TurnerFertility trial: fertility preservation in young girls with Turner syndrome by freezing ovarian cortex tissue-a prospective intervention study
Open accessAbstract
OBJECTIVE: To evaluate which girls with Turner syndrome (TS) could benefit from fertility preservation by ovarian tissue cryopreservation on the basis of karyotype, puberty status, and hormonal data. DESIGN: Prospective intervention study; participants were included between 2018 and 2020. SETTING: Tertiary hospital in the Netherlands. PATIENTS: In total, 106 girls with TS aged between 2 and 18 years were included. Girls with minor X chromosome deletions, Y chromosomal content, active infections, or contraindications for surgery were excluded. INTERVENTION: A laparoscopic unilateral ovariectomy was performed to obtain ovarian cortical tissue for cryopreservation. One tissue fragment per participant was used to determine the number of follicles per ovary by serial sectioning and staining. Chromosome analysis was performed on lymphocytes and buccal cells. A blood sample was taken before the ovariectomy for hormonal analysis. MAIN OUTCOME MEASURES: The presence of follicles in ovarian cortex tissue from girls with TS in relation to karyotype, puberty status, and hormonal data. RESULTS: A unilateral ovariectomy was performed on 93 girls with TS. Complications after surgery occurred in 5 girls, including luxation of psychological symptoms in 2 girls. In 13 (14%) girls, a 46,XX cell line was found in buccal cells that was absent in lymphocytes. Follicles were observed in 30 (32%) of the 93 girls and were found mainly in girls with a 46,XX cell line in lymphocytes or buccal cells (Phi coefficient = 0.55). Spontaneous onset of puberty (Phi coefficient = 0.59), antimüllerian hormone (AMH; point-biserial correlation [r] = 0.82), inhibin B (r = 0.67), and follicle-stimulating hormone (r = -0.46) levels were also correlated strongly with the presence of follicles. Furthermore, AMH levels had a significant correlation with the number of follicles per ovary (r = 0.66). CONCLUSION: Favorable predictive markers for the presence of follicles included either a 46,XX cell line, spontaneous onset of puberty, or a combination of measurable AMH and normal follicle-stimulating hormone levels. Karyotyping of two peripheral cell lines in girls with TS is recommended to reveal hidden mosaicisms. Ovarian tissue cryopreservation should be offered with caution in a research setting to those with a sufficient ovarian reserve, considering the significant loss of follicles after ovarian tissue cryopreservation and autotransplantation. Physicians should pay attention to the mental health of the girls during the whole process. CLINICAL TRIAL REGISTRATION NUMBER: Trial registration number: NCT03381300- Preservation of Ovarian Cortex Tissue in Girls With Turner Syndrome - Full Text View - ClinicalTrials.gov. Registered on: December 21, 2017. First patient recruited on January 1, 2018.
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In individuals with TS, AMH is associated with clinical features of ovarian reserve and has the strongest positive correlation with the presence of follicles in ovarian cortex tissue.
“In individuals with TS, AMH is associated with clinical features of ovarian reserve270,581 and has the strongest positive correlation with the presence of follicles in ovarian cortex tissue .263,579,582”
From Clinical practice guidelines for the care of girls and women with Turner syndrome. (2024) · cites this paper as [582]
Current knowledge on OTC in TS consists of four cohort studies and four case reports, involving a total of 185 TS patients with ages varying between 3 and 22 years.
“The current knowledge on OTC in TS consists of four cohort studies and four case reports, involving a total of 185 TS-patients with ages varying between 3 and 22 years.263,579,582,614”
From Clinical practice guidelines for the care of girls and women with Turner syndrome. (2024) · cites this paper as [582]
Patients with a mosaic karyotype have the highest prevalence of follicles, 67%-100%.
“Patients with a mosaic karyotype have the highest prevalence of follicles, respectively 67%-100%.263,579,582”
From Clinical practice guidelines for the care of girls and women with Turner syndrome. (2024) · cites this paper as [582]
Spontaneous puberty has a significant positive correlation with the presence of follicles.
“Spontaneous puberty has a significant positive correlation with the presence of follicles.263,579,582,618”
From Clinical practice guidelines for the care of girls and women with Turner syndrome. (2024) · cites this paper as [582]
Nadesapillai et al. performed a unilateral ovariectomy in 93 patients; in 30/93 (32%) follicles were found.
“Nadesapillai et al. performed a unilateral ovariectomy in 93 patients; in 30/93 (32%) follicles were found.263,582”
From Clinical practice guidelines for the care of girls and women with Turner syndrome. (2024) · cites this paper as [582]
No correlation was observed between age and follicle density in the ovarian cortex tissue.
“No correlation was observed between age and follicle density in the ovarian cortex tissue.582”
From Clinical practice guidelines for the care of girls and women with Turner syndrome. (2024) · cites this paper as [582]
FSH <10 IU/L has a positive correlation with the presence of follicles.
“An FSH <10 IU L−1 has a positive correlation with the presence of follicles.”
From Clinical practice guidelines for the care of girls and women with Turner syndrome. (2024) · cites this paper as [582]
Follicles were present in 50%-100% of TS girls with FSH <10 IU/L (including prepubertal girls).
“Follicles were present in 50%-100% of TS girls with FSH <10 IU L−1 (including prepubertal girls).263,579,582”
From Clinical practice guidelines for the care of girls and women with Turner syndrome. (2024) · cites this paper as [582]
The odds of finding follicles in patients with a structural X chromosome aberration or a 45,X/47,XXX karyotype is 23%-44%, and with a 45,X karyotype 4%-11%.
“The odds of finding follicles in patients with a structural X chromosome aberration or a 45,X/47,XXX karyotype is 23%-44% and with a 45, X karyotype 4%-11%.263,579,582”
From Clinical practice guidelines for the care of girls and women with Turner syndrome. (2024) · cites this paper as [582]
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Cited by
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Clinical practice guidelines for the care of girls and women with Turner syndrome.
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Self-citation
- Authors
- Nadesapillai, S., van der Velden, J., van der Coelen, S., Schleedoorn, M., Sedney, A., Spath, M., Schurink, M., Oerlemans, A., IntHout, J., Beerendonk, I., Braat, D., Peek, R., & Fleischer, K.
- Affiliations
- Radboud University Medical Center (NL)
- Corresponding author
- Nadesapillai, Sapthami
- ORCID
- Venue
- Fertility and Sterility
- Publisher
- Elsevier BV
- Published
- 2023-11
- Volume
- 120
- Issue
- 5
- Pages
- 1048-1060
- ISSN
- 0015-0282 (ISSN-L)
- OpenAlex
- W4385680803
- Cited by
- 38
- References
- 44
- Citations by year
- 2026: 12 · 2025: 12 · 2024: 12 · 2023: 2
- FWCI
- 9.73
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Fertility and Sterility (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Funders
- Merck KGaA
- EMD Serono (A16-1395)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Biology and Fertility
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
- Keywords
- Turner syndrome, fertility preservation, ovarian tissue cryopreservation, ovarian cortex, unilateral ovariectomy, ovarian follicles, mosaicism, karyology, anti-Müllerian hormone, follicle-stimulating hormone, young girls
- MeSH terms
- Adolescent, Child, Child, Preschool, Female, Freezing, Follicle Stimulating Hormone, Humans, Male, Mouth Mucosa, Ovary, Prospective Studies, Turner Syndrome, Cryopreservation, Fertility Preservation
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