Impact of Hodgkin or non-Hodgkin lymphoma and their treatments on sperm aneuploidy: a prospective study by the French CECOS network

Martinez, Guillaume; Walschaerts, Marie; Mitouard, Marine Le; Borye, Remi; Thomas, Claire; Auger, Jacques; Berthaut, Isabelle; Brugnon, Florence; Daudin, Myriam; Moinard, Nathalie; Ravel, Célia; Saïas, Jacqueline; Szerman, Ethel; Rives, Nathalie; Hennebicq, Sylviane; Bujan, Louis

doi:10.1016/j.fertnstert.2016.10.001

Cited by 43 publications

(42 citation statements)

References 53 publications

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“…Thus, a multicenter prospective study assessing sperm aneuploidy in lymphoma patients demonstrated that ABVD and CHOP/MOPP-ABV (mechlorethamine, vincristine, procarbazine, prednisone-doxorubicin, bleomycin, vinblastine) treatments resulted in increased aneuploidy frequencies three months after the completion of the treatment. In patients treated with ABVD, aneuploidy rates returned to lower values than before treatment one or two years following the chemotherapy, whereas these rates were still relatively high until two years after in patients who received CHOP/MOPP-ABV [121].…”

Section: Sperm Nuclear Abnormalitiesmentioning

confidence: 84%

“…In addition, a raised frequency of chromosome 13 and 21 nullisomy has been observed in testicular cancer patients and Hodgkin's lymphoma patients 18 to 24 months after the chemotherapy initiation [120]. Most of studies using FISH analysis report a sexual chromosome disomy in patients after CHOP/MOPP-ABV, ABVD, or BEP regimen [115,120,121]. Close to 40% of testicular cancer patients did not recover normal sperm aneuploidy rates after treatment, and it would be advisable to postpone the parental project up to 24 months after more than two BEP chemotherapy cycles to prevent a potential risk of aneuploid conceptus [115].…”

Section: Sperm Nuclear Abnormalitiesmentioning

confidence: 99%

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Exposure to Chemotherapy During Childhood or Adulthood and Consequences on Spermatogenesis and Male Fertility

Delessard

Saulnier

Rives

et al. 2020

IJMS

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Over the last decade, the number of cancer survivors has increased thanks to progress in diagnosis and treatment. Cancer treatments are often accompanied by adverse side effects depending on the age of the patient, the type of cancer, the treatment regimen, and the doses. The testicular tissue is very sensitive to chemotherapy and radiotherapy. This review will summarize the epidemiological and experimental data concerning the consequences of exposure to chemotherapy during the prepubertal period or adulthood on spermatogenic progression, sperm production, sperm nuclear quality, and the health of the offspring. Studies concerning the gonadotoxicity of anticancer drugs in adult survivors of childhood cancer are still limited compared with those concerning the effects of chemotherapy exposure during adulthood. In humans, it is difficult to evaluate exactly the toxicity of chemotherapeutic agents because cancer treatments often combine chemotherapy and radiotherapy. Thus, it is important to undertake experimental studies in animal models in order to define the mechanism involved in the drug gonadotoxicity and to assess the effects of their administration alone or in combination on immature and mature testis. These data will help to better inform cancer patients after recovery about the risks of chemotherapy for their future fertility and to propose fertility preservation options.

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Section: Sperm Nuclear Abnormalitiesmentioning

confidence: 84%

Section: Sperm Nuclear Abnormalitiesmentioning

confidence: 99%

Exposure to Chemotherapy During Childhood or Adulthood and Consequences on Spermatogenesis and Male Fertility

Delessard

Saulnier

Rives

et al. 2020

IJMS

Self Cite

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“…ABVD treatment also produced a transient high frequency of chromosomal alterations in spermatozoa of HL patients that decreased 3-18 months later [50,62]. In an interesting study, (Table 4).…”

Section: Impact Of Anticancer Therapy On Fertility and Germ Cell Genomentioning

confidence: 88%

“…The most aggressive treatment is MOPP since 90 to 100% of survivors have azoospermia [8,45,[48][49][50]. In contrast, ABVD is less toxic causing transient azoospermia in one-third of patients, and most of them recover sperm production [49][50][51] (Table 3). reported that damage "appeared to be not specific for chromosome pairs or regions to be involved in the structural exchanges", which may be interpreted as NCCA.…”

