Advances in non-invasive diagnostic tools for endometriosis: A narrative review of the past ten years

Advances in non-invasive diagnostic tools for endometriosis: A narrative review of the past ten years Corresponding Author Lauren Cosgriff Department of Obstetrics & Gynecology, MedStar Health/Georgetown University, Washington, District of Columbia, USA Correspondence Lauren Cosgriff, Department of Obstetrics & Gynecology, MedStar Health/Georgetown University,106 Irving Street, NW, Physicians Office Building, South Tower, Suite 405, Washington, DC 20010, USA. Email: [email protected] Search for more papers by this authorAvni Mukker Georgetown University School of Medicine, Washington, District of Columbia, USA Search for more papers by this authorCourtney Ford Department of Obstetrics & Gynecology, MedStar Health/Georgetown University, Washington, District of Columbia, USA Search for more papers by this authorJovana Tavcar Department of Obstetrics & Gynecology, MedStar Health/Georgetown University, Washington, District of Columbia, USA Search for more papers by this authorCorresponding Author Lauren Cosgriff Department of Obstetrics & Gynecology, MedStar Health/Georgetown University, Washington, District of Columbia, USA Correspondence Lauren Cosgriff, Department of Obstetrics & Gynecology, MedStar Health/Georgetown University,106 Irving Street, NW, Physicians Office Building, South Tower, Suite 405, Washington, DC 20010, USA. Email: [email protected] Search for more papers by this authorAvni Mukker Georgetown University School of Medicine, Washington, District of Columbia, USA Search for more papers by this authorCourtney Ford Department of Obstetrics & Gynecology, MedStar Health/Georgetown University, Washington, District of Columbia, USA Search for more papers by this authorJovana Tavcar Department of Obstetrics & Gynecology, MedStar Health/Georgetown University, Washington, District of Columbia, USA Search for more papers by this authorAbstract Endometriosis is a chronic condition defined by endometrium-like tissue outside the uterus, with symptoms including pain, infertility, and fatigue. Despite the high prevalence of disease, diagnosis is frequently delayed, in part due to reliance on invasive procedures such as laparoscopy. Over the past decade, scientific research and international collaborations have focused on the development of non-invasive diagnostic tools to allow earlier detection and reduce the burden of surgical diagnosis. This narrative review summarizes key developments in non-invasive tools over the past decade. These advances include those in the biomarker space, imaging techniques and protocols, and artificial intelligence applications. While no single test has yet replaced laparoscopy, significant strides have been made toward safer, earlier diagnosis. Continued interdisciplinary collaboration, standardization of imaging and research protocols, and large-scale validation studies are essential for translating these findings into clinical practice. CONFLICT OF INTEREST STATEMENT The authors have no conflicts of interest to disclose. DATA AVAILABILITY STATEMENT Research data are not shared. REFERENCES - 1Zondervan KT, Becker CM, Koga K, Missmer SA, Taylor RN, Viganò P. Endometriosis. Nat Rev Dis Primers. 2018; 4(1):9. doi:10.1038/s41572-018-0008-5 - 2 American College of Obstetricians and Gynecologists. Management of endometriosis. Practice Bulletin No. 114. Obstet Gynecol. 2010; 116: 223-236. 10.1097/AOG.0b013e3181e8b073Google Scholar - 3Fuldeore M, Yang H, Du EX, Soliman AM, Wu EQ, Winkel C. Healthcare utilization and costs in women diagnosed with endometriosis before and after diagnosis: a longitudinal analysis of claims databases. Fertil Steril. 