Sperm aneuploidy after testicular cancer treatment: data from a prospective multicenter study performed within the French Centre d'Étude et de Conservation des Oeufs et du Sperme network.

OBJECTIVE: To study sperm aneuploidy in a population of testicular cancer (TC) patients treated with the use of either bleomycin-etoposide-cisplatin (BEP) chemotherapy or radiotherapy. DESIGN: Multicenter prospective longitudinal study of TC patients analyzed before treatment and after 3, 6, 12, and 24 months (T3-T24). PATIENT(S): Fifty-four TC patients and a control group of 10 fertile sperm donors. SETTING: University hospital laboratories. INTERVENTION(S): Routine semen analyses; sperm aneuploidy and diploidy. MAIN OUTCOME MEASURE(S): Comparison of sperm characteristics and sperm chromosome abnormalities during TC patient follow-up. RESULT(S): Semen characteristics recovered pretreatment values 12 months after radiotherapy and 24 months after more than two BEP cycles. A significant increase in sperm disomy YY and XX was observed in the TC group before treatment compared with the control group. After more than two BEP cycles, the mean sperm aneuploidy rate increased significantly at T12 and reached the pretreatment value at T24. After radiotherapy, the mean sperm aneuploidy returned to the pretreatment value at T12. At T24, nearly 40% of TC patients did not recover their pretreatment sperm aneuploidy rate. CONCLUSION(S): Genetic counseling of TC patients should include information on the potential elevated risk of aneuploid conceptus from sperm recovered after treatment and the necessity to postpone conception up to ≥12 months after radiotherapy and ≥24 months after more than two BEP chemotherapy cycles. However, few men receiving one or two BEP cycles and some dropouts are the main limitations of this study.

A new mutation identified in SPATA16 in two globozoospermic patients.

PURPOSE: The aim of this study is to identify potential genes involved in human globozoopsermia. METHODS: Nineteen globozoospermic patients (previously screened for DPY19L2 mutations with no causative mutation) were recruited in this study and screened for mutations in genes implicated in human globozoospermia SPATA16 and PICK1. Using the candidate gene approach and the determination of Spata16 partners by Glutathione S-transferase (GST) pull-down four genes were also selected and screened for mutations. RESULTS: We identified a novel mutation of SPATA16: deletion of 22.6 Kb encompassing the first coding exon in two unrelated Tunisian patients who presented the same deletion breakpoints. The two patients shared the same haplotype, suggesting a possible ancestral founder effect for this new deletion. Four genes were selected using the candidate gene approach and the GST pull-down (GOPC, PICK1, AGFG1 and IRGC) and were screened for mutation, but no variation was identified. CONCLUSIONS: The present study confirms the pathogenicity of the SPATA16 mutations. The fact that no variation was detected in the coding sequence of AFGF1, GOPC, PICK1 and IRGC does not mean that they are not involved in human globozoospermia. A larger globozoospermic cohort must be studied in order to accelerate the process of identifying new genes involved in such phenotypes. Until sufficient numbers of patients have been screened, AFGF1, GOPC, PICK1 and IRGC should still be considered as candidate genes.

Impact of lymphoma treatments on spermatogenesis and sperm deoxyribonucleic acid: a multicenter prospective study from the CECOS network.

OBJECTIVE: To determine consequences of lymphoma treatments on sperm characteristics and sperm DNA, and to evaluate predictors of sperm recovery. DESIGN: Multicenter prospective longitudinal study of patients analyzed before treatment and after 3, 6, 12, and 24 months. SETTING: University hospitals. PATIENT(S): Seventy-five Hodgkin lymphoma and non-Hodgkin lymphoma patients and a control group of 257 fertile men. INTERVENTION(S): Semen analyses, and sperm DNA and chromatin assessments. MAIN OUTCOME MEASURE(S): Comparisons of sperm characteristics before and after treatment. RESULT(S): Patients already had altered sperm characteristics before lymphoma treatment, with no identified risk factor. Sperm count, total sperm count, motility, and vitality decreased after treatment, with lowest values at 3 and 6 months. Twelve months after treatment, mean sperm count recovered to pretreatment values after doxorubicin, bleomycin, vinblastine, darcarbacine (ABVD) or ABVD+radiotherapy, but not after doxorubicin, cyclophosphamide, vincristine, prednisone (CHOP) or mechlorethamine, oncovin, procarbazine, prednisone (MOPP) chemotherapies. It was noteworthy that 7% of patients remained azoospermic at 24 months. After 24 months, Kaplan-Meier estimates showed that more than 90% of patients will recover normal sperm count after ABVD or ABVD+radiotherapy vs. 61% for CHOP chemotherapies. In multivariate analyses including diagnosis and treatment protocol, only pretreatment total sperm count was related to recovery. Compared with a control group, lymphoma patients had higher sperm chromatin alterations and DNA fragmentation before any treatment. After treatment, DNA fragmentation assessed by TUNEL assay and sperm chromatin structure assay decreased from 3 and 6 months, respectively, while remaining higher than in the control group during follow-up. CONCLUSION(S): Lymphoma patients had altered sperm DNA and chromatin before treatment. Lymphoma treatment had damaging effects on spermatogenesis. These data on both the recovery period according to treatment modalities and the pre- and post-treatment chromatin status of sperm are useful tools for counseling patients wishing to conceive.

Impact of chemotherapy and radiotherapy for testicular germ cell tumors on spermatogenesis and sperm DNA: a multicenter prospective study from the CECOS network.

OBJECTIVE: To determine the consequences of adjuvant testicular germ cell tumor treatment (TGCT) on sperm characteristics and sperm DNA, and to evaluate the predictors of sperm recovery. DESIGN: Multicenter prospective longitudinal study of patients analyzed before treatment and after 3, 6, 12, and 24 months. SETTING: University hospitals. PATIENT(S): One hundred twenty-nine volunteer TGCT patients and a control group of 257 fertile men. INTERVENTION(S): Routine semen analyses, sperm DNA, and chromatin assessments. MAIN OUTCOME MEASURE(S): Comparisons of mean sperm characteristics before and after treatment, with sperm recovery analyzed by the Kaplan-Meier method. RESULT(S): The quantitative and qualitative sperm characteristics decreased after treatment, with lowest values at 3 and 6 months and with variations according to treatment type. The mean total sperm count recovered to pretreatment values at 12 months after treatment after two or fewer bleomycin, etoposide, and cisplatin (BEP) cycles, but not after radiotherapy or more than two BEP cycles. Only the treatment modalities and pretreatment sperm production were related to recovery of the World Health Organization reference sperm values. An increased proportion of patients had elevated high sperm DNA stainability at 6 months after radiotherapy. CONCLUSION(S): Adjuvant treatments for testicular germ cell tumor have drastic effects on spermatogenesis and sperm chromatin quality. These new data on both the recovery period according to treatment modalities and the post-treatment chromatin status of sperm are useful tools for counseling patients wishing to conceive.