The immune milieu after local endometrial injury in women with recurrent implantation failure

Recurrent implantation failure (RIF) occurs in 10-15% of IVF cycles with evidence from a few randomized control trials (RCTs) that local endometrial injury (LEI) leads to higher live birth rates whose exact mechanism is currently unknown. During the implantation period, modulation in immune milieu occur in tandem with profound morphologic and functional changes in the endometrium. The landscape of immune cells in the endometrium in pre- and post-LEI in RIF is currently unknown. Thirty-seven women with RIF (age 34.6 ± 3.3 years old) underwent LEI by two sequential mid-luteal phase endometrial biopsies prior to embryo transfer. To characterize the immunological landscape alterations in LEI, we performed immunophenotypic assessment with flow cytometry to provide insights into the basal (first biopsy) and altered (second biopsy) biology of dendritic cells (DC), macrophages, natural killer (NK), T and B cells in the RIF population before and after LEI. Clinical pregnancies occurred in seventeen women (46%). Among analysed immune cells, T (34.6%) and NK cells (26.2%) predominate in the mid-luteal endometrium. A consistent increase in lymphocytes and decrease in antigen presenting cells (APCs) were observed between the two biopsies although not statistically significant. Interrogation of the immune milieu in patients who either fell pregnant or not did not show any differences once cases with endometriosis were taken out of the analyses. There were no further difference in any of the other measured immune cell subsets between the first and second endometrial biopsy. We found limited changes in the immune cell compartments after LEI. Further research with higher resolution methods may provide more information on the effects of LEI.