2015; 103(1): 163-171. doi:10.1016/j.fertnstert.2014.10.011 - 4Surrey E, Soliman AM, Trenz H, Blauer-Peterson C, Sluis A. Impact of endometriosis diagnostic delays on healthcare resource utilization and costs. Adv Ther. 2020; 37(3): 1087-1099. doi:10.1007/s12325-019-01215-x - 5Singh SS, Allaire C, Al-Nourhji O, et al. Guideline No. 449: diagnosis and impact of endometriosis—a Canadian guideline. J Obstet Gynaecol Can. 2024; 46(5):102450. doi:10.1016/j.jogc.2024.102450 - 6Agrawal SK, Chapron C, Giudice LC, et al. Clinical diagnosis of endometriosis: a call to action. Am J Obstet Gynecol. 2019; 220(4): 354.e1-354.e12. doi:10.1016/j.ajog.2018.12.039 - 7Santos CM d AM, de Souza ATB, Neta APR, et al. Exosomal MicroRNAs as epigenetic biomarkers for endometriosis: a systematic review and bioinformatics analysis. Int J Mol Sci. 2025; 26(10):4564. doi:10.3390/ijms26104564 - 8Agrawal S, Tapmeier TT, Rahmioglu N, Kirtley S, Zondervan KT, Becker CM. The miRNA mirage: how close are we to finding a non-invasive diagnostic biomarker in endometriosis? A systematic review. Int J Mol Sci. 2018; 19(2):599. doi:10.3390/ijms19020599 - 9Ronsini C, Fumiento P, Iavarone I, Greco PF, Cobellis L, De Franciscis P. Liquid biopsy in endometriosis: a systematic review. Int J Mol Sci. 2023; 24(7): 1-17. doi:10.3390/ijms24076116 - 10Bjorkman S, Taylor HS. MicroRNAs in endometriosis: biological function and emerging biomarker candidates. Biol Reprod. 2019; 100(5): 1135-1146. doi:10.1093/biolre/ioz014 - 11O'Brien J, Hayder H, Zayed Y, Peng C. Overview of microRNA biogenesis, mechanisms of actions, and circulation. Front Endocrinol. 2018; 9(Aug): 1-12. doi:10.3389/fendo.2018.00402 - 12Vanhie A, Dorien O, Peterse D, et al. Plasma miRNAs as biomarkers for endometriosis. Hum Reprod. 2019; 34(9): 1650-1660. doi:10.1093/humrep/dez116 - 13Wei S, Xu H, Kuang Y. Systematic enrichment analysis of microRNA expression profiling studies in endometriosis. Iran J Basic Med Sci. 2015; 18(5): 423-429. - 14Arafah M, Rashid S, Akhtar M. Endometriosis: A comprehensive. Review. 2021; 28(1): 30-43. - 15Tal A, Tal R, Kliman HJ, Taylor HS. Loss of Cxcr4 in endometriosis reduces proliferation and lesion number while increasing intraepithelial lymphocyte infiltration. Am J Pathol. 2021; 191(7): 1292-1302. doi:10.1016/j.ajpath.2021.04.011 - 16Filigheddu N, Gregnanin I, Porporato PE, et al. Differential expression of micrornas between eutopic and ectopic endometrium in ovarian endometriosis. J Biomed Biotechnol. 2010; 2010: 1-29. doi:10.1155/2010/369549 10.1155/2010/369549Google Scholar - 17Joshi NR, Su RW, Chandramouli GVR, et al. Altered expression of microRNA-451 in eutopic endometrium of baboons (Papio anubis) with endometriosis. Hum Reprod. 2015; 30(12): 2881-2891. doi:10.1093/humrep/dev229 - 18Kats R, Metz CN, Akoum A. Macrophage migration inhibitory factor is markedly expressed in active and early-stage endometriotic lesions. J Clin Endocrinol Metab. 2002; 87(2): 883-889. doi:10.1210/jcem.87.2.8260 - 19Akoum A, Metz CN, Al-Akoum M, Kats R. Macrophage migration inhibitory factor expression in the intrauterine endometrium of women with endometriosis varies with disease stage, infertility status, and pelvic pain. Fertil Steril. 2006; 85(5): 1379-1385. doi:10.1016/j.fertnstert.2005.10.073 - 20Zubrzycka A, Migdalska-Sęk M, Jędrzejczyk S, Brzeziańska-Lasota E. Circulating mirnas related to epithelial–mesenchymal transitions (Emt) as the new molecular markers in endometriosis. Curr Issues Mol Biol. 2021; 43(2): 900-916. doi:10.3390/CIMB43020064 - 21Brulport A, Bourdon M, Vaiman D, et al. An integrated multi-tissue approach for endometriosis candidate biomarkers: a systematic review. Reprod Biol Endocrinol. 2024; 22(1): 1-26. doi:10.1186/s12958-023-01181-8 - 22Saunders PTK, Whitaker LHR, Horne AW. Endometriosis: improvements and challenges in diagnosis and symptom management. Cell Rep Med. 2024; 5(6):101596. doi:10.1016/j.xcrm.2024.101596 - 23Zhang Z, Liu T, Dong M, Ahamed MA, Guan W. Sample-to-answer salivary miRNA testing: new frontiers in point-of-care diagnostic technologies. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2024; 16(3): 1-31. doi:10.1002/wnan.1969 - 24Bendifallah S, Dabi Y, Suisse S, et al. Validation of a salivary miRNA signature of endometriosis—interim data. NEJM Evid. 2023; 2(7):EVIDoa2200282. doi:10.1056/evidoa2200282 - 25Evans-Hoeker E, Lessey BA, Jeong JW, et al. Endometrial BCL6 overexpression in Eutopic endometrium of women with endometriosis. Reprod Sci. 2016; 23(9): 1234-1241. doi:10.1177/1933719116649711 - 26Nezhat C, Rambhatla A, Miranda-Silva C, et al. Bcl-6 overexpression as a predictor for endometriosis in patients undergoing in vitro fertilization. JSLS. 2020; 24(4):e2020.00064. doi:10.4293/JSLS.2020.00064 - 27Almquist LD, Likes CE, Stone B, et al. Endometrial BCL6 testing for the prediction of in vitro fertilization outcomes: a cohort study. Fertil Steril. 2017; 108(6): 1063-1069. doi:10.1016/j.fertnstert.2017.09.017 - 28Nezhat C, Agarwal S, Lee DA, Tavallaee M. Can we accurately diagnose endometriosis without a diagnostic laparoscopy? J Turk Ger Gynecol Assoc. 2022; 23(2): 117-119. doi:10.4274/jtgga.galenos.2022.2022-2-2 - 29Bendifallah S, Suisse S, Puchar A, et al. Salivary MicroRNA signature for diagnosis of endometriosis. J Clin Med. 2022; 11(3): 1-12. doi:10.3390/jcm11030612 - 30Ferrier C, Bendifallah S, Suisse S, et al. Saliva microRNA signature to diagnose endometriosis: a cost-effectiveness evaluation of the Endotest®. BJOG. 2023; 130(4): 396-406. doi:10.1111/1471-0528.17348 - 31Jia SZ, Yang Y, Lang J, Sun P, Leng J. Plasma miR-17-5p, miR-20a and miR-22 are down-regulated in women with endometriosis. Hum Reprod. 2013; 28(2): 322-330. doi:10.1093/humrep/des413 - 32Moustafa S, Burn M, Mamillapalli R, Nematian S, Flores V, Taylor HS. Accurate diagnosis of endometriosis using serum microRNAs. Am J Obstet Gynecol. 2020; 223(4): 557.e1-557.e11. doi:10.1016/j.ajog.2020.02.050 - 33Ji S, Liu Y, Yan L, et al. DIA-based analysis of the menstrual blood proteome identifies association between CXCL5 and IL1RN and endometriosis. J Proteome. 2023; 289(February):104995. doi:10.1016/j.jprot.2023.104995 - 34Warren LA, Shih A, Renteira SM, et al. Analysis of menstrual effluent: diagnostic potential for endometriosis. Mol Med. 2018; 24(1): 1-12. doi:10.1186/s10020-018-0009-6 - 35Van den Bosch T, Van Schoubroeck D. Ultrasound diagnosis of endometriosis and adenomyosis: state of the art. Best Pract Res Clin Obstet Gynaecol. 2018; 51(2018): 16-24. doi:10.1016/j.bpobgyn.2018.01.013 - 36Moro F, Leombroni M, Testa AC. Ultrasound imaging in endometriosis. Obstet Gynecol Clin N Am. 2019; 46(4): 643-659. doi:10.1016/j.ogc.2019.07.004 - 37Nisenblat V, Bossuyt PMM, Farquhar C, Johnson N, Hull ML. Imaging modalities for the non-invasive diagnosis of endometriosis. Cochrane Database Syst Rev. 2016; 2(2):CD009591. doi:10.1002/14651858.CD009591.pub2 - 38Guerriero S, Condous G, van den Bosch T, et al. Systematic approach to sonographic evaluation of the pelvis in women with suspected endometriosis, including terms, definitions and measurements: a consensus opinion from the international deep endometriosis analysis (IDEA) group. Ultrasound Obstet Gynecol. 2016; 48(3): 318-332. doi:10.1002/uog.15955 - 39Leonardi M, Uzuner C, Mestdagh W, et al. Diagnostic accuracy of transvaginal ultrasound for detection of endometriosis using international deep endometriosis analysis (IDEA) approach: prospective international pilot study. Ultrasound Obstet Gynecol. 2022; 60(3): 404-413. doi:10.1002/uog.24936 - 40Condous G, Gerges B, Thomassin-Naggara I, et al. Non-invasive imaging techniques for diagnosis of pelvic deep endometriosis and endometriosis classification systems: an international consensus statement. Ultrasound Obstet Gynecol. 