Turner Syndrome Minipuberty Study

Recruiting

• Conditions: Turner Syndrome; Infertility, Female; Premature Ovarian Failure; Ovarian Diseases; Premature Menopause; Sex Chromosome Disorders; Gonadal Dysgenesis
• Interventions: Other: Venapunction

• Registration Number: NCT04189406
• Lead Sponsor: Radboud University Medical Center

Brief 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. 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

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2019-11-25
• Study First Submitted QC: 2019-12-04
• Study First Posted: 2019-12-06
• Study Start: 2020-02-01
• Status Verified: 2023-03
• Last Update Submitted: 2023-11-28
• Last Update Posted: 2023-11-29
• Primary Completion: 2024-12-01
• Study Completion: 2024-12-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 30

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.

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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)

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Girls with Turner syndrome	Venapunction	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.

Primary Outcome Measures

Name	Time	Method
Defining the testosterone range during minipuberty in girls with TS at 3 months of age and at 9 months of age	1 year	testosterone will be collected with a venapuncture and analysed with the LCMSMS analysis method.
Defining the FSH range during minipuberty in girls with TS at 3 months of age and at 9 months of age	1 year after venapuncture	FSH (follicle stimulating hormone) will be collected with a venapuncture and analysed with the Elecsys method on the Cobas E801system of Roche.
Defining the estradiol range during minipuberty in girls with TS at 3 months of age and at 9 months of age	1 year after venapuncture	estradiol will be collected with a venapuncture and analysed with the LCMSMS analysis method.
Defining the LH range in blood during minipuberty in girls with TS at 3 months of age and at 9 months of age	1 year after venapuncture	LH (luteinizing hormone) will be collected with a venapuncture and analysed with the Elecsys method on the Cobas E801system of Roche.
Defining the AMH range during minipuberty in girls with TS at 3 months of age and at 9 months of age	1 year after venapuncture	AMH (Anti-Müllerian hormone) will be collected with a venapuncture and analysed on the Access of Beckman Coulter.
Defining the inhibin B range during minipuberty in girls with TS at 3 months of age and at 9 months of age	1 year after venapuncture	inhibin B will be collected with a venapuncture and analysed with the GEN II ELISEA of Beckman Coulter.

Secondary Outcome Measures

Name	Time	Method
Patient's karyotype vs inhibin B	1 year after venapuncture	The association between patient's karyotype and inhibin B level at 3 months of age and 9 months of age
Patient's karyotype vs estradiol	1 year after venapuncture	The association between patient's karyotype and estradiol level at 3 months of age and 9 months of age
Patient's karyotype vs testosterone	1 year after venapuncture	The association between patient's karyotype and testosterone level at 3 months of age and 9 months of age
Patient's karyotype vs FSH	1 year after venapuncture	The association between patient's karyotype and FSH level at 3 months of age and 9 months of age
Patient's karyotype vs AMH	1 year after venapuncture	The association between patient's karyotype and AMH level at 3 months of age and 9 months of age
Patient's karyotype vs LH	1 year after venapuncture	The association between patient's karyotype and LH level at 3 months of age and 9 months of age

Trial Locations

Locations (13)

Justus-Liebig Universität Giessen; 🇩🇪 Gießen, Germany

University medical center Groningen; 🇳🇱 Groningen, Netherlands

Leiden University medical center; 🇳🇱 Leiden, Netherlands

Righospitalet, University of Copenhagen; 🇩🇰 Copenhagen, Denmark

Radboud University Medical Center; 🇳🇱 Nijmegen, Gelderland, Netherlands

Amsterdam University medical center; 🇳🇱 Amsterdam, Netherlands

Maastricht University medical center; 🇳🇱 Maastricht, Netherlands

Universitätsklinikum der Ruhr-Universität Bochum; 🇩🇪 Bochum, Germany

Universitätsklinikum Tübingen; 🇩🇪 Tübingen, Germany

Medical university of Silesia; 🇵🇱 Katowice, Poland

University hospital of Umea; 🇸🇪 Umeå, Sweden

Erasmus University medical center; 🇳🇱 Rotterdam, Netherlands

University medical Center Utrecht; 🇳🇱 Utrecht, Netherlands