Preservation of Ovarian Cortex Tissue in Girls With Turner Syndrome

NCT03381300 | Active Not Recruiting DMC

• 1 other identifier: NL57738.000.16
• Study Type: interventional
• Target: 106
• Locations: 1 country
• Sites: 1

Brief Summary

Rationale: Infertility due is a major concern for girls with Turner syndrome (TS) and their parents. Physicians are often asked about possible options to preserve their fertility. However, despite some experimental case reports, clear evidence for fertility preservation in these girls is lacking and many questions remain. Without evidence on the effectiveness of fertility preservation it cannot routinely be offered to girls with TS. Objective: To investigate the occurrence of live birth in women with TS after ovarian tissue cryopreservation in childhood followed by auto transplantation in adulthood. Study design: A national multicentre exploratory intervention study Study population: Girls diagnosed with Turner Syndrome, aged 2-18 years. Intervention: Ovarian tissue cryopreservation in childhood followed by auto transplantation in adulthood. In order to obtain the ovarian tissue for cryopreservation, all girls must undergo a laparoscopy under general anaesthesia which will be performed in academic/university clinics with paediatric surgery. During the laparoscopic intervention, a unilateral oophorectomy will be performed, thereby leaving the other ovary intact for hormone production, ovulation, spontaneous pregnancies and as an auto transplantation site for cryopreserved-thawed ovarian cortical tissue later on. Furthermore, a small sample of the ovarian cortex will be used to assess the oocyte quality and genetics (e.g. the presence of germ line mosaicism). Oocytes will be karyotyped by using Fluorescence in situ hybridization (FISH). Karyotypic and hormonal data will be collected once at the yearly clinical visit at the paediatric-endocrinologist. Therefore, a buccal swab and one extra blood sample will be taken and evaluated during the routine laboratory evaluation. In the future, auto transplantation of frozen-thawed ovarian cortex strips will be performed.

Conditions

Fertility Preservation; Ovarian Tissue Cryopreservation; Turner Syndrome; Live Birth; Premature Ovarian Failure

Outcome Measures

Primary Outcomes (2)

• Live birth ratio (LBR) (main outcome)

  • Live birth after auto transplantation of cryopreserved-thawed ovarian cortical tissue (i.e. live birth rate or LBR)

  Up to 3 years after auto transplantation of cryopreserved-thawed ovarian cortical tissue, and up to 45 years after ovarian tissue cryopreservation.

• Number of primordial follicles (proximate)

  The number of primordial follicles found in the ovarian tissue

  Within 1 month after ovarian tissue cryopreservation

Secondary Outcomes (4)

• Patient's age versus LBR

  Up to 3 years after auto transplantation of cryopreserved-thawed ovarian cortical tissue, and up to 45 years after ovarian tissue cryopreservation.

• Patient's genotype versus LBR

  Up to 3 years after auto transplantation of cryopreserved-thawed ovarian cortical tissue, and up to 45 years after ovarian tissue cryopreservation.

• Patient's Anti-Müllerian hormone (AMH) level versus LBR

  Up to 3 years after auto transplantation of cryopreserved-thawed ovarian cortical tissue, and up to 45 years after ovarian tissue cryopreservation.

• Patient's Follicle-stimulating hormone (FSH) level versus LBR

  Up to 3 years after auto transplantation of cryopreserved-thawed ovarian cortical tissue, and up to 45 years after ovarian tissue cryopreservation.

Other Outcomes (15)

• Study participation rate

  Up to 3 years after inclusion

• Eligible participants

  Up to 3 years after inclusion

• Age

  Up to 3 years after inclusion

Study Arms (1)

Single cohort

OTHER

Procedure: Ovarian tissue cryopreservation

Interventions

Ovarian tissue cryopreservation PROCEDURE

Laparoscopic unilateral oophorectomy followed by cryopreservation of ovarian cortex tissue

Single cohort

Eligibility Criteria

• Age: 2 Years - 18 Years
• Gender Eligibility Details: Patients 45X monosomy of mosaicism
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• In order to be eligible to participate in this study, a subject must meet all of the following criteria:
• Girls and young females with classic Turner (i.e. 45X monosomy) or Turner variants (e.g. 45X / 46XX mosaicism, ring X mosaicism, isochromosome X),
• Aged 2 through 18 years,
• who completed the diagnostic work up phase of TS including routine cardiac screening\*,
• whose agreement to participate in this study has been signed by the parents (girls 2-11 years old),
• whose agreement to participate in this study has been signed by the patient and her parents (girls 12-17 years old),
• whose agreement to participate in this study has been signed by the patient (adolescents of 18 years old).

