International consensus: ovarian tissue cryopreservation in young Turner syndrome patients: outcomes of an ethical Delphi study including 55 experts from 16 different countries
Open accessAbstract
STUDY QUESTION: What is the standpoint of an international expert panel on ovarian tissue cryopreservation (OTC) in young females with Turner syndrome (TS)? SUMMARY ANSWER: The expert panel states that OTC should be offered to young females with TS, but under strict conditions only. WHAT IS KNOWN ALREADY: OTC is already an option for preserving the fertility of young females at risk of iatrogenic primary ovarian insufficiency (POI). Offering OTC to females with a genetic cause of POI could be the next step. One of the most common genetic disorders related to POI is TS. Due to an early depletion of the ovarian reserve, most females with TS are confronted with infertility before reaching adulthood. However, before offering OTC as an experimental fertility preservation option to young females with TS, medical and ethical concerns need to be addressed. STUDY DESIGN, SIZE, DURATION: A three-round ethical Delphi study was conducted to systematically discuss whether the expected benefits exceed the expected negative consequences of OTC in young females with TS. The aim was to reach group consensus and form an international standpoint based on selected key statements. The study took place between February and December 2018. PARTICIPANTS/MATERIALS, SETTING, METHODS: Anonymous panel selection was based on expertise in TS, fertility preservation or medical ethics. A mixed panel of 12 gynaecologists, 13 (paediatric) endocrinologists, 10 medical ethicists and 20 patient representatives from 16 different countries gave consent to participate in this international Delphi study. In the first two rounds, experts were asked to rate and rank 38 statements regarding OTC in females with TS. Participants were offered the possibility to adjust their opinions after repetitive feedback. The selection of key statements was based on strict inclusion criteria. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 46 participants completed the first Delphi round (response rate 84%). Based on strict selection criteria, six key statements were selected, and 13 statements were discarded. The remaining 19 statements and two additional statements submitted by the expert panel were re-evaluated in the second round by 41 participants (response rate 75%). The analysis of the second survey resulted in the inclusion of two additional key statements. After the approval of these eight key statements, the majority of the expert panel (96%) believed that OTC should be offered to young females with TS, but in a safe and controlled research setting first, with proper counselling and informed consent procedures, before offering this procedure in routine care. The remaining participants (4%) did not object but did not respond despite several reminders. LIMITATIONS, REASONS FOR CAUTION: The anonymous nature of this study may have led to lack of accountability. The selection of experts was based on their willingness to participate. The fact that not all panellists took part in all rounds may have resulted in selection bias. WIDER IMPLICATIONS OF THE FINDINGS: This international standpoint is the first step in the global acceptance of OTC in females with TS. Future collaborative research with a focus on efficacy and safety and long-term follow-up is urgently needed. Furthermore, we recommend an international register for fertility preservation procedures in females with TS. STUDY FUNDING/COMPETING INTEREST(S): Unconditional funding (A16-1395) was received from Merck B.V., The Netherlands. The authors declare that they have no conflict of interest.
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Individuals with TS may derive comfort from learning about fertility preservation options through consultation with knowledgeable providers and the associated sense of having explored all possible options for future fertility.
“Individuals with TS may derive comfort from learning about fertility preservation options through consultation with knowledgeable providers and the associated sense of having explored all possible options for future fertility.572,622”
From Clinical practice guidelines for the care of girls and women with Turner syndrome. (2024) · cites this paper as [622]
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van Hagen, I. M., Duijnhouwer, A. L., Ten Kate-Booij, M. J., Dykgraaf, R. H. M., Duvekot, J. J., Utens, E. M. W. J., & Roos-Hesselink, J. W. (2017) · Journal of Psychosomatic Obstetrics & Gynecology · doi:10.1080/0167482x.2016.1216961 · Cited by 10 · see citing works
Non‐genetic Mothers and Their ‘Own’ Children: Infertility and IVF Donor Birth
Hallebone, E. (1991) · Australian Journal of Social Issues · doi:10.1002/j.1839-4655.1991.tb01229.x · Cited by 6 · see citing works
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[Oocyte vitrification: for whom?].
