Identifying genetic variants in non-obstructive azoospermia and primary ovarian insufficiency
Official title: 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)
Run by National Institutes of Health Clinical Center (CC) · NCT07357701 · Data updated 2026-11-12
This project will collect DNA from adults with NOA, oligospermia, or POI to try to find gene changes that may cause their infertility.
Quick facts
| Study type | Observational |
|---|---|
| Ages | 18 Years to 100 Years |
| Sex | All |
| Enrollment | 500 (estimated) |
| Sponsor | National Institutes of Health Clinical Center (CC) NIH |
| Drugs / interventions | chemotherapy, radiation |
| Locations | 2 sites (Bethesda, Maryland and 1 other locations) |
| Status | Recruiting |
| Started | March 11, 2026 |
| Main results expected | January 1, 2031 |
| Study ends | January 1, 2031 |
| Registry record updated | March 16, 2026 |
| Trial ID | NCT07357701 on ClinicalTrials.gov |
Is this trial a fit for you?
✓Likely a good fit
Adults of reproductive age with a clinical diagnosis of non-obstructive azoospermia, oligospermia, or primary ovarian insufficiency of unknown cause who are in generally good health and willing to provide consent and DNA samples are ideal candidates.
✕Probably not a fit
People with known causes of infertility (e.g., karyotype abnormalities, Y-chromosome microdeletions, prior chemotherapy or radiation, known monogenic diagnoses), those on infertility-causing medications, and pregnant or lactating individuals are excluded and unlikely to benefit from this study.
A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.
What this trial studies
Researchers will sequence genomic DNA from participants with non-obstructive azoospermia, oligospermia, or primary ovarian insufficiency, using whole-genome approaches plus targeted long-read (PacBio) sequencing for unstable loci. The study places special emphasis on PRDM9 and noncoding piRNA clusters, which are known to affect meiosis in animal models but have not been systematically characterized in humans. Samples are collected via mailed saliva kits or blood, and a subset of men undergoing clinically indicated testicular procedures may donate leftover biopsy tissue for research. Findings will be compared to reported candidate infertility genes and followed up with in vitro assays when appropriate.
Why it matters
Potential benefit: If successful, the study could identify genetic causes of infertility that improve diagnosis, genetic counseling, and reproductive decision-making for affected individuals.
How similar studies have gone: Prior genomic studies have identified candidate infertility genes and shown that sequencing can find causative variants, but systematic long-read analysis of PRDM9 and piRNA clusters in human infertility remains novel.
Who can join: the full rules
Show full inclusion / exclusion criteria
* 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).
Where it's running
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National Institutes of Health Clinical Center (Remote and In-Person)
Bethesda, Maryland, United States Recruiting -
Shady Grove Fertility
Rockville, Maryland, United States Recruiting
Study contacts
- Principal investigator: Todd S Macfarlan, M.D. — Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Study coordinator: Todd S Macfarlan, M.D.
- Email: MacfarlanLab@mail.nih.gov
- Phone: (301) 594-8496
Similar studies
Other studies for the same condition or treatment. Recruiting studies are listed first.
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This will try an AI-assisted imaging platform to find rare sperm in testicular samples from men with non-obstructive azoospermia when standard processing finds no sperm.
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This study tests whether starting estrogen replacement helps heart-health markers in women newly diagnosed with POI compared with healthy peers.
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How to take part
- Review the eligibility criteria above with your treating physician.
- Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
- Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.