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Turner SyndromeMinipubertyNCT04189406

Turner Syndrome Minipuberty Study

An observational study of Turner Syndrome and Infertility, Female, run by Radboud University Medical Center at 13 sites in 5 countries.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

Rationale: Due to accelerated germ cell loss, infertility is a major problem in girls with Turner syndrome (TS). Therefore, cryopreservation of ovarian tissue or oocytes before exhaustion of the ovarian reserve may preserve fertility in patients with TS. Read more about this study

Who is it for?
Ages 1 month to 3 months, women onlyHealthy volunteers can take part
What is being tested?
Venapunction
How many people
30 participants
Where
13 sitesin 5 countries
Study dates
1 Feb 2020to 1 Dec 2024
Phase
Observational
Are there results?
None posted in the registry

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 1 month to 3 months
  • Women only
  • Healthy volunteers accepted
  • Child

Study population: We include girls with the diagnosis TS before the age of 3 months based on full or partial absence of one X-chromosome or a mosaic pattern. We will recruit the girls with TS from all medical centres in the Netherlands. The control group consists of girls who have blood collected at 3 months and at 9 months of age for another indication. Participants in the control group will be recruited in the Radboudumc in Nijmegen.

Who may be able to join

  • In order to be eligible to participate in the TS group of this study, a subject must meet all of the following criteria:
  • A diagnosis of TS before the age of three months;
  • Girls with a diagnosis of classic TS or other variants (i.e. 45,X, 45,X/46XiXq, 45,X/46,XY, 45,X/46,XX, 45,X/47,XXX, 45,X/46,X,r(X), 46,XiXq, other);
  • Whose parents have agreed to participate in the study through a signed written informed consent form.
  • In order to be eligible to participate in the control group of this study, a subject must meet all of the following criteria:
  • No diagnosis of TS or any other diagnosis that might affect the HPG axis;
  • Girls that will have a blood collection within their usual care at 3 months and at 9 months of age.
  • Whose parents have agreed to participate in the study through a signed informed consent form.

Who cannot join

  • A potential subject who meets any of the following criteria will be excluded from participation in this study:
  • Any other diagnosis besides TS that might affect the HPG axis;
  • Ovarian surgery in the medical history;
  • Critical illness;
  • The use of medication affecting the HPG axis (e.g. estrogen suppletion therapy)

Trial locations and contacts

13 sites in 5 countries.

