{"paper_id":"17ae7bf0-2cd4-435d-a2ce-b1321f7d8ebf","body_text":"Endometriosis: An Overview\nTanvir Agnihotri, MD 1 Abheek Ghosh, BS 2 Ashley Lamba, BS 3 Charles E. Ray, Jr., MD, PhD 4\n1 Department of Radiology, New York University School of Medicine,\nNew York, New York\n2 University of Maryland School of Medicine, Baltimore, Maryland\n3 Zucker School of Medicine at Hofstra/Northwell, Manhasset, New York\n4 Department of Radiology, University of Illinois College of Medicine,\nChicago, Illinois\nSemin Intervent Radiol 2023;40:544 –548\nAddress for correspondence Charles E. Ray, Jr., MD, PhD, Department\nof Radiology, University of Illinois at Chicago, 1740 W. Taylor Street,\nMC 391, Chicago, IL 60612 (e-mail: chray@uic.edu).\nEndometriosis is a chronic, in flammatory gynecological\ncondition de fined by the presence of endometrial-like\nepithelium and/or stroma outside of the uterus ( ►Fig. 1 ).\nEndometriosis exists on a spectrum of presentations and can\nbe further classi fied by location into super ficial peritoneal\n(lesions involving the peritoneal surface), ovarian (formation\nof endometriomas or “chocolate cysts ” on the ovaries typi-\ncally containing ectopic tissue and bloody fluid), deep (nod-\nular implantation of tissue into the peritoneal surface with\nassociate fibrosis), extra-abdominal (outside the abdomen),\nand iatrogenic (dissemination of endometrium following\nsurgery).\n1 The clinical presentation of endometriosis is vari-\nable, and depends on the subtype of endometriosis and\nlocation(s) of involvement. While up to 20 to 25% of patients\nare asymptomatic, common clinical features include chronic\npelvic pain which worsens prior to the onset of menses,\ndysmenorrhea, dyspareunia, and infertility.\n2,3 Despite its\nstrong link to infertility in women, the pathophysiology of\nendometriosis remains poorly understood. Postulated to be a\ncombination of the development of a pro-invasive in flam-\nmatory milieu by endometrial cells and retrograde flux of\nendometrial tissue through the fallopian tubes into and\nbeyond the endometrial cavity, there remains a lack of\nconsensus regarding the etiology of endometriosis.\n1 Further-\nmore, this explanation does not account for the disparity\nbetween women with retrograde flo w ,s e e ni nu pt o9 0 %o f\nwomen, and the eventual development of endometriosis.\n4\nWith studies approximating the prevalence of endometriosis\nbetween 25 and 50% in infertile women, optimization of\nobstetric outcomes is a priority among patients seeking\ntreatment.3 While surgical outcomes typically improve\nsymptoms and increase the pregnancy rate, they come\nwith appreciable risk of damage to the ovaries and dimin-\nished ovarian reserve. 5 Given the signi ficant morbidity and\nimpairment in fertility associated with endometriosis, its\nexamination as a clinical entity, as well as the limitations and\nadvantages in its treatment, is warranted.\nEpidemiology\nEndometriosis most commonly affects individuals aged 18 to\n45 years, and is associated with several risk and protective\nfactors.6 Factors associated with increased risk include fami-\nly history, taller height, shorter menstrual cycle length,\nearlier age at menarche, alcohol use, and caffeine intake. 6\nInterestingly, protective factors include smoking, higher\nbody mass index, regular exercise, oral contraceptive use,\nand higher intake of omega 3 fatty acids. 6 The incidence and\nprevalence of endometriosis are poorly understood, largely\ngiven the signi ficant proportion of asymptomatic patients,\nheterogeneity in its classi fication within literature, and\nbarriers to its diagnosis. As such, the range reported in\nliterature greatly varies with prior meta-analyses noting a\nprevalence range from 0.2 to 71.4% depending on the popu-\nlation sampled, and current studies re flecting a stable prev-\nalence rate across the past 30 years.\n7 There remains a lack of\nconsensus on the trajectory of incidence, with estimates\nranging from a 1.6% increase in incidence to a 61% decrease\novertime (116 per 100,000 women in the 1980s to 45 per\n100,000 in the 2010s). 