Therapeutic efficacy of antioxidant supplementation containing selenium and vitamin E on male infertility: A systematic review and meta-analysis

Background: Recent studies highlight the impact of oxidative stress on sperm quality and male fertility. Given the potential antioxidant effects of selenium and vitamin E, this systematic review and meta-analysis assessed the impact of antioxidant supplementation containing selenium and vitamin E (Se+Vit E) on male infertility. Methods: 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. Results: Meta-analysis of data from 8 studies (736 participants) revealed that dual Se+Vit E supplementation enhanced motility (mean difference [MD]: 13.56%, 95%CI: 0.16–0.81; P=0.001; I2=41%), normal morphology (MD: 0.69%, 95%CI: 0.27–1.11; P=0.001; I2=0%), and vitality (MD: 23.24%, 95%CI: 16.66–29.82; P<0.00001; I2=41%). The sperm motility also increased in total (dual Se+Vit E in addition to antioxidants containing Se+Vit E) (13.56%, 95%CI: 0.16–0.81; P=0.001; I2=41%). No significant effects were observed on semen volume, sperm count, sperm concentration, or DNA fragmentation index (DFI) following dual Se+Vit E supplementation or antioxidants containing Se+Vit E (P>0.05). Single-arm studies reported some benefits in motility, morphology, concentration, and DFI. Antioxidant regimens including Se+Vit E reduced seminal reactive oxygen species (ROS) and apoptotic markers. Pregnancy data were limited and inconclusive. Conclusion: Antioxidants containing Se+Vit E may improve sperm motility. Moreover, supplementation with dual Se+Vit E can enhance sperm motility, normal morphology, and vitality. Due to the heterogeneity of studies, further large and high-quality trials with standardized protocols and critical endpoints like pregnancy rates are required.