Impact of Hodgkin or non-Hodgkin lymphoma and their treatments on sperm aneuploidy: a prospective study by the French CECOS network.
To assess sperm production and aneuploidy in Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) before and after treatments.



Multicenter, prospective, longitudinal study of lymphoma patients analyzed before treatment and after 3, 6, 12, and 24 months.



University hospitals.



Forty-five HL and 13 NHL patients were investigated before and after treatment. Treatment regimens were classified in two groups: ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) with or without (±) radiotherapy, and CHOP (doxorubicin, cyclophosphamide, vincristine, prednisone)/MOPP-ABV (mechlorethamine, oncovin, procarbazine, prednisone-doxorubicin, bleomycin, vinblastine). A control group of 29 healthy men was also studied.



Semen analyses and aneuploidy study by FISH were performed at each time point.



Comparison of mean sperm characteristics and percentage of sperm aneuploidy rates before and after treatment.



Before treatment, HL and NHL men had altered semen characteristics and higher sperm aneuploidy rates (median 0.76 [interquartile range 0.56-0.64]) than the control group (0.54 [0.46-0.74]). After treatment, sperm production was significantly lowered 3 and 6 months after ABVD ± radiotherapy or CHOP/MOPP-ABV. After ABVD ± radiotherapy, the aneuploidy rate increased significantly only at 3 months, and values obtained 1 or 2 years later were lower than pretreatment values. In contrast, in the CHOP/MOPP-ABV treatment group, semen characteristics and aneuploidy rate did not return to normal levels until 2 years after treatment.



Lymphoma itself has consequences on sperm aneuploidy frequency before treatment. Moreover, lymphoma treatments have deleterious effects on sperm chromosomes related to treatment type and time since treatment. Patient counseling is essential concerning the transient but significant sperm aneuploidy induced by lymphoma and its treatments.
Université Grenoble-Alpes, Institut National de la Santé et de la recherche Médicale (INSERM) U-1029, Grenoble, France; Laboratoire d'Aide à la Procréation-CECOS, Centre Hospitalier Universitaire (CHU) de Grenoble, Grenoble, France.
Guillaume
G
Martinez
Université de Toulouse III; Groupe de Recherche en Fertilité Humaine (EA 3694, Human Fertility Research Group), Toulouse, France.
Marie
M
Walschaerts
Université Grenoble-Alpes, Institut National de la Santé et de la recherche Médicale (INSERM) U-1029, Grenoble, France; Laboratoire d'Aide à la Procréation-CECOS, Centre Hospitalier Universitaire (CHU) de Grenoble, Grenoble, France.
Marine
M
Le Mitouard
Université Grenoble-Alpes, Institut National de la Santé et de la recherche Médicale (INSERM) U-1029, Grenoble, France; Laboratoire d'Aide à la Procréation-CECOS, Centre Hospitalier Universitaire (CHU) de Grenoble, Grenoble, France.
Remi
R
Borye
Université Grenoble-Alpes, Institut National de la Santé et de la recherche Médicale (INSERM) U-1029, Grenoble, France; Laboratoire d'Aide à la Procréation-CECOS, Centre Hospitalier Universitaire (CHU) de Grenoble, Grenoble, France.
Claire
C
Thomas
Département d'Histologie-Embryologie, Biologie de la Reproduction/CECOS, Site Port-Royal, Paris Centre University Hospitals, Paris, France; Federation Française des CECOS, Paris, France.
Jacques
J
Auger
Federation Française des CECOS, Paris, France; Service d'Histologie, Biologie de la Reproduction-CECOS, Hôpital Tenon, Paris, France.
Isabelle
I
Berthaut
Federation Française des CECOS, Paris, France; Assistance Médicale à la Procréation, CECOS, CHU Estaing, Clermont-Ferrand, France; Laboratoire Génétique Reproduction et Développement, GReD, UMR CNRS 6293, INSERM U1103, Université d'Auvergne, Faculté de Médecine, Clermont-Ferrand, France.
Florence
F
Brugnon
Université de Toulouse III; Groupe de Recherche en Fertilité Humaine (EA 3694, Human Fertility Research Group), Toulouse, France; Federation Française des CECOS, Paris, France; CECOS, Groupe d'activité de médecine de la reproduction, CHU Toulouse, Toulouse, France.
Myriam
M
Daudin
Université de Toulouse III; Groupe de Recherche en Fertilité Humaine (EA 3694, Human Fertility Research Group), Toulouse, France; Federation Française des CECOS, Paris, France; CECOS, Groupe d'activité de médecine de la reproduction, CHU Toulouse, Toulouse, France.
Nathalie
N
Moinard
Federation Française des CECOS, Paris, France; Service de Biologie de la Reproduction-CECOS CHU de Rennes, Rennes, France; INSERM U-1085- Institut Recherche Santé Environnement Travail (IRSET), Université de Rennes, Rennes, France.
Célia
C
Ravel
Federation Française des CECOS, Paris, France; Laboratoire de Biologie de la Reproduction-CECOS, Hôpital La Conception, Marseille, France.
Jacqueline
J
Saias
Federation Française des CECOS, Paris, France; Unité de BDR - CECOS, Pole de Biologie, CHU Côte de Nacre, Caen, France.
Ethel
E
Szerman
Federation Française des CECOS, Paris, France; CECOS Biologie de la Reproduction, CHU Rouen, and EA 4308 Gamétogenèse et Qualité du Gamète, Université de Rouen, Rouen, France.
Nathalie
N
Rives
Université Grenoble-Alpes, Institut National de la Santé et de la recherche Médicale (INSERM) U-1029, Grenoble, France; Laboratoire d'Aide à la Procréation-CECOS, Centre Hospitalier Universitaire (CHU) de Grenoble, Grenoble, France; Federation Française des CECOS, Paris, France.
Sylviane
S
Hennebicq
Université de Toulouse III; Groupe de Recherche en Fertilité Humaine (EA 3694, Human Fertility Research Group), Toulouse, France; Federation Française des CECOS, Paris, France; CECOS, Groupe d'activité de médecine de la reproduction, CHU Toulouse, Toulouse, France. Electronic address: bujan.l@chu-toulouse.fr.
Louis
L
Bujan
D000782:Aneuploidy; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D016022:Case-Control Studies; D059248:Chemoradiotherapy / Q000009:adverse effects*; D005602:France; D006689:Hodgkin Disease / Q000175:diagnosis / Q000628:therapy*; D006785:Hospitals, University; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008137:Longitudinal Studies; D008228:Lymphoma, Non-Hodgkin / Q000175:diagnosis / Q000628:therapy*; D008297:Male; D011446:Prospective Studies; D012307:Risk Factors; D055101:Semen Analysis; D013091:Spermatogenesis / Q000187:drug effects* / Q000528:radiation effects*; D013094:Spermatozoa / Q000187:drug effects* / Q000473:pathology / Q000528:radiation effects*; D013997:Time Factors; D016896:Treatment Outcome
Hodgkin; non-Hodgkin lymphoma; sperm aneuploidy; sperm chromosomes; treatment side effects