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Gonadotropin-releasing hormone antagonist versus progestin for the prevention of premature luteinising hormone surges in poor responders undergoing in vitro fertilisation treatment: study protocol for a randomised controlled trial.

ABSTRACT: Progress in vitrification techniques has allowed reproductive physicians to consider new strategies for using progestin as an alternative to a GnRH analogue to improve in vitro fertilisation (IVF). However, the role of progestin in blocking luteinising hormone (LH) surges and its potential in clinical practice are unclear, especially for poor responders. We designed a prospective randomised controlled trial (RCT) to compare the efficacy of a gonadotropin-releasing hormone (GnRH) antagonist and progestin in blocking LH surges and premature ovulation in poor responders.Poor responders who meet the Bologna criteria will be randomised to one of two stimulation regimens-gonadotropin-releasing hormone (GnRH) antagonist or progestin-primed ovarian stimulation (PPOS)-using a computer-generated random number. Fresh embryos were transferred in the GnRH antagonist group and frozen embryos were transferred in the PPOS group. The primary outcome is the incidence of premature LH surges. Secondary outcomes include the number of oocytes retrieved, the number of embryos available for transfer, implantation rates and clinical pregnancy. The sample size for this trial is estimated as 340 participants, with 170 participants in each group. The data analysis will be by intention to treat.To our knowledge, this is the first RCT to examine the efficacy of administering progestin orally to block LH surges and premature ovulation compared with the GnRH antagonist protocols in poor responders undergoing IVF treatment.www.chictr.org.cn . ChiCTR-IPR-17010906 . Registered on 18 March 2017.

SUBMITTER: Wang Y

PROVIDER: S-EPMC6106816 | biostudies-other | 2018 Aug

REPOSITORIES: biostudies-other

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Gonadotropin-releasing hormone antagonist versus progestin for the prevention of premature luteinising hormone surges in poor responders undergoing in vitro fertilisation treatment: study protocol for a randomised controlled trial.

Wang Yun Y Kuang Yanping Y Chen Qiuju Q Cai Renfei R

Trials 20180822 1

<h4>Background</h4>Progress in vitrification techniques has allowed reproductive physicians to consider new strategies for using progestin as an alternative to a GnRH analogue to improve in vitro fertilisation (IVF). However, the role of progestin in blocking luteinising hormone (LH) surges and its potential in clinical practice are unclear, especially for poor responders. We designed a prospective randomised controlled trial (RCT) to compare the efficacy of a gonadotropin-releasing hormone (GnR ...[more]

PMID: 30134964

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Project description:BACKGROUND:Recently, a novel approach with delaying the start of controlled ovarian stimulation along with gonadotropin-releasing hormone (GnRH) antagonist pretreatment for 7?days after estrogen priming for further suppression of endogenous follicle stimulating hormone (FSH) during the early follicular phase, resulting in more FSH-responsive follicles and thus improving synchronous follicular development was introduced. Two clinical trials have examined this strategy and reported controversial results. This study aimed to compare the effect of delayed-start GnRH antagonist protocol and standard GnRH antagonist in patients with poor ovarian response (POR) undergoing in vitro fertilization (IVF)/ intracytoplasmic sperm injection (ICSI). METHODS:This randomized clinical trial was conducted at infertility department of Royan Institute from January 2017 to June 2018. Poor ovarian response was defined according to the Bologna criteria. The eligible women were randomly allocated into an experimental and control groups. In experimental group, patients received delayed-start GnRH antagonist protocol with estrogen priming followed by early follicular-phase GnRH antagonist treatment for 7?days before ovarian stimulation with gonadotropin and in control group, patients treated with estrogen priming antagonist protocol. IVF/ICSI outcomes were compared between groups. RESULTS:Among all the 250 patients examined 156 women were eligible for study and finally 120 patients were allocated to intervention (n?=?60) and control (n?=?60) groups. Demographic characteristics and hormonal profiles of the patients did not differ between groups. The statistical analysis showed that there were significant differences between groups regarding the total dose of used gonadotropins (P?<?0.001), stimulation duration (P?<?0.001), number of retrieved oocytes (P?=?0.01) and top quality embryo (P?<?0.001) and also cancellation (P?=?0.002) and fertilization rates (P?=?0.002). CONCLUSION:On the basis of present results the delayed-start protocol in poor responders can improve the fertilization rate and quality of embryos and reduce the cycle cancellation but have no significant effect on clinical pregnancy rate; however, larger randomized clinical trials are required to compare it with other protocols. TRIAL REGISTRATION:NCT, NCT03134690. Registered 1 May 2017 - Retrospectively registered, http://www.clinicaltrial.gov / NCT03134690.

