Efficacy of sequential letrozole and gonadotropin therapy for ovulation induction in women with polycystic ovary syndrome: a systematic review and meta-analysis

Background: Polycystic ovarian syndrome (PCOS) is a genetically diverse endocrine disorder affecting 5% to 20% of reproductive-aged women worldwide. It is a significant cause of hyperandrogenism, anovulatory infertility, menstrual dysfunction, and hirsutism. This meta-analysis assesses the effectiveness of sequential letrozole and gonadotropin therapy as compared to other ovulation induction regimens in women with PCOS. Methods: A comprehensive search was conducted through the PubMed, Embase, Cochrane, Scopus, and clinicaltrials.gov databases for articles relevant from inception up to March 2024. Pooled outcome estimates were reported as odds ratios (OR) and 95% confidence intervals (CI) for dichotomous data, and as mean differences (MD) and 95% CI for continuous data. Statistical heterogeneity was assessed using I 2 and χ 2 statistics. All calculations were performed using RevMan 5.4. Results: This meta-analysis included 8 RCTs involving 932 anovulatory infertile women with PCOS diagnosed by Rotterdam Criteria. We found a statistically significant increase in ovulation rates (OR 1.74; 95% CI 1.02–2.99; P = 0.04; I 2 = 27%) in the treatment group compared to other ovulation induction regimens. There was no difference in pregnancy rates (OR 1.11; 95% CI 0.66–1.87;P = 0.01; I 2 = 60%), number of dominant follicles (MD 0.36; 95% CI −0.18 to 0.91; P = 0.19; I 2 = 97%). The treatment group showed statistically significant reduction in size of dominant follicles (mm) (MD −0.27; 95% CI −0.95 to 0.41;P = 0.04; I 2 = 88%) and increase in endometrial thickness (mm) (MD 0.78; 95% CI 0.19–1.38; P = 0.010; I 2 = 97%). Conclusion: The treatment group saw a significant rise in ovulation rates and endometrial thickness. LE + G may hold clinical significance, but further large-scale, high-quality studies are necessary to establish conclusive evidence.