Fertility preservation in boys: recent developments and new insights

cryopreservation fertility preservation fertility restoration in vitro spermatogenesis prepubertal boys spermatogonial stem cell testicular tissue freezing testis transplantation

Journal

Human reproduction open
ISSN: 2399-3529
Titre abrégé: Hum Reprod Open
Pays: England
ID NLM: 101722764

Informations de publication

Date de publication:
2020
Historique:
received: 22 01 2020
revised: 22 01 2020
entrez: 13 6 2020
pubmed: 13 6 2020
medline: 13 6 2020
Statut: epublish

Résumé

Infertility is an important side effect of treatments used for cancer and other non-malignant conditions in males. This may be due to the loss of spermatogonial stem cells (SSCs) and/or altered functionality of testicular somatic cells (e.g. Sertoli cells, Leydig cells). Whereas sperm cryopreservation is the first-line procedure to preserve fertility in post-pubertal males, this option does not exist for prepubertal boys. For patients unable to produce sperm and at high risk of losing their fertility, testicular tissue freezing is now proposed as an alternative experimental option to safeguard their fertility. With this review, we aim to provide an update on clinical practices and experimental methods, as well as to describe patient management inclusion strategies used to preserve and restore the fertility of prepubertal boys at high risk of fertility loss. Based on the expertise of the participating centres and a literature search of the progress in clinical practices, patient management strategies and experimental methods used to preserve and restore the fertility of prepubertal boys at high risk of fertility loss were identified. In addition, a survey was conducted amongst European and North American centres/networks that have published papers on their testicular tissue banking activity. Since the first publication on murine SSC transplantation in 1994, remarkable progress has been made towards clinical application: cryopreservation protocols for testicular tissue have been developed in animal models and are now offered to patients in clinics as a still experimental procedure. Transplantation methods have been adapted for human testis, and the efficiency and safety of the technique are being evaluated in mouse and primate models. However, important practical, medical and ethical issues must be resolved before fertility restoration can be applied in the clinic.Since the previous survey conducted in 2012, the implementation of testicular tissue cryopreservation as a means to preserve the fertility of prepubertal boys has increased. Data have been collected from 24 co-ordinating centres worldwide, which are actively offering testis tissue cryobanking to safeguard the future fertility of boys. More than 1033 young patients (age range 3 months to 18 years) have already undergone testicular tissue retrieval and storage for fertility preservation. The review does not include the data of all reproductive centres worldwide. Other centres might be offering testicular tissue cryopreservation. Therefore, the numbers might be not representative for the entire field in reproductive medicine and biology worldwide. The key ethical issue regarding fertility preservation in prepubertal boys remains the experimental nature of the intervention. The revised procedures can be implemented by the multi-disciplinary teams offering and/or developing treatment strategies to preserve the fertility of prepubertal boys who have a high risk of fertility loss. The work was funded by ESHRE. None of the authors has a conflict of interest.

Sections du résumé

BACKGROUND BACKGROUND
Infertility is an important side effect of treatments used for cancer and other non-malignant conditions in males. This may be due to the loss of spermatogonial stem cells (SSCs) and/or altered functionality of testicular somatic cells (e.g. Sertoli cells, Leydig cells). Whereas sperm cryopreservation is the first-line procedure to preserve fertility in post-pubertal males, this option does not exist for prepubertal boys. For patients unable to produce sperm and at high risk of losing their fertility, testicular tissue freezing is now proposed as an alternative experimental option to safeguard their fertility.
OBJECTIVE AND RATIONALE OBJECTIVE
With this review, we aim to provide an update on clinical practices and experimental methods, as well as to describe patient management inclusion strategies used to preserve and restore the fertility of prepubertal boys at high risk of fertility loss.
SEARCH METHODS METHODS
Based on the expertise of the participating centres and a literature search of the progress in clinical practices, patient management strategies and experimental methods used to preserve and restore the fertility of prepubertal boys at high risk of fertility loss were identified. In addition, a survey was conducted amongst European and North American centres/networks that have published papers on their testicular tissue banking activity.
OUTCOMES RESULTS
Since the first publication on murine SSC transplantation in 1994, remarkable progress has been made towards clinical application: cryopreservation protocols for testicular tissue have been developed in animal models and are now offered to patients in clinics as a still experimental procedure. Transplantation methods have been adapted for human testis, and the efficiency and safety of the technique are being evaluated in mouse and primate models. However, important practical, medical and ethical issues must be resolved before fertility restoration can be applied in the clinic.Since the previous survey conducted in 2012, the implementation of testicular tissue cryopreservation as a means to preserve the fertility of prepubertal boys has increased. Data have been collected from 24 co-ordinating centres worldwide, which are actively offering testis tissue cryobanking to safeguard the future fertility of boys. More than 1033 young patients (age range 3 months to 18 years) have already undergone testicular tissue retrieval and storage for fertility preservation.
LIMITATIONS REASONS FOR CAUTION CONCLUSIONS
The review does not include the data of all reproductive centres worldwide. Other centres might be offering testicular tissue cryopreservation. Therefore, the numbers might be not representative for the entire field in reproductive medicine and biology worldwide. The key ethical issue regarding fertility preservation in prepubertal boys remains the experimental nature of the intervention.
WIDER IMPLICATIONS CONCLUSIONS
The revised procedures can be implemented by the multi-disciplinary teams offering and/or developing treatment strategies to preserve the fertility of prepubertal boys who have a high risk of fertility loss.
STUDY FUNDING/COMPETING INTERESTS BACKGROUND
The work was funded by ESHRE. None of the authors has a conflict of interest.