Balkenende, E., Dahhan, T., Repping, S., de Melker, A. A., van der Veen, F., & Goddijn, M. (2015) · PubMed · Cited by 1 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- Pasquino AM, Passeri F, Pucarelli I, Segni M, Municchi G Spontaneous pubertal development in Turner's syndrome. Italian study Group for Turner’s syndrome. J Clin Endocrinol Metab 1997; 82: 1810– 1813. 9177387
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Gravholt, C. H., Andersen, N. H., Christin-Maitre, S., Davis, S. M., Duijnhouwer, A., Gawlik, A., Maciel-Guerra, A. T., Gutmark-Little, I., Fleischer, K., Hong, D., et al. (2024) · European Journal of Endocrinology · doi:10.1093/ejendo/lvae050 · Cited by 224 · see citing works
Self-citationThe changing face of Turner syndrome
Gravholt, C. H., Viuff, M., Just, J., Sandahl, K., Brun, S., van der Velden, J., Andersen, N. H., & Skakkebaek, A. (2023) · Endocrine Reviews · doi:10.1210/endrev/bnac016 · Cited by 149 · see citing works
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Self-citationClinical pregnancy in Turner syndrome following re-implantation of cryopreserved ovarian cortex
Dunlop, C. E., Jack, S., Telfer, E. E., Zahra, S., & Anderson, R. (2023) · Journal of Assisted Reproduction and Genetics · doi:10.1007/s10815-023-02905-w · Cited by 32 · see citing works
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Preservation of female fertility: The current therapeutic strategy
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Navigating fertility dilemmas across the lifespan in girls with Turner syndrome—a scoping review
van der Coelen, S., van der Velden, J. A. E. M., Nadesapillai, S., Braat, D. D. M., Peek, R., & Fleischer, K. (2024) · Human Reproduction Update · doi:10.1093/humupd/dmae005 · Cited by 31 · see citing works
Self-citationA synopsis of global frontiers in fertility preservation
Ataman, L., Laronda, M. M., Gowett, M. Q., Trotter, K., Anvari, H., Fei, F., Ingram, A., Minette, M., Suebthawinkul, C., Taghvaei, Z., et al. (2022) · Journal of Assisted Reproduction and Genetics · doi:10.1007/s10815-022-02570-5 · Cited by 23 · see citing works
van der Coelen, S., van der Velden, J., Nadesapillai, S., Peek, R., Braat, D., Schleedoorn, M., Fleischer, K., & Oerlemans, A. (2022) · Hormone Research in Paediatrics · doi:10.1159/000525374 · Cited by 22 · see citing works
Self-citationNovel insights in Turner syndrome
Aly, J. M., & Kruszka, P. S. (2022) · Current Opinion in Pediatrics · doi:10.1097/mop.0000000000001135 · Cited by 21 · see citing works
Nawroth, F., Schüring, A. N., & von Wolff, M. (2020) · Acta Obstetricia Et Gynecologica Scandinavica · doi:10.1111/aogs.13984 · Cited by 19 · see citing works
Brouillet, S., Ranisavljevic, N., Sonigo, C., Haquet, E., Bringer-Deutsch, S., Loup‐Cabaniols, V., Hamamah, S., Willems, M., & Anahory, T. (2023) · Human Reproduction · doi:10.1093/humrep/dead135 · Cited by 18 · see citing works
Reproductive health in Turner’s syndrome: from puberty to pregnancy
Porcu, E., Cipriani, L., & Damiano, G. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1269009 · Cited by 17 · see citing works
Reproductive health in Turner syndrome: A narrative review
Whigham, C., Vollenhoven, B. J., & Vincent, A. J. (2022) · Prenatal Diagnosis · doi:10.1002/pd.6261 · Cited by 18 · see citing works
Cheng, J., Ruan, X., Du, J., Jin, F., Gu, M., Wu, Y., & Mueck, A. O. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.959912 · Cited by 13 · see citing works
Neto, M. G., Brunaldi, V., Grecco, E., Silva, L. B., de Quadros, L. G., de Souza, T. F., Teixeira, A. F., de Morais, H. W. P., de Lima, J. H. F., Filho, A. C., et al. (2021) · Obesity Surgery · doi:10.1007/s11695-021-05795-y · Cited by 12 · see citing works
Więcek, M., Gawlik, J., Nowak, Z., & Gawlik, A. (2022) · Endocrine Connections · doi:10.1530/ec-22-0344 · Cited by 11 · see citing works
Turner syndrome: fertility counselling in childhood and through the reproductive lifespan
Bollig, K. J., Mainigi, M. A., Senapati, S., Lin, A. E., Levitsky, L. L., & Bamba, V. (2022) · Current Opinion in Endocrinology Diabetes and Obesity · doi:10.1097/med.0000000000000784 · Cited by 13 · see citing works
Subsequent menstrual disorder after spontaneous menarche in Turner syndrome
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Nadesapillai, S., van der Coelen, S., Goebel, L., Peek, R., Braat, D. D., van der Velden, J. A., Fleischer, K., & Oerlemans, A. J. (2023) · Reproductive BioMedicine Online · doi:10.1016/j.rbmo.2023.02.013 · Cited by 7 · see citing works
