Technical Feasibility of the cfDNA Test for Non-invasive Cytogenetic Analysis of Early Miscarriages Versus the Gold Standard Microarray

NCT ID: NCT05900076

Last Updated: 2024-09-20

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 78 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2023-07-18
• Study Completion Date: 2024-07-19

Brief Summary

Among the 15% of couples who experience a spontaneous early miscarriage (SEM) during their pregnancy, approximately 2 to 5% will suffer from recurrent SEM. It is only after the third SM that they will be offered a workup to look for a predisposition to SEM. This workup does not currently include a search for foetal chromosomal abnormalities that could be considered causal for this event. These anomalies are responsible for approximately 50% of SEM and their detection could lead to an explanation for half of the couples currently without a diagnosis after a standard workup. The diagnosis of chromosomal abnormalities can be made by karyotype analysis or by Cytogenetic Microarray Analysis (CMA) on the product of conception. Unfortunately, karyotyping has a high failure rate due to poor cell culture of samples that are often degraded or of low quantity. The CMA is not always feasible due to the absence of analyzable feto-placental material linked to the use of a drug strategy for its elimination.

The study of cell-free DNA of syncytiotrophoblastic origin (cfDNA) circulating in the maternal plasma could be a solution as it is for non-invasive prenatal screening of trisomy 21. cfDNA is detectable from 6 to 8 weeks of amenorrhea and released in the maternal blood as long as placental tissue is present in the uterus, can be easily obtained by maternal venous sampling. If maternal blood sampling is performed before complete removal of the product of conception, then detection of foetal chromosomal abnormalities would be possible. Thus, if failure rates of CMA and cfDNA techniques are comparable, cfDNA could be preferred as it applies for miscarriages for whom no fetoplacental material can be obtained.

This study therefore proposes to compare the failure rates of the two technologies (CMA and cfDNA) for the detection of chromosomal abnormalities in recurrent SEM.

Conditions

Spontaneous Miscarriage

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Patient group

This group corresponds to patients who have just suffered a miscarriage and are undergoing curettage for the evacuation of the product of conception.

Curettage for the evacuation of the product of conception

Intervention Type: DIAGNOSTIC_TEST

The product of conception taken during the intervention will be recovered at Day 1

Interventions

Curettage for the evacuation of the product of conception

The product of conception taken during the intervention will be recovered at Day 1

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

Inclusion Criteria

• Patient who has suffered a miscarriage and requires a curettage to collect the product of conception
• Patient consenting to constitutional cytogenetic analysis on cfDNA and product of conception
• Patient of legal age
• Patient affiliated to a Social Security system.

Exclusion Criteria

• Venous sampling impossible
• Miscarriage before 8 weeks of pregnancy (unusable cfDNA)
• Patient does not understand French
• Patient under legal protection

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Hospices Civils de Lyon

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Hopital Femme-Mère-Enfant; service gynécologie/obstétrique

Bron, Rhône, France

Hopital Femme-Mère-Enfant; service médecine de la reproduction

Bron, Rhône, France

Countries

France

Other Identifiers

69HCL21_0080

Identifier Type: -

Identifier Source: org_study_id