Identifiants

pubmed: 32529047
doi: 10.1093/hropen/hoaa016
pii: hoaa016
pmc: PMC7275639
doi:

Types de publication

Journal Article

Langues

eng

Pagination

hoaa016

Subventions

Organisme : Medical Research Council
ID : MR/N022556/1
Pays : United Kingdom

Informations de copyright

© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology.

Références

Hum Reprod. 2018 Apr 1;33(4):636-645
pubmed: 29452353
Med Pediatr Oncol. 1999 Jul;33(1):2-8
pubmed: 10401490
Genome Biol. 2005;6(2):209
pubmed: 15693956
Hum Reprod. 2019 Mar 1;34(3):403-413
pubmed: 30753464
Fertil Steril. 2014 Dec;102(6):1700-7.e1
pubmed: 25256932
JAMA. 2009 Nov 18;302(19):2127-34
pubmed: 19920237
Stem Cells Transl Med. 2014 Sep;3(9):1043-54
pubmed: 25038247
Fertil Steril. 2014 Aug;102(2):558-565.e5
pubmed: 24864010
Clin Med Insights Reprod Health. 2019 Nov 20;13:1179558119886342
pubmed: 31798308
Hum Reprod Update. 2010 May-Jun;16(3):312-28
pubmed: 20047952
J Reprod Fertil. 1965 Apr;9:243-8
pubmed: 14273758
Acta Obstet Gynecol Scand. 2019 May;98(5):679-680
pubmed: 30793287
Br J Urol. 1975;47(7):891-8
pubmed: 1222356
Proc Natl Acad Sci U S A. 1994 Nov 22;91(24):11298-302
pubmed: 7972053
Biol Reprod. 2003 Jun;68(6):2331-5
pubmed: 12606381
Hum Reprod. 2015 Nov;30(11):2463-75
pubmed: 26358785
Theriogenology. 2010 Mar 1;73(4):512-22
pubmed: 19962749
J Pediatr Oncol Nurs. 2008 Mar-Apr;25(2):102-6
pubmed: 18270309
Biol Reprod. 2010 Aug 1;83(2):261-7
pubmed: 20393168
Andrology. 2019 Sep 20;:
pubmed: 31539453
Endocr Dev. 2018;33:149-157
pubmed: 29886483
Cell Stem Cell. 2012 Nov 2;11(5):715-26
pubmed: 23122294
J Androl. 2012 Nov-Dec;33(6):1394-401
pubmed: 22837112
Int J Androl. 2009 Feb;32(1):66-73
pubmed: 17916184
Stem Cells Dev. 2018 Aug 1;27(15):1007-1020
pubmed: 29779447
Science. 2007 Apr 20;316(5823):404-5
pubmed: 17446391
Stem Cells Dev. 2017 Aug 1;26(15):1121-1131
pubmed: 28474535
Med Pediatr Oncol. 2000 Jul;35(1):52-63
pubmed: 10881008
Hum Reprod. 2011 Apr;26(4):737-47
pubmed: 21227939
Reprod Biomed Online. 2017 Aug;35(2):180-188
pubmed: 28583375
Sci Rep. 2017 Nov 13;7(1):15459
pubmed: 29133858
Hum Reprod. 2010 Jan;25(1):37-41
pubmed: 19861330
PLoS One. 2017 Jul 20;12(7):e0181377
pubmed: 28727831
Fertil Steril. 2011 May;95(6):2123.e9-12
pubmed: 21300331
Mol Hum Reprod. 2018 May 1;24(5):271-282
pubmed: 29538744
J Control Release. 2016 Jul 28;234:79-89
pubmed: 27189137
Pediatr Blood Cancer. 2014 Sep;61(9):1673-8
pubmed: 24777742
J Assist Reprod Genet. 2013 Jan;30(1):3-9
pubmed: 23242649
Cell Res. 2016 Jan;26(1):139-42
pubmed: 26369429
Am J Bioeth. 2013;13(3):46-8
pubmed: 23428041
Hum Reprod. 2014 Mar;29(3):413-7
pubmed: 24430776
Hum Reprod. 2005 Jun;20(6):1676-87
pubmed: 15860503
Hum Reprod. 2014 Sep;29(9):2018-31
pubmed: 24963164
Hum Reprod. 2007 May;22(5):1384-95
pubmed: 17259225
Biol Reprod. 2003 Aug;69(2):612-6
pubmed: 12700182
Fertil Steril. 2003 Mar;79 Suppl 1:795-801
pubmed: 12620493
Hum Reprod. 2018 Sep 1;33(9):1677-1683