8–13 This disagreement within litera-\nture can be largely attributed to the signi ficant challenges in\ndiagnosis of endometriosis, and the average delay between\nclinical presentation and diagnosis in symptomatic patients.\nDiagnosis\nFor a con firmatory diagnosis of endometriosis, laparoscopic\ninspection with histologic con firmation is the gold stan-\ndard.14 However, the diagnosis of endometriosis is typically\nstep-wise, with the decision to pursue laparoscopy aided by\nclinical presentation and imaging. Clinical suspicion typical-\nly arises in patients with a constellation of symptoms,\nnamely dysuria, chronic pelvic pain, and dyspareunia, and\nin patients with infertility issues and inconclusive workup\nbased on history and physical.\n14 The most common physical\nIssue Theme Liver Cancer (Part 1);\nGuest Editor, Donna L. D ’Souza, MD\n© 2023. Thieme. All rights reserved.\nThieme Medical Publishers, Inc.,\n333 Seventh Avenue, 18th Floor,\nNew York, NY 10001, USA\nDOI https://doi.org/\n10.1055/s-0043-1777748.\nISSN 0739-9529.\nClinical Corner544\nThis document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.\nArticle published online: 2024-01-24\n\nexam findings are visible blue, red, or hemorrhagic nodules\non the vagina or cervix, posterior vaginal fornix tenderness,\nand uterine motion tenderness.\n15 Transvaginal ultrasound is\nconsidered an appropriate initial imaging modality for en-\ndometriosis, with lesions varying in presentation based on\ntheir locations and internal contents.\n16 Typically, lesions\nappear as uni-/multilocular cysts with ground-glass echo-\ngenicity, and are avascular on color Doppler ultrasonogra-\nphy. Magnetic resonance imaging (MRI) is used as a second-\nline diagnostic modality for further characterization of\nlesions identi fied on ultrasound, in patients with high clini-\ncal suspicion who have not yet received imaging or those\nwho opt against laparoscopic intervention. Sensitivity and\nspecificity of ultrasound in the detection of endometriosis\nvaries based on the subtype of endometriosis and approach\nutilized. A transvaginal approach has a sensitivity and spec -\nificity of 62 to 73% and 67 to 93%, respectively, for endome-\ntriosis diagnosis.\n17,18 Across subtypes of endometriosis, MRI\nhas superior sensitivity and speci ficity when compared with\nultrasound in the detection or exclusion of endometriosis. 19\nEndometriosis is typically classi fied into four stages, as\nper the American Society for Reproductive Medicine\n(rASRM). The rASRM classi fication segments patients into\nfour groups, stage 1 (minimal), stage 2 (mild), stage 3\n(moderate), stage 4 (severe). Patients are classi fied by taking\ninto account the presence of posterior cul-de-sac oblitera-\ntion, location and site of implants, density of adhesions, and\nlocation of adhesions.\n20,21\nExisting Treatment Modalities\nEndometriosis management depends on severity of symp-\ntoms and can be strati fied based on decision to pursue\nmedical versus interventional management, and on the goals\nof the patient themselves. In patients primarily managing\npain with no efforts to conceive, NSAIDs, combined hormonal\ncontraceptives, dienogest, medroxyprogesterone acetate,\nand levonorgestrel intrauterine device implantation are\nconsidered first-line treatment.\n22–26 Second-line therapies\nused are GnRH agonists such as leuprolide acetate, GnRH\nantagonists such as elagolix, and aromatase inhibitors. 22–24\nIn those seeking to conceive, literature has shown a\nbenefit in removing endometrial implants on fertility out-\ncomes when compared with symptomatic management. In\ngeneral, laparoscopic resection and ablation have been show\nto result in higher rates of conception when compared\nagainst laparotomy.\n27,28 Patients in stage 1 and stage 2\nendometriosis with a history of infertility may experience\nincreased conception rates, /C24 8.6% greater when compared\nwith no intervention, in the year following surgery.