Recurrent Pregnancy LossGPRPLNCT05444283
Genomic Predictors of Recurrent Pregnancy Loss
An observational study of Recurrent Pregnancy Loss, run by Yale University at 10 sites in United States.
Trial summary
The overall goals of this proposal are to determine the genetic architecture of recurrent pregnancy loss (RPL) and to discover genomic predictors of RPL. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Recurrent Pregnancy Loss
- How many people
- 500 participants
- Where
- 10 sitesUnited States
- Study dates
- 1 Sep 2021to Dec 2026
- 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 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Study population: Couples who have had two or more previous pregnancy losses and have undiagnosed cause of recurrent pregnancy loss.
Who may be able to join
- Women with loss of a current singleton pregnancy at < 20 0/7 weeks gestation, documented by ultrasonography or histopathological examination
- History of one or more prior pregnancy losses
- Euploid current pregnancy confirmed by karyotype, microarray, or STORK (Short-read Transpore Rapid Karyotyping) sequencing Note: A limited number of aneuploid losses will be included as part of the pilot phase
- Women with a history of three or more pregnancy losses of unknown cause, with or without a liveborn child
Who cannot join
- History of parental karyotype abnormalities
- History of antiphospholipid antibody syndrome
- Evidence of uncontrolled diabetes
- Evidence of uncontrolled thyroid disease
- History of autoimmune disease related to pregnancy loss (e.g., systemic lupus erythematosus, rheumatoid arthritis)
- History of uterine anomalies
Show all 9Show fewer
- History of cervical insufficiency
- Cohort B - Maternal Effect Gene Cohort
- Known etiology for pregnancy loss
Trial locations and contacts
10 sites in 1 country. Contact the study team or a site near you to ask about taking part.
10 sites in 1 country
United States10 sites, 9 recruiting
- Recruiting
University of Colorado
Aurora, Colorado, 80045
Asma Giornazi, MS, 720-276-8941, asma.giornazi@ucdenver.edu
Nanette Santoro, MD
- Recruiting
University of Texas at Austin
Austin, Texas, 78712
Elizabeth Davis, RN, 512-495-2103, elizabethrose.davis@austin.utexas.edu
Brooke Lasher, 404-441-3186, brooke.lasher@austin.utexas.edu
- Recruiting
Johns Hopkins University
Baltimore, Maryland, 21205
Samya El Sayed, MD, 443-473-2674, selsaye4@jh.edu
James Segars, MD
- Recruiting
Northwestern University
Chicago, Illinois, 60611
Riley Bonaccorsi, 312-694-6678, riley.bonaccorsi@nm.org
Emily Jungheim, MD
- Active, not recruiting
University of Chicago
Chicago, Illinois, 60611
- Recruiting
Wayne State University
Detroit, Michigan, 48201
Michelle Yoscovits, 313-577-8016, mbrossoi@med.wayne.edu
Stephen Krawetz, PhD
- Recruiting
Pennsylvania State University
Hershey, Pennsylvania, 17033
Robinn Moyer, 717-531-6272, Rmoyer3@pennstatehealth.psu.ed
Sarah Horvath, MD
- Recruiting
Yale University
New Haven, Connecticut, 06511
Yong-Hui Jiang, MD, PhD, 203-785-2429, yong-hui.jiang@yale.edu
Mar T Giner-Calabuig, PhD, 203-737-2212, mar.giner-calabuig@yale.edu
- Recruiting
Columbia University
New York, New York, 10032
Jessica Giordano, CGC, 516-521-5604, jlg2197@cumc.columbia.edu
Alexandra Tinfow, CGC, 917-838-2196, at3452@cumc.columbia.edu
- Recruiting
University of Texas at San Antonio
San Antonio, Texas, 78299
Susie Reyes, RN, 210-450-5384, reyessr@uthscsa.edu
Winifred Mak, MD, PhD
About this study
Official title: Large Scale Genome Sequencing and Integrative Analyses to Define Genomic Predictors of Recurrent Pregnancy Loss
The overall goals of this proposal are to determine the genetic architecture of recurrent pregnancy loss (RPL) and to discover genomic predictors of RPL.
Read the detailed description
The following specific aims are proposed:
Aim 1: Collect clinically well-characterized samples from two distinct cohorts of participants with unexplained recurrent pregnancy loss (RPL).
- Cohort A will consist of trios (product of conception (POC), biological mother, and biological father) with unexplained RPL. Specifically, a cohort of up to 500 rigorously phenotyped trios will be recruited, for which couples' RPL is not attributable to known causes. POC tissues and parental DNA samples (blood or saliva) will be collected. If necessary for the purpose of determining the pathogenicity of sequence variants identified in the trio, collecting DNA samples from other family members after consent will also be considered. The study team may also request DNA or POC tissues from prior pregnancy loss(es) if available.
- Cohort B will consist of up to 100 women with a history of three or more pregnancy losses, with or without a liveborn child, and no known etiology. For these participants, DNA samples (blood or saliva) will be collected from the mothers. If high-impact variants are identified, DNA samples from parents or siblings may be collected for segregation analysis after consent.
