{"paper_id":"61536210-4e9c-4ad8-97b1-b43af956d07e","body_text":"Abstract\nObjective\nThe aim of this review is to analyze the patent filings and to systematize the main technological trends in patent protection for the diagnosis and therapeutics for endometriosis. Patent literature has also been explored to identify active inventors and applicants in this field.\nMethodology\nPatent search was carried out in the freely accessible patent search databases namely, patentscope using various combinations of the keywords “Endometriosis OR Adenomyosis” AND “Diagnostic OR Therapeutics” were used along with wildcard search queries in the “Title”, “Abstract” and “Descriptions” fields.\nResults\nA patent search revealed 144 patents describing inventions for diagnostic and therapeutic purposes of endometriosis. These patents include 26 patent applications in the diagnostic utility and 116 patent applications under the therapeutic approaches. Out of these 116 patent applications, 43 describe traditional medicines for endometriosis. Two patent applications describe inventions that can fall into both categories.\nConclusion\nEfforts are being made to improve current diagnostic instruments. Hormonal alteration methods is the most common field of invention, followed by surgical interventions for therapeutics. A general trend of increase in patent application filings has been observed with a slight decrease in recent years.\nSimilar content being viewed by others\nData availability\nThe supporting data is available in the supplementary table.\nReferences\nSaunders PTK, Horne AW (2021) Endometriosis: etiology, pathobiology, and therapeutic prospects. Cell 184:2807–2824. https://doi.org/10.1016/j.cell.2021.04.041\nGiudice LC, Kao LC (2004) Endometriosis. Lancet 364:1789–1799. https://doi.org/10.1016/S0140-6736(04)17403-5\nMeuleman C, Vandenabeele B, Fieuws S et al (2009) High prevalence of endometriosis in infertile women with normal ovulation and normospermic partners. Fertil Steril 92:68–74. https://doi.org/10.1016/j.fertnstert.2008.04.056\nSmolarz B, Szyłło K, Romanowicz H (2021) Endometriosis: epidemiology, classification, pathogenesis, treatment and genetics (review of literature). Int J Mol Sci 22:10554. https://doi.org/10.3390/ijms221910554\nMehedintu C, Plotogea M, Ionescu S, Antonovici M (2014) Endometriosis still a challenge. J Med Life 7:349–357\nHsu AL, Khachikyan I, Stratton P (2010) Invasive and noninvasive methods for the diagnosis of endometriosis. Clin Obstet Gynecol 53:413–419. https://doi.org/10.1097/GRF.0b013e3181db7ce8\nKido A, Himoto Y, Moribata Y et al (2022) MRI in the diagnosis of endometriosis and related diseases. Korean J Radiol 23:426. https://doi.org/10.3348/kjr.2021.0405\nSahin C, Mamillapalli R, Yi KW, Taylor HS (2018) microRNA Let-7b: a novel treatment for endometriosis. J Cell Mol Med 22:5346–5353. https://doi.org/10.1111/jcmm.13807\nLevy AR, Osenenko KM, Lozano-Ortega G et al (2011) Economic burden of surgically confirmed endometriosis in Canada. J Obstet Gynaecol Can JOGC 33:830–837. https://doi.org/10.1016/S1701-2163(16)34986-6\nBrown J, Kives S, Akhtar M (2012) Progestogens and anti-progestogens for pain associated with endometriosis. Cochrane Database Syst Rev. https://doi.org/10.1002/14651858.CD002122.pub2\nAngioni S, Cofelice V, Pontis A et al (2014) New trends of progestins treatment of endometriosis. Gynecol Endocrinol 30:769–773. https://doi.org/10.3109/09513590.2014.950646\nOzkan S, Arici A (2009) Advances in treatment options of endometriosis. Gynecol Obstet Investig 67:81–91. https://doi.org/10.1159/000163071\nVannuccini S, Clemenza S, Rossi M, Petraglia F (2022) Hormonal treatments for endometriosis: the endocrine background. Rev Endocr Metab Disord 23:333–355. https://doi.org/10.1007/s11154-021-09666-w\nWu Y, Zhu Y, Xie N et al (2022) A network pharmacology approach to explore active compounds and pharmacological mechanisms of a patented Chinese herbal medicine in the treatment of endometriosis. PLoS ONE 17:e0263614. https://doi.org/10.1371/journal.pone.0263614\nNirgianakis K, Egger