Controlled ovarian stimulation is affecting endometrial quality

Abstract

It has been demonstrated that uterine receptivity is diminished during controlled ovarian stimulation (COS). Moreover, clinical evidence suggest that endometrial cytotoxic Natural Killer (NK) cell counts or activity were related to reproductive failure. Particularly, IL15 and IFNγ are associated with NK cell activation. The aim of this study was to compare the impact of rFSH or hMG COS protocols on endometrial NK cell counts and cytokine expression on fertile oocyte donors. Analytical, experimental, prospective study. Endometrial biopsy and peripheral blood of 10 fertile women were obtained 5-8 days post-ovulation during three consecutive cycles: 1.stimulated with long GnRH agonist protocol + rFSH, 2. natural cycle (NC) and 3.stimulated with long GnRH agonist protocol + hMG. Steroid hormones were measured in serum by RIA. NK cytotoxic subset (CD9+CD56+CD16+) were determined by flow cytometry. mRNA expression of IL15 and IFNy were determined by RT-qPCR. Statistical analysis were performed by ANOVA or Friedman, and Tukey or Dunn's test for media comparison. Both COS protocols increased the levels of estradiol (E2), progesterone (P4) and the proportion of cytotoxic NK cells (P<0.05) compared with NC. Moreover, we found a positive correlation between the proportion of cytotoxic NK cells and E2 (r = 0.4047, P<0.05) or P4 (r = 0.4323, P<0.05). Only the use of hMG increased local mRNA levels of IL15 and IFNy (P<0.05). Ovarian stimulation has a deleterious effect on fertile endometrium by increasing the proportion of cytotoxic NK cells. This effect seems to be due to the supra-physiological levels of E2 and P4. The use of hMG seems to be related to NK cell activation, since we found higher levels of IFNy in compare to rFSH.