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

• ClinicalTrials.gov Identifier: NCT02262117
• Recruitment Status: Recruiting
• First Posted: October 10, 2014
• Last Update Posted: June 13, 2022
• Sponsor: Assistance Publique - Hôpitaux de Paris
• Information provided by (Responsible Party): Assistance Publique - Hôpitaux de Paris

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Reproductive Medicine	Other: standard care; Drug: specific treatment	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 400 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: February 20, 2015
• Estimated Primary Completion Date: August 2024
• Estimated Study Completion Date: August 2024

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. Live birth rate (without congenital abnormality or malformation)/transfer following the first (fresh) embryo transfer after uterine immune analysis [ Time Frame: up to 18 months ]
   Live birth rate/transfer

Secondary Outcome Measures :

1. Ongoing pregnancy rate/transfer following the first embryo transfer at 12 weeks of amenorrhea [ Time Frame: 12 amenorrhea weeks ]
   Ongoing pregnancy rate/transfer following the first embryo transfer
2. Number of physiological pregnancies after personalization [ Time Frame: up to 18 months ]
   Physiological pregnancies are defined by a normal growth of the fetus and a birth at term.
3. Pregnancy rate/transfer following the first embryo transfer [ Time Frame: 8 amenorrhea weeks ]
   Pregnancy rate/transfer following the first embryo transfer
4. Number of embryo implanted/number of embryos replaced) [ Time Frame: at 8, 12 and 40 amenorrhea weeks ]
   Implantation rate
5. Number of early miscarriage in the first trimester [ Time Frame: 12 amenorrhea weeks ]
   Number of early miscarriage in the first trimester
6. Number of late miscarriage [ Time Frame: between 13 and 24 amenorrhea weeks ]
   Number of late miscarriage
7. Term of birth (for babies without congenital anormality or malformation) [ Time Frame: up to 18 months ]
   Term of birth
8. Weight at birth [ Time Frame: up to 18 months ]
   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)
9. 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) [ Time Frame: between 28 and 37 amenorrhea weeks ]
   Number of prematurity (A birth below 37 weeks of amenorrhea)
10. 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) [ Time Frame: up to 18 months ]
    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)
11. Number of pathologic pregnancy included stillbirth and congenital abnormality [ Time Frame: up to 18 months ]
    Number of pathologic pregnancy included stillbirth and congenital abnormality
12. Investigate if immunologic events studying on endometrial level have an impact on blood level or are independent. [ Time Frame: up to 15 months ]
    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).

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Contacts

Contact: Nathalie LEDEE, MD; 06 41 67 46 25; nathalie-ledee@orange.fr

Locations

France

Hôpital Saint-Louis - Laboratoire MatriceLAb Innove; Recruiting

Paris, France, 75010

Contact: Nathalie LEDEE, MD 06 41 67 46 25 nathalie-ledee@orange.fr

Sponsors and Collaborators

Assistance Publique - Hôpitaux de Paris

Investigators

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

More Information

• Responsible Party: Assistance Publique - Hôpitaux de Paris
• ClinicalTrials.gov Identifier: NCT02262117
• Other Study ID Numbers: P130929
• First Posted: October 10, 2014
• Last Update Posted: June 13, 2022
• Last Verified: June 2022

Keywords provided by Assistance Publique - Hôpitaux de Paris:

IVF, immune endometrial profile, treatment personalization