THERAPEUTIC STRATEGIES IN INFERTILITY IN POLYCYSTIC OVARY SYNDROME: A COMPARATIVE ANALYSIS OF LETROZOLE, CLOMIPHENE CITRATE, AND METFORMIN

Abstract

Polycystic Ovary Syndrome (PCOS) is the leading cause of anovulatory infertility worldwide. This study aimed to perform a comparative analysis of therapeutic strategies for infertility in PCOS, focusing on the efficacy and safety of letrozole, clomiphene citrate (CC), and metformin. To this end, an integrative literature review was conducted based on 45 references selected from PubMed, SciELO, LILACS, and Cochrane platforms, published between 2020 and 2026. Results indicate that letrozole shows robust superiority over CC, especially in patients with high BMI, with birth rates up to 15% higher and a lower incidence of Ovarian Hyperstimulation Syndrome (OHSS) and multiple pregnancies (3.4% vs 7.2%). Metformin, although less effective as an isolated inducer, demonstrated indispensable benefits as an adjunct therapy, improving oocyte morphology, reducing DNA fragmentation, and optimizing ovulation rates in patients with severe insulin resistance (high HOMA-IR). Additionally, letrozole favored superior endometrial outcomes by maintaining uterine thickness and vascularization. It is concluded that letrozole has consolidated itself as the first-line therapy, while metformin acts as an essential metabolic adjuvant. Contemporary management of PCOS converges toward precision medicine, based on biomarkers such as AMH and BMI, aiming to maximize gestational success with maternal and fetal safety.