for reproductive medicine and an IVF unit. Women undergoing their first cycle of controlled ovarian hyperstimulation (COH) for in vitro fertilization (IVF). Basal levels of FSH and AMH as well as antral follicle count (AFC) were measured in 165 subjects. All patients were followed prospectively and their cycle outcomes recorded. Predictive value of FSH, AMH, and AFC for extremes of ovarian response to stimulation. Out of the 165 women, 134 were defined as normal responders, 15 as poor responders, and 16 as high responders. Subjects in the poor response group were significantly older then those in the other two groups. Anti-Müllerian hormone levels and AFC were markedly raised in the high responders and decreased in the poor responders. Compared with FSH and AFC, AMH performed better in the prediction of excessive response to ovarian stimulation-AMH area under receiver operating characteristic curve (ROC(AUC)) 0.81, FSH ROC(AUC) 0.66, AFC ROC(AUC) 0.69. For poor response, AMH (ROC(AUC) 0.88) was a significantly better predictor than FSH (ROC(AUC) 0.63) but not AFC (ROC(AUC) 0.81). AMH prediction of ovarian response was independent of age and PCOS. Anti-Müllerian hormone cutoffs of >3.75 ng/mL and stimulation with exogenous gonadotrophins. Overall, this biomarker is superior to basal FSH and AFC, and has the potential to be incorporated in to work-up protocols to predict patient's ovarian response to treatment and to individualize strategies aiming at reducing the cancellation rate and the iatrogenic complications of COH.

  15. Evidence that obesity and androgens have independent and opposing effects on gonadotropin production from puberty to maturity

    Science.gov (United States)

    Rosenfield, Robert L; Bordini, Brian

    2010-01-01

    Optimal fat mass is necessary for normal gonadotropin levels in adults, and both undernutrition and overnutrition suppress gonadotropins: thus, the gonadotropin response to relative adipose mass is biphasic. Adult obesity is associated with blunted luteinizing hormone (LH) pulse amplitude that is partially attributable to increased LH clearance rate. Testosterone appears to have a biphasic effect on gonadotropin production in females. Moderate elevations of testosterone appear to stimulate LH production at both the hypothalamic and pituitary level, while very high levels of testosterone suppress LH. Thus, obesity per se appears to suppress gonadotropin production, and moderate hyperandrogenemia in women appears to stimulate LH. The ordinary hypergonadotropic hyperandrogenism of obese women appears to be an exception to this model because it is usually due to polycystic ovary syndrome (PCOS), a condition in which intrinsic functional ovarian hyperandrogenism and excess adiposity share a common origin that involves insulin-resistant hyperinsulinemia. LH elevation seems to be secondary to hyperandrogenemia and is absent in the most obese cases. Overweight early pubertal girls have significant blunting of sleep-related LH production, which is the first hormonal change of puberty. The data are compatible with the possibility that excess adiposity may paradoxically subtly suppress hypothalamic-pituitary-gonadal function in early puberty although it is known to contribute to the early onset of puberty. PMID:20816944

  16. Random start ovarian stimulation for fertility preservation appears unlikely to delay initiation of neoadjuvant chemotherapy for breast cancer.

    Science.gov (United States)

    Letourneau, Joseph M; Sinha, Nikita; Wald, Kaitlyn; Harris, Eve; Quinn, Molly; Imbar, Tal; Mok-Lin, Evelyn; Chien, A Jo; Rosen, Mitchell

    2017-10-01

    Is random start ovarian stimulation associated with delays in initiation of neoadjuvant chemotherapy for breast cancer? Among women who complete fertility preservation (FP) consultation, random start ovarian stimulation is unlikely to delay time to initiation of neoadjuvant chemotherapy start. Neoadjuvant chemotherapy is now a widely accepted treatment modality for operable breast cancer and random start ovarian stimulation is an increasingly-utilized modality for FP. While conventional ovarian stimulation does not appear to delay starting adjuvant chemotherapy, the relationship between random start ovarian stimulation and neoadjuvant chemotherapy start is not well-understood. Cross-sectional study of all women seen between from January 2011 to April 2017 for FP consultation prior to starting neoadjuvant chemotherapy for breast cancer. A chart-review was performed. Study inclusion criteria were female sex; age 18-45; non-metastatic breast cancer diagnosis; underwent FP consultation; underwent neoadjuvant chemotherapy. Referrals for FP evaluation came from a regional referral base of oncology clinics. Various time-points related to cancer diagnosis, FP or chemotherapy were obtained from medical record review. We compared time-points between those who underwent ovarian stimulation for FP versus those who did not using T-tests and linear modeling. A total of 89 women who had FP consultation prior to neoadjuvant chemotherapy were identified. Sixty-seven percent underwent ovarian stimulation prior to cancer treatment and 33% did not. Women who underwent ovarian stimulation were similar in parity and clinical cancer stage to those who did not. Overall, the average time from cancer diagnosis to chemotherapy start was similar between the group that did undergo ovarian stimulation and those who did not (38.1 ± 11.3 versus 39.4 ± 18.5 days, P = 0.672). Those that underwent ovarian stimulation were referred 9.4 ± 6.8 days after diagnosis versus 17.9 ± 15.3 days for those

  17. Hormonal, functional and genetic biomarkers in controlled ovarian stimulation: tools for matching patients and protocols

    DEFF Research Database (Denmark)

    Alviggi, Carlo; Humaidan, Peter; Ezcurra, Diego

    2012-01-01

    single patient characteristics. These could potentially be used to match patients with the right treatment options to optimise efficacy, safety and tolerability during COS. Currently, age and follicle-stimulating hormone (FSH) level remain the most commonly used single patient characteristics in clinical...... practice. These variables only provide a basic prognosis for success and indications for standard COS treatment based on gross patient categorisation. In contrast, the anti-Müllerian hormone level appears to be an accurate predictor of ovarian reserve and response to COS, and could be used successfully...

  18. The steroid response to human chorionic gonadotropin (hCG) stimulation in men with Klinefelter syndrome does not change using immunoassay or mass spectrometry.

    Science.gov (United States)

    Roli, L; Santi, D; Belli, S; Tagliavini, S; Cavalieri, S; De Santis, M C; Baraldi, E; Fanelli, F; Mezzullo, M; Granata, A R; Pagotto, U; Pasquali, R; Rochira, V; Carani, C; Simoni, M; Trenti, T

    2017-08-01

    Liquid-chromatography tandem mass-spectrometry (LC-MS/MS) was developed in parallel to Immunoassays (IAs) and today is proposed as the "gold standard" for steroid assays. Leydig cells of men with Klinefelter syndrome (KS) are able to respond to human chorionic gonadotropin (hCG) stimulation, even if testosterone (T) production was impaired. The aim was to evaluate how results obtained by IAs and LC-MS/MS can differently impact on the outcome of a clinical research on gonadal steroidogenesis after hCG stimulation. A longitudinal, prospective, case-control clinical trial. (clinicaltrial.gov NCT02788136) was carried out, enrolling KS men and healthy age-matched controls, stimulated by hCG administration. Serum steroids were evaluated at baseline and for 5 days after intramuscular injection of 5000 IU hCG using both IAs and LC-MS/MS. 13 KS patients (36 ± 9 years) not receiving T replacement therapy and 14 controls (32 ± 8 years) were enrolled. T, progesterone, cortisol, 17-hydroxy-progesterone (17OHP) and androstenedione, were significantly higher using IAs than LC-MS/MS. IAs and LC-MS/MS showed direct correlation for all five steroids, although the constant overestimation detected by IAs. Either methodology found the same 17OHP and T increasing profile after hCG stimulation, with equal areas under the curves (AUCs). Although a linearity between IA and LC-MS/MS is demonstrated, LC-MS/MS is more sensitive and accurate, whereas IA shows a constant overestimation of sex steroid levels. This result suggests the need of reference intervals built on the specific assay. This fundamental difference between these two methodologies opens a deep reconsideration of what is needed to improve the accuracy of steroid hormone assays.

  19. Targeting of follicle stimulating hormone peptide-conjugated dendrimers to ovarian cancer cells

    Science.gov (United States)

    Modi, Dimple A.; Sunoqrot, Suhair; Bugno, Jason; Lantvit, Daniel D.; Hong, Seungpyo; Burdette, Joanna E.

    2014-02-01

    Ovarian cancer is the most lethal gynecological malignancy. Current treatment modalities include a combination of surgery and chemotherapy, which often lead to loss of fertility in premenopausal women and a myriad of systemic side effects. To address these issues, we have designed poly(amidoamine) (PAMAM) dendrimers to selectively target the follicle stimulating hormone receptor (FSHR), which is overexpressed by tumorigenic ovarian cancer cells but not by immature primordial follicles and other non-tumorigenic cells. Fluorescein-labeled generation 5 (G5) PAMAM dendrimers were conjugated with the binding peptide domain of FSH (FSH33) that has a high affinity to FSHR. The targeted dendrimers exhibited high receptor selectivity to FSHR-expressing OVCAR-3 cells, resulting in significant uptake and downregulation of an anti-apoptotic protein survivin, while showing minimal interactions with SKOV-3 cells that do not express FSHR. The selectivity of the FSH33-targeted dendrimers was further validated in 3D organ cultures of normal mouse ovaries. Immunostaining of the conjugates revealed their selective binding and uptake by ovarian surface epithelium (OSE) cells that express FSHR, while sparing the immature primordial follicles. In addition, an in vivo study monitoring tissue accumulation following a single intraperitoneal (i.p.) injection of the conjugates showed significantly higher accumulation of FSH33-targeted dendrimers in the ovary and oviduct compared to the non-targeted conjugates. These proof-of-concept findings highlight the potential of these FSH33-targeted dendrimers to serve as a delivery platform for anti-ovarian cancer drugs, while reducing their systemic side effects by preventing nonspecific uptake by the primordial follicles.Ovarian cancer is the most lethal gynecological malignancy. Current treatment modalities include a combination of surgery and chemotherapy, which often lead to loss of fertility in premenopausal women and a myriad of systemic side

  20. Follicle stimulating hormone alleviates radiation-induced degeneration of mouse ovarian follicles

    Energy Technology Data Exchange (ETDEWEB)

    Lee, C.J. [Hanyang Univ., Seoul (Korea, Republic of); Kim, J.K.; Chun, K.J.

    2000-05-01

    The present study was performed to analyze the influences of (FSH) follicle stimulating hormone and {gamma}-radiation on the morphological changes of ovarian follicles and serum concentrations of testosterone, and estradiol-17{beta} in prepubertal mice. Female mice (ICR strain, three weeks old) were irradiated with 8.33 Gy of {gamma}-ray and followed by a 5 IU i.p.-injection of FSH to know the effect of FSH on the ovarian follicles. Left ovaries were collected at 0 h, 1 d, and 2 d after irradiation or saline/ FSH injection. Another group was received 5 IU of FSH 2 hours before irradiation to analyze the changes of ovarian steroidogenic abilities. By the morphometrical analysis, the number of normal or atretic follicles was counted and the ratio of normal to atretic follicle numbers was calculated. The percentage of atretic follicles was significantly reduced by the treatment of FSH. In the case of the FSH-injected group, the cellular debris caused by radiation was engulfed by the immune cells and the neighboring granulosa cells within the follicles. In concurrence with the morphometric analysis, the changes of the serum concentrations (pg/ml) of testosterone (T) and estradiol (E{sub 2}) were determined by radioimmunoassays. The concentration of T was 336.8{+-}61.3 in the control mice. One day after irradiation, the concentration went up to 484.8{+-}80.0 in the irradiated group, and down to 243.5{+-}80.7 in the FSH-treated one. The concentration of E{sub 2} was 174.9{+-}15.0 in the control group. One day after irradiation, however, the concentration was decreased to 94.8{+-}19.8, and 155.9{+-}8.7 in the irradiated and FSH-treated group, respectively. The alleviation of the follicular degeneration by the treatment of FSH is closely related to the elimination of the cellular debris and to the activities of the steroidogenic enzymes. (Author)

  1. Is the birthweight of singletons born after IVF reduced by ovarian stimulation or by IVF laboratory procedures?

    NARCIS (Netherlands)

    Pelinck, M. J.; Hadders-Algra, M.; Haadsma, M. L.; Nijhuis, W. L.; Kiewiet, S. M.; Hoek, A.; Heineman, M. J.; Middleburg, K. J.

    Singletons born after IVF are at risk of adverse pregnancy outcome, the cause of which is unknown. The present study investigated the influence of ovarian stimulation and IVF laboratory procedure on birthweight. Birthweight of singleton pregnancies resulting from IVF treatment with (n = 161) and

  2. Is the birthweight of singletons born after IVF reduced by ovarian stimulation or by IVF laboratory procedures?

    NARCIS (Netherlands)

    Pelinck, M. J.; Hadders-Algra, M.; Haadsma, M. L.; Nijhuis, W. L.; Kiewiet, S. M.; Hoek, A.; Heineman, M. J.; Middelburg, K. J.

    2010-01-01

    Singletons born after IVF are at risk of adverse pregnancy outcome, the cause of which is unknown. The present study investigated the influence of ovarian stimulation and IVF laboratory procedure on birthweight. Birthweight of singleton pregnancies resulting from IVF treatment with (n = 161) and

  3. Individualized versus conventional ovarian stimulation for in vitro fertilization: a multicenter, randomized, controlled, assessor-blinded, phase 3 noninferiority trial

    DEFF Research Database (Denmark)

    Nyboe Andersen, Anders; Nelson, Scott M; Fauser, Bart C J M

    2017-01-01

    OBJECTIVE: To compare the efficacy and safety of follitropin delta, a new human recombinant FSH with individualized dosing based on serum antimüllerian hormone (AMH) and body weight, with conventional follitropin alfa dosing for ovarian stimulation in women undergoing IVF. DESIGN: Randomized, mul...

  4. Interleukin-8 stimulates progesterone production via the MEK pathway in ovarian theca cells.

    Science.gov (United States)

    Shimizu, Takashi; Imamura, Eri; Magata, Fumie; Murayama, Chiaki; Miyamoto, Akio

    2013-02-01

    Interleukin 8 (IL-8) is a chemoattractant associated with ovulation in the mammalian ovary. This chemokine is also involved in the recruitment and activation of neutrophils. Using bovine tissue, we examined the possible role of IL-8 in steroid production by theca cells of the large ovarian follicles. IL-8 promoted progesterone production and stimulated StAR expression in cultured theca cells. The inhibitor of p38 did not disturb the P4 production and StAR expression in IL-8-treated theca cells. On the other hand, the inhibitor of MEK disturbed the P4 production and expression of StAR in theca cells treated with IL-8. These results suggest that IL-8 is associated with progesterone production in bovine theca cells via the MEK pathway.

  5. Comparison of the effects of ovarian cauterization and gonadotropin-releasing hormone agonist and oral contraceptive therapy combination on endocrine changes in women with polycystic ovary disease.

    Science.gov (United States)

    Taskin, O; Yalcinoglu, A I; Kafkasli, A; Burak, F; Ozekici, U

    1996-06-01

    To study the effects of laparoscopic ovarian cauterization and combination of long-acting GnRH agonist (GnRH-a) and oral contraceptive (OC) therapy on endocrine changes in women with clomiphene citrate (CC)- resistant polycystic ovary disease (PCOD). Prospective, randomized. University-based infertility clinic. Seventeen women with CC-resistant PCOD were included randomly in the study to either laparoscopic ovarian cautery or GnRH-a and OC therapy for 3 months. Serum concentrations of LH, FSH, androstenedione (A), T, and sex hormone-binding globulin (SHBG) were determined before each therapeutic approach and during the follicular phase of first menstrual cycle after the cessation of each treatment. The mean serum concentrations and the clinical profiles were similar in both groups. Both groups showed significant changes in LH, FSH, A, T, and SHBG compared with pretreatment levels. There were no significant differences in the final concentrations of LH, FSH, and A between the two study groups after each treatment, whereas T and SHBG levels were significantly different in the goserelin and OC group. The decrease in LH and increase in SHBG serum concentrations were greater in the goserelin and OC-treated women [-59% and + 5.9% versus - 70% and + 13.5%, respectively]. Although the SHBG concentration increased in both groups, the serum SHBG concentration of the goserelin and OC group was significantly higher than the other group. Both therapeutic modalities revealed similar effects on the endocrine profiles in women with CC-resistant PCOD. Considering the invasiveness, cost, and potential complications of laparoscopic ovarian cauterization, noninvasive medical treatment with GnRH-a and OC combination may be more effective in restoring the optimal follicular environment in women with PCOD.

  6. Effect of endometrial biopsy on intrauterine insemination outcome in controlled ovarian stimulation cycle

    Directory of Open Access Journals (Sweden)

    Leena Wadhwa

    2015-01-01

    Full Text Available OBJECTIVE: The objective was to evaluate the effect of endometrial biopsy (EB on intrauterine insemination (IUI outcome in controlled ovarian stimulation (COS cycle. DESIGN: Prospective randomized control study. SETTING: Tertiary care center. MATERIALS AND METHODS: A total of 251 subjects were enrolled in the study. Subjects undergoing COS with IUI were randomly allocated into three groups. Group A: EB was taken between D19 and 24 of the spontaneous menstrual cycles that precedes the fertility treatment and IUI, which was done in next cycle (n = 86. Group B: EB was taken before D6 of the menstrual cycle, and fertility treatment and IUI was done in the same cycle (n = 90. Group C: (control group no EB in previous 3 cycle (n = 75. MAIN OUTCOME MEASURE: Clinical pregnancy rate (CPR. RESULTS: Clinical pregnancy rate was 19.77%, 31.11%, and 9.3% for Group A, Group B, and Group C, respectively. The results show a highly significant value for the paired t-test of intervention Group B and control Group C of the cases (P = 0.000957. CPR was maximum afterfirst cycle of ovulation induction and IUI following EB scratch in both Groups A and in Group B (P < 0.001. CONCLUSIONS: Endometrial biopsy done in early follicular phase in the same cycle of stimulation with IUI gives better CPR as compared with EB done in the luteal phase of the previous cycle.

  7. Effect of endometrial biopsy on intrauterine insemination outcome in controlled ovarian stimulation cycle.

    Science.gov (United States)

    Wadhwa, Leena; Pritam, Amrita; Gupta, Taru; Gupta, Sangeeta; Arora, Sarika; Chandoke, Rajkumar

    2015-01-01

    The objective was to evaluate the effect of endometrial biopsy (EB) on intrauterine insemination (IUI) outcome in controlled ovarian stimulation (COS) cycle. Prospective randomized control study. Tertiary care center. A total of 251 subjects were enrolled in the study. Subjects undergoing COS with IUI were randomly allocated into three groups. Group A: EB was taken between D19 and 24 of the spontaneous menstrual cycles that precedes the fertility treatment and IUI, which was done in next cycle (n = 86). Group B: EB was taken before D6 of the menstrual cycle, and fertility treatment and IUI was done in the same cycle (n = 90). Group C: (control group) no EB in previous 3 cycle (n = 75). Clinical pregnancy rate (CPR). Clinical pregnancy rate was 19.77%, 31.11%, and 9.3% for Group A, Group B, and Group C, respectively. The results show a highly significant value for the paired t-test of intervention Group B and control Group C of the cases (P = 0.000957). CPR was maximum after first cycle of ovulation induction and IUI following EB scratch in both Groups A and in Group B (P Endometrial biopsy done in early follicular phase in the same cycle of stimulation with IUI gives better CPR as compared with EB done in the luteal phase of the previous cycle.

  8. [Meiotic abnormalities of oocytes from patients with endometriosis submitted to ovarian stimulation].

    Science.gov (United States)

    Barcelos, Ionara Diniz Evangelista Santos; Vieira, Rodolpho Cruz; Ferreira, Elisa Melo; Araújo, Maria Cristina Picinato Medeiros de; Martins, Wellington de Paula; Ferriani, Rui Alberto; Navarro, Paula Andrea de Albuquerque Salles

    2008-08-01

    to evaluate the meiotic spindle and the chromosome distribution of in vitro mature oocytes from stimulated cycles of infertile women with endometriosis, and with male and/or tubal infertility factors (Control Group), comparing the rates of in vitro maturation (IVM) between the two groups evaluated. fourteen patients with endometriosis and eight with male and/or tubal infertility factors, submitted to ovarian stimulation for intracytoplasmatic sperm injection have been prospectively and consecutively selected, and formed a Study and Control Group, respectively. Immature oocytes (46 and 22, respectively, from the Endometriosis and Control Groups) were submitted to IVM. Oocytes presenting extrusion of the first polar corpuscle were fixed and stained for microtubules and chromatin evaluation through immunofluorescence technique. Statistical analysis has been done by the Fisher's exact test, with statistical significance at pControl Groups, respectively). The chromosome and meiotic spindle organization was observed in 18 and 11 oocytes from the Endometriosis and Control Groups, respectively. In the Endometriosis Group, eight oocytes (44.4%) presented themselves as normal metaphase II (MII), three (16.7%) as abnormal MII, five (27.8%) were in telophase stage I and two (11.1%) underwent parthenogenetic activation. In the Control Group, five oocytes (45.4%) presented themselves as normal MII, three (27.3%) as abnormal MII, one (9.1%) was in telophase stage I and two (18.2%) underwent parthenogenetic activation. There was no significant difference in meiotic anomaly rate between the oocytes in MII from both groups. the present study data did not show significant differences in the IVM or in the meiotic anomalies rate between the IVM oocytes from stimulated cycles of patients with endometriosis, as compared with controls. Nevertheless, they have suggested a delay in the outcome of oocyte meiosis I from patients with endometriosis, shown by the higher proportion of oocytes in

  9. Glutathione S-transferase activity in follicular fluid from women undergoing ovarian stimulation: role in maturation.

    Science.gov (United States)

    Meijide, Susana; Hernández, M Luisa; Navarro, Rosaura; Larreategui, Zaloa; Ferrando, Marcos; Ruiz-Sanz, José Ignacio; Ruiz-Larrea, M Begoña

    2014-10-01

    Female infertility involves an emotional impact for the woman, often leading to a state of anxiety and low self-esteem. The assisted reproduction techniques (ART) are used to overcome the problem of infertility. In a first step of the in vitro fertilization therapy women are subjected to an ovarian stimulation protocol to obtain mature oocytes, which will result in competent oocytes necessary for fertilization to occur. Ovarian stimulation, however, subjects the women to a high physical and psychological stress, thus being essential to improve ART and to find biomarkers of dysfunction and fertility. GSH is an important antioxidant, and is also used in detoxification reactions, catalysed by glutathione S-transferases (GST). In the present work, we have investigated the involvement of GST in follicular maturation. Patients with fertility problems and oocyte donors were recruited for the study. From each woman follicles at two stages of maturation were extracted at the preovulatory stage. Follicular fluid was separated from the oocyte by centrifugation and used as the enzyme source. GST activity was determined based on its conjugation with 3,4-dichloronitrobenzene and the assay was adapted to a 96-well microplate reader. The absorbance was represented against the incubation time and the curves were adjusted to linearity (R(2)>0.990). Results showed that in both donors and patients GST activity was significantly lower in mature oocytes compared to small ones. These results suggest that GST may play a role in the follicle maturation by detoxifying xenobiotics, thus contributing to the normal development of the oocyte. Supported by FIS/FEDER (PI11/02559), Gobierno Vasco (Dep. Educación, Universiades e Investigación, IT687-13), and UPV/EHU (CLUMBER UFI11/20 and PES13/58). The work was approved by the Ethics Committee of the UPV/EHU (CEISH/96/2011/RUIZLARREA), and performed according to the UPV/EHU and IVI-Bilbao agreement (Ref. 2012/01). Copyright © 2014. Published by

  10. The type of GnRH analogue used during controlled ovarian stimulation influences early embryo developmental kinetics

    DEFF Research Database (Denmark)

    Muñoz, Manuel; Cruz, María; Humaidan, Peter

    2013-01-01

    in the Instituto Valenciano de Infertilidad (IVI) Alicante and the Instituto Universitario-IVI Valencia, Spain, 2817 embryos deriving from 400 couples undergoing oocyte donation were analysed. After controlled ovarian stimulation and IVF/intracytoplamic sperm injection, the timing of embryonic cleavages......OBJECTIVE: To explore if the GnRH analogue used for controlled ovarian stimulation (COS) and the ovulation triggering factor (GnRH agonist+hCG triggering versus GnRH antagonist+GnRH agonist triggering) affect embryo development and kinetics. STUDY DESIGN: In a retrospective cohort study...... was assessed by a video time-lapse system. The results were analysed using Student's t test for comparison of timings (hours) and Chi-squared test for comparison of proportions. A p-value...

  11. Effect of human chorionic gonadotropin (hCG) on in vitro oocyte ...

    African Journals Online (AJOL)

    use

    2011-11-23

    Nov 23, 2011 ... In vitro exposure of Barilius vagra ovarian follicles to human chorionic gonadotropin (hCG) .... breakdown (GVBD) by treating them with egg clearing solution ..... trihydroxy-5Я-pregnen-20-one, in female plaice (Pleuronectes.

  12. Association Between Progesterone Elevation on the Day of Human Chronic Gonadotropin Trigger and Pregnancy Outcomes After Fresh Embryo Transfer in In Vitro Fertilization/Intracytoplasmic Sperm Injection Cycles.

    Science.gov (United States)

    Esteves, Sandro C; Khastgir, Gautam; Shah, Jatin; Murdia, Kshitiz; Gupta, Shweta Mittal; Rao, Durga G; Dash, Soumyaroop; Ingale, Kundan; Patil, Milind; Moideen, Kunji; Thakor, Priti; Dewda, Pavitra

    2018-01-01

    Progesterone elevation (PE) during the late follicular phase of controlled ovarian stimulation in fresh embryo transfer in vitro fertilization (IVF)/intracytoplasmic sperm injection cycles has been claimed to be associated with decreased pregnancy rates. However, the evidence is not unequivocal, and clinicians still have questions about the clinical validity of measuring P levels during the follicular phase of stimulated cycles. We reviewed the existing literature aimed at answering four relevant clinical questions, namely (i) Is gonadotropin type associated with PE during the follicular phase of stimulated cycles? (ii) Is PE on the day of human chorionic gonadotropin (hCG) associated with negative fresh embryo transfer IVF/intracytoplasmic sperm injection (ICSI) cycles outcomes in all patient subgroups? (iii) Which P thresholds are best to identify patients at risk of implantation failure due to PE in a fresh embryo transfer? and (iv) Should a freeze all policy be adopted in all the cycles with PE on the day of hCG? The existing evidence indicates that late follicular phase progesterone rise in gonadotropin releasing analog cycles is mainly caused by the supraphysiological stimulation of granulosa cells with exogenous follicle-stimulating hormone. Yet, the type of gonadotropin used for stimulation seems to play no significant role on progesterone levels at the end of stimulation. Furthermore, PE is not a universal phenomenon with evidence indicating that its detrimental consequences on pregnancy outcomes do not affect all patient populations equally. Patients with high ovarian response to control ovarian stimulation are more prone to exhibit PE at the late follicular phase. However, in studies showing an overall detrimental effect of PE on pregnancy rates, the adverse effect of PE on endometrial receptivity seems to be offset, at least in part, by the availability of good quality embryo for transfer in women with a high ovarian response. Given the limitations of

  13. Association Between Progesterone Elevation on the Day of Human Chronic Gonadotropin Trigger and Pregnancy Outcomes After Fresh Embryo Transfer in In Vitro Fertilization/Intracytoplasmic Sperm Injection Cycles

    Directory of Open Access Journals (Sweden)

    Sandro C. Esteves

    2018-04-01

    Full Text Available Progesterone elevation (PE during the late follicular phase of controlled ovarian stimulation in fresh embryo transfer in vitro fertilization (IVF/intracytoplasmic sperm injection cycles has been claimed to be associated with decreased pregnancy rates. However, the evidence is not unequivocal, and clinicians still have questions about the clinical validity of measuring P levels during the follicular phase of stimulated cycles. We reviewed the existing literature aimed at answering four relevant clinical questions, namely (i Is gonadotropin type associated with PE during the follicular phase of stimulated cycles? (ii Is PE on the day of human chorionic gonadotropin (hCG associated with negative fresh embryo transfer IVF/intracytoplasmic sperm injection (ICSI cycles outcomes in all patient subgroups? (iii Which P thresholds are best to identify patients at risk of implantation failure due to PE in a fresh embryo transfer? and (iv Should a freeze all policy be adopted in all the cycles with PE on the day of hCG? The existing evidence indicates that late follicular phase progesterone rise in gonadotropin releasing analog cycles is mainly caused by the supraphysiological stimulation of granulosa cells with exogenous follicle-stimulating hormone. Yet, the type of gonadotropin used for stimulation seems to play no significant role on progesterone levels at the end of stimulation. Furthermore, PE is not a universal phenomenon with evidence indicating that its detrimental consequences on pregnancy outcomes do not affect all patient populations equally. Patients with high ovarian response to control ovarian stimulation are more prone to exhibit PE at the late follicular phase. However, in studies showing an overall detrimental effect of PE on pregnancy rates, the adverse effect of PE on endometrial receptivity seems to be offset, at least in part, by the availability of good quality embryo for transfer in women with a high ovarian response. Given the

  14. Association Between Progesterone Elevation on the Day of Human Chronic Gonadotropin Trigger and Pregnancy Outcomes After Fresh Embryo Transfer in In Vitro Fertilization/Intracytoplasmic Sperm Injection Cycles

    Science.gov (United States)

    Esteves, Sandro C.; Khastgir, Gautam; Shah, Jatin; Murdia, Kshitiz; Gupta, Shweta Mittal; Rao, Durga G.; Dash, Soumyaroop; Ingale, Kundan; Patil, Milind; Moideen, Kunji; Thakor, Priti; Dewda, Pavitra

    2018-01-01

    Progesterone elevation (PE) during the late follicular phase of controlled ovarian stimulation in fresh embryo transfer in vitro fertilization (IVF)/intracytoplasmic sperm injection cycles has been claimed to be associated with decreased pregnancy rates. However, the evidence is not unequivocal, and clinicians still have questions about the clinical validity of measuring P levels during the follicular phase of stimulated cycles. We reviewed the existing literature aimed at answering four relevant clinical questions, namely (i) Is gonadotropin type associated with PE during the follicular phase of stimulated cycles? (ii) Is PE on the day of human chorionic gonadotropin (hCG) associated with negative fresh embryo transfer IVF/intracytoplasmic sperm injection (ICSI) cycles outcomes in all patient subgroups? (iii) Which P thresholds are best to identify patients at risk of implantation failure due to PE in a fresh embryo transfer? and (iv) Should a freeze all policy be adopted in all the cycles with PE on the day of hCG? The existing evidence indicates that late follicular phase progesterone rise in gonadotropin releasing analog cycles is mainly caused by the supraphysiological stimulation of granulosa cells with exogenous follicle-stimulating hormone. Yet, the type of gonadotropin used for stimulation seems to play no significant role on progesterone levels at the end of stimulation. Furthermore, PE is not a universal phenomenon with evidence indicating that its detrimental consequences on pregnancy outcomes do not affect all patient populations equally. Patients with high ovarian response to control ovarian stimulation are more prone to exhibit PE at the late follicular phase. However, in studies showing an overall detrimental effect of PE on pregnancy rates, the adverse effect of PE on endometrial receptivity seems to be offset, at least in part, by the availability of good quality embryo for transfer in women with a high ovarian response. Given the limitations of

  15. Predictive factors for pregnancy outcome following controlled ovarian stimulation and intrauterine insemination

    International Nuclear Information System (INIS)

    Yildrim, G.; Turkgeldi, L.S.; Koroglu, N.; Mervetalmac, A.

    2017-01-01

    To establish predictive factors for positive pregnancy outcome in cases of controlled ovarian stimulation and intrauterine insemination. Methods: The retrospective study was conducted at Kanuni Sultan Suleyman Training and Research Hospital and comprised subjects having undergone ovulation induction cycles and intrauterine insemination between June 2010 and June 2015. Data was analysed in terms of various parameters affecting clinical pregnancy rates. SPSS 23 was used for statistical analysis. Results: There were 475 patients having undergone a total of 923 cycles. Pregnancy was established in 133(28%) patients. Univariate analysis of biological/clinical variables revealed the presence of secondary infertility, high endometrial thickness, antral follicle number, post wash total motile sperm count and midluteal progesterone levels following intrauterine insemination to be associated with positive pregnancy outcomes (p<0.05 each). Multiple logistic regression analysis was performed to establish factors that affected the pregnancy rate. The aetiology and type of infertility and high midluteal progesterone levels following intrauterine insemination were found to be statistically significant predictors of pregnancy (p<0.05 each). Conclusion: The best chance of pregnancy was found in cases with anovulatory infertility, a history of prior pregnancy, and high midluteal progesterone levels following treatment with gonadotrophins and intrauterine insemination. (author)

  16. The combined effects of pituitary gonadotropin and estrogen on the ovarian response of rats to /sup 125/I-LH uptake

    Energy Technology Data Exchange (ETDEWEB)

    Hosomichi, T; Yoshida, H; Ichinohe, K [Wakayama Medical Coll. (Japan)

    1974-12-01

    It discussed the effect of estradiol on the ovarian response of mature rats and hypophysectomized mature rats to /sup 125/I-LH uptake and the combined effects of FSH and estradiol. The constant concentration on the change of blood concentration with time was maintained in about one hour when given with the intravenous infusion of /sup 125/I-LH prepared for radioimmunoassay. Moreover, increased uptake of /sup 125/I-LH was noted especially in ovaries, livers, kidneys and thyroid glands, and by giving estradiol the uptake was increased to a level which was about twice the normal. Of hypophysectomized rats, the uptake was increased to a level which was about four times the normal in the group of rats which were given estradiol for eight days and also in the group of rats which were given FSH for four days. The effect with four-day-estradiol administration following four-day-FSH administration was to increase to a level which was about six times the group which was given each single administration. These experimental results are apparently due to the effects of FSH and estradiol on follicles and thus follicles are ready for LH uptake.

  17. Repeated superovulation increases the risk of osteoporosis and cardiovascular diseases by accelerating ovarian aging in mice.

    Science.gov (United States)

    Zhang, Jinjin; Lai, Zhiwen; Shi, Liangyan; Tian, Yong; Luo, Aiyue; Xu, Zheyuan; Ma, Xiangyi; Wang, Shixuan

    2018-05-22

    Superovulation procedures and assisted reproductive technologies have been widely used to treat couples who have infertility problems. Although generally safe, the superovulation procedures are associated with a series of complications, such as ovarian hyper-stimulation syndrome, thromboembolism, and adnexal torsion. The role of long-term repeated superovulation in ovarian aging and especially in associated disorders such as osteoporosis and cardiovascular diseases is still unclear. In this study, we sought to determine if repeated superovulation by ten cycles of treatment with pregnant mare serum gonadotropin/human chorionic gonadotropin could affect ovarian reserve, ovarian function, bone density and heart function. Ovarian reserve and function were reflected by the size of the primordial follicle pool, anti-Mullerian hormone expressions, hormone levels and fertility status. Furthermore, we examined bone density and heart function by microCT and cardiovascular ultrasonography, respectively. After repeated superovulation, the size of the primordial follicle pool and the expression of anti-mullerian hormone decreased, along with the concentrations of estrogen and progesterone. Mice exposed to repeated superovulation showed an obvious decrease in fertility and fecundity. Furthermore, both bone density and heart ejection fraction significantly decreased. These results suggest that repeated superovulation may increase the risk of osteoporosis and cardiovascular diseases by accelerating ovarian aging.

  18. "hCG priming" effect in controlled ovarian stimulation through a long protocol

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    Antsaklis Aris

    2009-08-01

    Full Text Available Abstract Background Recently, it has been demonstrated that, in patients down-regulated by GnRH analogues (GnRHa, a short-term pre-treatment with recombinant LH (rLH, prior to recombinant FSH (rFSH administration, increases the number of small antral follicle prior to FSH stimulation and the yield of normally fertilized embryos. However, no data exist in the literature regarding the potential beneficial effect of "hCG priming" in controlled ovarian hyperstimulation (COH through a long GnRH-a protocol, which binds the same receptor (LH/hCGR, though it is a much more potent compared to LH. The primary aims of this study were to assess the effect of short-term pre-rFSH administration of hCG in women entering an ICSI treatment cycle on follicular development, quality of oocytes and early embryo development. The secondary endpoints were to record the effects on endometrial quality and pregnancy rate. Methods Patients with a history of at least one previous unsuccessful ICSI cycle were randomly assigned into two groups to receive treatment with either a long protocol with rFSH (control group or a long protocol with rFSH and pre-treatment with hCG (hCG group. In particular, in the latter group, a fixed 7 days course of 200 IU/day hCG was administered as soon as pituitary desensitization was confirmed. Results The mean number of oocytes retrieved was not significantly different between the two treatment groups, although the percentage of mature oocytes tended to be higher but not significantly different in hCG-treated patients. The percentage of patients with more than one grade 3 embryos was higher in the pre-treatment group, which also showed a higher pregnancy rate. Conclusion All the above clinical observations, in conjunction with previous data, suggest a point towards a beneficial "hCG priming" effect in controlled ovarian hyperstimulation through a long GnRH-a down-regulation protocol, particularly in patients with previous ART failures.

  19. Central hypogonadism due to a giant, "silent" FSH-secreting, atypical pituitary adenoma: effects of adenoma dissection and short-term Leydig cell stimulation by luteinizing hormone (LH) and human chorionic gonadotropin (hCG).

    Science.gov (United States)

    Santi, Daniele; Spaggiari, Giorgia; Casarini, Livio; Fanelli, Flaminia; Mezzullo, Marco; Pagotto, Uberto; Granata, Antonio R M; Carani, Cesare; Simoni, Manuela

    2017-06-01

    We present a case report of an atypical giant pituitary adenoma secreting follicle-stimulating hormone (FSH). A 55-year-old patient presented for erectile dysfunction, loss of libido and fatigue. The biochemical evaluation showed very high FSH serum levels in the presence of central hypogonadism. Neither testicular enlargement nor increased sperm count was observed, thus a secretion of FSH with reduced biological activity was supposed. The histological examination after neuro-surgery showed an atypical pituitary adenoma with FSH-positive cells. Hypogonadism persisted and semen analyses impaired until azoospermia in conjunction with the reduction in FSH levels suggesting that, at least in part, this gonadotropin should be biologically active. Thus, we hypothesized a concomitant primary testicular insufficiency. The patient underwent short-term treatment trials with low doses of either recombinant luteinizing hormone (LH) or human chorionic gonadotropin (hCG) in three consecutive treatment schemes, showing an equal efficacy in stimulating testosterone (T) increase. This is the first case of atypical, giant FSH-secreting pituitary adenoma with high FSH serum levels without signs of testicular hyperstimulation, in presence of hypogonadism with plausible combined primary and secondary etiology. Hypophysectomized patients may represent a good model to assess both pharmacodynamics and effective dose of LH and hCG in the male.

  20. Aromatase inhibitors in stimulated IVF cycles

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    Tournaye Herman

    2011-06-01

    Full Text Available Abstract Aromatase inhibitors have been introduced as a new treatment modality that could challenge clomiphene citrate as an ovulation induction regiment in patients with PCOS. Although several randomized trials have been conducted regarding their use as ovulation induction agents, only few trials are available regarding their efficacy in IVF stimulated cycles. Current available evidence support that letrozole may have a promising role in stimulated IVF cycles, either when administered during the follicular phase for ovarian stimulation. Especially for women with poor ovarian response, letrozole appears to have the potential to increase clinical pregnancy rates when combined with gonadotropins, whereas at the same time reduces the total gonadotropin dose required for ovarian stimulation. However, given that in all of the trials letrozole has been administered in GnRH antagonist cycles, it is intriguing to test in the future how it may perform when used in GnRH agonist cycles. Finally administration of letrozole during luteal phase in IVF cycles offers another treatment modality for patients at high risk for OHSS taking into account that it drastically reduces estradiol levels

  1. Intrafollicular Endocrine Milieu After Addition of hCG to Recombinant FSH During Controlled Ovarian Stimulation for In Vitro Fertilization

    DEFF Research Database (Denmark)

    Thuesen, L L; Andersen, A Nyboe; Loft, A

    2014-01-01

    CONTEXT: The role of human chorionic gonadotropin (hCG) supplementation on the intrafollicular steroid milieu has been studied. OBJECTIVE: The objective of the study was to assess the impact on steroid levels in follicular fluids (FFs) after different doses of hCG supplementation to recombinant FSH...... protocol with recombinant FSH 150 IU/d and randomized from stimulation day 1 to supplementation with hCG: D0, 0 IU/d; D50, 50 IU/d; D100, 100 IU/d; and D150, 150 IU/d. MAIN OUTCOME MEASURE: Intrafollicular hormone concentrations in relation to treatment groups, follicular sizes, and embryo quality were...... measured. RESULTS: In large follicles, hCG supplementation induced a nearly 3-fold increase of estradiol (nanomoles per liter) [D0: 1496; D50: 3138; D100: 4338; D150: 4009 (P

  2. Association between response to ovarian stimulation and miscarriage following IVF: an analysis of 124 351 IVF pregnancies.

    Science.gov (United States)

    Sunkara, Sesh Kamal; Khalaf, Yacoub; Maheshwari, Abha; Seed, Paul; Coomarasamy, Arri

    2014-06-01

    Is there a relationship between ovarian reserve, quantified as ovarian response to stimulation, and miscarriage rate following IVF treatment? There is a strong association between the number of oocytes retrieved and miscarriage rate following IVF treatment, with the miscarriage rate decreasing with an increasing number of oocytes and then levelling off: poor responders have a higher miscarriage rate across all age groups. Poor ovarian response is a manifestation of a decline in the quantity of the primordial follicle pool. Whether poor ovarian response is associated with a decline in oocyte quality contributing to miscarriage is however debated. Anonymous data were obtained from the Human Fertilization and Embryology Authority (HFEA), the statutory regulator of assisted reproduction treatment (ART) in the UK. The HFEA has collected data on all ART performed in the UK since 1991. Data from 1991 to June 2008 involving 402 185 stimulated fresh IVF cycles and 124 351 pregnancy outcomes were analysed. Data on all women undergoing a stimulated fresh IVF treatment cycle with at least one oocyte retrieved during the period from 1991 to June 2008 were analysed for their early pregnancy outcomes. There was a strong association between the number of oocytes retrieved and the clinical miscarriage rate. The miscarriage rate fell from 20 to 13% with an increasing number of oocytes before levelling off. Stepwise logistic regression identified three cut-off points (4, 10 and 15 oocytes) at or beyond which the probability of clinical miscarriage fell. There was no increase in miscarriage rate with very high oocyte numbers (>20 oocytes). The lowest risk of miscarriage (9.9%) was for women under 38 years of age, with primary infertility without a female cause and producing more than three oocytes. Although the analysis was performed only on stimulated IVF cycles (excluding unstimulated cycles), the data had the limitation that there was no information on the total gonadotrophin

  3. Fresh versus frozen embryo transfer after gonadotropin-releasing hormone agonist trigger in gonadotropin-releasing hormone antagonist cycles among high responder women: A randomized, multi-center study

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    Abbas Aflatoonian

    2018-02-01

    Full Text Available Background: The use of embryo cryopreservation excludes the possible detrimental effects of ovarian stimulation on the endometrium, and higher reproductive outcomes following this policy have been reported. Moreover, gonadotropin-releasing hormone agonist trigger in gonadotropin-releasing hormone (GnRH antagonist cycles as a substitute for standard human chorionic gonadotropin trigger, minimizes the risk of ovarian hyperstimulation syndrome (OHSS in fresh as well as frozen embryo transfer cycles (FET. Objective: To compare the reproductive outcomes and risk of OHSS in fresh vs frozen embryo transfer in high responder patients, undergoing in vitro fertilization triggered with a bolus of GnRH agonist. Materials and Methods: In this randomized, multi-centre study, 121 women undergoing FET and 119 women undergoing fresh ET were investigated as regards clinical pregnancy as the primary outcome and the chemical pregnancy, live birth, OHSS development, and perinatal data as secondary outcomes. Results: There were no significant differences between FET and fresh groups regarding chemical (46.4% vs. 40.2%, p=0.352, clinical (35.8% vs. 38.3%, p=0.699, and ongoing (30.3% vs. 32.7%, p=0.700 pregnancy rates, also live birth (30.3% vs. 29.9%, p=0.953, perinatal outcomes, and OHSS development (35.6% vs. 42.9%, p=0.337. No woman developed severe OHSS and no one required admission to hospital. Conclusion: Our findings suggest that GnRHa trigger followed by fresh transfer with modified luteal phase support in terms of a small human chorionic gonadotropin bolus is a good strategy to secure good live birth rates and a low risk of clinically relevant OHSS development in in vitro fertilization patients at risk of OHSS.

  4. Therapeutic Efficacy of Endometrial Scratching in Repeated Controlled Ovarian Stimulation (COS) Failure Cycles

    Science.gov (United States)

    Wadhwa, Leena; Mishra, Mona

    2018-01-01

    Objective: The objective of the study was (1) “to evaluate the therapeutic efficacy of endometrial scratching in repeated controlled ovarian stimulation (COS) failure cycles.” And (2) “to compare differences in pregnancy outcome by endometrial scratching in early (D2–D4) and late follicular phases (D7–D9) of the same stimulation cycle.” Materials and Methods: Women attending infertility clinic in a tertiary care center and who have two or more repeated COS failure cycles and planned for COS with intrauterine insemination (IUI) were included in the study which is a prospective parallel, interventional, single-blinded, randomized control study, in 1:1 allocation ratio. A total of 165 patients were recruited and randomly allocated into three groups: Group A (n = 55) underwent endometrial scratching on D2–D4 of the same COS cycle, Group B (n = 55) on D7–D9, and Group C (n = 55) no intervention done. All the patients underwent COS according to standard protocol followed by IUI. Results: Clinical pregnancy rate was 12.73% (odds ratio [OR] =0.87 95% confidence interval [CI] =0.288–2.55, P = 1), 16.36% (OR = 1.15; 95% CI = 0.40–3.23, P = 1), and 14.54%, respectively, in Group A, B, and C, respectively (P = 0.86), as per intention to treat analysis. Using Chi-square test, P value between Group A and B was 0.787, between Group A and C was 1.000, and between Group B and C was 1.000. As per protocol analysis, clinical pregnancy rate was 13.46% (OR = 0.83; 95% CI = 0.27–2.5, P = 0.74), 19.57% (OR = 1.3 95%; CI = 0.45–3.73, P = 0.41), and 15.69%. Using Chi-square test, Pvalue between Group A and B was 0.588, between Group A and C was 0.967, and between Group B and C was 0.815. No abortions and multiple pregnancies occurred in either of the groups. Conclusion: The effect found was of good quantum in Group B as per protocol analysis which could be of clinical relevance if larger sample size would have been taken. Endometrial scratching is a cost

  5. Anti-Mullerian Hormone: A Marker of Ovarian Reserve and its Association with Polycystic Ovarian Syndrome.

    Science.gov (United States)

    Verma, Anil Kumar; Rajbhar, Sarita; Mishra, Jyoti; Gupta, Mayank; Sharma, Mratunjai; Deshmukh, Geeta; Ali, Wahid

    2016-12-01

    Anti-Mullerian Hormone (AMH) is a useful endocrine marker for assessing the ovarian reserve. AMH serum level reflects the number of follicles that have made the transition from the primordial pool into the growing follicle pool, and it is not controlled by gonadotropins. The present study was conducted to correlate serum AMH levels with Polycystic Ovarian Syndrome (PCOS) and type of treatment protocol. Serum AMH levels were performed in the early follicular phase (on 2 nd day of menstrual cycle) both in infertile females including PCOS and control women. The results were analyzed in relation to age, Body Mass Index (BMI), ovarian volume, serum Follicle Stimulating Hormone (FSH) levels, Antral Follicle Count (AFC), type of treatment protocols and also in association with PCOS patients. The serum levels of AMH were measured in all the participants on 2 nd day of menstrual cycle using ultra sensitive Enzyme Linked Immunosorbent Assay (ELISA). The plasma AMH levels were significantly higher in women with polycystic ovarian syndrome. The significant association was seen between FSH and AFC with AMH. However, no significant association was observed between AMH levels with age, BMI, ovarian volume and type of treatment protocols. The serum AMH measurement was significantly higher in PCOS patients. No association with type of treatment protocol was obtained.

  6. PIVET rFSH dosing algorithms for individualized controlled ovarian stimulation enables optimized pregnancy productivity rates and avoidance of ovarian hyperstimulation syndrome.

    Science.gov (United States)

    Yovich, John L; Alsbjerg, Birgit; Conceicao, Jason L; Hinchliffe, Peter M; Keane, Kevin N

    2016-01-01

    The first PIVET algorithm for individualized recombinant follicle stimulating hormone (rFSH) dosing in in vitro fertilization, reported in 2012, was based on age and antral follicle count grading with adjustments for anti-Müllerian hormone level, body mass index, day-2 FSH, and smoking history. In 2007, it was enabled by the introduction of a metered rFSH pen allowing small dosage increments of ~8.3 IU per click. In 2011, a second rFSH pen was introduced allowing more precise dosages of 12.5 IU per click, and both pens with their individual algorithms have been applied continuously at our clinic. The objective of this observational study was to validate the PIVET algorithms pertaining to the two rFSH pens with the aim of collecting ≤15 oocytes and minimizing the risk of ovarian hyperstimulation syndrome. The data set included 2,822 in vitro fertilization stimulations over a 6-year period until April 2014 applying either of the two individualized dosing algorithms and corresponding pens. The main outcome measures were mean oocytes retrieved and resultant embryos designated for transfer or cryopreservation permitted calculation of oocyte and embryo utilization rates. Ensuing pregnancies were tracked until live births, and live birth productivity rates embracing fresh and frozen transfers were calculated. Overall, the results showed that mean oocyte numbers were 10.0 for all women algorithms in our clinic meant that the starting dose was not altered for 79.1% of patients and for 30.1% of those receiving the very lowest rFSH dosages (≤75 IU). Only 0.3% patients were diagnosed with severe ovarian hyperstimulation syndrome, all deemed avoidable due to definable breaches from the protocols. The live birth productivity rates exceeded 50% for women algorithms led to only 11.6% of women generating >15 oocytes, significantly lower than recently published data applying conventional dosages (38.2%; Palgorithms to each other, the outcomes were mainly comparable for

  7. Comparison of clinical outcome and costs with CC + gonadotropins and gnrha + gonadotropins during Ivf/ICSI cycles.

    Science.gov (United States)

    Kovacs, Peter; Matyas, Szabolcs; Bernard, l Artur; Kaali, Steven G

    2004-06-01

    To compare clinical outcome and costs of CC + gonadotropins with GnRHa + gonadotropins during IVF/ICSI cycles. Clinical outcome and expenses of 382 CC + gonadotropin and 964 GnRHa + gonadotropin cycles were compared. Medication costs were calculated on the basis of the mean number of ampoules and the proportion of various gonadotropins. Costs per clinical pregnancy were calculated on the basis of expenses and clinical pregnancy rates. Women in the CC + gonadotropin group were younger, and had fewer follicles, oocytes, embryos, and embryos transferred. Clinical pregnancy rates were higher in the GnRHa group (35.9 % vs 26.2%, p costs per cycle were higher in the GnRHa group (US dollars 357 vs 248). Expenses per pregnancy however were lower in the GnRHa group (USdollars 4197 vs 5335 with IVF; USdollars 5590 vs 7244 with ICSI). When different age subgroups with similar baseline characteristics and stimulation parameters were compared, pregnancy rates were significantly higher in the GnRHa groups. Medication cost per cycle was higher in the GnRHa subgroups, and the expense per pregnancy was lower with GnRHa protocol. Cost per cycle is higher with GnRHa + gonadotropin. However, because of the better performance of the GnRHa + gonadotropin stimulation, the cumulative costs are reduced by the time a clinical pregnancy is achieved.

  8. Stimulation of the young poor responder: comparison of the luteal estradiol/gonadotropin-releasing hormone antagonist priming protocol versus oral contraceptive microdose leuprolide.

    Science.gov (United States)

    Shastri, Shefali M; Barbieri, Elizabeth; Kligman, Isaac; Schoyer, Katherine D; Davis, Owen K; Rosenwaks, Zev

    2011-02-01

    To evaluate in vitro fertilization (IVF) cycle outcomes in young poor responders treated with a luteal estradiol/gonadotropin-releasing hormone antagonist (E(2)/ANT) protocol versus an oral contraceptive pill microdose leuprolide protocol (OCP-MDL). Retrospective cohort. Academic practice. Poor responders: 186 women, aged <35 years undergoing IVF with either E(2)/ANT or OCP-MDL protocols. None. Clinical pregnancies, oocytes retrieved, cancellation rate. Patients in the E(2)/ANT group had a greater gonadotropin requirement (71.9 ± 22.2 vs. 57.6 ± 25.7) and lower E(2) level (1,178.6 ± 668 vs. 1,627 ± 889), yet achieved similar numbers of oocytes retrieved and fertilized, and a greater number of embryos transferred (2.3 ± 0.9 vs. 2.0 ± 1.1) with a better mean grade (2.14 ± .06 vs. 2.7 ± 1.8) compared with the OCP/MDL group. The E2/ANT group exhibited a trend toward improved implantation rates (30.5% vs. 21.1%) and ongoing pregnancy rates per started cycle: 44 out of 117 (37%) versus 17 out of 69 (25%). Poor responders aged <35 years may be treated with the aggressive E(2)/ANT protocol to improve cycle outcomes. Both protocols remain viable options for this group. Adequately powered, randomized clinical comparison appears justified. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  9. Follicle-Stimulating Hormone Receptor Is Expressed by Most Ovarian Cancer Subtypes and Is a Safe and Effective Immunotherapeutic Target.

    Science.gov (United States)

    Perales-Puchalt, Alfredo; Svoronos, Nikolaos; Rutkowski, Melanie R; Allegrezza, Michael J; Tesone, Amelia J; Payne, Kyle K; Wickramasinghe, Jayamanna; Nguyen, Jenny M; O'Brien, Shane W; Gumireddy, Kiranmai; Huang, Qihong; Cadungog, Mark G; Connolly, Denise C; Tchou, Julia; Curiel, Tyler J; Conejo-Garcia, Jose R

    2017-01-15

    To define the safety and effectiveness of T cells redirected against follicle-stimulating hormone receptor (FSHR)-expressing ovarian cancer cells. FSHR expression was determined by Western blotting, immunohistochemistry, and qPCR in 77 human ovarian cancer specimens from 6 different histologic subtypes and 20 human healthy tissues. The effectiveness of human T cells targeted with full-length FSH in vivo was determined against a panel of patient-derived xenografts. Safety and effectiveness were confirmed in immunocompetent tumor-bearing mice, using constructs targeting murine FSHR and syngeneic T cells. FSHR is expressed in gynecologic malignancies of different histologic types but not in nonovarian healthy tissues. Accordingly, T cells expressing full-length FSHR-redirected chimeric receptors mediate significant therapeutic effects (including tumor rejection) against a panel of patient-derived tumors in vivo In immunocompetent mice growing syngeneic, orthotopic, and aggressive ovarian tumors, fully murine FSHR-targeted T cells also increased survival without any measurable toxicity. Notably, chimeric receptors enhanced the ability of endogenous tumor-reactive T cells to abrogate malignant progression upon adoptive transfer into naïve recipients subsequently challenged with the same tumor. Interestingly, FSHR-targeted T cells persisted as memory lymphocytes without noticeable PD-1-dependent exhaustion during end-stage disease, in the absence of tumor cell immunoediting. However, exosomes in advanced tumor ascites diverted the effector activity of this and other chimeric receptor-transduced T cells away from targeted tumor cells. T cells redirected against FSHR + tumor cells with full-length FSH represent a promising therapeutic alternative against a broad range of ovarian malignancies, with negligible toxicity even in the presence of cognate targets in tumor-free ovaries. Clin Cancer Res; 23(2); 441-53. ©2016 AACR. ©2016 American Association for Cancer Research.

  10. The use of anti-Müllerian hormone (AMH) for controlled ovarian stimulation in assisted reproductive technology and for fertility assessment and -counselling

    DEFF Research Database (Denmark)

    Pilsgaard, Fie; Grynnerup, Anna Garcia-Alix; Loessl, Kristine

    2018-01-01

    stimulation protocol and gonadotrophin dose can be chosen specifically for each woman enabling the so called 'individualized treatment' in line with the personalized treatment concept. Many benefits come with using AMH as a biomarker for ovarian reserve; the hormone is considered fairly cycle independent....... Currently, no international standardised assays exist. AMH is a valid predictor of the ovarian response to controlled ovarian stimulation and to some extent the chance of pregnancy in relation to assisted reproductive technology, but AMH is less optimal in prediction of spontaneous pregnancy and live birth...... after assisted reproductive technology. Accordingly, AMH can be used to optimize gonadotrophin stimulation in fertility treatment, but is not recommended as a screening tool in the general population. This article is protected by copyright. All rights reserved....

