Multicentric Prospective Study of Genetic and Physiopathology Concerning Dysregulation of Complement During Repeated Fetal Abortions

Study Overview
=================
Brief Summary
-----------------
The aim of the study is to assess the role of complement dysregulation and its impact on antiangiogenic factors (soluble Flt1 and endoglin) in patients with foetal losses.

Detailed Description
-----------------
Females with medical history of repeated foetal losses will have blood sampling to perform analyses. If pregnant, blood sampling will be performed at different times throughout the pregnancy. Controls will be females without medical history of repeated foetal losses. They will also have blood sampling to perform analyses. If pregnant, blood sampling will be performed at different times throughout the pregnancy. Blood analyses will focus on : mutations in genes coding for molecules that modulate complement activity serum levels of sFlt1 and endoglin and their link to complement activation

Official Title
-----------------
Multicentric Prospective Study of Genetic and Physiopathology Concerning Dysregulation of Complement During Repeated Fetal Abortions

Conditions
-----------------
Fetal Losses

Intervention / Treatment
-----------------
* Other: blood sample


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Inclusion criteria for females with repeated fetal losses: Age> 18 Female affiliated to French health insurance (Social Security), Informed consent form signed Patient with history of at least three foetal losses without any cause found (chromosomal abnormalities, uterine malformations, endocrine disorders, etc.) Exclusion criteria for females with repeated fetal losses : Patient not fulfilling inclusion criteria Age > 40 Female unable to understand benefits and risks of protocol Female with history of repeated foetal losses of infectious or endocrine origin. Inclusion criteria for females without repeated fetal losses: Age> 18 Female affiliated to the French health insurance (Social Security) Informed consent form signed Female without history of repeated foetal losses Exclusion criteria for females without repeated fetal losses: Patient not fulfilling inclusion criteria Female with age above 40 Female unable to understand benefits and risks of protocol

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| females with medical history of repeated foetal losses<br>The females can be pregnant | Other: blood sample<br>* blood sampling at inclusion and throughout pregnancy when pregnant<br>|
| females without medical history of repeated foetal losses<br>The females can be pregnant | Other: blood sample<br>* blood sampling at inclusion and throughout pregnancy when pregnant<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| mutations in genes coding for molecules that modulate complement activity | to determine frequency of mutations of genes (membrane-cofactor protein (MCP), decay accelerating factor (DAF), ....) involved in complement activation : Profiles of these genes will be analysed in blood sample of females with medical history of repeated foetal losses and compared to those analysed in blood sample of females without medical history of repeated foetal losses. | day1 (at inclusion) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| serum levels of sFlt1 and endoglin and their link to complement activation markers | To assess serum levels of sFlt1 and endoglin and their link to complement activation markers in blood samples removed throughout pregnancy of females with medical history of repeated foetal losses and throughout pregnancy of females without medical history of repeated foetal losses. | 4 weeks post pregnancy start | 
| serum levels of sFlt1 and endoglin and their link to complement activation | To assess serum levels of sFlt1 and endoglin and their link to complement activation markers in blood samples removed throughout pregnancy of females with medical history of repeated foetal losses and throughout pregnancy of females without medical history of repeated foetal losses. | 8 weeks post pregnancy start | 
| serum levels of sFlt1 and endoglin and their link to complement activation | To assess serum levels of sFlt1 and endoglin and their link to complement activation markers in blood samples removed throughout pregnancy of females with medical history of repeated foetal losses and throughout pregnancy of females without medical history of repeated foetal losses. | 16 weeks post pregnancy start | 
| serum levels of sFlt1 and endoglin and their link to complement activation | To assess serum levels of sFlt1 and endoglin and their link to complement activation markers in blood samples removed throughout pregnancy of females with medical history of repeated foetal losses and throughout pregnancy of females without medical history of repeated foetal losses. | 24 weeks post pregnancy start | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Foetal loss, complement, antiangiogenic factors, Repeated fetal losses