Project description:BackgroundThe main objective of the present work was to compare the effects of the gonadotropin-releasing hormone agonist (GnRH-a) and GnRH antagonist (GnRH-ant) on the gene expression profiles of oocytes obtained from Iranian infertile couples undergoing in vitro fertilization (IVF).MethodsFifty infertile couples who underwent IVF between June 2012 and November 2013 at the Infertility Center of Tehran Women General Hospital, Tehran University of Medical Sciences, were included in this study. We included women that had undergone IVF treatment because of male factor, tubal factor, or unexplained infertility. The women randomly underwent controlled ovarian stimulation (COS) with either the GnRH-a (n = 26) or the GnRH-ant (n = 24). We obtained 50 germinal vesicle (GV) oocytes donated by women in each group. After the sampling, pool of 50 GV oocytes for each group was separately analyzed by quantitative polymerase chain reaction (qPCR).ResultThe expression levels of Adenosine triphosphatase 6 (ATPase 6), Bone morphogenetic protein 15 (BMP15), and Neuronal apoptosis inhibitory protein (NAIP) genes were significantly upregulated in the GnRH-ant group compared to the GnRH-a group, with the fold change of 3.990 (SD ± 1.325), 6.274 (SD ± 1.542), and 2.156 (SD ± 1.443), respectively, (P < 0.001). Growth differentiation factor 9 (GDF9) mRNA did not have any expression in the GnRH-a group; however, GDF9 mRNA was expressed in the GnRH-ant group. Finally, it was found that the genes involved in the DNA repairing and cell cycle checkpoint did not have any expression in either group.ConclusionThe present study showed, for the first time, the expression levels of genes involved in the cytoplasmic maturity (BMP15, GDF9), adenosine triphosphate production (ATPase 6), and antiapoptotic process (NAIP), in human GV oocytes were significantly higher in the GnRH-anta group than in the GnRH-a group in COS. Higher expression level of these genes when GnRH-ant protocol is applied, this protocol seems to be a more appropriate choice for women with poly cystic ovarian syndrome, because it can probably improve the expression of the aforementioned genes.Trial registrationCurrent Controlled Trials: IRCT 2014031112307 N3.

Project description:Elagolix is an oral gonadotropin-releasing hormone receptor antagonist indicated for the management of endometriosis-associated pain and in combination with estradiol/norethindrone acetate indicated for the management of heavy menstrual bleeding associated with uterine leiomyomas (fibroids) in premenopausal women. Elagolix coadministered with estradiol/norethindrone acetate is in late-stage development for the management of heavy menstrual bleeding associated with uterine fibroids. Based on the in vitro profile of elagolix metabolism and disposition, 9 drug-drug interaction (DDI) studies evaluating the victim and perpetrator characteristics of elagolix were conducted in 144 healthy volunteers. As a victim of cytochrome P450 (CYPs) and transporter-mediated DDIs, elagolix area under the curve (AUC) increased by ∼2-fold following coadministration with ketoconazole and by ∼5- and ∼2-fold with single and multiple doses of rifampin, respectively. As a perpetrator, elagolix decreased midazolam AUC (90% confidence interval) by 54% (50%-59%) and increased digoxin AUC by 32% (23%-41%). Elagolix decreased rosuvastatin AUC by 40% (29%-50%). No clinically significant changes in exposure on coadministration with sertraline or fluconazole occurred. A elagolix 150-mg once-daily regimen should be limited to 6 months with strong CYP3A inhibitors and rifampin because of the potential increase in bone mineral density loss, as described in the drug label. A 200-mg twice-daily regimen is recommended for no more than 1 month with strong CYP3A inhibitors and not recommended with rifampin. Elagolix is contraindicated with strong organic anion transporter polypeptide B1 inhibitors (eg, cyclosporine and gemfibrozil). Consider increasing the doses of midazolam and rosuvastatin when coadministered with elagolix, and individualize therapy based on patient response. Clinical monitoring is recommended for P-glycoprotein substrates with a narrow therapeutic window (eg, digoxin). Dose adjustments are not required for sertraline, fluconazole, bupropion (or any CYP2B6 substrate), or elagolix when coadministered.

