Helen M Picton1, Christine Wyns2, Richard A Anderson3, Ellen Goossens4, Kirsi Jahnukainen5, Sabine Kliesch6, Rod T Mitchell3, G Pennings7, Natalie Rives8, Herman Tournaye9, Ans M M van Pelt10, Ursula Eichenlaub-Ritter11, Stefan Schlatt6. 1. Division of Reproduction and Early Development, Leeds Institute of Cardiovascular and Metabolic Medicine, Faculty of Medicine and Health, University of Leeds, Clarendon Way, Leeds LS2 9JT, UK h.m.picton@leeds.ac.uk. 2. Université Catholique de Louvain (UCL), Pôle de Recherche en Gynécologie, Institut de Recherche Expérimentale et Clinique (IREC), 1200 Brussels, Belgium Department of Gynecology-Andrology, Cliniques Universitaires Saint-Luc, Avenue Hippocrate, 10, 1200 Brussels, Belgium. 3. MRC Centre for Reproductive Health, Queens Medical Research Institute, University of Edinburgh, Edinburgh, UK. 4. Research Group Biology of the Testis (BITE), Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium. 5. Children's Hospital, Helsinki University Central Hospital, Helsinki, Finland Department of Women's and Children's Health, Karolinska Institute and University Hospital, Stockholm, Sweden. 6. Centre of Reproductive Medicine and Andrology, University Münster, Domagkstraße 11, 48149 Münster, Germany. 7. Bioethics Institute Ghent (BIG), Faculty of Philosophy and Moral Science, Ghent University, Ghent, Belgium. 8. Laboratoire de Biologie de la Reproduction - CECOS, Research Team EA 4308 'Gametogenesis and gamete quality', IRIB, Rouen University Hospital, University of Rouen, 76031 Rouen Cedex, France. 9. Centre for Reproductive Medicine, University Hospital of the Brussels Free University, Laarbeeklaan 101, 1090 Brussels, Belgium. 10. Center for Reproductive Medicine, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. 11. Faculty of Biology, Gene Technology/Microbiology, University of Bielefeld, Bielefeld 33501, Germany.
Abstract
STUDY QUESTION: What clinical practices, patient management strategies and experimental methods are currently being used to preserve and restore the fertility of prepubertal boys and adolescent males? SUMMARY ANSWER: Based on a review of the clinical literature and research evidence for sperm freezing and testicular tissue cryopreservation, and after consideration of the relevant ethical and legal challenges, an algorithm for the cryopreservation of sperm and testicular tissue is proposed for prepubertal boys and adolescent males at high risk of fertility loss. WHAT IS KNOWN ALREADY: A known late effect of the chemotherapy agents and radiation exposure regimes used to treat childhood cancers and other non-malignant conditions in males is the damage and/or loss of the proliferating spermatogonial stem cells in the testis. Cryopreservation of spermatozoa is the first line treatment for fertility preservation in adolescent males. Where sperm retrieval is impossible, such as in prepubertal boys, or it is unfeasible in adolescents prior to the onset of ablative therapies, alternative experimental treatments such as testicular tissue cryopreservation and the harvesting and banking of isolated spermatogonial stem cells can now be proposed as viable means of preserving fertility. STUDY DESIGN, SIZE, DURATION: Advances in clinical treatments, patient management strategies and the research methods used to preserve sperm and testicular tissue for prepubertal boys and adolescents were reviewed. A snapshot of the up-take of testis cryopreservation as a means to preserve the fertility of young males prior to December 2012 was provided using a questionnaire. PARTICIPANTS/MATERIALS, SETTING, METHODS: A comprehensive literature review was conducted. In addition, survey results of testis freezing practices in young patients were collated from 24 European centres and Israeli University Hospitals. MAIN RESULTS AND THE ROLE OF CHANCE: There is increasing evidence of the use of testicular tissue cryopreservation as a means to preserve the fertility of pre- and peri-pubertal boys of up to 16 year-old. The survey results indicate that of the 14 respondents, half of the centres were actively offering testis tissue cryobanking as a means of safeguarding the future fertility of boys and adolescents as more than 260 young patients (age range less than 1 year old to 16 years of age), had already undergone testicular tissue retrieval and storage for fertility preservation. The remaining centres were considering the implementation of a tissue-based fertility preservation programme for boys undergoing oncological treatments. LIMITATIONS, REASONS FOR CAUTION: The data collected were limited by the scope of the questionnaire, the geographical range of the survey area, and the small number of respondents. WIDER IMPLICATIONS OF THE FINDINGS: The clinical and research questions identified and the ethical and legal issues raised are highly relevant to the multi-disciplinary teams developing treatment strategies to preserve the fertility of prepubertal and adolescent boys who have a high risk of fertility loss due to ablative interventions, trauma or genetic pre-disposition.
