Hormonal stimulation for IVF treatment positively affects the CD56bright/CD56dim NK cell ratio of the endometrium during the window of implantation

Abstract
The effects of hormone stimulation for IVF treatment on endometrial receptivity remain controversial. Since CD56bright natural killer (NK) cells in the endometrium positively contribute to implantation and decidualization whereas CD56dim NK cells are negatively associated with reproduction, shifts in the balance between those cells will affect receptivity. Therefore, we compared the leukocyte composition in the endometrium of IVF women with non-pregnant women in a natural cycle, as a parameter for endometrial quality. Biopsies were obtained 7 days after ovulation. Histological dating of the endometrium showed no increased endometrial advancement after IVF treatment as compared to the control group. Flow cytometric analysis of leukocyte subsets showed that hormonal stimulation positively affected the CD56bright/CD56dim ratio in the endometrium by a relative decrease in the cytotoxic CD56dimCD16+ NK cell numbers. The relative number of T-cells remained unaffected, while the number of non-T and non-NK cells (i.e. B-cells and macrophages) was higher in the IVF group. These effects were restricted to the endometrium and not observed in peripheral blood. Within the CD56bright population we could identify a distinct subset of NK cells (CD56superbright) that was unique for the endometrium. We conclude that hormonal stimulation for IVF treatment positively affects the CD56bright/CD56dim ratio of the endometrium during the window of implantation and does not affect endometrial advancement.