{"paper_id":"97016198-b5be-4bc2-9011-2a4276e45256","body_text":"IN THIS  \nARTICLE\nCASE Painful, heavy menstruation and recur-\nrent pregnancy loss \nA 37-year-old woman (G3P0030) with a history \nof recurrent pregnancy loss presents for evalu -\nation. She had 3 losses—most recently a mis -\ncarriage at 22 weeks with a cerclage in place. \nShe did not undergo any surgical procedures \nfor these losses. Hormonal and thrombophilia \nworkup is negative and semen analysis is nor -\nmal. She reports a history of painful, heavy \nperiods for many years, as well as dyspareunia \nand occasional post-coital bleeding. Past medi-\ncal history was otherwise unremarkable. Pelvic \nmagnetic resonance imaging (MRI) revealed \nfocal thickening of the junctional zone up to 15 \nmm with 2 foci of T2 hyperintensities suggest -\ning adenomyosis (FIGURE 1, page 36). \nHow do you counsel this patient regarding \nthe MRI findings and their impact on her fertility?\nA\ndenomyosis is a condition in which \nendometrial glands and stroma are \nabnormally present in the uterine \nmyometrium, resulting in smooth muscle \nhypertrophy and abnormal uterine con -\ntractility. Traditional teaching describes a \nwoman in her 40s with heavy and painful \nmenses, a “boggy uterus” on examination, \nwho has completed childbearing and desires \ndefinitive treatment. Histologic diagnosis of \nadenomyosis is made from the uterine speci-\nmen at the time of hysterectomy, invariably \nconfounding our understanding of the epide-\nmiology of adenomyosis. \nMore recently, however, we are begin -\nning to learn that this narrative is misguided. \nImaging changes of adenomyosis can be \nseen in women who desire future fertility and \nin adolescents with severe dysmenorrhea, \nsuggesting an earlier age of incidence. 1 In a \nrecent systematic review, prevalence esti -\nmates ranged from 15% to 67%, owing to vary-\ning diagnostic methods and patient inclusion \ncriteria.2 It is increasingly being recognized \nAnatomy of the \nmyometrium\npage 35\nUltrasound \nindications\npage 39\nClinical \npresentation\npage 39\nDr. Haber is Fellow, Minimally Invasive \nGynecologic Surgery, Women’s \nHealth Center, Newton-Wellesley \nHospital, Newton, Massachusetts. \nDr. Fitzgerald is Resident, Department of \nObstetrics and Gynecology, Brigham and \nWomen’s Hospital, Boston, Massachusetts. \nDr. Isaacson is Associate Professor \nand Director of Minimally Invasive \nGynecologic Surgery, Women’s Health \nCenter, Newton-Wellesley Hospital. \nThe authors report no financial relationships relevant to  \nthis article.\ndoi: 10.12788/obgm.0303\n34  OBG Management  |  August 2023  |  Vol. 35  No. 8  mdedge.com/obgyn\nAdenomyosis: Why we need  \nto reassess our understanding  \nof this condition \nCould more instances of pregnancy loss and infertility be due to \nadenomyosis? The authors examine this condition, offering current \nprevalence estimates, pathology, and diagnosis. \nHilary R. Haber, MD; Allison C. Fitzgerald, MD; Keith B. Isaacson, MD\n\nmdedge.com/obgyn  Vol. 35  No. 8  |  August 2023  |  OBG Management   35\nas a primary contributor to infertility, with  \none study estimating a 30% prevalence of \ninfertility in women with adenomyosis.3 More-\nover, treatment with gonadotropin-releasing  \nhormone agonists and/or surgical excision \nmay improve fertility outcomes.4\nAs we learn more about this prevalent \nand life-altering condition, we owe it to our \npatients to consider this diagnosis when \ncounseling on dysmenorrhea, heavy men -\nstrual bleeding, or infertility.\nAnatomy of the myometrium\nThe myometrium is composed of the \ninner and outer myometrium: the inner  \nmyometrium (IM) and endometrium are of \nMüllerian origin, and the outer myometrium \n(OM) is of mesenchymal origin. The IM thick-\nens in response to steroid hormones during \nthe menstrual cycle with metaplasia of endo-\nmetrial stromal cells into myocytes and back \nagain, whereas the OM is not responsive to \nhormones.5 Emerging literature suggests \nthe OM is further divided into a middle and \nouter section based on different histologic \nmorphologies, though the clinical implica -\ntions of this are not understood. 