NOTCH1- and CD117-positive stem cells in human endometrium and their implications for successful implantation

Abstract

Objective: To investigate the quantity of 2 stem cell types in the endometrial stroma of women undergoing in vitro fertilization and their association with steroid hormone signaling and implantation success after embryo transfer.

Design: Prospective cohort study.

Setting: Private hospital.

Patient(s): A total of 109 patients undergoing in vitro fertilization.

Intervention(s): Not applicable.

Main outcome measure(s): Immunohistochemistry staining of endometrial biopsies taken during the midluteal phase using antibodies against NOTCH1 and CD117 was performed. The percentage of endometrial stromal cells positive for these markers was determined. The link of these stem cell percentages with the serum progesterone and estradiol levels and the endometrial expression of their respective receptors were assessed. After embryo transfer, the quantity of stained cells for each marker was also compared according to implantation outcome.

Result(s): The percentage of NOTCH1+ stromal cells ranged from 0.003%-2.112% (median, 0.062%) and was significantly higher than that of CD117+ cells, which ranged from 0.000%-0.210% (median, 0.020%) (Z = -7.035). The percentage of NOTCH1+ stem cells showed no difference between the studied serum hormone level groups and no relationship with the expression of their receptors in the endometrium. In contrast, the number of CD117+ cells significantly differed between patients with high and low levels of serum progesterone (cutoff, 14.9 ng/mL) and estradiol (cutoff, 135.6 pg/mL). Furthermore, the quantity of CD117+ stem cells was positively correlated with the progesterone receptor (R = 0.277) and estradiol receptor (R= 0.318) expression levels in the endometrium. Although the quantity of NOTCH1+ cells did not differ between the 2 implantation groups, the median percentage of CD117+ cells was significantly higher in patients with successful implantation than in those with unsuccessful implantation (0.03% vs. 0.01%, respectively). The cutoff value for the percentage of CD117+ cells predicting successful implantation was 0.018% (area under the curve, 0.66; 95% confidence interval, 0.56-0.77; sensitivity, 63.1%; specificity, 61.4%).

Conclusion(s): This study indicates that the quantity of certain stem cell types (CD117+), but not others (NOTCH1+), in the functional endometrium is associated with implantation success and sex hormone signaling during the midluteal phase. These findings highlight the role of CD117+ cells in preparing the endometrium for embryo implantation, and their quantity may be an indirect indicator of endometrial receptivity.

Keywords: Endometrium; implantation success; infertility; sex hormones; stem cells.