  11. Neuroendocrine regulation of gonadotropin secretion in seasonally breeding birds

    Directory of Open Access Journals (Sweden)

    Takayoshi eUbuka

    2013-03-01

    Full Text Available Seasonally breeding birds detect environmental signals, such as light, temperature, food availability and presence of mates to time reproduction. Hypothalamic neurons integrate external and internal signals, and regulate reproduction by releasing neurohormones to the pituitary gland. The pituitary gland synthesizes and releases gonadotropins which in turn act on the gonads to stimulate gametogenesis and sex steroid secretion. Accordingly, how gonadotropin secretion is controlled by the hypothalamus is key to our understanding of the mechanisms of seasonal reproduction. A hypothalamic neuropeptide, gonadotropin-releasing hormone (GnRH, activates reproduction by stimulating gonadotropin synthesis and release. Another hypothalamic neuropeptide, gonadotropin-inhibitory hormone (GnIH, inhibits gonadotropin synthesis and release directly by acting on the pituitary gland or indirectly by decreasing the activity of GnRH neurons. Therefore, the next step to understand seasonal reproduction is to investigate how the activities of GnRH and GnIH neurons in the hypothalamus and their receptors in the pituitary gland are regulated by external and internal signals. It is possible that locally-produced triiodothyronine resulting from the action of type 2 iodothyronine deiodinase on thyroxine stimulates the release of gonadotropins, perhaps by action on GnRH neurons. The function of GnRH neurons is also regulated by transcription of the GnRH gene. Melatonin, a nocturnal hormone, stimulates the synthesis and release of GnIH and GnIH may therefore regulate a daily rhythm of gonadotropin secretion. GnIH may also temporally suppress gonadotropin secretion when environmental conditions are unfavorable. Environmental and social milieus fluctuate seasonally in the wild. Accordingly, complex interactions of various neuronal and hormonal systems need to be considered if we are to understand the mechanisms underlying seasonal reproduction.

  12. Anti-Müllerian hormone serum values and ovarian reserve: can it predict a decrease in fertility after ovarian stimulation by ART cycles?

    Directory of Open Access Journals (Sweden)

    Tito Silvio Patrelli

    Full Text Available BACKGROUND: A variety of indicators of potentially successful ovarian stimulation cycles are available, including biomarkers such as anti-Mullerian hormone. The aim of our study was to confirm the usefulness of serum anti-Mullerian hormone assay in predicting ovarian response and reproductive outcome in women eligible for ART cycles. MATERIALS: Forty-six women undergoing ART cycles at the Centre for Reproductive Medicine in Parma were recruited from March-to-June 2010. INCLUSION CRITERIA: age<42 years; body-mass-index = 20-25; regular menstrual cycles; basal serum FSH concentration <12 IU/L and basal serum estradiol concentration <70 pg/mL. The couples included in our study reported a variety of primary infertility causes. All women underwent FSH stimulation and pituitary suppression (GnRH-agonist/GnRH-antagonist protocols. Women were considered poor-responders if they had ≤ 3 oocytes; normal-responders 4-9 oocytes and high-responders ≥ 10 oocytes. Serum samples for the AMH assays were obtained on the first and last days of stimulation. A P value ≤ 0.05 was considered statistically significant. RESULT: FSH levels increased significantly when AMH levels decreased. The total dose of r-FSH administered to induce ovulation was not correlated to AMH. The number of follicles on the hCG, serum estradiol levels on the hCG-day, and the number of retrieved oocytes were significantly correlated to AMH. The number of fertilized oocytes was significantly correlated to the AMH levels. No significant correlation was found between obtained embryos or transferred embryos and AMH. Basal serum AMH levels were significantly higher than those measured on the hCG-day, which appeared significantly reduced. There was a significant correlation between AMH in normal responders and AMH in both high and poor responders. CONCLUSIONS: Our data confirm the clinical usefulness of AMH in ART-cycles to customize treatment protocols and suggest the necessity of verifying an

  13. Addition of low dose hCG to rFSh benefits older women during ovarian stimulation for IVF

    Directory of Open Access Journals (Sweden)

    Gomaa Hala

    2012-08-01

    Full Text Available Abstract Background To compare the outcome of IVF cycles in women receiving controlled ovarian stimulation with recFSH or recFSH plus low dose hCG. Methods A retrospective case control study, performed at a private practice affiliated with an academic institute. Patients were infertile women who were treated with IVF/ICSI and controlled ovarian stimulation in a long GnRH agonist protocol using either low dose hCG in addition to recFSH [N = 88] or recFSH alone [N = 99]. Primary outcomes were mean FSH dose, number of mature eggs, number of fertilized eggs, and serum levels of estradiol. Secondary outcomes were endometrial thickness, cycle cancellations and pregnancy rates. Results A significant increase in number of mature and fertilized eggs was observed in women over 40 years of age using low dose hCG in addition to recFSH. The estradiol level was significantly higher on the day of hCG administration and the serum level of FSH on cycle day 7 and on the day of hCG administration were lower. Conclusion Addition of low dose hCG to recFSH compared with recFSH alone significantly modified cycle characteristics in patients >/= 40 years and could be of potential benefit for IVF cycles in older infertile women.

  14. Polycystic ovarian disease.

    Science.gov (United States)

    Raj, S G; Talbert, L M

    1984-01-01

    Polycystic ovarian disease (PCOD) was first described as a single disease by Stein and Leventhal in 1935, but now has been separated into several distinct entities, comprising a symptom complex. The most frequent presenting symptoms associated with PCOD are obesity, hirsutism, amenorrhea or anovulation, dysfunctional uterine bleeding, irregular menses, and infertility. The common finding of hirsutism in PCOD patients is a reflection of the hyperandrogenism resulting from elevation of all the androgens, including testosterone, androstenediol, dehydroepiandrostrone sulfate (DHEA-S), and androstenedione. Some patients with all the clinical features of PCOD can be shown, through appropriate testing, to have an attenuated form of classic congenital adrenal hyperplasia (CAH). Serum follicle stimulating hormone (FSH) levels are usually low or in the normal range, and serum luteinizing hormone (LH) levels are usually elevated in patients with PCOD, resulting in an altered LH/FSH ratio. Treatment for PCOD must be based on the needs and desires of the individual patient, and on the pathophysiology of the patient's particular abnormalities. When pregnancy is desired, ovulation induction with clomiphene is indicated. Clomiphene is a weak estrogen that induces a transient rise in serum LH and FSH, followed by a gonadotropic pattern similar to normal cycles. A 72% ovulation rate and a 41.8% conception rate have been reported after treatment with clomiphene. In patients who do not respond to clomiphene, or clomiphene with added human chorionic gonadotropin (hCG), human menopausal gonadotropin (hMG) can be used to induce ovulation, but the patient should be closely monitored for multiple ovulation, multiple pregnancy, or hyperstimulation syndrome. For patients not interested in conception, regular menstrual cyclicity can be restored and hyperandrogenism reduced with oral contraceptives (OCs).

  15. Neonatal outcomes and congenital malformations in children born after human menopausal gonadotropin and medroxyprogesterone acetate treatment cycles.

    Science.gov (United States)

    Zhang, Jie; Mao, Xiaoyan; Wang, Yun; Chen, Qiuju; Lu, Xuefeng; Hong, Qingqing; Kuang, Yanping

    2017-12-01

    To investigate neonatal outcomes and congenital malformations in children born after in vitro fertilization (IVF) and vitrified embryo transfer cycles using human menopausal gonadotrophin and medroxyprogesterone acetate (hMG + MPA) treatment. We performed a retrospective cohort study including 4596 live born babies. During January 2014-June 2016, children born after either hMG + MPA treatment, gonadotropin releasing hormone agonist short protocol, or mild ovarian stimulation were included. The main outcome measures were neonatal outcomes and congenital malformations. Neonatal outcomes both for singletons and twins such as mean birth weight and length, gestational age, the frequency of preterm birth were comparable between groups. Rate of stillbirth and perinatal death were also similar. No significant differences were found in the overall incidence of congenital malformations between the three groups. Multivariable logistic regression indicated that hMG + MPA regimen did not significantly increase the risk of congenital malformations compared with short protocol and mild ovarian stimulation, with adjusted odds ratio of 1.22 [95% confidence interval (CI) 0.61-2.44] and 1.38 (CI 0.65-2.93), respectively, after adjusting for confounding factors. Our data suggested that compared with conventional ovarian stimulations, hMG + MPA treatment neither compromised neonatal outcomes of IVF newborns, nor did increase the prevalence of congenital malformations.

  16. The effect of follicular fluid hormones on oocyte recovery after ovarian stimulation: FSH level predicts oocyte recovery

    Directory of Open Access Journals (Sweden)

    Rinaudo Paolo F

    2009-04-01

    Full Text Available Abstract Background Ovarian stimulation for assisted reproductive technology (ART overcomes the physiologic process to develop a single dominant follicle. However, following stimulation, egg recovery rates are not 100%. The objective of this study is to determine if the follicular fluid hormonal environment is associated with oocyte recovery. Methods This is a prospective study involving patients undergoing ART by standard ovarian stimulation protocols at an urban academic medical center. A total of 143 follicular fluid aspirates were collected from 80 patients. Concentrations of FSH, hCG, estradiol, progesterone, testosterone and prolactin were determined. A multivariable regression analysis was used to investigate the relationship between the follicular fluid hormones and oocyte recovery. Results Intrafollicular FSH was significantly associated with oocyte recovery after adjustment for hCG (Adjusted odds ratio (AOR = 1.21, 95%CI 1.03–1.42. The hCG concentration alone, in the range tested, did not impact the odds of oocyte recovery (AOR = 0.99, 95%CI 0.93–1.07. Estradiol was significantly associated with oocyte recovery (AOR = 0.98, 95% CI 0.96–0.99. After adjustment for progesterone, the strength of association between FSH and oocyte recovery increased (AOR = 1.84, 95%CI 1.45–2.34. Conclusion The relationship between FSH and oocyte recovery is significant and appears to work through mechanisms independent of the sex hormones. FSH may be important for the physiologic event of separation of the cumulus-oocyte complex from the follicle wall, thereby influencing oocyte recovery. Current methods for inducing the final stages of oocyte maturation, with hCG administration alone, may not be optimal. Modifications of treatment protocols utilizing additional FSH may enhance oocyte recovery.

  17. Comparative effects of sub-stimulating concentrations of non-human versus human Luteinizing Hormones (LH) or chorionic gonadotropins (CG) on adenylate cyclase activation by forskolin in MLTC cells.

    Science.gov (United States)

    Nguyen, Thi-Mong Diep; Filliatreau, Laura; Klett, Danièle; Combarnous, Yves

    2018-05-15

    We have compared various Luteinizing Hormone (LH) and Chorionic Gonadotropin (CG) preparations from non-human and human species in their ability to synergize with 10 µM forskolin (FSK) for cyclic AMP intracellular accumulation, in MLTC cells. LH from rat pituitary as well as various isoforms of pituitary ovine, bovine, porcine, equine and human LHs and equine and human CG were studied. In addition, recombinant human LH and CG were also compared with the natural human and non-human hormones. Sub-stimulating concentrations of all LHs and CGs (2-100 pM) were found to stimulate cyclic AMP accumulation in MLTC cells in the presence of an also non-stimulating FSK concentration (10 µM). Like rat LH, the most homologous available hormone for mouse MLTC cells, all non-human LHs and CG exhibit a strong potentiating effect on FSK response. The human, natural and recombinant hLH and hCG also do so but in addition, they were found to elicit a permissive effect on FSK stimulation. Indeed, when incubated alone with MLTC cells at non-stimulating concentrations (2-70 pM) hLH and hCG permit, after being removed, a dose-dependent cyclic AMP accumulation with 10 µM FSK. Our data show a clearcut difference between human LH and CG compared to their non-human counterparts on MLTC cells adenylate cyclase activity control. This points out the risk of using hCG as a reference ligand for LHR in studies using non-human cells. Copyright © 2018 Elsevier Inc. All rights reserved.

  18. PIVET rFSH dosing algorithms for individualized controlled ovarian stimulation enables optimized pregnancy productivity rates and avoidance of ovarian hyperstimulation syndrome

    Directory of Open Access Journals (Sweden)

    Yovich JL

    2016-08-01

    Full Text Available John L Yovich,1,2,* Birgit Alsbjerg,3,4,* Jason L Conceicao,1 Peter M Hinchliffe,1 Kevin N Keane1,2,* 1PIVET Medical Centre, Perth, 2School of Biomedical Science, Curtin Health Innovation Research Institute Bioscience, Curtin University, Perth, WA, Australia; 3The Fertility Clinic, Skive Regional Hospital, Skive, 4Faculty of Health, Aarhus University, Aarhus, Denmark *These authors contributed equally to this work Abstract: The first PIVET algorithm for individualized recombinant follicle stimulating hormone (rFSH dosing in in vitro fertilization, reported in 2012, was based on age and antral follicle count grading with adjustments for anti-Müllerian hormone level, body mass index, day-2 FSH, and smoking history. In 2007, it was enabled by the introduction of a metered rFSH pen allowing small dosage increments of ~8.3 IU per click. In 2011, a second rFSH pen was introduced allowing more precise dosages of 12.5 IU per click, and both pens with their individual algorithms have been applied continuously at our clinic. The objective of this observational study was to validate the PIVET algorithms pertaining to the two rFSH pens with the aim of collecting ≤15 oocytes and minimizing the risk of ovarian hyperstimulation syndrome. The data set included 2,822 in vitro fertilization stimulations over a 6-year period until April 2014 applying either of the two individualized dosing algorithms and corresponding pens. The main outcome measures were mean oocytes retrieved and resultant embryos designated for transfer or cryopreservation permitted calculation of oocyte and embryo utilization rates. Ensuing pregnancies were tracked until live births, and live birth productivity rates embracing fresh and frozen transfers were calculated. Overall, the results showed that mean oocyte numbers were 10.0 for all women <40 years with 24% requiring rFSH dosages <150 IU. Applying both specific algorithms in our clinic meant that the starting dose was not altered for

  19. Short-term androgen priming by use of aromatase inhibitor and hCG before controlled ovarian stimulation for IVF. A randomized controlled trial

    DEFF Research Database (Denmark)

    Lossl, K; Andersen, C Yding; Loft, A

    2008-01-01

    Temporary exposure of follicles to increased levels of androgens may augment follicular responsiveness. The present study tested whether short-term androgen priming by aromatase inhibitor and human chorionic gonadotrophin (hCG) before controlled ovarian stimulation (COS) increases the number of top......-quality embryos after IVF/ICSI....

  20. Single and repeated GnRH agonist stimulation tests compared with basal markers of ovarian reserve in the prediction of outcome in IVF

    NARCIS (Netherlands)

    Hendriks, D.J.; Broekmans, F.J.M.; Bancsi, L.F.J.M.M.; Looman, C.W.N.; Jong, F.H. de; Velde, E.R. te

    Purpose: To study the value of a single or repeated GnRH agonist stimulation test (GAST) in predicting outcome in IVF compared to basal ovarian reserve tests. Methods: A total of 57 women was included. In a cycle prior to the IVF treatment, on day 3, an antral follicle count (AFC) was performed

  1. Effects of ionizing radiation and pretreatment with [D-Leu6,des-Gly10] luteinizing hormone-releasing hormone ethylamide on developing rat ovarian follicles

    International Nuclear Information System (INIS)

    Jarrell, J.; YoungLai, E.V.; McMahon, A.; Barr, R.; O'Connell, G.; Belbeck, L.

    1987-01-01

    To assess the effects of a gonadotropin-releasing hormone agonist, [D-Leu6,des-Gly10] luteinizing hormone-releasing hormone ethylamide, in ameliorating the damage caused by ionizing radiation, gonadotropin-releasing hormone agonist was administered to rats from day 22 to 37 of age in doses of 0.1, 0.4, and 1.0 microgram/day or vehicle and the rats were sacrificed on day 44 of age. There were no effects on estradiol, progesterone, luteinizing, or follicle-stimulating hormone, nor an effect on ovarian follicle numbers or development. In separate experiments, rats treated with gonadotropin-releasing hormone agonist in doses of 0.04, 0.1, 0.4, or 1.0 microgram/day were either irradiated or sham irradiated on day 30 and all groups sacrificed on day 44 of age. Irradiation produced a reduction in ovarian weight and an increase in ovarian follicular atresia. Pretreatment with the agonist prevented the reduction in ovarian weight and numbers of primordial and preantral follicles but not healthy or atretic antral follicles. Such putative radioprotection should be tested on actual reproductive performance

  2. Effect of altering the intervals between consecutive superovulatory doses of porcine follicle-stimulating hormone on ovarian responses and embryo yields in anestrous ewes.

    Science.gov (United States)

    Bartlewski, P M; Murawski, M; Schwarz, T; Oliveira, M E F

    2017-05-01

    The effect of varying intervals between successive gonadotropin injections on the superovulatory outcomes in anestrous Rideau Arcott ewes superstimulated for ovarian follicular development with multiple doses of porcine FSH (pFSH) was evaluated in a single study. Twenty-five animals received six (1×2.5ml and 5×1.25ml) injections of Folltropin ® -V given at 0800 and 1600h or at 0800 and 2000h in Group 1 (n=9) or Group 2 (n=16), respectively. An i.m. injection of 500 IU of equine chorionic gonadotropin (eCG; Folligon ® ) was given concurrently with the first pFSH dose. Time of estrus was synchronized among ewes with intravaginal sponges containing 60mg of medroxyprogesterone acetate (Veramix ® ) that were left in place for 14days; sponges were removed at the time of the 5th pFSH injection. Six days after insertion of MAP sponges, all ewes received an i.m. injection of estradiol-17β dissolved in 1ml of sesame oil (350μg/ewe) to synchronize follicular wave emergence. Following the last pFSH dose, all animals were given a single i.m. injection of 50μg of gonadotropin-releasing hormone (GnRH; Cystorelin ® ) to induce ovulations before placing in a pen with four fertile rams for 36h. The ovarian responses were assessed and embryos recovered surgically 7days after GnRH injections. The mean number of corpora lutea was greater (Pewes (21.0±2.9 compared with 10.4±1.6, respectively; mean±SEM) but there was no difference (P>0.05) in the number of transferable embryos (5.4±2.4 compared with 5.4±1.3/ewe, respectively), and Group 1 animals had significantly more degenerated embryos than Group 2 ewes (2.6±1.2 compared with 0.6±0.3/ewe, respectively). A superovulatory protocol wherein pFSH injections were given at 0800 and 1600h was more effective in terms of inducing multiple ovulations than the protocol with 12-h intervals between consecutive pFSH doses, but it was not associated with an increased production of transferable quality embryos by anestrous ewes

  3. Suppression of LH during ovarian stimulation: analysing threshold values and effects on ovarian response and the outcome of assisted reproduction in down-regulated women stimulated with recombinant FSH.

    Science.gov (United States)

    Balasch, J; Vidal, E; Peñarrubia, J; Casamitjana, R; Carmona, F; Creus, M; Fábregues, F; Vanrell, J A

    2001-08-01

    It has been recently suggested that gonadotrophin-releasing hormone agonist down-regulation in some normogonadotrophic women may result in profound suppression of LH concentrations, impairing adequate oestradiol synthesis and IVF and pregnancy outcome. The aims of this study, where receiver-operating characteristic (ROC) analysis was used, were: (i) to assess the usefulness of serum LH measurement on stimulation day 7 (S7) as a predictor of ovarian response, IVF outcome, implantation, and the outcome of pregnancy in patients treated with recombinant FSH under pituitary suppression; and (ii) to define the best threshold value, if any, to discriminate between women with 'low' or 'normal' LH concentrations. A total of 144 infertile women undergoing IVF/intracytoplasmic sperm injection (ICSI) treatment were included. Seventy-two consecutive patients having a positive pregnancy test (including 58 ongoing pregnancies and 14 early pregnancy losses) were initially selected. As a control non-pregnant group, the next non-conception IVF/ICSI cycle after each conceptual cycle in our assisted reproduction programme was used. The median and range of LH values in non-conception cycles, conception cycles, ongoing pregnancies, and early pregnancy losses, clearly overlapped. ROC analysis showed that serum LH concentration on S7 was unable to discriminate between conception and non-conception cycles (AUC(ROC) = 0.52; 95% CI: 0.44 to 0.61) or ongoing pregnancy versus early pregnancy loss groups (AUC(ROC) = 0.59; 95% CI: 0.46 to 0.70). To assess further the potential impact of suppressed concentrations of circulating LH during ovarian stimulation on the outcome of IVF/ICSI treatment, the three threshold values of mid-follicular serum LH proposed in the literature (women with 'low' or 'normal' LH were applied to our study population. No significant differences were found with respect to ovarian response, IVF/ICSI outcome, implantation, and the outcome of pregnancy between 'low' and

  4. Outcomes of first IVF/ICSI in young women with diminished ovarian reserve.

    Science.gov (United States)

    Cohen, Jonathan; Mounsambote, Leonisse; Prier, Perrine; Mathieu d'ARGENT, Emmanuelle; Selleret, Lise; Chabbert-Buffet, Nathalie; Delarouziere, Vanina; Levy, Rachel; Darai, Emile; Antoine, Jean-Marie

    2017-08-01

    There is no consensual definition of diminished ovarian reserve and the best therapeutic strategy has not yet been demonstrated. We performed a retrospective study to evaluate outcomes following a first in-vitro fertilization/intra-cytoplasmic sperm injection (IVF/ICSI) cycle in young women with diminished ovarian reserve. Women with tubal factor, endometriosis or previous stimulation cycle were excluded. We defined diminished ovarian reserve as women ≤38 years with an AMH ≤1.1 ng/mL or antral follicular count ≤7. Among 59 IVF/ICSI cycles (40% IVF/60% ICSI), the pregnancy rate was 17% (10/59) and live birth rate 8.5% (5/59). Miscarriage rate was 50%. Baseline characteristics and IVF outcomes of the pregnant and not pregnant women were compared. No differences in age, antral follicular count, AMH, protocol used or number of harvested oocytes were found between the groups. A higher gonadotropin starting dose in the pregnancy group (397.5±87 IU vs. 314.8±103 IU; P=0.02) and a trend to a higher total dose received (4720±1349 IU vs. 3871±1367 IU; P=0.07) were noted. The present study confirms that women with diminished ovarian reserve have low live birth rates after a first IVF-ICSI cycle and that a higher gonadotropin starting dose might be associated with better outcomes.

  5. Regulation of P450 oxidoreductase by gonadotropins in rat ovary and its effect on estrogen production

    Directory of Open Access Journals (Sweden)

    Uesaka Miki

    2008-12-01

    Full Text Available Abstract Background P450 oxidoreductase (POR catalyzes electron transfer to microsomal P450 enzymes. Its deficiency causes Antley-Bixler syndrome (ABS, and about half the patients with ABS have ambiguous genitalia and/or impaired steroidogenesis. POR mRNA expression is up-regulated when mesenchymal stem cells (MSCs differentiate into steroidogenic cells, suggesting that the regulation of POR gene expression is important for steroidogenesis. In this context we examined the regulation of POR expression in ovarian granulosa cells by gonadotropins, and its possible role in steroidogenesis. Methods Changes in gene expression in MSCs during differentiation into steroidogenic cells were examined by DNA microarray analysis. Changes in mRNA and protein expression of POR in the rat ovary or in granulosa cells induced by gonadotropin treatment were examined by reverse transcription-polymerase chain reaction and western blotting. Effects of transient expression of wild-type or mutant (R457H or V492E POR proteins on the production of estrone in COS-7 cells were examined in vitro. Effects of POR knockdown were also examined in estrogen producing cell-line, KGN cells. Results POR mRNA was induced in MSCs following transduction with the SF-1 retrovirus, and was further increased by cAMP treatment. Expression of POR mRNA, as well as Cyp19 mRNA, in the rat ovary were induced by equine chorionic gonadotropin and human chorionic gonadotropin. POR mRNA and protein were also induced by follicle stimulating hormone in primary cultured rat granulosa cells, and the induction pattern was similar to that for aromatase. Transient expression of POR in COS-7 cells, which expressed a constant amount of aromatase protein, greatly increased the rate of conversion of androstenedione to estrone, in a dose-dependent manner. The expression of mutant POR proteins (R457H or V492E, such as those found in ABS patients, had much less effect on aromatase activity than expression of wild

  6. Maternal and fetal mechanisms of B cell regulation during pregnancy: human Chorionic Gonadotropin stimulates B cells to produce IL-10 while alpha-fetoprotein drives them into apoptosis

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    Franziska Fettke

    2016-12-01

    Full Text Available Maternal immune tolerance towards the fetus is an essential requisite for pregnancy. While T cell functions are well documented, little is known about the participation of B cells. We have previously suggested that IL-10 producing B cells are involved in pregnancy tolerance in mice and humans. By employing murine and human systems, we report now that fetal trophoblasts positively regulate the generation of IL-10 producing B cells. We next studied the participation of hormones produced by the placenta as well as the fetal protein alpha-fetoprotein (AFP in B cell modulation. Human Chorionic Gonadotropin (hCG, but not progesterone, estrogen or a combination of both, was able to promote changes in B cell phenotype and boost their IL-10 production, which was abolished after blocking hCG. The hCG-induced B cell phenotype was not associated with augmented galactosylation, sialylation or fucosylation of IgG subclasses in their Fc. In vitro, hCG induced the synthesis of asymmetrically glycosylated antibodies in their Fab region. Interestingly, AFP had dual effects depending on the concentration. At concentrations corresponding to maternal serum levels, it did not modify the phenotype or IL-10 secretion of B cells. At fetal concentrations, however, AFP was able to drive B cells into apoptosis, which may indicate a protective mechanism to avoid maternal B cells to reach the fetus.Our data suggests that the fetus secrete factors that promote a pregnancy-friendly B cell phenotype, unraveling interesting aspects of B cell function and modulation by pregnancy hormones and fetal proteins.

  7. Estradiol-Dependent Stimulation and Suppression of Gonadotropin-Releasing Hormone Neuron Firing Activity by Corticotropin-Releasing Hormone in Female Mice.

    Science.gov (United States)

    Phumsatitpong, Chayarndorn; Moenter, Suzanne M

    2018-01-01

    Gonadotropin-releasing hormone (GnRH) neurons are the final central regulators of reproduction, integrating various inputs that modulate fertility. Stress typically inhibits reproduction but can be stimulatory; stress effects can also be modulated by steroid milieu. Corticotropin-releasing hormone (CRH) released during the stress response may suppress reproduction independent of downstream glucocorticoids. We hypothesized CRH suppresses fertility by decreasing GnRH neuron firing activity. To test this, mice were ovariectomized (OVX) and either implanted with an estradiol capsule (OVX+E) or not treated further to examine the influence of estradiol on GnRH neuron response to CRH. Targeted extracellular recordings were used to record firing activity from green fluorescent protein-identified GnRH neurons in brain slices before and during CRH treatment; recordings were done in the afternoon when estradiol has a positive feedback effect to increase GnRH neuron firing. In OVX mice, CRH did not affect the firing rate of GnRH neurons. In contrast, CRH exhibited dose-dependent stimulatory (30 nM) or inhibitory (100 nM) effects on GnRH neuron firing activity in OVX+E mice; both effects were reversible. The dose-dependent effects of CRH appear to result from activation of different receptor populations; a CRH receptor type-1 agonist increased firing activity in GnRH neurons, whereas a CRH receptor type-2 agonist decreased firing activity. CRH and specific agonists also differentially regulated short-term burst frequency and burst properties, including burst duration, spikes/burst, and/or intraburst interval. These results indicate that CRH alters GnRH neuron activity and that estradiol is required for CRH to exert both stimulatory and inhibitory effects on GnRH neurons. Copyright © 2018 Endocrine Society.

  8. Differences in gene expression of granulosa cells from women undergoing controlled ovarian hyperstimulation with either recombinant follicle-stimulating hormone or highly purified human menopausal gonadotropin

    DEFF Research Database (Denmark)

    Grøndahl, Marie Louise; Borup, Rehannah; Lee, Young Bae

    2009-01-01

    randomized study. SETTING: University-based facilities for clinical services and research. PATIENT(S): Thirty women undergoing treatment with vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). INTERVENTION(S): Patients were randomly allocated to receive recombinant FSH or human (hMG) COH...

  9. Effects of acute feed restriction combined with targeted use of increasing luteinizing hormone content of follicle-stimulating hormone preparations on ovarian superstimulation, fertilization, and embryo quality in lactating dairy cows

    Science.gov (United States)

    Bender, R. W.; Hackbart, K. S.; Dresch, A. R.; Carvalho, P. D.; Vieira, L. M.; Crump, P. M.; Guenther, J. N.; Fricke, P. M.; Shaver, R. D.; Combs, D. K.; Wiltbank, M. C.

    2018-01-01

    Multiple metabolic and hormonal factors can affect the success of protocols for ovarian superstimulation. In this study, the effect of acute feed restriction and increased LH content in the superstimulatory FSH preparation on numbers of ovulations, fertilization, and embryo quality in lactating dairy cows was evaluated. Two experiments were performed using a Latin square design with treatments arranged as a 2 × 2 factorial: feed restriction (FR; 25% reduction in dry matter intake) compared with ad libitum (AL) feeding, combined with high (H) versus low (L) LH in the last 4 injections of the superstimulatory protocol. As expected, FR decreased circulating insulin concentrations (26.7 vs. 46.0 μU/mL). Two analyses were performed: one that evaluated the complete Latin square in experiment 2 and a second that evaluated only the first periods of experiments 1 and 2. For both analyses, follicle numbers, ovulation rates, and corpora lutea on d 7 were not different. In the first period analysis of experiments 1 and 2, we observed an interaction between feed allowance and amount of LH on fertilization rates, percentage of embryos or oocytes that were quality 1 and 2 embryos, and number of embryos or oocytes that were degenerate. Fertilization rates were greater for the AL-L (89.4%) and FR-H (80.1%) treatments compared with the AL-H (47.9%) and FR-L (59.9%) treatments. Similarly, the proportion of total embryos or oocytes designated as quality 1 and 2 embryos was greater for AL-L (76.7%) and FR-H (73.4%) treatments compared with AL-H (35.6%) and FR-L (47.3%) treatments. In addition, the number of degenerate embryos was decreased for AL-L (1.3) and FR-H (0.4) treatments compared with the AL-H (2.6) and FR-L (2.3) treatments. Thus, cows with either too low (FR-L) or too high (AL-H) insulin and LH stimulation had lesser embryo production after superstimulation because of reduced fertilization rate and increased percentage of degenerate embryos. Therefore, interaction of the

  10. Association of basal serum androgen levels with ovarian response and ICSI cycle outcome.

    Science.gov (United States)

    Abide Yayla, C; Ozkaya, E; Kayatas Eser, S; Sanverdi, I; Devranoglu, B; Kutlu, T

    2018-05-01

    The purpose of this study was to assess the predictive value of basal serum testosterone (T) and dehydroepiandrosterone sulfate (DHEAS) levels during follicular phase for ovarian response and outcome in intracytoplasmic sperm injection (ICSI) cycles of women with diminished ovarian reserve. We prospectively gathered data of basal serum androgen levels and ICSI cycle characteristics of 120 women with diminished ovarian reserve. Association of basal serum T and DHEAS levels with ovarian response was analyzed. Basal T and DHEAS levels were similar between pregnant and non-pregnant cases (P > 0.05). There were significant differences between groups with and without successful embryo implantation in terms of serum follicle-stimulating hormone (FSH), anti-Müllerian hormone (AMH), gonadotropin starting and total dose, and peak estradiol level (P stimulation due to unresponsiveness (n = 26, 21.7%), no oocyte at oocyte pickup (n = 11, 9.2%), no mature oocyte (n = 6, 5%), and failure of fertilization or embryo development (n = 15, 12.5%). Basal androgen levels were not significant predictors for any of the cycle outcome. AMH level was a significant predictor for failure of fertilization or embryo development (AUC 0.722, P = 0.01) and cancelation of stimulation (AUC 0.801, P stimulation (AUC 0.774, P basal T and DHEAS levels have no value in predicting any of the cycle outcome parameters.

  11. Association of Exon 10A and 10B inactivating mutation of follicle stimulating hormone receptor gene (FSHR) and Polycystic Ovarian Syndrome in Vellore cohort

    Science.gov (United States)

    Sekar, Nishu; Kulkarni, Rucha; Ozalkar, Sharvari; Prabhu, Yogamaya D.; Renu, Kaviyarasi; Ramgir, Shalaka S.; Abilash, V. G.

    2017-11-01

    Polycystic ovarian syndrome is the most common heterogenous endocrine disorder in women. Follicle stimulating hormone receptor is associated with normal development as well as maturation of follicles and triggers estrogen production in granulosa cells of the ovary. Inactivating mutation in FSHR gene correlated with reduction of ovarian function in women is due to damage to receptor function. This study aims to investigate whether inactivating mutations, in follicle stimulating hormone receptor gene is related to polycystic ovarian morphology in women with PCOS. Genomic DNA isolated from 15 subjects from Sandhya Hospital, Vellore (10 patients with PCOS and 5 healthy controls) was taken for this study. Patient data included a clinical report, hormonal levels, and ovarian morphological details. DNA isolation was followed by DNA amplification by polymerase chain reaction using Exon 10 A and Exon 10 B primers. The PCR-RFLP analysis was performed using Dde1 restriction enzyme. Here we discuss inactivating mutation found in Exon 10 of FSHR gene in patients with PCOS.The absence of inactivating mutation was observed through PCR-RFLP study on Exon 10A and Exon 10B.

  12. Paracrine stimulation of P2X7 receptor by ATP activates a proliferative pathway in ovarian carcinoma cells.

    Science.gov (United States)

    Vázquez-Cuevas, Francisco G; Martínez-Ramírez, Angélica S; Robles-Martínez, Leticia; Garay, Edith; García-Carrancá, Alejandro; Pérez-Montiel, Delia; Castañeda-García, Carolina; Arellano, Rogelio O

    2014-11-01

    P2X7 is a purinergic receptor-channel; its activation by ATP elicits a broad set of cellular actions, from apoptosis to signals for survival. Here, P2X7 expression and function was studied in human ovarian carcinoma (OCA) cells, and biopsies from non-cancerous and cancer patients were analyzed by immunohistochemistry. Ovarian surface epithelium in healthy tissue expressed P2X7 at a high level that was maintained throughout the cancer. The cell lines SKOV-3 and CAOV-3 were used to investigate P2X7 functions in OCA. In SKOV-3 cells, selective stimulation of P2X7 by 2'(3')-O-(4-benzoylbenzoyl) adenosine-5'-triphosphate (BzATP) induced a dose-dependent increase of intracellular Ca(2+) concentration ([Ca(2+)](i)) but not cell death. Instead, BzATP increased the levels of phosphorylated ERK and AKT (pERK and pAKT), with an EC(50) of 44 ± 2 and 1.27 ± 0.5 μM, respectively; 10 μM BzATP evoked a maximum effect within 15 min that lasted for 120 min. Interestingly, basal levels of pERK and pAKT were decreased in the presence of apyrase in the medium, strongly suggesting an endogenous, ATP-mediated phenomenon. Accordingly: (i) mechanically stimulated cells generated a [Ca(2+)](i) increase that was abolished by apyrase; (ii) apyrase induced a decrease in culture viability, as measured by the MTS assay for mitochondrial activity; and (iii) incubation with 10 μM AZ10606120, a specific P2X7 antagonist and transfection with the dominant negative P2X7 mutant E496A, both reduced cell viability to 70.1 ± 8.9% and to 76.5 ± 5%, respectively, of control cultures. These observations suggested that P2X7 activity was auto-induced through ATP efflux; this increased pERK and pAKT levels that generated a positive feedback on cell viability. © 2014 Wiley Periodicals, Inc.

  13. Standardization of androstenedione and estrone radioimmunoassay and profile of sex steroids, gonadotropins and prolactin - in patients with chronic anovulation due to inappropriate feedback (polycystic ovarian syndrome); Padronizacao do radioimunoensaio da androstenediona e da estrona e o perfil dos esteroides sexuais, gonadotrofinas e prolactina em pacientes com anovulacao cronica por retrocontrole improprio (sindrome dos ovarios policisticos)

    Energy Technology Data Exchange (ETDEWEB)

    Vilanova, Maria do Socorro Veras

    1992-12-01

    Full text. In order to evaluate the profile of the sex steroids gonadotropin and prolactin in polycystic ovarian syndrome (POS), 24 patients with POS were studied and compared with 20 normal women during the early follicular phase of the menstrual cycle. Radioimmunoassay techniques for androstenedione (A) and estrone (E{sub 1}) were standardized for the purpose of the study. Androstenedione and estrone were extracted from plasma with ethyl ether. The assays were maintained in equilibrium and the labelled hormone-antibody complex was then separated from the free hormone using dextran charcoal. The sensitivity of the method was 6.8 pg/tube for A and 3.7 pg/tube for E{sub 1}. Nonspecific binding ws 3.4 for A and 3.3 for E{sub 1}. The interessay error at the D50 level was 15.6 for A and 8.6 for E{sub 1}. Patients with POS had significantly higher basal levels of LH, A, T E{sub 1} and PRL and similar FSH and DHEA-S levels when compared with normal women. The LH/FSH ratio was significantly elevated and the A/T ratio was significantly decreased. The A/E{sub 1} and T/E{sub 2} ratios were elevated and the E{sub 1}/E{sub 2} was decreased, although the differences were not statistically significant. A positive correlation between A and E{sub 1} was observed in patients with POS. In view of the above data, it was concluded that: the quality control parameters of the radioimmunoassay for A and E{sub 1} standardized in the present study are considered satisfactory, and the assay could be used for diagnosis and research; the patients with POS have a different sex steroid and gonadotropin profile when compared normal women during the early follicular phase of the menstrual cycle

  14. Clinical pregnancy in a woman with idiopathic hypogonadotropic hypogonadism and low AMH: utility of ovarian reserve markers in IHH.

    Science.gov (United States)

    Chan, Crystal; Liu, Kimberly

    2014-10-01

    Serum anti-mullerian hormone (AMH) has been proposed as a useful marker of ovarian reserve that is cycle-independent and predictive of outcome in assisted reproduction cycles. However, there is evidence that AMH production is gonadotropin-dependent, and that under the influence of FSH, growing follicles contribute to circulating AMH levels. Therefore, AMH testing may not be universally reflective of the primordial follicle pool in certain conditions. We demonstrate that in patients with idiopathic hypogonadotropic hypogonadism (IHH) and deficient gonadotropin production, AMH and antral follicle count (AFC) may not be reliable markers of ovarian reserve. Case report. Fertility clinic at a tertiary academic hospital. A 30-year-old nulligravid patient with IHH who presented for fertility treatment with low FSH (0.3 IU/L), LH (0.1 IU/L), estradiol (77 pmol/L) and AMH levels (0.65 pmol/L), and an unmeasurable AFC. A three-month course of priming with oral micronized 17β-estradiol, followed by daily injections of human menopausal gonadotropins (hMG). AMH level and follicular development. After 60 days of stimulation with hMG, the patient's AMH level increased to a peak of 1.27 pmol/L. After 102 days of stimulation, her estradiol level rose to 480 pmol/L and a 19 mm dominant follicle was detected. The patient successfully conceived with intrauterine insemination. Ovarian reserve testing in patients with IHH can be challenging due to the contracted appearance of the ovaries and deficient FSH production. In these patients, AMH levels may underestimate ovarian reserve due to the lack of FSH-dependent growing follicles. When treated with a long course of hMG, these patients may exhibit increased AMH levels and demonstrate adequate follicular development.

  15. Association of basal serum testosterone levels with ovarian response and in vitro fertilization outcome

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    Sun Mei

    2011-01-01

    Full Text Available Abstract Background To evaluate basal testosterone (T levels during follicular phase of the menstrual cycle as a predictor for ovarian response and in vitro fertilization (IVF outcome. Method We analyzed data retrospectively from hospital-based IVF center including one thousand two hundred and sixty Chinese Han women under their first IVF cycle reached the ovum pick-up stage, without polycystic ovary syndrome (PCOS or endometriosis undergoing long IVF protocol. Patients were divided into 2 groups. Group 1: patients with diminished ovarian reserve (basal FSH >10 IU/L (n = 187; Group 2: patients with normal ovarian reserve (basal FSH Results Basal T levels were markly different between pregnant and non-pregnant women in Group 1; whereas not in Group 2. A testosterone level of 47.85 ng/dl was shown to predict pregnancy outcome with a sensitivity of 52.8% and specificity of 65.3%; and the basal T was correlated with the numbers of large follicles (> 14 mm on HCG day in Group 1. Significantly negative correlations were observed between basal T, days of stimulation and total dose of gonadotropins after adjusting for confounding factors in both groups. Conclusion In women with diminished ovarian reserve, basal T level was a predictor for the number of large follicles on HCG day and pregnancy outcome; but could not in those with normal serum FSH. Basal T levels were associated with both days of stimulation and total dose of gonadotropins, indicating that lower level of T might relate with potential ovarian poor response.

  16. Hormonal Changes After Laparoscopic Ovarian Diathermy in Patients with Polycystic Ovarian Syndrome.

    Science.gov (United States)

    Elnaggar, Elsayed A; Elwan, Youssef Abo; Ibrahim, Safaa A; Abdalla, Mena M

    2016-10-01

    To assess the changes in hormonal profile (serum FSH, LH, prolactin and total testosterone) following laparoscopic ovarian drilling (LOD) in patients with polycystic ovarian syndrome. Fifty patients with PCOS have been included in this study. Serum prolactin, total testosterone, follicular-stimulating hormone (FSH) and luteinizing hormone (LH) levels have been used as biochemical markers, before and after procedures. Laparoscopic ovarian drilling was successfully employed without any surgical complications and on an average follow-up time of 24 weeks after the procedure. During the follow-up serum values for prolactin, total testosterone and LH have decreased significantly and FSH levels remained unchanged after the procedure. The LOD in patients with PCOS may avoid or reduce the risk of OHSS and the multiple pregnancy rate induced by gonadotropin therapy. The high pregnancy rate and the economic aspect of the procedure offer an attractive management for patients with PCOS. However, LOD can be considered as second-line treatment after clomiphene citrate treatment failure and/or resistance.

  17. Ovarian stimulation with follicle-stimulating hormone under increasing or minimal concentration of progesterone in dairy cows.

    Science.gov (United States)

    El-Sherry, T M; Matsui, M; Kida, K; Miyamoto, A; Megahed, G A; Shehata, S H; Miyake, Y-I

    2010-03-01

    The objective of this study was to investigate the effect of the presence or absence of Corpus luteum (CL) on the follicular population during superstimulation in dairy cows (Holstein-Friesian cattle). Animals were divided into two groups as follows: (1) Growing CL group (G1): Cows (n=7) received a total dose of 28 Armour units (AU) follicle-stimulating hormone (FSH) through the first 4 d (twice daily) after spontaneous ovulation (Day 0). (2) CL Absence group (G2): Cows (n=10) received prostaglandin F(2alpha) (PGF(2alpha)) at 9 or 10 d after ovulation. After 36h, all the follicles (larger than 5mm) were aspirated (Day 0). The FSH treatment started 24h after aspiration and continued for 4 d. The number of small (3 to or = 8mm) follicles was examined on Days 1, 3, and 5 in all groups. Blood samples were collected daily for 5 d, and progesterone (P(4)), estradiol (E(2)), insulin-like growth factor-1 (IGF-1), and growth hormone (GH) in plasma were measured by enzyme immunoassays. The results showed that in G1, the P(4) level increased gradually from 0.5 ng/mL at Day 1 to 2 ng/mL at Day 5, whereas in G2, the P(4) level was completely below 0.5 ng/mL. All cows of the G2 group showed an increase of E(2) at Day 3 or Day 4 followed by an increase of IGF-1 within 24h, while GH increased concomitantly with the E(2) increase in 8 of 10 trials. On the other hand, cows of the G1 group showed neither E(2) nor IGF-1 increase. Moreover, at the end of the treatment, the number of follicles in the G2 group was significantly increased compared with that of the G1 group (22.8+/-2.0 vs. 11.6+/-2.0). In conclusion, low P(4) level during FSH treatment enhanced multiple follicular growth and E(2) secretion, which was followed by increase of IGF-1 and GH. Therefore, the absence of the CL may play a critical role in the superovulation response by controlling the number of growing follicles. Copyright 2010 Elsevier Inc. All rights reserved.

  18. Predictive value of repeated measurements of luteal progesterone and estradiol levels in patients with intrauterine insemination and controlled ovarian stimulation.

    Science.gov (United States)

    Bakas, Panagiotis; Simopoulou, Maria; Giner, Maria; Drakakis, Petros; Panagopoulos, Perikles; Vlahos, Nikolaos

    2017-10-01

    The objective of this study is to assess if the difference of repeated measurements of estradiol and progesterone during luteal phase predict the outcome of intrauterine insemination. Prospective study. Reproductive clinic. 126 patients with infertility. Patients underwent controlled ovarian stimulation with recombinant FSH (50-150 IU/d). The day of IUI patients were given p.o natural micronized progesterone in a dose of 100 mg/tds. The area under the receiver characteristic operating curve (ROC curve) in predicting clinical pregnancy for % change of estradiol level on days 6 and 10 was 0.892 with 95% CI: 0.82-0.94. A cutoff value of change > -29.5% had a sensitivity of 85.7 with a specificity of 90.2. The corresponding ROC curve for % change of progesterone level was 0.839 with 95% CI: 0.76-0.90. A cutoff value of change > -33% had a sensitivity of 85 with a specificity of 75. The % change of estradiol and progesterone between days 6 and 10 has a predictive ability of pregnancy after IUI with COS of 89.2% and 83.4%, respectively. The addition of % of progesterone to % change of estradiol does not improve the predictive ability of % estradiol and should not be used.

  19. INCIDENCE OF OVARIAN CYST IN HYPOTHYROIDISM: AN INSTITUTIONAL STUDY

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    Ramesan C

    2016-09-01

    Full Text Available BACKGROUND Primary hypothyroidism is the decrease in production and secretion of thyroid hormones by the thyroid gland. This is characterised by slackening of metabolism and leading to multiple system impairment. The important aetiological factors for primary hypothyroidism are congenital, iodine deficiency, autoimmune thyroiditis and iatrogenic.[1] Ovarian cysts are a common cause for gynaecological surgeries. The aetiology[2] of ovarian cysts can vary greatly including benign or malignant tumours, endometriosis and inflammation, etc. However, some cysts are direct result of endocrine disorders and do not require surgery. Hypothyroidism may cause reproductive and endocrinological disorders as well. The aetiopathogenesis is complex. In 1960 Van Wyk and Grumbach first described the relation between ovarian cyst and hypothyroidism. They proposed that there was a hormonal overlap in the pituitary feedback mechanism. It is due to the fact that TSH, GH, FSH and LH are all glycoproteins with a common alpha chain and may thus cross react. High TSH could produce FSH and LH like activity leading to luteinised ovarian cyst. The TRH may also act on pituitary cells to stimulate gonadotropin release and hence FSH and LH. Other postulated mechanisms are increased ovarian sensitivity to gonadotropins, altered metabolism of oestrogen, hypothalamopituitary dysfunction and altered prolactin metabolism. AIMS To study the percentage of ovarian cyst among the diagnosed cases of primary hypothyroidism and then to find out the association between hypothyroidism and ovarian cyst. To study the relation between level of TSH and size of ovarian cyst. To study the percentage of ovarian cyst among patients with TSH 100 mIU/L separately. SETTINGS Study Design: Descriptive: Cross-sectional study. Duration: One year. Period: March 2013 to February 2014. Sample Size: 100. Study Area: Government Medical College, Calicut. INCLUSION CRITERIA Female patients of age more than 12

  20. Early Alterations in Ovarian Surface Epithelial Cells and Induction of Ovarian Epithelial Tumors Triggered by Loss of FSH Receptor

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    Xinlei Chen

    2007-06-01

    Full Text Available Little is known about the behavior of the ovarian surface epithelium (OSE, which plays a central role in ovarian cancer etiology. It has been suggested that incessant ovulation causes OSE changes leading to transformation and that high gonadotropin levels during postmenopause activate OSE receptors, inducing proliferation. We examined the chronology of OSE changes, including tumor appearance, in a mouse model where ovulation never occurs due to deletion of follitropin receptor. Changes in epithelial cells were marked by pan-cytokeratin (CK staining. Histologic changes and CK staining in the OSE increased from postnatal day 2. CK staining was observed inside the ovary by 24 days and increased thereafter in tumor-bearing animals. Ovaries from a third of aged (1 year mutant mice showed CK deep inside, indicating cell migration. These tumors resembled serous papillary adenoma of human ovaries. Weak expression of GATA-4 and elevation of PCNA, cyclooxygenase-1, cyclooxygenase-2, and plateletderived growth factor receptors α and β in mutants indicated differences in cell proliferation, differentiation, and inflammation. Thus, we report that OSE changes occur long before epithelial tumors appear in FORKO mice. Our results suggest that neither incessant ovulation nor follicle-stimulating hormone receptor presence in the OSE is required for inducing ovarian tumors; thus, other mechanisms must contribute to ovarian tumorigenesis.

  1. Expression and Role of Gonadotropin-Releasing Hormone 2 and Its Receptor in Mammals

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    Amy T. Desaulniers

    2017-12-01

    Full Text Available Gonadotropin-releasing hormone 1 (GnRH1 and its receptor (GnRHR1 drive mammalian reproduction via regulation of the gonadotropins. Yet, a second form of GnRH (GnRH2 and its receptor (GnRHR2 also exist in mammals. GnRH2 has been completely conserved throughout 500 million years of evolution, signifying high selection pressure and a critical biological role. However, the GnRH2 gene is absent (e.g., rat or inactivated (e.g., cow and sheep in some species but retained in others (e.g., human, horse, and pig. Likewise, many species (e.g., human, chimpanzee, cow, and sheep retain the GnRHR2 gene but lack the appropriate coding sequence to produce a full-length protein due to gene coding errors; although production of GnRHR2 in humans remains controversial. Certain mammals lack the GnRHR2 gene (e.g., mouse or most exons entirely (e.g., rat. In contrast, old world monkeys, musk shrews, and pigs maintain the coding sequence required to produce a functional GnRHR2. Like GnRHR1, GnRHR2 is a 7-transmembrane, G protein-coupled receptor that interacts with Gαq/11 to mediate cell signaling. However, GnRHR2 retains a cytoplasmic tail and is only 40% homologous to GnRHR1. A role for GnRH2 and its receptor in mammals has been elusive, likely because common laboratory models lack both the ligand and receptor. Uniquely, both GnRH2 and GnRHR2 are ubiquitously expressed; transcript levels are abundant in peripheral tissues and scarcely found in regions of the brain associated with gonadotropin secretion, suggesting a divergent role from GnRH1/GnRHR1. Indeed, GnRH2 and its receptor are not physiological modulators of gonadotropin secretion in mammals. Instead, GnRH2 and GnRHR2 coordinate the interaction between nutritional status and sexual behavior in the female brain. Within peripheral tissues, GnRH2 and its receptor are novel regulators of reproductive organs. GnRH2 and GnRHR2 directly stimulate steroidogenesis within the porcine testis. In the female, GnRH2 and

  2. Predicting and preventing ovarian hyperstimulation syndrome (OHSS: the need for individualized not standardized treatment

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    Fiedler Klaus

    2012-04-01

    Full Text Available Abstract Ovarian hyperstimulation syndrome (OHSS is the most serious complication of controlled ovarian stimulation (COS as part of assisted reproductive technologies (ART. While the safety and efficacy of ART is well established, physicians should always be aware of the risk of OHSS in patients undergoing COS, as it can be fatal. This article will briefly present the pathophysiology of OHSS, including the key role of vascular endothelial growth factor (VEGF, to provide the foundation for an overview of current techniques for the prevention of OHSS. Risk factors and predictive factors for OHSS will be presented, as recognizing these risk factors and individualizing the COS protocol appropriately is the key to the primary prevention of OHSS, as the benefits and risks of each COS strategy vary among individuals. Individualized COS (iCOS could effectively eradicate OHSS, and the identification of hormonal, functional and genetic markers of ovarian response will facilitate iCOS. However, if iCOS is not properly applied, various preventive measures can be instituted once COS has begun, including cancelling the cycle, coasting, individualizing the human chorionic gonadotropin trigger dose or using a gonadotropin-releasing hormone (GnRH agonist (for those using a GnRH antagonist protocol, the use of intravenous fluids at the time of oocyte retrieval, and cryopreserving/vitrifying all embryos for subsequent transfer in an unstimulated cycle. Some of these techniques have been widely adopted, despite the scarcity of data from randomized clinical trials to support their use.

  3. Development of molecular markers for zebrafish (Danio rerio) ovarian follicle growth assessment following in-vitro culture in cryopreservation studies.

    Science.gov (United States)

    Anil, Siji; Rawson, David; Zhang, Tiantian

    2018-05-29

    Development of in vitro culture protocol for early stage ovarian follicles of zebrafish is important since cryopreserved early stage ovarian follicles would need to be matured in vitro following cryopreservation before they can be fertilised. Development of molecular markers for zebrafish (Danio rerio) ovarian follicle growth assessment following in vitro culture of early stage zebrafish ovarian follicles in ovarian tissue fragments is reported here for the first time although some work has been reported for in vitro culture of isolated early stage zebrafish ovarian follicles. The main aim of the present study was to develop molecular markers in an optimised in vitro culture protocol for stage I and stage II zebrafish ovarian follicles in ovarian tissue fragments. The effect of concentration of the hormones human chorionic gonadotropin and follicle stimulating hormones, and additives such as Foetal Bovine Serum and Bovine Serum Albumin were studied. The results showed that early stage zebrafish ovarian fragments containing stage I and stage II follicles which are cultured in vitro for 24 h in 20% FBS and 100mIU/ml FSH in 90% L-15 medium at 28 °C can grow to the size of stage II and stage III ovarian follicles respectively. More importantly the follicle growth from stage I to stage II and from stage II to stage III were confirmed using molecular markers such as cyp19a1a (also known as P450aromA) and vtg1 genes respectively. However, no follicle growth was observed following cryopreservation and in vitro culture. Copyright © 2018 Elsevier Inc. All rights reserved.

  4. Gonadotropins, their receptors, and the regulation of testicular functions in fish

    NARCIS (Netherlands)

    Schulz, Rüdiger W; Vischer, H F; Cavaco, J E; Dos Santos Rocha, M.E.; Tyler, R.C.; Goos, H.J.; Bogerd, J.

    The pituitary gonadotropins luteinizing hormone (LH) and follicle-stimulating hormone (FSH) regulate steroidogenesis and spermatogenesis by activating receptors expressed by Leydig cells (LH receptor) and Sertoli cells (FSH receptor), respectively. This concept is also valid in fish, although the

  5. In vitro fertilization outcome in women with endometriosis & previous ovarian surgery

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    Sonja Pop-Trajkovic

    2014-01-01

    Full Text Available Background & objectives: Women with endometriosis often need in vitro fertilization (IVF to concieve. There are conflicting data on the results of IVF in patients with endometriosis. This study was undertaken to elucidate the influence of endometriosis on IVF outcome to give the best counselling for infertile patient with this problem. Methods: The outcome measures in 78 patients with surgically confirmed endometriosis were compared with 157 patients with tubal factor infertility, all of whom have undergone IVF. The groups were matched for age and follicle stimulating hormone (FSH levels. Outcome measures included number of follicles, number of ocytes, peak oestradiol (E2 concentrations and mean number of ampoules of gonadotropins. Cumulative pregnancy, miscarriage and live birth rates were calculated in both the groups. Results: Higher cancelation rates, higher total gonadotropin requirements, lower peak E2 levels and lower oocyte yield were found in women with endometriosis and previous surgery compared with those with tubal factor infertility. However, no differences were found in fertilization, implantation, pregnancy, miscarriage, multiple births and delivery rates between the endometriosis and tubal factor infertility groups. Interpretation & conclusions: The present findings showed that women with endometriosis and previous surgery responded less well to gonadotropins during ovarian stimulation and hence the cost of treatment to achieve pregnancy was higher in this group compared with those with tubal factor infertility. However, the outcome of IVF treatment in patients with endometriosis was as good as in women with tubal factor infertility.