\n29,30 For\nmoderate to severe disease, or in patients with “deep”\nendometriosis, expectant management has been shown to\nhave pregnancy rates as low as 33% in stage 3 and 0% in stage\n4. In these patients, laparoscopic resection has been shown\nto improve pregnancy rates between 57 and 69% and 52 and\n68% for stage 3 and 4 patients, respectively.\n31 In those\nuninterested in preserving fertility, hysterectomy with\noophorectomy may be considered de finitive surgical\ntreatment.\nRationale for Endovascular Therapy\nWhile laparoscopy is considered the first-line option for\noptimizing fertility in patients with endometriosis, surgical\nintervention has been shown to have drawbacks as well,\nnamely with respect to impact on functional ovarian reserve\nin patients with endometriomas. Anti-mullerian hormone\n(AMH), expressed by granulosa cells of actively growing\nfollicles, is supported as a reliable and useful marker of\novarian reserve.\n32 While laparoscopy has been shown as a\npromising treatment for managing pain and improving\nfertility outcomes, it comes with an appreciable risk of\nimpacting ovarian reserve in patients with endometriomas.\nWhile the exact pathogenic mechanisms underpinning the\nFig. 1 Endometriosis is a chronic, in flammatory gynecological condition marked by the growth of endometrial-like epithelium and/or stroma\noutside of the uterus. Endometriotic lesions located within the ovary are referred to as endometriomas.\nSeminars in Interventional Radiology Vol. 40 No. 6/2023 © 2023. Thieme. All rights reserved.\nEndometriosis Agnihotri et al. 545\nThis document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.\n\n\ndecline of ovarian reserve remain to be delineated, it is\nbelieved that stripping of the cyst wall may result in collat-\neral damage to functional ovarian tissue, with potential loss\nof follicles.\n32 In addition to impacting ovarian reserve, lapa-\nroscopy may lead to additional morbidity in patients. Endo-\nvascular interventions offer several bene fits, leading to\ndecrease in the following parameters: surgical complications\n(i.e., adhesions), postoperative pain, blood loss, infection risk,\npostoperative admission length, and hospital costs.\n33 In\nhigher surgical risk candidates, sclerotherapy may offer\nfurther bene fits. As endometriosis is typically a recurrent\ncondition, endovascular treatments are not limited by adhe-\nsions from prior surgical intervention, as long as there is\nsufficient visualization of a given lesion. 34\nBrief Description of Technique\nInterventional radiology (IR) offers promising treatments for\npatients with endometriosis. While there is a paucity of\nliterature investigating the use of IR techniques in the\ntreatment of deep or diffuse super ficial endometriosis, there\nhas been considerable examination of the use of needle-\ndirected (NDS) and catheter-directed sclerotherapy (CDS) in\nthe treatment of endometriomas. Prior to CDS treatment,\nMRI is typically performed for patients using axial and\nsagittal fast spin echo T2-weighted images and contrast-\nenhanced T1-weighted images.\n34 During the procedure, a\ntransabdominal ultrasonographic approach is used in\npatients who can be successfully accessed with no interfering\nstructures between the abdominal wall and the lesion. In\nmost cases, procedures are performed with transvaginal\naccess. Ultrasound probes with in-plane needle guidance\nadaptors are placed following sterilization of the surgical\nsite. Typically, 16- or 18-gauge needles with length of/C24 20 cm\nare directed transabdominally or transvaginally toward\nlesions. Following lesion puncture, a guidewire is typically\ninserted under fluoroscopic guidance through the needle,\nwith exchange for a pigtail catheter. Endometrial contents\nare aspirated vigorously following catheter placement. To\navoid sclerosant leakage into the peritoneum, cyst rupture is\nexcluded through contrast injection into the lesion and\nsubsequent visualization. Following exclusion of rupture,\nthe pigtail catheter is clamped and varying concentrations\nof sclerosant (ethanol, methotrexate, tetracycline) are\ninjected into the cyst and are either retained there (in situ\nmethod) or washed out following a time interval (typically\n5–20 minutes).