Development of a Predictive Model for Optimization of Embryo Transfer Timing Using Blood-Based microRNA Expression Profile

Int J Mol Sci. 2023 Dec 20;25(1):76. doi: 10.3390/ijms25010076.

Abstract

MicroRNAs (miRNAs) can regulate the expression of genes involved in the establishment of the window of implantation (WOI) in the endometrium. Recent studies indicated that cell-free miRNAs in uterine fluid and blood samples could act as alternative and non-invasive sample types for endometrial receptivity analysis. In this study, we attempt to systematically evaluate whether the expression levels of cell-free microRNAs in blood samples could be used as non-invasive biomarkers for assessing endometrial receptivity status. We profiled the miRNA expression levels of 111 blood samples using next-generation sequencing to establish a predictive model for the assessment of endometrial receptivity status. This model was validated with an independent dataset (n = 73). The overall accuracy is 95.9%. Specifically, we achieved accuracies of 95.9%, 95.9%, and 100.0% for the pre-receptive group, the receptive group, and the post-respective group, respectively. Additionally, we identified a set of differentially expressed miRNAs between different endometrial receptivity statuses using the following criteria: p-value < 0.05 and fold change greater than 1.5 or less than -1.5. In conclusion, the expression levels of cell-free miRNAs in blood samples can be utilized in a non-invasive manner to distinguish different endometrial receptivity statuses.

Keywords: blood; cell-free microRNA; endometrial receptivity; next-generation sequencing; non-invasive biomarkers.

MeSH terms

  • Circulating MicroRNA*
  • Embryo Implantation / genetics
  • Embryo Transfer
  • Endometrium
  • Female
  • Humans
  • MicroRNAs* / genetics

Substances

  • Circulating MicroRNA
  • MicroRNAs

Grants and funding

This research was funded by Inti Labs, Taiwan, Inc. and Quark Biosciences, Inc.