Inflammation and Oxidative Stress in Male Infertility: A Narrative Review.

BACKGROUND: Male infertility affects 8%-15% of couples, with male factors implicated in about half of cases; many remain idiopathic despite improved diagnostics. This narrative review addresses this gap by examining chronic inflammation as an underappreciated driver of sperm dysfunction that forms a bidirectional, self-reinforcing cycle with oxidative stress (OS). METHODS: We synthesized studies from 2015 to 2025 identified via PubMed, Scopus, and Web of Science, examining links between inflammation and OS, key immune pathways, and related risk factors through qualitative narrative synthesis. RESULTS: Inflammation drives leukocyte infiltration, blood-testis-barrier breakdown, antisperm-antibody production, and inflammasome activation, mechanisms that amplify OS and cause sperm DNA damage, impaired motility, apoptosis, and poor semen quality. Intrinsic factors (prostatitis, infection, varicocele) and extrinsic factors (obesity, aging, psychological stress) sustain this cycle through both ROS-dependent and ROS-independent, immune-mediated pathways. Paternal inflammation may also induce epigenetic changes in sperm with potential consequences for offspring health. CONCLUSION: Antioxidant monotherapy alone is often insufficient when an underlying immune driver persists. Immune-focused diagnostics combined with individualized, mechanism-based treatment strategies may improve personalized care and fertility outcomes.