Louis Bujan1, Marie Walschaerts2, Florence Brugnon3, Myriam Daudin4, Isabelle Berthaut5, Jacques Auger6, Jacqueline Saias7, Ethel Szerman8, Nathalie Moinard4, Nathalie Rives9, Sylvianne Hennebicq10. 1. Université de Toulouse, University Paul Sabatier, Groupe de Recherche en Fertilité Humaine (Human Fertility Research Group) and CECOS, Toulouse, France; Fédération Française des CECOS, France, Paris. Electronic address: bujan.l@chu-toulouse.fr. 2. Université de Toulouse, University Paul Sabatier, Groupe de Recherche en Fertilité Humaine (Human Fertility Research Group) and CECOS, Toulouse, France. 3. Fédération Française des CECOS, France, Paris; Assistance Médicale à la Procréation, CECOS, Universitary Hospital Estaing, and Laboratoire Génétique Reproduction et Développement, Université d'Auvergne, Faculté de Médecine, Clermont-Ferrand, France. 4. Université de Toulouse, University Paul Sabatier, Groupe de Recherche en Fertilité Humaine (Human Fertility Research Group) and CECOS, Toulouse, France; Fédération Française des CECOS, France, Paris. 5. Fédération Française des CECOS, France, Paris; Service d'Histologie, Biologie de la Reproduction-CECOS, Hôpital Tenon, Paris, France. 6. Fédération Française des CECOS, France, Paris; Département d'Histologie-Embryologie, Biologie de la Reproduction-CECOS, Site Port-Royal, Paris Centre University Hospitals, Paris, France. 7. Fédération Française des CECOS, France, Paris; Laboratoire de Biologie de la Reproduction-Cecos, Hôpital La Conception, Marseille, France. 8. Fédération Française des CECOS, France, Paris; Unité de Biologie de la Reproduction-CECOS, Pole de Biologie, Universitary Hospital Côte de Nacre, Caen, France. 9. Fédération Française des CECOS, France, Paris; CECOS Biologie de la Reproduction, Universitary Hospital Rouen, and Gamétogenèse et Qualité du Gamète research group, Université de Rouen, Rouen, France. 10. Fédération Française des CECOS, France, Paris; Laboratoire d'Aide à la Procréation-CECOS, Laboratoire AGe, Imagerie, Modélisation, Équipe Génétique-Infertilité-Thérapeutique, Faculté de Médecine de Grenoble, Grenoble, France.
Abstract
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.
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 lymphomapatients 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, lymphomapatients 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): Lymphomapatients 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.
Authors: Sandro C Esteves; Armand Zini; Robert Matthew Coward; Donald P Evenson; Jaime Gosálvez; Sheena E M Lewis; Rakesh Sharma; Peter Humaidan Journal: Andrologia Date: 2020-10-27 Impact factor: 2.775
Authors: Janella N Hudson; Nathanael B Stanley; Leena Nahata; Meghan Bowman-Curci; Gwendolyn P Quinn Journal: Expert Rev Qual Life Cancer Care Date: 2017-03-28