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

NCT07357701 — Recruiting, 500 participants, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

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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)

Registry	NCT07357701
Status	Recruiting
Study type	Observational
Enrollment	500 (Estimated)
Sponsor	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (Nih)
Conditions	Primary Ovarian Insufficiency, Azoospermia, Oligospermia
Dates	start 2026-03-11, primary completion 2031-01-01 (estimated), completion 2031-01-01 (estimated), first posted 2026-01-22, last updated 2026-03-16
Locations	2 sites in United States

-Summary

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.

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+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.

+Arms and interventions

Arm	Type	Interventions	Description
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

+Outcome measures

Primary outcomes

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

+Eligibility

Sex: All, ages: 18 Years to 100 Years

* 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).

+Locations (2)

Facility	City	Country	Status
National Institutes of Health Clinical Center (Remote and In-Person)	Bethesda, Maryland	United States	Recruiting
Shady Grove Fertility	Rockville, Maryland	United States	Recruiting

+Investigators

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