Letrozole and Clomiphene Compared With Letrozole Alone for Ovulation Induction in Women With Polycystic Ovary Syndrome: A Systematic Review and Meta-analysis [ID 2683666

Abstract

INTRODUCTION: Nearly 70% of patients with polycystic ovary syndrome (PCOS) have anovulatory infertility. One therapeutic option is letrozole; however, its comparative efficacy and safety when compared with the association of letrozole and clomiphene citrate are unclear. Therefore, we aimed to compare letrozole and the combined use of letrozole and clomiphene citrate for ovulation induction in PCOS. METHODS: We systematically searched EMBASE, PubMed, and Cochrane databases for randomized controlled trials (RCTs) and observational studies comparing letrozole and clomiphene citrate versus letrozole alone in patients with PCOS. The primary endpoints rate of mature follicles and ovulation were calculated via a random-effects meta-analysis. Statistical analysis was performed using RevMan 5.4.1. Heterogeneity was assessed with I2 statistics and random-risk effect was used. RESULTS: Two RCTs and one observational study comprising 223 patients (mean age, 28.7 years; 49.3% combined therapy) were included. The combined therapy was associated with a higher number of women with mature follicles (>15 mm) (odds ratio [OR] 2.94; 95% CI, 1.66–5.21; P=.0002; I2=0) and ovulations (OR 3.31; 95% CI, 1.91–5.73; P<.0001; I2=0). There was no significant difference between groups in the number of pregnancies and thickness of the endometrial lining. Adverse events, including headache, abdominal bloating, fatigue, back pain, breast discomfort, and night sweats, were similar between groups. CONCLUSION: In women with PCOS and anovulatory infertility, letrozole and clomiphene citrate combined therapy promoted a significant benefit for the maturation of follicles and ovulation, with a similar safety profile compared to letrozole alone.