\n35 Of note, prior studies have shown an\nappreciable decrease in rate of recurrence with longer rates\nof incubation of sclerosant prior to wash out. 35–37 NDS is\nsimilar to CDS apart from the use of a needle, as compared\nwith a pigtail drainage catheter, for the aspiration and\ndrainage of endometrioma content.\nOutcomes of Puncture Sclerotherapy for\nEndometriomas\nAs mentioned earlier, despite the limited availability of\nevidence for the use of sclerotherapy in deep endometriosis,\nthere is a stronger base of literature for its use in endome-\ntriomas. To accurately characterize bene fit, a look at ovarian\nreserve, recurrence rate, pregnancy rate, and pain manage-\nment can be used as a way to quantify interventional bene fit.\nWith respect to ovarian reserve, studies have typically\nexamined AMH decrement postoperatively after sclerothera-\npy. In one prospective study of 56 patients, investigators found\nsimilar levels of AMH between sclerotherapy (n ¼ 31) and prior\ncystectomy (n ¼ 26; 2.20 vs. 1.09) in patients undergoing in\nvitro fertilization (IVF).38,39 The second study retrospectively\nanalyzed 71 patients, showing that patients with AMH had no\nappreciable decrease in AMH levels (2.3 –2.6 ng/mL) when\ncompared 6 months postprocedure, while patients in the\ncystectomy group did (3.0 –1.6 ng/mL, p < 0.05). When com-\npared against no intervention, sclerotherapy offers the poten-\ntial for improved pregnancy outcomes with minimal risk\ntoward the depletion of functional ovarian tissue.\nAmong three studies examining recurrence rate between\nsclerotherapy and cystectomy, the two aforementioned\nstudies examining ovarian reserve found no appreciable\ndifference in recurrence between sclerotherapy and cystec -\ntomy.\n34,38,39 In the remaining study, a prospective cross-\nsectional study (n ¼ 101), patients in the sclerotherapy group\n(n ¼ 44) were noted to have a higher recurrence rate than the\ncystectomy group ( n ¼ 57; 34.1 vs. 14.0%). 40 Of note, this\nstudy had a follow-up time of 7 years, which investigators\nattributed as a likely cause of their discrepant findings.\n40\nWith respect to spontaneous pregnancy rate, a prior\nmentioned prospective study in 56 patients undergoing\nIVF found a cumulative pregnancy rate of 55.2 versus\n26.9% ( p ¼ 0.03) when compared with patients undergoing\nIVF with prior cystectomy. While there remains a lack of\nadditional comparative studies, studies have shown a benefit\nto sclerotherapy versus no intervention in the improvement\nof fertility outcomes in patients with endometriomas.\n41,42\nPain management is important to consider in patients\nwith endometriosis, as palliation may be the key priority in\nindividuals not actively trying to conceive. A Cochrane\nanalysis examining randomized controlled studies, cohort\nstudies, and case –control studies of endometrial cyst sclero-\ntherapy noted a range of improvement between 68 and 96%\nin pain symptoms in ethanol sclerotherapy, and 80% after\nmethotrexate sclerotherapy.\n35 Furthermore, when compar-\ning in situ versus washing techniques for treating endome-\ntriomas, there existed no differences in pain reduction. 35\nEndometrioma sclerotherapy is a relatively safe proce-\ndure with multiple studies reporting a 0% complication rate\nwith patients. 34,40,42 The most frequent complication\nreported in literature is abdominal pain due to ethanol\nleakage into the peritoneum, although symptoms typically\nresolve shortly thereafter. On aggregate, sclerotherapy has\nbeen reported as a safe procedure with minimal incidence of\ncomplications noted in literature.\nConclusion\nSclerotherapy offers a promising approach for patients who\nwish to pursue fertility, have low ovarian reserve, and are\nSeminars in Interventional Radiology Vol. 40 No. 6/2023 © 2023. Thieme. All rights reserved.