Male fertility during and after immune checkpoint inhibitor therapy: A cross-sectional pilot study.


Journal

European journal of cancer (Oxford, England : 1990)
ISSN: 1879-0852
Titre abrégé: Eur J Cancer
Pays: England
ID NLM: 9005373

Informations de publication

Date de publication:
07 2021
Historique:
received: 02 03 2021
revised: 08 04 2021
accepted: 22 04 2021
pubmed: 2 6 2021
medline: 11 11 2021
entrez: 1 6 2021
Statut: ppublish

Résumé

Immune checkpoint inhibitors (ICIs) are widely used and may induce long-term survival in various types of cancer. Yet, there is scarce evidence on potential effects on patient fertility and the necessity of cryopreservation before treatment onset. The aim of our study was to assess the prevalence of male infertility after initiation of ICI treatment. This is a monocenter, cross-sectional pilot study. Fertility was investigated by spermiogram, analysis of sexual hormones and questionnaires on sexual function and sexual activity. Male patients under the age of 60 years previously or currently treated with ICI for cutaneous malignancies or uveal melanoma were included. Twenty-five patients were included, with a median age of 49 years. Eighteen of 22 (82%) available spermiograms showed no pathologies, all patients reported a normal sexual function and sexual activity. Of four patients with pathological spermiogram, three patients were diagnosed with azoospermia and one with oligoasthenoteratozoospermia. Three patients had significant confounding factors (previous inguinal radiotherapy, chemotherapy and chronic alcohol abuse, and bacterial orchitis). One patient with normal spermiogram before ICI treatment presented 1 year after initiation with azoospermia, showing an asymptomatic, inflammatory infiltrate with predominantly neutrophil granulocytes, macrophages and T-lymphocytes in the ejaculate. Infectious causes were ruled out; andrological examination was unremarkable. A second case with reduced sperm counts during treatment may be ICI-induced also. Most patients had no restrictions in fertility, yet an inflammatory loss of spermatogenesis seems possible. Cryopreservation should be discussed with all patients with potential future desire for children before treatment.

Sections du résumé

BACKGROUND
Immune checkpoint inhibitors (ICIs) are widely used and may induce long-term survival in various types of cancer. Yet, there is scarce evidence on potential effects on patient fertility and the necessity of cryopreservation before treatment onset. The aim of our study was to assess the prevalence of male infertility after initiation of ICI treatment.
METHODS
This is a monocenter, cross-sectional pilot study. Fertility was investigated by spermiogram, analysis of sexual hormones and questionnaires on sexual function and sexual activity. Male patients under the age of 60 years previously or currently treated with ICI for cutaneous malignancies or uveal melanoma were included.
RESULTS
Twenty-five patients were included, with a median age of 49 years. Eighteen of 22 (82%) available spermiograms showed no pathologies, all patients reported a normal sexual function and sexual activity. Of four patients with pathological spermiogram, three patients were diagnosed with azoospermia and one with oligoasthenoteratozoospermia. Three patients had significant confounding factors (previous inguinal radiotherapy, chemotherapy and chronic alcohol abuse, and bacterial orchitis). One patient with normal spermiogram before ICI treatment presented 1 year after initiation with azoospermia, showing an asymptomatic, inflammatory infiltrate with predominantly neutrophil granulocytes, macrophages and T-lymphocytes in the ejaculate. Infectious causes were ruled out; andrological examination was unremarkable. A second case with reduced sperm counts during treatment may be ICI-induced also.
CONCLUSIONS
Most patients had no restrictions in fertility, yet an inflammatory loss of spermatogenesis seems possible. Cryopreservation should be discussed with all patients with potential future desire for children before treatment.

Identifiants

pubmed: 34062486
pii: S0959-8049(21)00277-X
doi: 10.1016/j.ejca.2021.04.031
pii:
doi:

Substances chimiques

Immune Checkpoint Inhibitors 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

41-48

Informations de copyright

Copyright © 2021 Elsevier Ltd. All rights reserved.

Déclaration de conflit d'intérêts

Conflict of interest statement M.S.: honoraria and/or travel grants from Abbvie, Bristol-Myers Squibb (BMS), Merck, Merck Sharp & Dohme (MSD), Novartis and Pfizer. G.T.: advisory honoraria from Merck and Boston Scientific. M.He.: No conflict of interest to declare. D.S.: grants, personal fees, non-financial support and/or other from Novartis, BMS, Merck Serono, Amgen, Immunocore, Incyte, 4SC, Pierre Fabre, Sanofi/Regeneron, Array BioPharma, InFlarX, Philogen, Regeneron, Merck/MSD, Sandoz/Hexal, NeraCare, Roche/Genentech; outside the submitted work. I.M.: No conflict of interest to declare. A.H.E.: advisory honoraria from Biotest AG, MSD Oncology, Galderma, Janssen Cilag, AbbVie as well as speaker's honoraria from Roche Pharma. M.Ha.: No conflict of interest to declare. J.C.H.: honoraria for talks from BMS, MSD, Roche, Novartis; advisory board member for MSD, Pierre Fabre; scientific grant support from BMS; travel grants from BMS, Pierre Fabre.

Auteurs

Martin Salzmann (M)

Department of Dermatology and National Center for Tumor Diseases, University Hospital Heidelberg, Heidelberg, Germany. Electronic address: martin.salzmann@med.uni-heidelberg.de.

Georgi Tosev (G)

Department of Urology, University Hospital Heidelberg, Heidelberg, Germany.

Melanie Heck (M)

Department of Dermatology and National Center for Tumor Diseases, University Hospital Heidelberg, Heidelberg, Germany.

Dirk Schadendorf (D)

Department of Dermatology, University Hospital Essen, Essen, Germany.

Imad Maatouk (I)

Department of General Internal Medicine and Psychosomatics, Center for Psychosocial Medicine, University Hospital Heidelberg, Heidelberg, Germany.

Alexander H Enk (AH)

Department of Dermatology and National Center for Tumor Diseases, University Hospital Heidelberg, Heidelberg, Germany.

Martin Hartmann (M)

Department of Dermatology and National Center for Tumor Diseases, University Hospital Heidelberg, Heidelberg, Germany.

Jessica C Hassel (JC)

Department of Dermatology and National Center for Tumor Diseases, University Hospital Heidelberg, Heidelberg, Germany.

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Classifications MeSH