Aim 2: Whole genome sequencing (WGS) will be performed at the Yale Center for Genome Analysis (YCGA), along with bioinformatic analyses to identify pathogenic variants in both cohorts. For Cohort A, analyses will focus on pathogenic variants identified in RPL trios, and for Cohort B, analyses will focus on variants associated with maternal effect genes in the mothers. Pathogenic variants will be comprehensively defined, and fully annotated variant maps will be generated for all included samples to provide the substrate for subsequent novel gene discovery and, ultimately, the development of clinical diagnostic tests.
- Conditions
- Recurrent Pregnancy Loss
What is being measured
The primary outcome is the main question the study is designed to answer.
Determine genetic etiology for Recurrent Pregnancy Loss
The WGS tool will be used to analyze the POC sample and parental blood samples to determine the clinical reportable genetic cause for RPL
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 posted5 Jul 2022
- Study start1 Sep 2021
- Primary completionDec 2026 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Recurrent Pregnancy LossStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe sponsor's other registered studies.
- 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 500 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Collaborators
- Johns Hopkins University, University of Texas at Austin, Penn State University, Northwestern University, The University of Texas Health Science Center at San Antonio, Wayne State University, Columbia University, University of Colorado, Denver, University of Chicago, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), University of Utah
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05444283
- Sponsor's protocol ID
- 2000029802
- Other IDs
- 1R01HD105267-01
- Acronym
- GPRPL
- Status last verified
- May 2026
- First submitted
- 29 Jun 2022
- Last updated
- 22 May 2026
- Results posted
- No
- Data monitoring committee
- 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 22 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Large Scale Genome Sequencing and Integrative Analyses to Define Genomic Predictors of Recurrent Pregnancy Loss
- ClinicalTrials.gov ID
- NCT05444283
- Acronym / sponsor ID
- GPRPL / 2000029802
- Conditions
- Recurrent Pregnancy Loss
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 500 participants (estimated)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- Johns Hopkins University, University of Texas at Austin, Penn State University, Northwestern University, The University of Texas Health Science Center at San Antonio, Wayne State University, Columbia University, University of Colorado, Denver, University of Chicago, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), University of Utah
- Study start
- 1 Sep 2021 (actual)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 5 Jul 2022 (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.
The overall goals of this proposal are to determine the genetic architecture of recurrent pregnancy loss (RPL) and to discover genomic predictors of RPL.
Detailed description
The following specific aims are proposed:
Aim 1: Collect clinically well-characterized samples from two distinct cohorts of participants with unexplained recurrent pregnancy loss (RPL).
- Cohort A will consist of trios (product of conception (POC), biological mother, and biological father) with unexplained RPL. Specifically, a cohort of up to 500 rigorously phenotyped trios will be recruited, for which couples' RPL is not attributable to known causes. POC tissues and parental DNA samples (blood or saliva) will be collected. If necessary for the purpose of determining the pathogenicity of sequence variants identified in the trio, collecting DNA samples from other family members after consent will also be considered. The study team may also request DNA or POC tissues from prior pregnancy loss(es) if available.
- Cohort B will consist of up to 100 women with a history of three or more pregnancy losses, with or without a liveborn child, and no known etiology. For these participants, DNA samples (blood or saliva) will be collected from the mothers. If high-impact variants are identified, DNA samples from parents or siblings may be collected for segregation analysis after consent.
Aim 2: Whole genome sequencing (WGS) will be performed at the Yale Center for Genome Analysis (YCGA), along with bioinformatic analyses to identify pathogenic variants in both cohorts. For Cohort A, analyses will focus on pathogenic variants identified in RPL trios, and for Cohort B, analyses will focus on variants associated with maternal effect genes in the mothers. Pathogenic variants will be comprehensively defined, and fully annotated variant maps will be generated for all included samples to provide the substrate for subsequent novel gene discovery and, ultimately, the development of clinical diagnostic tests.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
- Study population
- Couples who have had two or more previous pregnancy losses and have undiagnosed cause of recurrent pregnancy loss.
Key inclusion criteria (4 listed)
- Women with loss of a current singleton pregnancy at < 20 0/7 weeks gestation, documented by ultrasonography or histopathological examination
- History of one or more prior pregnancy losses
- Euploid current pregnancy confirmed by karyotype, microarray, or STORK (Short-read Transpore Rapid Karyotyping) sequencing Note: A limited number of aneuploid losses will be included as part of the pilot phase
- Women with a history of three or more pregnancy losses of unknown cause, with or without a liveborn child
Key exclusion criteria (9 listed)
- History of parental karyotype abnormalities
- History of antiphospholipid antibody syndrome
- Evidence of uncontrolled diabetes
- Evidence of uncontrolled thyroid disease
- History of autoimmune disease related to pregnancy loss (e.g., systemic lupus erythematosus, rheumatoid arthritis)
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
Determine genetic etiology for Recurrent Pregnancy Loss
Time frame: 5 years
The WGS tool will be used to analyze the POC sample and parental blood samples to determine the clinical reportable genetic cause for RPL
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 22 May 2026.
- Individual participant dataSharing planned: No
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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.
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Recurrent Pregnancy Loss, run by Yale University at 10 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 4 inclusion and 9 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 22 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 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 Yong-Hui Jiang, MD, PhD (2037852429, yong-hui.jiang@yale.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Determine genetic etiology for Recurrent Pregnancy Loss (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 22 May 2026.