Endometrium Immunomodulation by in Utero Administration of Peripheral Blood Mononuclear Cells

Infertility

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.

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