A comparison of letrozole regimens for ovulation induction in women with polycystic ovary syndrome

Objective To determine the optimal letrozole regimen for ovulation induction (OI) in women with polycystic ovary syndrome (PCOS) Design Retrospective cohort study. Setting Single academic fertility clinic from 2015 – 2022 Patient(s) 189 OI cycles in 52 patients with PCOS Intervention(s) Patients were prescribed one of four letrozole regimens (group 1: 2.5mg for 5 days, group 2: 2.5mg for 10 days, group 3: 5mg for 5 days, and group 4: 5mg for 10 days). Main outcome measure(s) The primary outcome was ovulation, and secondary outcomes included multi-follicular development, and clinical pregnancy rate, which were analyzed with binary logistic regression. Kaplan-Meier cumulative response curves and a Cox proportional hazard regression model were used for time-dependent analyses. Results Mean age was 30.9 years (standard deviation (SD) 3.6) and body mass index was 32.1 (SD 4.0). Group 2 (odds ratio (OR) 9.12, 95% confidence interval (CI) 1.92-43.25, P=0.005), group 3 (OR 3.40, 95% CI 1.57-7.37, P=0.002), and group 4 (OR 5.94, 95% CI 2.48-14.23, P<0.001) had improved ovulation rates after the starting regimen as compared to group 1. Cumulative ovulation rates exceeded 84% in all groups (P=NS), yet those who received 5mg and/or 10 days achieved ovulation significantly sooner (P<0.01). Multifollicular development was not increased in groups 2-4 as compared to group 1 (P=NS). Groups 2-4 also demonstrated improved time to pregnancy (P<0.01). Conclusions Ovulation rates are improved when starting with letrozole at 5mg and/or a 10-day extended course as compared to the frequently-utilized 2.5mg for 5 days. This may shorten time to ovulation and pregnancy.