Sanne vd Coelen, MD contact

+31243098078

sanne.vandercoelen@radboudumc.nl

Janielle vd Velden, MD, PhD contact

+24 3614430

Janielle.vanderVelden@radboudumc.nl

13 sites in 5 countries

Netherlands7 sites, 7 recruiting

  • Amsterdam University medical center

    Amsterdam

    Martijn Finken

    Sabine Hannema

    Recruiting

  • University medical center Groningen

    Groningen

    Gianni Bocca

    Recruiting

  • Leiden University medical center

    Leiden

    Hester Vlaardingerbroek

    Recruiting

  • Maastricht University medical center

    Maastricht

    Saartje Straetemans

    Recruiting

  • Radboud University Medical Center

    Nijmegen, Gelderland, 6525GA

    Sanne vd Coelen, MD, +31243098078, sanne.vandercoelen@radboudumc.nl

    vd Velden, MD, PhD, +24 3614430, Janielle.vanderVelden@radboudumc.nl

    Recruiting

  • Erasmus University medical center

    Rotterdam

    Theo Sas

    Recruiting

  • University medical Center Utrecht

    Utrecht

    Annemarie Verrijn-Stuart

    Recruiting

Other trials in Netherlands

Germany3 sites, 3 recruiting

  • Universitätsklinikum der Ruhr-Universität Bochum

    Bochum

    Annette Richter-Unruh

    Recruiting

  • Justus-Liebig Universität Giessen

    Giessen

    Ivonne Bedei

    Recruiting

  • Universitätsklinikum Tübingen

    Tübingen

    Gerhard Binder

    Recruiting

Other trials in Germany

Denmark1 site, 1 recruiting

  • Righospitalet, University of Copenhagen

    Copenhagen

    Casper Hagen

    Recruiting

Other trials in Denmark

Poland1 site, 1 recruiting

  • Medical university of Silesia

    Katowice

    Aneta Gawlik

    Malgorzata Wiecek

    Recruiting

Other trials in Poland

Sweden1 site, 1 recruiting

  • University hospital of Umea

    Umeå

    Berit Kriström

    Elena Lundberg

    Recruiting

Other trials in Sweden

About this study

Official title: Turner Syndrome Minipuberty Study A Prospective, Descriptive Cohortstudy

Rationale: Due to accelerated germ cell loss, infertility is a major problem in girls with Turner syndrome (TS). Therefore, cryopreservation of ovarian tissue or oocytes before exhaustion of the ovarian reserve may preserve fertility in patients with TS. However, in the majority of females with TS , the ovarian reserve is exhausted before the age of menarche. Early markers indicating and predicting the ovarian reserve are necessary. During mid-childhood the hypothalamic-pituitary-gonadal (HPG) axis is quiescent and gonadotropins are usually unmeasurable. Nonetheless, this axis is active during infancy. Therefore, gonadotropins are measurable with peak values at 3 months of age and with lower (but still measurable) values at 9 months of age, in a period called the minipuberty. The aim of this study is to find markers of ovarian capacity, during the minipuberty, in order to predict ovarian reserve in the future.

Objective: The hormonal range of LH, FSH, AMH, inhibin B, testosterone and estradiol in girls with TS during the minipuberty and the relation of the hormone serum levels with the karyotype.

Read more

Study design: A prospective, cohort study with a duration of 3 years. Study population: Girls with a pre- or perinatal diagnosis TS who are born in a medical centre in the Netherlands during the duration of the study

Main study parameters/endpoints: Serum levels of FSH, LH, AMH, inhibin B, testosterone and estradiol at the age of 3 and 9 months.

Read the detailed description

Nature and extent of the burden and risks associated with participation, benefit and group relatedness:

The subjects will have twice an extra venapunction for collection of 3.5mL blood during their infancy, which is not stated in the guidelines for TS. There is very little risk for adverse events associated with this blood sample collection, however it is an extra procedure. The outcome parameters will not be helpful for individual study participants, however they are likely to help clinicians and researchers in understanding how the ovarian function operates develops in girls with TS. Furthermore, these markers could be used to estimate the ovarian reserve and the urgency of fertility preservation in young females with TS. This information could help clinicians, patients and their parents in decision making.

Being tested
Venapunction
Keywords
Minipuberty, Turner Syndrome, Infertility, Premature Ovarian Failure
Medical subject headings
Turner Syndrome, Infertility, Female, Primary Ovarian Insufficiency, Gonadal Dysgenesis, Menopause, Premature, Sex Chromosome Disorders, Ovarian Diseases, Infertility

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • VenapunctionOther

    A blood sample of 3.5 mL (0.2 mL serum for FSH and LH, 0.15 mL serum for E2, 0.15 mL serum for T, 0.15 mL serum for AMH and 0.25 mL serum for Inhibin B) will be collected of all girls with TS at 3 months and 9 months of age. For the girls with TS, this will be collected with an extra venapuncture during a regular outpatient visit within the usual care.

Study groups in NCT04189406
Study groupRoleWhat they receive
Girls with Turner syndromeGirls with a pre- or perinatal diagnosis TS who are born in a medical centre in the Netherlands during the duration of the study. The subjects will have an extra venapuncture of 3.5 mL blood at 3 and 9 months.
Receives: Other: Venapunction

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Defining the LH range in blood during minipuberty in girls with TS at 3 months of age and at 9 months of age

    LH (luteinizing hormone) will be collected with a venapuncture and analysed with the Elecsys method on the Cobas E801system of Roche.

