Fertility PreservationNCT03381300
Preservation of Ovarian Cortex Tissue in Girls With Turner Syndrome
A study testing Ovarian tissue cryopreservation in people with Fertility Preservation and Ovarian Tissue Cryopreservation, run by Radboud University Medical Center at 1 site in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 2 to 18 years, women only
- Conditions the study is for
- Fertility Preservation, Ovarian Tissue Cryopreservation, Turner Syndrome
- What is being tested?
- Ovarian tissue cryopreservation
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 106 participants
- Where
- 1 siteNetherlands
- Study dates
- 1 Jan 2018to 1 Nov 2071
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 18 years
- Women only
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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).
Who cannot join
- 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)
- Based on the international Cincinnati Turner Guideline consensus Meeting, July 2016 and consultation of Dutch cardiologists, paediatric-cardiologists and anaesthesists between 2016-2017 there are no absolute cardiovascular contra-indications for surgical intervention and/or pregnancy. Advice against surgical intervention and/or pregnancy should be based on the patient-specific cardiovascular risk profile. The 2% mortality risk due to acute aortic dissection is based on one survey and literature review study that reported the outcomes of 101 pregnancies in patients with TS after oocyte donation. Only 50% of the patients were screened by a cardiologist before entering the oocyte donation programme. Therefore, all girls who want to participate in this study should have completed the diagnostic work up phase of TS including routine cardiac screening and will be screened by a paediatric anaesthesist. Exclusion will be based on the patient specific risk profile. See: References.
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Radboud university medical center. Department Obstetrics & Gynaecology.
Nijmegen, Gelderland, 6500HB
About this study
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.
Read more
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.
Read the detailed description
Nature and extent of the burden and risks associated with participation, benefit and group relatedness:
The primary objective remains to preserve the fertility of the respective (minor) patient, facing a very high risk of premature ovarian insufficiency (POI) of 95-98%. Disadvantages of participating in this study are the potential risk of complications related to the laparoscopic unilateral oophorectomy and/or the unknown effect on future fertility of these girls. Moreover, the procedure might raise false hope in patients (and/or parents) about the chance of getting pregnant after auto transplantation of cryopreserved-thawed ovarian tissue in the future. However, we attempt to overcome this by extensive and objective information provision by both written materials and face to face counselling.
- Conditions
- Fertility Preservation, Ovarian Tissue Cryopreservation, Turner Syndrome, Live Birth, Premature Ovarian Failure
- Being tested
- Ovarian tissue cryopreservation
- Medical subject headings
- Turner Syndrome, Primary Ovarian Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ovarian tissue cryopreservationProcedure or surgery
Laparoscopic unilateral oophorectomy followed by cryopreservation of ovarian cortex tissue
| Study group | Role | What they receive |
|---|---|---|
| Single cohort | Other | Not described Receives: Procedure: Ovarian tissue cryopreservation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Live birth ratio (LBR) (main outcome)
- Live birth after auto transplantation of cryopreserved-thawed ovarian cortical tissue (i.e. live birth rate or LBR)
Measured: 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
Measured: Within 1 month after ovarian tissue cryopreservation
Secondary outcomes (4)
Patient's age versus LBR
The association between patient's age at cryopreservation and LBR
Measured: 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
The association between patient's genotype and LBR
Measured: 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
The association between patient's AMH level at cryopreservation and LBR
Measured: 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
The association between patient's FSH level at cryopreservation and LBR
Measured: Up to 3 years after auto transplantation of cryopreserved-thawed ovarian cortical tissue, and up to 45 years after ovarian tissue cryopreservation.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Dec 2017
- Study start1 Jan 2018
- Primary completion1 Nov 2071 (estimated)
- Study completion1 Nov 2071 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Fertility PreservationStudies of the same condition, open and under way.
- More trials run by Radboud University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 106 participants (actual)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Kathrin Fleischer, MD, PhD, Principal investigator, Head Department of Reproductive Medicine, Gynaecologist/Subspecialist Reproductive Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03381300
- Sponsor's protocol ID
- NL57738.000.16
- Status last verified
- Feb 2025
- First submitted
- 22 Nov 2017
- Last updated
- 17 Feb 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 28705803van 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.
PubMed 39433199Nadesapillai 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.
PubMed 37549836Nadesapillai 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.
PubMed 33342535Schleedoorn 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.
PubMed 31831533Peek 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.
PubMed 31398245
Study at a glance
From the registry record, last updated by the sponsor on 17 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Preservation of Ovarian Cortex Tissue in Girls With Turner Syndrome
- ClinicalTrials.gov ID
- NCT03381300
- Acronym / sponsor ID
- NL57738.000.16
- Conditions
- Fertility Preservation, Ovarian Tissue Cryopreservation, Turner Syndrome, Live Birth, Premature Ovarian Failure
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 106 participants (actual)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Study start
- 1 Jan 2018 (actual)
- Primary completion
- 1 Nov 2071 (estimated)
- Study completion
- 1 Nov 2071 (estimated)
- First posted
- 21 Dec 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Nature and extent of the burden and risks associated with participation, benefit and group relatedness:
The primary objective remains to preserve the fertility of the respective (minor) patient, facing a very high risk of premature ovarian insufficiency (POI) of 95-98%. Disadvantages of participating in this study are the potential risk of complications related to the laparoscopic unilateral oophorectomy and/or the unknown effect on future fertility of these girls. Moreover, the procedure might raise false hope in patients (and/or parents) about the chance of getting pregnant after auto transplantation of cryopreserved-thawed ovarian tissue in the future. However, we attempt to overcome this by extensive and objective information provision by both written materials and face to face counselling.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Single cohort | Other | Procedure: Ovarian tissue cryopreservation |
Who may qualify
- Ages
- 2 to 18 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (7 listed)
- 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),
Key exclusion criteria (4 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ovarian tissue cryopreservationLaparoscopic unilateral oophorectomy followed by cryopreservation of ovarian cortex tissue | Procedure or surgery | Single cohort |
Primary outcome
Live birth ratio (LBR) (main outcome)
Time frame: Up to 3 years after auto transplantation of cryopreserved-thawed ovarian cortical tissue, and up to 45 years after ovarian tissue cryopreservation.
• Live birth after auto transplantation of cryopreserved-thawed ovarian cortical tissue (i.e. live birth rate or LBR)
Number of primordial follicles (proximate)
Time frame: Within 1 month after ovarian tissue cryopreservation
The number of primordial follicles found in the ovarian tissue
4 secondary outcomes
Patient's age versus LBR
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Up to 3 years after auto transplantation of cryopreserved-thawed ovarian cortical tissue, and up to 45 years after ovarian tissue cryopreservation.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Feb 2025.
- Background: PubMed 28705803Gravholt 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.
- Derived from this study: PubMed 39433199van 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.
- Derived from this study: PubMed 37549836Nadesapillai 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.
- Derived from this study: PubMed 33342535Nadesapillai 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.
- Derived from this study: PubMed 31831533Schleedoorn 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.
- Derived from this study: PubMed 31398245Peek 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kathrin Fleischer, MD, PhD principal investigator
Head Department of Reproductive Medicine, Gynaecologist/Subspecialist Reproductive Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Ovarian tissue cryopreservation in people with Fertility Preservation and Ovarian Tissue Cryopreservation, run by Radboud University Medical Center at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 17 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Live birth ratio (LBR) (main outcome) (time frame: Up to 3 years after auto transplantation of cryopreserved-thawed ovarian cortical tissue, and up to 45 years after ovarian tissue cryopreservation.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03381300, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Feb 2025.