Outcomes of IVF programs with intrauterine administration of autologous mononuclear cells in women with repeated implantation failure

Abstract

Frequency of the repeated implantation failure (RIF) in assisted reproductive technology programs remains to be high, reaching 50-75%. Intrauterine administration of autologous mononuclear cells before embryo transfer is a technique for the RIF immunocorrection being used in assisted reproductive technology programs. Direct effect of mononuclear cells upon implantation was first studied in 2006 and showed that intrauterine administration of autologous mononuclear cells prior to embryo transfer proved to significantly increase implantation frequency, as well as incidence of clinical pregnancy, and frequency of delivery in the patients with a history of RIF. The aim of this study was to evaluate the effect of intrauterine administration of autologous peripheral blood mononuclear cells prior to embryo transfer upon the results of assisted reproductive technology programs in women with a history of RIF, and to evaluate cytokine profile of the supernates from the injected cultures of peripheral blood mononuclear cells.The study included 129 women with RIF included into the assisted reproductive technology programs. The patients were divided into three groups with intrauterine administration before embryo transfer in a stimulated cycle and in a cryocycle: group 1, treated with mononuclear cells activated by human chorionic gonadotropin; group 2, with mononuclear cells without activation by human chorionic gonadotropin; group 3 who received saline solution (placebo). Clinical and anamnestic data of the women from these groups did not differ. The age of women in all three groups was also similar. The number of RIFs in their anamnesis was comparable for the 3 groups. Analysis of the embryological parameters also showed that there were no significant differences in the number of transferred embryos, including those of good quality.The levels of IL-2 (p = 0.006), IL-4 (p = 0.012), IL-5 (p = 0.012), IL-12p70 (p = 0.011), IFNγ (p = 0.012), GM-CSF (p = 0.026), and TNFα (p = 0.021) were found to be higher in the supernatants of human chorionic gonadotropin-activated mononuclear cells of women with advanced cryocycle implantation, than in supernatants of inactivated chorionic gonadotropin mononuclear cells. Frequencies of implantation and clinical pregnancy were significantly higher in the groups with intrauterine administration of autologous mononuclear cells, both in stimulated cycle and the cryocycle compared to the placebo groups.The cytokine profile of the mononuclear cell culture supernates upon intrauterine administration affects the efficiency of assisted reproductive technology programs in the women with RIF. Hence, the data obtained may allow us to develop a personalized approach to usage of various immunotherapies in assisted reproductive technology programs for the patients with a history of repeated implantation failure.