Received June 23, 2025
Accepted February 20, 2026

Objective: This study aimed to synthesize available high-quality randomized controlled trials (RCTs) comparing reproductive outcomes between letrozole (LE) and clomiphene citrate (CC) for ovulation induction in women with PCOS. Methods: Following PRISMA guidelines, this review was registered in PROSPERO (CRD420251013416). A comprehensive search was conducted in PubMed, Cochrane Library, Elsevier, National Library of Medicine, and Google Scholar up to March 2025. A total of 32 RCTs were included. Statistical analysis used a random-effects model to calculate risk ratios (RR) with 95% confidence intervals (CI), using Review Manager. Heterogeneity was assessed with the I2 statistic. Risk of bias was evaluated using the Rob2 tool. Primary outcome was ovulation rate; secondary outcomes included pregnancy, live birth, miscarriage, and multiple pregnancy rates. Results: LE showed higher ovulation (RR: 1.18; 95% CI: 1.11–1.25; I2: 57%) and pregnancy rates (RR: 1.57; 95% CI: 1.39–1.76; I2: 21%) than CC. LE also had a higher live birth rate (RR: 1.54; 95% CI: 1.24–1.91; I2: 35%). Miscarriage rates were similar between groups (RR: 0.97; 95% CI: 0.73–1.28; I2: 0%). Multiple pregnancy rate was significantly lower in the LE group (RR: 0.42; 95% CI: 0.18–0.98; I2: 0%). Conclusion: Letrozole demonstrates greater effectiveness than clomiphene citrate for ovulation induction in women with PCOS, with a lower risk of multiple pregnancy and comparable miscarriage risk. These findings support its use as a first- line agent in clinical practice.