Is the time right for transplanting immature testicular tissue or cells to restore male fertility? Expert perspectives on clinical implementation of autotransplantation of cryopreserved testicular tissue or cells for fertility restoration

Myriam Safrai; Ellen Goossens; Rod T Mitchell; Kyle E Orwig; Callista L Mulder; Ans M M van Pelt; Debra A Gook; Aurélie Feraille; Emily Delgouffe; Jill P Ginsberg; Jan-Bernd Stukenborg; Kathleen Duffin; Kirsi Jahnukainen; Claus Yding Andersen; Marianne D van de Wetering; Michael P Rimmer; Virginie Barraud-Lange; Nina Neuhaus; Sheila Lane; Hooman Sadri-Ardekani; Nathalie Rives; Christine Wyns

doi:10.1016/j.bpobgyn.2025.102638

Is the time right for transplanting immature testicular tissue or cells to restore male fertility? Expert perspectives on clinical implementation of autotransplantation of cryopreserved testicular tissue or cells for fertility restoration

Best Pract Res Clin Obstet Gynaecol. 2025 Sep:102:102638. doi: 10.1016/j.bpobgyn.2025.102638. Epub 2025 Jul 11.

Authors

Myriam Safrai¹, Ellen Goossens², Rod T Mitchell³, Kyle E Orwig⁴, Callista L Mulder⁵, Ans M M van Pelt⁵, Debra A Gook⁶, Aurélie Feraille⁷, Emily Delgouffe², Jill P Ginsberg⁸, Jan-Bernd Stukenborg⁹, Kathleen Duffin¹⁰, Kirsi Jahnukainen¹¹, Claus Yding Andersen¹², Marianne D van de Wetering¹³, Michael P Rimmer¹⁴, Virginie Barraud-Lange¹⁵, Nina Neuhaus¹⁶, Sheila Lane¹⁷, Hooman Sadri-Ardekani¹⁸, Nathalie Rives⁷, Christine Wyns¹⁹

Affiliations

¹ IVF Unit, Department of Obstetrics and Gynecology, Chaim Sheba Medical Center (Tel Hashomer), Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
² Biology of the Testis (BITE) Laboratory, Research Group Genetics, Reproduction and Development (GRAD), Vrije Universiteit Brussel, (VUB), 1090, Brussels, Belgium.
³ Centre for Reproductive Health, Institute of Regeneration and Repair, University of Edinburgh, Edinburgh, UK; Royal Hospital for Children and Young People, Edinburgh, UK. Electronic address: rod.mitchell@ed.ac.uk.
⁴ Department of Obstetrics, Gynecology and Reproductive Sciences, Magee-Womens Research Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
⁵ Reproductive Biology Laboratory, Center for Reproductive Medicine, Amsterdam UMC Location University of Amsterdam, Amsterdam, the Netherlands; Amsterdam Reproduction and Development Research Institute, Amsterdam, the Netherlands.
⁶ Reproductive Services, The Royal Women's Hospital, Parkville, VIC, Australia; Department of Obstetrics and Gynaecology, Royal Women's Hospital, University of Melbourne, Parkville, VIC, Australia.
⁷ NorDIC, Team "Adrenal and Gonadal Pathophysiology, " Biology of Reproduction-CECOS Laboratory, Rouen University Hospital, Rouen Normandy University, Rouen, France.
⁸ Division of Oncology, Children's Hospital of Philadelphia, Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
⁹ NORDFERTIL Research Lab Stockholm, Childhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institutet, and Karolinska University Hospital, Solna, Sweden; NORDFERTIL Research Lab Uppsala, Department of Organismal Biology, Uppsala University, Uppsala, Sweden.
¹⁰ Centre for Reproductive Health, Institute of Regeneration and Repair, University of Edinburgh, Edinburgh, UK; Royal Hospital for Children and Young People, Edinburgh, UK.
¹¹ NORDFERTIL Research Lab Stockholm, Childhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institutet, and Karolinska University Hospital, Solna, Sweden; Division of Haematology-Oncology and Stem Cell Transplantation, New Children's Hospital, Pediatric Research Center, Department of Pediatrics, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
¹² The Fertility Clinic and the Urological Department Herlev University Hospital of Copenhagen & Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
¹³ Princess Maxima Center for Pediatric Oncology, Utrecht, the Netherlands.
¹⁴ Centre for Reproductive Health, Institute of Regeneration and Repair, University of Edinburgh, Edinburgh, UK.
¹⁵ Department of Reproductive Biology CECOS, Public Assistance-Paris Hospital (AP-HP) Paris Centre University Hospital (HUPC), Cochin Hospital, Paris, France; AYA Unit, Fertility Preservation Consultation, Haematology Department, Public Assistance-Paris Hospital (AP-HP), Paris North University Hospital (HUPN), Nord, University of Paris Cité, Saint-Louis Hospital, Paris, France.
¹⁶ Centre of Reproductive Medicine and Andrology, University of Münster, Münster, Germany.
¹⁷ Nuffield Department of Women's & Reproductive Health, University of Oxford, England, UK.
¹⁸ Institute of Regenerative Medicine and Department of Urology, Atrium Health Wake Forest Baptist, Winston-Salem, NC, 27157, USA.
¹⁹ Department of Gynecology and Andrology, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium.

PMID: 40695104
DOI: 10.1016/j.bpobgyn.2025.102638

Abstract

Transplantations of cryopreserved immature testicular tissue (ITT) or spermatogonial stem cells (SSCs) represent promising approaches to restore fertility in patients with testicular tissue or cell suspension cryopreserved for fertility preservation. With over 3000 testicular samples cryopreserved globally, clinically viable and standardized protocols restoring fertility using cryopreserved testicular tissue/cells are urgently needed. Decades of research demonstrate the feasibility of immature testicular tissue transplantation (ITTT) or spermatogonial stem cell transplantation (SSCT) in animal models, including non-human primates. However, significant challenges remain in translating these options to human clinical practice. Critical factors include rigorous patient selection, robust pre-transplant evaluations to mitigate risks of malignant cell reintroduction, and the optimization of transplantation timing to support spermatogenesis. Developing comprehensive follow-up protocols and international data-sharing frameworks is essential to optimize outcomes. While offering the potential for genetic parenthood and enhanced quality of life for cancer survivors, these techniques require further refinement to ensure safety, efficacy, and realistic expectations. This paper outlines the framework for advancing the clinical translation of autotransplantation of testicular tissue/cells through collaboration and innovation.

Keywords: Fertility preservation; Immature testicular tissue; Pre-pubertal boys; Spermatogonial stem cell transplantation; Testicular tissue cryopreservation; Testicular tissue transplantation.

Publication types

Review

MeSH terms

Adult Germline Stem Cells* / transplantation
Animals
Cryopreservation*
Fertility Preservation* / methods
Humans
Infertility, Male* / therapy
Male
Testis* / cytology
Testis* / transplantation
Transplantation, Autologous