pubmed: 30052981
Cell. 2011 Aug 19;146(4):519-32
pubmed: 21820164
Fertil Steril. 2016 Dec;106(7):1652-1657.e2
pubmed: 27717555
Front Physiol. 2018 Oct 09;9:1413
pubmed: 30356879
Biol Reprod. 2006 Aug;75(2):167-75
pubmed: 16571874
Endocr Connect. 2018 Feb;7(2):R69-R87
pubmed: 29351905
J Assist Reprod Genet. 2012 Sep;29(9):957-67
pubmed: 22735929
Reproduction. 2008 Nov;136(5):543-57
pubmed: 18663014
Ann Ital Med Int. 2000 Jul-Sep;15(3):189-94
pubmed: 11059058
Cancer Res. 2012 Oct 15;72(20):5174-8
pubmed: 22902414
Fertil Steril. 2011 Jun;95(7):2434.e11-3
pubmed: 21377156
Cell Rep. 2019 Feb 5;26(6):1501-1517.e4
pubmed: 30726734
Hum Reprod. 2015 Sep;30(9):2022-30
pubmed: 26141713
Nature. 2011 Mar 24;471(7339):504-7
pubmed: 21430778
Lancet Oncol. 2014 Oct;15(11):1215-23
pubmed: 25239573
J Clin Invest. 2013 Apr;123(4):1833-43
pubmed: 23549087
Endocrinology. 2012 Feb;153(2):887-900
pubmed: 22147017
Fertil Steril. 2016 May;105(5):1162-1169.e5
pubmed: 26868991
J Clin Oncol. 2012 Sep 20;30(27):3408-16
pubmed: 22649147
Hum Reprod. 2013 Nov;28(11):3012-25
pubmed: 24001715
Cancer. 2011 Jan 1;117(1):4-10
pubmed: 21235031
Nature. 2002 Aug 15;418(6899):778-81
pubmed: 12181567
Hum Reprod. 2008 Nov;23(11):2402-14
pubmed: 18664476
Pediatr Hematol Oncol. 2009 Jun;26(4):186-94
pubmed: 19437321
Cell Stem Cell. 2018 Oct 4;23(4):599-614.e4
pubmed: 30174296
Cell Res. 2017 Feb;27(2):241-252
pubmed: 28008926
J Androl. 2004 Nov-Dec;25(6):926-30
pubmed: 15477365
Hum Reprod. 2010 Jul;25(7):1836-42
pubmed: 20488806
Hum Reprod. 2018 Jan 1;33(1):81-90
pubmed: 29165614
JAMA. 2011 Jun 15;305(23):2416-8
pubmed: 21673293
Leukemia. 2017 Jun;31(6):1460-1463
pubmed: 28270690
Fertil Steril. 2011 Oct;96(4):837-42
pubmed: 21868007
Curr Opin Endocrinol Diabetes Obes. 2015 Jun;22(3):217-23
pubmed: 25871959
Fertil Steril. 2013 Apr;99(5):1264-1272.e1
pubmed: 23312508
Fertil Steril. 2018 Nov;110(6):1045-1057.e3
pubmed: 30396549
Biol Reprod. 2004 May;70(5):1500-3
pubmed: 14736818
Hum Reprod. 2007 Jun;22(6):1603-11
pubmed: 17483089
J Pediatr Urol. 2018 Jun;14(3):274.e1-274.e5
pubmed: 29571658
Pediatr Blood Cancer. 2014 Jun;61(6):1094-100
pubmed: 24851267
Reproduction. 2002 Sep;124(3):339-46
pubmed: 12201807
J Androl. 1994 Nov-Dec;15(6):608-13
pubmed: 7721664
Epigenetics. 2017 Jul 3;12(7):527-539
pubmed: 27786608
Fertil Steril. 2002 Dec;78(6):1225-33
pubmed: 12477516
Reproduction. 2007 Dec;134(6):767-79
pubmed: 18042634
Hum Reprod. 2011 Feb;26(2):282-93
pubmed: 21123192
Cell Res. 2018 Dec;28(12):1141-1157
pubmed: 30315278
Hum Reprod. 1999 Jan;14(1):144-50
pubmed: 10374111
Nat Commun. 2014 Jul 01;5:4320
pubmed: 24984101
Lancet Diabetes Endocrinol. 2015 Jul;3(7):556-67
pubmed: 25873571
PLoS One. 2015 Feb 25;10(2):e0116660
pubmed: 25714609
Hum Reprod Update. 2018 Mar 1;24(2):176-191
pubmed: 29281008
Endocrinology. 2008 Apr;149(4):1736-47
pubmed: 18174281
Radiat Res. 1974 Sep;59(3):665-78
pubmed: 4428015
Front Physiol. 2019 Sep 19;10:1155
pubmed: 31607938
