Long‐term effect of cytotoxic treatments on sperm DNA fragmentation in patients affected by testicular germ cell tumor

Abstract Introduction Testicular germ cell tumor is the most frequent neoplasia in men of reproductive age, with a 5‐year survival rate of 95%. Antineoplastic treatments induce sperm DNA fragmentation, especially within the first year post‐therapy. Data in the literature are heterogeneous concerning longer follow‐up periods, and the large majority is limited to 2 years. Objective To define the timing for the recovery of sperm DNA damage and the proportion of patients with severe DNA damage at 2 and 3 years from the end of therapy. Materials and methods Sperm DNA fragmentation was evaluated in 115 testicular germ cell tumor patients using terminal deoxynucleotidyl transferase dUTP nick end labeling assay coupled with flow cytometry before ( T 0 ) and 2 ( T 2 ) and 3 ( T 3 ) years post‐treatment. Patients were divided based on the type of treatment: carboplatin, bleomycin–etoposide–cisplatin, and radiotherapy. For 24 patients, paired sperm DNA fragmentation data were available at all time‐points ( T 0 – T 2 – T 3 ). Seventy‐nine cancer‐free, fertile normozoospermic men served as controls. Severe DNA damage was defined as the 95th percentile in controls (sperm DNA fragmentation = 50%). Results Comparing patients versus controls, we observed: (i) no differences at T 0 and T 3 and (ii) significantly higher sperm DNA fragmentation levels ( p < 0.05) at T 2 in all treatment groups. Comparing pre‐ and post‐therapy in the 115 patients, the median sperm DNA fragmentation values were higher in all groups at T 2 , reaching significance ( p < 0.05) only in the carboplatin group. While the median sperm DNA fragmentation values were also higher in the strictly paired cohort at T 2 , about 50% of patients returned to baseline. The proportion of severe DNA damage in the entire cohort was 23.4% and 4.8% of patients at T 2 and T 3 , respectively. Discussion Currently, testicular germ cell tumor patients are advised to wait 2 years post‐therapy before seeking natural pregnancy. Our results suggest that this period may not be sufficient for all patients. Conclusion The analysis of sperm DNA fragmentation may represent a useful biomarker for pre‐conception counseling following cancer treatment.