Impact of chemotherapy and radiotherapy for testicular germ cell tumors on spermatogenesis and sperm DNA: a multicenter prospective study from the CECOS network (original) (raw)
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Effect of chemo- or radiotherapy on sperm parameters of testicular cancer patients
Human Reproduction, 2006
BACKGROUND: The aims of our study were to investigate the short-and long-term effects of chemo-or radiotherapy on spermatogenesis in patients with testicular cancer and to establish any correlation between pre-therapy sperm parameters, histotype and treatment type/intensity and the progress of spermatogenesis during the post-therapy period. METHODS: We evaluated 166 patients affected by testicular cancer, who cryobanked about 1 month after the removal of the cancerous testis and before beginning chemo-(CH group; n = 71) or radiotherapy (RT group; n = 95). RESULTS: For the CH group, there was a statistically significant decrease in sperm parameters, which was most significant 3 months after the end of chemotherapy. For the RT group, this decrease was most relevant 6 months after the end of radiotherapy. Two years after therapy, 3% of the CH group and 6% of the RT group remained azoospermic. To evaluate whether spermatogenesis recovery is a function of baseline semen quality, we divided each group into two subgroups by pre-therapy total sperm count (A, <40 ´ 10 6 /ejaculate; B, ³40 ´ 10 6 /ejaculate). At t 24 , subgroup A of both the CH and RT groups showed improved sperm parameters over the baseline, whereas subgroup B for both CH and RT groups showed a return of sperm parameters to those of baseline values. CONCLUSIONS: In conclusion, the recovery of spermatogenesis after chemo-or radiotherapy in our group of testicular cancer patients was not a function of pre-therapy sperm parameter quality. Cryopreservation of sperm before performing such therapy is therefore imperative.
The impact of testicular carcinoma and its treatment on sperm DNA integrity
Cancer, 2004
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.
Frontiers in Pharmacology, 2016
Young males have testicular germ cells tumors (TGCT) as the most common malignancy and its incidence is increasing in several countries. Besides unilateral orchiectomy (UO), the treatment of TGCT may include surveillance, radiotherapy, or chemotherapy (CT), basing on tumor histology and stage of disease. It is well known that both radio and CT may have negative effects on testicular function, affecting spermatogenesis, and sex hormones. Many reports investigated these aspects in patients treated with bleomycin, etoposide, and cisplatin (BEP), after UO. In contrast no data are available on the side effects of carboplatin treatment in these patients. We included in this study 212 consecutive subjects who undergone to sperm banking at our Andrology and Human Reproduction Unit after UO for TGCT. Hundred subjects were further treated with one or more BEP cycles (BEP-group), 54 with carboplatin (CARB group), and 58 were just surveilled (S-group). All patients were evaluated for seminal parameters, sperm aneuploidy, sperm DNA, sex hormones, volume of the residual testis at baseline (T0) and after 12 (T1) and 24 months (T2) from UO or end of CT. Seminal parameters, sperm aneuploidies, DNA status, gonadic hormones, and testicular volume at baseline were not different between groups. At T1, we observed a significant reduction of sperm concentration and sperm count in the BEP group versus baseline and versus both Carb and S-group. A significant increase of sperm aneuploidies was present at T1 in the BEP group. Similarly, the same group at 1 had altered sperm DNA integrity and fragmentation compared with baseline, S-group and Carb group. These alterations were persistent after 2 years from the end of BEP treatment. Despite a slight improvement at T2, the BEP group had still higher percentages of sperm aneuploidies than other groups. No impairment of sperm aneuploidies and DNA status were observed in the Carb group both after 1 and 2 years from the end of treatment. Despite preliminary, these data demonstrate that in selected patients with TGCTs CT with carboplatin represents a therapeutic option that that seems to not affect sex hormones, spermatogenesis, and sperm nucleus.
British journal of cancer, 2012
The objective of this study was to assess markers of spermatogenesis in long-term survivors of testicular cancer (TC) according to treatment, and to explore correlations between the markers and associations with achieved paternity following TC treatment. In 1191 TC survivors diagnosed between 1980 and 1994, serum-follicle stimulating hormone (s-FSH; n=1191), s-inhibin B (n=441), and sperm counts (millions per ml; n=342) were analysed in a national follow-up study in 1998-2002. Paternity was assessed by a questionnaire. At median 11 years follow-up, 44% had oligo- (<15 millions per ml; 29%) or azoospermia (15%). Sperm counts and s-inhibin B were significantly lower and s-FSH was higher after chemotherapy, but not after radiotherapy (RT), when compared with surgery only. All measures were significantly more abnormal following high doses of chemotherapy (cisplatin (Cis)>850 mg, absolute cumulative dose) compared with lower doses (Cis ≤ 850 mg). Sperm counts were moderately correl...
