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

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.

Different Dosages of Progesterone in Luteal Phase Support Reflect Varying Endometrial microRNA Expression in Frozen Embryo Transfer Cycles

“…To date, more than 2500 microRNAs (miRNAs) have been discovered in the human genome. They play integral roles in diverse biological processes, including gametogenesis, embryogenesis, and the quality assessment of sperm, oocytes, and embryos, as well as diseases such as endometriosis, endometritis, and endometrial cancer [8][9][10][11]. Unlike messenger RNAs (mRNAs), miRNAs exhibit higher resilience to endogenous ribonuclease activity.…”

“…Specific miRNAs like miR-30b, miR-181, and miR-223-3p govern endometrial cyclic changes, receptive state maturation, and crucial implantation markers. Dysregulated miRNAs, such as miR-21 and miR-22, may contribute to RIF by impacting early cell processes essential for implantation [8,9]. The MicroRNA-based Endometrial Receptivity Analysis (MIRA) platform integrates miRNA biomarkers relevant to fertility physiological processes and endometrial receptivity, offering a 95% predictive accuracy in identifying the displaced window of implantation as a contributing factor to recurrent implantation failure [9].…”