title: Impact of lymphoma treatments on spermatogenesis and sperm deoxyribonucleic acid: a multicenter prospective study from the CECOS network.
abstract: OBJECTIVE
  To determine consequences of lymphoma treatments on sperm characteristics and sperm DNA, and to evaluate predictors of sperm recovery.
  
  
  METHODS
  Multicenter prospective longitudinal study of patients analyzed before treatment and after 3, 6, 12, and 24 months.
  
  
  METHODS
  University hospitals.
  
  
  METHODS
  Seventy-five Hodgkin lymphoma and non-Hodgkin lymphoma patients and a control group of 257 fertile men.
  
  
  METHODS
  Semen analyses, and sperm DNA and chromatin assessments.
  
  
  METHODS
  Comparisons of sperm characteristics before and after treatment.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Louis
authors.initials: L
authors.lastname: Bujan
authors.affiliation: Université de Toulouse, University Paul Sabatier, Groupe de Recherche en Fertilité Humaine (Human Fertility Research Group) and CECOS, Toulouse, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Walschaerts
authors.affiliation: 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.
authors.forename: Florence
authors.initials: F
authors.lastname: Brugnon
authors.affiliation: 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.
authors.forename: Myriam
authors.initials: M
authors.lastname: Daudin
authors.affiliation: Fédération Française des CECOS, France, Paris; Service d'Histologie, Biologie de la Reproduction-CECOS, Hôpital Tenon, Paris, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Berthaut
authors.affiliation: Fédération Française des CECOS, France, Paris; Département d'Histologie-Embryologie, Biologie de la Reproduction-CECOS, Site Port-Royal, Paris Centre University Hospitals, Paris, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Auger
authors.affiliation: Fédération Française des CECOS, France, Paris; Laboratoire de Biologie de la Reproduction-Cecos, Hôpital La Conception, Marseille, France.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Saias
authors.affiliation: Fédération Française des CECOS, France, Paris; Unité de Biologie de la Reproduction-CECOS, Pole de Biologie, Universitary Hospital Côte de Nacre, Caen, France.
authors.forename: Ethel
authors.initials: E
authors.lastname: Szerman
authors.affiliation: 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.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Moinard
authors.affiliation: 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.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Rives
authors.affiliation: 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.
authors.forename: Sylvianne
authors.initials: S
authors.lastname: Hennebicq
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D001761:Bleomycin / Q000009:adverse effects / Q000627:therapeutic use; D016022:Case-Control Studies; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000009:adverse effects / Q000627:therapeutic use; D004247:DNA / Q000737:chemistry / Q000187:drug effects* / Q000528:radiation effects; D004249:DNA Damage; D003606:Dacarbazine / Q000009:adverse effects / Q000627:therapeutic use; D004317:Doxorubicin / Q000009:adverse effects / Q000627:therapeutic use; D006689:Hodgkin Disease / Q000628:therapy*; D006801:Humans; D008137:Longitudinal Studies; D008228:Lymphoma, Non-Hodgkin / Q000628:therapy*; D008297:Male; D008466:Mechlorethamine / Q000009:adverse effects / Q000627:therapeutic use; D011241:Prednisone / Q000009:adverse effects / Q000627:therapeutic use; D011344:Procarbazine / Q000009:adverse effects / Q000627:therapeutic use; D055101:Semen Analysis; D013076:Sperm Count; D013091:Spermatogenesis / Q000187:drug effects* / Q000528:radiation effects; D013094:Spermatozoa / Q000187:drug effects* / Q000502:physiology / Q000528:radiation effects; D014747:Vinblastine / Q000009:adverse effects / Q000627:therapeutic use; D014750:Vincristine / Q000009:adverse effects / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D001761:Bleomycin; D011344:Procarbazine; D008466:Mechlorethamine; D014750:Vincristine; D014747:Vinblastine; D003606:Dacarbazine; D004317:Doxorubicin; D003520:Cyclophosphamide; D004247:DNA; D011241:Prednisone
keywords: Hodgkin; Lymphoma; chemotherapy; radiotherapy; sperm DNA; sperm chromatin; spermatogenesis