Redox Imbalance in Male Infertility: From Empirical Antioxidant Therapy to Precision Medicine and Epigenetic Insights.

Background: Oxidative stress (OS) is a critical factor in male infertility, where excessive reactive oxygen species (ROS) impair sperm quality and DNA integrity. Although physiological ROS levels support sperm maturation, imbalance can trigger oxidative or reductive stress (RS), both harmful to fertility. Thus, empirical antioxidant therapy without confirmed OS may be unwarranted and risk overtreatment. Methods: We searched PubMed for original and review articles on OS, RS, antioxidants, redox imbalance, and male infertility, emphasizing mechanisms, diagnostics, therapeutic outcomes, and epigenetic implications. Main Findings: Although antioxidants may improve semen parameters, their effect on pregnancy and live birth rates remains inconclusive. Conventional diagnostics often overlook redox imbalance, leading to empirical antioxidant use. A precision redox approach-guided by oxidative profiling to assess redox balance-offers a more effective strategy. Although multiple tools have been proposed to assess redox status, identifying a clinically robust and reliable assay remains challenging. Emerging evidence shows that redox imbalance alters nuclear and mitochondrial epigenetics, potentially affecting embryo development and transgenerational health. Conclusion: Managing male infertility should prioritize restoring redox balance rather than eliminating ROS. Future studies should prioritize standardized diagnostics, individualized antioxidant therapy, and a deeper understanding of how redox imbalance affects sperm epigenetics and offspring outcomes.