Comparison of Early Follicular-Phase Long-Acting GnRH Agonist and GnRH Antagonist Protocols in Non-overweight Women with Polycystic Ovary Syndrome: A Retrospective Cohort Study

Objective: We compared the risks of moderate-to-severe ovarian hyperstimulation syndrome (OHSS) and the probabilities of cumulative clinical pregnancy between non-overweight women with polycystic ovary syndrome (PCOS) who received early follicular-phase long-acting gonadotropin-releasing hormone (GnRH) agonist or GnRH antagonist protocols. Methods: This single-center retrospective study analyzed a cohort of 600 first-initiated in vitro fertilization/intracytoplasmic sperm injection cycles. Overlap weights were derived from treatment year and pre-treatment demographic, ovarian-reserve, endocrine, infertility, and metabolic variables. Moderate-to-severe OHSS and cumulative clinical pregnancy from linked fresh and frozen embryo transfers were reported as weighted risks, risk differences (RDs), and risk ratios (RRs) with 1000-replicate bootstrap confidence intervals (CIs). Results: All 600 initiated cycles (long agonist, n = 498; antagonist, n = 102) proceeded to oocyte retrieval, with 287 proceeding to fresh transfer, and 308 undergoing freeze-all. After overlap weighting, all modeled covariates had absolute standardized mean differences (SMDs) < 0.001. Moderate-to-severe OHSS occurred in 24/498 (4.8%) long-agonist and 12/102 (11.8%) antagonist cycles (crude P = 0.012); weighted risks were 6.1% and 10.2% (antagonist vs . long agonist: RD, 4.0 percentage points [95% CI, −2.1 to 9.8]; RR, 1.65 [95% CI, 0.69–3.23]). Cumulative clinical pregnancy occurred in 428/498 (85.9%) and 83/102 (81.4%) cycles; weighted risks were 85.3% and 81.4% (RD, −3.9 percentage points [95% CI, −12.2 to 4.6]; RR, 0.95 [95% CI, 0.86–1.05]). Antagonist cycles required a lower median total gonadotropin dose and shorter stimulation. Conclusions: The antagonist protocol reduced gonadotropin exposure and stimulation duration. Differences in moderate-to-severe OHSS and cumulative clinical pregnancy remained uncertain, and larger prospective studies are needed.