Clinical trial NCT05900076: Technical Feasibility of the cfDNA Test for Non-invasive Cytogenetic Analysis of Early Miscarriages Versus the Gold Standard Microarray
Official title: Technical Feasibility of the Cell-free DNA Test for Non-invasive Cytogenetic Analysis of Early Miscarriages Versus the Gold Standard Microarray
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Spontaneous Miscarriage
Keywords: Cell-free DNA
spontaneous miscarriage
chromosomal abnormalities
cytogenetic analysis
Lead sponsor: Hospices Civils de Lyon
Sponsor class: OTHER
First posted: 2023-06-12
Enrollment: 78
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.


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

Primary outcomes:
measure: Failure rate of cfDNA compared to CMA
timeFrame: The outcome measure (failure rates of both techniques) will be assessed through study completion ; estimated 6 months after last inclusion.
Secondary outcomes:
Other outcomes:
Locations:
city: Bron
country: France
facility: Hopital Femme-Mère-Enfant; service gynécologie/obstétrique
state: Rhône
city: Bron
country: France
facility: Hopital Femme-Mère-Enfant; service médecine de la reproduction
state: Rhône
Study officials:
References: