A Systematic Review on Novel Diagnostic Biomarkers of Endometriosis in Association with Moderate-to-Severe Disease

Endometriosis is a chronic, estrogen-dependent gynecological condition affecting approximately 11% of reproductive-aged women. It is characterized by ectopic implantation of endometrial-like tissue, causing pelvic pain, infertility, and systemic symptoms that severely impact quality of life. Currently, diagnosis relies on laparoscopic visualization, leading to prolonged diagnostic delays averaging 6.7 years. Given the limitations of imaging techniques such as MRI and transvaginal ultrasound (TVS) in detecting deep and superficial lesions, research efforts have focused on identifying novel non-invasive biomarkers. While CA-125 has been widely studied, it lacks specificity, limiting its diagnostic utility. Recent discoveries, including neutrophil gelatinase-associated lipocalin (NGAL), endocan, and tRNA-derived small RNAs (tsRNAs), show potential for early and accurate detection, particularly in advanced-stage disease (Stage III/IV). This systematic review aims to synthesize existing evidence on novel biomarkers associated with moderate-to-severe endometriosis, evaluating their diagnostic accuracy, clinical applicability, and potential for replacing invasive diagnostic methods. Expected Outcomes: - Comprehensive Analysis – Identification and classification of emerging biomarkers that differentiate Stage III/IV endometriosis from minimal disease. - Diagnostic Performance Evaluation – Assessment of biomarker sensitivity, specificity, and predictive value, compared to existing modalities. - Clinical Implications – Discussion on biomarker integration into routine diagnostics, aiming to reduce diagnostic delays and improve patient outcomes. - Future Research Directions – Highlighting gaps in biomarker research and proposing key areas for further investigation in translational medicine. This review seeks to bridge the gap between biomarker discovery and clinical application, ultimately contributing to non-invasive, efficient diagnostic strategies for moderate-to-severe endometriosis.