ESHRE 2024: Comparison of the Flexible Progestin-Primed Ovarian Stimulation (FPPOS) with the GnRH Antagonist Protocol in Predicted Suboptimal Responders: A Freeze-all Randomized Controlled Trial
Speaker- Zan Shi
Despite significant advancements in stimulation protocols, a considerable proportion of women with poor ovarian response (POR)—ranging from 6% to 35%—continue to exhibit suboptimal responses to controlled ovarian stimulation (COS). The Gonadotropin hormone-releasing hormone (GnRH) antagonist protocol, integral to COS in POR, utilizes early follicular phase progestin administration to suppress endogenous luteinizing hormone (LH) effectively. Alternatively, delaying progestin administration until the mid-follicular phase has shown efficacy in preventing premature LH surges. The progestin-primed ovarian stimulation (PPOS) protocol, characterized by mild pituitary suppression, holds promise for improving outcomes in POR. However, robust evidence from randomized controlled trials (RCTs) is needed to confirm its effectiveness and safety compared to conventional protocols.
The trial aimed to explore the potential of Flexible Protocol Pituitary Suppression (FPPOS) treatment in achieving live birth rates comparable to conventional GnRH antagonist treatment in predicted poor responders. The trial is a single-center prospective non-inferiority randomized controlled trial conducted at Northwest Women's and Children's Hospital in China. It included participants under 40 years old, with Antral follicle count (AFC) below 10, and no intention to undergo fresh embryo transfer. Participants are randomly assigned to undergo either FPPOS or a GnRH antagonist protocol. Controlled ovarian stimulation begins on the second day of the menstrual cycle, with daily injections of GnRH antagonist and Medroxyprogesterone acetate (MPA) tablets. The primary outcome measure is live birth per woman within 20 months of randomization.
The trial between July 2020 and June 2023 involved 484 participants divided into FPPOS and GnRH antagonist groups. Due to COVID-19, 22 women withdrew from the study. The results showed no differences in baseline characteristics, response to ovarian stimulation, duration of stimulation, or trigger method between the two groups. However, the FPPOS group exhibited significantly thinner endometrial thickness and higher serum LH levels on trigger days. The live birth rates were 32.9% in the FPPOS group compared to 13.8% in the GnRH antagonist group.
The study compared live birth outcomes between the FPPOS and GnRH Antagonist Protocol in autologous ovarian stimulation cycles. FPPOS emerged as an effective alternative for women predicted to have suboptimal responses. However, the study's single-center setting and the inability to mix medications are limitations. Some participants had embryos or blastocysts preserved without achieving live births, but these did not affect the study's results. The study concluded that the FPPOS protocol, utilized to prevent premature ovulation in women not intending fresh embryo transfer, is comparable to the GnRH antagonist protocol, which suggests the potential for further studies with greater statistical power.
It compared the Personalized Protocol Ovarian Stimulation (PPOS) and the GnRH antagonist protocol in POR. It found similar doses and durations of follicle-stimulating hormone (FSH) administration in both protocols. A low-dose GnRH regimen was tailored based on age, BMI, and AFC for specific patients. The PPOS protocol demonstrated flexibility in timing, administering progestin twice daily in divided doses of 5 mg each.
European Society of Human Reproduction and Embryology, July 7-10, Amsterdam, The Netherland
