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

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

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

Study Overview

• Status: Active, not recruiting
• Conditions: Reproductive Medicine
• Intervention / Treatment: Other: standard care; Drug: specific treatment

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 400
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Paris, France, 75010
    • Hôpital Saint-Louis - Laboratoire MatriceLAb Innove

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 38 years (Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: standard care; No specific treatment (standard care)	Other: standard care; No specific medical care
Experimental: specific treatment; 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; Regarding the immune endometrial profiling, medical care (personalization of treatment) should follow a step by step decision tree.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Nathalie LEDEE, MD, Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Actual): October 30, 2015
• Primary Completion (Estimated): August 1, 2024
• Study Completion (Estimated): August 1, 2024

Study Registration Dates

• First Submitted: October 7, 2014
• First Submitted That Met QC Criteria: October 9, 2014
• First Posted (Estimated): October 10, 2014

Study Record Updates

• Last Update Posted (Actual): May 7, 2024
• Last Update Submitted That Met QC Criteria: May 6, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: IVF, immune endometrial profile, treatment personalization
• Other Study ID Numbers: P130929