Immunomodulatory effect of granulocyte colony-stimulating factor in repeated implantation failures in embryo transfer programs

Abstract

The objective: to determine the effectiveness of intrauterine administration of granulocyte colony-stimulating factor depending on endometrium immune phenotype in patients with repeated implantation failures in embryo transfer programs.Material and methods. Endometrial biopsy during the implantation window in an artificial cycle before and (in some patients) after intrauterine administration of granulocyte colony-stimulating factor (G-CSF) was performed in 42 patients with repeated implantation failures and gestational carriers (20 women) as a control group. Flow cytometry was used to count classes and subclasses of endometrial lymphocytes in endometrial tissue samples.Results. The population of endometrial immune cells in patients with repeated implantation failures and fertile women was compared. Pregnancy and live birth rates depending on endometrium immune phenotype in patients with repeated implantation failures after intrauterine administration of granulocyte colony-stimulating factor in embryo transfer program were determined and the effect of intrauterine administration of granulocyte colony-stimulating factor on endometrial immune phenotype was evaluated.High expression of HLA-DR and CD16 on uterine natural killers is reliably associated with successful implantation after intrauterine administration of granulocyte colony-stimulating factor in an embryo transfer program. It was established that in the group with an immature immune endometrial phenotype the frequency of pregnancy (53.8 %) and the frequency of live births (53.8 %) were twice higher compared to the rest of the patients with other variants or the absence of changes in the immune profile (pregnancy rate and frequency live birth rate – 26.9 %).Conclusions. One-third of patients with repeated implantation failures in genetically tested embryos transfer programs have a unique immune status of endometrium characterized by high expression of HLA-DR and CD16 on uterine natural killers. Intrauterine administration of granulocyte colony-stimulating factor leads to decrease of HLA-DR and CD16 expression on uterine natural killers and promotes successful implantation in embryo transfer program in this group of patients.