The Journal of Urology, 1998
The hypothesis to be tested was that abnormal sperm chromatin structure is related to disturbed spermatogenesis in patients with testicular cancer. After orchiectomy but before further treatment (''pretreatment''), semen samples from 39 patients with testicular cancer were analyzed for sperm concentration by light microscopy and by the sperm chromatin structure assay (SCSA). In 28 patients assessment of sperm concentration was repeated 12-26 months after orchiectomy (''posttreatment''). The pretreatment SCSA results for the patients were compared to those from 18 healthy semen donors and assessed for correlation with the patients' posttreatment sperm concentration. Twenty-three patients displayed an abnormal chromatin structure in their pretreatment sample. For the nine evaluable patients on the surveillance program, the pretreatment SCSA results were not correlated with the posttreatment concentration. The results from 19 evaluable patients undergoing cytotoxic treatment (radiotherapy, 13; chemotherapy, 6) indicate that posttreatment recovery of spermatogenesis (recovery in 4 of 5 patients) is observed more often in patients with a normal pretreatment chromatin structure than in those with abnormal SCSA values before treatment (recovery in 2 of 14 patients; P 5 0.02). The results of SCSA display sperm characteristics beyond those of light microscopically assessed sperm concentration. Pretreatment SCSA results might help clinicians to identify those testicular cancer patients with a high risk of long-lasting posttreatment disturbance of spermatogenesis.
Higher Risk of Testis Failure after Radiotherapy Treatment for Testicular Cancer
2020
Testicular germ cell tumors (TGCTs) are prevalent in males of reproductive age. Among the available therapeutic choices, pelvic radiotherapy (RT) and simple surveillance (SURV) are usually pursued. However, RT is considered to have lifethreatening effects on testicular functions. In this study we sought to clarify this issue by evaluating sperm parameters and sex hormones in 131 TGCTs RT-treated-patients at both baseline (T0) and 12 (T1) and 24 months (T2) of follow-up. An agematched group of 61 SURV patients served as control. Sperm parameters were comparable between SURV and RT at T0.
Testicular cancer and sperm DNA damage: short- and long-term effects of antineoplastic treatment
Andrology, 2014
The aim of this study was to investigate sperm DNA damage induced by chemo-and radiotherapy in patients with testicular cancer to provide data on the extent and persistence of nuclear damage that might affect individual reproductive potential. We evaluated pre-and post-antineoplastic treatment sperm DNA integrity, expressed as DNA Fragmentation Index (DFI), in a large caseload of testicular cancer patients by sperm chromatin structure assay. The mean total DFI for all patients at T0 was 18.0 AE 12.5%. Sperm chromatin profile was markedly impaired at T3 (27.7 AE 17.4%) and T6 (23.2 AE 15.3%), improving considerably at T12 and T24 (14.0 AE 8.9% and 14.4 AE 10.3%). After chemotherapy, we found a marked increase in DFI at T3 and T6 and a significant reduction at T12 and T24 in comparison with the baseline. In contrast, DFI increased at T3 and T6 after radiotherapy but the subsequent reduction was far less marked, reaching baseline values at T12 and T24. Finally, post-treatment DNA damage was not age or histotype dependent, but was more marked in the advanced stage of cancer. In this study, we showed that the chromatin profile may be affected in the months immediately following the end of the treatment, improving after 12-24 months. Our results thus indicate that post-treatment DNA damage is influenced both by the type and intensity of the therapy and by the pathological and clinical stage of the disease.
Semen analysis of subfertility caused by testicular carcinoma
International Journal of Reproductive BioMedicine (IJRM)
Background: Infertility is a common problem in testicular cancer. Affected men often decide to undergo sperm banking before chemo/radiotherapy. The cumulative effects of therapy can considerably reduce fertility. Objective: Testicular cancers impair fertilizing ability, even before diagnosis. This study tries to verify individual traits and semen quality in patients with testicular cancer. Materials and Methods: This observational study analyzed 190 semen of patients with testicular cancer (16 to 47 yr old) referred to the sub-fertility laboratory at the St. Mary hospital for semen banking prior to treatment carcinoma. Several aspects of their semen analyses were examined. The cases were divided into four different categories: seminoma, teratoma, mixed germ cell tumors and others. Results: The results showed that 23 cases were azoospermic, and 13 of the patients who were not azoospermic, their sperm of “normal” morphology were too few to count. Among patients that could produce sper...
Sperm DNA integrity in testicular cancer patients
Human Reproduction, 2006
BACKGROUND: We evaluated the impact of testicular germ cell cancer (TGCC), its treatment and length of follow-up on sperm DNA integrity. METHODS: In 96 TGCC patients, semen was collected at specific intervals until 5 years after treatment. Sperm DNA integrity was assessed by the sperm chromatin structure assay (SCSA, n = 193) and by the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL, n = 159) assay. Results were expressed as DNA fragmentation index (DFI). Controls comprised of 278 military conscripts. RESULTS: Postsurgery testicular cancer (TC) patients did not differ from controls. Compared with pretreatment values, radiotherapy induced a transient increase in SCSA DFI (medians: 12 versus 19%; P = 0.03), normalizing after 3-5 years. One year or more after therapy, 5/13 (38%) of normozoospermic, irradiated patients had SCSA DFI >27% compared with 7% of normozoospermic controls (P = 0.002). More than two cycles of chemotherapy decreased DFI 3-5 years posttherapy (median SCSA DFI : 12 versus 9.1%, P = 0.02; median TUNEL DFI : 11 versus 7.5%, P = 0.03). CONCLUSION: Irradiation increases sperm DNA damage 1-2 years after treatment, and 38% of irradiated patients with normozoospermia had high (>27%) DNA damage, which may affect the sperm-fertilizing ability. TC per se is not associated with an increase of DFI, and DFI is reduced by three or more cycles of chemotherapy.