Sperm DNA Fragmentation in Infertile Men With Varicocele: Clinical Epidemiology and Comparative Assessment of Microsurgical Varicocelectomy and Antioxidant Therapy

Background: Varicocele, a common condition affecting male fertility, has been linked to impaired semen quality and elevated sperm DNA fragmentation (SDF). This study aimed to evaluate the epidemiological prevalence of varicocele and SDF in infertile men and compare the effectiveness of microsurgical varicocelectomy and antioxidant therapy in improving semen parameters and reducing SDF. Methods: This multi-center study included 3632 subfertile and 276 fertile men in the epidemiological phase (retrospective) and 182 infertile men in the comparative analysis phase (prospective). Patients were stratified into three groups: Group 1 (microsurgical varicocelectomy, n = 86), Group 2 (antioxidant therapy, n = 63), and Group 3 (control, n = 33). Varicocele prevalence, semen parameters, and SDF levels were assessed, with follow-up evaluations conducted three months post-intervention. Semen parameters were evaluated using the World Health Organization (WHO) Fifth Edition guidelines, and SDF was measured using the sperm chromatin dispersion test. Results: Varicocele was observed in 29.5% of subfertile men and 27.2% of fertile men, with no statistically significant difference noted (p = 0.18). However, subfertile men with varicocele exhibited significantly higher median SDF levels (20.8%, interquartile range (IQR): 14.1–27.9) compared to fertile men (12.3%, IQR: 9.1–16.5; p < 0.001). Microsurgical varicocelectomy significantly improved semen parameters, with the median sperm concentration increasing by +25.0 million/mL (IQR: 18.4–31.5; p < 0.001) and progressive motility by +67.0% (IQR: 50.0–83.5; p < 0.001). Antioxidant therapy yielded moderate improvements in sperm concentration (+11.0 million/mL, IQR: 8.0–14.5; p < 0.001) and motility (+6.0%, IQR: 4.0–8.5; p = 0.01). The control group showed no significant changes. Conclusion: This study reveals comparable varicocele prevalence between subfertile (29.5%) and fertile men (27.2%), with impaired semen quality and elevated SDF levels in subfertile cases. Microsurgical varicocelectomy proved most effective, while antioxidant therapy offered a viable alternative or adjunct for non-surgical candidates, underscoring the need for tailored varicocele infertility treatments.