Intrauterine administration of granulocyte colony-stimulating factor promotes the transformation of endometrium immune phenotype and the onset of pregnancy in patients with recurrent implantation failures

Abstract

Aim of the study: The aim of the study was to determine the effectiveness of intrauterine administration of granulocyte-colony-stimulating factor (G-CSF) depending on immune phenotype of endometrium in patients with recurrent implantation failures in embryo transfer programs. Material and methods: Patients with recurrent implantation failure underwent endometrial biopsy during the implantation window in an artificial cycle before and (in some patients) after intrauterine administration of G- CSF. Pregnancy and live birth rates were determined depending on the immune phenotype of the endometrium in patients with repeated implantation failures after intrauterine administration of G-CSF in an embryo transfer program. Flow cytometry was used to count the classes and subclasses of endometrial lymphocytes in endo- metrial tissue samples. Results: The endometria of patients who became pregnant as a result of embryo transfer after G-CSF irrigation of the uterine cavity showed significantly higher expression of HLA-DR on T cells and Th, and HLA-DR and CD16 on uterine natural killers (uNK). There was a high correlation between not transformed endometrium, that is, increased levels of HLA-DR (>55 %) and CD16 (>50 %) on uNK, with successful implantation after G-CSF irrigation of the uterine cavity (OR=7.700, p = 0.0174). In patients with a not transformed immune endometrial phenotype, the pregnancy (53.8 %) and live birth (46.1 %) rates were twice as high as those in patients with other variants of immune abnormalities or without immune profile changes (pregnancy and live birth rates - 19.2 %). Intrauterine G-CSF caused a significant decrease in the high expression of HLA-DR and CD16 in uNK cells without affecting other immune markers. Conclusions: Elevated expression of HLA-DR and CD16 on uNK was associated with successful implantation after intrauterine use of G-CSF in embryo transfer program.