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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Assisted Reproduction
• Intervention / Treatment: Biological: Unique blod sample

• Study Type: Interventional
• Enrollment (Estimated): 255
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Barbara SEITZ-POLSKI, MD, PhD; Phone Number: +33492035990; Email: seitz-polski.b@chu-nice.fr
• Study Contact Backup: Name: Pierre-Alexis GAUCI, MD; Phone Number: +33492036092; Email: gauci.pa@chu-nice.fr

Study Locations

• France
  • Nice, France, 06200
    • Recruiting
    • CHU de Nice
    • Contact: Céline FERNANDEZ; Phone Number: +33492038828; Email: fernandez.c3@chu-nice.fr
    • Contact: Pierre-Alexis DE NICE, MD; Phone Number: +33492036092; Email: gauci.pa@chu-nice.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Nice

Study record dates

Study Major Dates

• Study Start (Actual): May 4, 2023
• Primary Completion (Estimated): February 1, 2025
• Study Completion (Estimated): February 1, 2025

Study Registration Dates

• First Submitted: February 10, 2023
• First Submitted That Met QC Criteria: March 13, 2023
• First Posted (Actual): March 24, 2023

Study Record Updates

• Last Update Posted (Estimated): July 24, 2023
• Last Update Submitted That Met QC Criteria: July 21, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Embryo implantation; Repeated Implantation Failure (RIF); T cells activation
• Other Study ID Numbers: 22-PP-17

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Sharing data is not planned

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No