Parental human leukocyte antigen-C allotypes are predictive of live birth rate and risk of poor placentation in assisted reproductive treatment

Objective To study the pregnancy, miscarriages, and live birth rates (LBRs) according to maternal killer cell immunoglobulin-like receptor (KIR) genes expressed by uterine natural killer cells and paternal or oocyte donor human leukocyte antigen-C (HLA-C) genes expressed by trophoblast cells in patients with recurrent reproductive failure. Design Prospective observational cohort study. Setting Private infertility center. Patient(s) Participants included 204 women with recurrent miscarriage or recurrent implantation failure. Intervention(s) The KIR and HLA-C genotypes of all women and HLA-C of their partners, gamete donors, miscarriage tissue, and babies were analyzed. Main Outcome Measure(s) All clinical variables (pregnancy, miscarriage, and LBRs) were analyzed and categorized based on KIR, oocyte origin, and single embryo transfer (SET)/double embryo transfer (DET). Result(s) A higher miscarriage rate was observed after DETs in KIR AA mothers (47.8% egg donation and 37.5% in vitro fertilization [IVF]) compared with KIR AB (10.5% egg donation and 12.5% IVF) or KIR BB (6.7% egg donation and 0% IVF). A significantly decreased LBR was observed after DETs with oocyte donation in KIR AA patients (4.3%) compared with KIR AB (26.3%) or BB (46.7%). The LBR decreased significantly as the fetal HLA-C2 load increased in KIR AA women. Conclusion(s) Elective SET improves the reproductive outcomes compared with DET. An increased embryo HLA-C2 load has a negative impact on the LBR in KIR AA patients. The selection of HLA-C1 over HLA-C2 donors could have a positive impact on the LBR in KIR AA patients. Clinical Trial Registration Number NCT04052438.