Translational Assessment of Omics Approaches in Endometriosis: Bridging Molecular Discovery with Clinical Utility

Endometriosis affects an estimated 5-10% of women of reproductive age and presents with substantial clinical and biological heterogeneity. Recent clinical guidelines have shifted toward symptom-guided diagnosis supported by expert imaging, moving away from mandatory diagnostic laparoscopy and redefining the evidentiary standards for evaluating new diagnostic technologies. Advances across omics domains, including genomics, epigenomics, transcriptomics, proteomics, metabolomics, extracellular vesicle profiling, microbiome research, and multi-omics integration, have deepened understanding of lesion biology, immune dysregulation, metabolic alterations, and progesterone resistance. However, translation of these molecular insights into clinically actionable tools remains limited. Most candidate biomarkers remain at discovery or internal/developer-led validation stages, constrained by small sample sizes, heterogeneous analytical platforms, incomplete control of confounding variables, and limited independent multicenter validation. In this review, we apply a four-tier evidence-maturity framework, spanning discovery, internal or developer-led validation, independent external validation, and demonstrated clinical utility, to classify omics-based diagnostic, prognostic, and treatment-response applications in endometriosis. We also distinguish potential clinical roles, including triage, adjunctive testing, and replacement-test evaluation, each requiring different validation standards and performance thresholds. Salivary microRNA currently represents the most clinically advanced diagnostic omics candidate, but the available evidence remains developer-led and is best classified as advanced Tier 2/Tier 2+ rather than independent Tier 3 validation. Prognostic and treatment-response applications are less mature and remain discovery-stage because prospective patient-level longitudinal validation and biomarker-stratified treatment trials are lacking. Overall, no omics-derived biomarker has yet achieved independent Tier 3 validation or Tier 4 readiness for routine clinical implementation. At present, omics approaches should be regarded primarily as research and translational prioritization tools rather than determinants of routine clinical decision-making.