Self-citationGrin, L., Vo, K., Sato, Y., Mizrachi, Y., Kohara, M., SANKAI, T., & Kawamura, K. (2021) · Human Reproduction · doi:10.1093/humrep/deab191 · Cited by 6 · see citing works
Aversa, T., SANCTIS, L. D., Faienza, M. F., Gambineri, A., Balducci, A., D'Aprile, R., Somma, C. D., Giavoli, C., Grossi, A., Meriggiola, M. C., et al. (2024) · Journal of Endocrinological Investigation · doi:10.1007/s40618-024-02315-4 · Cited by 6 · see citing works
Management of a Girl With Delayed Puberty and Elevated Gonadotropins
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Ding, F., Xu, J., Xiong, J., Li, Q., Cheng, Z., & Deng, L. (2025) · Frontiers in Endocrinology · doi:10.3389/fendo.2025.1552300 · Cited by 5 · see citing works
Gravholt, C. H. (2024) · Elsevier eBooks · doi:10.1016/b978-0-12-815234-8.00002-1 · Cited by 4 · see citing works
What do families affected by Turner Syndrome think of ovarian tissue freezing in childhood?
Fearon, K. (2023) · Human Fertility · doi:10.1080/14647273.2023.2194555 · Cited by 2 · see citing works
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Freezing Time and Preserving Hope: Ovarian Tissue Cryopreservation for Girls with Turner Syndrome
Blackwood, J. D., Martin, M. A., Jafri, D., & Rehmann, D. (2025) · Georgetown Medical Review · doi:10.52504/001c.127875 · Cited by 1 · see citing works
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Ovarian Cryopreservation for Transplantation With Prepubertal and Adolescent Girls
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Turner’s Syndrome and Eating and Weight Disorders
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Psychosocial and Ethical Aspects of Ovarian Tissue Cryopreservation in Children and Adults
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Research Progress of Ovarian Tissue Cryopreservation and Transplantation
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Fertility preservation in patients with Turner syndrome: a SWOT analysis
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Nawroth, F., & von Wolff, M. (2026) · Springer eBooks · doi:10.1007/978-3-032-28679-6_23
- Authors
- Schleedoorn, M. J., Mulder, B. H., Braat, D. D. M., Beerendonk, C. C. M., Peek, R., Nelen, W. L. D. M., Van Leeuwen, E., Van der Velden, A. A. E. M., & Fleischer, K.
- Affiliations
- Radboud University Medical Center (NL)
- Medical Ethics, Radboud University Medical Centre, Nijmegen, The Netherlands
- Paediatric Endocrinology, Radboud University Medical Centre Amalia Children’s Hospital, Nijmegen, The Netherlands
- Corresponding author
- Schleedoorn, M J
- Venue
- Human Reproduction
- Publisher
- Oxford University Press (OUP)
- Published
- 2020-04-29
- Volume
- 35
- Issue
- 5
- Pages
- 1061-1072
- ISSN
- 0268-1161 (ISSN-L)
- 1460-2350
- PMC
- PMC7493129
- OpenAlex
- W2981157356
- Cited by
- 43
- References
- 82
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 6 · 2023: 10 · 2022: 12 · 2021: 5 · 2020: 1
- FWCI
- 5.25
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Human Reproduction (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion, other-oa)
- Pure Repository PThU (publishedVersion, cc-by-nc)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion, other-oa)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion, cc-by-nc)
- Radboud Repository (Radboud University) (submittedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion, cc-by-nc)
- Radboud Repository (Radboud University) (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- 58th Annual ESPE Meeting (ESPE 2019)
- Funders
- Unconditional (A16-1395)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Biology and Fertility
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Ethics and Legal Issues in Pediatric Healthcare
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Ethics and bioethics in healthcare
- Keywords
- ovarian tissue cryopreservation, Turner syndrome, fertility preservation, primary ovarian insufficiency, ethical consensus, Delphi method, expert panel, ovarian reserve depletion, informed consent, research ethics, patient representatives, medical ethics
- MeSH terms
- Adult, Child, Delphi Technique, Female, Humans, Netherlands, Turner Syndrome, Cryopreservation, Fertility Preservation
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