Clinical trial NCT05444283: Genomic Predictors of Recurrent Pregnancy Loss
Official title: Large Scale Genome Sequencing and Integrative Analyses to Define Genomic Predictors of Recurrent Pregnancy Loss
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Recurrent Pregnancy Loss
Lead sponsor: Yale University
Sponsor class: OTHER
Collaborators: name: Johns Hopkins University
name: University of Texas at Austin
name: Penn State University
name: Northwestern University
name: The University of Texas Health Science Center at San Antonio
name: Wayne State University
name: Columbia University
name: University of Colorado, Denver
name: University of Oklahoma
name: University of Chicago
name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2022-07-05
Enrollment: 1000
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Couples who have had two or more previous pregnancy losses and have undiagnosed cause of recurrent pregnancy loss.

Brief 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.

Detailed description: The following specific aims are proposed:

Aim 1: Collect clinically well-characterized samples from trios (product of conception (POC), biological mother, and biological father) with unexplained RPL. Specifically, a cohort of 1,000 trios that are rigorously-phenotyped will be recruited, and for which couples' RPL is not attributable to known causes. The POC and parental DNA samples will be collected. If it is necessary for the purpose of determining the pathogenicity of sequence variants from 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 a prior pregnancy loss(es) if available.

Aim 2: A whole genome sequencing (WGS) at the Yale Center for Genome Analysis (YCGA) will be performed and bioinformatic analyses to identify pathogenic variants in included trios will performed as well. Pathogenic variants will be comprehensively defined and fully annotated variant maps in all included trios to provide the substrate for subsequent novel gene discovery, and ultimately, the development of clinical diagnostic tests will be generated.

Eligibility criteria: 1. Women with loss of a current singleton pregnancy at \< 20 0/7 weeks gestation (documented by ultrasonography or histopathological examination) and one or more prior pregnancy losses.
2. Euploid current pregnancy by karyotype or microarray (a limited number of aneuploid losses will be included as part of the pilot)
3. No history of parental karyotype abnormalities
4. No history of antiphospholipid antibody syndrome
5. No evidence of uncontrolled diabetes
6. No evidence of uncontrolled thyroid disease
7. No history of autoimmune disease (SLE, RA)
8. No history of uterine anomalies
9. No history of cervical insufficiency

Primary outcomes:
measure: Determine genetic etiology for Recurrent Pregnancy Loss
timeFrame: 5 years
Secondary outcomes:
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Baltimore
country: United States
facility: Gaelle Massoud
state: Maryland
city: Detroit
country: United States
facility: Wayne State University
state: Michigan
city: New York
country: United States
facility: Columbia University
state: New York
city: Oklahoma City
country: United States
facility: University of Oklahoma
state: Oklahoma
city: Hershey
country: United States
facility: Pennsylvania State University
state: Pennsylvania
city: Austin
country: United States
facility: University of Texas at Austin
state: Texas
city: San Antonio
country: United States
facility: University of Texas at San Antonio
state: Texas
Study officials:
References: