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

NCT05900076 | Completed

• 1 other identifier: 69HCL21_0080
• Study Type: observational
• Target: 78
• Locations: 1 country
• Sites: 2

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

Keywords

Cell-free DNA; spontaneous miscarriage; chromosomal abnormalities; cytogenetic analysis

Outcome Measures

Primary Outcomes (1)

• Failure rate of cfDNA compared to CMA

  Failure rate of cfDNA compared to CMA Since the difference in failure rates between the two techniques (MCA and cfDNA) corresponds to a comparison of 2 proportions in a matched situation.

  The outcome measure (failure rates of both techniques) will be assessed through study completion ; estimated 6 months after last inclusion.

Study Arms (1)

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.

Diagnostic Test: Curettage for the evacuation of the product of conception

Interventions

Curettage for the evacuation of the product of conception DIAGNOSTIC_TEST

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

Patient group

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

15% of couples will experience spontaneous miscarriage during their reproductive life. Women that will go to the ObGyn Emergency Department of our Hospital where spontaneous miscarriage will be confirmed and curettage decided will be eligible for inclusion. No additional criterion applies.

You may qualify if:

• 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.

You may not qualify if:

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

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

Study Sites (2)

Hopital Femme-Mère-Enfant; service gynécologie/obstétrique

Bron, Rhône, 69500, France

Location

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

Bron, Rhône, 69500, France

Location

MeSH Terms

Conditions

Chromosome Aberrations

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 2, 2023
• First Posted: June 12, 2023
• Study Start: July 18, 2023
• Primary Completion: July 19, 2024
• Study Completion: July 19, 2024
• Last Updated: September 20, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

FR (2)