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

• Published in: Fertility and sterility Vol. 102; no. 3; pp. 667 - 674.e3
• Main Authors: Bujan, Louis, M.D., Ph.D, Walschaerts, Marie, Ph.D, Brugnon, Florence, M.D., Ph.D, Daudin, Myriam, M.D, Berthaut, Isabelle, Ph.D, Auger, Jacques, M.D., Ph.D, Saias, Jacqueline, M.D, Szerman, Ethel, Ph.D, Moinard, Nathalie, D.Pharm, Rives, Nathalie, M.D., Ph.D, Hennebicq, Sylvianne, M.D., Ph.D
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2014; Elsevier
• Subjects: Adult; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Bleomycin - adverse effects; Bleomycin - therapeutic use; Case-Control Studies; chemotherapy; Combined Modality Therapy; Cyclophosphamide - adverse effects; Cyclophosphamide - therapeutic use; Dacarbazine - adverse effects; Dacarbazine - therapeutic use; DNA - chemistry; DNA - drug effects; DNA - radiation effects; DNA Damage; Doxorubicin - adverse effects; Doxorubicin - therapeutic use; Hodgkin; Hodgkin Disease - therapy; Humans; Internal Medicine; Life Sciences; Longitudinal Studies; Lymphoma; Lymphoma, Non-Hodgkin - therapy; Male; Mechlorethamine - adverse effects; Mechlorethamine - therapeutic use; Obstetrics and Gynecology; Prednisone - adverse effects; Prednisone - therapeutic use; Procarbazine - adverse effects; Procarbazine - therapeutic use; radiotherapy; Reproductive Biology; Semen Analysis; sperm chromatin; Sperm Count; sperm DNA; spermatogenesis; Spermatogenesis - drug effects; Spermatogenesis - radiation effects; Spermatozoa - drug effects; Spermatozoa - physiology; Spermatozoa - radiation effects; Vinblastine - adverse effects; Vinblastine - therapeutic use; Vincristine - adverse effects; Vincristine - therapeutic use; Young Adult; sperm DNA; sperm chromatin; radiotherapy; spermatogenesis; Hodgkin; Lymphoma; chemotherapy
• ISSN: 0015-0282; 1556-5653
• DOI: 10.1016/j.fertnstert.2014.06.008

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.