Effect of letrozole doses on clinical pregnancy rates in polycystic ovary syndrome: a systematic review and network meta-analysis

• Published in: Gynecological endocrinology Vol. 41; no. 1; p. 2504977
• Main Authors: Sun, Yanting, Wang, Jun, Chen, Guofeng
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis Group 01.12.2025
• Subjects: Aromatase Inhibitors - administration & dosage; drug treatment; Female; Humans; Infertility, Female - drug therapy; Infertility, Female - etiology; letrozole; Letrozole - administration & dosage; network meta-analysis; Ovulation Induction - methods; Polycystic ovary syndrome; Polycystic Ovary Syndrome - drug therapy; Pregnancy; Pregnancy Outcome; Pregnancy Rate; letrozole; Polycystic ovary syndrome; network meta-analysis; pregnancy; drug treatment
• ISSN: 0951-3590; 1473-0766; 1473-0766
• DOI: 10.1080/09513590.2025.2504977

Letrozole, an aromatase inhibitor, is commonly used for ovulation induction in patients with polycystic ovary syndrome (PCOS). However, the effect of different doses of letrozole on pregnancy outcomes remains controversial. This systematic review and network meta‑analysis aims to compare the effects of different doses of letrozole on pregnancy outcomes in PCOS patients. A systematic search was performed in databases such as PubMed, WOS, and Wanfang for randomized clinical trials (RCTs) assessing different doses of letrozole in PCOS patients. The primary outcome was pregnancy outcome. A network meta‑analysis was conducted using Stata 17's network package and the 'netmeta' and 'gemtc' packages in R software. A total of 30 RCTs involving 3663 patients were included, comparing 11 intervention strategies. Compared with 2.5 mg letrozole, 5 mg letrozole (OR = 1.99, 95% CI: 1.47-2.68;  > 0.05), 7.5 mg letrozole (OR = 1.89, 95% CI: 1.17-3.06;  > 0.05), and 7.5 mg letrozole combined with clomiphene (OR = 7.60, 95% CI: 1.33-43.35;  > 0.05) all significantly improved pregnancy outcomes. Additionally, compared with 2.5 mg letrozole combined with human gonadotropin (HMG), 5 mg (OR = 1.12), 7.5 mg (OR = 1.19), and 20 mg (OR = 1.72) letrozole combined with HMG showed improvements in pregnancy rates, though the differences were not statistically significant (  > 0.05). The lack of unpublished studies and non‑English publications may have introduced publication bias. Letrozole treatment significantly improves pregnancy outcomes in PCOS patients. Moderate‑dose letrozole is recommended as the most effective strategy for improving pregnancy outcomes. Further clinical studies are required to confirm these findings.