Genomic Predictors of Recurrent Pregnancy Loss (GPRPL)

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.

Study Overview

• Status: Recruiting
• Conditions: Recurrent Pregnancy Loss

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.

• Study Type: Observational
• Enrollment (Estimated): 1000

Contacts and Locations

• Study Contact: Name: Yong-Hui Jiang, MD, PhD; Phone Number: 2037852429; Email: yong-hui.jiang@yale.edu
• Study Contact Backup: Name: Heping Zhang, PhD; Phone Number: 12037855185; Email: heping.zhang@yale.edu

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • University of Colorado
      • Contact: Katherine Khun, MS; Phone Number: 303-724-5276; Email: KATHERINE.KUHN@CUANSCHUTZ.EDU
      • Principal Investigator: Nanette Santoro, MD
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Recruiting
      • Yale University
      • Principal Investigator: Hugh Taylor, MD
      • Principal Investigator: Yong-Hui Jiang, MD, PhD
      • Contact: Yong-Hui Jiang, MD, PhD; Phone Number: 203-785-2429; Email: yong-hui.jiang@yale.edu
      • Contact: Dylan T Ochoa, MPH; Phone Number: 203-785-7534; Email: dylan.ochoa@yale.edu
      • Sub-Investigator: Heping Zhang, PhD
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Recruiting
      • Northwestern University
      • Contact: Jessica Almgren-Bell; Phone Number: 312-694-6678; Email: jessica.almgrenbell@nm.org
      • Principal Investigator: Emily Jungheim, MD
    • Chicago, Illinois, United States, 60611
      • Active, not recruiting
      • University of Chicago
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Recruiting
      • Gaelle Massoud
      • Contact: Gaelle Massoud, MD; Phone Number: 410-583-2763; Email: gmassou1@jhmi.edu
      • Principal Investigator: James Segars, MD
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Recruiting
      • Wayne State University
      • Contact: Michelle Yoscovits; Phone Number: 313-577-8016; Email: mbrossoi@med.wayne.edu
      • Principal Investigator: Stephen Krawetz, PhD
  • New York
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia University
      • Contact: Jessica Giordano, CGC; Phone Number: 516-521-5604; Email: jlg2197@cumc.columbia.edu
      • Contact: Alexandra Tinfow, CGC; Phone Number: 917-838-2196; Email: at3452@cumc.columbia.edu
      • Principal Investigator: Uma Reddy, MD, MPH
      • Principal Investigator: Samuel Z Williams, MD, PhD
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Recruiting
      • University of Oklahoma
      • Contact: Michelle Starkey-Scruggs, RN; Phone Number: 405-271-9204; Email: Michelle-StarkeyScruggs@ouhsc.edu
      • Contact: Ashley Moriarty, RN; Phone Number: (405) 271-1616; Email: Ashley-Moriarty@ouhsc.edu
      • Principal Investigator: Karl Hansen, MD, PhD
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Recruiting
      • Pennsylvania State University
      • Contact: Robinn Moyer; Phone Number: 717-531-6272; Email: Rmoyer3@pennstatehealth.psu.ed
      • Principal Investigator: Sarah Horvath, MD
  • Texas
    • Austin, Texas, United States, 78712
      • Recruiting
      • University of Texas at Austin
      • Contact: Brooke Lasher; Phone Number: 404-441-3186; Email: brooke.lasher@austin.utexas.edu
      • Contact: Elizabeth Davis, RN; Phone Number: 512-495-2103; Email: elizabethrose.davis@austin.utexas.edu
      • Principal Investigator: Winifred Mak, MD, PhD
    • San Antonio, Texas, United States, 78299
      • Recruiting
      • University of Texas at San Antonio
      • Principal Investigator: Winifred Mak, MD, PhD
      • Contact: Susie Reyes, RN; Phone Number: 210-450-5384; Email: reyessr@uthscsa.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: Yes

• 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.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	5 years

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: Johns Hopkins University; University of Colorado, Denver; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); Northwestern University; University of Chicago; Wayne State University; Columbia University; University of Oklahoma; Penn State University; The University of Texas Health Science Center at San Antonio; University of Texas at Austin

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2021
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2026

Study Registration Dates

• First Submitted: June 29, 2022
• First Submitted That Met QC Criteria: June 29, 2022
• First Posted (Actual): July 5, 2022

Study Record Updates

• Last Update Posted (Actual): August 14, 2023
• Last Update Submitted That Met QC Criteria: August 8, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Pregnancy Complications; Death; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Recurrence; Abortion, Spontaneous; Abortion, Habitual; Fetal Death
• Other Study ID Numbers: 2000029802; 1R01HD105267-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No