A Short Report on Current Fertility Preservation Strategies for Boys

Wei Li Cindy Ho; Harold Bourne; Debra Gook; Gary Clarke; Matthew Kemertzis; Kate Stern; Franca Agresta; Yves Heloury; Hannah Clark; Lisa Orme; Yasmin Jayasinghe; Margaret R. Zacharin

Disclosures

Clin Endocrinol. 2017;87(3):279-285. 

In This Article

Abstract and Introduction

Abstract

Background Advances in cancer treatment have led to improved long-term survival after childhood cancer, but often at a price of impaired future fertility. Fertility preservation (FP) in male children and early adolescents poses unique challenges as efficacy is unproven.

Objectives To describe characteristics of testicular tissue cryopreservation (TTCP) specimens taken from paediatric and adolescent patients, stratified by age, and prior chemotherapy, if any, and to demonstrate evidence for germ cells.

Materials and methods Retrospective review of gonadal biopsies and clinical records of patients consented into the Royal Children's Hospital FP programme between 1987 and 2015. Tissue was sliced into blocks, with one section sent for histopathology prior to cryopreservation. In boys ≥12 years where spermatogenesis could be expected, a portion of tissue was disaggregated completely to look for mature sperm and if found, additional tissue was dissected and the resulting suspension frozen.

Results Testicular tissue cryopreservation specimens in 44 males (0.3–16.8 years) provided an average of 7.8 slices per patient. All the specimens were taken at the same time as another necessary surgical procedure, under one general anaesthesic. There was only one complication of scrotal wound dehiscence. Seven of the forty-four (15.9%) patients had chemotherapy prior to testicular biopsy, while the rest were chemotherapy naïve. Five of these were prepubertal, and two were pubertal patients. Eleven subjects had tissue dissected with mature sperm found in eight. Of these eight patients where sperm were found, all were pubertal with testicular size of more than 10 mL and showing histological evidence of spermatogenesis. No histologic specimen demonstrated any malignant cells.

Conclusions Testicular tissue cryopreservation can be performed in young patients without delay, preferably prior to cancer treatment. As testicular tissue contains germ cells from which haploid spermatozoa are ultimately derived, future technologies may allow their utilization for fertility in humans. This may be the only hope for biological offspring in some patients undergoing fertility compromising treatment. Retrieval of mature sperm from some pubertal patients, however, offers realistic hope to these patients of future fertility.

Introduction

Advances in cancer treatment have led to improved long-term survival of children with childhood cancer.[1] The use of gonadotoxic chemotherapeutic agents such as alkylating agents and/or heavy metals cause dose-related male gonadal dysfunction.[2] The addition of radiation for treatment of cancer significantly increases the risk of gonadal dysfunction.[3] The prepubertal testis is not protected from gonadotoxic treatment, and all exposed germinal epithelium will be lost in the postpubertal boy.

Adolescent boys who have completed puberty have an established method of fertility preservation (FP) through the cryopreservation of mature sperm but this is not possible for prepubertal boys. Increasingly, testicular tissue cryopreservation (TTCP) is being offered to those prepubertal boys who are at high risk of infertility.[4]

Methods of fertility preservation are evolving quickly. Little has been published in the endocrinology literature regarding this topic. We report current fertility preservation strategies at the Royal Children's Hospital (RCH), Melbourne, for boys who are undergoing treatment that may impair future fertility. TTCP is offered as an experimental procedure and is undertaken under a three-tier governance structure: (a) Institutional governance as a Novel Technology with written clinical pathways and principles (approved by the novel Technologies committee); (b) Clinical Ethics governance, to assess complexities of individual cases; (c) Research Governance for data collection and reporting (HREC 33064). Informed consent was obtained from participants and/or their parents.

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