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, the 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), as determined using Review Manager. Heterogeneity was assessed with the I2 statistic. The risk of bias was evaluated using the ROB 2 tool. The 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%) compared to 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%). The multiple pregnancy rate was significantly lower in the LE group (RR: 0.42; 95% CI: 0.18-0.98; I2: 0%).
Conclusions: Letrozole shows greater effectiveness than clomiphene citrate for ovulation induction in women with PCOS, with a lower risk of multiple pregnancy and similar miscarriage risk. These findings support its use as a first-line treatment in clinical practice.
Keywords: PCOS; clomiphene citrate; infertility; letrozole; ovulation induction; polycystic ovary syndrome.