Genetic Variants in Idiopathic Premature Ovarian Insufficiency

May 14, 2026 updated by: Abdurrahman Hamdi İnan

Investigation of Pathogenic Variants in DNA Repair and Meiotic Genes Associated With Ovarian Reserve and Folliculogenesis in Idiopathic Premature Ovarian Insufficiency Using Whole Exome Sequencing: A Case-Control Study

Premature ovarian insufficiency is a condition in which ovarian function decreases or is lost before the age of 40 years. In many patients, the underlying cause remains unexplained. This prospective observational case-control study aims to investigate pathogenic and likely pathogenic genetic variants in DNA repair and meiotic genes related to ovarian reserve and folliculogenesis in women with idiopathic premature ovarian insufficiency.

The study will include women younger than 40 years with idiopathic premature ovarian insufficiency and age- and ethnicity-matched control participants with normal ovarian function. Clinical and reproductive data will be collected, and a peripheral blood sample will be obtained from each participant for whole exome sequencing. The frequency of pathogenic or likely pathogenic variants will be compared between the case and control groups. No investigational drug, device, or treatment intervention will be administered.

Study Overview

Status

Not yet recruiting

Conditions

Study Type

Observational

Enrollment (Estimated)

100

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Turkey (Türkiye)
    • İzmir
      • Bornova, İzmir, Turkey (Türkiye), 35100
        • University of Health Sciences Tepecik Training and Research Hospital, Department of Obstetrics and Gynecology
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

The study population will consist of women aged 18 to 39 years who are evaluated at the Department of Obstetrics and Gynecology/Reproductive Endocrinology clinics. The case group will include women diagnosed with idiopathic premature ovarian insufficiency, defined by spontaneous amenorrhea or marked menstrual irregularity lasting at least 4 months and elevated serum FSH levels. The control group will include age- and ethnicity-matched women with regular menstrual cycles, normal ovarian reserve findings for age, and no known history of infertility, premature ovarian insufficiency, gonadotoxic treatment, or ovarian surgery.

Description

Inclusion Criteria:

For the idiopathic premature ovarian insufficiency group:

  • Women aged 18 to 39 years.
  • Spontaneous amenorrhea or marked menstrual irregularity lasting at least 4 months.
  • Serum FSH level greater than 25 IU/L. In cases of diagnostic uncertainty, FSH measurement may be repeated after 4 to 6 weeks.
  • Diagnosis of idiopathic premature ovarian insufficiency, with no known chromosomal abnormality, FMR1 premutation, defined syndromic genetic diagnosis, or iatrogenic cause.
  • Willingness to participate in the study and ability to provide written informed consent.

For the control group:

  • Women aged 18 to 39 years.
  • Regular menstrual cycles.
  • Age-appropriate normal ovarian reserve findings, including FSH and AMH values within age-appropriate reference ranges and, when available, appropriate antral follicle count.
  • No known history of infertility, premature ovarian insufficiency, or early menopause.
  • No history of gonadotoxic treatment or ovarian surgery.
  • Willingness to participate in the study and ability to provide written informed consent.

Exclusion Criteria:

For both groups:

  • Known chromosomal abnormality, such as Turner syndrome or structural X chromosome abnormality.
  • FMR1 premutation carrier status.
  • Previously defined syndromic genetic diagnosis.
  • Active malignancy.
  • History of gonadotoxic chemotherapy or pelvic radiotherapy.
  • Iatrogenic ovarian damage or iatrogenic premature ovarian insufficiency after ovarian surgery.
  • Clear autoimmune, endocrine, or other clinical condition that may explain secondary amenorrhea.
  • Refusal to provide informed consent or request to withdraw study data.
  • Insufficient DNA sample quality or inability to complete genetic analysis for technical reasons.

Additional exclusion criteria for the control group:

  • Known history of infertility, premature ovarian insufficiency, or early menopause.
  • Ovarian reserve findings below the expected range for age.
  • Previous gonadotoxic treatment or ovarian surgery.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Idiopathic Premature Ovarian Insufficiency Group
Women younger than 40 years diagnosed with idiopathic premature ovarian insufficiency, defined by spontaneous amenorrhea or menstrual irregularity lasting at least 4 months and serum FSH level greater than 25 IU/L, with no known chromosomal abnormality, FMR1 premutation, syndromic genetic diagnosis, or iatrogenic cause.
Control Group
Women younger than 40 years with regular menstrual cycles, age-appropriate ovarian reserve findings, no known history of infertility or premature ovarian insufficiency, no previous gonadotoxic treatment, and no history of ovarian surgery. The control group will be selected to be similar to the case group in terms of age and ethnicity.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Prevalence of Pathogenic or Likely Pathogenic Variants in the Target Gene Set
Time Frame: Through study completion, up to 24 months
Proportion of participants in each group who carry pathogenic or likely pathogenic variants, classified according to ACMG/AMP criteria, in the predefined 57-gene target set related to ovarian reserve, folliculogenesis, DNA repair, and meiosis.
Through study completion, up to 24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Abdurrahman Hamdi İnan

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

June 10, 2026

Primary Completion (Estimated)

June 10, 2028

Study Completion (Estimated)

June 10, 2028

Study Registration Dates

First Submitted

April 29, 2026

First Submitted That Met QC Criteria

May 12, 2026

First Posted (Actual)

May 14, 2026

Study Record Updates

Last Update Posted (Actual)

May 19, 2026

Last Update Submitted That Met QC Criteria

May 14, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • POI-WES-2026-01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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