Fertility Preservation and Restoration Options for Pre-Pubertal Male Cancer Patients: Current Approaches
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Updated: Sep 5, 2025

Mouse Round Spermatid Injection
Published on: January 26, 2024
Elena Eugeni1,2, Iva Arato1, Rachele Del Sordo3
1Department of Medicine and Surgery, University of Perugia, Perugia, Italy.
Abstract:
Fertility preservation for prepubertal male patients undergoing gonadotoxic therapies, potentially depleting spermatogonial cells, is an expanding necessity, yet most of the feasible options are still in the experimental phase. We present our experience and a summary of current and novel possibilities regarding the different strategies to protect or restore fertility in young male patients, before proceeding with chemotherapy or radiotherapy for malignances or other diseases. Adult oncological patients should always be counselled to cryopreserve the semen before starting treatment, however this approach is not suitable for prepubertal boys, who aren't capable to produce sperm yet. Fortunately, since the survival rate of pediatric cancer patients has skyrocketed in the last decade and it's over 84%, safeguarding their future fertility is becoming a major concern for reproductive medicine. Surgical and medical approaches to personalize treatment or protect the gonads could be a valid first step to take. Testicular tissue autologous grafting or xenografting, and spermatogonial stem cells (SSCs) transplantation, are the main experimental options available, but spermatogenesis in vitro is becoming an intriguing alternative. All of these methods feature both strong and weak prospects. There is also relevant controversy regarding the type of testicular material to preserve and the cryopreservation methods. Since transplanted cells are bound to survive based on SSCs number, many ways to enrich their population in cultures have been proposed, as well as different sites of injection inside the testis. Testicular tissue graft has been experimented on mice, rabbits, rhesus macaques and porcine, allowing the birth of live offspring after performing intracytoplasmic sperm injection (ICSI), however it has never been performed on human males yet. In vitro spermatogenesis remains a mirage, although many steps in the right direction have been performed. The manufacturing of 3D scaffolds and artificial spermatogenetic niche, providing support to stem cells in cultures, seems like the best way to further advance in this field.
Insights
Fertility preservation for prepubertal boys facing gonadotoxic therapies is crucial. Experimental options like testicular tissue grafting and in vitro spermatogenesis show promise for restoring fertility in young cancer survivors.
Area of Science:
- Reproductive Medicine
- Oncology
- Pediatrics
Background:
- Fertility preservation is essential for prepubertal males undergoing gonadotoxic therapies.
- Increased survival rates in pediatric cancer necessitate fertility safeguarding.
- Established methods like semen cryopreservation are unsuitable for prepubertal boys.
Purpose of the Study:
- To review current and novel fertility preservation strategies for prepubertal males.
- To discuss experimental options and their prospects.
- To highlight challenges and future directions in the field.
Main Methods:
- Review of existing literature on fertility preservation techniques.
- Discussion of experimental approaches including testicular tissue grafting and spermatogonial stem cell transplantation.
- Exploration of in vitro spermatogenesis and artificial niche development.
Main Results:
- Testicular tissue grafting has shown success in animal models but not yet in humans.
- In vitro spermatogenesis is progressing, with 3D scaffolds showing potential.
- Spermatogonial stem cell enrichment and transplantation sites are areas of active research.
Conclusions:
- Fertility preservation for prepubertal males remains largely experimental.
- Testicular tissue grafting and in vitro spermatogenesis are promising avenues.
- Further research into optimizing cell culture and transplantation is needed.
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