Flexible progestin-primed ovarian stimulation is a safe and effective alternative to GnRH antagonist protocol in PGT-A cycles

Objective: To test the hypothesis that flexible progestin-primed ovarian stimulation (fPPOS) is non-inferior to the gonadotropin-releasing hormone (GnRH) antagonist protocol in terms of safety and efficacy for patients undergoing controlled ovarian hyperstimulation and preimplantation genetic testing for aneuploidy (PGT-A). Materials and Methods: This retrospective analysis included data from 548 cycles involving 367 women aged 35 to 45 years. The fPPOS and GnRH antagonist groups comprised 307 cycles (56%) and 241 cycles (44%), respectively. All participants underwent absolute blastocyst culture, trophectoderm biopsy, and PGT-A, with advanced maternal age as the sole indication. The primary outcomes were incidence of premature luteinizing hormone (LH) rise (>10 mIU/mL), cycle cancellation due to premature ovulation, and euploid blastocyst rate per injected metaphase II oocyte. Spearman's rho correlation and the generalized linear model (logit) were applied for statistical analysis. Results: The incidence of premature LH rise (8.2% versus 6.6%; p=0.302) and cycle cancellation due to premature ovulation (2% versus 0.4%; p=0.112) did not differ significantly between the fPPOS and GnRH antagonist groups. Maturation, fertilization, and blastulation rates were also similar (p>0.05). The euploid blastocyst rates per biopsy (50.12% versus 53.06%; p=0.317) and per injected metaphase II oocyte (23.84% versus 23.34%; p=0.231) were comparable between groups. Secondary outcomes, including rates of positive pregnancy tests, implantation, ongoing pregnancy, biochemical pregnancy losses, and early miscarriages, were also similar (p>0.05). Conclusion: The fPPOS protocol represents a viable alternative to the GnRH antagonist protocol for patients aged 35 years or older undergoing PGT-A.