METFORMIN VERSUS CLOMIPHENE CITRATE FOR OVULATION INDUCTION IN POLYCYSTIC OVARY SYNDROME: A SYSTEMATIC REVIEW

Introduction: Polycystic ovary syndrome is one of the most common causes of anovulatory infertility worldwide and represents a major clinical challenge in reproductive endocrinology. Pharmacological ovulation induction remains the cornerstone of treatment for women with this condition who desire pregnancy, with clomiphene citrate and metformin being among the most frequently prescribed agents. Despite decades of clinical use, uncertainty persists regarding the comparative effectiveness and safety of these drugs, particularly in different phenotypic presentations of the syndrome and in contemporary clinical practice. Objective: The main objective of this systematic review was to compare the efficacy of metformin versus clomiphene citrate for ovulation induction in women with polycystic ovary syndrome. Secondary objectives were to evaluate differences in ovulation rates, clinical pregnancy rates, live birth rates, adverse effects, and treatment tolerability between the two interventions. Methods: A systematic search was conducted in PubMed, Scopus, Web of Science, Cochrane Library, LILACS, ClinicalTrials.gov, and the International Clinical Trials Registry Platform. Randomized and non-randomized clinical studies comparing metformin and clomiphene citrate for ovulation induction in women with polycystic ovary syndrome were eligible. Study selection, data extraction, and risk of bias assessment were performed independently by two reviewers, with qualitative synthesis of outcomes. Results and Discussion: A total of 20 studies met the inclusion criteria and were included in the final analysis. Overall, clomiphene citrate demonstrated higher ovulation and pregnancy rates in the general polycystic ovary syndrome population, whereas metformin showed potential benefits in specific subgroups, particularly women with insulin resistance or obesity. Combined or sequential use of both agents was frequently associated with improved reproductive outcomes, although heterogeneity across studies and variable methodological quality limited definitive conclusions. Conclusion: Current evidence suggests that clomiphene citrate remains the first-line pharmacological agent for ovulation induction in most women with polycystic ovary syndrome, while metformin may play a complementary role in selected patients. Individualized treatment strategies based on metabolic profile and reproductive goals are essential to optimize clinical outcomes.