  6. Early hCG addition to rFSH for ovarian stimulation in IVF provides better results and the cDNA copies of the hCG receptor may be an indicator of successful stimulation

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    Paraskevis Dimitris

    2009-10-01

    Full Text Available Abstract A simple, safe and cost-effective treatment protocol in ovarian stimulation is of great importance in IVF practice, especially in the case of previous unsuccessful attempts. hCG has been used as a substitute of LH because of the degree of homology between the two hormones. The main aim of this prospective randomized study was to determine, for the first time, whether low dose hCG added to rFSH for ovarian stimulation could produce better results compared to the addition of rLH in women entering IVF-ET, especially in those women that had previous IVF failures. An additional aim was to find an indicator that would allow us to follow-up ovarian stimulation and, possibly, modify it in order to achieve a better IVF outcome; and that indicator may be the cDNA copies of the LH/hCG receptor. Group A patients (n = 58 were administered hCG and Group B rLH (n = 56 in addition to rFSH in the first days of ovarian stimulation. The number of follicles and oocytes and, most importantly, implantation and pregnancy rates were shown to be statistically significantly higher in the hCG group. This study has also determined, for the first time to our best knowledge, m-RNA for LH/hCG receptors in the lymphocytes of peripheral blood 40 h before ovum pick-up. cDNA levels of the hCG receptor after ovarian stimulation were significantly higher among women receiving hCG compared to those receiving LH. In addition, higher levels were encountered among women with pregnancy compared to those without, although this was not statistically significant due to the small number of pregnancies. It seems that hCG permits a highly effective and more stable occupancy of rLH/hCG receptors and gives more follicles and more oocytes. The determination of cDNA copies could be, in the future, a marker during ovulation induction protocols and of course a predictor for the outcome of ART in the special subgroup of patients with previous failures.

  7. Use of letrozole and clomiphene citrate combined with gonadotropins in clomiphene-resistant infertile women with polycystic ovary syndrome: a prospective study

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    Xi W

    2015-11-01

    Full Text Available Wenyan Xi,1 Shankun Liu,2 Hui Mao,1 Yongkang Yang,1 Xiang Xue,1 Xiaoning Lu1 1The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an City, Shaanxi, 2Taian City Central Hospital, Shandong, Taian, People’s Republic of China Background: Gonadotropin has been used to stimulate ovulation in clomiphene-resistant infertile women with polycystic ovary syndrome (PCOS, but it is associated with overstimulated cycles with the development of many follicles. The aim of the study was to evaluate the effectiveness and efficacy of letrozole and clomiphene citrate combined with human menopausal gonadotropin (HMG in CC-resistant infertile women with PCOS.Methods: Ninety-four women received the letrozole + HMG, 90 women received CC + HMG, and 71 women received HMG only. All women received one treatment regimen in one treatment cycle. All patients were given HMG 75 IU on alternate days daily starting on day 3 or day 7 until the day of administration of human chorionic gonadotropin.Results: The rate of monofollicular development was 80.2% in the letrozole + HMG group, 65.3% in the CC + HMG group, and 54.7% in the HMG-only group (P<0.05 for letrozole + HMG vs the other two groups. The number of developing follicles (≥14 mm follicles and the cycle cancellation rate due to ovarian hyperresponse were the lowest in the letrozole + HMG group, but the difference was not significant. The ovulation and pregnancy rate were similar among the three protocols. The HMG dose needed and the mean duration of treatment were significantly lower in the letrozole + HMG and CC + HMG groups compared with the HMG-only group.Conclusion: Letrozole in combination with HMG is an effective protocol for reducing the risks of hyperstimulation for ovarian induction in CC-resistant women with PCOS. This combination may be more appropriate in patients who are particularly sensitive to gonadotropin. Keywords: letrozole, clomiphene citrate, human menopausal gonadotropin

  8. Internal dose-effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in gonadotropin-primed weanling rat model

    Energy Technology Data Exchange (ETDEWEB)

    Shirota, Mariko [Food and Drug Safety Center, Hatano Research Institute, Kanagawa (Japan); Kaneko, Toyozo [National Institute of Health Sciences, Tokyo (Japan); Okuyama, Mitsunobu [Food and Drug Safety Center, Hatano Research Institute, Kanagawa (Japan); TEIZO Medical Co., Ltd., Kawasaki (Japan); Sakurada, Yosuke; Shirota, Kinji [Azabu University, Research Institute of Biosciences, Kanagawa (Japan); Matsuki, Yasuhiko [Food and Drug Safety Center, Hatano Research Institute, Kanagawa (Japan); Japan Food Hygiene Association, Tokyo (Japan)

    2007-04-15

    Single sc injection of 5 IU equine chorionic gonadotropin (eCG) induces ovulation in weanling female rats 3 days later. It has been shown that treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) 24 h before eCG injection reduces eCG-stimulated ovarian hypertrophy and inhibits ovulation. The present study intended to compare internal dose-effects of TCDD between these endpoints and representative endpoints for TCDD toxicity, such as weights of the liver and thymus, in weanling female rats given orally 0, 1, 4 or 16 {mu}g/kg TCDD 24 h before eCG injection on postnatal day 25. Measurement of plasma TCDD concentrations by ELISA at 6, 72 and 96 h after TCDD revealed that significant levels of TCDD were maintained in systemic circulation until 96 h (on the day of induced ovulation) with the highest level at 6 h after TCDD treatment. Ovarian TCDD concentrations varied similarly and tended to be higher than those in the thymus at all time points, whereas hepatic concentrations of TCDD were the highest among the tissues. Although {>=} 4 {mu}g/kg TCDD affected the weights of the thymus and liver, no differences were observed in ovarian weights at any time point or in ovulation between corn oil-treated and TCDD-treated groups. Furthermore, ovarian levels of representative mRNAs in follicles were not affected by TCDD treatment. Since TCDD increased the amount of cytochrome P450 1A1 mRNA in the ovary, the administered TCDD stimulated the aryl hydrocarbon receptor-signaling pathway. From these results, we concluded that thymus weights of weanling female rats responded to TCDD at a lower internal dose as compared with that ovarian hypertrophy and follicular growth from early antral stage to ovulation would respond to. (orig.)

  9. Follicular synchronization using transdermal estradiol patch and GnRH antagonists in the luteal phase; does it increase oocyte yield in poor responders to gonadotropin stimulation for in vitro fertilization (IVF)? A comparative study with microdose flare-up protocol.

    Science.gov (United States)

    Ata, Baris; Zeng, Xing; Son, Weon Y; Holzer, Hananel; Tan, Seang L

    2011-11-01

    The aim of this retrospective study was to compare the oocyte yield with the luteal estradiol patch (LPA) - GnRH antagonist and microdose (MD) flare-up protocols in anticipated poor responders. Fifty-seven women who underwent IVF treatment following stimulation with LPA or MD protocols at McGill Reproductive Centre were matched for age and markers of ovarian reserve. Numbers of oocytes collected (6 vs 7), mature oocytes collected (5 vs 5), and oocyte maturation rates (72% vs 74%) were similar. The numbers of good quality embryos available (2 vs 1) and embryos transferred (3 vs 3) were likewise similar. Embryo implantation rate of 16.7% and clinical pregnancy rate of 38.9% achieved in the LPA group were almost 50% higher than the corresponding figures at 10.3% and 22.2% in the MD group; however, the differences were not statistically significant (p > 0.05 for all comparisons). Although the results do not suggest an increased oocyte yield or follicular synchronization with the LPA protocol, the observed trend toward higher embryo implantation and clinical pregnancy rates requires further research.

  10. A multi-centre phase 3 study comparing efficacy and safety of Bemfola® versus Gonal-f® in women undergoing ovarian stimulation for IVF

    DEFF Research Database (Denmark)

    Rettenbacher, M; Andersen, A N; Garcia-Velasco, J A

    2015-01-01

    injection (n = 372) showed Bemfola yielding similar efficacy and safety profiles to Gonal-f. Women aged 20-38 years of age were randomized 2:1 to receive a single, daily, subcutaneous 150 IU dose of either Bemfola or Gonal-f. This study tested equivalence in the number of retrieved oocytes using a pre......Bemfola (follitropin alfa) (Finox AG, Switzerland), a new recombinant FSH, has a comparable pharmacological profile to that of Gonal-f (Merck Serono, Germany), the current standard for ovarian stimulation. A randomized, multi-centre, Phase 3 study in women undergoing IVF or intracytoplasmic sperm...

  11. Increasing age influences uterine integrity, but not ovarian function or oocyte quality, in the cheetah (Acinonyx jubatus).

    Science.gov (United States)

    Crosier, Adrienne E; Comizzoli, Pierre; Baker, Tom; Davidson, Autumn; Munson, Linda; Howard, JoGayle; Marker, Laurie L; Wildt, David E

    2011-08-01

    Although the cheetah (Acinonyx jubatus) routinely lives for more than 12 yr in ex situ collections, females older than 8 yr reproduce infrequently. We tested the hypothesis that reproduction is compromised in older female cheetahs due to a combination of disrupted gonadal, oocyte, and uterine function/integrity. Specifically, we assessed 1) ovarian response to gonadotropins; 2) oocyte meiotic, fertilization, and developmental competence; and 3) uterine morphology in three age classes of cheetahs (young, 2-5 yr, n = 17; prime, 6-8 yr, n = 8; older, 9-15 yr, n = 9). Ovarian activity was stimulated with a combination of equine chorionic gonadotropin and human chorionic gonadotropin (hCG), and fecal samples were collected for 45 days before gonadotropin treatment and for 30 days after oocyte recovery by laparoscopy. Twenty-six to thirty hours post-hCG, uterine morphology was examined by ultrasound, ovarian follicular size determined by laparoscopy, and aspirated oocytes assessed for nuclear status or inseminated in vitro. Although no influence of age on fecal hormone concentrations or gross uterine morphology was found (P > 0.05), older females produced fewer (P 0.05) nuclear status and ability to reach metaphase II and fertilize in vitro. A histological assessment of voucher specimens revealed an age-related influence on uterine tissue integrity, with more than 87% and more than 56% of older females experiencing endometrial hyperplasia and severe pathologies, respectively. Our collective findings reveal that lower reproductive success in older cheetahs appears to be minimally influenced by ovarian and gamete aging and subsequent dysfunction. Rather, ovaries from older females are responsive to gonadotropins, produce normative estradiol/progestogen concentrations, and develop follicles containing oocytes with the capacity to mature and be fertilized. A more likely cause of reduced fertility may be the high prevalence of uterine endometrial hyperplasia and related

  12. [Using an ovarian drilling by hydrolaparoscopy or recombinant follicle stimulating hormone plus metformin to treat polycystic ovary syndrome: Why a randomized controlled trial fail?].

    Science.gov (United States)

    Fernandez, H; Cedrin-Durnerin, I; Gallot, V; Rongieres, C; Watrelot, A; Mayenga-Mankezi, J-M; Arnoux, A

    2015-10-01

    To evaluate pregnancy rates after randomized controlled trial (RCT) between ovarian drilling by fertiloscopy or ovarian hyperstimulation+insemination+metformine after clomifène citrate (cc) treatment fails. Randomized controlled trial with 126 patients in each arm in 9 university centers. After 6-9 months of stimulation by cc, 2 groups were randomized: group 1, ovarian drilling with bipolar energy versus group 2: 3 months treatment by metformine followed by 3 hyperstimulation by FSH+insemination. The success rate was pregnancy rate above 12 weeks. RCT was stopped after the screening of 40 patients. In spite of the low number of patients, the pregnancy rate is significantly higher in medical group 8/16 versus 3/18 (p=0.04). The causes of fail of RCT were in relationship with difficulties of inclusion, with absence of final agreement by team included. Moreover, RCT between medical and surgical management is often root of difficulties for patients who decline surgical strategy. However, medical treatment appeared better than drilling in this RCT. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  13. Lutropin alpha, recombinant human luteinizing hormone, for the stimulation of follicular development in profoundly LH-deficient hypogonadotropic hypogonadal women: a review

    Directory of Open Access Journals (Sweden)

    Bernd Th Krause

    2009-06-01

    Full Text Available Bernd Th Krause1, Ralf Ohlinger2, Annette Haase31Center for Endocrinology and Reproductive Medicine, MVZ Uhlandstr, Berlin, Germany; 2Ernst-Moritz-Arndt-University, Department of Gynecology and Obstetrics, Greifswald, Germany; 3Uhlandstr. 162, 10719 BerlinAbstract: Hypogonadotropic hypogonadism is defined as a medical condition with low or undetectable gonadotropin secretion, associated with a complete arrest of follicular growth and very low estradiol. The main cause can be traced back to an irregular or absent hypothalamic GnRH secretion, whereas only a minority suffers from a pituitary disorder. The choice of treatment to reverse this situation is a pulsatile GnRH application or a direct ovarian stimulation using gonadotropin injections. The goal is to achieve a proper ovarian function in these cases for a short time to allow ovulation and chance of pregnancy. Since the pulsatile GnRH treatment lost its former importance, several gonadotropins are in use to stimulate follicular growth, such as urine-derived human menopausal gonadotropin, highly purified follicle stimulating hormone (FSH or recombinant FSH, all with different success. The introduction of recombinant luteinizing hormone (LH and FSH provided an opportunity to investigate the distinct influences of LH and FSH alone and in combination on follicular growth in monofollicular ovulation induction cycles, and additionally on oocyte maturation, fertilization competence of the oocyte and embryo quality in downregulated IVF patients. Whereas FSH was known to be indispensable for normal follicular growth, the role of LH remained questionable. Downregulated IVF patients with this short-term gonadotropin depletion displayed no advance in stimulation success with the use of recombinant LH. Patients with hypogonadotropic hypogonadism undergoing monofollicular stimulation for ovulation induction showed clearly a specific role and need for both hormones in normal follicular growth. Therefore, a

  14. Effects of triploidy incidence on clinical outcomes for IVF-ET cycles in different ovarian stimulation protocols.

    Science.gov (United States)

    Li, Mingzhao; Xue, Xia; Zhang, Silin; Li, Wei; Zhao, Xiaoli; Ren, Wenjuan; Shi, Juanzi

    2015-10-01

    To discuss the relationship between triploidy incidence and clinical outcomes of embryos derived from normally fertilized oocytes from the same cohort for in vitro fertilization-embryo transfer (IVF-ET) cycles in different ovarian stimulation protocol. This study included 2070 in vitro fertilization (IVF) cycles with long-term protocol, 802 IVF cycles with ultra short-term protocol and 508 IVF-D (in vitro fertilization by donor semen) cycles with long-term protocol from January 2013 to September 2014. According to the different 3PN rate, patients were divided into three groups as follows: Group 1 included patients with 0% 3PN zygotes, Group 2 included patients with 1-25% 3PN zygotes and Group 3 included patients with >25% 3PN zygotes. female age, no. of retrieved oocytes, normal fertilization rate, day-3 grade I + II embryos rate, day-3 grade I + II + III embryos rate, implantation rate, pregnancy rate and early abortion rate. Triploidy cycle incidence rate in IVF and IVF-D cycles with long-term protocol were significantly higher than in IVF cycles with ultra short-term protocol (p  0.05). In three protocols, normal fertilization rate in 3PN = 0% and 3PN = 1-25% groups were significantly higher compared to 3PN > 25% group (p cycles with long-term protocol, the day-3 grade I + II embryos, implantation and pregnancy rate in 3PN > 25% group were significantly lower than other two groups (p  0.05). In IVF cycles with ultra short-term protocol, there were no significant differences found in day-3 grade I + II embryos, day-3 grade I + II + III embryos, implantation, pregnancy and early abortion rate (p > 0.05). In IVF-D cycles with long-term protocol, the day-3 grade I + II embryos, day-3 grade I + II + III embryos and implantation rate in 3PN > 25% group were significantly lower than other two groups (p  0.05). We observed that high proportion of triploid zygotes made a negative effect on

  15. Polycystic ovarian syndrome management options.

    Science.gov (United States)

    Bates, G Wright; Propst, Anthony M

    2012-12-01

    Polycystic ovarian syndrome (PCOS) is a disorder of androgen excess and ovarian dysfunction. Hirsutism and elevated free testosterone levels are the most consistent signs of the androgen excess. Irregular, infrequent, or absent menses and infertility are symptoms of ovulatory dysfunction. Obesity is also a feature of this syndrome and contributes to associated metabolic abnormalities. Lifestyle modification should be the first treatment and is effective in reducing the signs and symptoms. The ovulatory infertility associated with PCOS can be overcome in most cases with oral (clomiphene citrate or letrozole) or injectable (gonadotropins) agents. Surgical intervention is reserved for cases resistant to medical management. Copyright © 2012 Elsevier Inc. All rights reserved.

  16. -Human Chorionic Gonadotropin Production

    Directory of Open Access Journals (Sweden)

    Michael J. Russell

    2008-01-01

    Full Text Available Dedifferentiated liposarcomas may display a variety of “heterologous” lines of differentiation, including osseous, vascular, skeletal, and/or smooth muscular. There have been six previously reported examples of leiomyosarcomas associated with high levels of serum human chorionic gonadotropin (hCG production, comprised of cases originating from the retroperitoneum, spermatic cord, small intestine, and uterus. This report describes the first example of a dedifferentiated liposarcoma that combined both of the aforementioned features: extensive heterologous (leiomyosarcomatous differentiation and -hCG production (maximum serum levels 1046 mIU/ml, reference <5 mIU/ml. The tumor, which originated in the retroperitoneum in the region of the right kidney, was rapidly progressive and ultimately fatal within three months of its diagnosis. In addition to characteristic morphologic features, lipogenic and smooth muscle differentiation were confirmed with immunohistochemical stains for MDM2 and smooth muscle actin, respectively. The tumor also displayed diffuse immunoreactivity for -hCG in both primary and metastatic sites. This case further expands the clinicopathologic spectrum of lipogenic tumors.

  17. Paclitaxel, ifosfamide and cisplatin with granulocyte colony-stimulating factor or recombinant human interleukin 3 and granulocyte colony-stimulating factor in ovarian cancer : A feasibility study

    NARCIS (Netherlands)

    Veldhuis, GJ; Willemse, PHB; Beijnen, JH; Piersma, H; vanderGraaf, WTA; deVries, EGE; Boonstra, J.

    1997-01-01

    The tolerability and efficacy of four courses of paclitaxel and ifosfamide plus cisplatin every 3 weeks was evaluated in patients with residual or refractory ovarian cancer. Additionally, supportive haematological effects of recombinant human interleukin 3 (rhIL-3) and recombinant human granulocyte

  18. Gonadotropin Regulation of Retinoic Acid Activity in the Testis

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    Seyedmehdi Nourashrafeddin

    2018-02-01

    Full Text Available Initiation of spermatogenesis in primates is triggered at puberty by an increase in gonadotropins; i.e., follicle-stimulating hormone (FSH and luteinizing hormone (LH. Prior to puberty, testis of the monkey contains only undifferentiated germ cells. However, sermatogonial differentiation and spermatogenesis may be initiated prior to puberty after stimulation with exogenous LH and FSH. Retinoic acid (RA signaling is considered to be a major component that drives spermatogonial differentiation. We were interested in evaluating the relative role of LH and FSH, either alone or in combination, in regulating the retinoic acid signaling in monkey testis. Sixteen juvenile male rhesus monkeys (Macaca mulatta were infused with intermittent recombinant single chain human LH (schLH or recombinant human FSH (rhFSH or a combination of both for 11 days. We then analyzed the expression of the several putative RA signaling pathway related genes; i.e. RDH10, RDH11, ALDH1A1, ALDH1A2, CYP26B1, CRABP1, CRABP2, STRA6, STRA8 in the testis after 11 days of stimulation with vehicle, LH, FSH and combination LH/FSH using quantitative real-time PCR (qPCR. The qPCR results analysis showed that administration of gonadotropins affected a significant change in expression of some RA signaling related genes in the monkey testis. The gonadotropins, either alone or in combination dramatically increased expression of CRABP2 (p≤0.001, whereas there was a decrease in ALDH1A2 expression (p≤0.001. Moreover, combined gonadotropin treatment led to the significant decrease in CRABP1 expression (p≤0.05. These findings are the first evidence that the activity of retinoic acid signaling in the monkey testis is regulated through gonadotropins (LH/FSH levels.

  19. A common polymorphic allele of the LH beta-subunit gene is associated with higher exogenous FSH consumption during controlled ovarian stimulation for assisted reproductive technology

    DEFF Research Database (Denmark)

    Alviggi, Carlo; Pettersson, Kim; Longobardi, Salvatore

    2013-01-01

    BACKGROUND: V-betaLH is a common genetic variant of LH caused by two polymorphic base changes in the beta subunit gene, altering the amino acid sequence (Trp8Arg and Ile15Thr). In a previous-preliminary trial performed in women undergoing IVF, it was demonstrated that carriers of v-betaLH show sub......-optimal ovarian response to a standard long GnRH-agonist down -regulation protocol when stimulated with pure recombinant FSH (r-hFSH). The aim of this study was to confirm the hypothesis that women with v-betaLH display hypo-sensitivity to exogenous FSH in a larger IVF population and to explore the frequency...... of this variant in a Danish female population. METHODS: In the present study, the effect of v-betaLH was retrospectively investigated in a larger series of women undergoing controlled ovarian stimulation (COS) and, for the first time, in a Danish IVF population. A total of 220 normogonadotrophic women following...

  20. High gonadotropin dosage does not affect euploidy and pregnancy rates in IVF PGS cycles with single embryo transfer.

    Science.gov (United States)

    Barash, Oleksii O; Hinckley, Mary D; Rosenbluth, Evan M; Ivani, Kristen A; Weckstein, Louis N

    2017-11-01

    Does high gonadotropin dosage affect euploidy and pregnancy rates in PGS cycles with single embryo transfer? High gonadotropin dosage does NOT affect euploidy and pregnancy rates in PGS cycles with single embryo transfer. PGS has been proven to be the most effective and reliable method for embryo selection in IVF cycles. Euploidy and blastulation rates decrease significantly with advancing maternal age. In order to recruit an adequate number of follicles, the average dosage of gonadotropins administered during controlled ovarian stimulation in IVF cycles often increases significantly with advancing maternal age. A retrospective study of SNP (Single Nucleotide Polymorphism) PGS outcome data from blastocysts biopsied on day 5 or day 6 was conducted to identify differences in euploidy and clinical pregnancy rates. Seven hundred and ninety four cycles of IVF treatment with PGS between January 2013 and January 2017 followed by 651 frozen embryo transfers were included in the study (506 patients, maternal age (y.o.) - 37.2 ± 4.31). A total of 4034 embryos were analyzed (5.1 ± 3.76 per case) for euploidy status. All embryos were vitrified after biopsy, and selected embryos were subsequently thawed for a hormone replacement frozen embryo transfer cycle. All cycles were analyzed by total gonadotropin dosage (5000 IU), by number of eggs retrieved (1-5, 5-10, 10-15 and >15 eggs) and patient's age (cycles) euploidy rates ranged from 62.3% (cycle) to 67.5% (>5000 IU were used in the IVF cycle) (OR = 0.862, 95% CI 0.687-1.082, P = 0.2) and from 69.5% (1-5 eggs retrieved) to 60.0% (>15 eggs retrieved) (OR = 0.658, 95% CI 0.405-1.071, P = 0.09). Similar data were obtained in the oldest group of patients (≥41 y.o. - 189 IVF cycles): euploidy rates ranged from 30.7 to 26.4% (OR = 0.811, 95% CI 0.452-1.454, P = 0.481) when analyzed by total dosage of gonadotropins used in the IVF cycle and from 40.0 to 30.7% (OR = 0.531, 95% CI 0.204-1.384, P = 0.19), when assessed by the total

  1. Do Different Stimulation Protocols Effect Oocyte Quality and IVF Outcomes in IVF-ET?

    Directory of Open Access Journals (Sweden)

    Nafiye Yilmaz

    2016-04-01

    Full Text Available Aim: This study was planned to compare the effect of different stimulation protocols (hMG and uFSH on oocyte maturation and in vitro fertilization outcomes. Material and Method: Eighty-two patients admitted Ankara University Obstetrics and Gynecology Clinic- IVF Department were included in this retrospective study. All patients used long GnRH agonist protocol. Fifty-nine patients used human menopausal gonadotropin (hMG (Group 1 and 23 patients used urine derived follicle-stimulating hormone (uFSH (Group 2 for ovulation induction. Maximum follicle diameter, dominant follicle number, endometrial thickness at human chorionic gonadotropin day, duration of induction, dose of gonadotropin, oocyte number and quality, fertilization rate, embryo number and quality, pregnancy rate per cycles and transfer were reported. Results: Maximum follicle diameter, dominant follicle number, immature oocyte number were significantly higher in hMG group vs. uFSH group (p0.05. Discussion: Clinical pregnancy rate was not significantly different in hMG vs. uFSH group. In developing countries, ovarian stimulation agents should be chosen based on patient characteristics and cost.

  2. Anti-Müllerian Hormone and Ovarian Morphology in Women With Isolated Hypogonadotropic Hypogonadism/Kallmann Syndrome: Effects of Recombinant Human FSH.

    Science.gov (United States)

    Bry-Gauillard, Hélène; Larrat-Ledoux, Florence; Levaillant, Jean-Marc; Massin, Nathalie; Maione, Luigi; Beau, Isabelle; Binart, Nadine; Chanson, Philippe; Brailly-Tabard, Sylvie; Hall, Janet E; Young, Jacques

    2017-04-01

    Isolated hypogonadotropic hypogonadism (IHH), characterized by gonadotropin deficiency and absent puberty, is very rare in women. IHH prevents pubertal ovarian stimulation, but anti-Müllerian hormone (AMH) and antral follicle count (AFC) have not been studied. (1) To compare, in IHH vs controls, AMH, ovarian volume (OV), and AFC. (2) To compare, in IHH, ovarian responses to recombinant human follicle-stimulating hormone (rhFSH) and rhFSH plus recombinant human luteinizing hormone (rhLH). Sixty-eight IHH women; 51 matched healthy women. Serum LH, FSH, sex steroids, inhibin B (InhB), AMH, and OV and AFC (sonography) were compared. Ovarian response during rhFSH administration was assessed in 12 IHH women with low AMH levels and low AFC and compared with hormonal changes observed in six additional IHH women receiving rhFSH plus rhLH. InhB was lower in IHH than in controls. AMH levels were also significantly lower in the patients, but two-thirds had normal values. Mean OV and total, larger, and smaller AFCs were lower in IHH than in controls. Ovarian stimulation by rhFSH led to a significant increase in serum estradiol and InhB levels and in the number of larger antral follicles. AMH and smaller AFC increased early during rhFSH stimulation but then declined despite continued stimulation. rhFSH plus rhLH stimulation led to a significantly higher increase in estradiol levels but to similar changes in circulating InhB and AMH than with rhFSH alone. IHH women have both low AMH levels and low AFC. However, their decrease can be reversed by follicle-stimulating hormone. Serum AMH and AFC should not serve as prognostic markers of fertility in this population. Copyright © 2017 by the Endocrine Society

  3. Shifting paradigms in diminished ovarian reserve and advanced reproductive age in assisted reproduction: customization instead of conformity.

    Science.gov (United States)

    Reed, Beverly G; Babayev, Samir N; Bukulmez, Orhan

    2015-05-01

    As women are increasingly delaying childbearing into their 30s and beyond, diminished ovarian reserve (DOR) and advanced reproductive age (ARA) patients are bound to become a large proportion of all assisted reproductive technology practices. Traditional controlled ovarian stimulation (COS) protocols for DOR and/or ARA have had some limited success, but pregnancy rates are lower and cycle cancellation rates are higher than their younger counterparts with normal ovarian reserve. Though many physicians have a selection of favorite standard protocols that they use, patients with DOR may require closer monitoring and customization of the treatment cycle to address the common problems that come with low ovarian reserve. Frequent issues that surface in women with DOR and/or ARA include poor follicular response, premature luteinizing hormone surge, and poor embryo quality. Limited published evidence exists to guide treatment for DOR. However, use of minimal or mild doses of gonadotropins, avoidance of severe pituitary suppression, and consideration for luteal phase stimulation and a "freeze all" approach are possible customized treatment options that can be considered for such patients who have failed more traditional COS protocols. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  4. Functional significance of the signal transduction pathways Akt and Erk in ovarian follicles: in vitro and in vivo studies in cattle and sheep

    Directory of Open Access Journals (Sweden)

    Ryan Kate E

    2008-10-01

    Full Text Available Abstract Background The intracellular signalling mechanisms that regulate ovarian follicle development are unclear; however, we have recently shown differences in the Akt and Erk signalling pathways in dominant compared to subordinate follicles. The aim of this study was to investigate the effects of inhibiting Akt and Erk phosphorylation on IGF- and gonadotropin- stimulated granulosa and theca cell function in vitro, and on follicle development in vivo. Methods Bovine granulosa and theca cells were cultured for six days and stimulated with FSH and/or IGF, or LH in combination with PD98059 (Erk inhibitor and/or LY294002 (Akt inhibitor and their effect on cell number and hormone secretion (estradiol, activin-A, inhibin-A, follistatin, progesterone and androstenedione determined. In addition, ovarian follicles were treated in vivo with PD98059 and/or LY294002 in ewes on Day 3 of the cycle and follicles were recovered 48 hours later. Results We have shown that gonadotropin- and IGF-stimulated hormone production by granulosa and theca cells is reduced by treatment with PD98059 and LY294002 in vitro. Furthermore, treatment with PD98059 and LY294002 reduced follicle growth and oestradiol production in vivo. Conclusion These results demonstrate an important functional role for the Akt and Erk signalling pathways in follicle function, growth and development.

  5. Transforming growth factor-β1 and its receptor soluble endoglin are altered in polycystic ovary syndrome during controlled ovarian stimulation.

    Science.gov (United States)

    Tal, Reshef; Seifer, David B; Shohat-Tal, Aya; Grazi, Richard V; Malter, Henry E

    2013-08-01

    To evaluate the relationship between transforming growth factor (TGF)-β1 and its receptor, soluble endoglin (sENG), in the serum and follicular fluid of women with polycystic ovarian syndrome (PCOS) compared with that of non-PCOS normal ovulating women during controlled ovarian stimulation (COS). Prospective case-control study. Academic-affiliated assisted reproductive technology unit. Fourteen PCOS and 14 matched non-PCOS control women undergoing COS. Serum was collected on day 3 (baseline), day of hCG, and day of retrieval. Follicular fluid (FF) was collected on day of oocyte retrieval. ELISA was performed to determine TGF-β1 and sENG protein levels. Serum and FF levels of TGF-β1 and sENG. Serum TGF-β1 did not change significantly during COS but was increased in PCOS compared with non-PCOS women on day 3 and days of hCG administration and oocyte retrieval. Serum sENG increased after hCG administration only in the non-PCOS control group. In addition, serum sENG was decreased in PCOS compared with non-PCOS control women on the days of hCG and retrieval. Accordingly, the bioavailability of TGF-β1 (TGF-β1/sENG ratio) was increased in women with PCOS compared with non-PCOS controls at all three time points. No differences in either factor were noted in FF between groups. The increased TGF-β1 bioavailability in PCOS is not only due to increased TGF-β1 levels but also to decreased levels of its receptor, sENG. These data suggest that increased TGF-β1 bioavailability may contribute to the pathogenesis of PCOS and its increased risk for ovarian hyperstimulation. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  6. Ovarian stimulation and embryo banking for fertility preservation in a woman with severe mixed connective tissue disease: Is it safe?

    Science.gov (United States)

    Sioulas, Vasileios D; Gracia, Clarisa R

    2012-03-01

    To report the first case of using assisted reproductive technologies (ART) for fertility preservation in a patient with mixed connective tissue disease (MCTD), secondary pulmonary hypertension (PH) and antiphospholipid syndrome (APS). Case-report and review of the literature. Academic infertility practice and tertiary care center. A 25-year-old woman with MCTD, complicated with PH and APS, who was scheduled for gonadotoxic therapy Controlled ovarian hyperstimulation, egg retrieval, embryo banking. Successful ART cycle leading to embryo banking without worsening her underlying disease. Following successful embryo cryopreservation, the patient experienced respiratory failure and other severe complications, resulting in a prolonged hospital stay. Controlled ovarian hyperstimulation for embryo banking in women with MCTD, PH and APS may pose a risk for potentially catastrophic complications. A multidisciplinary approach to these patients is necessary to optimize the outcomes of such procedures. More data are needed regarding the safety of fertility preservation technologies in patients with complex medical diseases.

  7. Effect of gonadotropin secretion rate on the radiosensitivity of the rat luteinizing hormone-releasing hormone neuron and gonadotroph

    International Nuclear Information System (INIS)

    Winterer, J.; Barnes, K.M.; Lichter, A.S.; Deluca, A.M.; Loriaux, D.L.; Cutler, G.B. Jr.

    1988-01-01

    To test the hypothesis that the functional state of hypothalamic LHRH neurons and pituitary gonadotrophs might alter their radiosensitivity, we determined the experimental conditions under which the gonadotropin response to castration could be impaired by a single dose of cranial irradiation. Single doses of cranial irradiation greater than 2000 rads were lethal to unshielded rats. Shielding of the oropharynx and esophagus allowed the animals to survive doses up to 5000 rads. Doses between 2000 and 5000 rads had no effect on basal gonadotropin levels for as long as 3 months after irradiation. Irradiation caused a dose- and time-dependent impairment, however, in the gonadotropin response to castration. Impairment of the gonadotropin levels of castrate animals occurred in animals that were irradiated either before or after castration. However, rats irradiated in the castrate state showed a decreased susceptibility to irradiation damage. Additionally, stimulation of the pituitary by LHRH agonist (LHRHa) 3 h before irradiation significantly reduced the impairment of gonadotropin secretion 12-20 weeks after irradiation (P less than 0.05). Thus, increased functional activity of the rat hypothalamus or pituitary at the time of irradiation, induced by either castration or acute LHRHa administration, was associated with some protection against the gonadotropin-lowering effect of irradiation. Based upon these data, we hypothesize that stimulation of gonadotropin secretion at the time of therapeutic cranial irradiation in humans might protect against subsequent impairment of gonadotropin secretion

  8. Serum bioactive and immunoreactive luteinizing hormone and follicle-stimulating hormone levels in women with cycle abnormalities, with or without polycystic ovarian disease.

    Science.gov (United States)

    Fauser, B C; Pache, T D; Lamberts, S W; Hop, W C; de Jong, F H; Dahl, K D

    1991-10-01

    Serum steroid, gonadotropin, and alpha-subunit levels were assessed in 35 women with cycle abnormalities [11 with and 24 without polycystic ovarian disease (PCOD) according to strict clinical and biochemical criteria] and 8 regularly cycling women in the early (cycle day 3 or 4) and mid (cycle day 7 or 8) follicular phase. LH and FSH levels were estimated using two immunological techniques [RIA and immunoradiometric assay (IRMA)] and in vitro bioassays (BIO), using mouse Leydig cells and rat granulosa cells, respectively. In PCOD patients mean alpha-subunit, free androgen index [FAI; testosterone x 100/sex hormone-binding globulin (SHBG)], androstenedione, estrone, and estradiol (E2) were significantly elevated compared to levels in the early follicular phase of control cycles and non-PCOD patients. In addition, in PCOD patients mean IRMA-LH and RIA-LH levels were distinctly increased (2.8- to 3.6 fold, respectively; both comparisons, P less than 0.001) compared to control values, but in the same order of magnitude (1.3- to 1.4-fold increments) as that in non-PCOD patients. However, the median BIO-LH level in PCOD patients was 5.9-fold higher than that in non-PCOD patients and 4.0-fold higher than the BIO-LH in the early follicular phase of control women. Consequently, the median BIO/IRMA-LH ratio was 4.8-fold higher in PCOD patients compared to non-PCOD patients. In women with cycle abnormalities, individual BIO/IRMA-LH ratios correlated with BIO-LH (rs = 0.48), FAI (rs = 0.39), free estrogens (E2/SHBG ratios; rs = 0 0.47), and dehydroepiandrosterone sulfate (rs = 0.60) concentrations. Mean IRMA-, RIA-, and BIO-FSH levels and BIO/IRMA-FSH ratios were not significantly different when various groups were compared. Although RIA- and IRMA-LH levels showed good correlation (rs = 0.88), RIA-LH levels were consistently higher, resulting in distinctly higher RIA-LH/FSH ratios (mean, 4.5) compared to IRMA-LH/FSH ratios (median, 1.8) in PCOD patients.(ABSTRACT TRUNCATED AT

  9. Cost-saving treatment strategies in in vitro fertilization: a combined economic evaluation of two large randomized clinical trials comparing highly purified human menopausal gonadotropin and recombinant follicle-stimulating hormone alpha.

    Science.gov (United States)

    Wechowski, Jaroslaw; Connolly, Mark; Schneider, Dirk; McEwan, Philip; Kennedy, Richard

    2009-04-01

    To assess the cost-effectiveness of two gonadotropin treatments that are available in the United Kingdom in light of limited public funding and the fundamental role of costs in IVF treatment decisions. An economic evaluation based on two large randomized clinical trials in IVF patients using a simulation model. Fifty-three fertility clinics in 13 European countries and Israel. Women indicated for treatment with IVF (N = 986), aged 18-38, participating in double-blind, randomized controlled trials. Highly purified menotropin (HP-hMG, Menopur) or recombinant follitropin alpha (rFSH, Gonal-F). Cost per IVF cycle and cost per live birth for HP-hMG and rFSH alpha. HP-hMG was more effective and less costly versus rFSH for both IVF cost per live birth and for IVF cost per baby (incremental cost-effectiveness ratio was negative). The mean costs per IVF treatment for HP-hMG and rFSH were 2408 pounds (95% confidence interval [CI], 2392 pounds, 2421 pounds) and 2660 pounds (95% CI 2644 pounds, 2678 pounds), respectively. The mean cost saving of 253 pounds per cycle using HP-hMG allows one additional cycle to be delivered for every 9.5 cycles. Treatment with HP-hMG was dominant compared with rFSH in the United Kingdom. Gonadotropin costs should be considered alongside live-birth rates to optimize outcomes using scarce health-care resources.

  10. Impact of The Endometrioma on Ovarian Response and Pregnancy Rate in In Vitro Fertilization Cycles

    Directory of Open Access Journals (Sweden)

    Mahnaz Ashrafi

    2014-03-01

    Full Text Available Background: Our objective was to evaluate the effect of ovarian endometrioma on ovarian stimulation outcomes in in vitro fertilization cycles (IVF. Materials and Methods: In this prospective cohort study, we followed 103 patients who underwent intra-cytoplasmic sperm injection (ICSI procedures over a 24-months period. The study group consisted of 47 infertile women with either unilateral or bilateral ovarian endometrial cysts of less than 3 cm. The control group consisting of 57 patients with mild male factor infertility was candidate for ICSI treatment during the same time period as the study groups. Both groups were compared for number of oocytes retrieved, grades of oocytes, as well as embryo quantity and quality. Results: Our results showed similar follicle numbers, good embryo grades (A or B and pregnancy rates in the compared groups. However, patients with endometrioma had higher gonadotropin consumption than the control group. The mean number of retrieved oocytes in patients with endometrioma was significantly lower than control group (6.6 ± 3.74 vs. 10.4 ± 5.25 (p<0.001. In addition, patients with endometrioma had significantly lower numbers of metaphase II (MII oocytes (5 ± 3.21 than controls (8.2 ± 5.4 (p<0.001. In patients with unilateral endometrioma, there were no significant differences in main outcome measures between normal and involved ovaries in the patients with endometrioma. Conclusion: Patients with ovarian endometrioma had poor outcome. They showed poor ovarian response with lower total numbers of retrieved oocytes and lower MII oocytes during the stimulation phase; however, it does not affect the total number of embryos transferred per patient, quality of embryos, and pregnancy rate per patient.

  11. Serum AMH Level to Predict the Hyper Response in Women with PCOS and Non-PCOS Undergoing Controlled Ovarian Stimulation in ART.

    Science.gov (United States)

    Vembu, Radha; Reddy, Nellepalli Sanjeeva

    2017-01-01

    It is essential to determine the cut-off value of serum anti-Mullerian hormone (AMH) to predict the hyper response in assisted reproductive technology (ART). There are few studies mentioning the cut-off value for the hyper response in infertile women but not specifically for polycystic ovary syndrome (PCOS) and non-PCOS groups. With this in background, this study was conducted. To determine the cut-off value of serum AMH to predict the hyper response in women with PCOS and non-PCOS undergoing a controlled ovarian stimulation (COS) in ART. To compare the outcome of stimulation in PCOS and non-PCOS groups. All 246 women enrolled for Intra Cytoplasmic Sperm Injection (ICSI) fulfilling the selection criteria were recruited. On the day 3 of the cycle, the serum AMH, Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH), estradiol and antral follicle count (AFC) were measured. They underwent COS as per the unit protocol. They were divided into PCOS and non-PCOS groups as per the Rotterdam's criteria. The mean age, duration of infertility, Body Mass Index (BMI), Ovarian reserve markers and outcome of stimulation were compared. Using the Statistical Package for the Social Sciences version 16.0 software, the significant difference was measured by multivariate analysis, as well as a one-way analysis of variance with Tukey's post-hoc test was used. Among 246 women, 31.3% were in PCOS group, and 68.7% were in non-PCOS group. Comparison of PCOS and non-PCOS groups showed a significant difference in the age with the mean age being 29.2 and 31.5 years, respectively. The mean AMH and AFC were 2-fold higher in PCOS group. The mean number of follicles, oocytes retrieved, MII and oocytes fertilised were significantly higher in PCOS group. The pregnancy rate was 52.6% in PCOS and 30.9% in non-PCOS group. In the PCOS group, 22.1% had ovarian hyper stimulation syndrome (OHSS), and only 4.7% had OHSS in non-PCOS group ( P = 0.0005). Receiving Operator Curve (ROC) curve was plotted

  12. Cumulus cells gene expression profiling in terms of oocyte maturity in controlled ovarian hyperstimulation using GnRH agonist or GnRH antagonist.

    Science.gov (United States)

    Devjak, Rok; Fon Tacer, Klementina; Juvan, Peter; Virant Klun, Irma; Rozman, Damjana; Vrtačnik Bokal, Eda

    2012-01-01

    In in vitro fertilization (IVF) cycles controlled ovarian hyperstimulation (COH) is established by gonadotropins in combination with gonadotropin-releasing hormone (GnRH) agonists or antagonists, to prevent premature luteinizing hormone (LH) surge. The aim of our study was to improve the understanding of gene expression profile of cumulus cells (CC) in terms of ovarian stimulation protocol and oocyte maturity. We applied Affymetrix gene expression profiling in CC of oocytes at different maturation stages using either GnRH agonists or GnRH antagonists. Two analyses were performed: the first involved CC of immature metaphase I (MI) and mature metaphase II (MII) oocytes where 359 genes were differentially expressed, and the second involved the two GnRH analogues where no differentially expressed genes were observed at the entire transcriptome level. A further analysis of 359 differentially genes was performed, focusing on anti-Müllerian hormone receptor 2 (AMHR2), follicle stimulating hormone receptor (FSHR), vascular endothelial growth factor C (VEGFC) and serine protease inhibitor E2 (SERPINE2). Among other differentially expressed genes we observed a marked number of new genes connected to cell adhesion and neurotransmitters such as dopamine, glycine and γ-Aminobutyric acid (GABA). No differential expression in CC between the two GnRH analogues supports the findings of clinical studies where no significant difference in live birth rates between both GnRH analogues has been proven.

  13. Effects of postoperative adjuvant chemotherapy and radiotherapy on ovarian function in women undergoing treatment for soft tissue sarcoma

    International Nuclear Information System (INIS)

    Shamberger, R.C.; Sherins, R.J.; Ziegler, J.L.; Glatstein, E.; Rosenberg, S.A.

    1981-01-01

    Ovarian function was evaluated in 11 women 16 to 43 years of age at treatment who received doxorubicin, cyclophosphamide, and high doses of methotrexate with or without radiotherapy in adjuvant therapy of soft tissue sarcoma. Five women (16-33 yr old) who received chemotherapy alone or combined with radiotherapy only at sites distant from the ovaries (chest wall, thigh, and leg) had minimal menstrual irregularities or temporary cessation of menses during therapy; cyclic menses returned promptly after therapy. Gonadotropin levels (expressed as means +/- SD) [follicle-stimulating hormone (FSH), 10 +/- 15 mlU/ml; luteinizing hormone (LH), 10 +/- 4 mlU/ml] and 17 β-estradiol (E 2 ) levels (means +/- SD, 208 +/- 147 pg/ml) were normal. By contrast, 4 older women (ages 36-43 yr) who received similar treatment developd persistent amenorrhea with postmenopausal levels of gonadotropin (FSH, 109 +/- 29 mlU/ml; LH, 72 +/- 19 mlU/ml) and E 2 (19 +/- 8 pg/ml). Two additional women (ages 21 and 39 yr) who received radiation (7000 rad) to the pelvis plus chemotherapy developed prompt cessation of menses and became functional castrates (FSH, 77 and 80mlU/ml; LH, 40 and 58 mlU/ml; E 2 , 10 and 19 pg/ml). However, this result would be expected from the radiation dose alone. The data demonstrated that ovarian dysfunction may follow the use of doxorubicin, cyclophosphamide, and high doses of methotrexate and that the injury is age related

  14. Effects of postoperative adjuvant chemotherapy and radiotherapy on ovarian function in women undergoing treatment for soft tissue sarcoma

    International Nuclear Information System (INIS)

    Shamberger, R.C.; Sherins, R.J.; Ziegler, J.L.; Glatstein, E.; Rosenberg, S.A.

    1981-01-01

    Ovarian function was evaluated in 11 women 16 to 43 years of age at treatment who received doxorubicin, cyclophosphamide, and high doses of methotrexate with or without radiotherapy in adjuvant therapy of soft tissue sarcoma. Five women (16-33 yr old) who received chemotherapy alone or combined with radiotherapy only at sites distant from the ovaries (chest wall, thigh, and leg) had minimal menstrual irregularities or temporary cessation of menses during therapy; cyclic menses returned promptly after therapy. Gonadotropin levels (expressed as means +/- SD [follicle-stimulating hormone (FSH), 10 +/- 5 mlU/ml; luteinizing hormone (LH), 10 +/- 4 mlU/ml] and 17 beta-estradiol (E2) levels (means +/- SD, 208 +/- 147 pg/ml) were normal. By contrast, 4 older women (ages 36-43 yr) who received similar treatment developed persistent amenorrhea with postmenopausal levels of gonadotropin (FSH, 108 +/- 29 mlU/ml; LH, 72 +/- 19 mlU/ml) and E2 (19 +/- 8 pg/ml). Two additional women (ages 21 and 39 yr) who received radiation (7,000 rad) to the pelvis plus chemotherapy developed prompt cessation of menses and became functional castrates (FSH, 77 and 80 mlU/ml; LH, 40 and 58 mlU/ml; E2, 10 and 19 pg/ml). However, this result would be expected from the radiation dose alone. The data demonstrated that ovarian dysfunction may follow the use of doxorubicin, cyclophosphamide, and high doses of methotrexate and that the injury is age related

  15. Effects of postoperative adjuvant chemotherapy and radiotherapy on ovarian function in women undergoing treatment for soft tissue sarcoma

    Energy Technology Data Exchange (ETDEWEB)

    Shamberger, R.C.; Sherins, R.J.; Ziegler, J.L.; Glatstein, E.; Rosenberg, S.A.

    1981-12-01

    Ovarian function was evaluated in 11 women 16 to 43 years of age at treatment who received doxorubicin, cyclophosphamide, and high doses of methotrexate with or without radiotherapy in adjuvant therapy of soft tissue sarcoma. Five women (16-33 yr old) who received chemotherapy alone or combined with radiotherapy only at sites distant from the ovaries (chest wall, thigh, and leg) had minimal menstrual irregularities or temporary cessation of menses during therapy; cyclic menses returned promptly after therapy. Gonadotropin levels (expressed as means +/- SD (follicle-stimulating hormone (FSH), 10 +/- 5 mlU/ml; luteinizing hormone (LH), 10 +/- 4 mlU/ml) and 17 beta-estradiol (E2) levels (means +/- SD, 208 +/- 147 pg/ml) were normal. By contrast, 4 older women (ages 36-43 yr) who received similar treatment developed persistent amenorrhea with postmenopausal levels of gonadotropin (FSH, 108 +/- 29 mlU/ml; LH, 72 +/- 19 mlU/ml) and E2 (19 +/- 8 pg/ml). Two additional women (ages 21 and 39 yr) who received radiation (7,000 rad) to the pelvis plus chemotherapy developed prompt cessation of menses and became functional castrates (FSH, 77 and 80 mlU/ml; LH, 40 and 58 mlU/ml; E2, 10 and 19 pg/ml). However, this result would be expected from the radiation dose alone. The data demonstrated that ovarian dysfunction may follow the use of doxorubicin, cyclophosphamide, and high doses of methotrexate and that the injury is age related.

  16. Exogenous induction of ovarian activity and ovulation and transfer of fresh embryos of domestic cat (Felis catus

    Directory of Open Access Journals (Sweden)

    Marcelo Lopes Santana

    2012-08-01

    Full Text Available The objective of the present study was the exogenous stimulation of ovarian activity and definition of embryo collection, and transfer protocols, in the domestic cat for potential application in non-domestic endangered species. Sixteen adult queens and two adult male reproducers kept in the experimental cat house at the Morphology sector at the Veterinary Department (DVT, UFV, were used in this study. All the queens received a single application of 150 IU Equine Chorionic Gonadotropin (eCG in the post estrus to induce ovarian activity and 80 to 84 hours later, received a single application of 100 UI Human Chorionic Gonadotropin (hCG to induce ovulation. After hCG application, only the donor queens were naturally mated. The receptor queens received extra stimulus for induction of ovulation through manipulation of an intravaginal swab. Five to six days after hCG application, the donor queens were subjected to a laparotomy for embryo collection that was performed by trans-horn uterine washing. On average, six embryos were surgically inovulated. They were classified as type I and III compact morula and blastocysts in four receptor queens. Three animals presented pregnancy confirmed by ultrasound at day 36 and two of these animals gave birth to litters of two and four offsprings, respectively, at 66 and 63 days after induction of ovulation. Except for one still birth, all the offspring developed normally.

  17. Seasonal relationship between gonadotropin, growth hormone, and estrogen receptor mRNA expression in the pituitary gland of largemouth bass.

    Science.gov (United States)

    Martyniuk, Christopher J; Kroll, Kevin J; Porak, Wesley F; Steward, Cheree; Grier, Harry J; Denslow, Nancy D

    2009-09-15

    The objectives of this study were to investigate the seasonal changes in pituitary gonadotropins, growth hormone (GH), and estrogen receptor (ER) isoform mRNA in wild female and male largemouth bass (LMB) (Micropterus salmoides) from an unpolluted habitat to better understand reproductive physiology in this ecologically important species. Female pituitary luteinizing hormone (LH) beta subunit and follicle stimulating hormone (FSH) beta subunit mRNA showed significant seasonal variation with levels peaking from January to April and were lowest from May to August. Male LMB showed more variation in gonadotropin subunit expression from month to month. Females had approximately 2-3 times higher gonadotropin mRNA levels in the pituitary when compared to males. All three gonadotropin mRNAs in females were positively correlated to gonadosomatic index (GSI), but only LHbeta mRNA was correlated to GSI in males. Gonadotropin mRNA expression also increased with increasing oocyte and sperm maturation. Gonadotropin beta subunit mRNA expression was positively correlated to GH mRNA in both sexes. The expression of all three ER isoforms was significantly correlated to each other in both sexes. The concurrent increase in all three ER mRNA isoforms with increasing gonadotropin mRNA in females and males suggests a prominent role for E2 feedback on pituitary gonadotropin synthesis in both sexes and that each of the three ER isoforms are likely to play a role in the pituitary during teleost reproduction.

  18. Use of equine chorionic gonadotropin to control reproduction of the dairy cow: a review.

    Science.gov (United States)

    De Rensis, F; López-Gatius, F

    2014-04-01

    Equine chorionic gonadotropin (eCG) is a member of the glycoprotein family of hormones along with LH, FSH and thyroid-stimulating hormone. In non-equid species, eCG shows high LH- and FSH-like activities and has a high affinity for both FSH and LH receptors in the ovaries. On the granulosa and thecal cells of the follicle, eCG has long-lasting LH- and FSH-like effects that stimulate oestradiol and progesterone secretion. Thus, eCG administration in dairy cattle results in fewer atretic follicles, the recruitment of more small follicles showing an elevated growth rate, the sustained growth of medium and large follicles and improved development of the dominant and pre-ovulatory follicle. In consequence, the quality of the ensuing CL is improved, and thereby progesterone secretion increased. Based on these characteristics, eCG treatment is utilized in veterinary medicine to control the reproductive activity of the cow by i) improving reproductive performance during early post-partum stages; ii) increasing ovulation and pregnancy rates in non-cyclic cows; iii) improving the conception rate in cows showing delayed ovulation; and finally, iv) eCG is currently included in protocols for fixed-time artificial insemination since after inducing the synchrony of ovulation using a progesterone-releasing device, eCG has beneficial effects on embryo development and survival. The above effects are not always observed in cyclic animals, but they are evident in animals in which LH secretion and ovarian activity are reduced or compromised, for instance, during the early post-partum period, under seasonal heat stress, in anoestrus animals or in animals with a low body condition score. © 2014 Blackwell Verlag GmbH.

  19. Melatonin supplementation during controlled ovarian stimulation for women undergoing assisted reproductive technology: systematic review and meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Seko, Ludimila M D; Moroni, Rafael M; Leitao, Valeria M S; Teixeira, Danielle M; Nastri, Carolina O; Martins, Wellington P

    2014-01-01

    To examine the best evidence available regarding the effect of melatonin supplementation during controlled ovarian stimulation (COS) on the main assisted reproductive technology (ART) outcomes. Systematic review and meta-analysis of randomized clinical trials (RCT). Not applicable. Women undergoing COS for ART. Melatonin supplementation during COS for women undergoing ART. Live birth rate, clinical pregnancy rate, number of retrieved oocytes, miscarriage rate, ovarian hyperstimulation syndrome (OHSS) rate, and number of congenital abnormalities. Comparisons were performed using risk ratio (RR) or mean difference (MD). Five RCTs were considered eligible, and their data were extracted and included in a meta-analysis. No studies reported live-birth or congenital abnormalities. Our estimates were imprecise for distinguishing between no effect and benefit considering clinical pregnancy (RR, 1.21; 95% confidence interval [CI], 0.98-1.50, five studies, 680 women, low quality-evidence) and the number of oocytes retrieved (MD, 0.6; 95% CI, -0.2-2.2, five studies, 680 women, low quality-evidence). Our estimates were imprecise for distinguishing among harm, no effect, and benefit considering miscarriage (RR, 1.07; 95% CI, 0.43-2.68, two studies, 143 clinical pregnancies, low quality-evidence) and interventions to reduce the risk of OHSS (RR,1.01; 95% CI, 0.33-3.08, one study, 358 women, low quality-evidence). More studies investigating the role of melatonin supplementation are still needed before recommending its use in clinical practice. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  20. Gonadotropin releasing hormone agonists: Expanding vistas

    Directory of Open Access Journals (Sweden)

    Navneet Magon

    2011-01-01

    Full Text Available Gonadotropin-releasing hormone (GnRH agonists are derived from native GnRH by amino acid substitution which yields the agonist resistant to degradation and increases its half-life. The hypogonadotropic hypogonadal state produced by GnRH agonists has been often dubbed as "pseudomenopause" or "medical oophorectomy," which are both misnomers. GnRH analogues (GnRH-a work by temporarily "switching off" the ovaries. Ovaries can be "switched off" for the therapy and therapeutic trial of many conditions which include but are not limited to subfertility, endometriosis, adenomyosis, uterine leiomyomas, precocious puberty, premenstrual dysphoric disorder, chronic pelvic pain, or the prevention of menstrual bleeding in special clinical situations. Rapidly expanding vistas of usage of GnRH agonists encompass use in sex reassignment of male to female transsexuals, management of final height in cases of congenital adrenal hyperplasia, and preserving ovarian function in women undergoing cytotoxic chemotherapy. Hypogonadic side effects caused by the use of GnRH agonists can be tackled with use of "add-back" therapy. Goserelin, leuprolide, and nafarelin are commonly used in clinical practice. GnRH-a have provided us a powerful therapeutic approach to the treatment of numerous conditions in reproductive medicine. Recent synthesis of GnRH antagonists with a better tolerability profile may open new avenues for both research and clinical applications. All stakeholders who are partners in women′s healthcare need to join hands to spread awareness so that these drugs can be used to realize their full potential.

