Abstract

ABSTRACT Research question What is the underlying mechanism of pregnancy failure in patients with elevated peripheral blood NK cell (pNK) counts? Design 486 patients undergoing IVF-ET (in vitro fertilization-embryo transfer) cycles for tubal obstruction or pelvic adhesion were assigned to three groups: high pNK (> 30% CD56 + CD16 + pNK [n = 49]), medium pNK (15-30% [n = 211]), and normal pNK (5-15% [n = 226]), and their general condition, previous pregnancy history, and IVF outcomes were compared. Uterine fluid and endometrial tissue from patients in the high and normal pNK groups were collected during the mid-secretory phase and studied to elucidate the molecular mechanism underlying impaired endometrial receptivity. Results Significantly higher incidences of three or more previous miscarriages, more IVF-ET cycles, and adverse IVF outcomes were observed in patients with pNK >30% than in those in the other two groups. Lower Septin11 (SEPT11) expression in the uterine fluid and endometrial epithelial cells (EECs), as well as higher endometrial IFN-γ was observed in patients with high pNK than in those with normal pNK. Ishikawa cell and HEEC adhesion was inhibited after SEPT11 knock-down. Further, elevated IFN-γ decreased the SEPT11 protein levels in Ishikawa cells and HEECs. Conclusions CD56 + CD16 + pNK >30% may be a threshold for adverse pregnancy outcomes. Low SEPT11 expression in EECs inhibits cell adhesion, which may be an important cause of impaired endometrial receptivity in patients with elevated pNK. SEPT11 level in mid-secretory uterine fluid could be used as a non-invasive marker to assess endometrial receptivity in these patients.