Evaluate the Interest of the Pre-conceptional Endometrial Immune Profiling to Increase Birth Rates

Study Overview
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Brief Summary
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A prospective, randomized, controlled, open two-arm study to evaluate the interest of the pre-conceptional endometrial immune profiling to increase birth rates.

Detailed Description
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Birth rates following an embryo transfer with a mean of two embryos transferred stagnate around 23% per transfer (annual report of the Agency of Biomedicine). Some estimates that half of infertile patients treated are partially or totally concerned by problem of inadequate uterine receptivity. The investigators' hypothesis is that a pre-conceptional immune endometrial evaluation may increase significantly birth rates since successful implantation results from both the matching of a competent embryo within a competent endometrium. The identification of endometrial biomarkers documenting the immune uterine environment during the implantation window would be able to improve the efficacy of ART through a personalization of treatment accordingly to the ability of the patients to receive their embryos. All patients with all inclusion criteria and no exclusion criteria will be included. Only patients with a deregulation (immune analysis) will be randomized.

Official Title
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A Prospective, Randomized, Controlled, Two-arm Study to Evaluate the Interest of the Pre-conceptional Endometrial Immune Profiling to Increase Birth Rates Through a Care Personalization in Reproductive Medicine Before IVF

Conditions
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Reproductive Medicine

Intervention / Treatment
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* Other: standard care
* Drug: specific treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Infertile patients will be included at the beginning of their medical care in reproduction once the indication to perform either an IVF with or without ICSI has been established. The indication for IVF will be: tubal infertility, endometriosis, ovarian dysovulation with failure of intra-uterine insemination, idiopathic infertility The indication for ICSI will be: male infertility (oligo-astheno-teratospermia), previous failure of oocytes fertilization in IVF Patients should be younger than 38 years old (Age < 38) with a normal ovarian reserve (AMH>1.5ng/ml, FSH<10 IU/l on day-3, antral follicles count (AFC) over 6 on day-3 of the cycle by ultrasound) The range of the IVF or ICSI attempt should be lower than 3 or equal at 2 (first or second IVF/ICSI). If a live birth occurred in the past by IVF/ICSI, the range of the new attempt is 1. With a signed informed and consent form With medical insurance Exclusion Criteria: Azoospermia or cryptozoospermia (Patient's partner) IVF/ICSI attempt scheduled in another ART unit Contraindication to any experimental treatment (Cortancyl, Intralipids, Human Chorionic Gonadotropin) Maternal serology positive for hepatite C or B

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 38 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: standard care<br>No specific treatment (standard care) | Other: standard care<br>* No specific medical care<br>|
| Experimental: specific treatment<br>As a deregulation has been diagnosed by immune analysis, a personalization of the medical care for this IVF/ICSI attempt will be dispensed Personalization of treatment should follow a step-to step decision tree. | Drug: specific treatment<br>* Regarding the immune endometrial profiling, medical care (personalization of treatment) should follow a step by step decision tree.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Live birth rate (without congenital abnormality or malformation)/transfer following the first (fresh) embryo transfer after uterine immune analysis | Live birth rate/transfer | up to 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ongoing pregnancy rate/transfer following the first embryo transfer at 12 weeks of amenorrhea | Ongoing pregnancy rate/transfer following the first embryo transfer | 12 amenorrhea weeks | 
| Number of physiological pregnancies after personalization | Physiological pregnancies are defined by a normal growth of the fetus and a birth at term. | up to 18 months | 
| Pregnancy rate/transfer following the first embryo transfer | Pregnancy rate/transfer following the first embryo transfer | 8 amenorrhea weeks | 
| Number of embryo implanted/number of embryos replaced) | Implantation rate | at 8, 12 and 40 amenorrhea weeks | 
| Number of early miscarriage in the first trimester | Number of early miscarriage in the first trimester | 12 amenorrhea weeks | 
| Number of late miscarriage | Number of late miscarriage | between 13 and 24 amenorrhea weeks | 
| Term of birth (for babies without congenital anormality or malformation) | Term of birth | up to 18 months | 
| Weight at birth | A weight of birth below the 10 percentile according to the table of reference with distribution of birth weight in function of the term of birth in the overall population define the intrauterine growth retardation (for babies without congenital anormality or malformation) | up to 18 months | 
| Number of prematurity (A birth below 37 weeks of amenorrhea defines the premature birth and before 28 weeks of amenorrhea the severe preterm birth) (for babies without congenital anormality or malformation) | Number of prematurity (A birth below 37 weeks of amenorrhea) | between 28 and 37 amenorrhea weeks | 
| Number of pre-eclampsia (defined as the association of hypertension over 14/9 mm of hg with proteinuria occuring during the pregnancy- this pathology is related to insufiscient invasion during the first trimester) | Number of pre-eclampsia (defined as the association of hypertension over 14/9 mm of hg with proteinuria occuring during the pregnancy- this pathology is related to insufiscient invasion during the first trimester) | up to 18 months | 
| Number of pathologic pregnancy included stillbirth and congenital abnormality | Number of pathologic pregnancy included stillbirth and congenital abnormality | up to 18 months | 
| Investigate if immunologic events studying on endometrial level have an impact on blood level or are independent. | Quantification by flow cytometry of circulating NK cells (CD56 +/CD16 -), T regulatory T cells (FoxP3) with study of the repretory of circulating and uterine NK receptors (NPp46, Nkp30, NKp44). | up to 15 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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IVF, immune endometrial profile, treatment personalization