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Eberhard, Jakob, et al.
(författare)
Impact of therapy and androgen receptor polymorphism on sperm concentration in men treated for testicular germ cell cancer: a longitudinal study.
2004
Ingår i: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 19:6, s. 1418-1425
Tidskriftsartikel (refereegranskat) abstract
Abstract in Undetermined BACKGROUND: Testicular cancer (TC) patients have a high survival rate, and the question of post-therapy recovery of sperm production and its dependence on genetic predisposition is of major interest. METHODS: Ejaculates were obtained from 112 TC patients at one or more of the following time points: post-orchidectomy, or 6, 12, 24, 36 and 60 months post-therapy. The lengths of the androgen receptor (AR) function modulating CAG and GGN repeats in leukocyte DNA were also analysed. RESULTS: No significant decrease in sperm concentration was seen in men who received 1-2 cycles of adjuvant chemotherapy (ACT). Radiotherapy (RT) or more than two cycles of chemotherapy (HCT) caused an initial decline in sperm concentration, which returned to pre-treatment levels 2-5 years after therapy. In the HCT group, sperm concentration 12-24 months post-treatment (T(12-24)) was inversely correlated with CAG length (rho = -0.72, P = 0.03). The type of treatment, but not the concentration at T(0), was an independent predictor of sperm concentration at T(6) (P < 0.0005) and T(12-24) (P = 0.004). CONCLUSION: ACT did not induce a significant decline in sperm concentration. After HCT and RT, a significant reduction of sperm concentration was observed, recovering to pre-treatment levels 2-5 years post-treatment. In HCT-treated patients, the AR CAG length influenced the recovery of spermatogenesis.
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4.
Ståhl, Olof, et al.
(författare)
The impact of testicular carcinoma and its treatment on sperm DNA integrity
2004
Ingår i: Cancer. - : Wiley. - 1097-0142 .- 0008-543X. ; 100:6, s. 1137-1144
Tidskriftsartikel (refereegranskat) abstract
BACKGROUND: 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.METHODS: 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.RESULTS: 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.CONCLUSIONS: 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.