K, Kalaitzopoulos DR et al (2022) Effectiveness of dietary interventions in the treatment of endometriosis: a systematic review. Reprod Sci 29:26–42. https://doi.org/10.1007/s43032-020-00418-w\nYalçınBahat P, Ayhan I, ÜreyenÖzdemir E et al (2022) Dietary supplements for treatment of endometriosis: a review. Acta Bio-medica Atenei Parmensis 93(1):e2022159. https://doi.org/10.23750/abm.v93i1.11237\nSmolarz B, Szyłło K, Romanowicz H (2020) The genetic background of endometriosis: can ESR2 and CYP19A1 genes be a potential risk factor for its development? Int J Mol Sci 21:8235. https://doi.org/10.3390/ijms21218235\nRuiz A, Ruiz L, Colón-Caraballo M et al (2018) Pharmacological blockage of the CXCR4–CXCL12 axis in endometriosis leads to contrasting effects in proliferation, migration, and invasion†. Biol Reprod 98:4–14. https://doi.org/10.1093/biolre/iox152\nRagni E, Colombini A, De Luca P et al (2021) miR-103a-3p and miR-22-5p are reliable reference genes in extracellular vesicles from cartilage, adipose tissue, and bone marrow cells. Front Bioeng Biotechnol 9:632440. https://doi.org/10.3389/fbioe.2021.632440\nYuguchi H, Tanabe A, Hayashi A et al (2013) The expression status of G protein-coupled receptor GPR30 is associated with the clinical characteristics of endometriosis. Endocr Res 38:223–231. https://doi.org/10.3109/07435800.2013.774011\nKarimi-Zarchi M, Dehshiri-Zadeh N, Sekhavat L, Nosouhi F (2016) Correlation of CA-125 serum level and clinico-pathological characteristic of patients with endometriosis. Int J Reprod Biomed 14:713–718\nPonomarenko I, Reshetnikov E, Polonikov A et al (2021) Candidate genes for age at menarche are associated with uterine leiomyoma. Front Genet 11:512940. https://doi.org/10.3389/fgene.2020.512940\nLi S, Fu X, Wu T et al (2017) Role of interleukin-6 and its receptor in endometriosis. Med Sci Monit 23:3801–3807. https://doi.org/10.12659/MSM.905226\nMathur SP, Holt VL, Lee JH et al (1998) Levels of antibodies to transferrin and alpha 2-HS glycoprotein in women with and without endometriosis. Am J Reprod Immunol (New York, N.Y.: 1989) 40(2):69–73. https://doi.org/10.1111/j.1600-0897.1998.tb00393.x\nChao X, Liu Y, Fan Q et al (2021) The role of the vaginal microbiome in distinguishing female chronic pelvic pain caused by endometriosis/adenomyosis. Ann Transl Med 9:771. https://doi.org/10.21037/atm-20-4586\nGratton S-M, Choudhry AJ, Vilos GA et al (2022) Diagnosis of endometriosis at laparoscopy: a validation study comparing surgeon visualization with histologic findings. J Obstet Gynaecol Can 44:135–141. https://doi.org/10.1016/j.jogc.2021.08.013\nMettler L, Schollmeyer T, Lehmann-Willenbrock E et al (2003) Accuracy of laparoscopic diagnosis of endometriosis. JSLS 7:15–18\nAlborzi S, Rasekhi A, Shomali Z et al (2018) Diagnostic accuracy of magnetic resonance imaging, transvaginal, and transrectal ultrasonography in deep infiltrating endometriosis. Medicine (Baltimore) 97:e9536. https://doi.org/10.1097/MD.0000000000009536\nPhilip C-A, Warembourg S, Dairien M et al (2020) Transrectal high-intensity focused ultrasound (HIFU) for management of rectosigmoid deep infiltrating endometriosis: results of phase-I clinical trial. Ultrasound Obstet Gynecol 56:431–442. https://doi.org/10.1002/uog.21937\nDi Spiezio SA, Calagna G, Santangelo F et al (2017) The role of hysteroscopy in the diagnosis and treatment of adenomyosis. BioMed Res Int 2017:1–7. https://doi.org/10.1155/2017/2518396\nOzkan ZS, Cilgin H, Simsek M et al (2013) Investigation of apelin expression in endometriosis. J Reprod Infertil 14:50–55\nFrontiers|A natural xenogeneic endometrial extracellular matrix hydrogel toward improving current human in vitro models and future in vivo applications. https://www.frontiersin.org/articles/https://doi.org/10.3389/fbioe.2021.639688/full. Accessed 4 Nov 2022\nZanelotti A, Decherney AH (2017) Surgery and endometriosis. Clin Obstet Gynecol 60:477–484. https://doi.org/10.1097/GRF.0000000000000291\nDai Y, Li X, Shi J, Leng J (2018) A review of the risk factors, genetics and treatment of endometriosis in Chinese