Evaluation of GnRH antagonist pre-treatment before ovarian stimulation in a delayed-start antagonist protocol in normal ovulatory women undergoing IVF/ICSI: a randomized controlled trial (RCT)

Abstract Background: Synchronization of follicles is key to improving ovulation stimulation with the GnRH antagonist protocol. GnRH antagonist administration in the early follicular phase can quickly decrease gonadotrophin (Gn) levels and achieve downregulation before stimulation, which improves synchronization. A small RCT showed that pre-treatment with a GnRH antagonist for three days before stimulation might increase oocyte retrieval but cannot increase the pregnancy rate. This study investigated whether the "delayed-start" protocol in ovulatory women can increase the synchronization of follicles and pregnancy outcomes compared with the conventional GnRH antagonist protocol.Methods: This RCT included 136 normal ovulatory women undergoing IVF/ICSI. Both groups were treated with recombinant FSH (r-FSH) and a flexible GnRH antagonist protocol. The women were randomized into two equal groups with or without GnRH antagonist from day 2 of the menstrual cycle. Our primary outcome was the number of oocytes retrieved. Secondary outcomes included the pregnancy and live birth rates.Results: Both groups had similar baseline characteristics. The number of oocytes retrieved 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 statistical significance among the follicular size differences. The fertilization rate, number of good-quality embryos, implantation rate, pregnancy rate, ongoing pregnancy rate, live birth rate per ET cycle, and miscarriage rate were all similar between the two groups.Conclusion: This large RCT analysed the "delayed-start" GnRH antagonist protocol applied to normal ovulatory women performing IVF/ICSI. The number of oocytes retrieved and pregnancy outcomes did not vary significantly. Future trials need to confirm these findings.Trial registration: Chinese Clinical Trial Registry, ChiCTR1800019730. Registered 26 November 2018,http://www.chictr.org.cn/showproj.aspx?proj=29969.