Fetal Genome Profiling Via Trophoblast Cells

NCT ID: NCT03832634

Last Updated: 2023-08-03

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: NA
• Total Enrollment: 1 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-07-02
• Study Completion Date: 2023-02-02

Brief Summary

The objective of this study is to utilize trophoblast cells accumulating in the endocervical canal at the beginning of pregnancy for non-invasive prenatal testing. If we are able to validate that trophoblast cells obtained at an early gestational age can be reliably used for prenatal testing, there is great potential to improve early pregnancy management and counseling options for potential parents. The target population will be all women between the age of 18-45 undergoing care at the Center for Reproductive Medicine (CRM) in order to achieve a pregnancy.

Detailed Description

The primary purpose of the study is to validate trophoblast retrieval and isolation from the cervix (TRIC) as a means of reliable non invasive prenatal genetic diagnosis (for both chromosomal abnormalities, as well as single gene defects).

The study population will be recruited from women, age 18 to 45, presenting to the Center for Reproductive Medicine (CRM) for medical care with the desire to become pregnant. Patients that achieve pregnancy will be invited by a physician to participate in the study. If prospective subjects agree to participate, they will meet with a co-investigator to go through the informed consent process.

Subjects will undergo a one-time non-invasive collection of trophoblast cells (trophoblast retrieval and isolation from the cervix, TRIC) at approximately 5-6 weeks of pregnancy as the experimental procedure for the study. TRIC is performed with ThinPrep kits using a cytobrush, the same method of Pap smear collection which is a routine part of prenatal care. The fetal trophoblast cells will then be isolated using immunomagnetic isolation. Once isolated, DNA fragmentation, fluorescent in situ hybridization (FISH), and single-cell PCR methods will be utilized to analyze the fetal genome at single nucleotide resolution. Any abnormal results identified by TRIC will be communicated to the subjects' by their physician in the office who will counsel them on the potential meaning of the results and recommend follow up testing to be ordered by their obstetrician to confirm results.

The cellular analysis from TRIC will then be compared to results obtained from CVS, amniocentesis, preimplantation genetic screening (PGS) and/or preimplantation genetic diagnosis (PGD) of the transferred embryo(s), or cytogenetic testing of fetal tissue in the event of miscarriage or pregnancy termination for validation. In the event that a patient does not undergo any of the aforementioned testing, TRIC results will be compared to birth outcomes.

Subjects will be followed via medical records through the final outcome of the pregnancy, whether termination of pregnancy, miscarriage, or live birth. If the pregnancy results in termination of pregnancy or miscarriage, cytogenetic testing of the fetus will be completed as standard care with the results compared to those obtained through TRIC testing. If the pregnancy results in live birth, basic neonatal information will be obtained via medical records, specifically whether the neonate is diagnosed with a disorder that can be identified through single gene testing (see attached table).

Conditions

Fetal Growth Retardation

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

Fetal Genome Profiling

Trophoblast cells will be collected from the cervix approximately 5-6 weeks once pregnancy is achieved.

Group Type: OTHER

Fetal Genome Profiling.

Intervention Type: DIAGNOSTIC_TEST

Once pregnancy is achieved, patients will undergo non-invasive collection of trophoblast cells (trophoblast retrieval and isolation from the cervix, TRIC) at an early gestational age, approximately 5-6 weeks. The patient will also be screened with blood work for carrier status for genetic conditions.

Interventions

Fetal Genome Profiling.

Once pregnancy is achieved, patients will undergo non-invasive collection of trophoblast cells (trophoblast retrieval and isolation from the cervix, TRIC) at an early gestational age, approximately 5-6 weeks. The patient will also be screened with blood work for carrier status for genetic conditions.

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

Inclusion Criteria

• Women 18 to 45 who achieve a pregnancy during study time period.
• If pregnancy result in miscarriage, cytogenetic testing must be completed on the product of conception.

Exclusion Criteria

• Women whose cervical sample collection containing inadequate number of trophoblast cells for analysis.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Weill Medical College of Cornell University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kangpu Xu, PhD, DVM

Role: PRINCIPAL_INVESTIGATOR

Weill Medical College of Cornell University

Locations

Weill Cornell Medicine

New York, New York, United States

Countries

United States

Other Identifiers

1703018076

Identifier Type: -

Identifier Source: org_study_id