IntroductionTesticular germ cell tumor is the most frequent neoplasia in men of reproductive age, with a 5âyear survival rate of 95%. Antineoplastic treatments induce sperm DNA fragmentation, especially within the first year postâtherapy. Data in the literature are heterogeneous concerning longer followâup periods, and the large majority is limited to 2 years.ObjectiveTo 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 methodsSperm 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 (T0) and 2 (T2) and 3 (T3) years postâtreatment. Patients were divided based on the type of treatment: carboplatin, bleomycinâetoposideâcisplatin, and radiotherapy. For 24 patients, paired sperm DNA fragmentation data were available at all timeâpoints (T0âT2âT3). Seventyânine cancerâfree, fertile normozoospermic men served as controls. Severe DNA damage was defined as the 95th percentile in controls (sperm DNA fragmentation = 50%).ResultsComparing patients versus controls, we observed: (i) no differences at T0 and T3 and (ii) significantly higher sperm DNA fragmentation levels (p < 0.05) at T2 in all treatment groups. Comparing preâ and postâtherapy in the 115 patients, the median sperm DNA fragmentation values were higher in all groups at T2, 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 T2, 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 T2 and T3, respectively.DiscussionCurrently, testicular germ cell tumor patients are advised to wait 2 years postâtherapy before seeking natural pregnancy. Our results suggest that this period may not be sufficient for all patients.ConclusionThe analysis of sperm DNA fragmentation may represent a useful biomarker for preâconception counseling following cancer treatment.