Endometrium Immunomodulation by in Utero Administration of Peripheral Blood Mononuclear Cells

NCT04648566 | Completed

• 1 other identifier: Immunomodulation
• Study Type: interventional
• Target: 423
• Locations: 1 country
• Sites: 1

Brief Summary

One of the most limiting factors in the field of assisted reproduction is implantation failure. A new approach to increase the chances of success involves the use of cells from the patient's blood, peripheral blood mononuclear cells (PBMC), which once isolated can be cultured for a few days and then inseminated back into the uterine cavity prior to embryo implantation. It has been shown that the immune system plays a major role in the process of embryo implantation. To date, at least three international clinical trials appear to confirm the usefulness of intrauterine administration of PBMC in the setting of repeated implantation failure (RIF) in in vitro fertilization (IVF) (RIF: absence of active pregnancy after ≥ 3 embryo transfers). The clinical pregnancy rate would be doubled or even tripled. This treatment has never been studied in a randomized double-blind clinical trial, in the context of fertilization without RIF or in a classic treatment such as intrauterine insemination (IUI) with the partner sperm. Our hypothesis is that the creation of an endometrial inflammatory reaction by the administration of PBMC in the uterine cavity allows a better receptivity and consequently a better implantation following an embryo transfer as part of an IVF treatment. The objective is to evaluate whether intrauterine administration of PBMC improves embryo implantation following assisted reproduction treatment. The investigators plan to recruit 148 women undergoing IVF and 220 patients undergoing UII with partner sperm to test our hypothesis. The investigators also plan to recruit all RIF patients accepting to participate in the clinical trial. The study will be prospective, randomized and double-blind. The treated group will receive an intrauterine administration of PBMC while the control group will be administered with sperm washing medium only. PBMC will be obtained from a blood sample (maximum 10 ml) a few days before embryo transfer in IVF cases or on the day of sperm insemination in IUI cases. PBMC will then be isolated in the laboratory on a Ficoll gradient in order to eliminate platelets, polynuclear cells and red blood cells. PBMCs will then be stimulated with phytohemagglutinin (PHA) and human chorionic gonadotropin hormone (hCG) for 48 hours. Lymphocyte phenotyping will be assessed before and after cell activation. In addition, the cytokine profile will be established from the supernatant of the stimulated cells. These data will make it possible to establish a link between the pro-versus anti-inflammatory cytokine profile and implantation success versus failure for each patient. Two days after cell seeding, PBMC will be administered into the uterine cavity of the patient. Embryo transfer will be performed in the same way as the standard treatment on day 3 or 5 according to the criteria established by the IVF laboratory and in agreement with the doctor.

Conditions

Infertility

Outcome Measures

Primary Outcomes (2)

• Biochemical pregnancy rate

  Two weeks following embryo transfer or 3 weeks following intrauterine insemination

• Clinical pregnancy rate

  Six to 8 weeks of gestation

Secondary Outcomes (3)

• Peripheral blood mononuclear cells populations distribution at Day 0

  The day of the patient's ovulation

• Peripheral blood mononuclear cells populations distribution at Day 2

  After 48 hours of culture

• Cytokines expression levels

  After 48 hours of culture

Study Arms (5)

IIU control group

PLACEBO COMPARATOR

Procedure: Intrauterine administration of sperm washing medium

IIU PBMC group

ACTIVE COMPARATOR

Procedure: Intrauterine administration of hCG-activated peripheral blood mononuclear cells

FIV control group

PLACEBO COMPARATOR

Procedure: Intrauterine administration of sperm washing medium

FIV PBMC group

ACTIVE COMPARATOR

Procedure: Intrauterine administration of hCG-activated peripheral blood mononuclear cells

RIF group

ACTIVE COMPARATOR

Procedure: Intrauterine administration of hCG-activated peripheral blood mononuclear cells

Interventions

Intrauterine administration of hCG-activated peripheral blood mononuclear cells PROCEDURE

Administration of hCG-activated peripheral blood mononuclear cells in the uterine cavity of the patient

FIV PBMC group; IIU PBMC group; RIF group

Intrauterine administration of sperm washing medium PROCEDURE

Administration of sperm washing medium instead of PBMC in the uterine cavity of the patient

FIV control group; IIU control group

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All infertile patients undergoing in vitro fertilization (IVF) or intrauterine insemination (IUI) with partner's sperm at Fertilys, agreeing to participate in the study and having signed the study participation consent form.
• Study participants must be over 18 years old.
• For the recurrent implantation failure (RIF) group only: Patients described as having RIF, i.e. having had ≥ 3 good quality embryo transfers.

You may not qualify if:

• For the randomized IUI and IVF groups only: Patients described as having RIF, i.e. having had ≥ 3 embryo transfers or having had a transfer of more than 3 embryos of good quality.
• Patients requiring a donation of gametes (eggs or spermatozoa).
• Couples in which one or the other has a chromosomal abnormality.
• Patients who are starting an IUI cycle under ovulation testing.

Sponsors & Collaborators

• Fertilys: lead
• Institut National de la Recherche Scientifique - Centre Armand Frappier Santé Biotechnologie: collaborator

Study Sites (1)

Fertilys inc.

Laval, Quebec, H7S1Z5, Canada

Location

MeSH Terms

Conditions

Infertility

Condition Hierarchy (Ancestors)

Genital Diseases; Urogenital Diseases

Study Officials

• Pierre Miron, MD, PhD

  Fertilys inc

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 18, 2020
• First Posted: December 1, 2020
• Study Start: March 22, 2017
• Primary Completion: February 1, 2020
• Study Completion: February 1, 2020
• Last Updated: December 1, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)