A Novel Letrozole Stair-Step Duration Regimen for Ovulation Induction in Women with Polycystic Ovary Syndrome and Letrozole Resistance

Abstract

Background: Letrozole is the first-line treatment for ovulation induction in women with polycystic ovary syndrome (PCOS). However, a subset of patients remains anovulatory despite standard treatment, a condition termed “letrozole resistance”. This retrospective cohort study aimed to evaluate the effectiveness and time efficiency of a novel “letrozole stair-step duration regimen”, which skips progestin-induced withdrawal bleeding and proceeds directly to an extended letrozole course after anovulatory cycles, compared with a previously established “2-step extended letrozole regimen”. Methods: We analyzed 158 women with PCOS and letrozole resistance who underwent ovulation induction at two university-affiliated reproductive centers between March 2018 and September 2024. Participants received either the stair-step duration regimen (n = 62) or the 2-step extended regimen (n = 96). Outcomes compared included follicular development, hormone profiles, ovulation, and pregnancy outcomes. The primary outcome was the ovulation rate. Results: Ovulation rates were comparable between groups [95.16% vs 94.79%]. Clinical pregnancy rates [23.73% (14/59) vs 20.88% (19/91), P = 0.681] and live birth rates [16.95% (11/59) vs 18.68% (17/91), P = 0.824] also showed no significant differences. However, the stair-step group achieved ovulation in a significantly shorter time, with a median of 36 days (interquartile range [IQR] 32–54) versus 47 days (IQR 45–51) in the extended regimen group (P < 0.001). Conclusion: The letrozole stair-step duration regimen is a time-saving and effective ovulation induction protocol for women with PCOS and letrozole resistance, yielding comparable reproductive outcomes in a shorter treatment duration.