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Fertility preservation in boys facing gonadotoxic cancer therapy

Abstract

Patient survival following childhood cancer has increased with contemporary radiation and chemotherapy techniques. However, gonadotoxicity associated with treatments means that infertility is a common consequence in survivors. Novel fertility preservation options are emerging, but knowledge about these options amongst urologists and other medical professionals is lacking. Pre-pubertal boys generally do not produce haploid germ cells. Thus, strategies for fertility preservation require cryopreservation of tissue containing spermatogonial stem cells (SSCs). Few centres worldwide routinely offer this option and fertility restoration (including testicular tissue engraftment, autotransplantation of SSCs and in vitro maturation of SSCs to spermatozoa) post-thaw is experimental. In pubertal boys, the main option for fertility preservation is masturbation and cryopreservation of the ejaculate. Assisted ejaculation using penile vibratory stimulation or electroejaculation and surgical sperm retrieval can be used in a sequential manner after failed masturbation. Physicians should inform boys and parents about the gonadotoxic effects of cancer treatment and offer fertility preservation. Preclinical experience has identified challenges in pre-pubertal fertility preservation, but available options are expected to be successful when today’s pre-pubertal boys with cancer become adults. By contrast, fertility preservation in pubertal boys is clinically proven and should be offered to all patients undergoing cancer treatment.

Key points

  • Childhood cancer therapy often results in infertility. Physicians should inform patients and caregivers and offer fertility preservation.

  • Freezing testis tissue with spermatogonial stem cells (SSCs) from pre-pubertal boys is possible, but fertility restoration techniques are still experimental.

  • Experimental options for fertility restoration in pre-pubertal boys include testicular tissue engraftment, autotransplantation of SSCs and in vitro maturation of SSCs to spermatozoa.

  • As a result of the progress in fertility restoration techniques, today’s pre-pubertal boys with cancer will most probably have opportunities to biologically father children when they become adults.

  • Semen cryopreservation (via masturbation or assisted ejaculation) is a clinically proven technique and is the preferred option among pubertal boys.

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Fig. 1: Gonadotoxic effects of cancer treatment on the germ cell population of the testes.
Fig. 2: Assisted ejaculation.

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C.F.S.J., L.D. and M.G. researched data for the article; C.F.S.J., L.D., M.G., M.F., S.H., J.T., E.H., D.C., J.F., C.Y.A., and J.S. made a substantial contribution to discussion of content; C.F.S.J., L.D. and M.G. wrote the article; and C.F.S.J. L.D., M.G., M.F., S.H., J.T., E.H., D.C., J.F., C.Y.A., and J.S. reviewed and/or edited the manuscript prior to submission.

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Correspondence to Christian F. S. Jensen.

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Nature Reviews Urology thanks the anonymous reviewer(s) for their contribution to the peer review of this work.

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Glossary

Cryopreservation protection agent

(CPA). Agent used for prevention of damaging ice crystal formation when freezing biological tissue.

Intracytoplasmic sperm injection

(ICSI). An in vitro fertilization procedure where a spermatozoon is injected directly into the cytoplasm of an oocyte.

Zoonosis

An infectious disease transferred from animals to humans.

Transplantation assay

Transplantation of stem cells into recipient organs as a functional measure of stem cell capacity.

Differential plating method

A method used for enrichment of spermatogonial stem cells by using coated and non-coated cell-culture dishes that differentially adhere spermatogonial stem cells and other cells.

Spermarche

The beginning of sperm development in the testicles of pubertal boys.

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Jensen, C.F.S., Dong, L., Gul, M. et al. Fertility preservation in boys facing gonadotoxic cancer therapy. Nat Rev Urol (2021). https://doi.org/10.1038/s41585-021-00523-8

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