Therapeutic Efficacy of Selenium-Vitamin E Co-Supplementation on Male Infertility: A Systematic Review and Meta-Analysis

This systematic review and meta-analysis assessed combined selenium and vitamin E (Se+vit E) supplementation's effects on male infertility. A systematic search (Web of Science, Medline, Embase, Scopus, ProQuest, Cochrane Library through April 2025) identified 19 studies (11 single-arm, 7 randomized controlled trials (RCTs), 1 non-randomized) evaluating sperm quality, oxidative stress, and pregnancy rates. Methodological quality was assessed using Cochrane guidelines. Meta-analysis of 8 studies (736 participants) revealed Se+vit E reduced semen volume (mean difference [MD]: −0.14 mL, 95%CI: −0.25 to −0.03; p=0.01; I²=0%) and total sperm count (MD: −14.18×10⁶, 95%CI: −26.31 to −2.05; p=0.02; I²=29%; 318 participants). Improvements occurred in sperm vitality (MD: +23.24%, 95%CI: 16.66–29.82; p<0.00001; I²=41%; 424 participants) and normal morphology (MD: +0.49%, 95%CI: 0.16–0.81; p=0.003; I²=0%; 926 participants). No overall effects on motility, concentration, or DNA fragmentation index (DFI) were observed, though subgroup analysis indicated Se+vit E monotherapy enhanced motility (p=0.001). Single-arm studies reported inconsistent benefits in motility, morphology, concentration, and DFI. Antioxidants reduced seminal reactive oxygen species (ROS) and apoptotic markers. Pregnancy data were limited and inconclusive. While Se+vit E may improve select sperm quality markers, adverse effects on semen volume and sperm count, alongside limited high-quality RCTs, underscore the necessity for rigorously designed trials to clarify efficacy and safety.