Primary Ovarian InsufficiencyNCT07357701
Identifying Genome Variants in Non-Obstructive Azoospermia (NOA) or Primary Ovarian Insufficiency (POI)
An observational study of Primary Ovarian Insufficiency and Azoospermia, run by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Primary Ovarian Insufficiency, Azoospermia, Oligospermia
- How many people
- 500 participants
- Where
- 2 sitesUnited States
- Study dates
- 11 Mar 2026to 1 Jan 2031
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- In order to be eligible to participate in this study, an individual must meet all of the following criteria:
- Provision of signed and dated informed consent form
- Stated willingness to comply with all study procedures and availability for the duration of the study
- Adult male or female, of reproductive age
- Clinical diagnosis of NOA, oligospermia, or POI.
- In good general health with no medical history suspected as the cause of infertility.
Who cannot join
- An individual who meets any of the following criteria will be excluded from participation in this study:
- Current use of medications that may cause infertility (chemotherapy, etc.)
- Pregnant or lactating
- 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).
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States2 sites, 2 recruiting
- Recruiting
National Institutes of Health Clinical Center (Remote and In-Person)
Bethesda, Maryland, 20892
- Recruiting
Shady Grove Fertility
Rockville, Maryland, 20850
About this study
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)
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.
Read more
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.
Read the 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.
- Conditions
- Primary Ovarian Insufficiency, Azoospermia, Oligospermia
- Keywords
- NOA, POI, Premature Ovarian Insufficiency, oligospermia, azoospermia, diminished ovarian reserve, nonobstructive azoospermia, Primary Ovarian Insufficiency, Infertility
- Medical subject headings
- Primary Ovarian Insufficiency, Azoospermia, Oligospermia, Azoospermia, Nonobstructive, Infertility
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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 being measured
The primary outcome is the main question the study is designed to answer.
Genetic associations with infertility (primary ovarian insufficiency, oligospermia, non obstructive azoospermia)
Across 5 years we will sequence patients with POI and NOA to determine genetic associations with infertility
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jan 2026
- Study start11 Mar 2026
- Primary completion1 Jan 2031 (estimated)
- Study completion1 Jan 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Primary Ovarian InsufficiencyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Cross-sectional
- Enrolment
- 500 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Todd S Macfarlan, M.D., Principal investigator, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07357701
- Sponsor's protocol ID
- 10002332
- Other IDs
- 002332-CH
- Status last verified
- 11 Mar 2026
- First submitted
- 21 Jan 2026
- Last updated
- 16 Mar 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT07357701
- Acronym / sponsor ID
- 10002332
- Conditions
- Primary Ovarian Insufficiency, Azoospermia, Oligospermia
- Keywords
- NOA, POI, Premature Ovarian Insufficiency, oligospermia, azoospermia, diminished ovarian reserve, nonobstructive azoospermia, Primary Ovarian Insufficiency
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 500 participants (estimated)
- Lead sponsor
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)US National Institutes of Health
- Study start
- 11 Mar 2026 (actual)
- Primary completion
- 1 Jan 2031 (estimated)
- Study completion
- 1 Jan 2031 (estimated)
- First posted
- 22 Jan 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Observational model
- Case only
- Time perspective
- Cross-sectional
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (6 listed)
- In order to be eligible to participate in this study, an individual must meet all of the following criteria:
- Provision of signed and dated informed consent form
- Stated willingness to comply with all study procedures and availability for the duration of the study
- Adult male or female, of reproductive age
- Clinical diagnosis of NOA, oligospermia, or POI.
Key exclusion criteria (4 listed)
- An individual who meets any of the following criteria will be excluded from participation in this study:
- Current use of medications that may cause infertility (chemotherapy, etc.)
- Pregnant or lactating
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Mar 2026.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: No
Related trials for Primary Ovarian Insufficiency
Not yet recruitingPhase 1
Oral GDC-0077 in Premature Ovarian Insufficiency
Primary Ovarian Insufficiency
RecruitingPhase 3
Hormone Replacement Therapy in Adolescents With Premature Ovarian Insufficiency
Premature Ovarian Insufficiency
RecruitingObservational study
Gonadotropin-releasing Hormone Agonist (GnRHa) in Ovarian Preservation in SLE Subjects Receiving Cyclophosphamide as Determined by Questionnaires
Systemic Lupus Erythematosus (Sle), Primary Ovarian Insufficiency (Poi)
RecruitingObservational study
Biorepository in Participants Who Undergo OTC for Gonadotoxic Therapy
Acute Ovarian Failure, Infertility
RecruitingObservational study
Gonadal Tissue Freezing for Fertility Preservation in Individuals at Risk for Ovarian Dysfunction, Premature Ovarian Insufficiency and Clinically Indicated Gonadectomy
Turner Syndrome, Post-menarcheal Adolescents
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Todd S Macfarlan, M.D. principal investigator
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Primary Ovarian Insufficiency and Azoospermia, run by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 16 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Todd S Macfarlan, M.D. ((301) 594-8496, MacfarlanLab@mail.nih.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Genetic associations with infertility (primary ovarian insufficiency, oligospermia, non obstructive azoospermia) (time frame: 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Mar 2026.