  1. Does the use of gonadotropin-releasing hormone antagonists in natural IVF cycles for poor responder patients cause more harm than benefit?

    Science.gov (United States)

    Aksoy, Senai; Yakin, Kayhan; Seyhan, Ayse; Oktem, Ozgur; Alatas, Cengiz; Ata, Baris; Urman, Bulent

    2016-06-01

    Poor ovarian response to controlled ovarian stimulation (COS) is one of the most critical factors that substantially limits the success of assisted reproduction techniques (ARTs). Natural and modified natural cycle IVF are two options that could be considered as a last resort. Blocking gonadotropin-releasing hormone (GnRH) actions in the endometrium via GnRH receptor antagonism may have a negative impact on endometrial receptivity. We analysed IVF outcomes in 142 natural (n = 30) or modified natural (n = 112) IVF cycles performed in 82 women retrospectively. A significantly lower proportion of natural cycles reached follicular aspiration compared to modified natural cycles (56.7% vs. 85.7%, p cycles ending in embryo transfer (26.7% vs. 44.6%) was not statistically significant between natural cycle and modified natural IVF cycles. Clinical pregnancy (6.7% vs. 7.1%) and live birth rates per initiated cycle (6.7% vs. 5.4%) were similar between the two groups. Notably, the implantation rate was slightly lower in modified natural cycles (16% vs. 25%, p > 0.05). There was a trend towards higher clinical pregnancy (25% vs. 16%) and live birth (25% vs. 12%) rates per embryo transfer in natural cycles compared to modified natural cycles, but the differences did not reach statistical significance.

  2. The action of trenbolone acetate, a synthetic anabolic steroid, on ovarian function in the Guinea pig

    International Nuclear Information System (INIS)

    Zarkawi, M.; Galbraith, H.

    1992-01-01

    The action of trenbolone acetate, a synthetic anabolic steroid, on ovarian function was investigated in the Guinea pig. Certain comparisons were made with testosterone, the naturally occurring androgen, administered as the phenylpropionate ester. Progesterone was analysed using radioimmunoassay. two milligrams trenbolone acetate per Kg given subcutaneously on alternate days for 20 days blocked oestrous cyclicity and ovulation in 9 of 10 animals. A similar effect was shown by 2.2 mg of testosterone phenylpropionate. Treatment of trenbolone acetate-treated animals with exogenous gonadotropins suggested that the production of follicle stimulating hormone had been suppressed. Signs of abnormality were seen in the livers of animals receiving 2 mg trenbolone acetate and 2.2 mg testosterone phenylpropionate. (author). 17 refs., 2 tabs

  3. Kisspeptin regulates ovarian steroidogenesis during delayed embryonic development in the fruit bat, Cynopterus sphinx.

    Science.gov (United States)

    Anuradha; Krishna, Amitabh

    2017-11-01

    Cynopterus sphinx, a fruit bat, undergoes delayed embryonic development during the winter months, a period that corresponds to low levels of progesterone and estradiol synthesis by the ovary. Kisspeptins (KPs) are a group of neuropeptide hormones that act via G-protein coupled receptor 54 (GPR54) to stimulate hypothalamic secretion of Gonadotropin-releasing hormone, thereby regulating ovarian steroidogenesis, folliculogenesis, and ovulation. GPR54 is also expressed in the ovary, suggesting a direct role for KPs in ovarian steroidogenesis. The aim of present study was to determine if a low serum level of KP is responsible for reduced progesterone and estradiol levels during the period of delayed embryonic development in C. sphinx. Indeed, low serum KP abundance corresponded to reduced expression of GPR54 in ovarian luteal cells during the period of delayed development compared to normal development. In vitro and in vivo treatment with KP increased GPR54 abundance, via Extracellular signal regulated kinase and its downstream mediators, leading to increased progesterone synthesis in the ovary during delayed embryonic development. KP treatment also increased cholesterol uptake and elevated expression of Luteinizing hormone receptor and Steroid acute regulatory protein in the ovary, suggesting that elevation in circulating KP during delayed embryonic development may reactivate luteal activity. KPs may also enhance cell survival (BCL-2, reduced Caspase 3 activity) and angiogenesis (Vascular endothelium growth factor) during this period. The findings of this study thus demonstrate a regulatory role for KPs in the maintenance of luteal steroidogenesis during pregnancy in C. sphinx. © 2017 Wiley Periodicals, Inc.

  4. A review of luteinising hormone and human chorionic gonadotropin when used in assisted reproductive technology

    DEFF Research Database (Denmark)

    Ezcurra, Diego; Humaidan, Peter

    2014-01-01

    to the purification process, thus hCG, mimicking LH action, is added to standardise the product. However, unlike LH, hCG plays a very minor role during the natural human menstrual cycle. It is secreted by the embryo and placenta, and its main role is to support implantation and pregnancy. More recently, recombinant......Gonadotropins extracted from the urine of post-menopausal women have traditionally been used to stimulate folliculogenesis in the treatment of infertility and in assisted reproductive technology (ART). Products, such as human menopausal gonadotropin (hMG), consist not only of a mixture...... of the hormones, follicle-stimulating hormone (FSH), luteinising hormone (LH) and human chorionic gonadotropin (hCG), but also other biologically active contaminants, such as growth factors, binding proteins and prions. The actual amount of molecular LH in hMG preparations varies considerably due...

  5. GnRHa trigger and individualized luteal phase hCG support according to ovarian response to stimulation

    DEFF Research Database (Denmark)

    Humaidan, Peter; Polyzos, N P; Alsbjerg, B

    2013-01-01

    , there was a lack of blinding in the RCTs. WIDER IMPLICATIONS OF THE FINDINGS: Although a non-significant result, one bolus of 1.500 IU hCG after GnRHa trigger tended to reduce the OHSS rate in patients with 15-25 follicles ≥11 mm as well as secure the ongoing pregnancy rate. In contrast, in patients at low risk......STUDY QUESTION: Does a GnRH agonist (GnRHa) trigger followed by a bolus of 1.500 IU hCG in a group of patients at risk of ovarian hyperstimulation syndrome (OHSS) reduce the OHSS incidence compared with hCG trigger? SUMMARY ANSWER: A GnRHa trigger followed by early luteal hCG support with one bolus...... of 1.500 IU hCG appears to reduce OHSS in patients at risk of OHSS; however, in a low-risk group a second bolus of 1.500 IU hCG induced two cases of late onset OHSS. WHAT IS KNOWN ALREADY: A GnRHa trigger is an alternative to hCG in GnRH antagonist co-treated cycles. STUDY DESIGN, SIZE, DURATION: Two...

  6. The Effects of Administrated Sildenafil Citrate on Uterine Luminal Epithelium Height Associated with Ovarian Angiogenesis: An Experimental Animal Study

    Directory of Open Access Journals (Sweden)

    Mohammad Hosein Golkar

    2017-01-01

    Full Text Available Background: Ovarian angiogenesis (OA remains in lifetime and normal ovarian function depends to this continual remodeling of a complex vascular system. Endometrial thickness (ET is one of the strongest predictors of successful implantation and pregnancy. Appropriate OA effects on ET by facilitating of ovarian hormone delivery. Materials and Methods: Thirty adult female mice and twenty adult male mice were purchased. The female mice were divided into three groups: (1 control group without any intervention (n = 10, (2 gonadotropin group: receiving human menopausal gonadotropin (HMG and human chorionic gonadotropin (n = 10, and (3 gonadotropin and sildenafil citrate (SC group: receiving HMG and SC administration (n = 10. After mating, animals were deeply anesthetized, and the ovary and uterus was rapidly removed for histology and immunohistochemistry process. Results: Four days after ovarian induction, all three layers of the uterus with specified thickness can be clearly seen. The heights of endometrial epithelial cells in gonadotropin group were not significantly different than those in control group. In gonadotropin and SC group, heights of the cells were significantly (P 0.05 each. Our results of immunohistochemistry survey for ovarian CD31 demonstrated that administrated SC increased OA but not significantly (P > 0.05 each. Conclusion: It may finally conclude that administration of SC does not cause notable alterations in OA and ET; although for realistic decision about the SC effects on aforementioned parameters, more molecular investigations and longer drug consumption period are necessary.

  7. Cost effectiveness of ovarian reserve testing in in vitro fertilization: a Markov decision-analytic model.

    Science.gov (United States)

    Moolenaar, Lobke M; Broekmans, Frank J M; van Disseldorp, Jeroen; Fauser, Bart C J M; Eijkemans, Marinus J C; Hompes, Peter G A; van der Veen, Fulco; Mol, Ben Willem J

    2011-10-01

    To compare the cost effectiveness of ovarian reserve testing in in vitro fertilization (IVF). A Markov decision model based on data from the literature and original patient data. Decision analytic framework. Computer-simulated cohort of subfertile women aged 20 to 45 years who are eligible for IVF. [1] No treatment, [2] up to three cycles of IVF limited to women under 41 years and no ovarian reserve testing, [3] up to three cycles of IVF with dose individualization of gonadotropins according to ovarian reserve, and [4] up to three cycles of IVF with ovarian reserve testing and exclusion of expected poor responders after the first cycle, with no treatment scenario as the reference scenario. Cumulative live birth over 1 year, total costs, and incremental cost-effectiveness ratios. The cumulative live birth was 9.0% in the no treatment scenario, 54.8% for scenario 2, 70.6% for scenario 3 and 51.9% for scenario 4. Absolute costs per woman for these scenarios were €0, €6,917, €6,678, and €5,892 for scenarios 1, 2, 3, and 4, respectively. Incremental cost-effectiveness ratios (ICER) for scenarios 2, 3, and 4 were €15,166, €10,837, and €13,743 per additional live birth. Sensitivity analysis showed the model to be robust over a wide range of values. Individualization of the follicle-stimulating hormone dose according to ovarian reserve is likely to be cost effective in women who are eligible for IVF, but this effectiveness needs to be confirmed in randomized clinical trials. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  8. Altered neuroendocrine regulation of gonadotropin secretion in women distance runners.

    Science.gov (United States)

    Veldhuis, J D; Evans, W S; Demers, L M; Thorner, M O; Wakat, D; Rogol, A D

    1985-09-01

    We tested the hypothesis that the neuroendocrine control of gonadotropin secretion is altered in certain women distance runners with secondary amenorrhea. To this end, we quantitated the frequency and amplitude of spontaneous pulsatile LH secretion during a 24-h interval in nine such women. The ability of the pituitary gland to release LH normally was assessed by administration of graded bolus doses of GnRH during the subsequent 8 h. Compared to normally menstruating women, six of nine amenorrheic distance runners had a distinct reduction in spontaneous LH pulse frequency, with one, three, six, five, four, or two pulses per 24 h (normal, 8-15 pulses/24 h). This reduction in LH pulse frequency occurred without any significant alterations in plasma concentrations of estradiol and free testosterone or 24-h integrated serum concentrations of LH, FSH, or PRL. Moreover, in long-distance runners, the capacity of the pituitary gland to release LH was normal or accentuated in response to exogenous pulses of GnRH. In the six women athletes with diminished spontaneous LH pulsatility, acute ovarian responsiveness also was normal, since serum estradiol concentrations increased normally in response to the GnRH-induced LH pulses. Although long-distance runners had significantly lower estimated percent body fat compared to control women, specific changes in pulsatile gonadotropin release did not correlate with degree of body leanness. In summary, certain long-distance runners with secondary amenorrhea or severe oligomenorrhea have unambiguously decreased spontaneous LH pulse frequency with intact pituitary responsiveness to GnRH. This neuroendocrine disturbance may be relevant to exercise-associated amenorrhea, since pulsatile LH release is a prerequisite for cyclic ovarian function. We speculate that such alterations in pulsatile LH release in exercising women reflect an adaptive response of the hypothalamic pulse generator controlling the intermittent GnRH signal to the

  9. Gonadotropin-releasing hormone agonist triggering of oocyte maturation in assisted reproductive technology cycles

    Directory of Open Access Journals (Sweden)

    Engin Türkgeldi

    2015-06-01

    Full Text Available Gonadotropin-releasing hormone agonists (GnRHa have gained increasing attention in the last decade as an alternative trigger for oocyte maturation in patients at high risk for ovarian hyperstimulation syndrome (OHSS. They provide a short luteinizing hormone (LH peak that limits the production of vascular endothelial growth factor, which is the key mediator leading to increased vascular permeability, the hallmark of OHSS. Initial studies showed similar oocyte yield and embryo quality compared with conventional human chorionic gonadotropin (hCG triggering; however, lower pregnancy rates and higher miscarriage rates were alarming in GnRHa triggered groups. Therefore, two approaches have been implemented to rescue the luteal phase in fresh transfers. Intensive luteal phase support (iLPS involves administiration of high doses of progesterone and estrogen and active patient monitoring. iLPS has been shown to provide satisfactory fertilization and clinical pregnancy rates, and to be especially useful in patients with high endogenous LH levels, such as in polycystic ovary syndrome. The other method for luteal phase rescue is low-dose hCG administiration 35 hours after GnRHa trigger. Likewise, this method results in statistically similar ongoing pregnancy rates (although slightly lower than to those of hCG triggered cycles. GnRHa triggering decreased OHSS rates dramatically, however, none of the rescue methods prevent OHSS totally. Cases were reported even in patients who underwent cryopreservation and did not receive hCG. GnRH triggering induces a follicle stimulating hormone (FSH surge, similar to natural cycles. Its possible benefits have been investigated and dual triggering, GnRHa trigger accompanied by a simultaneous low-dose hCG injection, has produced promising results that urge further exploration. Last of all, GnRHa triggering is useful in fertility preservation cycles in patients with hormone sensitive tumors. In conclusion, GnRHa triggering

  10. Overt leptin response to controlled ovarian hyperstimulation negatively correlates with pregnancy outcome in in vitro fertilization--embryo transfer cycle

    Directory of Open Access Journals (Sweden)

    Jana Chakrabarti

    2012-01-01

    Full Text Available Context: A critical body mass of adipose tissue is essential for the normal development of female reproductive functions. Leptin, an adipocyte-derived hormone encoded by the ′Ob′ gene has been proposed as a peripheral signal indicating the adequacy of nutritional status for reproductive functions. It is reported as a direct regulator of gametogenic and steroidogenic potential of ovary. Though leptin is widely present in reproductive tissues, its relationship to reproductive hormones is still poorly understood. Aims: Present investigation attempts to explore ovarian response to secretory profile of leptin and its impact on pregnancy outcome in women undergoing controlled ovarian hyperstimulation for in vitro fertilization and embryo transfer (IVF-ET. Settings and Design: Patients enrolled for IVF-ET underwent pituitary-ovarian suppression by ′Long Protocol′ GnRH-agonist downregulation followed by ovarian stimulation. Materials and Methods: Sera were procured at different phases of IVF-ET for the assay of estradiol, progesterone, human chorionic gonadotropin, and for leptin. Ovarian follicular fluids were also assayed for leptin. Luteinized granulosa cells were cultured in vitro to evaluate their steroidogenic potential. Statistical Analysis Used: Statistical analyses were done by student′s t-test, ANOVA, and Chi-square tests as applicable. All results were expressed as Mean ± SE. P values < 0.05 were considered significant. Results: Positive correlation was observed between serum and ovarian follicular fluid leptin. A negative correlation was noted between the serum leptin levels and endometrial thickness. Conclusions: Elevated leptin response may exert adverse impacts on pregnancy success during IVF-ET possibly by modulating uterine receptivity.

  11. Fertility preservation with ovarian stimulation and time to treatment in women with stage II-III breast cancer receiving neoadjuvant therapy.

    Science.gov (United States)

    Chien, A Jo; Chambers, Julia; Mcauley, Fiona; Kaplan, Tessa; Letourneau, Joseph; Hwang, Jimmy; Kim, Mi-Ok; Melisko, Michelle E; Rugo, Hope S; Esserman, Laura J; Rosen, Mitchell P

    2017-08-01

    To determine whether fertility preservation with ovarian stimulation (OS) results in treatment delay in breast cancer (BC) patients receiving neoadjuvant therapy (NAT). This is a retrospective study of women screened for the prospective neoadjuvant ISPY2 trial at the University of California San Francisco. All patients were years old, p = 0.06), and more likely to be childless (79.4 vs 31.2%, p 40 days, with no significant difference between STIM and control groups (mean 39.8 days vs 40.9 days, p = 0.75). Mean time from diagnosis to fertility consultation was 16.3 days. With median follow-up of 79 months, 16 (19.5%) patients have recurred or died from BC. Rates of pCR, recurrence, and death were similar in both groups. Six of 34 STIM patients have undergone embryo transfer, resulting in one patient with two live births. Fertility preservation with OS can be performed in the neoadjuvant setting without delay in initiation of systemic therapy and should be discussed with all early-stage BC patients of reproductive age.

  12. Serum androgen and gonadotropin levels decline after progestogen-induced withdrawal bleeding in oligomenorrheic women with or without polycystic ovaries.

    Science.gov (United States)

    Anttila, L; Koskinen, P; Kaihola, H L; Erkkola, R; Irjala, K; Ruutiainen, K

    1992-10-01

    To examine the effect of short-term progestogen treatment on androgen, gonadotropin, and sex hormone-binding globulin (SHBG) levels in oligomenorrheic women. Comparative study of changes in hormonal parameters in patients with or without ultrasonographically diagnosed polycystic ovarian disease (PCOD). Open patient clinic of reproductive endocrinology at University Central Hospital of Turku, Finland. Seventy-five oligomenorrheic women with (n = 51) or without (n = 24) PCOD. Serum concentrations of testosterone (T), androstenedione (A), dehydroepiandrosterone sulfate, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and SHBG. The levels of T, A, LH, and the LH:FSH ratios decreased significantly after oral treatment with medroxyprogesterone acetate (10 mg/d for 10 days) in non-PCOD women and in women with PCOD decreasing the frequencies of pathological laboratory findings, in particular elevated levels of LH:FSH ratio and A in PCOD women and of LH:FSH ratio in non-PCOD women. The levels of T, A, and LH as well as the LH:FSH ratio were significantly higher in women with PCOD. Obesity was associated with high free androgen indices, low LH:FSH ratios, and low concentrations of LH, A, and SHBG. The serum samples for hormonal analyses used as an aid in diagnosing PCOD should be obtained without pretreatment with progestogen because it masks the biochemical findings of PCOD.

  13. Ovarian Disorders

    Science.gov (United States)

    ... a pregnancy can occur. Ovaries also make the female hormones estrogen and progesterone. When a woman goes through menopause, her ovaries stop making those hormones and releasing eggs. Problems with the ovaries include Ovarian cancer Ovarian ...

  14. Bio-equivalent doses of recombinent HCG and recombinent LH during ovarian stimulation result in similar oestradiol output

    DEFF Research Database (Denmark)

    Alsbjerg, Birgit; Elbaek, Helle Olesen; Laursen, Rita Jakubcionyte

    2017-01-01

    In nature, HCG is secreted by the implanting embryo from peri-implantation and onwards. In contrast, LH is mandatory for steroidogenesis and follicular development during the follicular phase, working in synergy with FSH. Moreover, LH is mandatory for the function of the corpus luteum. Although LH...... and HCG bind to the same receptor, significant molecular, structural and functional differences exist, inducing differences in bioactivity. This randomized controlled study compared the effect of recombinant FSH stimulation combined with daily either micro-dose recombinant HCG or recombinant LH...

  15. Effectiveness of a recombinant human follicle stimulating hormone on the ovarian follicles, peripheral progesterone, estradiol-17β, and pregnancy rate of dairy cows

    Directory of Open Access Journals (Sweden)

    Mohamed Ali

    2016-07-01

    Full Text Available Aims: This study aimed at elucidating the effects of recombinant human follicle stimulating hormone (r-hFSH on the ovarian follicular dynamics, progesterone, estradiol-17β profiles, and pregnancy of dairy cows. Materials and Methods: Three groups (G, n=5 cows of multiparous dairy cows were used. G1 (C control cows were given controlled internal drug release (CIDR and prostaglandin F2α; G2 (L cows were given low dose (525 IU and G3 (H cows were given high dose (1800 IU of r-hFSH on twice daily basis at the last 3 days before CIDR removal. All cows were ultrasonically scanned for follicular growth and dynamics, and blood samples were collected every other day for two consecutive estrus cycles for the determination of estradiol-17β and progesterone. Results: Estrus was observed in all C and L but not in H cows. Dominant follicle was bigger in L compared to C and H cows. Dominant follicle in C (16.00±2.5 mm and L cows (17.40±2.3 mm disappeared at 72 h after CIDR removal. However, in H cows, no ovulation has occurred during 7 days post-CIDR removal. Progesterone was not different (p>0.10 among groups, whereas estradiol-17β revealed significant (p<0.01 reduction in H (15.96±2.5 pg/ml cows compared to C (112.26±26.1 pg/ml and L (97.49±15.9 pg/ml cows. Pregnancy rate was higher in L cows (60% compared with C cows (20%. However, H cows were not artificially inseminated due to non-ovulation. Only a cow of C group has calved one calf, however, 2 of the L cows gave birth of twins and a cow gave single calf. Conclusion: Administration of a low dose (525 IU of r-hFSH resulted in an optimal size of dominant follicle, normal values of progesterone and estradiol-17β, and 40% twinning rate, howeverusing 1800 IU of r-hFSH, have adverse effects on ovarian follicular dynamics and hormonal profiles with non-pregnancy of dairy cows raised under hot climate.

  16. Co-expression of the Follicle Stimulating Hormone Receptor and Stem Cell Markers: A Novel Approach to Target Ovarian Cancer Stem Cells

    Science.gov (United States)

    2012-09-01

    ovarian cancer stem cell markers to consider it as a new experimental target for novel nanotechnology approaches capable of destroying ovarian cancer stem...FSHR mRNA after several generations in an amount consistent with stem cell characteristics. Nude mouse experiments to confirm co-expression in vivoare

  17. Expression of estrogen receptor α 36 (ESR36) in the hamster ovary throughout the estrous cycle: effects of gonadotropins.

    Science.gov (United States)

    Chakraborty, Prabuddha; Roy, Shyamal K

    2013-01-01

    Estradiol-17β (E) plays an important role in ovarian follicular development. Evidence indicates that some of the effect of E is mediated by the transmembrane estrogen receptor. In this study, we examined the spatio-temporal expression of recently discovered ERα36 (ESR36), a splice variant of Esr1 and a receptor for non-genomic E signaling, in the hamster ovary during the estrous cycle and the role of gonadotropins and ovarian steroid hormones in ESR36 expression. ESR36 expression was high on estrus (D1:0900 h) and declined precipitously by proestrus (D4:0900 h) and remained low up to D4:1600 h. Immunofluorescence findings corroborated immunoblot findings and revealed that ESR36 was expressed only in the cell membrane of both follicular and non-follicular cells, except the oocytes. Ovarian ESR36 was capable of binding to the E-affinity matrix, and have different molecular weight than that of the ESR1 or GPER. Hypophysectomy (Hx) resulted in a marked decline in ESR36 protein levels. FSH and LH, alone or combined, markedly upregulated ESR36 protein in Hx hamsters to the levels observed in D1 hamsters, but neither E nor P had any effect. Inhibition of the gonadotropin surge by phenobarbital treatment on D4:1100 h attenuated ESR36 expression in D1:0900 h ovaries, but the decline was restored by either FSH or LH replacement on D4 afternoon. This is the first report to show that ESR36, which is distinct from ESR1 or GPER is expressed in the plasma membrane of ovarian follicular and non-follicular cells, binds to E and its expression is regulated directly by the gonadotropins. In light of our previous findings, the results suggest that ovarian cells contain at least two distinct membrane estrogen receptors, such as GPER and ESR36, and strongly suggest for a non-genomic action of E regulating ovarian follicular functions.

  18. Isolation and characterization of gonadotropin isohormones from the pituitary gland of pike eel (Muraenesox cinereus)

    International Nuclear Information System (INIS)

    Huang, F.-L.; Huang, C.-J.; Lin, S.-H.; Lo, T.-B.; Papkoff, H.

    1981-01-01

    Pike eel gonadotropins were isolated from pituitary glands by 40% alcohol-6% ammonium acetate, pH 5.1 extraction and were purified by DEAE-cellulose chromatography and electrophoresis into four electrophoretically homogeneous forms. These four isohormones were biologically identified as gonadotropins by the stimulation of 32 P-uptake in 1-day-old chick testes, by the induction of ovulation in catfish, and by the in vitro production of testosterone from isolated rat Leydig cells and of androgen from carp testes. The amino acid composition of the isohormones were similar to other known piscine gonadotropins (carp and salmon) and were composed of two non-identical subunits with Tyr and Ser as N-terminal amino acid residues. The molecular weights of two subunits were 15000 and 10500, respectively, as estimated by SDS-gel disc electrophoresis. (author)

  19. Clinical outcome of one-third-dose depot triptorelin is the same as half-dose depot triptorelin in the long protocol of controlled ovarian stimulation

    Directory of Open Access Journals (Sweden)

    Yu Li

    2012-01-01

    Full Text Available Objective: Appropriate dosage of the long-acting depot gonadotrophin releasing hormone (GnRH agonist has not been determined in long protocol for IVF, and one-third-dose depot triptorelin was compared with half-dose in a luteal long protocol of in-vitro fertilization/ intra cytoplasmic sperm injection (IVF/ICSI treatment in this study. Materials and Methods: This is a prospective, randomized, open clinical trial. 100 patients were randomized into two groups. Group I received one-third-dose (1.25 mg depot triptorelin. Group II received half-dose (1.87 mg. The clinical and experimental parameters were compared between the two groups. Results: There was no premature luteinizing hormone (LH surge in both groups. On Day 3-5 of menstrual cycle after down-regulation, fewer patients showed low-level LH (<1.0 IU/L and estradiol (<30 pg/mL in group I (P <0.05. There were fewer oocytes retrieved (P =0.086, fewer total embryos and available embryos for cryopreservation in Group I (P <0.05, while good-quality embryo rate was higher in group I (P <0.05. The length and dose of ovarian stimulation was lower in Group I, but not significantly. The clinical pregnancy (52% versus 40%, implantation (48% versus 37.5%, delivery (46% versus 32%, or live birth (42% versus 32% rates and the abortion (8% versus 20% rates showed no significant differences. Conclusion: Depot triptorelin 1.25 mg can be successfully used with reduced pituitary suppression and lower cost in a long protocol for in-vitro fertilization.

  20. Clinical Value of Basal Serum Progesterone Prior to Initiate Ovarian Hyper-Stimulation with GnRH Antagonists: A Retrospective Cohort Study.

    Science.gov (United States)

    Faulisi, Sonia; Reschini, Marco; Borroni, Raffaella; Paffoni, Alessio; Busnelli, Andrea; Somigliana, Edgardo

    2017-01-01

    The routine assessment of day 3 serum progesterone prior to initiation of ovarian hyper-stimulation with the use of GnRH antagonists is under debate. In this study, we evaluated the clinical utility of this policy. Retrospective cohort study of women undergoing in vitro fertilization (IVF) with the use of GnRH antagonists aimed at determining the frequency of cases with progesterone levels exceeding the recommended threshold of 1,660 pg/ml and at evaluating whether this assessment may be predictive of pregnancy. Serum progesterone exceeded the recommended threshold in one case (0.3%, 95% CI 0.01-1.5). The median (interquartile range) basal progesterone in women who did (n = 95) and did not (n = 217) become pregnant were 351 (234-476) and 380 (237-531) pg/ml, respectively (p = 0.28). The 90th percentile of the basal progesterone distribution in women who became pregnant was 660 pg/ml. Cases with serum progesterone exceeding this threshold in successful and unsuccessful cycles were 10 (10%) and 30 (14%), respectively (p = 0.47). The capacity of basal progesterone to predict pregnancy was evaluated using receiver operating characteristic curve (area under the curve = 0.54, 95% CI 0.47-0.61, p = 0.28). No graphically evident threshold emerged. Routine day 3 serum progesterone assessment in IVF cycles with the use of GnRH antagonists is not justified. Further evidence is warranted prior to claiming its systematic use. © 2016 S. Karger AG, Basel.

  1. Regulation of the angiopoietin-2 gene by hCG in ovarian cancer cell line OVCAR-3.

    Science.gov (United States)

    Pietrowski, D; Wiehle, P; Sator, M; Just, A; Keck, C

    2010-05-01

    Angiogenesis is a crucial step in growing tissues including many tumors. It is regulated by pro- and antiangiogenic factors including the family of angiopoietins and their corresponding receptors. In previous work we have shown that in human ovarian cells the expression of angiopoietin 2 (ANG2) is regulated by human chorionic gonadotropin (hCG). To better understand the mechanisms of hCG-dependent regulation of the ANG2-gene we have now investigated upstream regulatory active elements of the ANG2-promoter in the ovarian carcinoma cell line OVCAR-3. We cloned several ANG2-promoter-fragments of different lengths into a luciferase reporter-gene-vector and analyzed the corresponding ANG2 expression before and after hCG stimulation. We identified regions of the ANG2-promoter between 1 048 bp and 613 bp upstream of the transcriptional start site where hCG-dependent pathways promote a significant downregulation of gene expression. By sequence analysis of this area we found several potential binding sites for transcription factors that are involved in regulation of ANG2-expression, vascular development and ovarian function. These encompass the forkhead family transcription factors FOXC2 and FOXO1 as well as the CCAAT/enhancer binding protein family (C/EBP). In conclusion, we have demonstrated that the regulation of ANG2-expression in ovarian cancer cells is hCG-dependent and we suggest that forkhead transcription factor and C/EBP-dependent pathways are involved in the regulation of ANG2-expression in ovarian cancer cells. Georg Thieme Verlag KG Stuttgart-New York.

  2. Laparoscopic ovarian drilling: An alternative but not the ultimate in the management of polycystic ovary syndrome

    Science.gov (United States)

    Mitra, Subarna; Nayak, Prasanta Kumar; Agrawal, Sarita

    2015-01-01

    Since its introduction in 1984, laparoscopic ovarian drilling has evolved into a safe and effective surgical treatment for anovulatory, infertile women with polycystic ovary syndrome (PCOS), unresponsive to clomiphene citrate. It is as effective as gonadotropins in terms of pregnancy and live birth rates, but without the risks of ovarian hyperstimulation syndrome and multiple pregnancies. It improves ovarian responsiveness to successive ovulation induction agents. Its favorable reproductive and endocrinal effects are sustained long. Despite its advantages, its use in unselected cases of PCOS or for non-fertility indications is not prudent owing to the potential risks of iatrogenic adhesions and ovarian insufficiency. PMID:25810633

  3. Ovarian function after autologous bone marrow transplantation in childhood: high-dose busulfan is a major cause of ovarian failure.

    Science.gov (United States)

    Teinturier, C; Hartmann, O; Valteau-Couanet, D; Benhamou, E; Bougneres, P F

    1998-11-01

    We studied pubertal status and ovarian function in 21 girls aged 11-21 years who had earlier received 1.2-13 years (median 7 years) high-dose chemotherapy and autologous BMT without TBI for malignant tumors. Ten of them were given busulfan (600 mg/m2) and melphalan (140 mg/m2) with or without cyclophosphamide (3.6 g/m2). Eleven others did not receive busulfan. Twelve girls (57%) had clinical and hormonal evidence of ovarian failure. Among nine others who had completed normal puberty, six had normal gonadotropin levels, one had elevated gonadotropin levels and two had gonadotropin levels at the upper limit of normal. The 10 girls who received busulfan all developed severe and persistent ovarian failure. High-dose busulfan is therefore a major cause of ovarian failure even when given in the prepubertal period. These findings emphasize the need for long-term endocrine follow-up of these patients in order to initiate estrogen replacement therapy.

  4. Origin of estradiol fatty acid esters in human ovarian follicular fluid.

    Science.gov (United States)

    Pahuja, S L; Kim, A H; Lee, G; Hochberg, R B

    1995-03-01

    The estradiol fatty acid esters are the most potent of the naturally occurring steroidal estrogens. These esters are present predominantly in fat, where they are sequestered until they are hydrolyzed by esterases. Thus they act as a preformed reservoir of estradiol. We have previously shown that ovarian follicular fluid from patients undergoing gonadotropin stimulation contains very high amounts of estradiol fatty acid esters (approximately 10(-7) M). The source of these esters is unknown. They can be formed by esterification of estradiol in the follicular fluid by lecithin:cholesterol acyltransferase (LCAT), or in the ovary by an acyl coenzyme A:acyltransferase. In order to determine which of these enzymatic processes is the source of the estradiol esters in the follicular fluid, we incubated [3H]estradiol with follicular fluid and cells isolated from human ovarian follicular fluid and characterized the fatty acid composition of the [3H]estradiol esters biosynthesized in each. In addition, we characterized the endogenous estradiol fatty acid esters in the follicular fluid and compared them to the biosynthetic esters. The fatty acid composition of the endogenous esters was different than those synthesized by the cellular acyl coenzyme A:acyltransferase, and the same as the esters synthesized by LCAT, demonstrating that the esters are produced in situ in the follicular fluid. Although the role of these estradiol esters in the ovary is not known, given their remarkable estrogenic potency it is highly probable that they have an important physiological role.

  5. The follicle-stimulating hormone (FSH) and luteinizing hormone (LH) response to a gonadotropin-releasing hormone analogue test in healthy prepubertal girls aged 10 months to 6 years

    DEFF Research Database (Denmark)

    Vestergaard, Esben T; Schjørring, Mia Elbek; Kamperis, Konstantinos

    2017-01-01

    and bone age were determined in all participants. Forty-eight healthy normal-weight girls aged 3.5 ± 0.2 years (range: 0.8-5.9 years) were included. Serum concentrations of LH and FSH were measured before and 30 min after the gonadorelin injection. RESULTS: The 30-min LH responses (mean ± 2 s.d.) were 5.......2 ± 4.0 and 2.9 ± 2.5 IU/L and the FSH responses were 23.3 ± 16.2 and 14.5 ± 10.3 IU/L in girls aged 0.8-3.0 years and 3.0-5.9 years respectively. This corresponds to upper cut-off limits for LH of 9.2 IU/L (3 years) and 5.3 IU/L (3-6 years). The stimulated LH/FSH ratio was 0.23 ± 0.19 (range 0.......06-0.43) and did not correlate with age. CONCLUSIONS: We found that LH increases up to 9.2 IU/L during GnRH test in healthy normal-weight girls below 3 years of age and that the stimulated LH/FSH ratio did not exceed 0.43. Our findings have important implications for appropriate diagnosis of central precocious...

  6. Use of a GnRH antagonist in controlled ovarian hyperstimulation for assisted conception in women with polycystic ovary disease: a randomized, prospective, pilot study.

    Science.gov (United States)

    Bahçeci, Mustafa; Ulug, Ulun; Ben-Shlomo, Izhar; Erden, Halit Firat; Akman, Mehmet Ali

    2005-02-01

    To compare the outcome of using gonadotropin-releasing hormone (GnRH) antagonists versus agonists in women with polycystic ovary disease (PCOD) who underwent controlled ovarian hyperstimulation (COH) for assisted reproductive techniques (ART). A total of 129 patients with PCOD were randomly allocated to undergo COH with a GnRH antagonist (59 patients) and GnRH agonist (leuprolide acetate) (70 patients) to prevent a premature luteinizing hormone (LH) surge. Assisted fertilization following oocyte retrieval and embryo transfer was performed. None of the cycles were cancelled due to a premature LH surge. There was no significant difference between the antagonist and agonist arms in the number of gonadotropin ampules consumed per cycle. However, in the antagonist arm a shorter duration of ovarian stimulation was recorded as compared to the agonist arm. Although similar numbers of oocytes was retrieved from both groups of patients, the quality of the oocytes, as measured by metaphase 2/total oocyte ratio, was lower in the antagonist arm as compared to the agonist arm. Pregnancy rates were 57.6% and 58.5% in the antagonist and agonist arms, respectively (p > 0.05). Implantation rates were not different (34.0% and 34.6%, respectively). The frequency of ovarian hyperstimulation syndrome also did not differ between the treatment groups (5% and 7.1%, respectively). The size of our study, on a specific subgroup of patients, does not allow a reliable conclusion regarding ART outcomefollowing the use of a GnRH antagonist versus agonist. Nevertheless, the protocol with the antagonist gave results that were as good as those of the protocol with the agonist in this PCOD patient population.

  7. Equine Chorionic Gonadotropin Modulates the Expression of Genes Related to the Structure and Function of the Bovine Corpus Luteum.

    Science.gov (United States)

    Sousa, Liza Margareth Medeiros de Carvalho; Mendes, Gabriela Pacheco; Campos, Danila Barreiro; Baruselli, Pietro Sampaio; Papa, Paula de Carvalho

    2016-01-01

    We hypothesized that stimulatory and superovulatory treatments, using equine chorionic gonadotropin (eCG), modulate the expression of genes related to insulin, cellular modelling and angiogenesis signaling pathways in the bovine corpus luteum (CL). Therefore, we investigated: 1-the effect of these treatments on circulating insulin and somatomedin C concentrations and on gene and protein expression of INSR, IGF1 and IGFR1, as well as other insulin signaling molecules; 2-the effects of eCG on gene and protein expression of INSR, IGF1, GLUT4 and NFKB1A in bovine luteal cells; and 3-the effect of stimulatory and superovulatory treatments on gene and protein expression of ANG, ANGPT1, NOS2, ADM, PRSS2, MMP9 and PLAU. Serum insulin did not differ among groups (P = 0.96). However, serum somatomedin C levels were higher in both stimulated and superovulated groups compared to the control (P = 0.01). In stimulated cows, lower expression of INSR mRNA and higher expression of NFKB1A mRNA and IGF1 protein were observed. In superovulated cows, lower INSR mRNA expression, but higher INSR protein expression and higher IGF1, IGFR1 and NFKB1A gene and protein expression were observed. Expression of angiogenesis and cellular modelling pathway-related factors were as follows: ANGPT1 and PLAU protein expression were higher and MMP9 gene and protein expression were lower in stimulated animals. In superovulated cows, ANGPT1 mRNA expression was higher and ANG mRNA expression was lower. PRSS2 gene and protein expression were lower in both stimulated and superovulated animals related to the control. In vitro, eCG stimulated luteal cells P4 production as well as INSR and GLUT4 protein expression. In summary, our results suggest that superovulatory treatment induced ovarian proliferative changes accompanied by increased expression of genes providing the CL more energy substrate, whereas stimulatory treatment increased lipogenic activity, angiogenesis and plasticity of the extracellular matrix

  8. Equine Chorionic Gonadotropin Modulates the Expression of Genes Related to the Structure and Function of the Bovine Corpus Luteum.

    Directory of Open Access Journals (Sweden)

    Liza Margareth Medeiros de Carvalho Sousa

    Full Text Available We hypothesized that stimulatory and superovulatory treatments, using equine chorionic gonadotropin (eCG, modulate the expression of genes related to insulin, cellular modelling and angiogenesis signaling pathways in the bovine corpus luteum (CL. Therefore, we investigated: 1-the effect of these treatments on circulating insulin and somatomedin C concentrations and on gene and protein expression of INSR, IGF1 and IGFR1, as well as other insulin signaling molecules; 2-the effects of eCG on gene and protein expression of INSR, IGF1, GLUT4 and NFKB1A in bovine luteal cells; and 3-the effect of stimulatory and superovulatory treatments on gene and protein expression of ANG, ANGPT1, NOS2, ADM, PRSS2, MMP9 and PLAU. Serum insulin did not differ among groups (P = 0.96. However, serum somatomedin C levels were higher in both stimulated and superovulated groups compared to the control (P = 0.01. In stimulated cows, lower expression of INSR mRNA and higher expression of NFKB1A mRNA and IGF1 protein were observed. In superovulated cows, lower INSR mRNA expression, but higher INSR protein expression and higher IGF1, IGFR1 and NFKB1A gene and protein expression were observed. Expression of angiogenesis and cellular modelling pathway-related factors were as follows: ANGPT1 and PLAU protein expression were higher and MMP9 gene and protein expression were lower in stimulated animals. In superovulated cows, ANGPT1 mRNA expression was higher and ANG mRNA expression was lower. PRSS2 gene and protein expression were lower in both stimulated and superovulated animals related to the control. In vitro, eCG stimulated luteal cells P4 production as well as INSR and GLUT4 protein expression. In summary, our results suggest that superovulatory treatment induced ovarian proliferative changes accompanied by increased expression of genes providing the CL more energy substrate, whereas stimulatory treatment increased lipogenic activity, angiogenesis and plasticity of the

  9. Predictive factors of early moderate/severe ovarian hyperstimulation syndrome in non-polycystic ovarian syndrome patients: a statistical model.

    Science.gov (United States)

    Ashrafi, Mahnaz; Bahmanabadi, Akram; Akhond, Mohammad Reza; Arabipoor, Arezoo

    2015-11-01

    To evaluate demographic, medical history and clinical cycle characteristics of infertile non-polycystic ovary syndrome (NPCOS) women with the purpose of investigating their associations with the prevalence of moderate-to-severe OHSS. In this retrospective study, among 7073 in vitro fertilization and/or intracytoplasmic sperm injection (IVF/ICSI) cycles, 86 cases of NPCO patients who developed moderate-to-severe OHSS while being treated with IVF/ICSI cycles were analyzed during the period of January 2008 to December 2010 at Royan Institute. To review the OHSS risk factors, 172 NPCOS patients without developing OHSS, treated at the same period of time, were selected randomly by computer as control group. We used multiple logistic regression in a backward manner to build a prediction model. The regression analysis revealed that the variables, including age [odds ratio (OR) 0.9, confidence interval (CI) 0.81-0.99], antral follicles count (OR 4.3, CI 2.7-6.9), infertility cause (tubal factor, OR 11.5, CI 1.1-51.3), hypothyroidism (OR 3.8, CI 1.5-9.4) and positive history of ovarian surgery (OR 0.2, CI 0.05-0.9) were the most important predictors of OHSS. The regression model had an area under curve of 0.94, presenting an allowable discriminative performance that was equal with two strong predictive variables, including the number of follicles and serum estradiol level on human chorionic gonadotropin day. The predictive regression model based on primary characteristics of NPCOS patients had equal specificity in comparison with two mentioned strong predictive variables. Therefore, it may be beneficial to apply this model before the beginning of ovarian stimulation protocol.

  10. Biphasic action of cyclic adenosine 3',5'- monophosphate in gonadotropin-releasing hormone (GnRH) analog-stimulated hormone release from GH3 cells stably transfected with GnRH receptor complementary deoxyribonucleic acid.

    Science.gov (United States)

    Stanislaus, D; Arora, V; Awara, W M; Conn, P M

    1996-03-01

    GH3 cells are a PRL-secreting adenoma cell line derived from pituitary lactotropes. These cells have been stably transfected with rat GnRH receptor complementary DNA to produce four cell lines: GGH(3)1', GGH(3)2', GGH(3)6', and GGH(3)12'. In response to either GnRH or Buserelin (a metabolically stable GnRH agonist), these cell lines synthesize PRL in a cAMP-dependent manner. Only GGH(3)6' cells desensitize in response to persistent treatment with 10(-7) g/ml Buserelin. GGH(3)1', GGH(3)2', and GGH(3)12' cells, however, can be made refractory to Buserelin stimulation by raising cAMP levels either by the addition of (Bu)2cAMP to the medium or by treatment with cholera toxin. In GGH(3) cells, low levels of cAMP fulfill the requirements for a second messenger, whereas higher levels appear to mediate the development of desensitization. The observation that in GGH(3)6' cells, cAMP production persists after the onset of desensitization is consistent with the view that the mechanism responsible for desensitization is distal to the production of cAMP. Moreover, the absence of any significant difference in the amount of cAMP produced per cell in GGH(3)2', GGH(3)6', or GGH(3)12' cells suggests that elevated cAMP production per cell does not explain the development of desensitization in GGH(3)6' cells. We suggest that Buserelin-stimulated PRL synthesis in GGH(3)6' cells is mediated by a different cAMP-dependent protein kinase pool(s) than that in nondesensitizing GGH(3) cells. Such a protein kinase A pool(s) may be more susceptible to degradation via cAMP-mediated mechanisms than the protein kinase pools mediating the Buserelin response in nondesensitizing GGH(3) cells. A similar mechanism has been reported in other systems.

  11. Persistence of insulin resistance in polycystic ovarian disease after inhibition of ovarian steroid secretion.

    Science.gov (United States)

    Geffner, M E; Kaplan, S A; Bersch, N; Golde, D W; Landaw, E M; Chang, R J

    1986-03-01

    Six nonobese women with polycystic ovarian disease (PCOD) showed significant hyperinsulinemia, compared with controls after oral glucose (P less than 0.05). As an indicator of insulin sensitivity, in vitro proliferation of erythrocyte progenitor cells of PCOD subjects exposed to physiologic concentrations of insulin was significantly blunted (P less than 0.001). Monocyte insulin receptor binding was not impaired in the PCOD subjects. Three of the PCOD patients were treated with a long-acting gonadotropin-releasing hormone agonist for 6 months, which resulted in marked suppression of ovarian androgen secretion but no demonstrable changes in in vivo or in vitro indicators of insulin resistance. Thus insulin resistance in PCOD subjects appears to be unrelated to ovarian hyperandrogenism (or acanthosis or obesity). Although certain tissues are insulin-resistant in PCOD patients, the ovary may remain sensitive and overproduce androgens in response to high circulating insulin levels.

  12. Ovulation induction with pulsatile gonadotropin-releasing hormone (GnRH) or gonadotropins in a case of hypothalamic amenorrhea and diabetes insipidus.

    Science.gov (United States)

    Georgopoulos, N A; Markou, K B; Pappas, A P; Protonatariou, A; Vagenakis, G A; Sykiotis, G P; Dimopoulos, P A; Tzingounis, V A

    2001-12-01

    Hypothalamic amenorrhea is a treatable cause of infertility. Our patient was presented with secondary amenorrhea and diabetes insipidus. Cortisol and prolactin responded normally to a combined insulin tolerance test (ITT) and thyrotropin-releasing hormone (TRH) challenge, while thyroid-stimulating hormone (TSH) response to TRH was diminished, and no response of growth hormone to ITT was detected. Both luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels increased following gonadotropin-releasing hormone (GnRH) challenge. No response of LH to clomiphene citrate challenge was detected. Magnetic resonance imaging findings demonstrated a midline mass occupying the inferior hypothalamus, with posterior lobe not visible and thickened pituitary stalk. Ovulation induction was carried out first with combined human menopausal gonadotropins (hMG/LH/FSH) (150 IU/day) and afterwards with pulsatile GnRH (150 ng/kg/pulse). Ovulation was achieved with both pulsatile GnRH and combine gonadotropin therapy. Slightly better results were achieved with the pulsatile GnRH treatment.

  13. The potential of follicle-stimulating hormone peptide-modified triptolide-loaded nanoparticles to induce a mouse model of premature ovarian insufficiency

    Directory of Open Access Journals (Sweden)

    Chen XY

    2015-04-01

    Full Text Available Xiu-Ying Chen,1–3 Wu-Lian Chen,4 Min Ma,1–3 Chao Gu,1,2 Xi-Rong Xiao,1,2 Bin Li1,2 1Obstetrics and Gynecology Hospital, Fudan University, 2Department of Obstetrics and Gynecology of Shanghai Medical College, Fudan University, 3Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, 4State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, Shanghai, People’s Republic of ChinaAbstract: The use of triptolide (TP is limited by its poor water solubility and severe toxicity. In this study, we developed an active drug delivery system (TP-loaded nanoparticles that could help improve the water solubility of TP and decrease its toxicity. Then, we investigated whether TP-loaded nanoparticles could be used to establish a novel premature ovarian insufficiency mouse model. The mice treated with TP-loaded nanoparticles for 35 days displayed normal growth, decreased serum antimullerian hormone, prominent ovarian fibrosis and vacuolar changes, fewer follicles and corpus lutea, increased collapsed oocytes and follicle apoptosis, and sterility. In conclusion, this model appears to show the reproductive characteristics associated with premature ovarian insufficiency in women and will allow us to study the mechanism of the effects of traditional Chinese medicine on gonadal toxicity. Keywords: peptide, nanoparticles, drug delivery, premature ovarian insufficiency, animal model

  14. OVX1, macrophage-colony stimulating factor, and CA-125-II as tumor markers for epithelial ovarian carcinoma - A critical appraisal

    NARCIS (Netherlands)

    van Haaften-Day, C; Shen, Y; Xu, FJ; Yu, YH; Berchuck, A; Havrilesky, LJ; de Bruijn, HWA; van der Zee, AGJ; Bast, RC; Hacker, NF

    2001-01-01

    BACKGROUND. Ovarian carcinoma remains the leading cause of death from gynecologic malignancy in Australia, the Netherlands, and the United States. CA-125-II, the most widely used serum marker, has limited sensitivity and specificity for detecting small-volume, early-stage disease. Therefore, a panel

  15. Primary Ovarian Insufficiency: X chromosome defects and autoimmunity.

    Science.gov (United States)

    Persani, Luca; Rossetti, Raffaella; Cacciatore, Chiara; Bonomi, Marco

    2009-08-01

    Premature ovarian failure (POF) is a primary ovarian defect characterized by absent menarche or premature depletion of ovarian follicles before the age of 40 years. However, in several instances the distinction between definitive or intermittent POF may be difficult on clinical bases, therefore the more appropriate term Primary Ovarian Insufficiency (POI) has been recently proposed and will be used in this review. POI is a heterogeneous disorder affecting approximately 1% of women disappearance of menstrual cycles (secondary amenorrhea) associated with a defective folliculogenesis. POI is generally characterized by low levels of gonadal hormones (estrogens and inhibins) and high levels of gonadotropins (LH and FSH) (hypergonadotropic amenorrhea). Heterogeneity of POI is reflected by the variety of possible causes, including autoimmunity, toxics, drugs, as well as genetic defects. Several data indicate that POI has a strong genetic component. In this manuscript we discuss the X chromosome abnormalities that are associated with POI.

  16. Different gonadotropin releasing hormone agonist doses for the final oocyte maturation in high-responder patients undergoing in vitro fertilization/intra-cytoplasmic sperm injection

    Directory of Open Access Journals (Sweden)

    Emre Goksan Pabuccu

    2015-01-01

    Full Text Available Context: Efficacy of gonadotropin releasing hormone agonists (GnRH-a for ovulation in high-responders. Aims: The aim of the current study is to compare the impact of different GnRH-a doses for the final oocyte maturation on cycle outcomes and ovarian hyperstimulation syndrome (OHSS rates in high-responder patients undergoing ovarian stimulation. Settings And Designs: Electronic medical records of a private in vitro fertilization center, a retrospective analysis. Subjects and Methods: A total of 77 high-responder cases were detected receiving GnRH-a. Group I consisted of 38 patients who received 1 mg of agonist and Group II consisted of 39 patients who received 2 mg of agonist. Statistical Analysis: In order to compare groups, Student′s t-test, Mann-Whitney U-test, Pearson′s Chi-square test or Fisher′s exact test were used where appropriate. A P < 0.05 was considered as statistically significant. Result: Number of retrieved oocytes (17.5 vs. 15.0, P = 0.510, implantation rates (46% vs. 55.1%, P = 0.419 and clinical pregnancy rates (42.1% vs. 38.5%, P = 0.744 were similar among groups. There were no mild or severe OHSS cases detected in Group I. Only 1 mild OHSS case was detected in Group II. Conclusion: A volume of 1 or 2 mg leuprolide acetate yields similar outcomes when used for the final oocyte maturation in high-responder patients.

  17. Effects of postoperative adjuvant chemotherapy and radiotherapy on ovarian function in women undergoing treatment for soft tissue sarcoma

    Energy Technology Data Exchange (ETDEWEB)

    Shamberger, R.C. (National Inst. of Health, Bethesda, MD); Sherins, R.J.; Ziegler, J.L.; Glatstein, E.; Rosenberg, S.A.

    1981-12-01

    Ovarian function was evaluated in 11 women 16 to 43 years of age at treatment who received doxorubicin, cyclophosphamide, and high doses of methotrexate with or without radiotherapy in adjuvant therapy of soft tissue sarcoma. Five women (16-33 yr old) who received chemotherapy alone or combined with radiotherapy only at sites distant from the ovaries (chest wall, thigh, and leg) had minimal menstrual irregularities or temporary cessation of menses during therapy; cyclic menses returned promptly after therapy. Gonadotropin levels (expressed as means +/- SD) (follicle-stimulating hormone (FSH), 10 +/- 15 mlU/ml; luteinizing hormone (LH), 10 +/- 4 mlU/ml) and 17 ..beta..-estradiol (E/sub 2/) levels (means +/- SD, 208 +/- 147 pg/ml) were normal. By contrast, 4 older women (ages 36-43 yr) who received similar treatment developd persistent amenorrhea with postmenopausal levels of gonadotropin (FSH, 109 +/- 29 mlU/ml; LH, 72 +/- 19 mlU/ml) and E/sub 2/ (19 +/- 8 pg/ml). Two additional women (ages 21 and 39 yr) who received radiation (7000 rad) to the pelvis plus chemotherapy developed prompt cessation of menses and became functional castrates (FSH, 77 and 80mlU/ml; LH, 40 and 58 mlU/ml; E/sub 2/, 10 and 19 pg/ml). However, this result would be expected from the radiation dose alone. The data demonstrated that ovarian dysfunction may follow the use of doxorubicin, cyclophosphamide, and high doses of methotrexate and that the injury is age related.

  18. Active immunization against gonadotropin-releasing hormone : an effective tool to block the fertility axis in mammals

    NARCIS (Netherlands)

    Turkstra, Jouwert Anne

    2005-01-01

    Gonadotropin releasing hormone (GnRH) plays a pivotal role in fertility and reproduction in mammals. It induces the release of luteinising hormone (LH) en follicle stimulating hormone (FSH) from the pituitary. These hormones are responsible for gonadal steroid production and indirectly for

  19. Mathematical modeling of gonadotropin-releasing hormone signaling.

    Science.gov (United States)

    Pratap, Amitesh; Garner, Kathryn L; Voliotis, Margaritis; Tsaneva-Atanasova, Krasimira; McArdle, Craig A

    2017-07-05

    Gonadotropin-releasing hormone (GnRH) acts via G-protein coupled receptors on pituitary gonadotropes to control reproduction. These are G q -coupled receptors that mediate acute effects of GnRH on the exocytotic secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), as well as the chronic regulation of their synthesis. GnRH is secreted in short pulses and GnRH effects on its target cells are dependent upon the dynamics of these pulses. Here we overview GnRH receptors and their signaling network, placing emphasis on pulsatile signaling, and how mechanistic mathematical models and an information theoretic approach have helped further this field. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  20. Abrogation by human menopausal gonadotropin on testicular ...

    African Journals Online (AJOL)

    Cisplatin is one of the most effective chemotherapeutic agents used in the treatment of cancer cells including testicular cancer. Human Menopausal Gonadotropin (HMG) is a natural hormone necessary for human reproduction. This hormone is a leading modality of treatment for infertility as it contains equal amount of ...

  1. Ovarian lymphoma

    International Nuclear Information System (INIS)

    Bonet Fonseca, Ivan; Diaz Anaya, Amnia; Francis, Tabu

    2012-01-01

    50 % of pediatric oncologic pathology corresponds to mass or solid tumors, reaching about 20 % of total abdomen. The tumors that most frequently occur in the abdomen are nephroblastoma or Wilms tumor, Burkitts lymphoma, neuroblastoma, and ovarian germ cell tumors

  2. Ovarian cancer

    Science.gov (United States)

    ... injected directly into the abdominal cavity (intraperitoneal, or IP). Radiation therapy is rarely used to treat ovarian ... About MedlinePlus Site Map FAQs Customer Support Get email updates Subscribe to RSS Follow us Disclaimers Copyright ...

  3. Ovarian Cancer

    Science.gov (United States)

    ... I find more information about ovarian and other gynecologic cancers? Centers for Disease Control and Prevention: 800-CDC-INFO or www. cdc. gov/ cancer/ gynecologic National Cancer Institute: 800-4-CANCER or www. ...

  4. Pregnancy outcome in women with polycystic ovary syndrome comparing the effects of laparoscopic ovarian drilling and clomiphene citrate stimulation in women pre-treated with metformin: a retrospective study.

    Science.gov (United States)

    Ott, Johannes; Kurz, Christine; Nouri, Kazem; Wirth, Stefan; Vytiska-Binstorfer, Elisabeth; Huber, Johannes C; Mayerhofer, Klaus

    2010-05-13

    Ovarian stimulation in women with polycystic ovary syndrome (PCOS) increases the risk for perinatal complications. Ovulation induction by laparoscopic ovarian drilling (LOD) might improve the overall pregnancy outcomes. The aim of our study was to assess the adverse events or effects on pregnancy of LOD and clomiphene citrate (CC) stimulation in patients who received metformin. Academic research institution. We retrospectively analyzed the courses of 40 spontaneous pregnancies after LOD for CC-resistance, 40 pregnancies after CC stimulation, and 40 pregnancies after metformin treatment alone. Patients in the LOD and the CC groups had been pre-treated with Metformin. Primary outcome parameters were: the rate of multiple pregnancies; the rate of early pregnancy losses/miscarriages; the development of gestational diabetes, pregnancy-induced hypertension, and preeclampsia/HELLP-syndrome; premature delivery; and birth weight. The rate of twin pregnancies did not differ between the CC group (12.5%), the LOD group (7.5%), and the metformin only group (2.5%, p=0.239). Seventeen women suffered an early miscarriage. There were no differences with regard to the rates of gestational diabetes, pregnancy-induced hypertension, preeclampsia, and preterm delivery. By analyzing all pregnancy complications together, the overall pregnancy complication rate was highest in the CC group (70.0%, 28/40), followed by the LOD group (45.0%, 18/40), and the metformin only group (47.5%, 19/40; p=0.047). CC, but not LOD, increases the complication rate in pregnant patients who received metformin.

  5. Pregnancy outcome in women with polycystic ovary syndrome comparing the effects of laparoscopic ovarian drilling and clomiphene citrate stimulation in women pre-treated with metformin: a retrospective study

    Directory of Open Access Journals (Sweden)

    Vytiska-Binstorfer Elisabeth

    2010-05-01

    Full Text Available Abstract Background Ovarian stimulation in women with polycystic ovary syndrome (PCOS increases the risk for perinatal complications. Ovulation induction by laparoscopic ovarian drilling (LOD might improve the overall pregnancy outcomes. The aim of our study was to assess the adverse events or effects on pregnancy of LOD and clomiphene citrate (CC stimulation in patients who received metformin. Methods Setting: Academic research institution. We retrospectively analyzed the courses of 40 spontaneous pregnancies after LOD for CC-resistance, 40 pregnancies after CC stimulation, and 40 pregnancies after metformin treatment alone. Patients in the LOD and the CC groups had been pre-treated with Metformin. Primary outcome parameters were: the rate of multiple pregnancies; the rate of early pregnancy losses/miscarriages; the development of gestational diabetes, pregnancy-induced hypertension, and preeclampsia/HELLP-syndrome; premature delivery; and birth weight. Results The rate of twin pregnancies did not differ between the CC group (12.5%, the LOD group (7.5%, and the metformin only group (2.5%, p = 0.239. Seventeen women suffered an early miscarriage. There were no differences with regard to the rates of gestational diabetes, pregnancy-induced hypertension, preeclampsia, and preterm delivery. By analyzing all pregnancy complications together, the overall pregnancy complication rate was highest in the CC group (70.0%, 28/40, followed by the LOD group (45.0%, 18/40, and the metformin only group (47.5%, 19/40; p = 0.047. Conclusions CC, but not LOD, increases the complication rate in pregnant patients who received metformin.

  6. Induction of Gonadotropins for Reproductive Control

    Directory of Open Access Journals (Sweden)

    Elza Ibrahim Auerkari

    2015-10-01

    Full Text Available Much of the recent research on gonadotropin – related control processes of reproduction and reproductive maturation has concentrated on the neuronal and molecular biology of gonadotropin release. The reproductive development of healthy mammals requires appropriate fetal develompment and migration of the neural network controlling and including the gonadotropin releasing hormone (GnRH – producing neurons that are needed to regulate GnRH and luteinizing hormone (LH release. GnRH is also necessary for the development of the gonadotropin – producing pituitary gland. The fetal gonads respon to GnRH – induced LH production by producing the gonadal steroids required for further reproductive differentiation. Pubertal maturation is characterised by increases in LH levels, representing the corresponding pulsatile release of GnRH. This GnRH pulse generator appears to be an intrinsic property of the arcuate nucleus at the medial basal hypothalamus. The generator activity can be mediated by the neurotransmitter aspartate which activates neurons of the hypothalamus, inducing acuate releases of GnRH and hence initiates puberty. A major factor in human reproductive maturation is the decrease in the age of puberty, caused by improvement of nutritional conditions due to the socio – economic development. This implies that the pubertal activation of GnRH secretion depends on metabolic conditions. Of the substances that mediate the metabolic condition to the neuronal network regulating GnRH secretion, the role of the neuropeptide Y (NPY appears instrumental : for healthy mammals less food means more NPY, and accumulated NPY makes food to become sex. NPY does this by regulating the appropriate hypothalamic functions including the neuroendocrine control of gonadotropin release.

  7. Thoracic manifestations of ovarian hyperstimulation syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Levin, M.F.; Hutton, L.C.; Kaplan, B.R. [University of Western Ontario, London, ON (Canada)

    1995-02-01

    In order to determine the thoracic manifestations of severe ovarian hyperstimulation syndrome, the medical records and available images of 771 patients who had received gonadotropins to induce superovulation, were reviewed. In 22 patients (3%) severe hyperstimulation syndrome was diagnosed clinically and confirmed with ultrasonography (US). Pleural effusion occurred in five of these (23%), one of whom required thoracentesis. Atelectasis and internal jugular vein thrombosis developed in one patient, and ventilation-perfusion mismatch occurred in another. The study concluded that respiratory distress in patients with ovarian hyperstimulation syndrome was most likely due to lung restriction. Pulmonary manifestations formed an important part of this syndrome, and radiologic input were considered necessary for assessment, monitoring and management. 10 refs., 2 figs., 1 tab.

  8. Microdose flare protocol with interrupted follicle stimulating hormone and added androgen for poor responders--an observational pilot study.

    Science.gov (United States)

    Mitri, Frederic; Behan, Lucy Ann; Murphy, Courtney A; Hershko-Klement, Anat; Casper, Robert F; Bentov, Yaakov

    2016-01-01

    To investigate whether temporarily withholding FSH and adding androgen could improve follicular response during a microdose flare protocol in women with slow follicular growth or asynchronous follicular development. Observational pilot study. University-affiliated private fertility center. Twenty-six women aged 34-47 years with poor response to stimulation or a previous cancelled IVF cycle and with slow or asynchronous follicular growth during a microdose flare cycle. For 13 women, after initiation of ovarian stimulation using the microdose flare protocol, gonadotropin administration was interrupted and transdermal testosterone gel was added for several days (4.4 ± 1.2 d) starting after cycle day 7 (mean cycle day 10 ± 2.6). FSH, E2, follicular growth, and total number of mature oocytes retrieved were determined for all of the patients. Cycle cancellation rate as well as pregnancy rate following embryo transfer were also documented when applicable. FSH levels declined (25.2 ± 6.5 to 6.8 ± 3.2 IU/L), E2 levels increased (896 ± 687 to 2,163 ± 1,667 pmol/L), and follicular growth improved significantly during gonadotropin interruption and were tracked for 2 days during this time frame. The average number of oocytes retrieved was 5.3 ± 2.6, and the ratio of mature to total oocytes was 4:5. Four of the 13 women in the interruption group conceived following frozen embryo transfer, whereas none in the control group did. The androgen-interrupted FSH protocol may improve follicular response to gonadotropins in cycles that might otherwise be cancelled. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  9. Expression of estrogen receptor α 36 (ESR36 in the hamster ovary throughout the estrous cycle: effects of gonadotropins.

    Directory of Open Access Journals (Sweden)

    Prabuddha Chakraborty

    Full Text Available Estradiol-17β (E plays an important role in ovarian follicular development. Evidence indicates that some of the effect of E is mediated by the transmembrane estrogen receptor. In this study, we examined the spatio-temporal expression of recently discovered ERα36 (ESR36, a splice variant of Esr1 and a receptor for non-genomic E signaling, in the hamster ovary during the estrous cycle and the role of gonadotropins and ovarian steroid hormones in ESR36 expression. ESR36 expression was high on estrus (D1:0900 h and declined precipitously by proestrus (D4:0900 h and remained low up to D4:1600 h. Immunofluorescence findings corroborated immunoblot findings and revealed that ESR36 was expressed only in the cell membrane of both follicular and non-follicular cells, except the oocytes. Ovarian ESR36 was capable of binding to the E-affinity matrix, and have different molecular weight than that of the ESR1 or GPER. Hypophysectomy (Hx resulted in a marked decline in ESR36 protein levels. FSH and LH, alone or combined, markedly upregulated ESR36 protein in Hx hamsters to the levels observed in D1 hamsters, but neither E nor P had any effect. Inhibition of the gonadotropin surge by phenobarbital treatment on D4:1100 h attenuated ESR36 expression in D1:0900 h ovaries, but the decline was restored by either FSH or LH replacement on D4 afternoon. This is the first report to show that ESR36, which is distinct from ESR1 or GPER is expressed in the plasma membrane of ovarian follicular and non-follicular cells, binds to E and its expression is regulated directly by the gonadotropins. In light of our previous findings, the results suggest that ovarian cells contain at least two distinct membrane estrogen receptors, such as GPER and ESR36, and strongly suggest for a non-genomic action of E regulating ovarian follicular functions.

  10. Thyrotropic action of human chorionic gonadotropin.

    Science.gov (United States)

    Yoshimura, M; Hershman, J M

    1995-10-01

    Hyperthyroidism or increased thyroid function has been reported in many patients with trophoblastic tumors. In these cases, greatly increased human chorionic gonadotropin (hCG) levels and suppressed TSH levels suggest that hCG has thyrotropic activity. Recent investigations have clarified the structural homology not only in the hCG and TSH molecules but also in their receptors, and this homology suggests the basis for the reactivity of hCG with the TSH receptor. The clinical significance of the thyrotropic action of hCG is now also recognized in normal pregnancy and hyperemesis gravidarum. Highly purified hLH binds to recombinant hTSH receptor and is about 10 times as potent as purified hCG in increasing cAMP. The beta-subunits of hCG and hLH share 85% sequence identity in their first 114 amino acids but differ in the carboxy-terminal peptide because hCG beta contains a 31-amino acid extension (beta-CTP). A recombinant mutant hCG that lacks beta-CTP showed almost identical potency to LH on stimulation of recombinant hTSH receptor. If intact hCG were as potent as hLH in regard to its thyrotropic activity, most pregnant women would become thyrotoxic. One of the roles of the beta-CTP may be to prevent overt hyperthyroidism in the first trimester of pregnancy when a large amount of hCG is produced by the placenta. Nicked hCG preparations, obtained from patients with trophoblastic disease or by enzymatic digestion of intact hCG, showed approximately 1.5- to 2-fold stimulation of recombinant hTSH receptor compared with intact hCG. This suggests that the thyrotropic activity of hCG may be influenced by the metabolism of the hCG molecule itself. Deglycosylation and/or desialylation of hCG enhances its thyrotropic potency. Basic hCG isoforms with lower sialic acid content extracted from hydatidiform moles were more potent in activating adenylate cyclase, and showed high bioactivity/immunoactivity (B/I) ratio in CHO cells expressing human TSH receptors. This is consistent

  11. Angiotensin II type 2 receptor stimulation improves fatty acid ovarian uptake and hyperandrogenemia in an obese rat model of polycystic ovary syndrome.

    Science.gov (United States)

    Leblanc, Samuel; Battista, Marie-Claude; Noll, Christophe; Hallberg, Anders; Gallo-Payet, Nicole; Carpentier, André C; Vine, Donna F; Baillargeon, Jean-Patrice

    2014-09-01

    Polycystic ovary syndrome (PCOS) is mainly defined by hyperandrogenism but is also characterized by insulin resistance (IR). Studies showed that overexposure of nonadipose tissues to nonesterified fatty acids (NEFA) may explain both IR and hyperandrogenism. Recent studies indicate that treatment with an angiotensin II type 2 receptor (AT2R)-selective agonist improves diet-induced IR. We thus hypothesized that PCOS hyperandrogenism is triggered by ovarian NEFA overexposure and is improved after treatment with an AT2R agonist. Experiments were conducted in 12-week-old female JCR:LA-cp/cp rats, which are characterized by visceral obesity, IR, hyperandrogenism, and polycystic ovaries. Control JCR:LA +/? rats have a normal phenotype. Rats were treated for 8 days with saline or the selective AT2R agonist C21/M24 and then assessed for: 1) fasting testosterone, NEFA, and insulin levels; and 2) an iv 14(R,S)-[(18)F]fluoro-6-thia-heptadecanoic acid test to determine NEFA ovarian tissue uptake (Km). Compared with controls, saline-treated PCOS/cp rats displayed higher insulin (100 vs 5.6 μU/mL), testosterone (0.12 vs 0.04 nmol/L), NEFA (0.98 vs 0.48 mmol/L), and Km (20.7 vs 12.9 nmol/g·min) (all P < .0001). In PCOS/cp rats, C21/M24 did not significantly improve insulin or NEFA but normalized testosterone (P = .004) and Km (P = .009), which were strongly correlated together in all PCOS/cp rats (ρ = 0.74, P = .009). In conclusion, in an obese PCOS rat model, ovarian NEFA uptake and testosterone levels are strongly associated and are both significantly reduced after short-term C21/M24 therapy. These findings provide new information on the role of NEFA in PCOS hyperandrogenemia and suggest a potential role for AT2R agonists in the treatment of PCOS.

  12. Diminished ovarian reserve in patients with psoriasis

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    Burcu Tuğrul Ayanoğlu

    2018-04-01

    Full Text Available Objective: Psoriasis is a multi-systemic chronic inflammatory skin disease. Previous data suggests that women with some chronic inflammatory diseases have diminished ovarian reserve. This study explores ovarian reserve in patients with psoriasis. Materials and methods: We prospectively analyzed 14 female patients with psoriasis and 35 healthy age and body mass index matched controls. An interview explored demographic characteristics, obstetrical history and menstrual characteristics. Psoriatic area severity index (PASI in patients was assessed. Estrogen, follicle-stimulating hormone (FSH, luteinizing hormone (LH, thyroid stimulating hormone and with gynecologic ultrasonography, ovarian volume and antral follicular count (AFC were measured in both study and control groups. These values were analyzed with changes of the PASI in the patient group. Results: Patients with psoriasis had significantly higher levels of FSH and FSH/LH ratio than healthy controls (p = 0.039, p = 0.005 respectively. AFC of psoriasis patients were significantly lower than healthy controls (p = 0.002.There were no significant difference among other hormone levels and ovarian volumes (p > 0.05. The hormone levels, ovarian volume and AFC were not correlated with PASI of the patients. Conclusion: The results of the study suggest that patients with psoriasis may have diminished ovarian reserve. Keywords: Psoriasis, Ovarian reserve, Psoriatic area severity index, Antral follicular count, Follicle-stimulating hormone

  13. Clinical, biological and genetic analysis of prepubertal isolated ovarian cyst in 11 girls.

    Directory of Open Access Journals (Sweden)

    Raja Brauner

    Full Text Available BACKGROUND: The cause of isolated gonadotropin-independent precocious puberty (PP with an ovarian cyst is unknown in the majority of cases. Here, we describe 11 new cases of peripheral PP and, based on phenotypes observed in mouse models, we tested the hypothesis that mutations in the GNAS1, NR5A1, LHCGR, FSHR, NR5A1, StAR, DMRT4 and NOBOX may be associated with this phenotype. METHODOLOGY/PRINCIPAL FINDINGS: 11 girls with gonadotropin-independent PP were included in this study. Three girls were seen for a history of prenatal ovarian cyst, 6 girls for breast development, and 2 girls for vaginal bleeding. With one exception, all girls were seen before 8 years of age. In 8 cases, an ovarian cyst was detected, and in one case, suspected. One other case has polycystic ovaries, and the remaining case was referred for vaginal bleeding. Four patients had a familial history of ovarian anomalies and/or infertility. Mutations in the coding sequences of the candidate genes GNAS1, NR5A1, LHCGR, FSHR, NR5A1, StAR, DMRT4 and NOBOX were not observed. CONCLUSIONS/SIGNIFICANCE: Ovarian PP shows markedly different clinical features from central PP. Our data suggest that mutations in the GNAS1, NR5A1, LHCGR, FSHR StAR, DMRT4 and NOBOX genes are not responsible for ovarian PP. Further research, including the identification of familial cases, is needed to understand the etiology of ovarian PP.

  14. Ontogenic studies of the neural control of adenohypophyseal hormones in the rat: gonadotropins.

    Science.gov (United States)

    Becú-Villalobos, D; Lacau-Mengido, I M; Libertun, C

    1990-12-01

    1. Serotonergic, dopaminergic, and opioid systems controlling luteinizing hormone (LH) and follicle stimulating hormone (FSH) secretion develop with particular characteristics in the male and female prepubertal rats. 2. Serotonergic pathways evoke a maximal release of LH and FSH in female rats from day 12 to day 20 of age, but not in males of the same age. 3. Antidopaminergic drugs increase LH and FSH levels only in the female infantile rats. This effect is absent at birth and disappears after 20 days of age. 4. Naloxone markedly increases gonadotropins in 12-day-old females. 5. On the other hand, in 12-day-old male rats some neurotropic drugs such as diazepam could enhance LH levels, the effect being absent at other ages or in female littermates. 6. A period of high sensitivity of gonadotropins to neurotropic drugs is present during the second and third weeks of life of the rat and it is related to the sexual differentiation of the brain.

  15. An incidental ovarian mass: A case of ovarian hemangioma with prominent stromal luteinization

    Directory of Open Access Journals (Sweden)

    Babak Shirazi

    2015-01-01

    Full Text Available Ovarian hemangioma is a rare benign tumor of female genital tract. Stromal luteinization in ovarian hemangioma is an uncommon process and the pathogenesis is controversial. In this regard, two hypotheses have been suggested whether luteinization is a reactive process or it is the stimulator for development of ovarian hemangioma. Here, we report a case of a 55-year-old woman who referred to our center due to incidental finding of left ovarian mass in pelvic sonography. Microscopically, the mass showed a mixed cavernous and capillary hemangioma and the peripheral stroma contained several small and large clusters of stromal cells, which were luteinized. It should be noted that an ovarian hemangioma could be associated with stromal luteinization although its pathogenesis is not clearly known. Yet, we believe the stromal luteinization around ovarian hemangioma could be a reactive phenomenon.

  16. Stromal cell-derived factor-1α (SDF-1α/CXCL12) stimulates ovarian cancer cell growth through the EGF receptor transactivation

    International Nuclear Information System (INIS)

    Porcile, Carola; Bajetto, Adriana; Barbieri, Federica; Barbero, Simone; Bonavia, Rudy; Biglieri, Marianna; Pirani, Paolo; Florio, Tullio; Schettini, Gennaro

    2005-01-01

    Ovarian cancer (OC) is the leading cause of death in gynecologic diseases in which there is evidence for a complex chemokine network. Chemokines are a family of proteins that play an important role in tumor progression influencing cell proliferation, angiogenic/angiostatic processes, cell migration and metastasis, and, finally, regulating the immune cells recruitment into the tumor mass. We previously demonstrated that astrocytes and glioblastoma cells express both the chemokine receptor CXCR4 and its ligand stromal cell-derived factor-1 (SDF-1), and that SDF-1α treatment induced cell proliferation, supporting the hypothesis that chemokines may play an important role in tumor cells' growth in vitro. In the present study, we report that CXCR4 and SDF-1 are expressed in OC cell lines. We demonstrate that SDF-1α induces a dose-dependent proliferation in OC cells, by the specific interaction with CXCR4 and a biphasic activation of ERK1/2 and Akt kinases. Our results further indicate that CXCR4 activation induces EGF receptor (EGFR) phosphorylation that in turn was linked to the downstream intracellular kinases activation, ERK1/2 and Akt. In addition, we provide evidence for cytoplasmic tyrosine kinase (c-Src) involvement in the SDF-1/CXCR4-EGFR transactivation. These results suggest a possible important 'cross-talk' between SDF-1/CXCR4 and EGFR intracellular pathways that may link signals of cell proliferation in ovarian cancer

  17. Ovarian failure due to cancer treatment and fertility preservation options

    Directory of Open Access Journals (Sweden)

    Soheila Aminimoghaddam

    2016-04-01

    Full Text Available Primary ovarian insufficiency (POI, commonly referred to premature ovarian failure, is defined as ovarian failure before the age of 40 years. It is the loss of ovarian function caused by a process directly affecting ovaries. Cancer therapy which includes surgery, radiotherapy, and chemotherapy influence ovarian function, leading to premature menopause and loss of fertility. POI is idiopathic in most cases (74-90%. The known causes, in addition to anticancer treatment, are other processes like chromosomal abnormalities, autoimmunity, and natural aging can result in secondary ovarian failure, which is detected by an increase in serum gonadotropin levels (FSH and LH. There are evident risks of POI in women treated for cancer. Those who receive anticancer treatments have an increased risk of developing POI. There by, anticancer drugs and radiation therapy are considered as the most common toxins of ovaries. Although cancer incidence rates in women less than 50 years old continue to increase during recent years, mortality rates are dramatically decreasing due to modern advances in treatment. Increasing numbers of survivors are now confronted with the long-term consequences of exposure to these treatments. The pool of primordial follicles in the ovary is fixed and any injury to the ovary can potentially reduce this ovarian reserve, effectively advancing the patient’s reproductive age, thus narrowing the window of reproductive opportunity. Ovarian failure occurs in a significant percentage of childhood cancer survivors and many of them will seek care for reproductive dysfunction. Nevertheless, Embryo cryopreservation, oocyte cryopreservation, ovary tissue cryopreservation, ovarian suppression and oophoro-pexy are some options to preserve fertility in these groups. As a result, having foreknowledge of potential treatment related ovarian failure will allow the physician to give a better counsel to patients and their family regarding the importance and

  18. Use of various gonadotropin and biosimilar formulations for in vitro fertilization cycles: results of a worldwide Web-based survey.

    Science.gov (United States)

    Christianson, Mindy S; Shoham, Gon; Tobler, Kyle J; Zhao, Yulian; Monseur, Brent; Leong, Milton; Shoham, Zeev

    2017-08-01

    The purpose of this study was to identify trends in gonadotropin therapy in patients undergoing in vitro fertilization (IVF) treatment worldwide. Retrospective evaluation utilizing the results of a Web-based survey, IVF-Worldwide ( www.IVF-worldwide.com ) was performed. Three hundred fourteen centers performing a total of 218,300 annual IVF cycles were evaluated. Respondents representing 62.2% of cycles (n = 135,800) did not believe there was a difference between urinary and recombinant gonadotropins in terms of efficacy and live birth rate. Of the respondents, 67.3% (n = 146,800) reported no difference between recombinant and urinary formulations in terms of short-term safety and risk of ovarian hyperstimulation syndrome. In terms of long-term safety using human urinary gonadotropins, 50.6% (n = 110,400) of respondents believe there are potential long-term risks including prion disease. For 95.3% of units (n = 208,000), the clinician was the decision maker determining which specific gonadotropins are used for IVF. Of the units, 62.6% (n = 136,700) identified efficacy as the most important factor in deciding which gonadotropin to prescribe. While most (67.3%, n = 146,800) were aware of new biosimilar recombinant FSH products entering the market, 92% (n = 201,000) reported they would like more information. A fraction of respondents (25.6%, n = 55,900) reported having experience with these new products, and of these, 80.3% (n = 46,200) reported that they were similar in efficacy as previously used gonadotropins in a similar patient group. Respondents representing the majority of centers do not believe a difference exists between urinary and recombinant gonadotropins with respect to efficacy and live birth rates. While many are aware of new biosimilar recombinant FSH products entering the market, over 90% desire more information on these products.

  19. Ovarian hormones and obesity.

    Science.gov (United States)

    Leeners, Brigitte; Geary, Nori; Tobler, Philippe N; Asarian, Lori

    2017-05-01

    Obesity is caused by an imbalance between energy intake, i.e. eating and energy expenditure (EE). Severe obesity is more prevalent in women than men worldwide, and obesity pathophysiology and the resultant obesity-related disease risks differ in women and men. The underlying mechanisms are largely unknown. Pre-clinical and clinical research indicate that ovarian hormones may play a major role. We systematically reviewed the clinical and pre-clinical literature on the effects of ovarian hormones on the physiology of adipose tissue (AT) and the regulation of AT mass by energy intake and EE. Articles in English indexed in PubMed through January 2016 were searched using keywords related to: (i) reproductive hormones, (ii) weight regulation and (iii) central nervous system. We sought to identify emerging research foci with clinical translational potential rather than to provide a comprehensive review. We find that estrogens play a leading role in the causes and consequences of female obesity. With respect to adiposity, estrogens synergize with AT genes to increase gluteofemoral subcutaneous AT mass and decrease central AT mass in reproductive-age women, which leads to protective cardiometabolic effects. Loss of estrogens after menopause, independent of aging, increases total AT mass and decreases lean body mass, so that there is little net effect on body weight. Menopause also partially reverses women's protective AT distribution. These effects can be counteracted by estrogen treatment. With respect to eating, increasing estrogen levels progressively decrease eating during the follicular and peri-ovulatory phases of the menstrual cycle. Progestin levels are associated with eating during the luteal phase, but there does not appear to be a causal relationship. Progestins may increase binge eating and eating stimulated by negative emotional states during the luteal phase. Pre-clinical research indicates that one mechanism for the pre-ovulatory decrease in eating is a

  20. Luteinizing hormone-stimulated pituitary adenylate cyclase-activating polypeptide system and its role in progesterone production in human luteinized granulosa cells.

    Science.gov (United States)

    Park, Hyun-Jeong; Choi, Bum-Chae; Song, Sang-Jin; Lee, Dong-Sik; Roh, Jaesook; Chun, Sang-Young

    2010-01-01

    The present study examined the gonadotropin regulation of pituitary adenylate cyclase-activating polypeptide (PACAP) and PACAP type I receptor (PAC(1)-R) expression, and its role in progesterone production in the human luteinized granulosa cells. The stimulation of both PACAP and PAC(1)-R mRNA levels by LH was detected using a competitive reverse transcription-polymerase chain reaction (RT-PCR). PACAP transcript was stimulated by LH reaching maximum levels at 12 hours in a dose dependent manner. LH treatment also stimulated PAC(1)-R mRNA levels within 24 hours. Addition of PACAP-38 (10(-7) M) as well as LH significantly stimulated progesterone production during 48 hours culture. Furthermore, co-treatment with PACAP antagonist partially inhibited LH-stimulated progesterone production. Treatment with vasoactive intestinal peptide, however, did not affect progesterone production. Taken together, the present study demonstrates that LH causes a transient stimulation of PACAP and PAC(1)-R expression and that PACAP stimulates progesterone production in the human luteinized granulosa cells, suggesting a possible role of PACAP as a local ovarian regulator in luteinization.

  1. Testosterone for Poor Ovarian Responders

    DEFF Research Database (Denmark)

    Polyzos, Nikolaos P; Davis, Susan R; Drakopoulos, Panagiotis

    2016-01-01

    Testosterone, an androgen that directly binds to the androgen receptor, has been shown in previous small randomized controlled trials to increase the reproductive outcomes of poor ovarian responders. In most of these studies, transdermal testosterone in relatively high doses was administered before...... ovarian stimulation with a duration varying from 5 to 21 days. Nevertheless, the key question to be asked is whether, based on ovarian physiology and testosterone pharmacokinetics, a short course of testosterone administration of more than 10 mg could be expected to have any beneficial effect...... stages. In addition, extreme testosterone excess is not only likely to induce adverse events but has also the potential to be ineffective and even detrimental. Thus, evidence from clinical studies is not enough to either "reopen" or "close" the "androgen chapter" in poor responders, mainly because...

  2. Prediction of Ovarian Hyperstimulation Syndrome in Patients Treated with Corifollitropin alfa or rFSH in a GnRH Antagonist Protocol.

    Directory of Open Access Journals (Sweden)

    Georg Griesinger

    Full Text Available What is the threshold for the prediction of moderate to severe or severe ovarian hyperstimulation syndrome (OHSS based on the number of growing follicles ≥ 11 mm and/or estradiol (E2 levels?The optimal threshold of follicles ≥11 mm on the day of hCG to identify those at risk was 19 for both moderate to severe OHSS and for severe OHSS. Estradiol (E2 levels were less prognostic of OHSS than the number of follicles ≥ 11 mm.In comparison to long gonadotropin-releasing hormone (GnRH agonist protocols, the risk of severe OHSS is reduced by approximately 50% in a GnRH antagonist protocol for ovarian stimulation prior to in vitro fertilisation (IVF, while the two protocols provide equal chances of pregnancy per initiated cycle. Nevertheless, moderate to severe OHSS may still occur in GnRH antagonist protocols if human chorionic gonadotropin (hCG is administered to trigger final oocyte maturation, especially in high responder patients. Severe OHSS following hCG trigger may occur with an incidence of 1-2% in a relatively young (aged 18 to 36 years IVF population treated in a GnRH-antagonist protocol.From the Engage, Ensure and Trust trials, in total, 2,433 women who received hCG for oocyte maturation and for whom the number of follicles ≥ 11 mm and the level of E2 on the day of hCG administration were known were included in the analyses.The threshold for OHSS prediction of moderate and severe OHSS was assessed in women treated with corifollitropin alfa or daily recombinant follicle stimulation hormone (rFSH in a gonadotropin-releasing hormone (GnRH-antagonist protocol. Receiver operating characteristics curve analyses for moderate to severe OHSS and severe OHSS were performed on the combined dataset and the sensitivity and specificity for the optimal threshold of number of follicles ≥ 11 mm, E2 levels on the day of (hCG, and a combination of both, were determined.The optimal threshold of follicles ≥ 11 mm on the day of hCG to identify those at

  3. Ovarian failure following abdominal irradiation in childhood

    International Nuclear Information System (INIS)

    Shalet, S.M.; Beardwell, C.G.; Jones, P.H.M.; Pearson, D.; Orrell, D.H.

    1976-01-01

    Ovarian function was studied in 18 female patients treated for abdominal tumours during childhood. All received abdominal radiotherapy as part of their treatment and were studied between 1 and 26 years after irradiation. The serum gonadotrophins and oestradiol levels were consistent with ovarian failure in each case and there was a disproportionate elevation in serum follicle stimulating hormone (FSH) when compared to serum luteinizing hormone (LH) in 16. In 2 patients, the radiotherapeutic field extended downwards only as far as the sacral promontory. However, these 2 girls show similar evidence of ovarian failure to that in the other 16. (author)

  4. Prospective, randomized comparison between pulsatile GnRH therapy and combined gonadotropin (FSH+LH) treatment for ovulation induction in women with hypothalamic amenorrhea and underlying polycystic ovary syndrome.

    Science.gov (United States)

    Dubourdieu, Sophie; Fréour, Thomas; Dessolle, Lionel; Barrière, Paul

    2013-05-01

    To compare the efficacy of pulsatile GnRH therapy versus combined gonadotropins for ovulation induction in women with both hypothalamic amenorrhoea and polycystic ovarian syndrome (HA/PCOS) according to their current hypothalamic status. This single-centre, prospective, randomized study was conducted in the Nantes University Hospital, France. Thirty consecutive patients were treated for ovulation induction with either pulsatile GnRH therapy or combined gonadotropins (rFSH+rLH). Frequency of adequate ovarian response (mono- or bi-follicular) and clinical pregnancy rate were then compared between both groups. Ovarian response was similar in both groups with comparable frequency of adequate ovarian response (73% vs 60%), but the clinical pregnancy rate was significantly higher in the pulsatile GnRH therapy group than in the combined gonadotropin group (46% vs 0%). HA/PCOS is a specific subgroup of infertile women. Pulsatile GnRH therapy is an effective and safe method of ovulation induction that can be used successfully in these patients. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  5. Oral contraceptives increase insulin-like growth factor binding protein-1 concentration in women with polycystic ovarian disease.

    Science.gov (United States)

    Suikkari, A M; Tiitinen, A; Stenman, U H; Seppälä, M; Laatikainen, T

    1991-05-01

    Insulin-like growth factor-I (IGF-I) stimulates ovarian androgen production. Insulin-like growth factor binding protein-1 (IGFBP-1) inhibits IGF actions in vitro. To investigate the effect of oral contraceptive (OC) pills, given for 3 months, on serum gonadotropin, androgen, IGF-I, and IGFBP-1 concentrations, and glucose tolerance in seven women with polycystic ovarian disease (PCOD) and in five healthy control subjects. Seven women with PCOD and five healthy control subjects. An oral glucose tolerance test (OGTT) was performed before and after treatment with OC. After treatment with OC, serum luteinizing hormone, androstenedione, and free testosterone levels decreased, and sex hormone-binding globulin concentration increased in the women with PCOD as well as in the control subjects. The cumulative response of serum insulin to OGTT was larger in the women with PCOD than in the control subjects both before and after treatment. Serum IGF-I concentration, which was unchanged during OGTT, decreased from basal level of 326 +/- 70 micrograms/L to 199 +/- 28 micrograms/L after treatment with OC in the women with PCOD, whereas no change was found in the control subjects (from 235 +/- 11 micrograms/L to 226 +/- 11 micrograms/L). Treatment with OC caused an increase of the mean basal IGFBP-1 concentration from 24 +/- 7 micrograms/L to 73 +/- 14 micrograms/L in the women with PCOD. This increase was constant during the OGTT. In the control subjects, treatment with OC did not result in any significant change in IGFBP-1 concentrations (from 44 +/- 11 micrograms/L to 61 +/- 9 micrograms/L). The combination of decreased total IGF-I concentration and increased IGFBP-1 concentration induced by OC may decrease ovarian androgen production in PCOD.

  6. [Spermatogenesis of pulsatile gonadotropin-releasing hormone infusion versus gonadotropin therapy in male idiopathic hypogonadotropic hypogonadism].

    Science.gov (United States)

    Huang, Bingkun; Mao, Jiangfeng; Xu, Hongli; Wang, Xi; Liu, Zhaoxiang; Nie, Min; Wu, Xueyan

    2015-05-26

    To compare the efficacies of pulsatile gonadotropin-releasing hormone (GnRH) versus human chorionic gonadotropin/human menopausal gonadotropin (HCG/HMG) for spermatogenesis in male idiopathic hypogonadotropic hypogonadism (IHH). For this retrospective study, a total of 92 male IHH outpatients from May 2010 to October 2014 were recruited and categorized into GnRH (n = 40) and HCG/HMG (n = 52) groups. Each subject selected one specific therapy voluntarily. The gonadotropin levels were measured in the first week and monthly post-treatment in GnRH group. And serum total testosterone (TT), testicular volume (TV) and rate of spermatogenesis were observed monthly post-treatment in two groups. Spermatogenesis, TT and TV were compared between two groups. All IHH patients were treated for over 3 months. The median follow-up periods in GnRH and HCG/HMG groups was 8.2 (3.0-18.4) and 9.2 (3.0-18.6) months respectively (P = 0.413). In GnRH group, LH ((0.5 ± 0.6) vs (3.4 ± 2.4) U/L, P treatment. In GnRH group, at the end of follow-up, TT ((1.0 ± 1.0) vs (7.4 ± 5.2) nmol/L, P treatment time for initial sperm appearance than HCG/HMG group ((6.5 ± 3.1) vs (10.8 ± 3.7) months, P = 0.001). Pulsatile GnRH requires a shorter time for initiation of spermatogenesis than gonadotropin therapy in IHH male patients.

  7. The Forkhead Transcription Factor, FOXP3, Is Required for Normal Pituitary Gonadotropin Expression in Mice1

    Science.gov (United States)

    Jung, Deborah O.; Jasurda, Jake S.; Egashira, Noboru; Ellsworth, Buffy S.

    2012-01-01

    ABSTRACT The hypothalamic-pituitary-gonadal axis is central to normal reproductive function. This pathway begins with the release of gonadotropin-releasing hormone in systematic pulses by the hypothalamus. Gonadotropin-releasing hormone is bound by receptors on gonadotroph cells in the anterior pituitary gland and stimulates the synthesis and secretion of luteinizing hormone and, to some extent, follicle-stimulating hormone. Once stimulated by these glycoprotein hormones, the gonads begin gametogenesis and the synthesis of sex hormones. In humans, mutations of the forkhead transcription factor, FOXP3, lead to an autoimmune disorder known as immunodysregulation, polyendocrinopathy, and enteropathy, X-linked syndrome. Mice with a mutation in the Foxp3 gene have a similar autoimmune syndrome and are infertile. To understand why FOXP3 is required for reproductive function, we are investigating the reproductive phenotype of Foxp3 mutant mice (Foxp3sf/Y). Although the gonadotroph cells appear to be intact in Foxp3sf/Y mice, luteinizing hormone beta (Lhb) and follicle-stimulating hormone beta (Fshb) expression are significantly decreased, demonstrating that these mice exhibit a hypogonadotropic hypogonadism. Hypothalamic expression of gonadotropin-releasing hormone is not significantly decreased in Foxp3sf/Y males. Treatment of Foxp3sf/Y males with a gonadotropin-releasing hormone receptor agonist does not rescue expression of Lhb or Fshb. Interestingly, we do not detect Foxp3 expression in the pituitary or hypothalamus, suggesting that the infertility seen in Foxp3sf/Y males is a secondary effect, possibly due to loss of FOXP3 in immune cells. Pituitary expression of glycoprotein hormone alpha (Cga) and prolactin (Prl) are significantly reduced in Foxp3sf/Y males, whereas the precursor for adrenocorticotropic hormone, pro-opiomelanocortin (Pomc), is increased. Human patients diagnosed with IPEX often exhibit thyroiditis due to destruction of the thyroid gland by

  8. A randomized controlled dose-response pilot study of addition of hCG to recombinant FSH during controlled ovarian stimulation for in vitro fertilization

    DEFF Research Database (Denmark)

    Loft, A; Egeberg, Anne Noes; Smitz, J

    2012-01-01

    Is it possible to define an optimal dose of hCG in combination with rFSH from the first day of stimulation in the GnRH agonist protocol applied to IVF? SUMMARY ANSWER: Supplementation with hCG from the first day of stimulation may increase the number of top-quality embryos per patient. Daily doses...... has been previously reported. We suggest a large clinical trial to be proceeded with a group given 100 IU hCG daily versus a control group. WHAT IS KNOWN AND WHAT THIS PAPER ADDS: Prospective multicentre studies have indicated increased live birth rates and increased number of top-quality embryos when...

  9. Is IVF-served two different ways-more cost-effective than IUI with controlled ovarian hyperstimulation?

    NARCIS (Netherlands)

    Tjon-Kon-Fat, R. I.; Bensdorp, A. J.; Bossuyt, P. M. M.; Koks, C.; Oosterhuis, G. J. E.; Hoek, A.; Hompes, P.; Broekmans, F. J.; Verhoeve, H. R.; de Bruin, J. P.; van Golde, R.; Repping, S.; Cohlen, B. J.; Lambers, M. D. A.; van Bommel, P. F.; Slappendel, E.; Perquin, D.; Smeenk, J.; Pelinck, M. J.; Gianotten, J.; Hoozemans, D. A.; Maas, J. W. M.; Groen, H.; Eijkemans, M. J. C.; van der Veen, F.; Mol, B. W. J.; van Wely, M.

    2015-01-01

    STUDY QUESTION: What is the cost-effectiveness of in vitro fertilization(IVF) with conventional ovarian stimulation, single embryotransfer (SET) and subsequent cryocycles or IVF in a modified natural cycle (MNC) compared with intrauterine insemination with controlled ovarian hyperstimulation

  10. Is IVF-served two different ways-more cost-effective than IUI with controlled ovarian hyperstimulation?

    NARCIS (Netherlands)

    Tjon-Kon-Fat, R. I.; Bensdorp, A. J.; Bossuyt, P. M M; Koks, C.; Oosterhuis, G. J E; Hoek, A.; Hompes, P.; Broekmans, F. J.; Verhoeve, H. R.; De Bruin, J. P.; Van Golde, R.; Repping, S.; Cohlen, B. J.; Lambers, M. D A; Van Bommel, P. F.; Slappendel, E.; Perquin, D.; Smeenk, J.; Pelinck, M. J.; Gianotten, J.; Hoozemans, D. A.; Maas, J. W M; Groen, H.; Eijkemans, M. J C; Van Der Veen, F.; Mol, B. W J; Van Wely, M.

    2015-01-01

    STUDY QUESTION What is the cost-effectiveness of in vitro fertilization (IVF) with conventional ovarian stimulation, single embryo transfer (SET) and subsequent cryocycles or IVF in a modified natural cycle (MNC) compared with intrauterine insemination with controlled ovarian hyperstimulation

  11. Basal progesterone level as the main determinant of progesterone elevation on the day of hCG triggering in controlled ovarian stimulation cycles.

    Science.gov (United States)

    Papaleo, Enrico; Corti, Laura; Vanni, Valeria Stella; Pagliardini, Luca; Ottolina, Jessica; De Michele, Francesca; La Marca, Antonio; Viganò, Paola; Candiani, Massimo

    2014-07-01

    Modest increases of serum progesterone at human chorionic gonadotrophin (hCG) administration in controlled ovarian hyperstimulation (COH) cycles have been shown to have a negative impact on pregnancy outcomes. The aim of this study was to identify early predictors of progesterone elevation at hCG. Pregnancy outcome of 303 consecutive patients undergoing COH and fresh day-3 embryo transfer was analysed. Considering the non-linear relationship between progesterone at hCG triggering and pregnancy outcomes, partial area under the curve (pAUC) analysis was used to implement marker identification potential of receiver operating characteristic (ROC) curve analysis. Multivariate logistic analysis was then performed to identify predictors of progesterone rise. Pregnancy outcomes could be predicted by pAUC analysis (pAUC = 0.58, 95 % CI 0.51-0.66, p = 0.02) and a significant detrimental cut-off could be calculated (progesterone at hCG > 1.35 ng/ml). Total dose of rFSH administered, E2 level at hCG but mostly basal progesterone level (OR = 12.21, 95 % CI 1.82-81.70) were predictors of progesterone rise above the cut-off. Basal progesterone is shown to be the main prognostic factor for progesterone elevation. This observation should be taken into consideration in the clinical management of IVF/ICSI cycles to improve pregnancy outcomes.

  12. Negative feedback governs gonadotrope frequency-decoding of gonadotropin releasing hormone pulse-frequency.

    Directory of Open Access Journals (Sweden)

    Stefan Lim

    Full Text Available The synthesis of the gonadotropin subunits is directed by pulsatile gonadotropin-releasing hormone (GnRH from the hypothalamus, with the frequency of GnRH pulses governing the differential expression of the common alpha-subunit, luteinizing hormone beta-subunit (LHbeta and follicle-stimulating hormone beta-subunit (FSHbeta. Three mitogen-activated protein kinases, (MAPKs, ERK1/2, JNK and p38, contribute uniquely and combinatorially to the expression of each of these subunit genes. In this study, using both experimental and computational methods, we found that dual specificity phosphatase regulation of the activity of the three MAPKs through negative feedback is required, and forms the basis for decoding the frequency of pulsatile GnRH. A fourth MAPK, ERK5, was shown also to be activated by GnRH. ERK5 was found to stimulate FSHbeta promoter activity and to increase FSHbeta mRNA levels, as well as enhancing its preference for low GnRH pulse frequencies. The latter is achieved through boosting the ultrasensitive behavior of FSHbeta gene expression by increasing the number of MAPK dependencies, and through modulating the feedforward effects of JNK activation on the GnRH receptor (GnRH-R. Our findings contribute to understanding the role of changing GnRH pulse-frequency in controlling transcription of the pituitary gonadotropins, which comprises a crucial aspect in regulating reproduction. Pulsatile stimuli and oscillating signals are integral to many biological processes, and elucidation of the mechanisms through which the pulsatility is decoded explains how the same stimulant can lead to various outcomes in a single cell.

  13. Ovarian Autoantibodies Predict Ovarian Cancer

    Science.gov (United States)

    2010-11-01

    Expression of thymidine 459 phosphorylase in epithelial ovarian cancer: correlation with angiogenesis, apoptosis , and 460 ultrasound-derived peak...trafficking, activation of S1P1 can promote or inhibit apoptosis of 41 immune cells depending on the balance of cytokines [7]. Knockout of S1P1 (LP(B1...EDG-1) in 42 mice is embryologically lethal [8]. S1P1 also has a role in inflammatory disease such as graft 43 versus host disease and multiple

  14. Acute respiratory failure following ovarian hyperstimulation syndrome

    Directory of Open Access Journals (Sweden)

    Antonello Nicolini

    2013-03-01

    Full Text Available Ovarian hyperstimulation syndrome is a serious and potentially life-threatening physiological complication that may be encountered in patients who undergo controlled ovarian hyperstimulation cycles. The syndrome is typically associated with regimes of exogenous gonadotropins, but it can be seen, albeit rarely, when clomiphene is administered during the induction phase. Although this syndrome is widely described in scientific literature and is well known by obstetricians, the knowledge of this pathological and potentially life-threatening condition is generally less than satisfactory among physicians. The dramatic increase in therapeutic strategies to treat infertility has pushed this condition into the realm of acute care therapy. The potential complications of this syndrome, including pulmonary involvement, should be considered and identified so as to allow a more appropriate diagnosis and management. We describe a case of a woman with an extremely severe (Stage 6 ovarian hyperstimulation syndrome who presented ascites, bilateral pleural effusion and severe respiratory failure treated with non-invasive ventilation. The patient was admitted to the intensive care unit because of severe respiratory failure, ascites, and bilateral pleural effusion due to ovarian hyperstimulation syndrome. Treatment included non-invasive ventilation and three thoracentesis procedures, plus the administration of albumin, colloid solutions and high-dose furosemid. Severe form of ovarian hyperstimulation syndrome is observed in 0.5-5% of the women treated, and intensive care may be required for management of thromboembolic complications, renal failure and severe respiratory failure. Pulmonary intensive care may involve thoracentesis, oxygen supplementation and, in more severe cases, assisted ventilation. To our knowledge, there have been only two studies in English language medical literature that describe severe respiratory failure treated with non

  15. Involvement of phospholipase C and intracellular calcium signaling in the gonadotropin-releasing hormone regulation of prolactin release from lactotrophs of tilapia (Oreochromis mossambicus)

    DEFF Research Database (Denmark)

    Tipsmark, Christian Kølbæk; Weber, G M; Strom, C N

    2005-01-01

    Gonadotropin-releasing hormone (GnRH) is a potent stimulator of prolactin (PRL) secretion in various vertebrates including the tilapia, Oreochromis mossambicus. The mechanism by which GnRH regulates lactotroph cell function is poorly understood. Using the advantageous characteristics of the teleost...

  16. Effect of light intensity on ovarian gene expression, reproductive performance and body weight of rabbit does.

    Science.gov (United States)

    Sun, Liangzhan; Wu, Zhenyu; Li, Fuchang; Liu, Lei; Li, Jinglin; Zhang, Di; Sun, Chaoran

    2017-08-01

    The objective of the experiment was to find the minimum light intensity which could improve reproduction by examining its effect on ovarian gene expression, reproductive performance and body weight of rabbit does with three different light intensities: 60 (L), 80 (M), and 100 (H)lx. A total of 144 Rex-rabbits submitted to a 49-day reproductive regimen were used in this study. Ovaries were collected and relative abundance of mRNA for ovarian proteins of interest was examined with real-time PCR. Amount of protein for proteins of interest was examined by immunohistochemistry. Reproductive performance and doe bodyweight of the first three consecutive reproductive periods after initiation of the light intensity treatments were evaluated. The results provided evidence that light intensity had no effect on relative abundance of estradiol receptor-α (ER-α), follicle stimulating hormone receptor (FSHR), luteinizing hormone receptor (LHR), gonadotropin releasing hormone receptor 1 (GnRHR1) and progesterone receptor (PGR) mRNA. The relative abundance of growth hormone receptor (GHR) mRNA was, however, greater in Group L than M and H (Plight intensities (P>0.05). The bodyweight of the does in Group L was greater than the other two groups at first insemination, second insemination and the second postpartum period (P0.05). These observations suggest that light intensity between 60 and 100lx has no effect on the reproductive performance of rabbit does, however, the amounts of GHR mRNA and growth hormone (GH) protein were affected and the greater light intensity had a negative effect on bodyweight between the time of the first insemination and the second partum period. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. The Pathogenesis of Polycystic Ovary Syndrome (PCOS): The Hypothesis of PCOS as Functional Ovarian Hyperandrogenism Revisited

    Science.gov (United States)

    Ehrmann, David A.

    2016-01-01

    Polycystic ovary syndrome (PCOS) was hypothesized to result from functional ovarian hyperandrogenism (FOH) due to dysregulation of androgen secretion in 1989–1995. Subsequent studies have supported and amplified this hypothesis. When defined as otherwise unexplained hyperandrogenic oligoanovulation, two-thirds of PCOS cases have functionally typical FOH, characterized by 17-hydroxyprogesterone hyperresponsiveness to gonadotropin stimulation. Two-thirds of the remaining PCOS have FOH detectable by testosterone elevation after suppression of adrenal androgen production. About 3% of PCOS have a related isolated functional adrenal hyperandrogenism. The remaining PCOS cases are mild and lack evidence of steroid secretory abnormalities; most of these are obese, which we postulate to account for their atypical PCOS. Approximately half of normal women with polycystic ovarian morphology (PCOM) have subclinical FOH-related steroidogenic defects. Theca cells from polycystic ovaries of classic PCOS patients in long-term culture have an intrinsic steroidogenic dysregulation that can account for the steroidogenic abnormalities typical of FOH. These cells overexpress most steroidogenic enzymes, particularly cytochrome P450c17. Overexpression of a protein identified by genome-wide association screening, differentially expressed in normal and neoplastic development 1A.V2, in normal theca cells has reproduced this PCOS phenotype in vitro. A metabolic syndrome of obesity-related and/or intrinsic insulin resistance occurs in about half of PCOS patients, and the compensatory hyperinsulinism has tissue-selective effects, which include aggravation of hyperandrogenism. PCOS seems to arise as a complex trait that results from the interaction of diverse genetic and environmental factors. Heritable factors include PCOM, hyperandrogenemia, insulin resistance, and insulin secretory defects. Environmental factors include prenatal androgen exposure and poor fetal growth, whereas acquired

  18. The Pathogenesis of Polycystic Ovary Syndrome (PCOS): The Hypothesis of PCOS as Functional Ovarian Hyperandrogenism Revisited.

    Science.gov (United States)

    Rosenfield, Robert L; Ehrmann, David A

    2016-10-01

    Polycystic ovary syndrome (PCOS) was hypothesized to result from functional ovarian hyperandrogenism (FOH) due to dysregulation of androgen secretion in 1989-1995. Subsequent studies have supported and amplified this hypothesis. When defined as otherwise unexplained hyperandrogenic oligoanovulation, two-thirds of PCOS cases have functionally typical FOH, characterized by 17-hydroxyprogesterone hyperresponsiveness to gonadotropin stimulation. Two-thirds of the remaining PCOS have FOH detectable by testosterone elevation after suppression of adrenal androgen production. About 3% of PCOS have a related isolated functional adrenal hyperandrogenism. The remaining PCOS cases are mild and lack evidence of steroid secretory abnormalities; most of these are obese, which we postulate to account for their atypical PCOS. Approximately half of normal women with polycystic ovarian morphology (PCOM) have subclinical FOH-related steroidogenic defects. Theca cells from polycystic ovaries of classic PCOS patients in long-term culture have an intrinsic steroidogenic dysregulation that can account for the steroidogenic abnormalities typical of FOH. These cells overexpress most steroidogenic enzymes, particularly cytochrome P450c17. Overexpression of a protein identified by genome-wide association screening, differentially expressed in normal and neoplastic development 1A.V2, in normal theca cells has reproduced this PCOS phenotype in vitro. A metabolic syndrome of obesity-related and/or intrinsic insulin resistance occurs in about half of PCOS patients, and the compensatory hyperinsulinism has tissue-selective effects, which include aggravation of hyperandrogenism. PCOS seems to arise as a complex trait that results from the interaction of diverse genetic and environmental factors. Heritable factors include PCOM, hyperandrogenemia, insulin resistance, and insulin secretory defects. Environmental factors include prenatal androgen exposure and poor fetal growth, whereas acquired obesity

  19. Seasonal Relationship between Gonadotropin, Growth Hormone, and Estrogen Receptor mRNA Expression in the Pituitary Gland of Largemouth Bass

    OpenAIRE

    Martyniuk, Christopher J; Kroll, Kevin J.; Porak, Wesley F.; Steward, Cheree; Grier, Harry J.; Denslow, Nancy D.

    2009-01-01

    The objectives of this study were to investigate the seasonal changes in pituitary gonadotropins, growth hormone (GH), and estrogen receptor (ER) isoform mRNA in wild female and male largemouth bass (LMB) (Micropterus salmoides) from an unpolluted habitat to better understand reproductive physiology in this ecologically important species. Female pituitary luteinizing hormone (LH) β subunit and follicle-stimulating hormone (FSH) β subunit mRNA showed significant seasonal variation with levels ...

  20. Effects of X-irradiation on gonadotropin secretion in rat anterior pituitary cells

    International Nuclear Information System (INIS)

    Li Xinmin; Liu Shuzheng

    1988-01-01

    The dispersed rat anterior pituitary cells cultured in 3 days was exposed to single doses of X-irradiation in the range of 0.5-8.0 Gy. LH and FSH contents in both the supernatant and the cells were measured. The LH secretion was significantly increased at the doses greater than 0.5 Gy and FSH secretion was also significantly enhanced at the dose of 4.0 Gy. The cellular contents of both LH and FSH remained near the control levels. It is concluded that gonadotropin secretion can be stimulated by single doses of X-rays in the range of 0.5-8.0 Gy

  1. Monoclonal antibodies to human chorionic gonadotropin and their application to two-site sandwich radioimmunoassay

    International Nuclear Information System (INIS)

    Mizuchi, A.; Iio, M.; Miyachi, Y.

    1984-01-01

    Monoclonal antibodies were prepared against human chorionic gonadotropin (HCG). One monoclonal antibody recognized a conformational determinant expressed only on native HCG molecule and another monoclonal antibody had the specificity for the epitopes located on the β-subunit of HCG. Monoclonal antibodies reacting with different antigenic determinants on the HCG molecule were used to develop a simplified 2-site sandwich radioimmunoassay in which one monoclonal antibody was immobilized and another labeled with 125 iodine. This assay was highly specific for HCG and there was no cross-reactivity with α,β-subunit of HCG, luteinizing hormone and follicle stimulating hormone. (Auth.)

  2. Function of gonadotropin-releasing hormone in olfaction.

    Science.gov (United States)

    Wirsig-Wiechmann, C R

    2001-06-01

    Gonadotropin-releasing hormone (GnRH) is present within neurons of the nervus terminalis, the zeroeth cranial nerve. In all vertebrate species, except in sharks where it is a separate nerve, the nervus terminalis consists of a chain of neurons embedded within olfactory or vomeronasal nerves in the nasal cavity. The function of the GnRH component of the nervus terminalis is thought to be neuromodulatory. Our research on GnRH effects on olfaction confirms this hypothesis. The processes of GnRH neural cell bodies located within chemosensory nerves project centrally into the ventral forebrain and peripherally into the lamina propria of the nasal chemosensory mucosa. GnRH receptors are expressed by chemosensory neurons as shown by RT-PCR/Southern blotting and GnRH agonist binding studies. Patch-clamp studies have shown that GnRH alters the responses of isolated chemosensory neurons to natural or electrophysiological stimulation through the modulation of voltage-gated and receptor-gated channels. Behavioral experiments demonstrate that interfering with the nasal GnRH system leads to deficits in mating behavior. These studies suggest that the function of the intranasal GnRH system is to modify olfactory information, perhaps at reproductively auspicious times. We speculate that the purpose of this altered olfactory sense is to make pheromones more detectable and salient.

  3. Recombinant LH supplementation to recombinant FSH during the final days of controlled ovarian stimulation for in vitro fertilization. A multicentre, prospective, randomized, controlled trial

    DEFF Research Database (Denmark)

    Nyboeandersen, A.; Humaidan, P.; Fried, G.