STUDY QUESTION: What clinical practices, patient management strategies and experimental methods are currently being used to preserve and restore the fertility of prepubertal boys and adolescent males? SUMMARY ANSWER: Based on a review of the clinical literature and research evidence for sperm freezing and testicular tissue cryopreservation, and after consideration of the relevant ethical and legal challenges, an algorithm for the cryopreservation of sperm and testicular tissue is proposed for prepubertal boys and adolescent males at high risk of fertility loss. WHAT IS KNOWN ALREADY: A known late effect of the chemotherapy agents and radiation exposure regimes used to treat childhood cancers and other non-malignant conditions in males is the damage and/or loss of the proliferating spermatogonial stem cells in the testis. Cryopreservation of spermatozoa is the first line treatment for fertility preservation in adolescent males. Where sperm retrieval is impossible, such as in prepubertal boys, or it is unfeasible in adolescents prior to the onset of ablative therapies, alternative experimental treatments such as testicular tissue cryopreservation and the harvesting and banking of isolated spermatogonial stem cells can now be proposed as viable means of preserving fertility. STUDY DESIGN, SIZE, DURATION: Advances in clinical treatments, patient management strategies and the research methods used to preserve sperm and testicular tissue for prepubertal boys and adolescents were reviewed. A snapshot of the up-take of testis cryopreservation as a means to preserve the fertility of young males prior to December 2012 was provided using a questionnaire. PARTICIPANTS/MATERIALS, SETTING, METHODS: A comprehensive literature review was conducted. In addition, survey results of testis freezing practices in young patients were collated from 24 European centres and Israeli University Hospitals. MAIN RESULTS AND THE ROLE OF CHANCE: There is increasing evidence of the use of testicular tissue cryopreservation as a means to preserve the fertility of pre- and peri-pubertal boys of up to 16 year-old. The survey results indicate that of the 14 respondents, half of the centres were actively offering testis tissue cryobanking as a means of safeguarding the future fertility of boys and adolescents as more than 260 young patients (age range less than 1 year old to 16 years of age), had already undergone testicular tissue retrieval and storage for fertility preservation. The remaining centres were considering the implementation of a tissue-based fertility preservation programme for boys undergoing oncological treatments. LIMITATIONS, REASONS FOR CAUTION: The data collected were limited by the scope of the questionnaire, the geographical range of the survey area, and the small number of respondents. WIDER IMPLICATIONS OF THE FINDINGS: The clinical and research questions identified and the ethical and legal issues raised are highly relevant to the multi-disciplinary teams developing treatment strategies to preserve the fertility of prepubertal and adolescent boys who have a high risk of fertility loss due to ablative interventions, trauma or genetic pre-disposition.
Authors: Gunapala Shetty; Jennifer M Mitchell; Jennifer M Meyer; Zhuang Wu; Truong N A Lam; Thien T Phan; Jie Zhang; Lorraine Hill; Ramesh C Tailor; Karen A Peters; Maria C Penedo; Carol Hanna; Kyle E Orwig; Marvin L Meistrich Journal: Andrology Date: 2020-05-18 Impact factor: 3.842
Authors: A Balduzzi; J-H Dalle; K Jahnukainen; M von Wolff; G Lucchini; M Ifversen; K T Macklon; C Poirot; T Diesch; A Jarisch; D Bresters; I Yaniv; B Gibson; A M Willasch; R Fadini; L Ferrari; A Lawitschka; A Ahler; N Sänger; S Corbacioglu; M Ansari; R Moffat; A Dalissier; E Beohou; P Sedlacek; A Lankester; C D De Heredia Rubio; K Vettenranta; J Wachowiak; A Yesilipek; E Trigoso; T Klingebiel; C Peters; P Bader Journal: Bone Marrow Transplant Date: 2017-07-24 Impact factor: 5.483
Authors: J-H Dalle; G Lucchini; A Balduzzi; M Ifversen; K Jahnukainen; K T Macklon; A Ahler; A Jarisch; M Ansari; E Beohou; D Bresters; S Corbacioglu; A Dalissier; C Diaz de Heredia Rubio; T Diesch; B Gibson; T Klingebiel; A Lankester; A Lawitschka; R Moffat; C Peters; C Poirot; N Saenger; P Sedlacek; E Trigoso; K Vettenranta; J Wachowiak; A Willasch; M von Wolff; I Yaniv; A Yesilipek; P Bader Journal: Bone Marrow Transplant Date: 2017-03-13 Impact factor: 5.483
Authors: Molly B Moravek; Leslie C Appiah; Antoinette Anazodo; Karen C Burns; Veronica Gomez-Lobo; Holly R Hoefgen; Olivia Jaworek Frias; Monica M Laronda; Jennifer Levine; Lillian R Meacham; Mary Ellen Pavone; Gwendolyn P Quinn; Erin E Rowell; Andrew C Strine; Teresa K Woodruff; Leena Nahata Journal: J Adolesc Health Date: 2019-01-14 Impact factor: 5.012
Authors: Hanneke M van Santen; Marry M van den Heuvel-Eibrink; Marianne D van de Wetering; W Hamish Wallace Journal: Horm Res Paediatr Date: 2019-01-31 Impact factor: 2.852