Cohort of Patients Presenting Unexplained Recurrent Miscarriages and Identification of Early Miscarriage Recidivism Factors (FALCO)

About 1 to 3% of women of childbearing age suffer repeated early spontaneous miscarriages (RCF) defined by at least 3 fetal losses before 14 weeks of gestation. RCFs may be linked to parental chromosomal abnormalities, congenital or acquired uterine abnormalities, hormonal causes (e.g. type 1 and 2 diabetes, ovarian failure), infectious etiology, constitutional or acquired thrombophilia or sickle cell disease.

The presence of antiphospholipid antibodies, antithyroid and anti-transglutaminase antibodies in approximately 10% of cases suggests an autoimmune origin for these fetal losses. The role of other antibodies, in particular non-conventional antiphospholipid antibodies, remains to be established. Indeed half of RCF cases are thought to be due to an immunological dysregulation of the mother leading to a decrease in tolerance to the fetus. Several studies have shown immune abnormalities, such as an imbalance of pro and anti-inflammatory cytokines, an increase in cytotoxic cells and a defect in regulatory cells in the blood of patients. The assessment of these immune abnormalities is not currently performed routinely in France in women presenting with recurrent early miscarriages. When one of these known causes is excluded, it is unexplained RCF which represents 50% of RCF. Over half of these women with RCF may be linked to aneuploidies and primary spontaneous recurrent abortions. Assessing the degree of aneuploidy and the genetic origin of foetal losses remains difficult to date, as examination of the miscarriage product is rarely available, due to the spontaneous nature of the loss.

An implantation failure (IF) is defined as the absence of pregnancy following the transfer of a good-quality embryo into the uterine cavity. These implantation failures can be due to embryonic factors, maternal factors, or caused by inappropriate stimulation and/or difficult transfers. In the literature, recurrent implantation failure (RIF) is defined as the absence of pregnancy after 3 attempts of transferring good-quality embryos, taking maternal age into account Setting up a prospective cohort of patients with RFC is an essential step in exploring the aetiological factors of RCF and in order to enable better treatment.

Study Overview

• Status: Recruiting
• Conditions: Miscarriage; Early Pregnancy Loss
• Intervention / Treatment: Biological: Lymphocyte immunophenotyping

Detailed Description

The study population will be followed as part of routine care, in the same way as all patients presenting with RPL, in internal medicine or obstetrics-gynecology.

On the day of inclusion, the patient's medical history will be reviewed (demographic data, lifestyle factors, medical and obstetric-gynecologic history, biological tests performed).

Data for each of the patient's pregnancies will also be collected (date of pregnancy onset, type of pregnancy, pregnancy outcome, treatments taken during pregnancy, maternal/fetal complications during pregnancy).

• Study Type: Observational
• Enrollment (Estimated): 700

Contacts and Locations

• Study Contact: Name: Arsene MEKINIAN, MD, PhD; Phone Number: +33 1 71 97 07 65; Email: arsene.mekinian@aphp.fr

Study Locations

• France
  • Paris, France, 75012
    • Recruiting
    • Internal medicine department, hospital Saint Antoine
    • Contact: Arsene MEKINIAN; Email: arsene.mekinian@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 46 years (Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with recurrent early pregnancy losses (at least 3 fetal losses before 14 weeks of amenorrhea) and/or recurrent implantation failures (at least 3 failures).

Description

Inclusion Criteria:

• Age 18 to 50 years
• Patients who have had 3 (or more) early pregnancy losses occurring before 14 weeks of amenorrhea and/or at least 3 implantation failures.
• Patients who have been informed and have not objected to participating in the study.
• Patients covered by a social security system.

Exclusion Criteria:

• patients who do not agree the use of their data
• Patients on AME
• Patients under legal protection

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Miscarriage; Patients with recurrent early pregnancy losses (at least 3 fetal losses before 14 weeks of amenorrhea) and/or recurrent implantation failures (at least 3 failures).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To build a cohort of patients in order to describe clinical characteristics, tests carried out and medical care of patients presenting spontaneous recurrent miscarriages	Description of the clinical and biological characteristics of patients with recurrent early pregnancy losses and/or recurrent implantation failures	through study completion, an average of 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To compare the efficacy of immunomodulatory drugs (corticosteroids, hydroxycholoroquin, Intravenous Immunoglobulin Therapy, intralipids, biotherapies)	Description of the efficacy of the various drugs : number of full term pregnancies	through study completion, an average of 5 years
To evaluate the psychological state of patients and the impact on pregnancy	Evaluation of the patients' lifestyle using the Baecke questionnaire and medical interrogation.	through study completion, an average of 5 years
to evaluate patients' lifestyle and the impact on pregnancy	through study completion, an average of 5 years	evaluation of the patients' lifestyle using the Baecke questionnaire and medical interrogation.
To describe the recurrence rate of repeated early pregnancy loss	Proportion of recurrence of early pregnancy loss (EPL) over the entire duration of the study: according to the number of previous early pregnancy losses; according to abnormalities found in the etiological work-up; according to age at onset, associated infertility, type of pregnancy loss with or without live children, and according to the different treatments used	Through study completion, an average of 5 years
To describe the recurrence rate of repeated implantation failure	Proportion of recurrence of RIF over the entire duration of the study: according to the number of previous implantation failures, according to abnormalities found in the etiological work-up, according to age at onset, associated infertility, and according to the different treatments used	Through study completion, an average of 5 years

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Arsene MEKINIAN, MD, PhD, Assistance Publique - Hopitaux de Paris

Publications and helpful links

General Publications

• Dernoncourt A, Hedhli K, Abisror N, Cheloufi M, Cohen J, Kolanska K, McAvoy C, Selleret L, Ballot E, Mathieu d'Argent E, Chabbert Buffet N, Fain O, Kayem G, Mekinian A. Hydroxychloroquine in recurrent pregnancy loss: data from a French prospective multicenter registry. Hum Reprod. 2024 Sep 1;39(9):1934-1941. doi: 10.1093/humrep/deae146.

Study record dates

Study Major Dates

• Study Start (Actual): October 24, 2022
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): October 1, 2029

Study Registration Dates

• First Submitted: September 8, 2022
• First Submitted That Met QC Criteria: September 26, 2022
• First Posted (Actual): September 27, 2022

Study Record Updates

• Last Update Posted (Estimated): December 19, 2025
• Last Update Submitted That Met QC Criteria: December 12, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Miscarriage; repeated implantation failure; Prognostic factors; Biological collection; recurrent early pregnancy losses
• Additional Relevant MeSH Terms: Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Pregnancy Complications; Abortion, Spontaneous
• Other Study ID Numbers: APHP220747; IDRCB 2022-A00273-40 (Other Identifier: ANSM)

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