    2008-01-01

    BACKGROUND: The purpose of this multicentre, multinational trial was to study whether rLH supplementation to recombinant FSH (rFSH) during the late follicular phase increased pregnancy rates. METHODS: After down-regulation with nafarelin, 526 women were randomized on Day 1 of stimulation to use...... either rFSH (Gonal-F) alone (n = 261) or to continue after Day 6 of stimulation with both rFSH (Gonal-F) and rLH (Luveris) (n = 265) from Day 6. The starting dose of rFSH was 150-225 IU/day according to age below or above 35 years. RESULTS: Ongoing pregnancy rate at week 10-12 was 28.7% after rFSH alone...... and 27.2% after rFSH + rLH. This showed no evidence of a difference. Administration of rLH significantly (Prates in patients with low LH levels (

  4. Recombinant LH supplementation to recombinant FSH during the final days of controlled ovarian stimulation for in vitro fertilization. A multicentre, prospective, randomized, controlled trial

    DEFF Research Database (Denmark)

    Nyboeandersen, A; Al Humaidan, Peter Samir Heskjær; Fried, G

    2008-01-01

    BACKGROUND: The purpose of this multicentre, multinational trial was to study whether rLH supplementation to recombinant FSH (rFSH) during the late follicular phase increased pregnancy rates. METHODS: After down-regulation with nafarelin, 526 women were randomized on Day 1 of stimulation to use...... either rFSH (Gonal-F) alone (n = 261) or to continue after Day 6 of stimulation with both rFSH (Gonal-F) and rLH (Luveris) (n = 265) from Day 6. The starting dose of rFSH was 150-225 IU/day according to age below or above 35 years. RESULTS: Ongoing pregnancy rate at week 10-12 was 28.7% after rFSH alone...... and 27.2% after rFSH + rLH. This showed no evidence of a difference. Administration of rLH significantly (PLH. Ongoing pregnancy rates in patients with low LH levels (

  5. Gonadotropin Releasing Hormone Agonists or Antagonists for Preimplantation Genetic Diagnosis (PGD)? A Prospective Randomised Trial.

    Science.gov (United States)

    Verpoest, Willem; De Vos, Anick; De Rycke, Martine; Parikh, Shruti; Staessen, Catherine; Tournaye, Herman; De Vos, Michel; Vloeberghs, Veerle; Blockeel, Christophe

    2017-11-10

    The use of GnRH analogue medication is essential in reproductive medicine to avoid premature ovulation by pituitary suppression for the duration of ovarian stimulation by gonadotrophins. The type of pituitary suppression by either GnRH agonist analogues versus GnRH antagonist analogues may result in different embryological hence clinical results. Preimplantation genetic diagnosis is a subtype of IVF in which embryos are created for genetic diagnosis of hereditary disorders in order to avoid genetically affected children. Embryological quality hence ovarian stimulation in preimplantation genetic diagnosis is crucial as genetic selection will reduce the number of available embryos to a fraction of the total. The aim of this study was to assess the efficiency of GnRH antagonist versus GnRH agonist treatment for pituitary suppression in ovarian stimulation for PGD, by proxy of number and quality of embryos at cleavage stage available for biopsy. We conducted a prospective randomised controlled trial comparing pituitary suppression by GnRH antagonist versus GnRH agonist in ovarian stimulation for PGD. The primary outcome measure was the number of embryos of sufficient quality for biopsy at cleavage stage. Secondary outcome parameters were the number of blastocysts available of top quality, and clinical pregnancy rate. There was no difference in number of oocytes retrieved, embryos at cleavage stage available for biopsy or embryo quality. The clinical pregnancy rate was higher in the GnRH agonist group; however the sample size was insufficient to allow conclusions. The use of GnRH agonist versus antagonist treatment does not result in differences in a number of oocytes, embryos or embryo quality in ovarian stimulation for preimplantation genetic diagnosis. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  6. Ovarian maldescent

    Energy Technology Data Exchange (ETDEWEB)

    Trinidad, Carmen; Tardaguila, Francisco; Fernandez, Gabriel C.; Martinez, Concepcion; Chavarri, Elena; Rivas, Isabel [Departments of Radiology and Gynecology, Povisa Medical Center, Salamanca St. 5, 36211, Vigo (Pontevedra) (Spain)

    2004-05-01

    Undescended ovary is a rare disorder that can be associated with muellerian malformations. There is an unclear association with infertility and malignant disease. When an ovary is not in its normal location, it is sought in other locations above the pelvic brim. This is important in cases of undetermined cyclical abdominal pain, follicle aspiration and surgical castration. MRI has proven to be the best imaging method for finding an ovary in an anomalous position and for disregarding associated malformations. We report two patients with unilateral ovarian maldescent, one of them with Rokitansky-Kuester-Hauser syndrome. A review of the literature is included. (orig.)

  7. Cost-effectiveness of short COH protocols with GnRH antagonists using different types of gonadotropins for in vitro fertilization

    Directory of Open Access Journals (Sweden)

    Guenka Petrova

    2016-05-01

    Full Text Available The aim of this study was to explore the cost-effectiveness of short protocols including different types of gonadotropins for controlled ovarian hyperstimulation (COH for in vitro fertilization (IVF. A retrospective, observational study of the real-life practice in a specialized IVF gynaecology clinic in 2009–2013 was carried out. All women on short COH protocols were recruited into three groups: COH including recombinant follicle stimulating hormone (rFSH and urinary-FSH (urFSH (n = 173; including urFSH alone (n = 289; and including rFSH alone (n = 212. The cost-effectiveness of the COH protocols was explored in two different case scenarios for possible outcomes. The first case scenario took into consideration a successful live birth, and the second one, the women to achieve pregnancy with live birth. Decision modelling was done using the TreeAge 2014 Software. According to the results in the first case scenario, the rFSH plus urFSH COH approach showed the highest weighted probability (p = 0.38 of live birth, but the urFSH alternative was cost-effective. The results in the second case scenario demonstrated that the urFSH protocol was again the cost-effective alternative. These results suggest that the strategy with urFSH should be preferred in both cases, but rFSH could also be considered as a cost-effective alternative for successful live birth and achieving pregnancy and delivery, since the incremental cost-effectiveness ratio in comparison with the urFSH protocol is below the gross domestic product per capita. The combined approach of rFSH and urFSH was shown not to be cost-effective in both explored scenarios.

  8. Markers of stem cells in human ovarian granulosa cells: is there a clinical significance in ART?

    Directory of Open Access Journals (Sweden)

    Varras Michail

    2012-11-01

    Full Text Available Abstract Background The purpose of the study was to determine the incidence of gene expression of Oct-4 and DAZL, which are typical markers for stem cells, in human granulosa cells during ovarian stimulation in women with normal FSH levels undergoing IVF or ICSI and to discover any clinical significance of such expression in ART. Methods Twenty one women underwent ovulation induction for IVF or ICSI and ET with standard GnRH analogue-recombinant FSH protocol. Infertility causes were male and tubal factor. Cumulus–mature oocyte complexes were denuded separately and granulosa cells were analyzed for each patient separately using quantitative reverse-transcription–polymerase chain reaction analysis for Oct-4 and DAZL gene expression with G6PD gene as internal standard. Results G6PD and Oct-4 mRNA was detected in the granulosa cells in 47.6% (10/21. The median of Oct-4 mRNA/G6PD mRNA was 1.75 with intra-quarteral range from 0.10 to 98.21. The OCT-4 mRNA expression was statistically significantly correlated with the number of oocytes retrieved; when the Oct-4 mRNA expression was higher, then more than six oocytes were retrieved (p=0.037, Wilcoxon rank-sum. No detection of DAZL mRNA was found in granulosa cells. There was no additional statistically significant correlation between the levels of Oct-4 expression and FSH basal levels or estradiol peak levels or dosage of FSH for ovulation induction. No association was found between the presence or absence of Oct-4 mRNA expression in granulosa cells and ovarian response to gonadotropin stimulation. Also, no influence on pregnancy was observed between the presence or absence of Oct-4 mRNA expression in granulosa cells or to its expression levels accordingly. Conclusions Expression of OCT-4 mRNA, which is a typical stem cell marker and absence of expression of DAZL mRNA, which is a typical germ cell marker, suggest that a subpopulation of luteinized granulosa cells in healthy ovarian follicles (47

  9. Hyperprolactinemia after laparoscopic ovarian drilling: An unknown phenomenon

    Directory of Open Access Journals (Sweden)

    Omrani Gholamhossein R

    2005-08-01

    Full Text Available Abstract Background The effects of ovarian drilling on the serum levels of gonadotropins and androgens have been studied previously. The aim of this study is to evaluate the effects of ovarian drilling on the serum prolactin levels and its relation to ovulation in women with polycystic ovary syndrome. Methods This is a prospective controlled study. Thirty-six women with PCOS underwent ovarian electrocauterization in university hospitals. Control group consisted of 35 ovulatory women with unexplained infertility. Hormonal assessment performed in early follicular phase of spontaneous or induced cycle before operation in the two groups and repeated one week after operation. Hormonal assay was also performed in the early follicular phase of the first post-operative menstruation, folliculometry and progesterone assay were also performed in the same cycle. Data were analyzed by "repeated measurement design, discriminant analysis, correlation coefficient, and Fisher exact test". Results Six to ten weeks after operation the serum mean +/- SD prolactin levels increased from 284.41 +/- 114.32 mIU/ml to 354.06 +/- 204.42 mIU/ml (P = 0.011. The same values for the control group were 277.73 +/- 114.65 to 277.4 +/- 111.4 (P = 0.981 respectively. Approximately 45% of subjects in PCOS group remained anovulatory in spite of decreased level of LH and testosterone. Prolactin level remained elevated in 73.2% of women who did not ovulate 6–10 weeks after the procedure. Conclusion Hyperprolactinemia after ovarian cauterization may be considered as a possible cause of anovulation in women with polycystic ovaries and improved gonadotropin and androgen levels. The cause of hyperprolactinemia is unknown. Hormonal assay particularly PRL in anovulatory patients after ovarian cauterization is recommended.

  10. Fanconi Anemia a Is a Nucleocytoplasmic Shuttling Molecule Required for Gonadotropin-Releasing Hormone (GnRH) Transduction of the GnRH Receptor

    OpenAIRE

    Larder, Rachel; Karali, Dimitra; Nelson, Nancy; Brown, Pamela

    2006-01-01

    GnRH binds its cognate G protein-coupled GnRH receptor (GnRHR) located on pituitary gonadotropes and drives expression of gonadotropin hormones. There are two gonadotropin hormones, comprised of a common α- and hormone-specific β-subunit, which are required for gonadal function. Recently we identified that Fanconi anemia a (Fanca), a DNA damage repair gene, is differentially expressed within the LβT2 gonadotrope cell line in response to stimulation with GnRH. FANCA is mutated in more than 60%...

  11. An overview about mitochondrial DNA mutations in ovarian cancer

    African Journals Online (AJOL)

    Iyer Mahalaxmi

    2017-07-29

    Jul 29, 2017 ... which ends up as a global increase in incidence rates. There are 2 per cent ... In ovarian cancer follicle-stimulating hormone receptor gene poly- morphism is ... of respiratory deficit in dividing cells which were characterised by.

  12. Benzophenone-1 stimulated the growth of BG-1 ovarian cancer cells by cell cycle regulation via an estrogen receptor alpha-mediated signaling pathway in cellular and xenograft mouse models

    International Nuclear Information System (INIS)

    Park, Min-Ah; Hwang, Kyung-A; Lee, Hye-Rim; Yi, Bo-Rim; Jeung, Eui-Bae; Choi, Kyung-Chul

    2013-01-01

    results suggest that BP-1 is an endocrine disrupting chemical (EDC) that exerts xenoestrogenic effects by stimulating the proliferation of BG-1 ovarian cancer via ER signaling pathway associated with cell cycle as did E2

  13. Unilateral laparoscopic ovariectomy in a red fox (Vulpes vulpes) with an ovarian cyst.

    Science.gov (United States)

    Lee, Seung Y; Jung, Dong H; Park, Se J; Seek, Seong H; Yang, Jeong J; Lee, Jae W; Lee, Bae K; Lee, Hee C; Yeon, Seong C

    2014-09-01

    Unilateral laparoscopic ovariectomy was attempted in a red fox (Vulpes vulpes) with an ovarian cyst through single portal access. The ovarian cyst was resistant to conservative therapy using gonadotropin-releasing hormone. A 10-mm laparoscope with an operating channel was introduced into the abdomen via a 12-mm umbilical portal. The left ovary and cyst (34.1 x 30.8 mm) were fixed to the left abdominal wall by a transabdominal suspension suture. The ovarian pedicles and ligaments were progressively cauterized and transected with a multifunction bipolar electrocoagulation forceps. The resected cystic ovary was exteriorized through the umbilical portal site. The surgical time was 42 min, and no intra- and postoperative complications were encountered. Two months after the surgery mating was observed, and the fox gave birth to three healthy cubs 56 days after the mating. This is the first report of using laparoscopy in the red fox with an ovarian cyst.

  14. Temporary ovarian failure in thyroid cancer patients after thyroid remnant ablation with radioactive iodine

    International Nuclear Information System (INIS)

    Raymond, J.P.; Izembart, M.; Marliac, V.; Dagousset, F.; Merceron, R.E.; Vulpillat, M.; Vallee, G.

    1989-01-01

    We studied ovarian function retrospectively in 66 women who had regular menstrual cycles before undergoing complete thyroidectomy for differentiated thyroid cancer and subsequent thyroid remnant ablation with 131 I. Eighteen women developed temporary amenorrhea accompanied by increased serum gonadotropin concentrations during the first year after 131 I therapy. No correlation was found between the radioactive iodine dose absorbed, thyroid uptake before treatment, oral contraceptive use, or thyroid autoimmunity. Only age was a determining factor, with the older women being the most affected. We conclude that radioiodine ablation therapy is followed by transient ovarian failure, especially in older women

  15. Temporary ovarian failure in thyroid cancer patients after thyroid remnant ablation with radioactive iodine

    Energy Technology Data Exchange (ETDEWEB)

    Raymond, J.P.; Izembart, M.; Marliac, V.; Dagousset, F.; Merceron, R.E.; Vulpillat, M.; Vallee, G.

    1989-07-01

    We studied ovarian function retrospectively in 66 women who had regular menstrual cycles before undergoing complete thyroidectomy for differentiated thyroid cancer and subsequent thyroid remnant ablation with /sup 131/I. Eighteen women developed temporary amenorrhea accompanied by increased serum gonadotropin concentrations during the first year after /sup 131/I therapy. No correlation was found between the radioactive iodine dose absorbed, thyroid uptake before treatment, oral contraceptive use, or thyroid autoimmunity. Only age was a determining factor, with the older women being the most affected. We conclude that radioiodine ablation therapy is followed by transient ovarian failure, especially in older women.

  16. The steroidogenic response and corpus luteum expression of the steroidogenic acute regulatory protein after human chorionic gonadotropin administration at different times in the human luteal phase.

    Science.gov (United States)

    Kohen, Paulina; Castro, Olga; Palomino, Alberto; Muñoz, Alex; Christenson, Lane K; Sierralta, Walter; Carvallo, Pilar; Strauss, Jerome F; Devoto, Luigi

    2003-07-01

    This study was designed 1) to assess corpus luteum (CL) steroidogenesis in response to exogenous human chorionic gonadotropin (hCG) at different times during the luteal phase, 2) to examine the effect of hCG on steroidogenic acute regulatory protein (StAR) expression within the CL, 3) to correlate StAR expression and luteal steroidogenic responses to hCG, and 4) to determine whether endogenous LH regulates ovarian steroidogenesis in the early luteal phase. Blood was collected before and after hCG treatment for steroid and hCGbeta determinations. CL were obtained at the time of surgery to assess StAR gene and protein expression. During the early luteal phase various women received the GnRH antagonist for 24-48 h; some of them also received hCG 24 h after the GnRH antagonist. A slight steroidogenic response to hCG was observed in early luteal phase; 17alpha-hydroxyprogesterone, but not progesterone (P4), levels were significantly increased 8 h post-hCG, indicating a differential response by the granulosa and theca-lutein cells. The 1.6- and 4.4-kb StAR transcripts and the 37-kDa preprotein and 30-kDa mature StAR protein did not change post-hCG administration in early luteal phase CL. In contrast, the StAR 4.4- and 1.6-kb transcripts diminished significantly (P < 0.05) after the antagonist treatment. Immunohistochemical staining for StAR protein was weak, particularly in granulosa-lutein cells. Treatment with hCG restored StAR mRNA and protein and plasma P4 levels within 24 h in antagonist-treated women. hCG stimulated the highest plasma concentrations of P4 and estradiol in the midluteal phase, indicating its greatest steroidogenic capacity. Midluteal tissue StAR gene and protein expression increased by 1.6- and 1.4-fold after 24 h of hCG treatment, respectively. Administration of hCG resulted in the greatest increment in plasma P4 (4-fold) and 17alpha-hydroxyprogesterone (3-fold) levels over baseline in the late luteal phase. This was associated with an increase in

  17. Characterization and Targeting of the Aldehyde Dehydrogenase Subpopulation in Ovarian Cancer

    Science.gov (United States)

    2013-07-01

    interactions R01 Role: Co-I (van Waardenburg ) Sponsor: NIH/NCI The DNA repair enzyme tyrosyl-DNA phosphodiesterase I as therapeutic target Major...ports the hypothesis that incessant ovulation is the culprit for tumor initi- ation. For example, women with poly- cystic ovarian syndrome , who by...nulliparous women, women with poly- cystic ovary syndrome , and women with other types of primary infertility who also have increased gonadotropin pro

  18. Ultrasound in evaluating ovarian reserve

    Directory of Open Access Journals (Sweden)

    Eman Ahmaed Shawky Sabek

    2015-12-01

    Full Text Available The objective of this study was to compare the diagnostic accuracy of transvaginal ultrasound (TVS, as a less invasive technique instead of hormonal assay to evaluate the ovarian reserve. This study included fifty-five females with breast cancer and we compared the ovarian reserve for these patients by hormonal assay through measuring the serum AntiMullerian Hormone (AMH level and follicular stimulating hormone (FSH level before and after chemotherapy, and by transvaginal ultrasound through the ovarian volume (OV calculation and counting the Antral follicles (AFC before and after chemotherapy treatment. There was decline in the AntiMullerian Hormone level after chemotherapy by 27 ± 11.19% and decrease in the Antral follicle counts by 21 ± 13.43%. In conclusion there was strong relation between AMH level and AFC which makes the use of transvaginal ultrasound is a reliable alternative method to the hormonal assay to detect the ovarian reserve.

  19. A novel approach to breast cancer prevention: reducing excessive ovarian androgen production in elderly women.

    Science.gov (United States)

    Secreto, Giorgio; Sieri, Sabina; Agnoli, Claudia; Grioni, Sara; Muti, Paola; Zumoff, Barnett; Sant, Milena; Meneghini, Elisabetta; Krogh, Vittorio

    2016-08-01

    Minimizing endogenous estrogen production and activity in women at high risk for breast cancer is a prominent approach to prevention of the disease. A number of clinical trials have shown that the administration of selective-estrogen receptor modulators or aromatase inhibitors significantly reduces the incidence of breast cancer in healthy women. Unfortunately, these drugs often produce adverse effects on the quality of life and are, therefore, poorly accepted by many women, even those who are at high risk for breast cancer. We propose a novel alternative approach to decreasing estrogen production: suppression of ovarian synthesis of the androgen precursors of estrogens by administration of long-acting gonadotropin-releasing hormone analogs to women with ovarian stromal hyperplasia. The specific target population would be elderly postmenopausal women, at increased risk of breast cancer, and with high blood levels of testosterone, marker of ovarian hyperandrogenemia, and recognized factor of risk for breast cancer. Testosterone levels are measured at baseline to identify women at risk and during the follow-up to evaluate the effectiveness of therapy. The postmenopausal ovary is an important source of excessive androgen production which originates from the ovarian interstitial cell hyperplasia frequently present in breast cancer patients. We propose to counter the source of androgen excess in women with ovarian stromal hyperplasia, thus reducing the substrate for estrogen formation without completely inhibiting estrogen synthesis. Available evidence indicates that gonadotropin-releasing hormone analogs can be safely used for breast cancer prevention in postmenopausal women.

  20. Weigh the pros and cons to ovarian reserve before stripping ovarian endometriomas prior to IVF/ICSI: A meta-analysis.

    Science.gov (United States)

    Tao, Xin; Chen, Lei; Ge, Shuqi; Cai, Lisi

    2017-01-01

    To explore the effects of conservative surgery for endometriomas on ovarian responsiveness during assisted reproductive technology (ART) and provide reproductive and gynecological doctors with a more reliable reference program for the treatment of endometriomas. A literature search was performed by searching the PubMed, Embase, Cochrane Library, Web of Science and Science Direct databases. Studies with inter- and intra-patient comparisons of ovarian responses and oocyte quality between operated and unoperated ovaries and that met the inclusion criteria were retrieved, and the data from the outcome measures were extracted and pooled for this meta-analysis. Twenty-one published studies (2649 ART cycles) were included. The total amount of gonadotropin (Gn) used (inverse variance (IV):0.48; 95% confidence interval (CI): [0.13, 1.82], P = 0.0007) was significantly increased in the women with endometriomas who had a history of cystectomy. The estrogen (E) level on the day of hCG administration (IV: -0.29; 95% CI: [-0.41, -0.17], P<0.00001), the number of mature or dominant follicles (IV: -1.17; 95% CI: [-1.51, -0.82], P<0.00001) and the total number of oocytes retrieved (IV: -1.78; 95% CI: [-2.38, -1.17], P<0.00001) were significantly decreased in the women with endometriomas who had a history of cystectomy. The duration of stimulation (IV: 0.02; 95% CI: [-0.09, 0.13], P = 0.77), the total number of formed embryos (IV: -0.06; 95% CI: [-0.17, 0.04], P = 0.25), the pregnancy rate(IV:0.98;95%CI[0.82,1.18], P = 0.83) and the live birth rate(IV:0.93;95%CI[0.70,1.23], P = 0.61)were not statistically different between the two groups. Similar intra-patient results were found in the number of mature or dominant follicles (IV: -0.88; 95% CI: [-1.25, -0.52], P<0.00001) and the total number of oocytes retrieved (IV: -3.48; 95% CI: [-4.77, -2.19], P<0.00001). ART might be a better therapeutic method for ovarian endometrioma-related infertility than cystectomy.

  1. Identification of new ovulation-related genes in humans by comparing the transcriptome of granulosa cells before and after ovulation triggering in the same controlled ovarian stimulation cycle

    DEFF Research Database (Denmark)

    Wissing, M L; Kristensen, S G; Andersen, C Y

    2014-01-01

    . Many new ovulation-related genes were revealed, such as CD24, ANKRD22, CLDN11 and FBXO32. FF estrogen, androstenedione and anti-Müllerian hormone decreased significantly while progesterone increased, accompanied by radical changes in the expression of steroidogenic genes (CYP17A, CYP19A, HSD11B1......, REASONS FOR CAUTION: The present dataset was generated from women under hormonal stimulation. However, comparison with a macaque natural cycle whole follicle ovulation dataset revealed major overlap, supporting the idea that the ovulation-related genes found in this study are relevant in the human natural...... cycle. WIDER IMPLICATIONS OF THE FINDINGS: These data will serve as a research resource for genes involved in human ovulation and final oocyte maturation. Ovulation-related genes might be good candidate biomarkers of follicle and oocyte health. Further, some of the ovulation-related genes may serve...

  2. Fertility status of Hodgkin lymphoma patients treated with chemotherapy and adjuvant gonadotropin-releasing hormone analogues.

    Science.gov (United States)

    Huser, M; Smardova, L; Janku, P; Crha, I; Zakova, J; Stourac, P; Jarkovsky, J; Mayer, J; Ventruba, P

    2015-08-01

    Aim of this prospective observational study was to analyze fertility status of Hodgkin lymphoma (HL) patients treated with different types of chemotherapy while receiving GnRH analogues to preserve ovarian function. Fertility status was assessed among 108 females in reproductive age treated by curative chemotherapy for freshly diagnosed HL between 2005 and 2010 in university-based tertiary fertility and oncology center. All patients received GnRH analogues during chemotherapy to preserve their ovarian function. Their reproductive functions were assessed by follicle-stimulating hormone (FSH) measurement and pregnancy achievement. Ovarian function was determined separately in three groups with increasing gonadotoxicity of chemotherapy. One year following the treatment, normal ovarian function was found in 89 (82.4%) of patients. Two years after chemotherapy, 98 (90.7%) of patients retained their ovarian function, and 23 (21.3%) achieved clinical pregnancy during the follow-up period. Average FSH after chemotherapy was 11.6 ± 17.9 IU/l 1 year after the treatment resp. 9.0 ± 13.8 at the 2 years interval. There were significantly more patients with chemotherapy induced diminished ovarian reserve (chDOR) among the group receiving escalated BEACOPP chemotherapy in comparison with the other types of treatment (58.1% vs. 87.9% resp. 95.5%). The rate of chDOR is significantly higher after EB poly-chemotherapy and there is no tendency for improvement in time. The 2 + 2 chemotherapy with GnRH-a required for more advanced HL retained ovarian function significantly better after 2 years. Another important advantage of GnRH-a co-treatment is the excellent control of patient's menstrual cycle.

  3. The IVF Outcome Counseling Based on the Model Combining DHEAS and Age in Patients with Low AMH Prior to the First Cycle of GnRH Antagonist Protocol of Ovarian Stimulation

    Directory of Open Access Journals (Sweden)

    Miro Šimun Alebić

    2013-01-01

    Full Text Available Objective. To investigate the endocrine and/or clinical characteristics of women with low anti-Müllerian hormone (AMH that could improve the accuracy of IVF outcome prediction based on the female age alone prior to the first GnRH antagonist IVF cycle. Methods. Medical records of 129 patients with low AMH level (<6.5 pmol/L who underwent their first GnRH antagonist ovarian stimulation protocol for IVF/ICSI were retrospectively analyzed. The main outcome measure was the area under the ROC curve (AUC-ROC for the models combining age and other potential predictive factors for the clinical pregnancy. Results. Clinical pregnancy rate (CPR per initiated cycles was 11.6%. For the prediction of clinical pregnancy, DHEAS and age showed AUC-ROC of 0.726 (95%CI 0.641–0.801 and 0.662 (95%CI 0.573–0.743, respectively (. The predictive accuracy of the model combining age and DHEAS (AUC-ROC 0.796; 95%CI 0.716–0.862 was significantly higher compared to that of age alone (. In patients <37.5 years with DHEAS  pmol/L, 60% (9/15 of all pregnancies were achieved with CPR of 37.5%. Conclusions. DHEAS appears to be predictive for clinical pregnancy in younger women (<37.5 years with low AMH after the first GnRH antagonist IVF cycle. Therefore, DHEAS-age model could refine the pretreatment counseling on pregnancy prospects following IVF.

  4. Reserva endocrina ovárica en mujeres con falla ovárica prematura Endocrine ovarian reserve in women with premature ovarian failure

    Directory of Open Access Journals (Sweden)

    Rubén S. Padrón Durán

    2002-12-01

    complementary examinations were made to define the cause. The basal levels of follicle-stimulating hormone (FSH, luteinizing hormone (LH, estradiol (E2, Prolactin (Prl, and Thyrotropin (TSH were determined.The steroideal ovarian reserve was also determined by the dynamic test of hypophyseal inhibition of gonadotropins (Gn with ethynyl estradiol and, later, it was estimulated with gonadotropic menopausic hormone (GMH.The basal levels of FSH, LH, E2, testosterone (T and androstenedione (A'd were calculated during inhibition and after the stimulation with GMH. It was found that the mean basal levels of FSH were higher than those of LH, the levels of E2 were low and Prl was normal on analyzing them as a group. The mean basal level of E2 was low and there was no increase of its mean levels after the stimulation with GMH. The mean basal levels of T were normal, unlike A'd that was low. No rise was observed poststimulation on being analyzed as a group. It was proved that 52.6 % of these patients have an ovarian estrogenic reserve, whereas only 20 % have an androgenic reserve. There were no important differences in the results of the dynamic test on dividing patients into 2 groups, according to the chronological age, time of amenorrhea and cause of POF, excepting that the reserve of T that was only found in those of idiopathic cause, which was not observed in those of immunological cause.

  5. Primary ovarian leiomyoma

    International Nuclear Information System (INIS)

    Mathew, Marian; Krolikowski, Anderzj; Al-Haddabi, Ibrahim; Nirmala, Vadakkepat

    2005-01-01

    Ovarian leiomyoma is a rare and incidentally detected neoplasm, clinically indistinguishable from subserous leiomyomas and ovarian fibromas, until histopathological confirmation. We present a case of leiomyoma arising primarily from the ovary in a 35 year old woman. (author)

  6. Ovarian cancer and smoking

    DEFF Research Database (Denmark)

    Beral, V; Gaitskell, K; Hermon, C

    2012-01-01

    Smoking has been linked to mucinous ovarian cancer, but its effects on other ovarian cancer subtypes and on overall ovarian cancer risk are unclear, and the findings from most studies with relevant data are unpublished. To assess these associations, we review the published and unpublished evidence....

  7. Effects of aqueous extract from Asparagus officinalis L. roots on hypothalamic-pituitary-gonadal axis hormone levels and the number of ovarian follicles in adult rats

    Directory of Open Access Journals (Sweden)

    Hojatollah Karimi Jashni

    2016-02-01

    Full Text Available Background: Asparagus is a plant with high nutritional, pharmaceutical, and industrial values. Objective: The present study aimed to evaluate the effect of aqueous extract of asparagus roots on the hypothalamic-pituitary-gonadal axis hormones and oogenesis in female rats. Materials and Methods: In this experimental study, 40 adult female Wistar rats were divided into five groups, which consist 8 rats. Groups included control, sham and three experimental groups receiving different doses (100, 200, 400 mg/kg/bw of aqueous extract of asparagus roots. All dosages were administered orally for 28 days. Blood samples were taken from rats to evaluate serum levels of Gonadotropin releasing hormone (GnRH, follicular stimulating hormone (FSH, Luteinal hormone (LH, estrogen, and progesterone hormones. The ovaries were removed, weighted, sectioned, and studied by light microscope. Results: Dose-dependent aqueous extract of asparagus roots significantly increased serum levels of GnRH, FSH, LH, estrogen, and progestin hormones compared to control and sham groups. Increase in number of ovarian follicles and corpus luteum in groups treated with asparagus root extract was also observed (p<0.05. Conclusion: Asparagus roots extract stimulates secretion of hypothalamic- pituitary- gonadal axis hormones. This also positively affects oogenesis in female rats.

  8. GnRH dysregulation in polycystic ovarian syndrome (PCOS) is a manifestation of an altered neurotransmitter profile.

    Science.gov (United States)

    Chaudhari, Nirja; Dawalbhakta, Mitali; Nampoothiri, Laxmipriya

    2018-04-11

    GnRH is the master molecule of reproduction that is influenced by several intrinsic and extrinsic factors such as neurotransmitters and neuropeptides. Any alteration in these regulatory loops may result in reproductive-endocrine dysfunction such as the polycystic ovarian syndrome (PCOS). Although low dopaminergic tone has been associated with PCOS, the role of neurotransmitters in PCOS remains unknown. The present study was therefore aimed at understanding the status of GnRH regulatory neurotransmitters to decipher the neuroendocrine pathology in PCOS. PCOS was induced in rats by oral administration of letrozole (aromatase inhibitor). Following PCOS validation, animals were assessed for gonadotropin levels and their mRNA expression. Neurotrasnmitter status was evaluated by estimating their levels, their metabolism and their receptor expression in hypothalamus, pituitary, hippocampus and frontal cortex of PCOS rat model. We demonstrate that GnRH and LH inhibitory neurotransmitters - serotonin, dopamine, GABA and acetylcholine - are reduced while glutamate, a major stimulator of GnRH and LH release, is increased in the PCOS condition. Concomitant changes were observed for neurotransmitter metabolising enzymes and their receptors as well. Our results reveal that increased GnRH and LH pulsatility in PCOS condition likely result from the cumulative effect of altered GnRH stimulatory and inhibitory neurotransmitters in hypothalamic-pituitary centre. This, we hypothesise, is responsible for the depression and anxiety-like mood disorders commonly seen in PCOS women.

  9. Outcomes of in vitro fertilization cycles among patients with polycystic ovary syndrome following ovarian puncture for in vitro maturation.

    Science.gov (United States)

    Lin, Jia; Wang, Peiyu; Zhao, Junzhao; Xiao, Shiquan; Yu, Rong; Jin, Congcong; Zhu, Ruru

    2016-12-01

    To investigate the effects of ovarian puncture for in vitro maturation (IVM) on subsequent in vitro fertilization (IVF) embryo transfer cycles in patients with polycystic ovary syndrome (PCOS). A retrospective study included data from patients admitted to the First Affiliated Hospital of Wenzhou Medical University, China, between January 1, 2008 and December 31, 2014. Patients with PCOS undergoing IVF cycles after having been treated with IVM unsuccessfully were included as the study group and an IVF-procedure data-matched control group of patients undergoing their first IVF cycles was included in a 1:4 ratio. Patients with reproductive anomalies were excluded. Endocrine-hormone levels and antral follicle counts were measured and fertilization-related outcomes were evaluated. There were 49 patients included in the study group and 196 included in the control group. Within the study group, basal luteal-hormone, testosterone, and antral follicle count levels were significantly lower following IVM treatment. The total gonadotropin dose was lower (Povarian hyper-stimulation syndrome (P=0.633). Previous IVM resulted in improved endocrine profiles and increased clinical-pregnancy rates among patients with PCOS undergoing IVF cycles. Copyright © 2016 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

  10. Clinical value of serum anti-mullerian hormone and inhibin B in prediction of ovarian response in patients with polycystic ovary syndrome.

    Science.gov (United States)

    Zhang, Fan; Liu, Xiao-Ling; Rong, Nan; Huang, Xiao-Wen

    2017-02-01

    The present study aimed to investigate the clinical value of serum anti-mullerian hormone (AMH) and inhibin B (INHB) in predicting the ovarian response of patients with polycystic ovary syndrome (PCOS). A total of 120 PCOS patients were enrolled and divided into three groups in terms of the ovarian response: a low-response group (n=36), a normal-response group (n=44), and a high-response group (n=40). The serum AMH and INHB levels were measured by enzyme-linked immunosorbent assay (ELISA). The follicle stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) levels were determined by chemiluminescence microparticle immunoassay. The correlation of the serum AMH and INHB levels with other indicators was analyzed. A receiver operating characteristic (ROC) curve was established to analyze the prediction of ovarian response by AMH and INHB. The results showed that there were significant differences in age, body mass index (BMI), FSH, total gonadotropin-releasing hormone (GnRH), LH, E2, and antral follicle counts (AFCs) between the groups (Povarian response of PCOS patients increasing (Povarian response showed that the area under the ROC curve (AUC) value of the serum AMH level was 0.817, with a cut-off value of 1.29 ng/mL. The sensitivity and specificity were 71.2% and 79.6%, respectively. The AUC value of serum INHB was 0.674, with a cut-off value of 38.65 ng/mL, and the sensitivity and specificity were 50.7% and 74.5%, respectively. ROC curve analysis showed when the serum AMH and INHB levels were used to predict a high ovarian response, the AUC value of the serum AMH level was 0.742, with a cut-off value of 2.84 ng/mL, and the sensitivity and specificity were 72.7% and 65.9%, respectively; the AUC value of the serum INHB level was 0.551 with a cut-off of 45.76 ng/mL, and the sensitivity and specificity were 76.3% and 40.2%, respectively. It was suggested the serum AMH and INHB levels have high clinical value in predicting the ovarian response of PCOS

  11. Benefits and risks of ovarian function and reproduction for cancer development and prevention.

    Science.gov (United States)

    Schindler, Adolf E

    2011-12-01

    Ovarian function and menstrual cycle disturbances, pregnancy, and reproductive medicine procedures can either increase gynecological cancer risk or prevent cancer development. For ovarian cancer development, there are two hypotheses, which are connected with ovulation and gonadotropin secretion. Most of the ovarian cancers seem to be derived from displaced ovarian surfice epithelial cells. One year of ovulatory cycles increases the ovarian cancer risk by 6%. Ovulation between 22 and 29 years of age causes the highest risk increase per year. In contrast, progesterone or progestins appear to create protection. Lifestyle can affect or modify ovarian cancer risk. Breast cancer risk is very much related to age of menarche and menopause, pregnancy, and breast feeding. All of which are related to ovarian function and progestogenic impact that translates either into breast cancer risk increase or decrease. This is modified by body mass index, physical activity, and lifestyle in general. The risk of endometrial cancer is most closely related to endogenous progesterone during the menstrual cycle and pregnancy or by exogenous progestogens as in oral contraceptives. These effects are progestogen dose and time dependent. Endometrial cancer risk can also be increased by estrogen-producing tumors or long-term estrogen treatment.

  12. Kisspeptin stimulates growth hormone release by utilizing Neuropeptide Y pathways and is dependent on the presence of ghrelin

    Science.gov (United States)

    Although kisspeptin is the primary stimulator of gonadotropin releasing hormone secretion and therefore the hypothalamic-pituitary gonadal axis, new findings suggest kisspeptin can also regulate additional neuroendocrine processes including release of growth hormone (GH). Central delivery of kisspep...

  13. Anomalias meióticas de oócitos de pacientes com endometriose submetidas à estimulação ovariana Meiotic abnormalities of oocytes from patients with endometriosis submitted to ovarian stimulation

    Directory of Open Access Journals (Sweden)

    Ionara Diniz Evangelista Santos Barcelos

    2008-08-01

    Full Text Available OBJETIVO: avaliar o fuso meiótico e a distribuição cromossômica de oócitos maturados in vitro, obtidos de ciclos estimulados de mulheres inférteis com endometriose e fatores masculino e/ou tubário de infertilidade (Grupo Controle, comparando as taxas de maturação in vitro (MIV entre os dois grupos avaliados. MÉTODOS: quatorze pacientes com endometriose e oito com fator tubário ou masculino, submetidas à estimulação ovariana para injeção intracitoplasmática de espermatozóide, foram selecionadas, prospectiva e consecutivamente, e constituíram os Grupos de Estudo e Controle, respectivamente. Oócitos imaturos (46 e 22, respectivamente, dos Grupos Endometriose e Controle foram submetidos à MIV. Oócitos que apresentaram a extrusão do primeiro corpúsculo polar foram fixados e corados para avaliação dos microtúbulos e cromatina por técnica de imunofluorescência. A análise estatística foi realizada utilizando o teste exato de Fisher, com significância estatística quando pPURPOSE: to evaluate the meiotic spindle and the chromosome distribution of in vitro mature oocytes from stimulated cycles of infertile women with endometriosis, and with male and/or tubal infertility factors (Control Group, comparing the rates of in vitro maturation (IVM between the two groups evaluated. METHODS: fourteen patients with endometriosis and eight with male and/or tubal infertility factors, submitted to ovarian stimulation for intracytoplasmatic sperm injection have been prospectively and consecutively selected, and formed a Study and Control Group, respectively. Immature oocytes (46 and 22, respectively, from the Endometriosis and Control Groups were submitted to IVM. Oocytes presenting extrusion of the first polar corpuscle were fixed and stained for microtubules and chromatin evaluation through immunofluorescence technique. Statistical analysis has been done by the Fisher's exact test, with statistical significance at p<0.05. RESULTS

  14. Evaluation of the ovarian reserve in women transplanted with frozen and thawed ovarian cortical tissue

    DEFF Research Database (Denmark)

    Greve, Tine; Schmidt, Kirsten Tryde; Kristensen, Stine Gry

    2012-01-01

    To investigate ovarian reserve and ovarian function in women transplanted with frozen/thawed ovarian tissue.......To investigate ovarian reserve and ovarian function in women transplanted with frozen/thawed ovarian tissue....

  15. Effect of cortisol on gonadotropin inhibitory hormone (GnIH) in the cinnamon clownfish, Amphiprion melanopus.

    Science.gov (United States)

    Choi, Young Jae; Habibi, Hamid R; Kil, Gyung-Suk; Jung, Min-Min; Choi, Cheol Young

    2017-04-01

    Hypothalamic peptides, gonadotropin-releasing hormone (GnRH) and gonadotropin inhibitory hormone (GnIH), play pivotal roles in the control of reproduction and gonadal maturation in fish. In the present study we tested the possibility that stress-mediated reproductive dysfunction in teleost may involve changes in GnRH and GnIH activity. We studied expression of brain GnIH, GnIH-R, seabream GnRH (sbGnRH), as well as circulating levels of follicle stimulating hormone (FSH), and luteinizing hormone (LH) in the cinnamon clownfish, Amphiprion melanopus. Treatment with cortisol increased GnIH mRNA level, but reduced sbGnRH mRNA and circulating levels of LH and FSH in cinnamon clownfish. Using double immunofluorescence staining, we found expression of both GnIH and GnRH in the diencephalon region of cinnamon clownfish brain. These findings support the hypothesis that cortisol, an indicator of stress, affects reproduction, in part, by increasing GnIH in cinnamon clownfish which contributes to hypothalamic suppression of reproductive function in A. melanopus, a protandrous hermaphroditic fish. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Possible role of serum testosterone, gonadotropins and prolactin in patients with premature ejaculation.

    Science.gov (United States)

    Abu El-Hamd, M; Farah, A

    2018-02-01

    Premature ejaculation (PE) is the most common male sexual dysfunction. This study aimed to investigate the role of serum testosterone, gonadotropins and prolactin in patients with PE. In a prospective a case-controlled study, it was conducted on 90 male patients with PE and 90 male healthy participants as controls. Patients were evaluated by Premature Ejaculation Diagnostic Tool (PEDT) and intravaginal ejaculatory latency time (IELT). Patients with mean IELT values ≤60 s and PEDT total scores ≥11 were considered to have PE. Serum levels of total testosterone (TT), free testosterone (FT), follicle-stimulating hormone (FSH), luteinising hormone (LH) and prolactin (PL) were investigated in patients with PE and controls. There was no statistically significant difference between patients with PE and controls regarding the serum levels of TT, FT, FSH, LH and PL (p value ˃.05). There was no significant correlation between the sex hormones levels (TT, FT, FSH, LH and PL) and (age, body mass index (BMI), IELTS and total PEDT scores of the patients; p value ˃.05). This study concluded that there was no disturbance in serum levels of testosterone, gonadotropins and prolactin in patients with PE and controls. These hormones could not relate to pathogenesis of PE. © 2017 Blackwell Verlag GmbH.

  17. Neurokinin B and serum albumin limit copper binding to mammalian gonadotropin releasing hormone.

    Science.gov (United States)

    Gul, Ahmad Samir; Tran, Kevin K; Jones, Christopher E

    2018-02-26

    Gonadotropin releasing hormone (GnRH) triggers secretion of luteinizing hormone and follicle stimulating hormone from gonadotropic cells in the anterior pituitary gland. GnRH is able to bind copper, and both in vitro and in vivo studies have suggested that the copper-GnRH complex is more potent at triggering gonadotropin release than GnRH alone. However, it remains unclear whether copper-GnRH is the active species in vivo. To explore this we have estimated the GnRH-copper affinity and have examined whether GnRH remains copper-bound in the presence of serum albumin and the neuropeptide neurokinin B, both copper-binding proteins that GnRH will encounter in vivo. We show that GnRH has a copper dissociation constant of ∼0.9 × 10 -9  M, however serum albumin and neurokinin B can extract metal from the copper-GnRH complex. It is therefore unlikely that a copper-GnRH complex will survive transit through the pituitary portal circulation and that any effect of copper must occur outside the bloodstream in the absence of neurokinin B. Copyright © 2018 Elsevier Inc. All rights reserved.

  18. A MALE CASE OF KALLMANN'S SYNDROME : FERTILITY INDUCED BY GONADOTROPIN (hCG/hMG) THERAPY

    OpenAIRE

    Okamoto, Shingo; Mayumi Mimura, Mayumi; Moch, Tadao; Sakamoto, Takemi; Izumi, Yukiko; Matzui, Yuhji; Hosokawa, Akiko; Kuriyama, Shigeki; Fukui, Hiroshi

    1998-01-01

    A 24-year-old male patient with Kallmann's syndrome who fathered two children after gonadotropin therapy is reported here. He was diagnosed with Kallmann's syndrome because of hypothalamic hypogonadism associated with anosmia. The gonadotropin therapy was initiated which involved treatment with human chorionic gonadotropin (hCG) and human menopausal gonadotropin (hMG). After 3 years of treatment, his secondary sexual characteristics developed to near the adult level and sperm were detected in...

  19. Extending the duration of treatment with progesterone and equine chorionic gonadotropin improves fertility in suckled beef cows with low body condition score subjected to timed artificial insemination.

    Science.gov (United States)

    Bilbao, M G; Massara, N; Ramos, S; Zapata, L O; Farcey, M F; Pesoa, J; Turic, E; Vázquez, M I; Bartolome, J A

    2016-07-15

    The objective of this study was to evaluate the effect of an extended progesterone treatment on follicular development and fertility in postpartum, suckled beef cows subjected to timed artificial insemination (TAI). In experiment 1, cows (n = 24) with body condition score (BCS) ≥4.5 received either a 2-g progesterone intravaginal device on Day -23 or a 0.558-g progesterone intravaginal device on Day -9. Then, all cows received 2 mg of estradiol benzoate on Day -9; removal of the device, 1-mg estradiol cypionate, and PGF2α on Day -2; and TAI on Day 0. Metabolic status was assessed between Days -9 and -2. Ovarian structures and plasma progesterone were determined weekly from Day -23 to -9, daily from Day -9 to 0, and weekly until Day 28. In experiment 2, cows (n = 302) with BCS ≥4.5 received identical treatment to cows in experiment 1, but on Day -2, cows received 400 IU of two different commercial preparations of equine chorionic gonadotropin (eCG). Ovarian structures were determined on Days -23 and -9 on a subset of cows (n = 40). Pregnancy was determined 39 days after TAI. In experiment 3, multiparous cows (n = 244) with BCS cows in experiment 1 initiated on Day -18, and on Day -2, cows received 400 IU of eCG or no treatment. Ovarian structures were determined in a subset of cows (n = 31) on Days -3, -2, -1, 0, 1, and on Day 10. Pregnancy was determined 39 days after TAI. The results indicated that in experiment 1, plasma progesterone was higher in treated than nontreated (control cows) during the first 14 days (P = 0.0001). The extended progesterone treatment increased the size of the largest follicle between Days -23 and Day -5 (Group by Day, P = 0.04) and tended to increase the size of the dominant follicle from Day -5 to Day -1 (Group by Day, P = 0.06). There was no effect of metabolic status or interaction between metabolic status and day on follicular growth. In experiment 2, extended progesterone treatment tended to increase the

  20. Is There a Relationship between Ovarian Epithelial Dysplasia and Infertility?

    Directory of Open Access Journals (Sweden)

    Gautier Chene

    2012-01-01

    Full Text Available Aim. Ovarian epithelial dysplasia was initially described in material from prophylactic oophorectomies performed in patients at genetic risk of ovarian cancer. Similar histopathological abnormalities have been revealed after ovulation stimulation. Since infertility is also a risk factor for ovarian neoplasia, the aim of this study was to study the relationship between infertility and ovarian dysplasia. Methods. We blindly reviewed 127 histopathological slides of adnexectomies or ovarian cystectomies according to three groups—an exposed group to ovulation induction (n = 30, an infertile group without stimulation (n = 35, and a spontaneously fertile control group (n = 62—in order to design an eleven histopathological criteria scoring system. Results. The ovarian dysplasia score was significantly higher in exposed group whereas dysplasia score was low in infertile and control groups (resp., 8.21 in exposed group, 3.69 for infertile patients, and 3.62 for the controls. In the subgroup with refractory infertility there was a trend towards a more severe dysplasia score (8.53 in ovulation induction group and 5.1 in infertile group. Conclusion. These results raise questions as to the responsibility of drugs used to induce ovulation and/or infertility itself in the genesis of ovarian epithelial dysplasia.

  1. Ethnicity as a determinant of ovarian reserve: differences in ovarian aging between Spanish and Indian women.

    Science.gov (United States)

    Iglesias, Carlos; Banker, Manish; Mahajan, Nalini; Herrero, Leyre; Meseguer, Marcos; Garcia-Velasco, Juan A

    2014-07-01

    To investigate differences in ovarian reserve markers (antimüllerian hormone [AMH] and antral follicle count [AFC]) in Indian and Spanish women. Cross-sectional study. In vitro fertilization (IVF) clinics. Infertile Spanish (n=229) and Indian (n=236) women who underwent controlled ovarian stimulation for IVF from January to October 2012. None. Data on ovarian reserve markers and results after ovarian stimulation were collected. The mean age of women undergoing their first or second IVF cycle was significantly higher in Spanish than in Indian women (37.5±3.3 years vs. 31.5±3.8 years). Despite this 6-year age gap, AFCs were similar (9.5±4.7 vs. 9.9±4.6), as were day 3 FSH levels (7.5±4.5 IU/L vs. 6.9±2.3 IU/L). AMH levels were slightly lower in Spanish women (1.6±1.7 ng/mL vs. 2.5±1.6 ng/mL). Multivariate regression analysis showed that being Indian decreased AFC by 2.3, such that AFC in Indian women was similar to that in Spanish women 6.3 years older (95% confidence interval 3.39-1.10). Similar ovarian reserve markers and ovarian response were observed in women with a 6-year age difference in favor of the Spanish, suggesting ethnic differences in ovarian aging. Further research is needed to understand whether these differences are genetically induced or are caused by other variables, such as nutrition. Our results may help clinicians to counsel infertile women when discussing assisted reproductive technology outcomes according to age and ethnic background. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  2. Expression and Activation of Gonadotropin Receptors

    NARCIS (Netherlands)

    R. Kraaij (Robert)

    1996-01-01

    textabstractAmong the many hormones that are produced by the anterior pituitary gland, luteinizing hormone (LH, lutropin), follicle-stimulating hormone (FSH, follitropin), and thyroidstimulating hormone (TSH, thyrotropin) form the separate family of so-called glycoprotein hormones (reviewed by

  3. Premature ovarian failure

    Directory of Open Access Journals (Sweden)

    Persani Luca

    2006-04-01

    Full Text Available Abstract Premature ovarian failure (POF is a primary ovarian defect characterized by absent menarche (primary amenorrhea or premature depletion of ovarian follicles before the age of 40 years (secondary amenorrhea. It is a heterogeneous disorder affecting approximately 1% of women e.g. Turner syndrome represent the major cause of primary amenorrhea associated with ovarian dysgenesis. Despite the description of several candidate genes, the cause of POF remains undetermined in the vast majority of the cases. Management includes substitution of the hormone defect by estrogen/progestin preparations. The only solution presently available for the fertility defect in women with absent follicular reserve is ovum donation.

  4. Influence of Human Chorionic Gonadotropin on the Fertility Rate in ...

    African Journals Online (AJOL)

    An experiment was carried out on the influence of human chorionic gonadotropin hormone (hCG) on the fertility rate of rabbit does under artificial insemination. The rabbit does (7-8 months old) were used for the trial. The hCG was administered to the rabbit does at varying doses: 0, 50, 100 and 150 I.U representing ...

  5. Steroid Cell Ovarian Neoplasm, Not Otherwise Specified: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Paul Singh

    2012-01-01

    Full Text Available Background. Steroid cell ovarian tumors, not otherwise specified, represent a unique cause of female virilization. Most commonly encountered in premenopausal women, these tumors can exist throughout a women’s lifetime, from before puberty until after menopause. Case. Steroid cell, not otherwise specified, was diagnosed in a 70-year-old female significant for hirsutism. The patient demonstrated elevated total testosterone levels with normal gonadotropins, DHEA, and DHEA-S levels. CT imaging revealed a right ovarian mass and subsequent laparoscopic right oophorectomy yielded clinical improvement promptly. Conclusion. Virilization in females can occur based on ovarian or adrenal pathology. In terms of ovarian-based female virilization, many tumors exist that may induce women to demonstrate masculine features, such as pure Sertoli, pure Leydig, Sertoli-Leydig combinations, and gynandroblastomas. Each of these tumor types possesses a unique histologic pattern that allows for pathologic identification after removal. A rare source of ovarian-based female virilization is steroid cell neoplasms, not otherwise specified, that do not demonstrate these specific histologic characteristics and thus represent a diagnosis of exclusion after other causes of ovarian-based female virilization have been ruled out.

  6. Exaggerated gonadotropin response to luteinizing hormone-releasing hormone in amenorrheic runners.

    Science.gov (United States)

    Yahiro, J; Glass, A R; Fears, W B; Ferguson, E W; Vigersky, R A

    1987-03-01

    Most studies of exercise-induced amenorrhea have compared amenorrheic athletes (usually runners) with sedentary control subjects. Such comparisons will identify hormonal changes that develop as a result of exercise training but cannot determine which of these changes play a role in causing amenorrhea. To obviate this problem, we assessed reproductive hormone status in a group of five amenorrheic runners and compared them to a group of six eumenorrheic runners matched for body fatness, training intensity, and exercise performance. Compared to the eumenorrheic runners, the amenorrheic runners had lower serum estradiol concentrations, similar basal serum luteinizing hormone and follicle-stimulating hormone concentrations, and exaggerated responses of serum gonadotropins after administration of luteinizing hormone-releasing hormone (100 micrograms intravenous bolus). Serum prolactin levels, both basally and after thyrotropin-releasing hormone administration (500 micrograms intravenous bolus) or treadmill exercise, was similar in the two groups, as were serum thyroid function tests (including thyrotropin response to thyrotropin-releasing hormone). Changes in serum cortisol levels after short-term treadmill exercise were similar in both groups, and serum testosterone levels increased after exercise only in the eumenorrheic group. In neither group did such exercise change serum luteinizing hormone, follicle-stimulating hormone, or thyrotropin levels. We concluded that exercise-induced amenorrhea is not solely related to the development of increased prolactin output after exercise training. The exaggerated gonadotropin response to luteinizing hormone-releasing hormone seen in amenorrheic runners in comparison with matched eumenorrheic runners is consistent with a hypothalamic etiology for the menstrual dysfunction, analogous to that previously described in "stress-induced" or "psychogenic" amenorrhea.

  7. Comparison of the ultrashort gonadotropin-releasing hormone agonist-antagonist protocol with microdose flare -up protocol in poor responders: a preliminary study.

    Science.gov (United States)

    Berker, Bülent; Duvan, Candan İltemir; Kaya, Cemil; Aytaç, Ruşen; Satıroğlu, Hakan

    2010-01-01

    To determine the potential effect of the ultrashort gonadotropin-releasing hormone (GnRH) agonist/GnRH antagonist protocol versus the microdose GnRH agonist protocol in poor responders undergoing intracytoplasmic sperm injection (ICSI). The patients in the Agonist-Antagonist Group (n=41) were administered the ultrashort GnRH-agonist/ antagonist protocol, while the patients in the Microdose Group (n=41) were stimulated according to the microdose flare-up protocol. The mean number of mature oocytes retrieved was the primary outcome measure. Fertilization rate, implantation rate per embryo and clinical pregnancy rates were secondary outcome measures. There was no differenc between the mean number of mature oocytes retrieved in the two groups. There were also no statistical differences between the two groups in terms of peak serum E2 level, canceled cycles, endometrial thickness on hCG day, number of 2 pronucleus and number of embryos transferred. However, the total gonadotropin consumption and duration of stimulation were significantly higher with the Agonist-Antagonist Group compared with the Microdose Group. The implantation and clinical pregnancy rates were similar between the two groups. Despite the high dose of gonadotropin consumption and longer duration of stimulation with the ultrashort GnRH agonist/ antagonist protocol, it seems that the Agonist-Antagonist Protocol is not inferior to the microdose protocol in poor responders undergoing ICSI.

  8. Presence of gonadotropin-releasing hormone-like peptide in the central nervous system and reproductive organs of the male blue swimming crab, Portunus pelagicus, and its effect on spermatogenesis.

    Science.gov (United States)

    Senarai, Thanyaporn; Saetan, Jirawat; Tamtin, Montakan; Weerachatyanukul, Wattana; Sobhon, Prasert; Sretarugsa, Prepee

    2016-08-01

    Our previous studies have demonstrated that lamprey gonadotropin-releasing hormone-III (lGnRH-III)-like peptide occurs in the central nervous system (CNS) of decapod crustaceans (Macrobrachium rosenbergii, Penaeus monodon, Portunus pelagicus), and that lGnRH-III is the most potent in stimulating ovarian maturation compared with other GnRH isoforms. In this study, we examined the localization of lGnRH-III-like peptide in the CNS and male reproductive organs of the blue swimming crab by using anti-lGnRH-III as a probe. In the brain, lGnRH-III immunoreactivity (-ir) was detected in neurons of clusters 6, 10, 11, 14/15, 16, and 17 and in many neuropils. In the subesophageal ganglion, lGnRH-III-ir was present in neurons of the dorso-lateral and ventro-medial clusters. In the thoracic ganglia, lGnRH-III-ir was observed in the large-sized neurons between the thoracic neuropils and in the ventromedial cluster of the abdominal ganglia. In the testis, lGnRH-III-ir was detected in nurse cells, hemocytes, spermatids 2, and the outer and inner zones of the acrosomes of spermatozoa. Bioassay showed that lGnRH-III significantly increased the testis-somatic index, the percentage of late stages of seminiferous tubules (stages VII-IX), the diameter of the seminiferous tubules, and the number of BrdU-labeled early germ cells compared with the control groups. Thus, lGnRH-III-like peptide exists in the male crab and possibly enhances germ cell proliferation and maturation in the testes, leading to increased sperm production.

