Comparative Outcomes of Letrozole Versus Clomiphene Citrate for Ovulation Induction in Patients With PCOS: Systematic Review and Meta-Analysis.

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.