HLA-C and KIR interactions as a possible cause of reproductive failures

Abstract

Objective: Despite advancements in assisted reproduction, the cause of up to 50% of cases of idiopathic fertility disorders remains unclear. The immune system, particularly the interaction between human leukocyte antigen-C (HLA-C) molecules on the trophoblast and killer--cell immunoglobulin-like receptors (KIR) on uterine natural killer (NK) cells, plays a crucial role in implantation and placental development. The aim of this analysis was to evaluate our experience with testing KIR/HLA-C compatibility and its potential role in personalizing infertility treatment. Methods: This is an interventional study examining the success of therapy in 23 couples who underwent infertility treatment with donated gametes between 1/2023 and 12/2024, with additional consideration of KIR/HLA-C compatibility between the recipient and the donor. For better homogeneity of the sample, patients in the intervention group were divided into two subgroups. The first subgroup consisted of 14 couples undergoing their first therapy with donated gametes. The second subgroup consisted of 9 couples with a history of repeated unsuccessful embryo transfers from donated gametes. A control group of 320 single embryo transfers with donated gametes from couples treated using standard methods between 1/2023 and 12/2024 was used for comparison. Results: In both intervention subgroups, success rates were comparable. Clinical pregnancy was achieved in 62.5% and 63.6%, resp., which exceeded the average success rate of 55.2% in the control group. Conclusion: The high number of achieved clinical pregnancies in a prognostically unfavorable group, burdened by repeated unsuccessful embryo transfers, appears to be a therapeutic success. It is important to bear in mind the low number of evaluated transfers; however, this result suggests that testing KIR/HLA-C compatibility between the recipient and the donor and taking it into account when selecting a donor may significantly increase the success of therapy in indicated cases.