Turner Syndrome Minipuberty Study

NCT ID: NCT04189406

Last Updated: 2023-11-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

30 participants

Study Classification

OBSERVATIONAL

Study Start Date

2020-02-01

Study Completion Date

2024-12-01

Brief Summary

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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.

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.

Detailed Description

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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.

Conditions

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Turner Syndrome Infertility, Female Premature Ovarian Failure Gonadal Dysgenesis Premature Menopause Sex Chromosome Disorders Ovarian Diseases

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Girls with Turner syndrome

Girls 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.

Venapunction

Intervention Type OTHER

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.

Interventions

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Venapunction

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.

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

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.

Exclusion Criteria

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)
Minimum Eligible Age

1 Month

Maximum Eligible Age

3 Months

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

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Radboud University Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Janielle vd Velden, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Paediatric endocrinologist, Radboudumc, Nijmegen

Locations

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Righospitalet, University of Copenhagen

Copenhagen, , Denmark

Site Status RECRUITING

Universitätsklinikum der Ruhr-Universität Bochum

Bochum, , Germany

Site Status RECRUITING

Justus-Liebig Universität Giessen

Giessen, , Germany

Site Status RECRUITING

Universitätsklinikum Tübingen

Tübingen, , Germany

Site Status RECRUITING

Radboud University Medical Center

Nijmegen, Gelderland, Netherlands

Site Status RECRUITING

Amsterdam University medical center

Amsterdam, , Netherlands

Site Status RECRUITING

University medical center Groningen

Groningen, , Netherlands

Site Status RECRUITING

Leiden University medical center

Leiden, , Netherlands

Site Status RECRUITING

Maastricht University medical center

Maastricht, , Netherlands

Site Status RECRUITING

Erasmus University medical center

Rotterdam, , Netherlands

Site Status RECRUITING

University medical Center Utrecht

Utrecht, , Netherlands

Site Status RECRUITING

Medical university of Silesia

Katowice, , Poland

Site Status RECRUITING

University hospital of Umea

Umeå, , Sweden

Site Status RECRUITING

Countries

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Denmark Germany Netherlands Poland Sweden

Central Contacts

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Sanne vd Coelen, MD

Role: CONTACT

+31243098078

Janielle vd Velden, MD, PhD

Role: CONTACT

+24 3614430

Facility Contacts

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Casper Hagen

Role: primary

Annette Richter-Unruh

Role: primary

Ivonne Bedei

Role: primary

Gerhard Binder

Role: primary

Sanne vd Coelen, MD

Role: primary

+31243098078

vd Velden, MD, PhD

Role: backup

+24 3614430

Martijn Finken

Role: primary

Sabine Hannema

Role: backup

Gianni Bocca

Role: primary

Hester Vlaardingerbroek

Role: primary

Saartje Straetemans

Role: primary

Theo Sas

Role: primary

Annemarie Verrijn-Stuart

Role: primary

Aneta Gawlik

Role: primary

Malgorzata Wiecek

Role: backup

Berit Kriström

Role: primary

Elena Lundberg

Role: backup

References

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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.

Reference Type BACKGROUND
PMID: 26874361 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18957497 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21256486 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 3906118 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16968797 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18056118 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29917083 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30093882 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 9177387 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16849410 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16252273 (View on PubMed)

Other Identifiers

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2019-5955

Identifier Type: -

Identifier Source: org_study_id