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

Capsule:
Lymphoma treatments had highly damaging effects on spermatogenesis and sperm chromatin quality. Mean pretreatment sperm concentrations were recovered at 12months after doxorubicin, bleomycin, vinblastine, darcarbacine (ABVD) or ABVD + radiotherapy, but at 24 months after doxorubicin, cyclophosphamide, vincristine, prednisone(CHOP) ormechlorethamine, oncovin, procarbazine, prednisone (MOPP) therapies.

Authors:
Louis Bujan, M.D., Ph.D., Marie Walschaerts, Ph.D., Florence Brugnon, M.D., Ph.D., Myriam Daudin, M.D., Isabelle Berthaut, Ph.D., Jacques Auger, M.D., Ph.D., Jacqueline Saias, M.D., Ethel Szerman, Ph.D., Nathalie Moinard, D.Pharm., Nathalie Rives, M.D., Ph.D., Sylvianne Hennebicq, M.D., Ph.D.

Volume 102, Issue 3, Pages 667-674

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.

  • msamplaski

    It is interesting that the choice of chemotherapeutic regimen did not relate to recovery of total sperm count, as in general ABVD has been shown to be less gonadotoxic than CHOP. However, there is presently minimal literature on DNA fragmentation in lymphoma patients, and this study does reinforce that the effects of both cancer and its treatment extend beyond that which is seen on the standard semen analysis.

  • ranjithrama

    The authors need to be commended on this study. One of the most important numbers from this study is that 7% of men remained azoospermic at the end of 2 years. The importance and benefits of fertility preservation cannot be stressed enough!!

Translate »