women: a comparative update. Reprod Health 15:82. https://doi.org/10.1186/s12978-018-0506-7\nHughes E, Brown J, Collins JJ et al (2007) Ovulation suppression for endometriosis for women with subfertility. Cochrane Database Syst Rev. https://doi.org/10.1002/14651858.CD000155.pub2\nChantalat E, Valera M-C, Vaysse C et al (2020) Estrogen receptors and endometriosis. Int J Mol Sci 21:2815. https://doi.org/10.3390/ijms21082815\nGezer A, Oral E (2015) Progestin therapy in endometriosis. Womens Health 11:643–652. https://doi.org/10.2217/whe.15.42\nRafique S, DeCherney AH (2017) Medical management of endometriosis. Clin Obstet Gynecol 60:485–496. https://doi.org/10.1097/GRF.0000000000000292\nMettler L, Ruprai R, Alkatout I (2014) Impact of medical and surgical treatment of endometriosis on the cure of endometriosis and pain. BioMed Res Int 2014:264653. https://doi.org/10.1155/2014/264653\nMuraoka A, Osuka S, Yabuki A et al (2021) Impact of perioperative use of GnRH agonist or dienogest on ovarian reserve after cystectomy for endometriomas: a randomized controlled trial. Reprod Biol Endocrinol 19:179. https://doi.org/10.1186/s12958-021-00866-2\nKüpker W, Felberbaum RE, Krapp M et al (2002) Use of GnRH antagonists in the treatment of endometriosis. Reprod Biomed Online 5:12–16. https://doi.org/10.1016/s1472-6483(10)61590-8\nSchweppe K-W (2001) Current place of progestins in the treatment of endometriosis-related complaints. Gynecol Endocrinol 15:22–28. https://doi.org/10.1080/gye.15.s6.22.28\nSchindler AE (2011) Dienogest in long-term treatment of endometriosis. Int J Womens Health 3:175–184. https://doi.org/10.2147/IJWH.S5633\nQu F (2006) Effects of Yiweining Recipe on expressions of metalloproteinase-2 and cyclooxygenase-2 mRNAs in ectopic endometrium of rats with endometriosis. J Chin Integr Med. https://doi.org/10.3736/jcim20060619\nHarada T, Iwabe T, Terakawa N (2001) Role of cytokines in endometriosis. Fertil Steril 76:1–10. https://doi.org/10.1016/S0015-0282(01)01816-7\nKato T, Yasuda K, Matsushita K et al (2019) Interleukin-1/-33 signaling pathways as therapeutic targets for endometriosis. Front Immunol 10:2021. https://doi.org/10.3389/fimmu.2019.02021\nLu P, Takai K, Weaver VM, Werb Z (2011) Extracellular matrix degradation and remodeling in development and disease. Cold Spring Harb Perspect Biol 3:a005058–a005058. https://doi.org/10.1101/cshperspect.a005058\nGünal MY, Ozansoy M, Kılıç Ü et al (2019) Role of erythropoietin and its receptor in the development of endometriosis in rats. J Turk Ger Gynecol Assoc 20:41–46. https://doi.org/10.4274/jtgga.galenos.2018.2018.0039\nStringer EM, Fleming GF (2013) Hormone therapy plus mTOR inhibitors in the treatment of endometrial carcinoma. Oncol Hematol Rev 9(1):41–44. https://doi.org/10.17925/ohr.2013.09.1.41\nGainer EE, Ulmann A (2003) Pharmacologic properties of CDB(VA)-2914. Steroids 68:1005–1011. https://doi.org/10.1016/S0039-128X(03)00130-2\nXu H, Becker CM, Lui WT et al (2011) Green tea epigallocatechin-3-gallate inhibits angiogenesis and suppresses vascular endothelial growth factor C/vascular endothelial growth factor receptor 2 expression and signaling in experimental endometriosis in vivo. Fertil Steril 96:1021-1028.e1. https://doi.org/10.1016/j.fertnstert.2011.07.008\nKoppitz M, Bräuer N, Ter Laak A et al (2019) Discovery and optimization of pyridyl-cycloalkyl-carboxylic acids as inhibitors of microsomal prostaglandin E synthase-1 for the treatment of endometriosis. Bioorg Med Chem Lett 29:2700–2705. https://doi.org/10.1016/j.bmcl.2019.07.007\nFoster PA (2021) Steroid sulphatase and its inhibitors: past, present, and future. Molecules 26:2852. https://doi.org/10.3390/molecules26102852\nNoble LS, Takayama K, Zeitoun KM et al (1997) Prostaglandin E2 stimulates aromatase expression in endometriosis-derived stromal cells1. J Clin Endocrinol Metab 82:600–606. https://doi.org/10.1210/jcem.82.2.3783\nMurakami K, Nomura K, Shinohara K et al (2006) Danazol inhibits aromatase activity of endometriosis-derived stromal cells by a competitive mechanism. Fertil Steril 