  9. The influence of ovarian hyperstimulation drugs on morphometry and morphology of human oocytes in ICSI program.

    Science.gov (United States)

    Taheri, Fatemeh; Alemzadeh Mehrizi, Arezoo; Khalili, Mohammad Ali; Halvaei, Iman

    2018-04-01

    To compare the influences of controlled ovarian hyperstimulation (COH) drugs using recombinant follicular stimulating hormone (rFSH) versus human menopausal gonadotropins (hMG) on morphometry and morphology of MII oocytes in ICSI cycles. In this prospective study, 363 MII oocytes from 50 ICSI cycles with male factor infertility were evaluated. The patients were divided into two groups according to the protocols of COH: I- rFSH and II- hMG. The immature oocytes were excluded from the study. All oocytes were categorized into four morphological groups of normal, and those with single, double, or multiple defects. The inclusive morphometrical criteria were: areas and diameters of oocyte, ooplasm, and zona pellucida (ZP). Also, circumferences of oocyte and ooplasm were assessed. The ZP area and ooplasm diameter for both normal and abnormal oocytes were significantly higher in group I (P: .05; P: .028, respectively) compared to group II (P: .023; P: .003, respectively). In abnormal oocytes, ooplasm diameter was higher in group I compared to group II. Furthermore, ooplasm area for abnormal oocytes was significantly higher in group I compared to group II. There was an increasing trend for number of mature oocytes, in abnormal oocytes, for group I (5.53 ± 3.1) in comparison with group II (4.4 ± 2.97; P = .25). The rate of oocytes with normal morphology was significantly higher in hMG, when compared to rFSH groups. Morphometrical parameters were increased in rFSH group, but the normal morphology of oocytes were significantly enhanced in hMG group. Treatment with proper dosage of ovulation induction drugs may enhance the number of normal sized oocytes. Copyright © 2018. Published by Elsevier B.V.

  10. A COMPARISON OF CLOMIPHENE CITRATE AND SEQUENTIAL CLOMIPHENE CITRATE PLUS HUMAN MENOPAUSAL GONADOTROPIN FOR USE IN CONJUNCTION WITH INTRAUTERINE INSEMINATION

    Directory of Open Access Journals (Sweden)

    B. H. Rashidi

    2005-06-01

    Full Text Available There are currently ‎many different protocols in use for controlled ovarian hyperstimulation (COH, but the optimal method has ‎not yet been determined. To compare the outcome of COH using ‎clomiphene citrate (CC versus CC plus human menopausal gonadotropin (hMG in conjunction with intrauterine insemination (IUI, we studied 117 infertile couples‎. IUI with CC was used in 92 cycles ‎(group A and IUI with CC plus hMG was used in 66 cycles (group B. ‎Data analysis demonstrated no significant difference between the two ‎groups with respect to patients’ age, duration and type of infertility, prior COH and endometrial thickness and pattern. Group A had a little ‎longer follicular phase length than group B. ‎Pregnancy rate for group A and B were 6.52% and 12.12%, respectively (P= 0.22. ‎Endometrial pattern and thickness had no impact on pregnancy rate. ‎There were no multiple gestation and obvious hyperstimulation syndrome. ‎For patients undergoing controlled ovarian hyperstimulation with IUI, ‎CC plus hMG protocol yields higher pregnancy rate than one using CC, although this ‎difference was not statistically significant because of limitation of number of ‎cycles.

  11. Clinical analyses of successful and previously failed intracytoplasmic sperm injection cycle parameters in patients with poor ovarian reserve

    Directory of Open Access Journals (Sweden)

    Tayfun Kutlu

    2017-03-01

    Full Text Available Objective: To determine some major characteristic differences between two consecutive successful and unsuccessful intracytoplasmic sperm injection (ICSI cycles in poor responders. Materials and Methods: Sixty women with poor ovarian response as determined using the Bologna criteria underwent ICSI cycles following an unsuccessful trial. Some parameters of both cycles including age, body mass index (BMI, serum follicle-stimulating hormone (FSH and estradiol levels, antral follicle count, gonadotropin dosage, duration of stimulation, antagonist starting day, duration of antagonist administration, endometrial thickness at trigger day, number of total and fertilized oocytes, embryo transfer day, number of embryo cells, and fertilization rate were compared in the same patients to identify predictors of cycles with clinical pregnancy. Results: The mean age, BMI, serum FSH, estradiol concentrations, and antral follicle count were 35.9 years (range, 30-42 years, 25.9 kg/m2 (range, 18.4-33.5 kg/m2, 10.9 IU/mL (range, 7-13 IU/mL, 52.9 pg/mL (range, 11.6-75 pg/mL, and 4.7 (range, 2-10, respectively. A comparison of cycle characteristics showed a significantly higher total number of mature and fertilized oocytes in successful cycles. The fertilization rate was also significantly higher in cycles with clinical pregnancy. Early initiation of antagonist was shown to result in favorable outcomes. A comparison of embryo characteristics showed that transfer of higher-stage embryos and embryos with higher numbers of cells had a significant impact on cycle outcomes. Conclusion: Our comparison of parameters of failed and successful ICSI cycles in poor responders revealed significantly earlier antagonist initiation, higher total number of mature and fertilized oocytes, fertilization rate, and significantly higher stage of embryo development and cell numbers at transfer in cycles that resulted in clinical pregnancy.

  12. The non-target bi-ovarian branches occlusion in fibroids embolization on resumption of menses and ovarian function

    International Nuclear Information System (INIS)

    Guo Wenbo; Yang Jianyong; Chen Wei; Zhuang Wenquan; Yao Shuzhong

    2005-01-01

    Objective: To evaluate the effect of the non-target bi-ovarian branches occlusion in fibroids embolization on resumption of menses and ovarian function. Methods: The patients with the non-target bi-ovarian branches occlusion in uterine fibroids embolization (UFE) were classified into two groups, one for lipiodol deposited in bi-ovarian areas (Group A) , another for non lipiodol deposited in ovarian areas or in single ovarian area (Group B of non lipiodol deposited in bi-ovarian areas). The statistical difference between the data of group A and group B were assessed with Fisher test. All UFE were performed with the mixture of lipiodol and pingyangmycin. The serum level of Follicle stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E2) were measured before UFE and 6 months after UFE. The statistical difference between the data of before and after UFE was assessed with t test. Results: Fifteen patients [age ranged 26-46 years, average (39.00 ± 5.62) years] had been followed up for an average (30.5±6.4) months (range 16-47 months). In 12 of 15, regular menses resumed after an average of (3.0 ±0.3) weeks (range 2-6 weeks). In 3 of 15 (20%), regular menses did not resume. The sexual hormone findings of menopause were found in three cases with amenorrhea after UFE. Amenorrhea was found in three cases with lipiodol deposited in bi-ovarian areas (Group A). Non-amenorrhea was found in the group of non-lipiodol deposited in bi-ovarian areas (Group B). There were significant statistical difference between Group A and Group B (P=0.002 19). Non amenorrhea was found in the patients aged over 45 years old. Three patients were found amenorrhea in the patients aged younger than 45 years old. There were no significant statistical difference between the serum level of FSH, LH and E2 before and 6 months after UFE (P>0.05). Conclusion: The incidence of amenorrhea is very high in the patients with lipiodol deposited in bi-ovarian areas when the bi-ovarian branches of

  13. Ectopic ovarian pregnancy

    International Nuclear Information System (INIS)

    Sachdev, P.S.; Jatoi, N.; Memon, R.A.; Sachdev, C.S.

    2003-01-01

    A case of ectopic ovarian pregnancy is presented occurring in a 24 years old woman after natural conception. The clinical diagnosis was ruptured tubal pregnancy. Gross findings were suggestive of ruptured corpus luteum cyst on exploration. The histopathological examination of specimen brought forward the diagnosis of ovarian pregnancy. (author)

  14. Effect of Melatonin on the Outcome of Assisted Reproductive Technique Cycles in Women with Diminished Ovarian Reserve: A Double-Blinded Randomized Clinical Trial

    Directory of Open Access Journals (Sweden)

    Bahia Namavar Jahromi

    2017-01-01

    Full Text Available Diminished ovarian reserve (DOR significantly decreases the success rate of the assisted reproductive technique (ART. In this study, we assessed the effect of melatonin on the ART outcomes in women with DOR. A double-blinded, randomized, clinical trial was performed on 80 women with DOR as a pilot study in Shiraz, between 2014 and 2015. DOR was defined as the presence of 2 of the following 3 criteria: 1 anti-Müllerian hormone ≤1, 2 folliclestimulating hormone ≥10, and 3 bilateral antral follicle count ≤6. The women received 3 mg/d melatonin or a placebo since the fifth day of one cycle prior to gonadotropin stimulation and continued the treatment up to the time of ovum pickup. The ART outcomes were compared between the groups using SPSS software. Finally, there were 32 women in the case and 34 in the placebo groups. The mean age and basal ovarian reserve test were the same between the groups. The serum estradiol level on the triggering day was significantly higher in the case group (P=0.005. The mean number of MII oocytes was higher in the case group, but the difference did not reach statistical significance. Number of the patients who had mature MII oocytes (P=0.014, top-quality embryos with grade 1 (P=0.049, and embryos with grades 1 and 2 (P=0.014 was higher among the women who received melatonin. However, the other ART outcomes were not different between the groups. The serum estradiol level was higher and more women with DOR had good-quality oocytes and embryos after receiving melatonin; however, no other outcome was different between the case and control groups. Trial Registration Number: IRCT2014041417264N1

  15. Administration of L-thyroxine does not improve the response of the hypothalamo-pituitary-ovarian axis to clomiphene citrate in functional hypothalamic amenorrhea.

    Science.gov (United States)

    De Leo, V; la Marca, A; Lanzetta, D; Morgante, G

    2000-05-01

    To investigate the hypothalamo-pituitary-ovarian axis in women with functional hypothalamic amenorrhea to determine whether the combination of L-thyroxine and clomiphene citrate produces a qualitative and quantitative increase in induced ovulatory cycles. Gynecological Endocrinology Research Center, University of Siena (Italy). 16 young women with functional hypothalamic amenorrhea and 15 women with normal cycles in early follicular phase. Administration of 50 microgram GnRH and 200 microgram TRH. The women with functional hypothalamic amenorrhea were divided into groups A (n=8) and B (n=8). Both groups were given 100 mg/day clomiphene for 5 days/month for 3 months. Women in group A were also given 75 mcg/day thyroid hormone (L-thyroxine) for 3 months. Comparison of basal and stimulated levels of gonadotropins, TSH and Prl, in groups A and B. Qualitative and quantitative comparison of ovulatory cycles induced in the groups. Administration of clomiphene and clomiphene plus L-thyroxine was evaluated in the second and third months of treatment and was followed by a total of 11 ovulatory cycles, six in group A and five in group B. No significant difference was found between groups. Mean progesterone concentrations measured 16 days after the last clomiphene tablet were 5.5+/-1.2 ng/ml in group A and 5.1+/-1.3 ngl/ml in group B. Administration of L-thyroxine with clomiphene does not improve the response of the hypothalamo-pituitary-ovarian axis to clomiphene citrate or the number of ovulatory cycles and does not reduce luteal phase defects.

  16. Autoimmune premature ovarian failure

    Directory of Open Access Journals (Sweden)

    Beata Komorowska

    2017-02-01

    Full Text Available Premature ovarian failure (POF, also termed as primary ovarian insufficiency (POI, is a highly heterogenous condition affecting 0.5-3.0% of women in childbearing age. These young women comprise quite a formidable group with unique physical and psychological needs that require special attention. Premature ovarian senescence (POS in all of its forms evolves insidiously as a basically asymptomatic process, leading to complete loss of ovarian function, and POI/POF diagnoses are currently made at relatively late stages. Well-known and well-documented risk factors exist, and the presence or suspicion of autoimmune disorder should be regarded as an important one. Premature ovarian failure is to some degree predictable in its occurrence and should be considered while encountering young women with loss of menstrual regularity, especially when there is a concomitant dysfunction in the immune system.

  17. Prevention of ovarian cancer.

    Science.gov (United States)

    Hanna, Louise; Adams, Malcolm

    2006-04-01

    Ovarian cancer is the leading cause of death from gynaecological malignancy. The incidence is high in the Western world. The incidence of ovarian cancer is reduced by pregnancy, lactation, the oral contraceptive pill and tubal ligation. Lifestyle factors are important in the aetiology of ovarian cancer and current evidence suggests the risk can be reduced by eating a diet rich in fruit and vegetables, taking regular exercise, avoiding smoking, avoiding being overweight and avoiding long-term use of hormonal replacement therapy (HRT). Familial ovarian cancer is responsible for about 10% of ovarian cancer cases. Strategies available to high-risk women include screening (covered elsewhere) and prophylactic salpingo-oophorectomy. The precise role of chemoprevention for high-risk women in the form of the oral contraceptive pill is unclear.

  18. Glucocorticoid regulation of gonadotropin release from gonadotropes of ovine pituitary gland in vitro

    International Nuclear Information System (INIS)

    Nangalama, A.W.

    1989-01-01

    In order to understand the role of glucocorticoids in the regulation of gonadotropin release by the pituitary gland, the short-term effects of cortisol perifusion (1.5 h to 8 hrs) on GnRH-induced LH secretion were investigated. To determine the biochemical mechanism(s) by which cortisol can act to modulate GnRH-induced LH release, the interactions of cortisol and arachidonic acid in GnRH-stimulated LH release were examined. Cortisol perifusion for 1.5 hr had no effect on GnRH-induced LH release, but longer treatment periods (4 hr-8 hrs) significantly reduced GnRH-stimulated LH release (4.0 hr, p -4 M AA was administered for 20 min before a 10 min, 10 -10 M GnRH pulse. Like cortisol, chloroquine also failed to inhibit AA-induced LH release. Perifusion with 10 -6 M cortisol for 6.0 hours significantly (p 3 ]AA release 24% below the basal (100%) [ 3 H]AA secretion. Reduction of [ 3 H]AA release was accompanied by decreased GnRH-stimulated LH secretion

  19. Characterization of the Chicken Ovarian Cancer Model

    National Research Council Canada - National Science Library

    Rodriguez, Gustavo

    2002-01-01

    .... Unlike other ovarian cancer models, which require experimental induction of ovarian tumors, chickens develop ovarian adenocarcinoma spontaneously, with an incidence ranging from 13 to 40 percent...

  20. Characterization of the Chicken Ovarian Cancer Model

    National Research Council Canada - National Science Library

    Rodriguez, Gustavo C

    2004-01-01

    .... Unlike other ovarian cancer models, which require experimental induction of ovarian tumors, chickens develop ovarian adenocarcinoma spontaneously, with an incidence ranging from 13 to 40 percent...

  1. Characterization of the Chicken Ovarian Cancer Model

    National Research Council Canada - National Science Library

    Rodriguez, Gustavo C

    2005-01-01

    .... Unlike other ovarian cancer models, which require experimental induction of ovarian tumors, chickens develop ovarian adenocarcinoma spontaneously, with an incidence ranging from 13 to 40 percent...

  2. Characterization of the Chicken Ovarian Cancer Model

    National Research Council Canada - National Science Library

    Rodriguez, Gustavo

    2003-01-01

    .... Unlike other ovarian cancer models, which require experimental induction of ovarian tumors, chickens develop ovarian adenocarcinoma spontaneously, with an incidence ranging from 13 to 40 percent...

  3. Characterization of the Chicken Ovarian Cancer Model

    National Research Council Canada - National Science Library

    Rodriquez, Gustavo

    2001-01-01

    .... Unlike other ovarian cancer models, which require experimental induction of ovarian tumors, chickens develop ovarian adenocarcinoma spontaneously, with an incidence ranging from 13 to 40 percent...

  4. Women with clomiphene citrate resistant polycystic ovarian disease: predictors of spontaneous ovulation after laparoscopic ovarian drilling.

    Science.gov (United States)

    Abuelghar, Wessam M; Bayoumy, Hassan A; Ellaithy, Mohamed I; Khalil, Marian S

    2014-04-01

    To evaluate the role of different clinical, biochemical and sonographic factors as predictors of spontaneous ovulation after laparoscopic ovarian drilling (LOD) in women with clomiphene citrate resistant polycystic ovarian disease (CCR-PCOD). This prospective study recruited 251 infertile women with CCR-PCOD. Several clinical, biochemical and sonographic criteria were tested as possible predictors of spontaneous ovulation after LOD using multivariate analysis. Women with higher preoperative levels of LH, FSH and/or androstenedione had significantly higher rates of spontaneous ovulation within the first eight weeks after LOD, but only FSH and androstenedione were found to be independent predictors. Other factors including age, BMI, type of infertility, duration of infertility, menstrual pattern, testosterone level, ovarian volume and SHBG were insignificant predictors. Receiver-operating characteristic (ROC) curves derived from FSH, LH, androstenedione, and a logistic regression model showed that the best cut-off values were 4.1IU/l, 7.8IU/l, 1.2ng/ml, and 0.4897, respectively, with sensitivity of 91.18%, 100%, 73.53%, and 88.24% and specificity of 69.57%, 69.57%, 65.22%, and 73.91% for FSH, LH, androstenedione, and logistic regression model respectively. An extended follow up (9 months after LOD) was conducted for the anovulatory and the non-pregnant ovulatory women, who were treated individually according to their clinical situation. Of these women, 53.5% (69/129) got pregnant, resulting in a cumulative pregnancy rate of 48% (82/171). Of these pregnancies, 16/82 (19.5%) were spontaneous while 35.4% (29/82) and 45.1% (37/82) occurred after ovulation induction by CC and gonadotropins, respectively. This study supports the use of androstenedione, LH and FSH as a simple reliable tool in triaging patients with CCR-PCOD to select the ideal candidates for LOD. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  5. Induction of ovarian cystic follicles in sheep.

    Science.gov (United States)

    Christman, S A; Bailey, M T; Head, W A; Wheaton, J E

    2000-10-01

    Cystic follicles are a significant cause of infertility in women, dairy cattle and sheep. Sheep were used as a model to identify factors that may elicit formation of cystic follicles. Insulin resistance and elevated LH activity were tested in overweight ewes because of associations among these factors and the formation of cystic follicles. Sheep were synchronized using a progesterone-releasing pessary and insulin resistance was induced during the synchronization period through administration of bovine somatotropin. Following removal of pessaries follicular growth was stimulated by treatment with eCG or eCG and hCG (PG-600). Follicular growth was monitored via daily transrectal ultrasonography and blood samples were collected for hormonal analyses. Six of 18 ewes had a subnormal or absent preovulatory gonadotropin surge and developed cystic follicles. Neither insulin resistance nor elevated LH activity were associated with formation of cystic follicles. Ewes that developed cystic follicles were heavier (93 +/- 4 kg) than ewes that ovulated (81 +/- 3 kg; P = 0.02). Furthermore, following pessary removal and initiation of daily ultrasonography, ewes that developed cystic follicles lost body weight (-3 +/- 1%), while ovulatory ewes continued to gain body weight (1 +/- 1%; P = 0.005). It is speculated that in heavy ewes metabolic factors associated with acute body weight loss inhibit the positive feedback of estradiol and thereby suppress the preovulatory gonadotropin surge leading to formation of cystic follicles.

  6. Effects of pelvic telecobalt irradiation on gonadotropin secretin

    International Nuclear Information System (INIS)

    Pfenninger, R.

    1978-01-01

    The pitnitary reaction in women operated according to Wertheim who had menstruated regularly was investigated during telecobalt irradiation. The pitnitary reaction was observed with the aid of the gonadotropin releasing factor. A dose of 25 mcg RH-LH was applied. Releasing factor examinations were carried out before exposure with functioning ovaries, after a dose of 2000 R (i.e., after 10 exposures), and after 6000 R. In the meantime, separate gonadotropin examinations were carried out continuously. A FSH reaction was observed already after 14 days, and the values were raised to almost menopause values. After this, the FSH increased further, while the LH reaction was not observed until much later. The investigation suggests an interrelation between follicle apparatus and FSH, oestrogens and LH. (orig./AJ) [de

  7. Ovarian volume throughout life

    DEFF Research Database (Denmark)

    Kelsey, Thomas W; Dodwell, Sarah K; Wilkinson, A Graham

    2013-01-01

    conception to 82 years of age. This model shows that 69% of the variation in ovarian volume is due to age alone. We have shown that in the average case ovarian volume rises from 0.7 mL (95% CI 0.4-1.1 mL) at 2 years of age to a peak of 7.7 mL (95% CI 6.5-9.2 mL) at 20 years of age with a subsequent decline...... to about 2.8 mL (95% CI 2.7-2.9 mL) at the menopause and smaller volumes thereafter. Our model allows us to generate normal values and ranges for ovarian volume throughout life. This is the first validated normative model of ovarian volume from conception to old age; it will be of use in the diagnosis......The measurement of ovarian volume has been shown to be a useful indirect indicator of the ovarian reserve in women of reproductive age, in the diagnosis and management of a number of disorders of puberty and adult reproductive function, and is under investigation as a screening tool for ovarian...

  8. Endocrine dynamics during pulsatile GnRH administration in patients with hypothalamic amenorrhea and polycystic ovarian disease.

    Science.gov (United States)

    Rossmanith, W G; Wirth, U; Benz, R; Wolf, A S

    1989-01-01

    The LH secretory patterns and ovarian endocrine responses have been determined during pulsatile gonadotropin-releasing hormone (GnRH) administration for induction of ovulation in patients with hypothalamic amenorrhea (HA). However, until now these endocrine dynamics during GnRH therapy have not been thoroughly investigated in patients with polycystic ovarian disease (PCOD). Seven patients with HA and 4 patients with PCOD have therefore been studied to determine changes in LH pulsatile activity and in serum sex steroid levels in response to chronic intermittent GnRH stimulation. GnRH was administered intravenously (5-10 micrograms/90 minutes) by means of a portable infusion pump. Blood samples were obtained at 15-minute intervals for 4 hours on the day before the start of GnRH stimulation (control day) and on treatment days 5, 10 and 15. LH was determined in all samples and FSH, serum androgens and estrogens were measured in baseline samples by RIA. While 8 (62%) ovulations and 5 conceptions were observed in 13 treatment cycles in patients with HA, no ovulations were achieved during 9 treatment cycles in patients with PCOD. On the control day significantly (p less than 0.05) higher basal LH and testosterone (T) levels and significantly (p less than 0.05) lower FSH levels were found in the PCOD patients. The LH pulsatile profiles of the PCOD patients showed significantly (p less than 0.05) higher pulse amplitudes and areas under the curve (integrated responses). Pulsatile GnRH administration induced a significant (p less than 0.05) increase in LH pulse amplitudes in both HA and PCOD patients, and also increased (p less than 0.05) the integrated responses in patients with HA. During the GnRH stimulation, the LH interpulse intervals of both HA and PCOD patients were found to be similar to the frequency in which exogenous GnRH was administered. FSH levels rose continuously (p less than 0.001) during stimulation in patients with HA, but remained unchanged in patients

  9. Anabolic steroid induced hypogonadism treated with human chorionic gonadotropin.

    OpenAIRE

    Gill, G. V.

    1998-01-01

    A case is presented of a young competitive body-builder who abused anabolic steroid drugs and developed profound symptomatic hypogonadotrophic hypogonadism. With the help of prescribed testosterone (Sustanon) he stopped taking anabolic drugs, and later stopped Sustanon also. Hypogonadism returned, but was successfully treated with weekly injections of human chorionic gonadotropin for three months. Testicular function remained normal thereafter on no treatment. The use of human chorionic gonad...

  10. Pattern of human chorionic gonadotropin binding in the polycystic ovary

    International Nuclear Information System (INIS)

    Brawer, J.; Richard, M.; Farookhi, R.

    1989-01-01

    The histologic evolution of polycystic ovaries in the estradiol valerate-treated rat coincides with the development of a unique plasma pattern of luteinizing hormone. To assess the role of luteinizing hormone in polycystic ovaries, it is necessary to evaluate the luteinizing hormone sensitivity of the specific tissues in the polycystic ovary. Therefore, we examined the pattern of luteinizing hormone binding sites in polycystic ovaries. Rats at 4 or 8 weeks after estradiol valerate treatment each received an intrajugular injection of iodine 125-labeled human chorionic gonadotropin. Some rats also received a 1000-fold excess of unlabeled human chorionic gonadotropin in the same injection. Ovaries were prepared for autoradiography. Dense accumulations of grains occurred over the theca of normal and atretic secondary follicles in all ovaries and over clusters of secondary interstitial cells. The iodine label was variable over the typically hypertrophied theca of precystic follicles. The theca of definitive cysts showed little or no label. These results indicate that cyst formation coincides with the loss of luteinizing hormone/human chorionic gonadotropin binding to the affected follicles

  11. Pattern of human chorionic gonadotropin binding in the polycystic ovary

    Energy Technology Data Exchange (ETDEWEB)

    Brawer, J.; Richard, M.; Farookhi, R. (McGill Univ., Montreal, Quebec (Canada))

    1989-08-01

    The histologic evolution of polycystic ovaries in the estradiol valerate-treated rat coincides with the development of a unique plasma pattern of luteinizing hormone. To assess the role of luteinizing hormone in polycystic ovaries, it is necessary to evaluate the luteinizing hormone sensitivity of the specific tissues in the polycystic ovary. Therefore, we examined the pattern of luteinizing hormone binding sites in polycystic ovaries. Rats at 4 or 8 weeks after estradiol valerate treatment each received an intrajugular injection of iodine 125-labeled human chorionic gonadotropin. Some rats also received a 1000-fold excess of unlabeled human chorionic gonadotropin in the same injection. Ovaries were prepared for autoradiography. Dense accumulations of grains occurred over the theca of normal and atretic secondary follicles in all ovaries and over clusters of secondary interstitial cells. The iodine label was variable over the typically hypertrophied theca of precystic follicles. The theca of definitive cysts showed little or no label. These results indicate that cyst formation coincides with the loss of luteinizing hormone/human chorionic gonadotropin binding to the affected follicles.

  12. Premature ovarian failure and ovarian autoimmunity

    NARCIS (Netherlands)

    J.A. Schoemaker (Joop); H.A. Drexhage (Hemmo); A. Hoek (Annemieke)

    1997-01-01

    textabstractPremature ovarian failure (POF) is defined as a syndrome characterized by menopause before the age of 40 yr. The patients suffer from anovulation and hypoestrogenism. Approximately 1% of women will experience menopause before the age of 40 yr. POF is a

  13. Ovarian Damage during Chemotherapy in Autoimmune Diseases: Broad Health Implications beyond Fertility

    Directory of Open Access Journals (Sweden)

    Wendy Marder

    2012-01-01

    Full Text Available Women with autoimmune diseases such as lupus, scleroderma, and vasculitis receiving cyclophosphamide for severe disease manifestations risk primary ovarian insufficiency (POI due to gonadotoxicity of this therapy. In addition to loss of reproductive potential, POI is associated with increased risk of morbidity and mortality. Practitioners caring for women requiring gonadotoxic therapies should be familiar with long-term health implications of POI and strategies for ovarian preservation. Accumulating evidence supports the effectiveness of adjunctive gonadotropin releasing hormone analog (GnRH-a for ovarian protection during gonadotoxic therapy in cancer and autoimmune populations. GnRH-a is less costly and invasive than assisted reproductive technologies used for achievement of future pregnancies, but is not Food and Drug Administration approved for ovarian preservation. This review focuses on POI comorbidities and strategies for mitigation of related sequelae, which can accumulate over decades of hypoesteogenism. These issues are arguably more pronounced for women with chronic autoimmune diseases, in whom superimposed POI further heightens risks of cardiovascular disease and osteoporosis. Therefore, even if future pregnancy is not desired, ovarian protection during gonadotoxic therapy should be a major goal of disease management.

  14. Ovarian Cancer and Comorbidity

    DEFF Research Database (Denmark)

    Noer, Mette Calundann; Sperling, Cecilie Dyg; Ottesen, Bent

    2017-01-01

    OBJECTIVES: Comorbidity influences survival in ovarian cancer, but the causal relations between prognosis and comorbidity are not well characterized. The aim of this study was to investigate the associations between comorbidity, system delay, the choice of primary treatment, and survival in Danish...... ovarian cancer patients. METHODS: This population-based study was conducted on data from 5317 ovarian cancer patients registered in the Danish Gynecological Cancer Database. Comorbidity was classified according to the Charlson Comorbidity Index and the Ovarian Cancer Comorbidity Index. Pearson χ test...... and multivariate logistic regression analyses were used to investigate the association between comorbidity and primary outcome measures: primary treatment ("primary debulking surgery" vs "no primary surgery") and system delay (more vs less than required by the National Cancer Patient Pathways [NCPPs]). Cox...

  15. Ovarian Cancer FAQ

    Science.gov (United States)

    ... vein thrombosis (DVT) , heart attack, and stroke. Current theories suggest that some types of ovarian cancer may ... Annual Meeting CME Overview CREOG Meetings Calendar Congressional Leadership Conference Advocacy Legislative Priorities GR & Outreach State Advocacy ...

  16. Management of ovarian cysts

    DEFF Research Database (Denmark)

    Knudsen, Ulla Breth; Tabor, Ann; Mosgaard, Berit Jul

    2004-01-01

    BACKGROUND: The treatment of an ovarian cyst relies on its nature, and accurate preoperative discrimination of benign and malignant cysts is therefore of crucial importance. This study was undertaken to review the literature concerning the preoperative diagnosis and treatment of ovarian cysts....... METHODS: Articles concerning ovarian cysts from a medline literature search during the period 1985-2003 were included in addition to articles found as references in the initial publications. RESULTS: Different methods for discriminating between benign and malignant ovarian cysts are discussed....... The diagnosis and the treatment are assessed in relation to age, menopausal status, pregnancy, and whether the cyst is presumed to be benign or malignant. In general, expectant management is the choice in premenopausal and pregnant women with non-suspicious cysts and normal levels of CA-125. In postmenopausal...

  17. Primary ovarian malignant melanoma

    Directory of Open Access Journals (Sweden)

    Kostov Miloš

    2010-01-01

    Full Text Available Background. Primary ovarian malignant melanoma is extremely rare. It usually appears in the wall of a dermoid cyst or is associated with another teratomatous component. Metastatic primary malignant melanoma to ovary from a primary melanoma elsewhere is well known and has been often reported especially in autopsy studies. Case report. We presented a case of primary ovarian malignant melanoma in a 45- year old woman, with no evidence of extraovarian primary melanoma nor teratomatous component. The tumor was unilateral, macroscopically on section presented as solid mass, dark brown to black color. Microscopically, tumor cells showed positive immunohistochemical reaction for HMB-45, melan-A and S-100 protein, and negative immunoreactivity for estrogen and progesteron receptors. Conclusion. Differentiate metastatic melanoma from rare primary ovarian malignant melanoma, in some of cases may be a histopathological diagnostic problem. Histopathological diagnosis of primary ovarian malignant melanoma should be confirmed by immunohistochemical analyses and detailed clinical search for an occult primary tumor.

  18. Intrauterine human chorionic gonadotropin infusion in oocyte donors promotes endometrial synchrony and induction of early decidual markers for stromal survival: a randomized clinical trial.

    Science.gov (United States)

    Strug, Michael R; Su, Renwei; Young, James E; Dodds, William G; Shavell, Valerie I; Díaz-Gimeno, Patricia; Ruíz-Alonso, Maria; Simón, Carlos; Lessey, Bruce A; Leach, Richard E; Fazleabas, Asgerally T

    2016-07-01

    Does a single intrauterine infusion of human chorionic gonadotropin (hCG) at the time corresponding to a Day 3 embryo transfer in oocyte donors induce favorable molecular changes in the endometrium for embryo implantation? Intrauterine hCG was associated with endometrial synchronization between endometrial glands and stroma following ovarian stimulation and the induction of early decidual markers associated with stromal cell survival. The clinical potential for increasing IVF success rates using an intrauterine hCG infusion prior to embryo transfer remains unclear based on previously reported positive and non-significant findings. However, infusion of CG in the non-human primate increases the expression of pro-survival early decidual markers important for endometrial receptivity, including α-smooth muscle actin (α-SMA) and NOTCH1. Oocyte donors (n=15) were randomly assigned to receive an intrauterine infusion of 500 IU hCG (n=7) or embryo culture media vehicle (n=8) 3 days following oocyte retrieval during their donor stimulation cycle. Endometrial biopsies were performed 2 days later, followed by either RNA isolation or tissue fixation in formalin and paraffin embedding. Reverse transcription of total RNA from endometrial biopsies generated cDNA, which was used for analysis in the endometrial receptivity array (ERA; n = 5/group) or quantitative RT-PCR to determine relative expression of ESR1, PGR, C3 and NOTCH1. Tissue sections were stained with hematoxylin and eosin followed by blinded staging analysis for dating of endometrial glands and stroma. Immunostaining for ESR1, PGR, α-SMA, C3 and NOTCH1 was performed to determine their tissue localization. Intrauterine hCG infusion was associated with endometrial synchrony and reprograming of stromal development following ovarian stimulation. ESR1 and PGR were significantly elevated in the endometrium of hCG-treated patients, consistent with earlier staging. The ERA did not predict an overall positive impact of

  19. Estradiol potentiation of gonadotropin-releasing hormone responsiveness in the anterior pituitary is mediated by an increase in gonadotropin-releasing hormone receptors

    International Nuclear Information System (INIS)

    Menon, M.; Peegel, H.; Katta, V.

    1985-01-01

    In order to investigate the mechanism by which 17 beta-estradiol potentiates the action of gonadotropin-releasing hormone on the anterior pituitary in vitro, cultured pituitary cells from immature female rats were used as the model system. Cultures exposed to estradiol at concentrations ranging from 10(-10) to 10(-6) mol/L exhibited a significant augmentation of luteinizing hormone release in response to a 4-hour gonadotropin-releasing hormone (10 mumol/L) challenge at a dose of 10(-9) mol/L compared to that of control cultures. The estradiol augmentation of luteinizing hormone release was also dependent on the duration of estradiol exposure. When these cultures were incubated with tritium-labeled L-leucine, an increase in incorporation of radiolabeled amino acid into total proteins greater than that in controls was observed. A parallel stimulatory effect of estradiol on iodine 125-labeled D-Ala6 gonadotropin-releasing hormone binding was observed. Cultures incubated with estradiol at different concentrations and various lengths of time showed a significant increase in gonadotropin-releasing hormone binding capacity and this increase was abrogated by cycloheximide. Analysis of the binding data showed that the increase in gonadotropin-releasing hormone binding activity was due to a change in the number of gonadotropin-releasing hormone binding sites rather than a change in the affinity. These results suggest that (1) estradiol treatment increases the number of pituitary receptors for gonadotropin-releasing hormone, (2) the augmentary effect of estradiol on luteinizing hormone release at the pituitary level might be mediated, at least in part, by the increase in the number of binding sites of gonadotropin-releasing hormone, and (3) new protein synthesis may be involved in estradiol-mediated gonadotropin-releasing hormone receptor induction

  20. Highly purified human-derived follicle-stimulating hormone (Bravelle® has equivalent efficacy to follitropin-beta (Follistim ® in infertile women undergoing in vitro fertilization

    Directory of Open Access Journals (Sweden)

    Webster Bobby W

    2003-10-01

    Full Text Available Abstract Background These data compare the efficacy and safety of highly purified human-derived follicle-stimulating hormone (Bravelle(R and recombinant follitropin-β (Follistim(R in women undergoing in vitro fertilization. Methods This report describes the pooled data from two, nearly identical, randomized, controlled, parallel-group, multicenter studies conducted in a total of 19 academic and private IVF-ET centers in the United States. Infertile premenopausal women underwent pituitary down-regulation using leuprolide acetate followed by a maximum of 12 days of subcutaneous Bravelle(R (n = 120 or Follistim(R (n = 118, followed by administration of human chorionic gonadotropin, oocyte retrieval and embryo transfer. The primary efficacy measure was the mean number of oocytes retrieved; secondary efficacy measures included the total dose and duration of gonadotropin treatment; peak serum estradion levels; embryo transfer and implantation rates; chemical, clinical and continuing pregnancies; and live birth rates. All adverse events were recorded and injection site pain was recorded daily using a patient, self-assessment diary. Results Similar efficacy responses were observed for all outcome parameters in the two treatment groups. Although patients receiving Bravelle(R consistently reported a greater number of chemical, clinical and continuing pregnancies, as well as an increased rate of live birth, the data did not attain statistical significance (P > 0.05. The overall incidence of adverse events was similar in both groups, but compared to Follistim(R, injections of Bravelle(R were reported by patients to be significantly less painful (P Conclusions Bravelle(R and Follistim(R had comparable efficacy in controlled ovarian hyperstimulation in women undergoing IVF-ET. There were no differences in the nature or number of adverse events between the treatment groups although Bravelle(R injections were reported to be significantly less painful.

  1. Toward developing recombinant gonadotropin-based hormone therapies for increasing fertility in the flatfish Senegalese sole.

    Directory of Open Access Journals (Sweden)

    François Chauvigné

    Full Text Available Captive flatfishes, such as the Senegalese sole, typically produce very low volumes of sperm. This situation is particularly prevalent in the first generation (F1 of reared sole males, which limits the development of artificial fertilization methods and the implementation of selective breeding programs. In this study, we investigated whether combined treatments with homologous recombinant follicle-stimulating (rFsh and luteinizing (rLh hormones, produced in a mammalian host system, could stimulate spermatogenesis and enhance sperm production in Senegalese sole F1 males. In an initial autumn/winter experiment, weekly intramuscular injections with increasing doses of rFsh over 9 weeks resulted in the stimulation of gonad weight, androgen release, germ cell proliferation and entry into meiosis, and the expression of different spermatogenesis-related genes, whereas a subsequent single rLh injection potentiated spermatozoa differentiation. In a second late winter/spring trial corresponding to the sole's natural prespawning and spawning periods, we tested the effect of repeated rLh injections on the amount and quality of sperm produced by males previously treated with rFsh for 4, 6, 8 or 10 weeks. These latter results showed that the combination of rFsh and rLh treatments could increase sperm production up to 7 times, and slightly improve the motility of the spermatozoa, although a high variability in the response was found. However, sustained administration of rFsh during spawning markedly diminished Leydig cell survival and the steroidogenic potential of the testis. These data suggest that in vivo application of rFsh and rLh is effective at stimulating spermatogenesis and sperm production in Senegalese sole F1 males, setting the basis for the future establishment of recombinant gonadotropin-based hormone therapies to ameliorate reproductive dysfunctions of this species.

  2. Ovarian response and pregnancy outcome related to mid-follicular LH levels in women undergoing assisted reproduction with GnRH agonist down-regulation and recombinant FSH stimulation

    DEFF Research Database (Denmark)

    Humaidan, P; Bungum, L; Bungum, M

    2002-01-01

    stimulation with recombinant FSH. METHODS: Blood samples were prospectively collected from a total of 207 normal women undergoing assisted reproduction and analysed retrospectively. Based on LH levels on stimulation day 8 patients were divided into four groups: 1.51 IU/l. RESULTS...

  3. Minimal stimulation IVF vs conventional IVF: a randomized controlled trial

    NARCIS (Netherlands)

    Zhang, John J.; Merhi, Zaher; Yang, Mingxue; Bodri, Daniel; Chavez-Badiola, Alejandro; Repping, Sjoerd; van Wely, Madelon

    2016-01-01

    Minimal stimulation in vitro fertilization (mini-in vitro fertilization) is an alternative in vitro fertilization treatment protocol that may reduce ovarian hyperstimulation syndrome, multiple pregnancy rates, and cost while retaining high live birth rates. We performed a randomized noninferiority

  4. Update on management of ovarian hyperstimulation syndrome

    Directory of Open Access Journals (Sweden)

    Chin-Der Chen

    2011-03-01

    Full Text Available Ovarian hyperstimulation syndrome (OHSS is a relatively common complication of ovarian stimulation and can be life threatening. The pathophysiology of OHSS is characterized by increased capillary permeability, leading to leakage of fluid from the vascular compartment, with third-space fluid accumulation and intravascular dehydration. The increased intra-abdominal pressure indicated that OHSS may be considered a compartment syndrome. Vascular endothelial growth factor, also known as vascular permeability factor, has emerged as one of the mediators intrinsic to the development of OHSS. Conventional management is focused on supportive care until the spontaneous resolution of the condition. The standard of care for treatment—monitoring of appropriate clinical parameters, fluid balance management, thrombosis prophylaxis, and ascites treatment—should prevent severe morbidity in most cases. This review will cover inpatient and outpatient management. The potential therapeutic approach targeting the vascular endothelial growth factor system will be discussed.

  5. [Genetic aspects of premature ovarian failure].

    Science.gov (United States)

    Warenik-Szymankiewicz, Alina; Słopień, Radosław

    2005-01-01

    Among the causes of premature ovarian failure (POF) two groups of factors are reported: factors which lead to decrease of follicular number and factors which stimulate follicular atresia. In the first group genetic factors are the most important whereas in the second: enzymatic autoimmunological, iatrogenic, toxins and infections are reported. In 1986 familiar POF on the background of long arm of chromosome X deletion was reported. Other chromosomes which are important for normal ovarian function are: chromosome 21 (AIRE gene), chromosome 11 (gene of beta FSH, ATM gene), chromosome 3 (gene responsible for BEPS syndrome) and chromosome 2 (genes of FSH and LH receptors). In this review the role of these genes and results of several epidemiological studies are reported.

  6. FSH-FSHR3-stem cells in ovary surface epithelium: basis for adult ovarian biology, failure, aging, and cancer.

    Science.gov (United States)

    Bhartiya, Deepa; Singh, Jarnail

    2015-01-01

    Despite extensive research, genetic basis of premature ovarian failure (POF) and ovarian cancer still remains elusive. It is indeed paradoxical that scientists searched for mutations in FSH receptor (FSHR) expressed on granulosa cells, whereas more than 90% of cancers arise in ovary surface epithelium (OSE). Two distinct populations of stem cells including very small embryonic-like stem cells (VSELs) and ovarian stem cells (OSCs) exist in OSE, are responsible for neo-oogenesis and primordial follicle assembly in adult life, and are modulated by FSH via its alternatively spliced receptor variant FSHR3 (growth factor type 1 receptor acting via calcium signaling and the ERK/MAPK pathway). Any defect in FSH-FSHR3-stem cell interaction in OSE may affect folliculogenesis and thus result in POF. Ovarian aging is associated with a compromised microenvironment that does not support stem cell differentiation into oocytes and further folliculogenesis. FSH exerts a mitogenic effect on OSE and elevated FSH levels associated with advanced age may provide a continuous trigger for stem cells to proliferate resulting in cancer, thus supporting gonadotropin theory for ovarian cancer. Present review is an attempt to put adult ovarian biology, POF, aging, and cancer in the perspective of FSH-FSHR3-stem cell network that functions in OSE. This hypothesis is further supported by the recent understanding that: i) cancer is a stem cell disease and OSE is the niche for ovarian cancer stem cells; ii) ovarian OCT4-positive stem cells are regulated by FSH; and iii) OCT4 along with LIN28 and BMP4 are highly expressed in ovarian cancers. © 2015 Society for Reproduction and Fertility.

  7. Gestational Tubal Choriocarcinoma Presenting as a Pregnancy of Unknown Location following Ovarian Induction

    Directory of Open Access Journals (Sweden)

    Lawrence Hsu Lin

    2018-01-01

    Full Text Available The management of pregnancy of unknown location (PUL can be a challenging situation, since it can present as several different conditions. Here we describe a rare case of gestational choriocarcinoma arising in the fallopian tube after ovarian induction in an infertile patient. The patient received clomiphene for ovarian induction and had rising levels of human chorionic gonadotropin (hCG over nine months without sign of pregnancy. After referral to our center, the patient was diagnosed with a paraovarian tumor, which revealed a gestational choriocarcinoma arising in the fallopian tube; the final diagnosis was supported by pathological and cytogenomic analysis. Malignancies, such as gestational trophoblastic disease, should be in the differential diagnosis of PUL; the early recognition of these conditions is key for the proper treatment and favorable outcome.

  8. Dual Actions of Mammalian and Piscine Gonadotropin-Inhibitory Hormones, RFamide-Related Peptides and LPXRFamide Peptides, in the Hypothalamic–Pituitary–Gonadal Axis

    Directory of Open Access Journals (Sweden)

    Takayoshi Ubuka

    2018-01-01

    Full Text Available Gonadotropin-inhibitory hormone (GnIH is a hypothalamic neuropeptide that decreases gonadotropin synthesis and release by directly acting on the gonadotrope or by decreasing the activity of gonadotropin-releasing hormone (GnRH neurons. GnIH is also called RFamide-related peptide in mammals or LPXRFamide peptide in fishes due to its characteristic C-terminal structure. The primary receptor for GnIH is GPR147 that inhibits cAMP production in target cells. Although most of the studies in mammals, birds, and fish have shown the inhibitory action of GnIH in the hypothalamic–pituitary–gonadal (HPG axis, several in vivo studies in mammals and many in vivo and in vitro studies in fish have shown its stimulatory action. In mouse, although the firing rate of the majority of GnRH neurons is decreased, a small population of GnRH neurons is stimulated by GnIH. In hamsters, GnIH inhibits luteinizing hormone (LH release in the breeding season when their endogenous LH level is high but stimulates LH release in non-breeding season when their LH level is basal. Besides different effects of GnIH on the HPG axis depending on the reproductive stages in fish, higher concentration or longer duration of GnIH administration can stimulate their HPG axis. These results suggest that GnIH action in the HPG axis is modulated by sex-steroid concentration, the action of neuroestrogen synthesized by the activity of aromatase stimulated by GnIH, estrogen membrane receptor, heteromerization and internalization of GnIH, GnRH, and estrogen membrane receptors. The inhibitory and stimulatory action of GnIH in the HPG axis may have a physiological role to maintain reproductive homeostasis according to developmental and reproductive stages.

  9. Premature ovarian failure and ovarian autoimmunity

    OpenAIRE

    Schoemaker, Joop; Drexhage, Hemmo; Hoek, Annemieke

    1997-01-01

    textabstractPremature ovarian failure (POF) is defined as a syndrome characterized by menopause before the age of 40 yr. The patients suffer from anovulation and hypoestrogenism. Approximately 1% of women will experience menopause before the age of 40 yr. POF is a heterogeneous disorder with a multicausal pathogenesis involving chromosomal, genetic, enzymatic, infectious, and iatrogenic causes. There remains, however, a group of POF patients without a known etiology, the so-called "idiopathic...

  10. Multiple metastases from ovarian cancer

    African Journals Online (AJOL)

    Ovarian cancer affects women in the age group >60 years much ... ovarian cancer presenting with liver and thoracic vertebral metastases 4 months after ... manifested by parenchymal liver or lung ... categorised as stage Ic as per International.

  11. The Effect of Oral Feeding of Tribulus terrestris L. on Sex Hormone and Gonadotropin Levels in Addicted Male Rats

    Science.gov (United States)

    Ghosian Moghaddam, Mohammad Hassan; Khalili, Mohsen; Maleki, Maryam; Ahmad Abadi, Mohammad Esmail

    2013-01-01

    Background: Opioids can exert adverse effects on the body. Morphine, an opioid drug, reduces hormone levels and fertility, and causes sexual activity disorders. Tribulus terrestris (TT) is a traditional herbal medicine used to enhance sexual activities. This study investigates the possible role of TT on sex hormones and gonadotropins with the intent to show its usefulness in treating fertility disorders in opioid users. Materials and Methods: In this experimental study, we randomly divided 48 rats into four groups: i. control, ii. TT-treated, iii. addicted and iv. TT-treated addicted. Watersoluble morphine was administrated orally for 21 days to induce addiction, after which the treated groups 2 and 4 received plant-mixed pelleted food (6.25%) orally for four weeks. At the end of the treatment period, the sex hormone and gonadotropin levels of all rats’ sera were determined by radioimmunoassay and Elisa kits. The data obtained were statistically analyzed using the one-way analysis of variance, followed by post-hoc Tukey test. P<0.05 was considered significant. Results: The addicted group had a significantly lower luteinizing hormone (LH) level than the control group (p<0.027). LH levels increased significantly in the TT-treated addicted group (p<0.031). The testosterone level in the treated addicted group was lower than the treated control group. The addicted group had a significantly low testosterone level (p<0.001). The estrogen level was significantly (p<0.002) lower in the addicted group than in the control group. In addition, there was a significant difference between the treated addicted group and the treated control group (p<0.048). The treated control group had a significant increase in its progesterone level (p<0.002). Overall, except for follicle-stimulating hormone (FSH), morphine reduced most of the gonadotropins and sexual hormones. Whereas TT caused a considerable increase (p<0.05) in the hormones in the treated addicted group, there was only a

  12. The Effect of Oral Feeding of Tribulus terrestris L. on Sex Hormone and Gonadotropin Levels in Addicted Male Rats

    Directory of Open Access Journals (Sweden)

    Maryam Maleki

    2013-01-01

    Full Text Available Background: Opioids can exert adverse effects on the body. Morphine, an opioid drug,reduces hormone levels and fertility, and causes sexual activity disorders. Tribulus terrestris(TT is a traditional herbal medicine used to enhance sexual activities. This studyinvestigates the possible role of TT on sex hormones and gonadotropins with the intent toshow its usefulness in treating fertility disorders in opioid users.Materials and Methods: In this experimental study, we randomly divided 48 rats intofour groups: i. control, ii. TT-treated, iii. addicted and iv. TT-treated addicted. Watersolublemorphine was administrated orally for 21 days to induce addiction, after whichthe treated groups 2 and 4 received plant-mixed pelleted food (6.25% orally for fourweeks. At the end of the treatment period, the sex hormone and gonadotropin levels of allrats’ sera were determined by radioimmunoassay and Elisa kits. The data obtained werestatistically analyzed using the one-way analysis of variance, followed by post-hoc Tukeytest. P<0.05 was considered significant.Results: The addicted group had a significantly lower luteinizing hormone (LH levelthan the control group (p<0.027. LH levels increased significantly in the TT-treated addictedgroup (p<0.031. The testosterone level in the treated addicted group was lowerthan the treated control group. The addicted group had a significantly low testosteronelevel (p<0.001. The estrogen level was significantly (p<0.002 lower in the addictedgroup than in the control group. In addition, there was a significant difference betweenthe treated addicted group and the treated control group (p<0.048. The treated controlgroup had a significant increase in its progesterone level (p<0.002. Overall, except forfollicle-stimulating hormone (FSH, morphine reduced most of the gonadotropins andsexual hormones. Whereas TT caused a considerable increase (p<0.05 in the hormonesin the treated addicted group, there was only a slight increase in

  13. 77 FR 4227 - Implantation or Injectable Dosage Form New Animal Drugs; Gonadotropin Releasing Factor Analog...

    Science.gov (United States)

    2012-01-27

    ... Factor Analog-Diphtheria Toxoid Conjugate AGENCY: Food and Drug Administration, HHS. ACTION: Final rule... extends the slaughter interval for intact male swine injected with gonadotropin releasing factor analog...-322 for IMPROVEST (gonadotropin releasing factor analog-diphtheria toxoid conjugate) Sterile Solution...

  14. 76 FR 27888 - Implantation or Injectable Dosage Form New Animal Drugs; Gonadotropin Releasing Factor-Diphtheria...

    Science.gov (United States)

    2011-05-13

    ... Factor-Diphtheria Toxoid Conjugate AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. [[Page... veterinary prescription use of gonadotropin releasing factor-diphtheria toxoid conjugate by subcutaneous... provides for the veterinary prescription use of IMPROVEST (gonadotropin releasing factor-diphtheria toxoid...

  15. Gonadotropin-releasing hormone agonist versus HCG for oocyte triggering in antagonist assisted reproductive technology cycles

    NARCIS (Netherlands)

    Youssef, Mohamed A. F. M.; van der Veen, Fulco; Al-Inany, Hesham G.; Griesinger, Georg; Mochtar, Monique H.; Aboulfoutouh, Ismail; Khattab, Sherif M.; van Wely, Madelon

    2011-01-01

    Background Gonadotropin-releasing hormone (GnRH) antagonist protocols for pituitary down regulation in in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI) allow the use of GnRH agonists for triggering final oocyte maturation. Currently, human chorionic gonadotropin (HCG) is

  16. Expression and role of gonadotropin-releasing hormone 2 and its receptor in mammals

    Science.gov (United States)

    Gonadotropin-releasing hormone (GnRH1) and its receptor (GnRHR1) drive mammalian reproduction via regulation of the gonadotropins. Yet, a second form of GnRH (GnRH2) and its receptor (GnRHR2) also exist in some mammals. GnRH2 has been completely conserved throughout 500 million years of evolution, s...

  17. Elevation of plasma gonadotropin concentration in response to mammalian gonadotropin releasing hormone (GRH) treatment of the male brown trout as determined by radioimmunoassay

    International Nuclear Information System (INIS)

    Crim, L.W.; Cluett, D.M.

    1974-01-01

    Rapid increase of the plasma gonadotropin concentration as measured by radioimmunoassay has been demonstrated in response to GRH treatment of the sexually mature male brown trout. Peak gonadotropin values were observed within 15 minutes of GRH treatment, however, the return to baseline values was prolonged compared with the mammalian response. These data support the concept that the brain, operating via releasing hormones, plays a role in the control of pituitary hormone secretion in fish

  18. Ovarian Stem Cell Nests in Reproduction and Ovarian Aging.

    Science.gov (United States)

    Ye, Haifeng; Zheng, Tuochen; Li, Wei; Li, Xiaoyan; Fu, Xinxin; Huang, Yaoqi; Hu, Chuan; Li, Jia; Huang, Jian; Liu, Zhengyv; Zheng, Liping; Zheng, Yuehui

    2017-01-01

    The fixed primordial follicles pool theory, which monopolized reproductive medicine for more than one hundred years, has been broken by the discovery, successful isolation and establishment of ovarian stem cells. It has brought more hope than ever of increasing the size of primordial follicle pool, improving ovarian function and delaying ovarian consenescence. Traditional view holds that stem cell aging contributes to the senility of body and organs. However, in the process of ovarian aging, the main factor leading to the decline of the reproductive function is the aging and degradation of ovarian stem cell nests, rather than the senescence of ovarian germ cells themselves. Recent studies have found that the immune system and circulatory system are involved in the formation of ovarian germline stem cell niches, as well as regulating the proliferation and differentiation of ovarian germline stem cells through cellular and hormonal signals. Therefore, we can improve ovarian function and delay ovarian aging by improving the immune system and circulatory system, which will provide an updated program for the treatment of premature ovarian failure (POF) and infertility. © 2017 The Author(s). Published by S. Karger AG, Basel.

  19. Ovarian tubercular abscess mimicking ovarian carcinoma: A rare case report

    Directory of Open Access Journals (Sweden)

    Abinash Agarwala

    2015-01-01

    Full Text Available Although genito-urinary tuberculosis is common, reports of isolated ovarian tubercular abscess are rare. Ovarian tubercular abscess may mimics that of an ovarian tumor, leading to diagnostic difficulties. We reported a case report of 35 years woman presented with chronic pain abdomen, weight loss, low-grade fever and a right ovarian mass on ultrasound, with a significantly elevated CA-125 level. On clinical and radiological evidence, diagnosis of ovarian carcinoma was made, and laparotomy was performed with resection of the ovary. Postoperative specimen sent for histological examination that revealed classic epithelioid granuloma and acid-fast bacilli were present in Ziehl-Neelsen stain. Patient was put on antitubercular regimen from our Dots center. She is improving clinical after taking antitubercular drug and is on regular follow up at our chest outpatient department. Ovarian tubercular abscess is common in young women living in endemic zones, but case report of isolated tubercular abscess is rarely reported. CA-125 can be raised in both ovarian tubercular abscess and ovarian carcinoma, and only imaging is not always conclusive. Laparotomy followed by tissue diagnosis can be helpful in this situation. As the prognosis and treatment outcome of ovarian tubercular abscess and ovarian carcinoma is different, proper diagnosis by laparotomy should be done. Early diagnosis of ovarian tubercular abscess is vital as untreated disease can lead to infertility.

  20. Hyperglycosylated human chorionic gonadotropin does not increase progesterone production by luteinized granulosa cells.