\nEndometriosis Agnihotri et al.546\nThis document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.\n\n\ncontraindicated from or choose not to pursue more invasive\ninterventions. While there remains variability within studies\nassessing the impact of sclerotherapy on patient outcomes,\nthere appears to be a growing body of literature validating its\nuse in the management of patients seeking treatment.\nAdditionally, the targeted focus on endometriomas due, in\npart, to the inability of sclerotherapy to treat deep endome-\ntriosis hinders the generalizability of current literature\ntoward patients with endometriosis at large. Nonetheless,\ngiven the promising data thus far, further evaluation of\nsclerotherapy in additional subtypes of endometriosis is\nwarranted.\nConflict of Interest\nNone declared.\nAcknowledgment\nNone.\nReferences\n1 Horne AW, Missmer SA. Pathophysiology, diagnosis, and manage-\nment of endometriosis. BMJ 2022;379:e070750\n2 Agarwal SK, Chapron C, Giudice LC, et al. Clinical diagnosis of\nendometriosis: a call to action. Am J Obstet Gynecol 2019;220\n(04):354.e1–354.e12\n3 Bulletti C, Coccia ME, Battistoni S, Borini A. 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J Obstet Gynecol India 2015;65(01):11 –16\n31 Dunselman GAJ, Vermeulen N, Becker C, et al; European Society of\nHuman Reproduction and Embryology. ESHRE guideline: man-\nagement of women with endometriosis. Hum Reprod 2014;29\n(03):400–412\n32 Somigliana E, Berlanda N, Benaglia L, Viganò P, Vercellini P, Fedele\nL. Surgical excision of endometriomas and ovarian reserve: a\nsystematic review on serum antimüllerian hormone level mod-\nifications. Fertil Steril 2012;98(06):1531 –1538\n33 Ghasemi Tehrani H, Tavakoli R, Hashemi M, Haghighat S. Ethanol\nsclerotherapy versus laparoscopic surgery in management of\novarian endometrioma; a randomized clinical trial. Arch Acad\nEmerg Med 2022;10(01):e55\n34 Koo JH, Lee I, Han K, et al. Comparison of the therapeutic ef ficacy\nand ovarian reserve between catheter-directed sclerotherapy and\nsurgical excision for ovarian endometrioma. Eur Radiol 2021;31\n(01):543–548\n35 Cohen A, Almog B, Tulandi T. Sclerotherapy in the management of\novarian endometrioma: systematic review and meta-analysis.\nFertil Steril 2017;108(01):117 –124.e5\n36 Noma J, Yoshida N. Ef ficacy of ethanol sclerotherapy for ovarian\nendometriomas. Int J Gynaecol Obstet 2001;72(01):35 –39\nSeminars in Interventional Radiology Vol. 40 No. 6/2023 © 2023. Thieme. All rights reserved.\nEndometriosis Agnihotri et al. 547\nThis document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.\n\n\n37 Wang LL, Dong XQ, Shao XH, Wang SM. Ultrasound-guided\ninterventional therapy for recurrent ovarian chocolate cysts.\nUltrasound Med Biol 2011;37(10):1596 –1602\n38 Jee BC. Efficacy of ablation and sclerotherapy for the management\nof ovarian endometrioma: a narrative review. Clin Exp Reprod\nMed 2022;49(02):76 –86\n39 Yazbeck C, Madelenat P, Ayel JP, et al. Ethanol sclerotherapy: a\ntreatment option for ovarian endometriomas before ovarian\nstimulation. Reprod Biomed Online 2009;19(01):121 –125\n40 Alborzi S, Askary E, Keramati P, et al. Assisted reproductive\ntechnique outcomes in patients with endometrioma undergoing\nsclerotherapy vs laparoscopic cystectomy: prospective cross-\nsectional study. Reprod Med Biol 2021;20(03):313 –320\n41 Lee KH, Kim CH, Lee YJ, Kim SH, Chae HD, Kang BM.\nSurgical resection or aspiration with ethanol sclerotherapy\nof endometrioma before in vitro fertilization in infertile\nwomen with endometrioma. Obstet Gynecol Sci 2014;57\n(04):297 –303\n42 Aflatoonian A, Rahmani E, Rahsepar M. Assessing the ef ficacy of\naspiration and ethanol injection in recurrent endometrioma\nbefore IVF cycle: a randomized clinical trial. Iran J Reprod Med\n2013;11(03):179–184\nSeminars in Interventional Radiology Vol. 40 No. 6/2023 © 2023. Thieme. All rights reserved.\nEndometriosis Agnihotri et al.548\nThis document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.","source_license":"public-domain-us","license_restricted":false}