Assessing the efficacy of varicocelectomy, antioxidants, FSH treatment, and lifestyle modifications on sperm DNA fragmentation: a systematic review and meta-analysis

Infertility affects 15% of couples in developed countries, 50% accounting for male origin. In 2021, sperm DNA fragmentation (SDF) testing was incorporated into male fertility evaluations as an evidence-based functional test. We aimed to assess the effect of interventions that could potentially improve SDF. A random-effect meta-analysis was performed with a systematic search in three databases. Pooled mean differences (MD) with 95% confidence intervals (CI) were calculated. Initially, 36,531 articles were found, of which 86 papers with over 8,000 patients were included. Three months following varicocelectomy, the decrease in SDF was -6.74% (CI: -9.40, -4.08) compared to preoperative data of patients, whereas it was -12.39% (CI: -22.41, -2.36) after six months and -10.06% (CI: -22.69, + 2.56) at twelve months. A dose-dependent effect could also be observed in grade II and III varicoceles. The overall SDF decrease at three months was -4.27% (CI: -6.11, -2.43) for antioxidants, -4.51% (CI: -6.81, -2.20) for combined antioxidant therapy and -3.36% (CI: -4.44, -2.28) for monotherapy. In terms of follicle-stimulating hormone treatment (FSH) at three months, the change in SDF was -6.66% (CI: -9.64, -3.69). For lifestyle modifications, a change of -3.24% (CI: -5.33, -1.16) was observed at three months. Other interventions are narratively summarized in the systematic review. Of the interventions reviewed, varicocelectomy is the most effective in reducing SDF at six months, FSH treatment might be useful, antioxidants appear questionable, and lifestyle interventions require more studies of similar designs to draw firm conclusions. © The Author(s) 2025.