Reproduction. 2006 Jun;131(6):1091-8
pubmed: 16735548
Psychooncology. 2017 Oct;26(10):1684-1690
pubmed: 28734133
BMC Cancer. 2018 Feb 17;18(1):192
pubmed: 29452595
Hum Reprod. 2013 Mar;28(3):578-89
pubmed: 23315062
J Reprod Fertil. 1981 Nov;63(2):347-53
pubmed: 7299743
Mol Hum Reprod. 2016 Sep;22(9):601-12
pubmed: 27430551
Fertil Steril. 2008 Nov;90(5):2019-22
pubmed: 18439593
Am J Bioeth. 2013;13(3):28-35
pubmed: 23428034
Fertil Steril. 2014 Apr;101(4):1072-1078.e1
pubmed: 24581582
Patient Educ Couns. 2008 Sep;72(3):402-10
pubmed: 18621502
Hum Reprod. 2013 Jul;28(7):1816-26
pubmed: 23569082
Biol Reprod. 2004 Aug;71(2):494-501
pubmed: 15070832
Cell Rep. 2018 Nov 6;25(6):1650-1667.e8
pubmed: 30404016
J Urol. 2015 Nov;194(5):1420-4
pubmed: 26032139
Stem Cell Reports. 2014 Oct 14;3(4):663-75
pubmed: 25358793
Fertil Steril. 2009 May;91(5 Suppl):2264-72
pubmed: 18394623
J Adolesc Health. 2017 Nov;61(5):571-576
pubmed: 28917444
Hum Reprod. 2017 Dec 1;32(12):2366-2372
pubmed: 29040511
Exp Cell Res. 1964 Oct;36:19-27
pubmed: 14222741
Lancet. 1999 Feb 13;353(9152):555-6
pubmed: 10028987
Reproduction. 2009 Oct;138(4):667-77
pubmed: 19633133
Reprod Biomed Online. 2016 Jul;33(1):29-38
pubmed: 27156003
Lancet Oncol. 2014 Sep;15(10):1129-36
pubmed: 25130994
Fertil Steril. 2015 Feb;103(2):478-86.e1
pubmed: 25527232
Reproduction. 2019 Nov;158(5):F1-F14
pubmed: 30844751
Hum Reprod. 2018 Jun 1;33(6):1009-1022
pubmed: 29684126
Clin Endocrinol (Oxf). 2017 Sep;87(3):279-285
pubmed: 28504866
Fertil Steril. 2012 Dec;98(6):1443-8.e1
pubmed: 22981175
Science. 2019 Mar 22;363(6433):1314-1319
pubmed: 30898927
Biol Reprod. 2010 Feb;82(2):363-72
pubmed: 19846602
Mol Reprod Dev. 1999 Jun;53(2):142-8
pubmed: 10331452
Hum Reprod. 2006 Feb;21(2):484-91
pubmed: 16210383
Reprod Biomed Online. 2019 Jul;39(1):119-133
pubmed: 31005581
Biol Reprod. 2004 Dec;71(6):2087-91
pubmed: 15317690
Br J Haematol. 2015 Sep;170(5):719-26
pubmed: 25974284
Lancet Oncol. 2017 Feb;18(2):e75-e90
pubmed: 28214419
Reprod Biomed Online. 2017 Mar;34(3):291-297
pubmed: 28040413
Hum Reprod. 2014 Nov;29(11):2497-511
pubmed: 25267789
Reproduction. 2003 Jun;125(6):769-84
pubmed: 12773099
Hum Reprod. 2019 Jun 4;34(6):966-977
pubmed: 31111889
Biol Reprod. 2016 Oct;95(4):89
pubmed: 27580986
Hum Reprod. 2009 Sep;24(9):2255-63
pubmed: 19525299
J Med Ethics. 2018 Jan;44(1):27-31
pubmed: 29084865
Hum Reprod. 2008 Jan;23(1):17-28
pubmed: 17989070
Reprod Toxicol. 2001 Nov-Dec;15(6):611-7
pubmed: 11738514
Development. 2005 Sep;132(18):4155-63
pubmed: 16107472
Hum Reprod. 2016 Sep;31(9):1952-9
pubmed: 27412247
Biomed Res Int. 2014;2014:138350
pubmed: 24738045
Bull Acad Natl Med. 2013 Apr-May;197(4-5):877-86; discussion 886
pubmed: 25518156
Proc Natl Acad Sci U S A. 2005 Nov 29;102(48):17430-5
pubmed: 16293688
J Androl. 2006 Jul-Aug;27(4):527-33
pubmed: 16598031
Fertil Steril. 2013 Oct;100(4):981-8
pubmed: 23850302
Arch Dis Child. 1982 Apr;57(4):287-91
pubmed: 7082042