    Science.gov (United States)

    Crochet, John R; Shah, Anish A; Schomberg, David W; Price, Thomas M

    2012-09-01

    Trophoblast-derived human chorionic gonadotropin (hCG) promotes corpus luteum progesterone (P4) production, and wide ranges of serum P4 levels are noted in various pregnancy outcomes, despite similar hCG concentrations. There are five unique biologically active hCG variants in human pregnancy urine, and previous studies of P4 production in response to hCG have used only preparations containing all isoforms. Understanding exactly which hCG variant is primarily responsible for stimulating corpus luteum steroidogenesis may have great clinical and diagnostic implications, including in the setting of ectopic pregnancy. Our objective was to delineate the role of the standard and hyperglycosylated (H)-hCG isoforms in stimulating P4 production by luteinized granulosa cells. Cell culture, ELISA, and fluorometric-based protein assays were done at Duke University Medical Center. Patients were anonymous oocyte donors. Cultured luteinized granulosa cells were treated with 0.25, 0.5, and 1.0 ng/ml total hCG, which contains all isoforms, purified standard hCG (37.1 kDa), and purified H-hCG (42.8 kDa). P4 produced per total cellular protein (nanograms per microgram) was measured via ELISA and fluorometric protein determination kits. Both total hCG (P = 0.0003) and purified standard hCG (P production. Purified H-hCG did not change the P4 produced per total cellular protein response (P value not significant). Standard hCG stimulated P4 production by cultured granulosa cells and likely supports corpus luteum function via interactions with the LH/hCG receptor. In contrast, H-hCG did not increase P4 production, which indicates a nonsteroidogenic role for this protein during early gestation.

  1. Is IVF-served two different ways-more cost-effective than IUI with controlled ovarian hyperstimulation?

    NARCIS (Netherlands)

    Tjon-Kon-Fat, R. I.; Bensdorp, A. J.; Bossuyt, P. M. M.; Koks, C.; Oosterhuis, G. J. E.; Hoek, A.; Hompes, P.; Broekmans, F. J.; Verhoeve, H. R.; de Bruin, J. P.; van Golde, R.; Repping, S.; Cohlen, B. J.; Lambers, M. D. A.; van Bommel, P. F.; Slappendel, E.; Perquin, D.; Smeenk, J.; Pelinck, M. J.; Gianotten, J.; Hoozemans, D. A.; Maas, J. W. M.; Groen, H.; Eijkemans, M. J. C.; van der Veen, F.; Mol, B. W. J.; van Wely, M.

    2015-01-01

    What is the cost-effectiveness of in vitro fertilization (IVF) with conventional ovarian stimulation, single embryo transfer (SET) and subsequent cryocycles or IVF in a modified natural cycle (MNC) compared with intrauterine insemination with controlled ovarian hyperstimulation (IUI-COH) as a

  2. Human chorionic gonadotropin, angiogenic factors, and preeclampsia risk: a nested case-control study.

    Science.gov (United States)

    Asvold, Bjørn O; Eskild, Anne; Vatten, Lars J

    2014-05-01

    To study whether human chorionic gonadotropin concentrations during pregnancy or combinations of human chorionic gonadotropin and other angiogenic factors, soluble fms-like tyrosine kinase 1 and placental growth factor (PlGF), are associated with preeclampsia risk. Nested case-control study. Population cohort of pregnant women. A total of 121 cases of preterm (cases of term preeclampsia (≥37 weeks of gestation) and 356 women without preeclampsia (controls). Women with preeclampsia were identified by linkage to the Medical Birth Registry of Norway. Concentrations of human chorionic gonadotropin, soluble fms-like tyrosine kinase 1 and PlGF were measured in maternal serum samples collected in each trimester of pregnancy. Odds ratios of preterm and term preeclampsia. High human chorionic gonadotropin concentrations (highest quartile) in the first trimester were associated with reduced risk for preterm preeclampsia (OR 0.3, 95% CI 0.1-0.9), compared with low human chorionic gonadotropin (lowest quartile), whereas high human chorionic gonadotropin concentrations in the second trimester were associated with increased risk for preterm preeclampsia (OR 4.0, 95% CI 1.8-8.9). High human chorionic gonadotropin concentrations in the third trimester were associated with increased risk for term preeclampsia (OR 4.8, 95% CI 1.8-13.3). Concentrations of human chorionic gonadotropin above the median value combined with PlGF below the median in the second trimester were associated with very high risk for preterm preeclampsia (OR 36.9, 95% CI 8.2-165.8). The results suggest an important role of human chorionic gonadotropin in the pathophysiological processes that lead to preeclampsia. The combined association of human chorionic gonadotropin and PlGF indicates a possible synergism between underlying biological pathways. © 2014 Nordic Federation of Societies of Obstetrics and Gynecology.

  3. Congenital gonadotropin deficiency in boys: management during childhood.

    Science.gov (United States)

    Adan, L; Couto-Silva, A C; Trivin, C; Metz, C; Brauner, R

    2004-02-01

    To analyze the features of boys with congenital gonadotropin deficiency (CGD), and to determine the value of plasma inhibin B and anti-Müllerian hormone (AMH) for predicting testicular function and the effect of testosterone treatment. We followed 19 boys for CGD, including five with Kallmann syndrome. The boys were seen before 14 years of age for micropenis (9 boys) or later for delayed puberty (10 boys). No testis was palpable in the scrotum in 13 patients, bilaterally in seven of them. Luteinizing hormone (LH) peak after a gonadotropin releasing hormone (GnRH) test was between 0.5 and 5.6 U/l. Plasma inhibin B was low in the four patients evaluated at less than 1 year old. AMH was low in one of them and normal in four others. Of the older patients, three lad low plasma inhibin B and four had normal concentrations; plasma AMH was low in three of them and increased in four. Testosterone treatment restored penis length to normal in all patients. Low plasma inhibin B and AMH concentrations may indicate testicular damage in boys with CGD.

  4. Ovarian cancer surgery

    DEFF Research Database (Denmark)

    Seibaek, Lene; Blaakaer, Jan; Petersen, Lone Kjeld

    2013-01-01

    PURPOSE: The study objective was to survey general health and coping in women undergoing ovarian cancer surgery, and subsequently to develop and test a supportive care intervention. METHODS/MATERIALS: Women who underwent surgery on the suspicion of ovarian cancer participated in a follow...... standard levels. Concerning mental health, levels were below standard during the entire period, but did improve with time, also in women in whom the potential cancer diagnosis was refuted. The preoperative differences between these groups leveled out postoperatively in terms of physical health. At the end...

  5. Ovarian Hyperstimulation Syndrome Presenting with Polyserositis: A Case Report

    Directory of Open Access Journals (Sweden)

    Nilay Şengül Samancı

    2014-03-01

    Full Text Available Ovarian hyperstimulation syndrome (OHSS is an iatrogenic complication of ovulation induction with exogenous gonadotropins. Pleural effusion and abdominal ascites frequently accompany this syndrome. In this paper, we present the case of a 22-year-old female patient who was admitted to our clinic with the complaints of sudden chest pain and dyspnea and was treated with ovulation induction. Exudative pleural effusion and ascites were determined in the patient. Pelvic ultrasonography revealed enlarged ovaries with numerous follicular cysts compatible with ovarian hyperstimulation syndrome (OHSS. Her estradiol level was >5054 pg/ml. The diagnosis of OHSS was established after elimination of other causative factors of polyserositis (pleural effusion and ascites. The disappearance of pleural effusion and ascites spontaneously in a week supported our diagnosis. Herein, we aimed to emphasize that OHSS should be considered in the differential diagnosis of polyserositis in young female patients with a history of ovulation induction history. (The Me­di­cal Bul­le­tin of Ha­se­ki 2014; 52: 56-9

  6. Alternative treatment of ovarian cysts with Tribulus terrestris extract: a rat model.

    Science.gov (United States)

    Dehghan, A; Esfandiari, A; Bigdeli, S Momeni

    2012-02-01

    Tribulus terrestris has long been used in traditional medicine to treat impotency and improve sexual functions in man. The aim of this study was to evaluate the efficiency of T. terrestris extract in the treatment of polycystic ovary (PCO) in Wistar rat. Estradiol valerate was injected to 15 mature Wistar rats to induce PCO. Rats were randomly divided into three groups (control, low-dose and high-dose groups) of five each and received 0, 5 and 10 mg of T. terrestris extract, respectively.Treatments began on days 50 and 61 after estradiol injection; at the same time, vaginal smear was prepared. The ovaries were removed on day 62, and histological sections were prepared accordingly. The number and diameter of corpora lutea, thickness of the theca interna layer and the number of all follicles were evaluated in both ovaries. In comparison with the control group, the number of corpora lutea and primary and secondary follicles significantly increased following T. terrestris treatment; however, the number of ovarian cysts significantly decreased. It can be concluded that T. terrestris have a luteinizing effect on ovarian cysts, which may relate to its gonadotropin-like activity; also, a high dose of the extract can efficiently remove ovarian cysts and resume ovarian activity. © 2011 Blackwell Verlag GmbH.

  7. Chorionic gonadotropin regulates the transcript level of VHL, p53, and HIF-2alpha in human granulosa lutein cells.

    Science.gov (United States)

    Herr, D; Keck, C; Tempfer, C; Pietrowski, Detlef

    2004-12-01

    The ovarian corpus luteum plays a critical role in reproduction being the primary source of circulating progesterone. After ovulation the corpus luteum is build by avascular granulosa lutein cells through rapid vascularization regulated by gonadotropic hormones. The present study was performed to investigate whether this process might be influenced by the human chorionic gonadotropin (hCG)-dependent expression of different tumor suppressor genes and hypoxia dependent transcription factors. RNA was isolated from cultured granulosa lutein cells, transcribed into cDNA, and the transcript level of following genes were determined: RB-1, VHL, NF-1, NF-2, Wt-1, p53, APC, and hypoxia inducible factor-1 (HIF-1), -2, and -3alpha. Additionally, the influence of hCG on the expression of VHL, p53, and HIf2alpha were investigated. We demonstrate that in human granulosa lutein cells the tumor suppressor genes RB-1, VHL, NF-1, NF-2, Wt-1, p53, and APC and the hypoxia dependent transcription factors HIF-1alpha, -2alpha, and -3alpha are expressed. In addition, we showed that hCG regulates the expression of p53, VHL, and HIF-2alpha. Our results indicate that hCG may determine the growth and development of the corpus luteum by mediating hypoxic and apoptotic pathways in human granulosa lutein cells. Copyright 2004 Wiley-Liss, Inc.

  8. Biological and biochemical properties of human chorionic gonadotropin from urine of patients with hydatidiform mole and its radioimmunoassay

    International Nuclear Information System (INIS)

    Nishimura, Ryuichiro; Hamamoto, Tamotsu; Tanabe, Keizo; Takemori, Masayuki; Ashitaka, Yoshihiko

    1981-01-01

    Human chorionic gonadotropin (hCG) was extracted and purified from the urine of four patients with hydatidiform mole. The immunological activities of the hCG-hydatidiform mole by hCG radioimmunoassay (RIA) ranged from 9,380 to 9,700 IU/mg, and the biological activities measured by the immature rat ovarian weight method ranged from 7,250 to 7,780 IU/mg. The results of the amino acid compositions of all the hCG-hydatidiform moles were practically identical with those of hCG-normal pregnancies. The carbohydrate moiety of the hCG-hydatidiform mole was also suspected to be almost similar to that of hCG-normal pregnancies by the results of their in vitro and in vivo biological activities. It was demonstrated that hCG-hydatidiform mole was composed of α and β subunits (similar to a hCG-normal pregnancy) when hCG-hydatidiform mole was separated into subunits by SDS disc electrophoresis after treatment with mercaptoethanol. The RIA system of hCG-hydatidiform mole can be established. The concentrations of hCG in sera of normal pregnant women and patients with trophoblastic diseases assayed by hCG-hydatidiform mole RIA were equivalent to those obtained by a standard hCG RIA. Hence, a standard hCG-immunoassay method used in the management of trophoblastic diseases is considered reasonable so far as the immunoantigenecity of hCG is concerned. (author)

  9. Effects of a single administration of different gonadotropins on day 7 post-insemination on pregnancy outcomes of rabbit does.

    Science.gov (United States)

    Hashem, N M; Aboul-Ezz, Z R

    2018-01-01

    This study aimed to investigate the effects of a single administration of one of three different gonadotropins on Day 7 post-insemination on ovarian activity, progesterone (P 4 ) concentration and pregnancy outcomes of rabbit does. Multiparous, non-lactating, V-line does were artificially inseminated after synchronization and ovulation induction with equine chorionic gonadotropin (eCG; 25 IU im) and gonadotropin releasing hormone (GnRH; 0.8  μg buserelin im) 48 h later. On Day 7 post-inseminarion, does were randomly allocated into four groups (n = 40/group). Does of each group were intramuscularly injected with a single dose of one of physiological saline (placebo; control), GnRH (0.8  μg buserelin), human chorionic gonadotropin (hCG; 25 IU) or eCG (25 IU). Concentration of serum P 4 was determined on Days 6, 9, 11 and 18 post-insemination. On Day 14 post-insemination, the ovaries and reproductive tracts of pregnant does were removed and weighed. Also, numbers of visible follicles, hemorrhagic follicles, corpora lutea of pregnancy (pCLs), new CLs (nCLs; formed after Day 7 post-insemination) and implantation sites were recorded. Conception rate, parturition rate, abortion rate, litter size/weight and litter viability were recorded. The highest (P reproductive tract and ovary weights were for eCG. The highest (P rate of fetal loss was in does treated with GnRH. The concentration of serum P 4 decreased (P conception and parturition rates by 24 and 22%; respectively, while GnRH and hCG treatments decreased (P < 0.05) them by 57 and 47.6%; respectively. Litter size and litter weight at birth were improved by eCG, but were adversely affectd by GnRH and hCG. In conclusion, a single administration of eCG 7 Days post-insemination could be recommended for improving pregnancy outcomes in rabbits. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Gonadotropin-Releasing Hormone Modulates Vomeronasal Neuron Response to Male Salamander Pheromone

    Directory of Open Access Journals (Sweden)

    Celeste R. Wirsig-Wiechmann

    2012-01-01

    Full Text Available Electrophysiological studies have shown that gonadotropin-releasing hormone (GnRH modifies chemosensory neurons responses to odors. We have previously demonstrated that male Plethodon shermani pheromone stimulates vomeronasal neurons in the female conspecific. In the present study we used agmatine uptake as a relative measure of the effects of GnRH on this pheromone-induced neural activation of vomeronasal neurons. Whole male pheromone extract containing 3 millimolar agmatine with or without 10 micromolar GnRH was applied to the nasolabial groove of female salamanders for 45 minutes. Immunocytochemical procedures were conducted to visualize and quantify relative agmatine uptake as measured by labeling density of activated vomeronasal neurons. The relative number of labeled neurons did not differ between the two groups: pheromone alone or pheromone-GnRH. However, vomeronasal neurons exposed to pheromone-GnRH collectively demonstrated higher labeling intensity, as a percentage above background (75% as compared with neurons exposed to pheromone alone (63%, P < 0.018. Since the labeling intensity of agmatine within neurons signifies the relative activity levels of the neurons, these results suggest that GnRH increases the response of female vomeronasal neurons to male pheromone.

  11. Fertility Rates of Ewes Treated with Medroxyprogesterone and Injected with Equine Chorionic Gonadotropin plus Human Chorionic Gonadotropin in Anoestrous Season

    Directory of Open Access Journals (Sweden)

    I. W. Santos

    2010-01-01

    Full Text Available The aim of the present paper was to investigate the efficiency of the equine chorionic gonadotropin (eCG plus human chorionic gonadotropin (hCG associated with medroxyprogesterone acetate (MAP to estrous ewes synchronization. Ninety Texel ewes were investigated during seasonal anoestrous. The ewes received intravaginal sponges containing MAP (60 mg for nine days. At the time of sponges' withdrawal, the ewes were divided into three groups (G: (1 receiving 2 mL of saline i.m. (n=30, (2 receiving eCG 400 IU i.m. (n=30, and (3 receiving eCG 400 IU plus hCG 200 IU i.m. (n=30. Twelve h after sponges' removal, teaser rams were used to estrus check and remained with the ewes for 96 h. The artificial insemination was made with fresh semen 10 h after estrus detection. The effect of the treatment was not significant for the estrous rates among the groups: 73%, 90%, and 86%, respectively. The main effect was observed in the pregnancy and lambing rates among the groups: 70%, 86%, 56%, and 80%, 120%, 56%, respectively. Based on these results from our study, the use of the MAP—eCG is the best choice to improve the fertility rate on ewes.

  12. Development of New Gonadotropin-Releasing Hormone-Modified Dendrimer Platforms with Direct Antiproliferative and Gonadotropin Releasing Activity.

    Science.gov (United States)

    Varamini, Pegah; Rafiee, Amirreza; Giddam, Ashwini Kumar; Mansfeld, Friederike M; Steyn, Frederik; Toth, Istvan

    2017-10-26

    Gonadotropin-releasing hormone (GnRH) agonists (e.g., triptorelin) are used for androgen suppression therapy. They possess improved stability as compared to the natural GnRH, yet they suffer from a poor pharmacokinetic profile. To address this, we used a GnRH peptide-modified dendrimer platform with and without lipidation strategy. Dendrimers were synthesized on a polylysine core and bore either native GnRH (1, 2, and 5) or lipid-modified GnRH (3 and 4). Compound 3, which bore a lipidic moiety in a branched tetramer structure, showed approximately 10-fold higher permeability and metabolic stability and 39 times higher antitumor activity against hormone-resistant prostate cancer cells (DU145) relative to triptorelin. In gonadotropin-release experiments, dendrimer 3 was shown to be the most potent construct. Dendrimer 3 showed similar luteinizing hormone (LH)-release activity to triptorelin in mice. Our findings indicate that dendrimer 3 is a promising analog with higher potency for the treatment of hormone-resistant prostate cancer than the currently available GnRH agonists.

  13. Premature ovarian failure

    OpenAIRE

    Pacheco, José

    2011-01-01

    Premature ovarian failure is characterized by secondary amenorrhea affecting a woman before the age of 40, leading to hypoestrogenism, infertility, and consequences of premature menopause, such as osteoporosis, cardiovascular disease, neurovegetative alterations, and others. Follicular exhaustion is due to either follicles shortage or oocytes accelerated destruction. Main causes are genetic, autoimmune and iatrogenic. Among genetic causes Xq and Xp deletions, translocations, numeric aberratio...

  14. Polycystic ovarian syndrome

    OpenAIRE

    Nina Madnani; Kaleem Khan; Phulrenu Chauhan; Girish Parmar

    2013-01-01

    Polycystic ovarian syndrome (PCOS) is a "multispeciality" disorder suspected in patients with irregular menses and clinical signs of hyperandrogenism such as acne, seborrhoea, hirsutism, irregular menses, infertility, and alopecia. Recently, PCOS has been associated with the metabolic syndrome. Patients may develop obesity, insulin resistance, acanthosis nigricans, Type 2 diabetes, dyslipidemias, hypertension, non-alcoholic liver disease, and obstructive sleep apnoea. Good clinical examinatio...

  15. Developmental programming: gestational bisphenol-A treatment alters trajectory of fetal ovarian gene expression.

    Science.gov (United States)

    Veiga-Lopez, Almudena; Luense, Lacey J; Christenson, Lane K; Padmanabhan, Vasantha

    2013-05-01

    Bisphenol-A (BPA), a ubiquitous environmental endocrine disrupting chemical, is a component of polycarbonate plastic and epoxy resins. Because of its estrogenic properties, there is increasing concern relative to risks from exposures during critical periods of early organ differentiation. Prenatal BPA treatment in sheep results in low birth weight, hypergonadotropism, and ovarian cycle disruptions. This study tested the hypothesis that gestational exposure to bisphenol A, at an environmentally relevant dose, induces early perturbations in the ovarian transcriptome (mRNA and microRNA). Pregnant Suffolk ewes were treated with bisphenol A (0.5 mg/kg, sc, daily, produced ∼2.6 ng/mL of unconjugated BPA in umbilical arterial samples of BPA treated fetuses approaching median levels of BPA measured in maternal circulation) from days 30 to 90 of gestation. Expression of steroidogenic enzymes, steroid/gonadotropin receptors, key ovarian regulators, and microRNA biogenesis components were measured by RT-PCR using RNA derived from fetal ovaries collected on gestational days 65 and 90. An age-dependent effect was evident in most steroidogenic enzymes, steroid receptors, and key ovarian regulators. Prenatal BPA increased Cyp19 and 5α-reductase expression in day 65, but not day 90, ovaries. Fetal ovarian microRNA expression was altered by prenatal BPA with 45 down-regulated (>1.5-fold) at day 65 and 11 down-regulated at day 90 of gestation. These included microRNAs targeting Sry-related high-mobility-group box (SOX) family genes, kit ligand, and insulin-related genes. The results of this study demonstrate that exposure to BPA at an environmentally relevant dose alters fetal ovarian steroidogenic gene and microRNA expression of relevance to gonadal differentiation, folliculogenesis, and insulin homeostasis.

  16. A new heterozygous mutation of the FOXL2 gene is associated with a large ovarian cyst and ovarian dysfunction in an adolescent girl with blepharophimosis/ptosis/epicanthus inversus syndrome.

    Science.gov (United States)

    Raile, K; Stobbe, H; Tröbs, R B; Kiess, W; Pfäffle, R

    2005-09-01

    Blepharophimosis/ptosis/epicanthus inversus syndrome (BPES), an autosomal dominant syndrome in which eyelid malformation is associated with (type I BPES) or without premature ovarian failure (type II BPES). Mutations of a putative winged helix/forkhead transcription factor FOXL2 account for both types of BPES. We report on a 16-year-old adolescent girl with blepharophimosis and ptosis. Subsequently she developed oligomenorrhea, secondary amenorrhea for 6 months, and an extremely large cyst of one ovary. The cyst contained 8 l of cyst fluid and histopathology displayed a large corpus luteum cyst. Following laparotomy, gonadotropin levels were elevated (LH 17.2 U/l, FSH 29.4 U/l) and estradiol levels decreased (67 pmol/l). Because of clinical aspects of BPES and abnormal ovarian function we suspected a mutation of her FOXL2 gene and found a new in-frame mutation (904_939dup36) on one allele, leading to a 12 alanine expansion within the polyalanine domain. We conclude that the FOXL2 mutation 904_939dup36 may account not only for blepharophimosis and ptosis but also for ovarian dysfunction and growth of the large corpus luteum cyst. In contrast to known FOXL2 mutations with polyalanine expansions and association with BPES type II, clinical aspects of our girl may indicate some degree of ovarian dysfunction that might finally lead to BPES type I with premature ovarian failure.

  17. Acne tarda and male-pattern baldness unmasking primary ovarian insufficiency: a case and review.

    Science.gov (United States)

    Zouboulis, Christos C; Achenbach, Alexander; Makrantonaki, Eugenia

    2014-01-01

    A 30-year-old woman presented with recurrent acne lesions and progressing male-pattern baldness. Furthermore, she reported amenorrhea, weight loss, mucosal xerosis and dyspareunia since discontinuation of hormonal contraception 6 months earlier in order to conceive. Acne tarda and androgenetic alopecia of female pattern were diagnosed. Hormonal and immunologic serological and ultrasound examinations revealed an autoimmune hypergonadotropic primary ovarian insufficiency (POI) with no ovarian cysts but ovarian fibrosis with marked reduced follicle pool. Immediate ovarian stimulation and in vitro fertilization led to pregnancy and the patient gave birth to a healthy child. Though presenting with clinical findings similar to menopause, 50% of patients with POI exhibit varying and unpredictable ovarian function, and only 5-10% are able to accomplish pregnancy. Genetic disorders affect the X chromosome. In 14-30% of cases POI has been associated with autoimmunity. POI may occur after discontinuation of hormonal contraception, like in our case.

  18. Ovarian chocolate cysts

    International Nuclear Information System (INIS)

    Sugimura, Kazuro; Ishida, Tetsuya; Takemori, Masayuki; Kitagaki, Hajime; Tanaka, Yutaka; Yamasaki, Katsuhito; Shimizu, Tadafumi; Kono, Michio.

    1988-01-01

    Accurate preoperative staging of ovarian chocolate cysts is very important because recent hormonal therapy has been effective in low stage patients. However, it has been difficult to assess the preoperative stage of ovarian chocolate cysts. We evaluated the diagnostic potential of MRI in preoperative staging of 15 overian chocolate cysts. It was well known that the older the ovarian chocolate cyst was the more iron content it had. We examined the iron contents effect on T1 and T2 relaxation times in surgically confirmed chocolate cysts (stage II: 3 cases, stage III: 3 cases and stage IV: 9 cases by AFS classification, 1985) employing the 0.15-T MR system and 200 MHz spectrometer. There was a positive linear relation between T1 of the lesion using the MR system (T1) and T1 of the resected contents using the spectrometer (sp-T1); r = 0.93. The same relation was revealed between T2 and sp-T2; r = 0.87. It was indicated that T1 and T2 using the MR system was accurate. There was a negative linear relation between T1 and the iron contents ( r = -0.81) but no relation between T2 and the iron contents. T1 was 412 ± 91 msec for stage II, 356 ± 126 msec for stage III and 208 ± 30 msec for stage IV. T1 for stage IV was shorter than that for stage II and III, statistically significant differences were noted (p < 0.05). Thus, T1 was useful in differentiating a fresh from an old ovarian chocolate cyst. We concluded that T1 relaxation time using the MR system was useful for the staging of an ovarian chocolate cyst without surgery. (author)

  19. Growth and development in Syrian Awassi ewes during patterns of ovarian follicular different reproductive stages monitored by laparoscopy

    International Nuclear Information System (INIS)

    Zarkawi, M.; Soukouti, A.

    2009-06-01

    An in situ study was conducted on Syrian Awassi ewes, inside and outside the breeding season, untreated or treated with vaginal sponges together with or without equine chorionic gonadotropin aiming at monitoring the ovaries' diameters, number of different follicular categories, number, diameters and lifespan of corpora lutea in each ovary using a laparoscope and finding out the relationship among these parameters and progesterone concentration. For the first time, it has been possible to characterise the Syrian Awassi sheep at the ovarian follicles level during different reproductive stages using a laparoscope. (author)

  20. Does metformin affect ovarian morphology in patients with polycystic ovary syndrome? A retrospective cross-sectional preliminary analysis.

    Science.gov (United States)

    Falbo, Angela; Orio, Francesco; Venturella, Roberta; Rania, Erika; Materazzo, Caterina; Tolino, Achille; Zullo, Fulvio; Palomba, Stefano

    2009-05-31

    The significance of polycystic ovarian morphology and its relation to polycystic ovary syndrome (PCOS) is unclear, but probably it is associated with higher androgen and insulin levels and lower sex hormone binding globulin (SHBG) in absence of identifiable differences in gonadotropin dynamics. The aim of this study was to evaluate ovarian morphology in patients affected by PCOS with different ovulatory responses to metformin. In this cross-sectional analysis, we studied 20 young normal-weight PCOS patients who had received a six-month course of metformin treatment. Ten of these patients remained anovulatory (anovulatory group), whereas other ten became ovulatory, but failed to conceive (ovulatory group). Other ten age- and body mass index (BMI)-matched PCOS subjects were also enrolled as controls and observed without any treatment (control group). After six months of metformin, in both PCOS treated groups, a similar improvement in testosterone (T) and insulin resistance indexes was observed. Moreover, in one (10.0%) and nine (90.0%) subjects from anovulatory and ovulatory PCOS groups, respectively, ovarian morphology changed, whereas a significant reduction in ovarian dimension was observed in the PCOS ovulatory group only. PCOS patients under metformin administration demonstrate a change in ovarian morphology closely related to ovulatory response.

  1. Effect of estradiol on the expression of angiogenic factors in epithelial ovarian cancer.

    Science.gov (United States)

    Valladares, Macarena; Plaza-Parrochia, Francisca; Lépez, Macarena; López, Daniela; Gabler, Fernando; Gayan, Patricio; Selman, Alberto; Vega, Margarita; Romero, Carmen

    2017-11-01

    Ovarian cancer presents a high angiogenesis (formation of new blood vessels) regulated by pro-angiogenic factors, mainly vascular endothelial growth factor (VEGF) and nerve growth factor (NGF). An association between endogenous levels of estrogen and increased risk of developing ovarian cancer has been reported. Estrogen action is mediated by the binding to its specific receptors (ERα and ERβ), altered ERα/ERβ ratio may constitute a marker of ovarian carcinogenesis progression. To determine the effect of estradiol through ERα on the expression of NGF and VEGF in epithelial ovarian cancer (EOC). Levels of phosphorylated estrogen receptor alpha (pERα) were evaluated in well, moderate and poorly differentiated EOC samples (EOC-I, EOC-II, EOC-III). Additionally, ovarian cancer explants were stimulated with NGF (0, 10 and 100 ng/ml) and ERα, ERβ and pERα levels were detected. Finally, human ovarian surface epithelial (HOSE) and epithelial ovarian cancer (A2780) cell lines were stimulated with estradiol, where NGF and VEGF protein levels were evaluated. In tissues, ERs were detected being pERα levels significantly increased in EOC-III samples compared with EOC-I (p<0.05). Additionally, ovarian explants treated with NGF increased pERα levels meanwhile total ERα and ERβ levels did not change. Cell lines stimulated with estradiol revealed an increase of NGF and VEGF protein levels (p<0.05). Estradiol has a positive effect on pro-angiogenic factors such as NGF and VEGF expression in EOC, probably through the activation of ERα; generating a positive loop induced by NGF increasing pERα levels in epithelial ovarian cells.

  2. Human Chorionic Gonadotropin: The Pregnancy Hormone and More

    Directory of Open Access Journals (Sweden)

    Charalampos Theofanakis

    2017-05-01

    Full Text Available To thoroughly review the uses of human chorionic gonadotropin (hCG related to the process of reproduction and also assess new, non-traditional theories. Review of the international literature and research studies. hCG and its receptor, LH/CGR, are expressed in numerous sites of the reproductive tract, both in gonadal and extra-goanadal tissues, promoting oocyte maturation, fertilization, implantation and early embryo development. Moreover, hCG seems to have a potential role as an anti-rejection agent in solid organ transplantation. Future research needs to focus extensively on the functions of hCG and its receptor LH/CGR, in an effort to reveal known, as well as unknown clinical potentials.

  3. Regulation of gonadotropin-releasing hormone neurons by glucose

    Science.gov (United States)

    Roland, Alison V.; Moenter, Suzanne M.

    2011-01-01

    Reproduction is influenced by energy balance, but the physiological pathways mediating their relationship have not been fully elucidated. As the central regulators of fertility, gonadotropin-releasing hormone (GnRH) neurons integrate numerous physiological signals, including metabolic cues. Circulating glucose levels regulate GnRH release and may in part mediate the effects of negative energy balance on fertility. Existing evidence suggests that neural pathways originating in the hindbrain, as well as in the hypothalamic feeding nuclei, transmit information concerning glucose availability to GnRH neurons. Here we review recent evidence suggesting that GnRH neurons may directly sense changes in glucose availability by a mechanism involving adenosine monophosphate-activated protein kinase (AMPK). These findings expand our understanding of how metabolic signaling in the brain regulates reproduction. PMID:21855365

  4. Does obesity compromise ovarian reserve markers? A clinician's perspective.

    Science.gov (United States)

    Malhotra, Neena; Bahadur, Anupama; Singh, Neeta; Kalaivani, Mani; Mittal, Suneeta

    2013-01-01

    The aim of the study was to ascertain if increasing body mass index (BMI) adversely affects ovarian reserve among infertile women of Asian origin undergoing in vitro fertilization (IVF). This prospective study on 183 women was carried out in the infertility clinic of All India Institute of Medical Sciences, New Delhi, India. Blood hormonal assay in all patients including follicle-stimulating hormone (FSH), luteinizing hormone (LH) and inhibin B was performed on day 2/3 of a spontaneous cycle. A transvaginal ultrasonographic examination on day 2-5 of the menstrual cycle was done for antral follicle count (AFC) and ovarian volume. A correlation between BMI and ovarian reserve parameters like FSH, LH, inhibin B, antral follicle count and ovarian volume was noted. Age was comparable in the three BMI groups. The mean duration of infertility was 8.38 years. Compared to the normal weight, the overweight and obese women had a statistically significantly low inhibin B (p women had a significantly low AFC (p right side. Incorporating anti-mullerian hormone, a newer marker for ovarian reserve, may benefit these obese infertile women. Further work is required to elucidate the mechanisms underlying the effect of obesity on inhibin B as a marker of ovarian reserve in infertile women. The best marker to check the ovarian reserve is perhaps the woman's performance during an IVF cycle. However, considering the psychological and financial stress of the procedure, it may seem wise to consider counseling of obese women on their expected performance in the first cycle of IVF through such studies.

  5. Unilateral Versus Bilateral Laparoscopic Ovarian Drilling Using Thermal Dose Adjusted According to Ovarian Volume in CC-Resistant PCOS, A Randomized Study.

    Science.gov (United States)

    El-Sayed, Mohamed Lotfy Mohamed; Ahmed, Mostafa Abdo; Mansour, Marwa Abdel Azim; Mansour, Shymma Abdel Azim

    2017-10-01

    This study aimed to evaluate the efficacy of unilateral laparoscopic ovarian drilling versus bilateral laparoscopic ovarian drilling with thermal dose adjusted according to ovarian volume in clomiphene citrate (CC)-resistant PCOS patients in terms of endocrine changes, menstrual cycle resumption, ovulation and pregnancy rates. This study was conducted in the Department of Obstetrics and Gynecology, Zagazig university hospitals. One hundred CC-resistant PCOS patients were divided into two groups. Group (I) (50 patients) underwent unilateral laparoscopic ovarian drilling with thermal dose adjusted according to ovarian volume (60 J/cm 3 of ovarian tissue), and group (II) (50 patients) underwent bilateral laparoscopic ovarian drilling using the same previously mentioned thermal dose. Endocrinal changes and menstrual cycle resumption were assessed within 8 weeks postoperatively, but the ovulation and pregnancy rates were estimated after 6-month follow-up period. There was no statistically significant difference between the two groups as regards demographic data ( p  > 0.05). As regards menstruation cycle resumption (62.5 vs. 81%) ( p  = 0.047), total ovulation rate (54.2 vs. 78.7%) ( p  = 0.011) and cumulative pregnancy rate (33.3 vs. 55.3%) ( p  = 0.031), there was statistically significant difference between both groups. After drilling, there were highly statistically significant decrease in the mean serum levels of luteinizing hormone (LH) and significant decrease in the mean serum levels of testosterone in both groups. Mean serum level of follicle stimulating hormone (FSH) did not change significantly in both groups after drilling. Bilateral laparoscopic ovarian drilling with thermal dose adjusted according to ovarian volume is more effective than the right-sided unilateral technique with thermal dose adjusted according to ovarian volume in terms of menstrual cycle resumption, ovulation and cumulative pregnancy rates in CC-resistant PCOS patients.

  6. GnRH Analogues in the Prevention of Ovarian Hyperstimulation Syndrome

    Science.gov (United States)

    Alama, Pilar; Bellver, Jose; Vidal, Carmen; Giles, Juan

    2013-01-01

    The GnRH analogue (agonist and antagonist GnRH) changed ovarian stimulation. On the one hand, it improved chances of pregnancy to obtain more oocytes and better embryos. This leads to an ovarian hyper-response, which can be complicated by the ovarian hyperstimulation syndrome (OHSS). On the other hand, the GnRH analogue can prevent the incidence of OHSS: GnRH antagonist protocols, GnRH agonist for triggering final oocyte maturation, either together or separately, coasting, and the GnRH analogue may prove useful for avoiding OHSS in high-risk patients. We review these topics in this article. PMID:23825982

  7. Towards prevention of ovarian cancer.

    Science.gov (United States)

    Ali, Aus Tariq

    2018-01-01

    Ovarian cancer is the leading cause of death of all gynaecological cancers. To date, there is no reliable, specific screening procedure for detecting ovarian cancer. The risk factors of ovarian cancer include modifiable and non-modifiable factors. The main goal of the ovarian cancer prevention program is to significantly reduce the risk of development of ovarian cancer and other cancers such as breast and/or peritoneal cancer. The application of non-surgical preventive approaches such as oral contraceptives, parity and breastfeeding has been shown to be highly protective against ovarian cancer development. Targeting inflammation has been also reported to be associated with a protective trend against ovarian cancer and can be achieved through either non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin or lifestyle modifications or both. Lifestyle modification that includes regular exercise, healthy diet supplemented with anti-oxidants and anti-inflammatory elements reduces the risk of the disease even further. Surgical protective approaches include; tubal ligation, hysterectomy and prophylactic bilateral salpingo-oophorectomy and the former is the most effective approach to protect against ovarian cancer. A better understanding of the risk factors of ovarian cancer and the current approaches to prevent it may increase the awareness and help to decrease the incidence of ovarian cancer, increase the five-year survival rate and decrease the mortality rate significantly in the general population especially among those at high risk for ovarian cancer. This review is an attempt to outline a potential program of ovarian cancer prevention and the potential challenges. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  8. Acupuncture for polycystic ovarian syndrome

    Science.gov (United States)

    Jo, Junyoung; Lee, Yoon Jae; Lee, Hyangsook

    2017-01-01

    Abstract Background: This systematic review aimed at summarizing and evaluating the evidence from randomized controlled trials (RCTs) using acupuncture to treat polycystic ovarian syndrome (PCOS), specifically focusing on ovulation rate, menstrual rate, and related hormones. Methods: Fifteen databases were searched electronically through February 2016. Our review included RCTs of women with PCOS; these RCTs compared acupuncture with sham acupuncture, medication, or no treatment. Two reviewers independently extracted data. Data were pooled and expressed as mean differences (MDs) for continuous outcomes and risk ratios for dichotomous outcomes, with 95% confidence intervals (CIs) using a random-effects model. Results: We found a low level of evidence that acupuncture is more likely to improve ovulation rate (MD 0.35, 95% CI: 0.14–0.56) and menstruation rate (MD 0.50, 95% CI: 0.32–0.68) compared with no acupuncture. We found statistically significant pooled benefits of acupuncture treatment as an adjunct to medication in luteinizing hormone (LH), LH/follicular stimulating hormone (FSH) ratio, testosterone, fasting insulin, and pregnancy rates, but the level of evidence was low/very low. Conclusion: There is limited evidence to judge the efficacy and safety of acupuncture on key reproductive outcomes in women with PCOS. Large-scale, long-term RCTs with rigorous methodological input are needed. PMID:28591042

  9. Adjuvant Growth Hormone for Ovulation Induction with Gonadotropins in the Treatment of a Woman with Hypopituitarism

    Directory of Open Access Journals (Sweden)

    Ariadne Daniel

    2012-01-01

    Full Text Available Objective. To report the prestimulation use of adjuvant GH for gonadotropin ovulation induction in a woman with hypopituitarism and GH deficiency who previously failed to respond. Design, Patients, and Measurements. A 31-year-old nulliparous woman presented with hypopituitarism and GH deficiency after failing ovulation induction with high dose gonadotropins. A trial of GH was undertaken for 5 months prior to ovulation induction resulting in normalization of IGF-I levels. Results. Women with hypopituitarism are known to have lower pregnancy rates after ovulation induction with need for higher doses of gonadotropins. A small subset of these patients do not ovulate. This patient had successful ovulation induction and pregnancy with prestimulation GH. Conclusions. This case suggests that the use of adjuvant GH in a GH-deficient patient several months before the use of human menopausal gonadotropin results in ovulation and pregnancy.

  10. GONAD REMATURATION ON Pangasionodon hypophthalmus FEMALE THROUGH INJECTION OF PREGNANT MARE SERUM GONADOTROPIN AND HUMAN CHORIONIC GONADOTROPIN

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    Evi Tahapari

    2014-06-01

    Full Text Available The success of spawning is influenced by internal and external factors. One of the factors that affect the var iabi li ty of Pangasianodon hypophthalmus female reproductive is the change of seasons that cause disrupted continuity of the seed availability, especially in the dry season. In the present study, combination of PMSG (pregnant mare serum gonadotropin + HCG (hormone chorionic gonadotropin hormone injections was done to induce gonad development. The treatments in this study were without hormone injections as control (A, injection of PMSG 10 IU/kg + HCG 10 IU/kg (B, and injection of PMSG 20 IU/kg HCG + 10 IU/kg (C. Injections were conducted at intervals of two weeks as many as six times. The results showed that gonad maturation generally occurs 2-4 weeks after estradiol-17 peak. PMSG + HCG hormone injections gave a significant effect on increasing the quantity and quality of eggs production. The fecundity in the A, B, C treatments, were 233,700±220,676; 300,305±24,581 and 488,433±142,228; respectively. Number of larvae produced from the A, B, C treatments, were 156,979±170,838; 229,997±18,081 and 362,713±101,850; respectively. Combination of PMSG 20 IU/kg + HCG 10 IU/kg hormone injection gave the best result on fecundity and the number of larvae production.

  11. Association of blood groups with ovarian reserve and outcome of in vitro fertilization treatment.

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    Awartani, Khalid; Al Ghabshi, Rahma; Al Shankiti, Hanan; Al Dossari, Mohamed; Coskun, Serdar

    2016-01-01

    The association between ABO blood groups and ovarian reserve in infertile patients has been a point of controversy. The aim of this study was to assess the correlation of certain blood groups with ovarian reserve and response to treatment in patients undergoing infertility treatment. Retrospective medical record review. Infertility clinic in the assisted reproductive technology (ART) unit at King Faisal Specialist Hospital and Research Center, Riyadh Saudi Arabia. All patients under 40 years of age who attended the infertility clinic at a tertiary care centre in 2010 and underwent in vitro fertilization (IVF) treatment in 2010 and 2011 were divided into groups according to blood type, and clinical parameters were compared. The association between blood groups and ovarian reserve using day 3 luteinzing hormone (LH) and follicular stimulating hormone (FSH) levels, and antral follical count (AFC). In 424 patients who underwent 566 IVF cycles, age, LH, FSH and AFC were similar among the different blood groups (P=.9, .1, .5, respectively). with controlled ovarian stimulation, no difference was observed among the four groups in menopausal gonadotrophin (hMG) dose or the duration of stimulation. The number of oocytes retrieved, fertilization rate, cleavage rate, and number of embryos transferred were similar. There was no difference in the cancellation rate or pregnancy rate among the groups. There was no significant association between blood type and ovarian reserve or response during IVF treatment in our population. Anti-Mullerian hormone levels are best correlated with ovarian reserve testing. Unavailability of AMH levels. Retrospective design.

  12. Tubo-ovarian actinomycosis.

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    Shroff C

    1981-01-01

    Full Text Available Actinomycotic infection of the female genital tract is rare. Actinomycosis is a chronic suppurative granulomatous infection that is characterized by formation of abscesses, multiple draining sinuses and appearance of tangled mycelial masses or granules in the discharges and tissue sections. 2 cases of tubo-ovarian actinomycosis are reported. The 1st case presented clinical with gastrointestinal symptoms and a ventral scar hernia following an operation for a non-healing abdominal wound 6 months earlier. The 2nd case sought medical attention for backache and leucorrhea of 4 years′ duration. Exploratory laparotomy in the 1st case revealed tubo-ovarian masses; the vermiform appendix was not traceable. The uterine cavity in the 2nd case harbored a wooden stick. Direct extension from established ileocacal actinomycosis was believed to involve the female genital adnexae in the past. Association of tubo-ovarian actinomycosis with the presence of a foreign body in the female genital tract has been reported sporadically in the literature, yet an increase in the incidence may be expected because of the frequent use of intrauterine contraceptive devices in recent times. It is suggested that in women presenting clinically with vague abdominal symptoms, backache and discharge, actinomycosis should be considered and ruled out with the help of cytologic and proper microbial culture methods. Once the diagnosis is established, the infection can be treated with good results with penicillin.

  13. Intravital Microscopy in Evaluating Patients With Primary Peritoneal, Fallopian Tube, or Stage IA-IV Ovarian Cancer

    Science.gov (United States)

    2018-06-04

    Fallopian Tube Carcinoma; Primary Peritoneal Carcinoma; Stage I Ovarian Cancer; Stage IA Ovarian Cancer; Stage IB Ovarian Cancer; Stage IC Ovarian Cancer; Stage II Ovarian Cancer; Stage IIA Ovarian Cancer; Stage IIB Ovarian Cancer; Stage IIC Ovarian Cancer; Stage III Ovarian Cancer; Stage IIIA Ovarian Cancer; Stage IIIB Ovarian Cancer; Stage IIIC Ovarian Cancer; Stage IV Ovarian Cancer

  14. Decreased Expression of Arginine-Phenylalanine-Amide-Related Peptide-3 Gene in Dorsomedial Hypothalamic Nucleus of Constant Light Exposure Model of Polycystic Ovarian Syndrome

    Science.gov (United States)

    Shaaban, Zahra; Jafarzadeh Shirazi, Mohammad Reza; Nooranizadeh, Mohammad Hossein; Tamadon, Amin; Rahmanifar, Farhad; Ahmadloo, Somayeh; Ramezani, Amin; Zamiri, Mohammad Javad; Razeghian Jahromi, Iman; Sabet Sarvestani, Fatemeh; Hosseinabadi, Omid Koohi

    2018-01-01

    Background An abnormality in pulse amplitude and frequency of gonadotropin releasing hormone (GnRH) secretion is the most characteristics of polycystic ovarian syndrome (PCOS). On the other hand, arginine-phenylalanine-amide (RFamide)-related peptide-3 (RFRP3) inhibits the secretion of GnRH in mammalian hypothalamus. The current study performed in order to investigate the expression of RFRP3 mRNA in the dorsomedial hypothalamic nucleus (DMH) after the induction of PCOS in a rat model of constant light exposure, and the possible role of parity on occurrence of PCOS. Materials and Methods In the experimental study, female nulliparous (n=12) and primiparous (n=12) rats were randomly subdivided into control and PCOS subgroups (n=6). PCOS were induced by 90 days exposure to constant light. After 90 days, blood, brain, and ovaries were sampled. Serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), and testosterone were evaluated. In addition, six adult female ovariectomized rats as a control of real-time polymerase chain reaction (PCR) tests were prepared and in the DMH of all rats, the relative mRNA expression of RFRP3 was assessed. Results Histological evaluation of ovaries represented the polycystic features. In addition, serum concentrations of testosterone in the PCOS subgroups were more than the controls (P<0.05). Furthermore, the relative expression of RFRP3 mRNA in PCOS subgroups was lower than the controls (P<0.05). Conclusion Constant light model of the PCOS-induced rats decreased the gene expression of RFRP3 in the DMH that suggests the decrease of RFRP3 may reduce its inhibitory effect on GnRH during the PCOS pathogenesis. This effect was stronger in the nulliparous rats than the primiparous. PMID:29334206

  15. Comparison between Unilateral and Bilateral Ovarian Drilling in Clomiphene Citrate Resistance Polycystic Ovary Syndrome Patients: A Randomized Clinical Trial of Efficacy

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    Zahiri Sorouri, Ziba; Sharami, Seyede Hajar; Tahersima, Zinab; Salamat, Fatemeh

    2015-01-01

    Background Laparoscopic ovarian drilling (LOD) is an alternative method to induce ovulation in polycystic ovary syndrome (PCOS) patients with clomiphene citrate (CC) resistant instead of gonadotropins. This study aimed to compare the efficacy of unilateral LOD (ULOD) versus bilateral LOD (BLOD) in CC resistance PCOS patients in terms of ovulation and pregnancy rates. Materials and Methods In a prospective randomized clinical trial study, we included 100 PCOS patients with CC resistance attending to Al-Zahra Hospital in Rasht, Guilan Province, Iran, from June 2011 to July 2012. Patients were randomly divided into two ULOD and BLOD groups with equal numbers. The clinical and biochemical responses on ovulation and pregnancy rates were assessed over a 6-month follow-up period. Results Differences in baseline characteristics of patients between two groups prior to laparoscopy were not significant (p>0.05). There were no significant differences between the two groups in terms of clinical and biochemical responses, spontaneous menstruation (66.1 vs. 71.1%), spontaneous ovulation rate (60 vs. 64.4%), and pregnancy rate (33.1 vs. 40%) (p>0.05). Following drilling, there was a significant decrease in mean serum concentrations of luteinizing hormone (LH) (p=0.001) and testosterone (p=0.001) in both the groups. Mean decrease in serum LH (p=0.322) and testosterone concentrations (p=0.079) were not statistically significant between two groups. Mean serum level of follicle stimulating hormone (FSH) did not change significantly in two groups after LOD (p>0.05). Conclusion Based on results of this study, ULOD seems to be equally efficacious as BLOD in terms of ovulation and pregnancy rates (Registration Number: IRCT138903291306N2). PMID:25918587

  16. Decreased Expression of Arginine-Phenylalanine-Amide-Related Peptide-3 Gene in Dorsomedial Hypothalamic Nucleus of Constant Light Exposure Model of Polycystic Ovarian Syndrome

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    Zahra Shaaban

    2018-01-01

    Full Text Available Background An abnormality in pulse amplitude and frequency of gonadotropin releasing hormone (GnRH secretion is the most characteristics of polycystic ovarian syndrome (PCOS. On the other hand, arginine-phenylalanine-amide (RFamide-related peptide-3 (RFRP3 inhibits the secretion of GnRH in mammalian hypothalamus. The current study performed in order to investigate the expression of RFRP3 mRNA in the dorsomedial hypothalamic nucleus (DMH after the induction of PCOS in a rat model of constant light exposure, and the possible role of parity on occurrence of PCOS. Materials and Methods In the experimental study, female nulliparous (n=12 and primiparous (n=12 rats were randomly subdivided into control and PCOS subgroups (n=6. PCOS were induced by 90 days exposure to constant light. After 90 days, blood, brain, and ovaries were sampled. Serum levels of follicle stimulating hormone (FSH, luteinizing hormone (LH, and testosterone were evaluated. In addition, six adult female ovariectomized rats as a control of real-time polymerase chain reaction (PCR tests were prepared and in the DMH of all rats, the relative mRNA expression of RFRP3 was assessed. Results Histological evaluation of ovaries represented the polycystic features. In addition, serum concentrations of testosterone in the PCOS subgroups were more than the controls (P<0.05. Furthermore, the relative expression of RFRP3 mRNA in PCOS subgroups was lower than the controls (P<0.05. Conclusion Constant light model of the PCOS-induced rats decreased the gene expression of RFRP3 in the DMH that suggests the decrease of RFRP3 may reduce its inhibitory effect on GnRH during the PCOS pathogenesis. This effect was stronger in the nulliparous rats than the primiparous.

  17. Improvement of ovarian response and oocyte quality of aged female by administration of bone morphogenetic protein-6 in a mouse model

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    Park Seung S

    2012-12-01

    Full Text Available Abstract Background Advancing female age remains a difficult problem in infertility treatment. Ovarian angiogenesis plays an important role in follicular development and the activation of ovarian angiogenesis has been emerged as a new strategy for the improvement of age-related decline of oocyte quality. BMP-6 affect gonadotropin signals in granulosa cells and it promotes normal fertility by enabling appropriate response to LH and normal oocyte quality. BMP-6 has a potential role in regulation of angiogenesis and regulates the expression of inhibitor of DNA-binding proteins (Ids. Ids involved in the control and timing of follicle selection and granulosa cells differentiation. Especially, Id-1 is well-characterized target of BMP-6 signaling. Therefore, this study investigated whether co-administration of BMP-6 during superovulation process improves ovarian response, oocyte quality and expression of Id-1 and vascular endothelial growth factor (VEGF in the ovary of aged female using a mouse model. Methods Aged C57BL/6 female mice (26–31 weeks old were superovulated by injection with 0.1 mL of 5 IU equine chorionic gonadotropin (eCG containing recombinant mouse BMP-6 at various doses (0, 0.01, 0.1, 1, and 10 ng, followed by injection with 5 IU human chorionic gonadotropin (hCG 48 h later. Then, the mice were immediately paired with an individual male. The aged control group was superovulated without BMP-6. Young mice of 6–9 weeks old were superovulated without BMP-6 as a positive control for superovulation and in vitro culture of embryos. Eighteen hours after hCG injection, zygotes were retrieved and cultured for 4 days. Both ovaries of each mouse were provided in the examination of ovarian expression of Id-1 and VEGF by reverse transcriptase-polymerase chain reaction, western blot, and immunohistochemistry. Results Administration of 0.1 ng BMP-6 significantly increased the number and blastocyst formation rate of oocytes ovulated and ovarian

  18. Lead, selenium and nickel concentrations in epithelial ovarian cancer, borderline ovarian tumor and healthy ovarian tissues.

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    Canaz, Emel; Kilinc, Metin; Sayar, Hamide; Kiran, Gurkan; Ozyurek, Eser

    2017-09-01

    Wide variation exists in ovarian cancer incidence rates suggesting the importance of environmental factors. Due to increasing environmental pollution, trace elements and heavy metals have drawn attention in studies defining the etiology of cancer, but scant data is available for ovarian cancer. Our aim was to compare the tissue concentrations of lead, selenium and nickel in epithelial ovarian cancer, borderline tumor and healthy ovarian tissues. The levels of lead, selenium and nickel were estimated using atomic absorption spectrophotometry in formalin-fixed paraffin-embedded tissue samples. Tests were carried out in 20 malignant epithelial ovarian cancer, 15 epithelial borderline tumor and 20 non-neoplastic healthy ovaries. Two samples were collected for borderline tumors, one from papillary projection and one from the smooth surface of cyst wall. Pb and Ni concentrations were found to be higher both in malignant and borderline tissues than those in healthy ovaries. Concentrations of Pb and Ni in malignant tissues, borderline papillary projections and capsular tissue samples were not different. Comparison of Se concentrations of malignant, borderline and healthy ovarian tissues did not reveal statistical difference. Studied metal levels were not found to be different in either papillary projection or in cyst wall of the borderline tumors. This study revealed the accumulation of lead and nickel in ovarian tissue is associated with borderline and malignant proliferation of the surface epithelium. Accumulation of these metals in epithelial ovarian cancer and borderline ovarian tumor has not been demonstrated before. Copyright © 2017 Elsevier GmbH. All rights reserved.

  19. Increased risk for ovarian cancer and borderline ovarian tumours in subfertile women with endometriosis

    NARCIS (Netherlands)

    Buis, C. C. M.; van Leeuwen, F. E.; Mooij, T. M.; Burger, C. W.; Lambalk, Cornelis B.; Kortman, Marian; Laven, Joop S. E.; Jansen, Cees A. M.; Helmerhorst, Frans M.; Cohlen, Ben J.; Willemsen, Wim N. P.; Smeenk, Jesper M. J.; Simons, Arnold H. M.; van der Veen, Fulco; Evers, Johannes L. H.; van Dop, Peter A.; Macklon, Nicholas S.

    2013-01-01

    Is ovarian or extra-ovarian endometriosis associated with an increased risk of ovarian cancer and borderline ovarian tumours (BOT)? We found a 3- to 8-fold increased risk of ovarian tumours associated with endometriosis: the magnitude of the risk increase depended on the definition of endometriosis.

  20. Bisphenol A and Ovarian Reserve among Infertile Women with Polycystic Ovarian Syndrome

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    Wei Zhou

    2016-12-01

    Full Text Available To better understand possible effects of bisphenol A (BPA exposure on ovarian reserve in women with polycystic ovary syndrome (PCOS, we measured creatinine adjusted urinary BPA (BPA_Cre concentrations and used regression models to evaluate the association between urinary BPA level and antral follicle count (AFC, antimullerian hormone (AMH, day-3 follicle stimulating hormone levels (FSH and inhibin B (INHB in 268 infertile women diagnosed with PCOS. BPA was detected in all women with a median concentration of 2.35 ng/mL (the 25th and 75th percentiles of 1.47 ng/mL and 3.95 ng/mL. A unit increase in BPA_Cre was associated with a significant decrease of 0.34 in AFC (β = −0.34, 95% CI = −0.60, −0.08; p = 0.01. Likewise, BPA was negatively associated with AMH and day-3 FSH levels, but neither of them reached statistical significance. No association was observed between BPA and INHB. Our results suggest that in women with PCOS, BPA may affect ovarian follicles and, therefore, reduce ovarian reserve.

  1. Bisphenol A and Ovarian Reserve among Infertile Women with Polycystic Ovarian Syndrome.

    Science.gov (United States)

    Zhou, Wei; Fang, Fang; Zhu, Wenting; Chen, Zi-Jiang; Du, Yanzhi; Zhang, Jun

    2016-12-27

    To better understand possible effects of bisphenol A (BPA) exposure on ovarian reserve in women with poly