Analysis of endometrial mRNA in patients with different pregnancy outcomes after immunotherapy: A cohort study

Purpose: The efficacy of immunomodulators in improving pregnancy outcomes in infertile patients is controversial, with some reports finding improvements in pregnancy outcomes and some studies finding lack of efficacy in unselected patient populations. Therefore, the aim of this study was to identify people who could benefit from immunotherapy. Methods: 29 patients who had at least one previous embryo transfer failure and planned to undergo another frozen-thawed embryo transfer (FET) cycle were included. Peripheral blood of the patients was collected for detection of serum cytokines, T cell subsets at D3-D9 days of menstrual cycle before FET, mRNA was extracted from endometrial tissues during the window of implantation (WOI) for analysis. All patients began treatment with immunomodulators, including prednisone, hydroxychloroquine, cyclosporine, on the first day of the FET cycle. They were divided into pregnant group and non-pregnant group according to clinical pregnancy. Results: There were no differences in cytokines and T cell subsets between the two groups. Functional annotation of endometrial mRNA revealed functional enrichment in leucocyte mediated immunity, innate immune response, regulation of T cell receptor (TCR) signaling, T cell activation and positive T cell selection. Conclusion: The cytokines and immune cell subsets of peripheral blood cannot accurately predict the outcome of pregnancy after immunotherapy, and endometrial biopsy on the WOI may be a target to identify people who benefit from immunotherapy.