Clomiphene citrate (CC) and
letrozole are the predominant medical interventions for the management of
infertility in patients with
polycystic ovary syndrome (PCOS). To comprehensively summarize the evidence, a systematic review and meta-analysis of randomized clinical trials (RCTs) was carried out to assess the effect of
letrozole and CC on pregnancy outcomes in PCOS patients. We searched PubMed/MEDLINE, Scopus, and Cochrane Central Register of Controlled Trials from inception to January 2023. We included RCTs conducted on PCOS women comparing
letrozole to CC and assessing endometrial thickness, the number and size of follicles, and ovulation and pregnancy rates. The endpoints were summarized as risk ratio (RR) or standardized mean difference (SMD) with 95% confidence interval (CI) using the random-effects model. Heterogeneity was examined using the I2 statistic. Fifty trials met our inclusion criteria. The mean endometrial thickness was significantly higher in the
letrozole group compared to CC group (SMD: 0.89; 95% CI: 0.49, 1.28; I2=97.72%); however, the number of follicles was higher in the CC group (SMD: -0.56; 95% CI: -0.96, -0.17; I2=96.34%). Furthermore,
letrozole intake induced higher ovulation rate (RR: 1.20; 95% CI: 1.13, 1.26; I2=54.49%) and pregnancy rate (RR: 1.44; 95% CI: 1.28, 1.62; I2=65.58%) compared to CC. Compared to CC,
letrozole has a positive effect on endometrial thickness, monofollicular development, and ovulation and pregnancy rates suggesting that
letrozole may be a strong alternative to CC as a first-line medical intervention for chronic
anovulation in PCOS women. Larger studies are warranted to further clarify these findings.