    Measured: 1 year after venapuncture

  2. Defining the FSH range during minipuberty in girls with TS at 3 months of age and at 9 months of age

    FSH (follicle stimulating hormone) will be collected with a venapuncture and analysed with the Elecsys method on the Cobas E801system of Roche.

    Measured: 1 year after venapuncture

  3. Defining the AMH range during minipuberty in girls with TS at 3 months of age and at 9 months of age

    AMH (Anti-Müllerian hormone) will be collected with a venapuncture and analysed on the Access of Beckman Coulter.

    Measured: 1 year after venapuncture

  4. Defining the estradiol range during minipuberty in girls with TS at 3 months of age and at 9 months of age

    estradiol will be collected with a venapuncture and analysed with the LCMSMS analysis method.

    Measured: 1 year after venapuncture

  5. Defining the testosterone range during minipuberty in girls with TS at 3 months of age and at 9 months of age

    testosterone will be collected with a venapuncture and analysed with the LCMSMS analysis method.

    Measured: 1 year

  6. Defining the inhibin B range during minipuberty in girls with TS at 3 months of age and at 9 months of age

    inhibin B will be collected with a venapuncture and analysed with the GEN II ELISEA of Beckman Coulter.

    Measured: 1 year after venapuncture

Secondary outcomes (6)

  1. Patient's karyotype vs LH

    The association between patient's karyotype and LH level at 3 months of age and 9 months of age

    Measured: 1 year after venapuncture

  2. Patient's karyotype vs FSH

    The association between patient's karyotype and FSH level at 3 months of age and 9 months of age

    Measured: 1 year after venapuncture

  3. Patient's karyotype vs AMH

    The association between patient's karyotype and AMH level at 3 months of age and 9 months of age

    Measured: 1 year after venapuncture

  4. Patient's karyotype vs estradiol

    The association between patient's karyotype and estradiol level at 3 months of age and 9 months of age

    Measured: 1 year after venapuncture

  5. Patient's karyotype vs testosterone

    The association between patient's karyotype and testosterone level at 3 months of age and 9 months of age

    Measured: 1 year after venapuncture

  6. Patient's karyotype vs inhibin B

    The association between patient's karyotype and inhibin B level at 3 months of age and 9 months of age

    Measured: 1 year after venapuncture

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Dec 2019
  2. Study start1 Feb 2020
  3. Primary completion1 Dec 2024 (estimated)
  4. Study completion1 Dec 2024 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Prospective
Enrolment
30 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04189406
Sponsor's protocol ID
2019-5955
Acronym
Minipuberty
Status last verified
Mar 2023
First submitted
25 Nov 2019
Last updated
29 Nov 2023
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Bernard V, Donadille B, Zenaty D, Courtillot C, Salenave S, Brac de la Perriere A, Albarel F, Fevre A, Kerlan V, Brue T, Delemer B, Borson-Chazot F, Carel JC, Chanson P, Leger J, Touraine P, Christin-Maitre S; CMERC Center for Rare Disease. Spontaneous fertility and pregnancy outcomes amongst 480 women with Turner syndrome. Hum Reprod. 2016 Apr;31(4):782-8. doi: 10.1093/humrep/dew012. Epub 2016 Feb 13.

    PubMed 26874361

  • Borgstrom B, Hreinsson J, Rasmussen C, Sheikhi M, Fried G, Keros V, Fridstrom M, Hovatta O. Fertility preservation in girls with turner syndrome: prognostic signs of the presence of ovarian follicles. J Clin Endocrinol Metab. 2009 Jan;94(1):74-80. doi: 10.1210/jc.2008-0708. Epub 2008 Oct 28.