Section: Impact Of Anticancer Therapy On Fertility and Germ Cell Genomentioning

confidence: 99%

Non-Clonal Chromosome Aberrations and Genome Chaos in Somatic And Germ Cells from Patients and Survivors of Hodgkin Lymphoma, Induced by Anticancer Treatment

Frias¹,

Ramos²,

Salas-Labadía³

et al. 2018

Preprint

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Anticancer regimens for Hodgkin lymphoma (HL) patients include highly genotoxic drugs that have been very successful in killing tumor cells and providing a 90% disease-free survival at five years. However, these treatments do not have a specific cell target, damaging both cancerous and normal cells. Thus, HL survivors have a high risk of developing new primary cancers, both hematologic and solid tumors, that have been related to treatment. Several studies have shown that after-treatment, HL patients and survivors present persistent chromosomal instability, including non-clonal chromosomal aberrations. The frequency and type of chromosomal abnormalities appear to depend on the type of therapy and the cell type examined. For example, MOPP chemotherapy affects hematopoietic and germ stem cells leading to long-term genotoxic effects and azoospermia, while ABVD chemotherapy affects transiently sperm cells, with most of the patients showing recovery of spermatogenesis. Both regimens have long-term effects in somatic cells, presenting non-clonal chromosomal aberrations and genomic chaos in a fraction of non-cancerous cells. This is a source of karyotypic heterogeneity that could eventually generate a more stable population acquiring clonal chromosomal aberrations and leading towards the development of a new cancer. 

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“…Genomic analyses of sperm samples are consistent with these results. FISH analysis of spermatozoa from patients given chemotherapy that lacked alkylating agents and/or with gonadal radiation doses of <1 Gy all showed no increase in aneuploidy (errors in chromosome number), at 1 year after treatment . In patients given chemotherapy that included alkylating agents or cisplatin, aneuploidy completely returned to pre‐treatment values 2 years after treatment .…”

Section: Absence Of Significant Induction Of Mutations In Human Stem mentioning

confidence: 98%

Risks of genetic damage in offspring conceived using spermatozoa produced during chemotherapy or radiotherapy

Meistrich

2020

Andrology

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Background: Men who have just started cytotoxic therapy for cancer are uncertain and concerned about whether spermatozoa collected or pregnancies occurring during therapy might be transmitting genetic damage to offspring. There are no comprehensive guidelines on the risks of different doses of the various cytotoxic, and usually genotoxic, antineoplastic agents. Objectives:To develop a schema showing the risks of mutagenic damage when spermatozoa, exposed to various genotoxic agents during spermatogenesis, are collected or used to produce a pregnancy. Materials and methods:A comprehensive literature review was performed updating the data on genetic and epigenetic effects of genotoxic agents on animal and human spermatozoa exposed during spermatogenic development.Results: Relevant data on human spermatozoa and offspring are extremely limited, but there are extensive genetic studies in experimental animals that define sensitivities for specific drugs and times. The animal data were extrapolated to humans based on the stage when the cells were exposed and the relative kinetics of spermatogenesis and were consistent with the limited human data. In humans, alkylating agents and radiation should already induce a high risk of mutations in spermatozoa produced within 1 or 2 weeks after initiation of therapy. Topoisomerase II inhibitors and possibly microtubule inhibitors produce the greatest risk at weeks 5-7 of therapy.Nucleoside analogs, antimetabolites, and bleomycin exert their mutagenic effects on spermatozoa collected at 7-10 weeks of therapy. Discussion and conclusions:A schema showing the time from initiation of therapy at which specific antineoplastic agents can cause significant levels of genetic damage in conceptuses and live offspring was developed. The estimates and methods for computing the level of such risk from an individual patient's treatment regimen will enable patients and counselors to make informed decisions on the use of spermatozoa or continuation of a pregnancy. K E Y W O R D Schemotherapy, radiotherapy, mutations, chromosome aberrations, human, animal models

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Impact of Hodgkin or non-Hodgkin lymphoma and their treatments on sperm aneuploidy: a prospective study by the French CECOS network

Cited by 43 publications

References 53 publications

Exposure to Chemotherapy During Childhood or Adulthood and Consequences on Spermatogenesis and Male Fertility

Exposure to Chemotherapy During Childhood or Adulthood and Consequences on Spermatogenesis and Male Fertility

Non-Clonal Chromosome Aberrations and Genome Chaos in Somatic And Germ Cells from Patients and Survivors of Hodgkin Lymphoma, Induced by Anticancer Treatment

Risks of genetic damage in offspring conceived using spermatozoa produced during chemotherapy or radiotherapy

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