Auteurs

E Goossens (E)

Biology of the Testis, Research Laboratory for Reproduction, Genetics and Regenerative Medicine, Vrije Universiteit Brussel (VUB), 1090 Brussels, Belgium.

K Jahnukainen (K)

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, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

R T Mitchell (RT)

MRC Centre for Reproductive Health, The Queen's Medical Research Institute, The University of Edinburgh; and the Edinburgh Royal Hospital for Sick Children, Edinburgh, UK.

Amm van Pelt (A)

Center for Reproductive Medicine, Amsterdam UMC, Amsterdam Reproduction and Development Research Institute, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.

G Pennings (G)

Bioethics Institute Ghent, Ghent University, 9000 Ghent, Belgium.

N Rives (N)

Normandie Univ, UNIROUEN, EA 4308 "Gametogenesis and Gamete Quality", Rouen University Hospital, Biology of Reproduction-CECOS Laboratory, F 76000, Rouen, France.

J Poels (J)

Department of Gynecology and Andrology, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium.

C Wyns (C)

Department of Gynecology and Andrology, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium.

S Lane (S)

Department of Paediatric Oncology and Haematology, Children's Hospital Oxford, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.

K A Rodriguez-Wallberg (KA)

Department of Oncology Pathology, Karolinska Institutet, Solna, Sweden.
Section of Reproductive Medicine, Division of Gynecology and Reproduction, Karolinska University Hospital, Stockholm, Sweden.

A Rives (A)

Normandie Univ, UNIROUEN, EA 4308 "Gametogenesis and Gamete Quality", Rouen University Hospital, Biology of Reproduction-CECOS Laboratory, F 76000, Rouen, France.

H Valli-Pulaski (H)

Magee-Womens Research Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.

S Steimer (S)

Magee-Womens Research Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.

S Kliesch (S)

Centre of Reproductive Medicine and Andrology, Institute of Reproductive and Regenerative Biology, University of Münster, Münster, Germany.

A Braye (A)

Biology of the Testis, Research Laboratory for Reproduction, Genetics and Regenerative Medicine, Vrije Universiteit Brussel (VUB), 1090 Brussels, Belgium.

M M Andres (MM)

Reproductive Medicine Unit, Hospital Universitario y Politécnico La Fe, Valencia, Spain.

J Medrano (J)

Reproductive Medicine Unit, Hospital Universitario y Politécnico La Fe, Valencia, Spain.

L Ramos (L)

Departement of Obstetrics and Gynacology, Division Reproductive Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.

S G Kristensen (SG)

Laboratory of Reproductive Biology, The Juliane Marie Centre for Women, Children and Reproduction, University Hospital of Copenhagen, Denmark.

C Y Andersen (CY)

Laboratory of Reproductive Biology, The Juliane Marie Centre for Women, Children and Reproduction, University Hospital of Copenhagen, Denmark.

R Bjarnason (R)

Children's Medical Center, Landspítali University Hospital, Reykjavik, Iceland and Faculty of Medicine, University of Iceland, Reykjavik, Iceland.

K E Orwig (KE)

Magee-Womens Research Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.

N Neuhaus (N)

Centre of Reproductive Medicine and Andrology, Institute of Reproductive and Regenerative Biology, University of Münster, Münster, Germany.

J B Stukenborg (JB)

NORDFERTIL Research Lab Stockholm, Childhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institutet and Karolinska University Hospital, Solna, Sweden.

Classifications MeSH