A novel platform for discovery of differentially expressed microRNAs in patients with repeated implantation failure

Abstract

Objective: To identify predictor microRNAs (miRNAs) from patients with repeated implantation failure (RIF). Design: Systemic analysis of miRNA profiles from the endometrium of patients undergoing in vitro fertilization (IVF). Setting: University research institute, private IVF center, and molecular testing laboratory. Patient(s): Twenty five infertile patients in the discovery cohort and 11 patients in the validation cohort. Interventions(s): None. Main Outcome Measure(s): A signature set of miRNA associated with the risk of RIF. Result(s): We designed a reproductive disease-related PanelChip to access endometrium miRNA profiles in patients undergoing IVF.Three major miRNA signatures, including hsa-miR-20b-5p, hsa-miR-155-5p, and hsa-miR-718, were identified using infinite combination signature search algorithm analysis from 25 patients in the discovery cohort undergoing IVF. These miRNAs were used as biomarkers in the validation cohort of 11 patients. Finally, the 3-miRNA signature was capable of predicting patients with RIF with an accuracy >90%. Conclusion(s):Our findings indicated that specific endometrial miRNAs can be applied as diagnostic biomarkers to predict RIF. Such information will definitely help to increase the success rate of implantation practice. (Fertil Steril Ò 2021;116:181-8. Ó2021 by American Society for Reproductive Medicine.) El resumen está disponible en Español al final del artículo.

Endometrial receptivity: miRNAs signing in?

“…It is evident from published studies that one of the main causes of RIF is issues with endometrial receptivity and the timing of the WOI. These findings were confirmed further in the investigation performed by Chen et al (2), who identified three miRNAs that could provide an endometrial signature for RIF with an accuracy of approximately 91%. MicroRNAs have been identified previously as potentially useful biomarkers of, for example, embryo viability, but there was a lack of consensus in the identified miRNA molecules among different studies.…”

“…The function of miRNAs in reproduction is complex. This probably is the reason why Chen et al (2) were not able to establish many common miRNAs with other studies as they point out in their investigation.…”

“…One of these studies determined that women with RIF have a higher rate of nonreceptive endometrium (26%) when compared with women without RIF (12%). These findings are echoed in the study of Chen et al (2). Moreover, a recently published multicenter randomized controlled trial (RCT) examining the clinical effectiveness of pET after the ERA test, reported a statistically significant improvement in outcomes, such as pregnancy, implantation, and cumulative live birth rates, when pET took place, compared with frozen and fresh embryo transfers.…”

“…Examples include endometrial thickness and pattern, Doppler indices, and the identification of patterns of endometrial gene expression considered to be representative of its receptive status (1). Another such group of potentially clinically useful biomarkers are microRNAs (miRNAs) which have been shown to be involved in the regulation of the genes responsible for the WOI timing (reviewed by Chen et al [2]).…”

Biomolecular Markers of Recurrent Implantation Failure—A Review

“…MicroRNAs, recognized function modulators, could control the expression of many genes involved in the peri-implantation period and in this way could play a vital role in fetal/placental development. On the other hand, these factors might be closely involved in recurrent implantation failure (IVF) and recurrent pregnancy loss (RPL) pathogenesis [ 28 ].…”