Identifying genetic factors in recurrent pregnancy loss

Large Scale Genome Sequencing and Integrative Analyses to Define Genomic Predictors of Recurrent Pregnancy Loss

This study is trying to find out if certain genetic factors are linked to recurrent pregnancy loss by looking at DNA from families who have experienced this issue.

Quick facts

• Study type: Observational
• Enrollment: 500 (estimated)
• Ages: 18 Years to 50 Years
• Sex: All
• Sponsor: Yale University (Academic / other)
• Locations: 10 sites (Aurora, Colorado and 9 other locations)
• Trial ID: NCT05444283 on ClinicalTrials.gov

What this trial studies

This observational study aims to explore the genetic basis of recurrent pregnancy loss (RPL) by collecting and analyzing DNA samples from trios consisting of the product of conception, the biological mother, and the biological father. The study will recruit 1,000 rigorously characterized trios with unexplained RPL and perform whole genome sequencing at the Yale Center for Genome Analysis. The goal is to identify pathogenic genetic variants that could lead to novel gene discoveries and the development of clinical diagnostic tests for RPL.

Who should consider this trial

Good fit: Ideal candidates for this study are women who have experienced recurrent pregnancy loss and have a current singleton pregnancy that is euploid.

Not a fit: Patients with known causes of pregnancy loss, such as karyotype abnormalities or autoimmune diseases, may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide insights into the genetic causes of recurrent pregnancy loss, leading to better diagnostic tools and treatment options for affected patients.

How similar studies have performed: Other studies have shown promise in identifying genetic factors related to pregnancy loss, but this specific approach is novel in its comprehensive genomic analysis of trios.

Eligibility criteria

Cohort A - Fetal Intolerome Cohort

Inclusion Criteria:

* 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

Exclusion Criteria:

* 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
* History of cervical insufficiency

Cohort B - Maternal Effect Gene Cohort

Inclusion Criteria:

\- Women with a history of three or more pregnancy losses of unknown cause, with or without a liveborn child

Exclusion Criteria:

\- Known etiology for pregnancy loss

Where this trial is running

Aurora, Colorado and 9 other locations

• University of Colorado — Aurora, Colorado, United States (Recruiting)
• Yale University — New Haven, Connecticut, United States (Recruiting)
• Northwestern University — Chicago, Illinois, United States (Recruiting)
• University of Chicago — Chicago, Illinois, United States (Active_not_recruiting)
• Gaelle Massoud — Baltimore, Maryland, United States (Recruiting)
• Wayne State University — Detroit, Michigan, United States (Recruiting)
• Columbia University — New York, New York, United States (Recruiting)
• Pennsylvania State University — Hershey, Pennsylvania, United States (Recruiting)
• University of Texas at Austin — Austin, Texas, United States (Recruiting)
• University of Texas at San Antonio — San Antonio, Texas, United States (Recruiting)

Study contacts

• Study coordinator: Yong-Hui Jiang, MD, PhD

Conditions Recurrent Pregnancy Loss