An update on miRNAs as non-invasive diagnostic markers for endometriosis: Why have we not reached consensus?

Abstract

The objective of this narrative review is to provide an update on microRNAs (miRNAs) as non-invasive biomarkers for endometriosis diagnosis focusing on publications from 2016 to 2026. In addition to updating miRNAs reported during this time frame, we also discuss why consensus has not been reached on identification of miRNAs with suitable sensitivity and specificity as diagnostic markers. A literature search was performed on PubMed from January 1, 2016 to September 1, 2026 using the keywords endometriosis, miRNA, and biomarker. A total of 238 articles were retrieved of which 101 were reviews, meta-analysis, or database searches, 46 articles focused on tissue or cell assessment of miRNA expression limiting the non-invasive approach, 24 were not focused on endometriosis but diseases comorbid with endometriosis, 17 focused on exosomes, 15 focused on other body fluid assessment of miRNAs, 4 focused on AI/machine learning, and 2 focused on animal model assessment of miRNA expression leaving 29 publications for further evaluation. The search for non-invasive biomarkers for endometriosis remains ongoing. From the studies presented in this review, while several miRNAs have emerged as candidate biomarkers, there is still considerable variability with respect to differentially expressed miRNAs between women with and without endometriosis. Focused assessment on methodologies employed for isolating serum/plasma, extraction of RNA/miRNAs, amplification and data normalization from these samples and if and how sample hemolysis was assessed and revealed differences among the studies all which impact miRNA profiles. As such, it is imperative to develop a standardized protocol when assessing miRNAs from blood if we hope to identify miRNAs which may prove useful in non-invasive diagnosis of endometriosis.