Fertility Preservation for Prepubertal Patients at Risk of Infertility: Present Status and Future Perspectives

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Abstract

The increasing cure rate of cancer has led to a vast population of survivors having to face the late adverse effects of oncological treatments, with fertility impairment being one of the most sensitive issues for patients. Different options to preserve the fertility of adult patients are routinely used in clinical practice. However, fertility preservation strategies for prepubertal patients at risk of infertility are limited to the cryopreservation of immature gonadal tissue. In recent decades, many research efforts have been focused on the future use of cryopreserved gonadal tissue. This review discusses the common status of fertility preservation measures for pediatric patients undergoing gonadotoxic treatment, focusing especially on the challenges that remain to be solved in order to implement this fundamental service.

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Fertility Preservation in Patients With Cancer: ASCO Clinical Practice Guideline Update

Erica Wang, Alison Loren, Joyce D Reinecke … (2018)

Purpose To provide current recommendations about fertility preservation for adults and children with cancer. Methods A systematic review of the literature published from January 2013 to March 2017 was completed using PubMed and the Cochrane Library. An Update Panel reviewed the identified publications. Results There were 61 publications identified and reviewed. None of these publications prompted a significant change in the 2013 recommendations. Recommendations Health care providers should initiate the discussion on the possibility of infertility with patients with cancer treated during their reproductive years or with parents/guardians of children as early as possible. Providers should be prepared to discuss fertility preservation options and/or to refer all potential patients to appropriate reproductive specialists. Although patients may be focused initially on their cancer diagnosis, providers should advise patients regarding potential threats to fertility as early as possible in the treatment process so as to allow for the widest array of options for fertility preservation. The discussion should be documented. Sperm, oocyte, and embryo cryopreservation are considered standard practice and are widely available. There is conflicting evidence to recommend gonadotrophin-releasing hormone agonists (GnRHa) and other means of ovarian suppression for fertility preservation. The Panel recognizes that, when proven fertility preservation methods are not feasible, and in the setting of young women with breast cancer, GnRHa may be offered to patients in the hope of reducing the likelihood of chemotherapy-induced ovarian insufficiency. GnRHa should not be used in place of proven fertility preservation methods. The panel notes that the field of ovarian tissue cryopreservation is advancing quickly and may evolve to become standard therapy in the future. Additional information is available at www.asco.org/survivorship-guidelines .

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In vitro production of functional sperm in cultured neonatal mouse testes.

Takuya Sato, Kumiko Katagiri, Ayako Gohbara … (2011)

Spermatogenesis is one of the most complex and longest processes of sequential cell proliferation and differentiation in the body, taking more than a month from spermatogonial stem cells, through meiosis, to sperm formation. The whole process, therefore, has never been reproduced in vitro in mammals, nor in any other species with a very few exceptions in some particular types of fish. Here we show that neonatal mouse testes which contain only gonocytes or primitive spermatogonia as germ cells can produce spermatids and sperm in vitro with serum-free culture media. Spermatogenesis was maintained over 2 months in tissue fragments positioned at the gas-liquid interphase. The obtained spermatids and sperm resulted in healthy and reproductively competent offspring through microinsemination. In addition, neonatal testis tissues were cryopreserved and, after thawing, showed complete spermatogenesis in vitro. Our organ culture method could be applicable through further refinements to a variety of mammalian species, which will serve as a platform for future clinical application as well as mechanistic understanding of spermatogenesis.

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Reconstitution in vitro of the entire cycle of the mouse female germ line.

Orie Hikabe, Nobuhiko Hamazaki, Go Nagamatsu … (2016)

The female germ line undergoes a unique sequence of differentiation processes that confers totipotency to the egg. The reconstitution of these events in vitro using pluripotent stem cells is a key achievement in reproductive biology and regenerative medicine. Here we report successful reconstitution in vitro of the entire process of oogenesis from mouse pluripotent stem cells. Fully potent mature oocytes were generated in culture from embryonic stem cells and from induced pluripotent stem cells derived from both embryonic fibroblasts and adult tail tip fibroblasts. Moreover, pluripotent stem cell lines were re-derived from the eggs that were generated in vitro, thereby reconstituting the full female germline cycle in a dish. This culture system will provide a platform for elucidating the molecular mechanisms underlying totipotency and the production of oocytes of other mammalian species in culture.

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Journal

Journal ID (publisher-id): HRP

Journal ID (nlm-ta): Horm Res Paediatr

Journal ID (doi): 10.1159/issn.1663-2818

Title: Hormone Research in Paediatrics

Publisher: S. Karger AG

ISSN (Print): 1663-2818

ISSN (Electronic): 1663-2826

Publication date Subscription-year: 2020

Publication date (Print): May 2021

Publication date (Electronic): 22 April 2021

Volume: 93

Issue: 11-12

Pages: 599-608

Affiliations

[_a] _aDipartimento Pediatrico Universitario Ospedaliero, Ospedale Pediatrico Bambino Gesù, Rome, Italy

[_b] _bChildhood Cancer Research Unit, Department of Women’s and Children’s Health, NORDFERTIL Research Laboratory Stockholm, Karolinska Institutet, and Karolinska University Hospital, Stockholm, Sweden

[_c] _cDivision of Obstetrics and Gynecology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, and Karolinska University Hospital, Stockholm, Sweden

[_d] _dDivision of Hematology-Oncology and Stem Cell Transplantation, Children’s Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland

Author information

Valentina Pampanini https://orcid.org/0000-0002-8107-8015

Article

Publisher ID: 516087 Other ID: Horm Res Paediatr 2020;93:599–608

DOI: 10.1159/000516087

PubMed ID: 33887724

SO-VID: d59fdff2-46dc-4fba-952a-6c4d12067873

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Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

History

Date received : 09 February 2021

Date accepted : 23 March 2021

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Figures: 3, Tables: 1, Pages: 10

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Fertility Preservation for Prepubertal Patients at Risk of Infertility: Present Status and Future Perspectives

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Karger: Endocrinology

Most cited references 87

Fertility Preservation in Patients With Cancer: ASCO Clinical Practice Guideline Update

In vitro production of functional sperm in cultured neonatal mouse testes.

Reconstitution in vitro of the entire cycle of the mouse female germ line.

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