Predictive Value of Th1, Th2 and Th17 Cytokines on the Success of Embryo Implantation (ImmuNoFertilité)

Study Overview
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Brief Summary
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Infertility affects approximately 10-15% of the population. The number of assisted reproduction procedures has increased by a factor of 3 to 5.3 worldwide over the last 20 years. Despite recent techniques, pregnancy rates seem to be limited to 35% by embryo transfer. Embryo implantation depends on two factors: the quality of the embryo and the endometrial receptivity. Although good quality embryos are transferred, implantation may not occur. Changes in the maternal cytokine profile at the time of implantation may result in poor implantation or early abortions. Consequently, a misdirection of the immunological profile could be responsible for repeated implantation failure (RIF). The definition of RIF is not consensual, but most commonly refers to 3 failures after good quality embryo transfer, and would affect between 5 and 10% of patients. The possibility of defining a predictive immune profile for RIF from a peripheral blood sample is debated. However, after stimulation of immune cells in peripheral blood, patients with RIF show an excessive pro-inflammatory profile. Our objective is to assess the activation of T cells and innate immune cells (via an anti-CD3 agonist and a TLR7-8 ligand, respectively) from a blood sample to predict implantation success after frozen embryo transfer. This functional test is easy to use and applicable in a clinical routine.

Official Title
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To Study the Predictive Value of Th1, Th2 and Th17 Cytokine Serum Levels Produced After Non-specific Stimulation on the Success of Embryo Implantation

Conditions
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Assisted Reproduction

Intervention / Treatment
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* Biological: Unique blod sample


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult women (aged 18 and above) treated in the Medically Assisted Procreation (MAP) center of the University Hospital of Nice, in the process of a frozen embryo transfer Social security affiliation Signed consent Exclusion Criteria: Contra-indication to frozen embryo transfer Ongoing infection Patients under guardianship

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Women treated in the Medically Assisted Procreation (MAP) center of Nice<br> | Biological: Unique blod sample<br>* sampling of 4mL of blood on lithium heparin tube, the day of frozen embryo implantation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ex vivo comparison of the immune profile between patients with Repeated Implantation Failure and patients with successful implantation. | The immune profiles are defined as the concentrations (in IU/mL or pg/mL) and ratios of proinflammatory and anti-inflammatory cytokines measured after nonspecific stimulation of peripheral blood cells from each patient: IFNγ, IL6, IL1β, TNFα, IL4, IL10, TGFβ, IFNγ/IL4, IFNγ/IL10, IFNγ/TGFβ, IL6/IL4, IL6/IL10, IL6/TGFβ, IL1β/IL4, IL1β/IL10, IL1β/TGFβ, TNFα/IL4, TNFα/IL10, TNFα/TGFβ. | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ex vivo comparison of the immune profile between patients with one implantation failure and patients with successful implantation. | The immune profiles are defined as the concentrations (in IU/mL or pg/mL) and ratios of proinflammatory and anti-inflammatory cytokines measured after nonspecific stimulation of peripheral blood cells from each patient: IFNγ, IL6, IL1β, TNFα, IL4, IL10, TGFβ, IFNγ/IL4, IFNγ/IL10, IFNγ/TGFβ, IL6/IL4, IL6/IL10, IL6/TGFβ, IL1β/IL4, IL1β/IL10, IL1β/TGFβ, TNFα/IL4, TNFα/IL10, TNFα/TGFβ. | 24 months | 
| Ex vivo comparison of the immune profile between patients with one implantation failure in the context of inflammatory disorder (such as endometriosis) and patients with successful implantation. | The immune profiles are defined as the concentrations (in IU/mL or pg/mL) and ratios of proinflammatory and anti-inflammatory cytokines measured after nonspecific stimulation of peripheral blood cells from each patient: IFNγ, IL6, IL1β, TNFα, IL4, IL10, TGFβ, IFNγ/IL4, IFNγ/IL10, IFNγ/TGFβ, IL6/IL4, IL6/IL10, IL6/TGFβ, IL1β/IL4, IL1β/IL10, IL1β/TGFβ, TNFα/IL4, TNFα/IL10, TNFα/TGFβ. | 24 months | 
| Ex vivo comparison of the immune profile between patients with a pregnancy failure and patients with an active pregnancy at the end of the first trimester. | The immune profiles are defined as the concentrations (in IU/mL or pg/mL) and ratios of proinflammatory and anti-inflammatory cytokines measured after nonspecific stimulation of peripheral blood cells from each patient: IFNγ, IL6, IL1β, TNFα, IL4, IL10, TGFβ, IFNγ/IL4, IFNγ/IL10, IFNγ/TGFβ, IL6/IL4, IL6/IL10, IL6/TGFβ, IL1β/IL4, IL1β/IL10, IL1β/TGFβ, TNFα/IL4, TNFα/IL10, TNFα/TGFβ. Pregnancy test: βhCG concentration on blood sample in IU/L. Result of the ultrasound performed routinely during the first trimester (between 4 and 11 amenorrhea weeks): presence or absence of intrauterine pregnancy , progressive or not. | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Repeated Implantation Failure (RIF), Embryo implantation, T cells activation