Project description:Background: The availability and use of frozen-thawed embryos after controlled ovarian hyperstimulation for assisted reproduction have increased with improvements in vitrification techniques and the rise of gonadotropin-releasing hormone (GnRH) antagonist protocols. Although evidence has shown that frozen-thawed embryo transfers (FETs) result in higher live birth rates than fresh embryo transfers, it is uncertain whether this association exists in cycles employing the GnRH antagonist protocol. Objective: To test the hypothesis that FETs are more likely to result in a live birth than fresh embryo transfers in a GnRH antagonist protocol cycle and to investigate whether frozen blastocyst transfer increases live birth rates compared to fresh blastocyst transfer. Design: A retrospective historical cohort study was conducted using data collected from the Department of Reproductive Medicine of Liuzhou Maternity and Child Healthcare Hospital for 1,437 patients who underwent the GnRH antagonist protocol between 1 January 2015, and 31 December 2020. The primary outcome was the live birth rate, which was compared between fresh embryo transfer and FET, and the secondary outcomes were clinical pregnancy rate and miscarriage rate, which were compared between the two groups. Analyses were adjusted to account for the age of the patient, number of embryo transfers, day of embryo transfer, and type of infertility. Results: Fresh embryo transfers accounted for 1,026 (71.4%) of the 1,437 patients who underwent the GnRH antagonist protocol in our analysis, while FETs accounted for 411 (28.6%). Patients with fresh and frozen-thawed embryos had comparable median body mass index (body mass index; 22.3 [IQR, 24.6-20.0] vs. 22.0 [IQR, 24.5-19.9]). There was a significant difference in the median age of the fresh embryo transfer group (34.0 [IQR, 39.0-30.0]) and the Frozen-thawed embryo transfer group (32.0 [IQR, 37.0-29.0]). Blastocysts were transferred in 14.6% of the fresh embryo transfer cycles and 45.5% of the FET cycles, whereas they account for 10.4% and 13.0% of all patients, respectively. The mean number of embryos transferred was 2 (IQR, 2.0-1.0) for the fresh embryo transfer group and 1 (IQR, 2.0-1.0) for the FET group, with a significant difference in the mean number of embryos transferred. The live birth rate after fresh embryo transfer vs. FET was 28.7% vs. 34.5% (absolute difference, 5.9%; adjusted relative risk [aRR], 1.15 [95% CI, 0.88-1.51]). The clinical pregnancy rates were 39.9% vs. 46.0%, respectively (absolute difference, 6.1%; aRR, 1.10 [95% CI, 0.85-1.43]). The miscarriage rates were 22.5% vs. 23.8%, respectively (absolute difference, 1.3%; aRR, 1.13 [95% CI, 0.75-1.70]). Conclusion: In this retrospective study of women who underwent assisted reproduction using GnRH antagonists, FETs resulted in a higher live birth rates and clinical pregnancy rates than fresh embryo transfers, which parts of these differences were attributable to embryo stage. However, the interpretation of the findings is limited by the possibility of selection and confounding biases.

Dataset Information

Gonadotropin-releasing hormone antagonist versus progestin for the prevention of premature luteinising hormone surges in poor responders undergoing in vitro fertilisation treatment: study protocol for a randomised controlled trial.

Publications

Gonadotropin-releasing hormone antagonist versus progestin for the prevention of premature luteinising hormone surges in poor responders undergoing in vitro fertilisation treatment: study protocol for a randomised controlled trial.

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