86:291–297. https://doi.org/10.1016/j.fertnstert.2005.12.074\nPiacenti I, Viscardi MF, Masciullo L et al (2021) Dienogest versus continuous oral levonorgestrel/EE in patients with endometriosis: what’s the best choice? Gynecol Endocrinol 37:471–475. https://doi.org/10.1080/09513590.2021.1892632\nIlhan M, Dereli FTG, Akkol EK (2019) Novel drug targets with traditional herbal medicines for overcoming endometriosis. Curr Drug Deliv 16:386–399. https://doi.org/10.2174/1567201816666181227112421\nWieser F, Cohen M, Gaeddert A et al (2007) Evolution of medical treatment for endometriosis: back to the roots? Hum Reprod Update 13:487–499. https://doi.org/10.1093/humupd/dmm015\nWieser F, Yu J, Park J et al (2009) A botanical extract from channel flow inhibits cell proliferation, induces apoptosis, and suppresses CCL5 in human endometriotic stromal cells1. Biol Reprod 81:371–377. https://doi.org/10.1095/biolreprod.108.075069\nChapron C, Marcellin L, Borghese B, Santulli P (2019) Rethinking mechanisms, diagnosis and management of endometriosis. Nat Rev Endocrinol 15:666–682. https://doi.org/10.1038/s41574-019-0245-z\nClemenza S, Sorbi F, Noci I et al (2018) From pathogenesis to clinical practice: emerging medical treatments for endometriosis. Best Pract Res Clin Obstet Gynaecol 51:92–101. https://doi.org/10.1016/j.bpobgyn.2018.01.021\nSimsa P, Mihalyi A, Kyama CM et al (2007) Future of endometriosis research. Womens Health 3:647–654. https://doi.org/10.2217/17455057.3.5.647\nPavone ME, Bulun SE (2012) Aromatase inhibitors for the treatment of endometriosis. Fertil Steril 98:1370–1379. https://doi.org/10.1016/j.fertnstert.2012.08.053\nHudson QJ, Proestling K, Perricos A et al (2021) The role of long non-coding RNAs in endometriosis. Int J Mol Sci 22:11425. https://doi.org/10.3390/ijms222111425\nMiller JE, Monsanto SP, Ahn SH et al (2017) Interleukin-33 modulates inflammation in endometriosis. Sci Rep 7(1):17903. https://doi.org/10.1038/s41598-017-18224-x\nMotavalli R, Majidi T, Pourlak T el al (2021) The clinical significance of the glucocorticoid receptors: Genetics and epigenetics. J Steroid Biochem Mol Biol 213:105952. https://doi.org/10.1016/j.jsbmb.2021.105952\nMargatho D, Carvalho NM, Bahamondes L (2020) Endometriosis-associated pain scores and biomarkers in users of the etonogestrel-releasing subdermal implant or the 52-mg levonorgestrel-releasing intrauterine system for up to 24 months. Eur J Contracept Reprod Health Care 25(2):133–140. https://doi.org/10.1080/13625187.2020.1725461\nde Freitas Fonseca M, Aragao LC, Sessa FV et al (2018) Interrelationships among endometriosis-related pain symptoms and their effects on health-related quality of life: a sectional observational study. Obstet Gynecol Sci. 61(5):605–614. https://doi.org/10.5468/ogs.2018.61.5.605\nFunding\nThe authors declare that no funds, grants, or other support were received during the preparation of this manuscript.\nAuthor information\nAuthors and Affiliations\nContributions\nMS: data collection and analysis, draft writing. RJ: data collection and analysis, draft writing. PK: conceptualization, supervision and manuscript checking and finalization.\nCorresponding author\nEthics declarations\nConflict of interest\nThe authors have no relevant financial or non-financial interests to disclose.\nEthical standards\nThe manuscript complies with ethical standards. The study does not involve human samples.\nAdditional information\nPublisher's Note\nSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.\nSupplementary Information\nBelow is the link to the electronic supplementary material.\nRights and permissions\nSpringer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.\nAbout this article\nCite this article\nSingh, M., Jassal, R. & Khetarpal, P. Diagnostic and therapeutic approaches for endometriosis: a patent landscape. Arch Gynecol Obstet 309, 831–842 (2024). https://doi.org/10.1007/s00404-023-07151-0\nReceived:\nAccepted:\nPublished:\nVersion of record:\nIssue date:\nDOI: https://doi.org/10.1007/s00404-023-07151-0","source_license":"CC0","license_restricted":false}