Non-Invasive Methods for Early Diagnosis of Endometriosis—A Comprehensive Narrative Literature Review

Endometriosis is a common gynecological pathology, with an incidence of nearly 10% in patients of reproductive age, and is still underdiagnosed. A thorough and well-spread diagnostic study of endometriosis based on epigenetic factor dysregulation can highlight potential areas for improvement. To quantify the potential and utility of non-invasive tools in the early diagnosis of endometriosis, an overview of current knowledge on epigenetic factors, based on DNA and RNA, is presented. Among these tools, it is important to highlight the role of miRNAs (microRNAs), cfDNA (cell-free DNA), and rRNAs (ribosomal RNAs), which are small molecules involved in endometriosis and numerous other pathologies. To evaluate their potential and utility in endometriosis, a salivary miRNA diagnostic test was conducted, the cfDNA methylation patterns of fragmented DNA circulating in bodily fluids (e.g., plasma) were analyzed, and cervical and uterine microbiomes were profiled for bacterial rRNA in patients with clinical suspicion of incipient endometriosis. Specific molecular profiles associated with endometriosis were analyzed. The first profile, a 109-miRNA saliva signature, was validated as a product of miRNA biomarkers and artificial intelligence modeling. In addition, peripheral blood cfDNA methylation biomarkers were identified by investigating nine genes in a molecular signature that requires validation. A profile was also obtained from cervical swabs and uterine washes, including molecular analysis of 16S rRNA amplicon sequencing to evaluate alterations in the cervical bacterial community. This review aims to optimize the integration of a non-invasive diagnostic tool for early endometriosis diagnosis. Genetic biomarkers can be correlated with clinical factors to improve diagnostic accuracy. Of the assessed diagnostic tools, salivary miRNA tests, a peripheral blood cfDNA methylation biomarker, and a microbiome rRNA signature may be useful for early diagnosis of endometriosis, as well as, implicitly, therapeutic attitude and follow-up.