    PubMed 18957497

  • Bryman I, Sylven L, Berntorp K, Innala E, Bergstrom I, Hanson C, Oxholm M, Landin-Wilhelmsen K. Pregnancy rate and outcome in Swedish women with Turner syndrome. Fertil Steril. 2011 Jun 30;95(8):2507-10. doi: 10.1016/j.fertnstert.2010.12.039. Epub 2011 Jan 22.

    PubMed 21256486

  • Burgoyne PS, Baker TG. Perinatal oocyte loss in XO mice and its implications for the aetiology of gonadal dysgenesis in XO women. J Reprod Fertil. 1985 Nov;75(2):633-45. doi: 10.1530/jrf.0.0750633.

    PubMed 3906118

  • Fechner PY, Davenport ML, Qualy RL, Ross JL, Gunther DF, Eugster EA, Huseman C, Zagar AJ, Quigley CA; Toddler Turner Study Group. Differences in follicle-stimulating hormone secretion between 45,X monosomy Turner syndrome and 45,X/46,XX mosaicism are evident at an early age. J Clin Endocrinol Metab. 2006 Dec;91(12):4896-902. doi: 10.1210/jc.2006-1157. Epub 2006 Sep 12.

    PubMed 16968797

  • Huang JY, Tulandi T, Holzer H, Lau NM, Macdonald S, Tan SL, Chian RC. Cryopreservation of ovarian tissue and in vitro matured oocytes in a female with mosaic Turner syndrome: Case Report. Hum Reprod. 2008 Feb;23(2):336-9. doi: 10.1093/humrep/dem307. Epub 2007 Dec 2.

    PubMed 18056118

  • Johannsen TH, Main KM, Ljubicic ML, Jensen TK, Andersen HR, Andersen MS, Petersen JH, Andersson AM, Juul A. Sex Differences in Reproductive Hormones During Mini-Puberty in Infants With Normal and Disordered Sex Development. J Clin Endocrinol Metab. 2018 Aug 1;103(8):3028-3037. doi: 10.1210/jc.2018-00482.

    PubMed 29917083

  • Lanciotti L, Cofini M, Leonardi A, Penta L, Esposito S. Up-To-Date Review About Minipuberty and Overview on Hypothalamic-Pituitary-Gonadal Axis Activation in Fetal and Neonatal Life. Front Endocrinol (Lausanne). 2018 Jul 23;9:410. doi: 10.3389/fendo.2018.00410. eCollection 2018.

    PubMed 30093882

  • 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 Jun;82(6):1810-3. doi: 10.1210/jcem.82.6.3970.

    PubMed 9177387

  • Stochholm K, Juul S, Juel K, Naeraa RW, Gravholt CH. Prevalence, incidence, diagnostic delay, and mortality in Turner syndrome. J Clin Endocrinol Metab. 2006 Oct;91(10):3897-902. doi: 10.1210/jc.2006-0558. Epub 2006 Jul 18.

    PubMed 16849410

  • Sutton EJ, McInerney-Leo A, Bondy CA, Gollust SE, King D, Biesecker B. Turner syndrome: four challenges across the lifespan. Am J Med Genet A. 2005 Dec 1;139A(2):57-66. doi: 10.1002/ajmg.a.30911.

    PubMed 16252273

Questions about this trial

What is this clinical trial studying?

An observational study of Turner Syndrome and Infertility, Female, run by Radboud University Medical Center at 13 sites in 5 countries.

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 8 inclusion and 5 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: status not confirmed, as of the sponsor's last update on 29 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites in Netherlands, Germany, Denmark, Poland, Sweden. 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?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Sanne vd Coelen, MD (+31243098078, sanne.vandercoelen@radboudumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Defining the LH range in blood during minipuberty in girls with TS at 3 months of age and at 9 months of age (time frame: 1 year after venapuncture). The study lists 6 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 NCT04189406, which also lists 11 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 29 Nov 2023; AzTrials last refreshed its copy on 28 Oct 2026.

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