N-Acetylcysteine for Improving Fertility and Metabolic Outcome in Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis

Introduction: N-acetylcysteine (NAC) has emerged as a potential therapeutic agent due to its antioxidant properties and insulin-sensitizing effects. The multifaceted mechanisms of NAC, including glutathione precursor activity and modulation of steroidogenic enzymes, suggest its potential in addressing the complex pathophysiology of PCOS. To evaluate the effectiveness of NAC in improving fertility and metabolic outcomes among women of reproductive age with PCOS through systematic review and meta-analysis of randomized controlled trials. Material/Methods: A comprehensive systematic search was conducted across three databases (PubMed, Scopus, and Science Direct) from January 2010 to November 2025. Only randomized controlled trials involving women with PCOS. Risk of bias was assessed using the Cochrane Collaboration ROB2 tool. Data were analyzed using Review Manager 5.4 software, with risk ratios calculated for dichotomous outcomes and mean differences for continuous outcomes. Results: Eight studies were included in the meta-analysis, which involved 566 participants. NAC-based interventions significantly improved pregnancy rates and ovulation rates. Compared to metformin, NAC demonstrated superior effects in reducing fasting insulin levels and HOMA-IR values. Subgroup analysis revealed that NAC combined with letrozole produced the most pronounced benefits for pregnancy rate and ovulation rate, indicating high consistency of treatment effects across all included studies. Conclusion: NAC significantly improved pregnancy rates, ovulation rates, and insulin sensitivity parameters in women with PCOS, demonstrating its potential as an effective alternative or adjunctive therapy for polycystic ovary syndrome management, particularly when combined with standard ovulation induction agents.