O-224 Novel bio-markers of Immunological response to the implanting embryo

Abstract

Abstract Embryos, as allograft, will fail to implant unless they can escape rejection by maternal immune response. It is postulated that embryos escape Immune surveillance using a mechanism similar to that of cancer cells via Immune check point pathways: (a) via producing a surface protein called PD-L1, which binds to PD-1 receptor in T-cells; and (b) via producing a surface protein called Galectin-9 which binds to T-cell immunoglobulin and mucin domain 3 (TIM-3). The binding of these ligands to the corresponding receptors in the T-cells would prevent the latter from recognizing them as foreign, hence escape destruction. In a prospective, longitudinal, observational cohort study involving subjects undergoing blastocyst transfer, it was found that among women who conceived, there was an instant, transient and significant reduction of Tim-3 expression on the surface of peripheral NK cells, T cells and NK-like T cells on days 3 and 6 after ET, which returned to baseline level by day 9 after ET. The change in women who did not conceive appeared in an opposite direction. Furthermore, reduction in Tim-3 expression in pNK cells predates the occurrence of miscarriage by 3 weeks in women with miscarriage when compared with those with live birth. These observations are accompanied by significant changes in peripheral blood cytokine profiles which may be used as clinically useful biomarkers to monitor the maternal immunological response to successful implantation.