6 The term \n“junctional zone” (JZ) refers to the imaging \nappearance of what is thought to be the IM. \nInterestingly it cannot be identified on tradi -\ntional hematoxylin and eosin staining. When \nILLUSTRATION: KIMBERLY MARTENS FOR OBG MANAGEMENT\n\n36  OBG Management  |  August 2023  |  Vol. 35  No. 8  mdedge.com/obgyn\nAdenomyosis: Why we need to reassess our understanding \nthe JZ is thickened or demonstrates irregular \nborders, it is used as a diagnostic marker for \nadenomyosis and is postulated to play an \nimportant role in adenomyosis pathophysi -\nology, particularly heavy menstrual bleeding \nand infertility.7\nSubtypes of adenomyosis\nWhile various disease classifications have \nbeen suggested for adenomyosis, to date \nthere is no international consensus. Adeno -\nmyosis is typically described in 3 forms: dif -\nfuse, focal, or adenomyoma. 8 As implied, the \nterm focal adenomyosis refers to discrete \nlesions surrounded by normal myome -\ntrium, whereas abnormal glandular changes \nare pervasive throughout the myometrium \nin diffuse disease. Adenomyomas are a  \nsubgroup of focal adenomyosis that are \nthought to be surrounded by leiomyomatous  \nsmooth muscle and may be well demarcated  \non imaging.9\nRecent research uses novel histologic \nimaging techniques to explore adenomyotic \ngrowth patterns in 3-dimensional (3D) recon-\nstructions. Combining tissue-clearing meth -\nods with light-sheet fluorescence microscopy \nenables highly detailed 3D representations \nof the protein and nucleic acid structure of \norgans.10 For example, Yamaguchi and col -\nleagues used this technology to explore the \n3D morphological features of adenomyotic \ntissue and observed direct invasion of the \nendometrial glands into the myometrium \nand an “ant colony ̶ like network” of ecto -\npic endometrial glands in the myometrium  \n(FIGURE 2 ).11 These abnormal glandular net -\nworks have been visualized beyond the IM, \nwhich may not be captured on ultrasonog -\nraphy or MRI. While this work is still in its \ninfancy, it has the potential to provide impor-\ntant insight into disease pathogenesis and to \ninform future therapy.\nPathogenesis\nProposed mechanisms for the development \nof adenomyosis include endometrial inva -\nsion, tissue injury and repair (TIAR) mecha -\nnisms, and the stem cell theory. 12 According \nto the endometrial invasion theory, glan -\ndular epithelial cells from the basalis layer \ninvaginate through an altered IM, slipping \nthrough weak muscle fibers and attracted by \ncertain growth factors. In the TIAR mecha -\nnism theory, micro- or macro-trauma to the \nIM (whether from pregnancy, surgery, or \ninfection) results in chronic proliferation and \ninflammation leading to the development of \nadenomyosis. Finally, the stem cell theory \nproposes that adenomyosis might develop \nfrom de novo ectopic endometrial tissue. \nWhile the exact pathogenesis of adeno -\nmyosis is largely unknown, it has been asso -\nciated with predictable molecular changes \nin the endometrium and surrounding myo -\nmetrium.12 Myometrial hypercontractility \nis seen in patients with adenomyosis and \ndysmenorrhea, whereas neovascularization, \nhigh microvessel density, and abnormal \nFIGURE 1  Adenomyosis on pelvic MRI\nSagittal T2-weighted pelvic magnetic resonance image showing thickened \njunctional zone up to 15 mm (blue marker) and 2 foci of adenomyosis in the \nanterior uterine body (yellow arrows).\n\nmdedge.com/obgyn  Vol. 35  No. 8  |  August 2023  |  OBG Management   37\nuterine contractility are seen in those with \nabnormal uterine bleeding. 13 In patients \nwith infertility, increased inflammation, \nabnormal endometrial receptivity, and \nalterations in the myometrial architecture \nhave been suggested to impair contractility \nand sperm transport. 12,14 \nDifferential growth factor expression and \nabnormal estrogen and progesterone signal -\ning pathways have been observed in the IM \nin patients with adenomyosis, along with dys-\nregulation of immune factors and increased \ninflammatory oxidative stress. 12 This in turn \nresults in myometrial hypertrophy and fibro -\nsis, impairing normal uterine contractility \npatterns. This abnormal contractility may \nalter sperm transport and embryo implanta -\ntion, and animal models that target pathways \nleading to fibrosis may improve endometrial \nreceptivity.14,15 Further research is needed to \nelucidate specific molecular pathways and \ntheir complex interplay in this disease.\nDiagnosis\nThe gold standard for diagnosis of adeno -\nmyosis is histopathology from hysterectomy \nspecimens, but specific definitions vary. Pub-\nlished criteria include endometrial glands \nwithin the myometrial layer greater than  \n0.5 to 1 low power field from the basal layer \nof the endometrium, endometrial glands \nextending deeper than 25% of the myome -\ntrial thickness, or endometrial glands a cer -\ntain distance (ranging from 1-3 mm) from \nthe basalis layer of the endometrium. 