Determinants of Repeated Spontaneous Miscarriages and Unexplained Fetal Deaths

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.

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.

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