You may not qualify if:

• A potential subject who meets any of the following criteria will be excluded from participation in this study:
• Contra-indications for laparoscopic unilateral oophorectomy under general anaesthesia (e.g. severe cardiovascular comorbidity and/or BMI \>40 kg/m2)\*,
• Contra-indications for cryopreservation (i.e. active HIV, hepatitis-B or hepatitis-C infection)

Sponsors & Collaborators

• Radboud University Medical Center: lead

Study Sites (1)

Radboud university medical center. Department Obstetrics & Gynaecology.

Nijmegen, Gelderland, 6500HB, Netherlands

Location

Related Publications (6)

• Gravholt CH, Andersen NH, Conway GS, Dekkers OM, Geffner ME, Klein KO, Lin AE, Mauras N, Quigley CA, Rubin K, Sandberg DE, Sas TCJ, Silberbach M, Soderstrom-Anttila V, Stochholm K, van Alfen-van derVelden JA, Woelfle J, Backeljauw PF; International Turner Syndrome Consensus Group. Clinical practice guidelines for the care of girls and women with Turner syndrome: proceedings from the 2016 Cincinnati International Turner Syndrome Meeting. Eur J Endocrinol. 2017 Sep;177(3):G1-G70. doi: 10.1530/EJE-17-0430.

  PMID: 28705803 BACKGROUND

• van der Coelen S, Nadesapillai S, Peek R, Braat D, Bocca G, Finken M, Hannema S, de Kort S, Sas T, Straetemans S, van Tellingen V, Stuart AV, Fleischer K, van der Velden J. Puberty progression in girls with Turner syndrome after ovarian tissue cryopreservation. Fertil Steril. 2025 Apr;123(4):583-592. doi: 10.1016/j.fertnstert.2024.10.025. Epub 2024 Oct 19.

  PMID: 39433199 DERIVED

• 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. TurnerFertility trial: fertility preservation in young girls with Turner syndrome by freezing ovarian cortex tissue-a prospective intervention study. Fertil Steril. 2023 Nov;120(5):1048-1060. doi: 10.1016/j.fertnstert.2023.08.004. Epub 2023 Aug 5.

  PMID: 37549836 DERIVED

• Nadesapillai S, van der Velden J, Smeets D, van de Zande G, Braat D, Fleischer K, Peek R. Why are some patients with 45,X Turner syndrome fertile? A young girl with classical 45,X Turner syndrome and a cryptic mosaicism in the ovary. Fertil Steril. 2021 May;115(5):1280-1287. doi: 10.1016/j.fertnstert.2020.11.006. Epub 2020 Dec 17.

  PMID: 33342535 DERIVED

• Schleedoorn M, van der Velden J, Braat D, Beerendonk I, van Golde R, Peek R, Fleischer K. TurnerFertility trial: PROTOCOL for an observational cohort study to describe the efficacy of ovarian tissue cryopreservation for fertility preservation in females with Turner syndrome. BMJ Open. 2019 Dec 11;9(12):e030855. doi: 10.1136/bmjopen-2019-030855.

  PMID: 31831533 DERIVED

• Peek R, Schleedoorn M, Smeets D, van de Zande G, Groenman F, Braat D, van der Velden J, Fleischer K. Ovarian follicles of young patients with Turner's syndrome contain normal oocytes but monosomic 45,X granulosa cells. Hum Reprod. 2019 Sep 29;34(9):1686-1696. doi: 10.1093/humrep/dez135.

  PMID: 31398245 DERIVED

MeSH Terms

Conditions

Turner Syndrome; Primary Ovarian Insufficiency

Condition Hierarchy (Ancestors)

Gonadal Dysgenesis; Disorders of Sex Development; Urogenital Abnormalities; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Sex Chromosome Disorders of Sex Development; Male Urogenital Diseases; Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Sex Chromosome Disorders; Chromosome Disorders; Genetic Diseases, Inborn; Gonadal Disorders; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Genital Diseases

Study Officials

• Kathrin Fleischer, MD, PhD

  Head Department of Reproductive Medicine, Gynaecologist/Subspecialist Reproductive Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 22, 2017
• First Posted: December 21, 2017
• Study Start: January 1, 2018
• Primary Completion (Estimated): November 1, 2071
• Study Completion (Estimated): November 1, 2071
• Last Updated: February 17, 2025

Record last verified: 2025-02

Locations

NL (1)