Identifying Genome Variants in Non-Obstructive Azoospermia (NOA) or Primary Ovarian Insufficiency (POI)

March 13, 2026 updated by: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Identifying Genome Variants and Evaluating PRDM9 and piRNA Clusters as Candidates for Infertility in a Cohort of Individuals With Non-Obstructive Azoospermia (NOA) or Primary Ovarian Insufficiency (POI)

Background:

Infertility affects 1 in 6 people. Often, the causes of infertility are unknown. Treatments are successful in only about 50% of cases. Infertility caused by non obstructive azoospermia in males and primary ovarian insufficiency in females can have genetic causes. Researchers want to learn more about these genes.

Objective:

To identify genes that may cause infertility.

Eligibility:

Adult men and women with non-obstructive azoospermia (NOA) or primary ovarian insufficiency (POI) of unknown cause.

Design:

Participants will provide a saliva sample. A kit will be sent to their home. The kit will contain a collection tube and a cotton swab. They will swirl the swab inside their mouth and then seal it in the tube. They will mail the tube back to the researchers.

Male participants who are having a procedure done to collect tissue from their testes may opt to have leftover tissue provided to study researchers. This tissue would otherwise have been discarded. No new procedures will be performed just for this study.

Data may be collected from participants medical records.

Study Overview

Status

Recruiting

Conditions

Detailed Description

Study Description:

PRDM9 and the piRNA pathway have well established roles in meiosis and are known to cause infertility in mouse, yet have not been systematically evaluated for a role in human infertility. We will utilize a combination of genome sequencing, targeted PacBio sequencing, and in vitro assays to evaluate these compelling candidates as causative for human infertility. All participants will be asked to provide saliva or blood samples as a source of genomic DNA for sequencing. A small subset of participants who undergo surgery as part of their diagnosis and treatment plan will be asked to consent to research use of leftover testicular biopsies from these procedures.

Objectives:

Primary Objective:

To determine the sequence of PRDM9 and noncoding piRNA clusters in a cohort of individuals with infertility. These loci are inherently unstable in the genome, and we hypothesize that sequence variants in these loci are causative for infertility.

Secondary Objectives:

Identify genome variants in novel or previously reported infertility candidate genes. Genome variants in hundreds of genes have been reported as candidates for infertility, and collective data from additional cohorts is needed to evaluate the gene-disease relationship of these infertility candidate genes.

Study Type

Observational

Enrollment (Estimated)

500

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

  • United States
    • Maryland
      • Bethesda, Maryland, United States, 20892
        • Recruiting
        • National Institutes of Health Clinical Center (Remote and In-Person)
      • Rockville, Maryland, United States, 20850
        • Recruiting
        • Shady Grove Fertility

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
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Patients seeking infertility care diagnosed with primary ovarian insufficiency, non obstructive azoospermia, or oligospermia will be offered the opportunity to enroll in genetic sequencing to further evaluate genetic causes of infertility.

Description

  • INCLUSION CRITERIA:

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

  1. Provision of signed and dated informed consent form
  2. Stated willingness to comply with all study procedures and availability for the duration of the study
  3. Adult male or female, of reproductive age
  4. Clinical diagnosis of NOA, oligospermia, or POI.
  5. In good general health with no medical history suspected as the cause of infertility.

EXCLUSION CRITERIA:

An individual who meets any of the following criteria will be excluded from participation in this study:

  1. Current use of medications that may cause infertility (chemotherapy, etc.)
  2. Pregnant or lactating
  3. Medical history indicating known common cause of infertility such as karyotype anomalies, Y-chromosome microdeletions, known monogenic causes, or other medical history affecting gamete production (i.e. injuries, surgical operations, infections, radiation, or chemotherapy).

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
Non obstructive azoospermia
Men aged 18 and older who have no semen in the ejaculate with no evidence of pathologic transport of sperm
Oligospermia
Men aged 18 or older who have a concentration less than 5 million/mL in ejaculate with no other known cause of oligospermia.
Primary ovarian insufficiency
Women who have been diagnosed with primary ovarian insufficiency

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Genetic associations with infertility (primary ovarian insufficiency, oligospermia, non obstructive azoospermia)
Time Frame: 5 years
Across 5 years we will sequence patients with POI and NOA to determine genetic associations with infertility
5 years

Collaborators and Investigators

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

Sponsor

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Investigators

  • Principal Investigator: Todd S Macfarlan, M.D., Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

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.

Helpful Links

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 (Actual)

March 11, 2026

Primary Completion (Estimated)

January 1, 2031

Study Completion (Estimated)

January 1, 2031

Study Registration Dates

First Submitted

January 21, 2026

First Submitted That Met QC Criteria

January 21, 2026

First Posted (Actual)

January 22, 2026

Study Record Updates

Last Update Posted (Actual)

March 16, 2026

Last Update Submitted That Met QC Criteria

March 13, 2026

Last Verified

March 11, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 10002332
  • 002332-CH

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

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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