Abstract
BackgroundSynchronization of follicles is key to improving ovulation stimulation with the gonadotropin-releasing hormone (GnRH) antagonist protocol. GnRH antagonist administration in the early follicular phase can quickly decrease gonadotrophin (Gn) levels and achieve downregulation before stimulation, which may improves synchronization. A previous small randomized controlled study (RCT) showed that pretreatment with a GnRH antagonist for 3 days before stimulation may increase oocyte retrieval but cannot increase the pregnancy rate. This study investigated whether the GnRH antagonist pretreatment protocol in ovulatory women can increase the synchronization of follicles and pregnancy outcomes compared with the conventional GnRH antagonist protocol.MethodsThis RCT included 136 normal ovulatory women undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI). Both groups were treated with recombinant follicle-stimulating hormone (r-FSH) and a flexible GnRH antagonist protocol. The women were randomized into two equal groups with or without GnRH antagonist administration from day 2 of the menstrual cycle for 3 days before stimulation. Our primary outcome was the number of retrieved oocytes. Secondary outcomes included the pregnancy rate and live birth rate.ResultsBoth groups had similar baseline characteristics. The number of retrieved oocytes in the study group was comparable to that in the control group (9.5 [8.0–13.0] vs. 11.0 [7.0–14.8], P = 0.469). There was no significant difference in the follicle size. The fertilization rate, number of good-quality embryos, implantation rate, pregnancy rate, ongoing pregnancy rate, live birth rate per embryonic transfer cycle, and miscarriage rate were similar between the two groups.ConclusionThis large RCT analysed GnRH antagonist pretreatment with the GnRH antagonist protocol applied to normal ovulatory women undergoing IVF/ICSI. The number of retrieved oocytes and pregnancy outcomes did not significantly vary.Trial registrationChinese Clinical Trial Registry, ChiCTR1800019730. Registered 26 November 2018.
Highlights
Synchronization of follicles is key to improving ovulation stimulation with the gonadotropin-releasing hormone (GnRH) antagonist protocol
We evaluated the following secondary adverse safety and pregnancy outcomes among the two study groups: the incidence of moderate to severe ovarian hyperstimulation syndrome (OHSS) [18] and miscarriage rate, which was defined as foetal loss before the 28th week of gestation [17]
There was no significant difference in the amount of GnRH antagonist added after stimulation between the control and study groups (1.08 ± 0.3 vs. 1.09 ± 0.3, P = 0.830); there was a significant difference in the total amount of GnRH antagonist between the control and study groups (1.1 ± 0.3 vs. 1.8 ± 0.3, P < 0.001)
Summary
Synchronization of follicles is key to improving ovulation stimulation with the gonadotropin-releasing hormone (GnRH) antagonist protocol. Zhang et al Reprod Biol Endocrinol (2021) 19:158 application, GnRH antagonists have become widely used tools for controlled ovarian stimulation (COS) cycles because of its advantages, including its shorter duration of stimulation, low cost, and low incidence of ovarian hyperstimulation syndrome (OHSS) [1,2,3]. It has been recognized as being practical and cost-effective for patients with high or poor ovarian responses [4]. Some studies have shown that pretreatment with the oral contraceptive pill (OCP) in the previous menstrual cycle may reduce the ongoing pregnancy rate (OPR) and LBR of the GnRH antagonist protocol [10]; the routine use of oral hormone pretreatment in an antagonist protocol may not be recommended
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