Endometrial immune assessment in patients with a history of previous euploid blastocyst failure

Influx and establishment of key endometrial immune factors in the mid-luteal phase of the menstrual cycle is paramount for successful embryo implantation. Endometrial immune dysregulation is associated with repeated embryo implantation failure and miscarriage. In fertilisation cycles, approximately 30% of embryos diagnosed as chromosomally normal will still fail to produce a viable live birth, yet factors such as the endometrium are rarely clinically explored. In this retrospective analysis, clinical outcomes were compared between patients undergoing their first euploid transfer in a conventional substituted cycle (n=612), patients undergoing a euploid transfer in a similar cycle after previous euploid failure (n=149) and the study group of patients with previous euploid transfer failure who received a modified endometrial preparatory regimen following endometrial immune profiling targeting uterine natural killer cell recruitment, maturity and activity as well as their key regulatory counterparts (n=37). Significant differences were found between first euploid attempt outcomes and patients with previous failures who didn't use endometrial testing (implantation rate 63% vs 51, =0.02; clinical pregnancy rates 55% vs 40%, =0.002; live birth rates 50% vs 38%, =0.02). Patients with previous failures who underwent endometrial immune profiling and a subsequent personalised plan exhibited a trend towards improved clinical outcomes than those with previous failures and no testing (implantation rate 65% vs 51%; clinical pregnancy rate 57% vs 40%; live birth rate 54% vs 38%, respectively) although statistical significance was not demonstrated. Clinical outcomes were comparable between the endometrial immune profiling group and those undergoing a first euploid attempt (implantation rate 65% vs 63%; clinical pregnancy rate 57% vs 55%; live birth rate 54% vs 50%, respectively). Patients who had a failed attempt when using a euploid embryo had lower chances of pregnancy when repeating their treatment, unless they received a personalised endometrial preparation regimen derived from the results of endometrial immune profiling. These preliminary findings indicate the potential value of guiding management based on immune endometrial testing.