Letrozole in GnRH Antagonist IVF for PCOS: A Propensity Score-Matched Study

INTRODUCTION: To evaluate the association of letrozole co-treatment with laboratory and clinical outcomes in women with polycystic ovary syndrome (PCOS) undergoing gonadotropin-releasing hormone (GnRH) antagonist in vitro fertilization (IVF), with live birth as the primary endpoint.
METHODS: This retrospective single-center cohort study included 1,157 eligible cycles (424 letrozole, 733 standard antagonist) treated between January 2015 and December 2023. Letrozole 5 mg/day was administered on cycle days 2–6. The primary outcome was live birth per cycle with embryo transfer, analyzed with multivariable-adjusted modified Poisson regression. Sensitivity analyses included inverse probability of treatment weighting, propensity score matching (n=834), and per-retrieval analysis (n=1,271).
RESULTS: Letrozole was associated with lower peak estradiol (1,187 vs 2,971 pg/mL; p<0.001) and gonadotropin use (1,351 vs 1,497 IU; p<0.001), and higher oocyte (14.4 vs 13.2; p<0.001), mature oocyte (11.2 vs 10.2; p<0.001), and good-quality blastocyst yields (2.0 vs 1.7; p<0.001). Clinical pregnancy (60.4% vs 63.0%; p=0.57) and moderate-to-severe OHSS (5.2% vs 5.9%; p=0.34) did not differ. Live birth was similar (46.9% vs 47.3%; adjusted risk ratio 1.02; 95% CI 0.90–1.15; p=0.80) and remained consistent across all sensitivity analyses.
DISCUSSION AND CONCLUSION: Letrozole co-treatment improved laboratory outcomes and reduced gonadotropin use but did not improve live birth in antagonist IVF for PCOS. These findings do not support routine co-treatment when higher live birth is the goal; selective use may be considered when reducing peak estradiol or gonadotropin requirements is a secondary clinical objective.

Keywords: Polycystic ovary syndrome, In vitro fertilization, Letrozole, GnRH antagonist protocol, Live birth rate