The impact of testicular carcinoma and its treatment on sperm DNA integrity

Abstract

In patients with testicular germ cell carcinoma (TGCC), spermatogenesis and fertility are impaired. Intracytoplasmic sperm injection has improved their possibility of fatherhood, but might also impose a risk of transmitting DNA defects to the offspring. The aim of the current study was to evaluate the impact of chemotherapy and irradiation on sperm DNA integrity. The study included 74 patients with TGCC. Semen samples were collected before and at specific time points after patients received therapy. Sperm DNA integrity was assessed by the sperm chromatin structure assay. Controls comprised 278 military conscripts. There was no significant difference in the fraction of sperm with fragmented DNA (DNA fragmentation index [DFI]) between controls and patients with TGCC before postoperative cancer treatment (11% vs. 13%). Men treated with adjuvant radiotherapy had a transiently (up to 2 years) higher DFI than nontreated patients (18% vs. 13%; P = 0.03). Patients who received 1-2 cycles of adjuvant chemotherapy had a significantly lower DFI 6 months after treatment than after 1-2 years (9.1% vs. 13%; P = 0.004). Higher doses of chemotherapy among patients resulted in a significantly lower DFI compared with controls (7.3% vs. 11%; P = 0.028), which persisted throughout the 5 years of follow-up. Postorchiectomy, the DFI in sperm samples from patients with testicular carcinoma was at the level of controls. Radiotherapy caused a transient increase in the proportion of DFI, whereas this value decreased after chemotherapy. The biologic implications of such changes in sperm DNA after cancer therapy need to be elucidated.