Clinically Meaningful Improvements in Sperm DNA Fragmentation Severity in Infertile Men Treated with Superoxide Dismutase Supplementation: A Single-Center Experience

Background. Antioxidants are commonly used for the treatment of idiopathic male infertility. Previous studies have shown that antioxidants are able to improve sperm quality, but little is known about their impact on sperm DNA fragmentation (SDF). Preliminary findings showed that superoxide-dismutase (SOD)-based antioxidant plus hydroxytyrosol and carnosol (FertiPlus (R) SOD) therapy was associated with SDF improvement in a small cohort of infertile men. Therefore, we aimed to assess rates of and predictors of semen parameters and SDF improvements in infertile men treated with FertiPlus (R) SOD therapy (SOD+) or with other antioxidants without SOD (SOD-) in the real-life setting. Methods. Data from 60 consecutive infertile men with baseline SDF >= 30% and treated with SOD+ or SOD- for at least three months were analyzed. Clinical parameters and serum hormones were collected. Sperm parameters and SDF were requested at baseline and after SOD+ or SOD- treatment. Clinically meaningful SDF change after treatment was defined as SDF improvement >20% compared to baseline. Propensity score matching was performed to adjust for baseline differences between groups. Descriptive statistics were used to compare clinical and hormonal characteristics between SOD+ and SOD- groups. Semen characteristics were compared before and after treatment. Logistic regression models investigated the association between clinical variables and SDF improvement. Results. Groups were similar in terms of clinical, serum hormones and semen parameters at baseline after matching. Compared to baseline, sperm progressive motility (17 (10-36)% vs. 27 (12-41)%) and normal morphology (2 (1-6)% vs. 4 (2-6)%) significantly improved after SOD+ treatment (all p < 0.01), but not after SOD-. SDF values significantly improved after treatment in both groups, compared to the baseline evaluation (all p < 0.01). However, SDF values were lower after SOD+ than SOD- treatment (30 (22-36)% vs. 37 (31-42)%, p = 0.01). Similarly, a clinically meaningful improvement in SDF at follow-up was more frequently found after SOD+ than SOD- treatment (76.7% vs. 20.0%, p = 0.001). Multivariable logistic regression analysis showed that SOD+ treatment (OR 5.4, p < 0.001) was an independent predictor of clinically meaningful SDF improvement, after accounting for age and baseline FSH values. Conclusions. This cross-sectional study showed that, in a cohort of primary infertile men with SDF >= 30%, SOD-based treatment was significantly effective in improving SDF compared to antioxidants without SOD. Approximately 80% of men treated with SOD+ achieved clinically meaningful improvement in SDF after three months of treatment. Sperm progressive motility and normal morphology also improved after SOD+ therapy but not after SOD-. These results suggest that SOD+ treatment could be considered an effective option for the management of idiopathic infertile men with elevated SDF.