Clinical trial NCT04189406: Turner Syndrome Minipuberty Study
Official title: Turner Syndrome Minipuberty Study A Prospective, Descriptive Cohortstudy
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Turner Syndrome
Infertility, Female
Premature Ovarian Failure
Gonadal Dysgenesis
Premature Menopause
Sex Chromosome Disorders
Ovarian Diseases
Keywords: Minipuberty
Turner Syndrome
Infertility
Premature Ovarian Failure
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
First posted: 2019-12-06
Enrollment: 30
Sex: FEMALE
Minimum age (years): 1
Maximum age (years): 3
Standard ages: CHILD
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
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.

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Defining the LH range in blood during minipuberty in girls with TS at 3 months of age and at 9 months of age
timeFrame: 1 year after venapuncture
measure: Defining the FSH range during minipuberty in girls with TS at 3 months of age and at 9 months of age
timeFrame: 1 year after venapuncture
measure: Defining the AMH range during minipuberty in girls with TS at 3 months of age and at 9 months of age
timeFrame: 1 year after venapuncture
measure: Defining the estradiol range during minipuberty in girls with TS at 3 months of age and at 9 months of age
timeFrame: 1 year after venapuncture
measure: Defining the testosterone range during minipuberty in girls with TS at 3 months of age and at 9 months of age
timeFrame: 1 year
measure: Defining the inhibin B range during minipuberty in girls with TS at 3 months of age and at 9 months of age
timeFrame: 1 year after venapuncture
Secondary outcomes:
measure: Patient's karyotype vs LH
timeFrame: 1 year after venapuncture
measure: Patient's karyotype vs FSH
timeFrame: 1 year after venapuncture
measure: Patient's karyotype vs AMH
timeFrame: 1 year after venapuncture
measure: Patient's karyotype vs estradiol
timeFrame: 1 year after venapuncture
measure: Patient's karyotype vs testosterone
timeFrame: 1 year after venapuncture
measure: Patient's karyotype vs inhibin B
timeFrame: 1 year after venapuncture
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Righospitalet, University of Copenhagen
city: Bochum
country: Germany
facility: Universitätsklinikum der Ruhr-Universität Bochum
city: Gießen
country: Germany
facility: Justus-Liebig Universität Giessen
city: Tübingen
country: Germany
facility: Universitätsklinikum Tübingen
city: Nijmegen
country: Netherlands
facility: Radboud University Medical Center
state: Gelderland
city: Amsterdam
country: Netherlands
facility: Amsterdam University medical center
city: Groningen
country: Netherlands
facility: University medical center Groningen
city: Leiden
country: Netherlands
facility: Leiden University medical center
city: Maastricht
country: Netherlands
facility: Maastricht University medical center
city: Rotterdam
country: Netherlands
facility: Erasmus University medical center
city: Utrecht
country: Netherlands
facility: University medical Center Utrecht
city: Katowice
country: Poland
facility: Medical university of Silesia
city: Umeå
country: Sweden
facility: University hospital of Umea
Study officials:
affiliation: Paediatric endocrinologist, Radboudumc, Nijmegen
name: Janielle vd Velden, MD, PhD
role: PRINCIPAL_INVESTIGATOR
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