Determinants of Repeated Spontaneous Miscarriages and Unexplained Fetal Deaths (DEFI-2)

Determinants of Repeated Spontaneous Miscarriages and Unexplained Fetal Deaths (DEFI-2)

The DEFI-1 study recruited 625 women witnesses and 299 of their spouses. With regard to case couples, 271 cases were recruited from the spontaneous repeated miscarriages (SRM) subgroup (≥3 spontaneous miscarriage (SM) from trimester 1 of pregnancy) and 93 from the unexplained fetal death in utero (FDIU) subgroup from trimesters 2 and 3 of pregnancy.

The main objective of the DEFI 2 study is to increase the number of case-pairs in these 2 particular subgroups to replicate the results of the genetic determinants highlighted from cases and controls with extreme phenotypes and obtain a sufficient number of women with FDIUs to identify specific determinants.

Study Overview

• Status: Not yet recruiting
• Conditions: Repeated Spontaneous Miscarriages; Fetal Deaths in Utero
• Intervention / Treatment: Biological: biological sample

Detailed Description

The spontaneous repeated miscarriages (SRM) affect one to two fertile couples on 100, a fetal death in utero (FDIU) complicates the evolution of a pregnancy on 200. The SRM remain unexplained in 50% of the cases although a beam indirect arguments sometimes encourage to evoke a prothrombotic process and / or endothelial dysfunction, immunological disorders, an alteration of the ovarian reserve, and possibly the impact of genetic determinants. Regarding SRM, in the absence of a fetal, funicular cause or obvious preeclampsia, very diverse mechanisms are evoked depending on the placental histology (vasculoplacental, inflammatory, intervillitis, immunological, etc.). Thus, while these mechanisms remain for some to be demonstrated and are probably not unequivocal, clinicians are faced with a pressing request for therapeutic intervention on the part of patients. This is why, after having studied in DEFI-1 the 2 main constitutional thrombophilia in the 2 members of the couple, the procoagulant circulating microparticles and the generation of thrombin in the mother on the one hand, the modalities of inactivation of an X in the mother, on the other hand, a further investigation in subgroups of particular cases would be appropriate.

• Study Type: Interventional
• Enrollment (Anticipated): 200
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Elisabeth Pasquier, MD; Phone Number: +33 0298145013; Email: elisabeth.pasquier@chu-brest.fr

Study Locations

• France
  • Brest, France, 29200
    • CHRU Brest
    • Contact: Elisabeth Pasquier, MD; Phone Number: +33 0298145013; Email: elisabeth.pasquier@chu-brest.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• couples whose wife is over 18 and under 40 inclusive,
• couples having undergone at least 3 unexplained SM in the first trimester or an FDIU in the trimesters 2 and 3 of pregnancy (excluding funicular and fetal causes and proven preeclampsia)
• the man must be over 18 years old.
• each member of the couple must consent to the investigation.
• Subjects benefiting from a social security scheme.

Exclusion Criteria:

• couples where the woman is under 18 or over 40,
• couples whose man is under 18,
• identified cause of SRM or FDIU
• Inability to consent for one of the members of the couple,
• refusal to participate for one of the members of the couple.
• treatment with anticoagulants or anti-aggregating platelet for women.
• Person under legal protection
• Subjects not benefiting from a social security scheme
• Refusal to participate

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cases	Biological: biological sample; biological samples will be taken from the subjects included

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency difference of the determinant between the cases and the controls	The frequency difference of the determinant under study between the cases (studies DEFI-1 and DEFI-2) and the controls (study DEFI-1) will be measured.	34 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of a new medical event	Occurrence of a new medical event in prospective follow-up will be evaluated	34 years

Collaborators and Investigators

• Sponsor: University Hospital, Brest
• Investigators: Study Director: Elisabeth Pasquier, MD, Brest University Hospital in France

Study record dates

Study Major Dates

• Study Start (Anticipated): January 1, 2020
• Primary Completion (Anticipated): January 1, 2054
• Study Completion (Anticipated): January 1, 2054

Study Registration Dates

• First Submitted: December 19, 2019
• First Submitted That Met QC Criteria: December 19, 2019
• First Posted (Actual): December 23, 2019

Study Record Updates

• Last Update Posted (Actual): December 23, 2019
• Last Update Submitted That Met QC Criteria: December 19, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Pregnancy Complications; Death; Abortion, Spontaneous; Fetal Death
• Other Study ID Numbers: DEFI-2 (29BRC19.0241)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All collected data that underlie results in a publication
• IPD Sharing Time Frame: Data will be available after the publication of result and ending fifteen years following the last visit of the last patient
• IPD Sharing Access Criteria: Data access requests will be reviewed by the internal committee of Brest UH. Requestors will be required to sign and complete a data access agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No