2024; 64(1): 129-144. doi:10.1002/uog.27560 - 41Goncalves MO, Siufi Neto J, Andres MP, Siufi D, De Mattos LA, Abrao MS. Systematic evaluation of endometriosis by transvaginal ultrasound can accurately replace diagnostic laparoscopy, mainly for deep and ovarian endometriosis. Hum Reprod. 2021; 36(6): 1492-1500. doi:10.1093/humrep/deab085 - 42Becker CM, Bokor A, Heikinheimo O, et al. Eshre Guidelines. 2022. 1–26. - 43Pang E, Shergill A, Chang S, et al. CAR/CSAR Practice Statement on Pelvic MRI for Endometriosis. 2024. doi:10.1177/08465371241306658 - 44Feldman MK, Wasnik AP, Adamson M, et al. ACR appropriateness criteria® endometriosis. J Am Coll Radiol. 2024; 21(11): S384-S395. doi:10.1016/j.jacr.2024.08.017 - 45 RANZCOG Melbourne Australia. Australian clinical practice guideline for the diagnosis and management of endometriosis (2021). 2021. http://ranzcog.edu.au/wp-content/uploads/2022/02/Endometriosis-clinical-practice-guideline.pdf - 46 Endometriosis: Diagnosis and Management. National Institute for Health and Care Excellence (NICE); 2024. - 47Bazot M, Bharwani N, Huchon C, et al. European society of urogenital radiology (ESUR) guidelines: MR imaging of pelvic endometriosis. Eur Radiol. 2017; 27(7): 2765-2775. doi:10.1007/s00330-016-4673-z - 48Dungate B, Tucker DR, Goodwin E, Yong PJ. Assessing the utility of artificial intelligence in endometriosis: promises and pitfalls. Womens Health. 2024; 20:17455057241248121. doi:10.1177/17455057241248121 - 49Avery JC, Deslandes A, Freger SM, et al. Noninvasive diagnostic imaging for endometriosis part 1: a systematic review of recent developments in ultrasound, combination imaging, and artificial intelligence. Fertil Steril. 2024; 121(2): 164-188. doi:10.1016/j.fertnstert.2023.12.008 - 50Chapron C, Marcellin L, Borghese B, Santulli P. Rethinking mechanisms, diagnosis and management of endometriosis. Nat Rev Endocrinol. 2019; 15(11): 666-682. doi:10.1038/s41574-019-0245-z - 51Pascoal E, Wessels JM, Aas-Eng MK, et al. Strengths and limitations of diagnostic tools for endometriosis and relevance in diagnostic test accuracy research. Ultrasound Obstet Gynecol. 2022; 60(3): 309-327. doi:10.1002/uog.24892 - 52Vigano P, Vercellini P, Somigliana E, et al. “I'm looking through you”: what consumers and manufacturers need to know about non-invasive diagnostic tests for endometriosis. J Endometr Uterine Disord. 2023; 2(June):100031. doi:10.1016/j.jeud.2023.100031 10.1016/j.jeud.2023.100031Google Scholar - 53Canis M, Abbott J, Abrao M, et al. A call for new theories on the pathogenesis and pathophysiology of endometriosis. J Minim Invasive Gynecol. 2024; 31(5): 371-377. doi:10.1016/j.jmig.2024.02.004 Citing Literature Article Metrics Total unique accesses to an article’s full text in HTML or PDF/ePDF format.More metric information Scite metrics Explore this article's citation statements on scite.ai Share QR Code Generating QR code QR code copied to clipboard! Something went wrong while generating your QR code. Please try again in a moment. If the issue persists, refresh the page or contact support. Export citation Unable to load citation data. Please try again in a moment. How to cite Elkins, L. J., & Spiegelman, M. (2021). pyUserCalc: A revised Jupyter notebook calculator for uranium-series disequilibria in basalts. Earth and Space Science, 8, e2020EA001619. https://doi.org/10.1029/2020EA001619 Download Citation If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click on download. This feature enables you to download the bibliographic information (also called citation data, header data, or metadata) for the articles on our site. Citation manager file format Use the dropdown list to choose how to format the bibliographic data you're harvesting. Several citation manager formats are available, including EndNote and BibTex. You can then copy the formatted citation (as displayed) or download it as file, to your device. If the RefWorks format is chosen, the 'Download' button will be replaced with an option to directly export to RefWorks