P-296 Relationship between the percentage of stem cells and implantation success in women with in-vitro fertilization
Authors: Parvanov D , Ganeva R , Ruseva M , Handzhiyska M , Vidolova N , Metodiev D , Stamenov G 
Published: June 2022

Abstract

Study question
Is there a relationship between the percentage of stem cells in human endometrial stroma during the mid-luteal phase of the menstrual cycle and implantation success?

Summary answer
Women with successful implantation have significantly higher percentage of endometrial stromal CD117-positive stem cells during the mid-luteal phase of the menstrual cycle.

What is known already
Human endometrium as a highly regenerative dynamic tissue has a population of certain types of adult stem cells localized in the stroma and epithelium. These cells, including mesenchymal and hematopoietic stromal stem cells, participate in the immense cellular turnover in the human endometrium before and during the implantation process. General adult stem cell markers such as CD117 and NOTCH1 have been identified in human endometrium. However, there is a scarce data about the quantity of these endometrial stromal stem cells and their influence on the process of implantation.

Study design, size, duration
This is a cohort study of 109 women who had an endometrial biopsy during the mid-lutheal phase (LH + 7) in a natural cycle and positive or negative hCG test after in-vitro fertilization (IVF) with euploid embryos within 6 months of biopsy. We used immunohistochemical biomarkers NOTCH1 (E-AB-12815, Elabscience), CD117 (CD117/c-Kit/SCF-Receptor) (RB-9038-RQ, Epredia), to identify stem cells in endometrial stroma. The study was conducted between March 2020 and January 2022.

Participants/materials, setting, methods
The percentages of NOTCH1-positive and CD117-positive stem cells in the stroma were calculated after enumeration by two independent investigators in multiple endometrial sections. After embryo transfer women were divided into the following groups: unsuccessful embryo implantation (negative hCG test) ( n = 45) and successful implantation (positive hCG test) ( n = 64). The percentage of NOTCH1-positive and CD117-positive cells in the endometrial stroma were compared between these groups through Wilcoxon signed-rank test.

Main results and the role of chance
The percentage of CD117-positive stem cells in the endometrial stroma ranged between 0% and 0.21%, with a median of 0.02%. The percentage of NOTCH1-positive stem cells in the endometrial stroma ranged between 0.003% and 2.11%, with a median of 0.06%. There was no significant difference in female age (years), BMI (kg/m2) and blastocyst quality between the studied patient groups (P &lt; 0.05). The quantity of NOTCH1-positive cells also did not differ significantly between the two groups (P = 0.18). However, the mean percentage of CD117-positive stromal cells was significantly higher in women with successful implantation compared to patients with unsuccessful implantation (0.04% vs. 0.02%, respectively, P = 0.004). The optimal successful implantation cut-off value for the percentage of CD117-positive stromal cells, was 0.018% (AUC 0.67, 95% CI 0.56-0.77). Therefore, a percentage of 0.018% of CD117-positive stem cells in the endometrial stroma was associated with 63.1% sensitivity and 61.4% specificity for predicting successful implantation after IVF.

Limitations, reasons for caution
The study cohort was limited in sample size. Not all confounding factors such as potential immunological and genetic reasons for unsuccessful implantation have been taken into account. In addition, the endometrial biopsy could also have an effect on endometrial receptivity and pregnancy outcome.

Wider implications of the findings
The results of this study revealed that the quantity of certain types of stem cells is associated with successful embryo implantation. These findings emphasize the essential impact of stem cells in human endometrium on the process of implantation.

Trial registration number
not applicable