16 Vari-\nous methods of non -hysterectomy tissue \nsampling have been proposed for diagnosis, \nincluding needle, hysteroscopic, or laparo -\nscopic sampling, but the sensitivity of these \nmethods is poor. 17 Limiting the diagnosis of \nadenomyosis to specimen pathology relies on \ninvasive methods and clearly we cannot con-\nfirm the diagnosis by hysterectomy in patients \nwith a desire for future fertility. It is for this \nreason that the prevalence of the disease is  \nwidely unknown. \nThe alternative to pathologic diagnosis is \nto identify radiologic changes that are associ-\nated with adenomyosis via either transvaginal \nultrasound (TVUS) or MRI. Features sug -\ngestive of adenomyosis on MRI overlap with \nTVUS features, including uterine enlarge -\nment, anteroposterior myometrial asymme -\ntry, T1- or T2-intense myometrial cysts or \nfoci, and a thickened JZ. 18 A JZ thicker than  \n12 mm has been thought to be predictive of \nadenomyosis, whereas a thickness of less than \n8 mm is predictive of its absence, although \nthe JZ may vary in thickness with the men -\nstrual cycle.19,20 A 2021 systematic review and \nmeta-analysis comparing MRI diagnosis with \nhistopathologic findings reported a pooled \nsensitivity and specificity of 60% and 96%, \nrespectively.21 The reported range for sensi -\ntivity and specificity is wide: 70% to 93% for \nsensitivity and 67% to 93% for specificity.22-24 \nKey TVUS features associated with ade-\nnomyosis were defined in 2015 in a consensus \nstatement released by the Morphological Uterus \nFIGURE 2  3D depiction of adenomyosis11\n3-dimensional depiction of adenomyosis using novel tissue-clearing methods \nwith light-sheet microscopy. Red object shows direct invasion of endometrial \nglands into the myometrium. Yellow objects show ectopic endometrial glands \nin the myometrium.\nReproduced with permission from Yamaguchi M, et al. Three-dimensional understanding of the \nmorphological complexity of the human uterine endometrium. iScience. 2021;24:102258. doi: 10.1016/j.\nisci.2021.10225811 \n\n38  OBG Management  |  August 2023  |  Vol. 35  No. 8  mdedge.com/obgyn\nAdenomyosis: Why we need to reassess our understanding \nSonographic Assessment (MUSA) group. 25 \nThese include a globally enlarged uterus, \nanteroposterior myometrial asymmetry, myo-\nmetrial cysts, fan-shaped shadowing, mixed \nmyometrial echogenicity, translesional vas -\ncularity, echogenic subendometrial lines and \nbuds, and a thickened, irregular or discontinu-\nous JZ (FIGURES 3 AND 4 ).25 The accuracy of \nultrasonographic diagnosis of adenomyosis \nusing these features has been investigated in \nmultiple systematic reviews and meta-analy-\nses, most recently by Liu and colleagues who \nfound a pooled sensitivity of TVUS of 81% and \npooled specificity of 87%.23 The range for ultra-\nsonographic sensitivity and specificity is wide, \nhowever, ranging from 33% to 84% for sensitiv-\nity and 64% to 100% for specificity. 22 Consen-\nsus is lacking as to which TVUS features are \nmost predictive of adenomyosis, but in general, \nthe combination of multiple MUSA criteria  \n(particularly myometrial cysts and irregular JZ \non 3D imaging) appears to be more accurate \nthan any one feature alone.23 The presence of \nfibroids may decrease the sensitivity of TVUS, \nand one study suggested elastography may \nincrease the accuracy of TVUS. 24,26 Moreover, \ngiven that most radiologists receive limited train-\ning on the MUSA criteria, it behooves gynecolo-\ngists to become familiar with these sonographic \nfeatures to be able to identify adenomyosis in  \nour patients. \nAdenomyosis also may be suspected \nbased on hysteroscopic findings,  \nalthough a normal hysteroscopy cannot rule \nout the disease and data are lacking to sup -\nport these markers as diagnostic. Visual \nfindings can include a “strawberry” pat -\ntern, mucosal elevation, cystic hemorrhagic \nlesions, localized vascularity, or endometrial \ndefects.27 Hysteroscopy may be effective in \nFIGURE 3  Adenomyosis on ultrasound\nUltrasound findings associated with adenomyosis, as defined by the Morphological Uterus Sonographic Assessment consensus. \nFindings include (A) asymmetrical myometrial thickening; (B) myometrial cysts; (C) hyperechoic myometrial islands; (D) fan-shaped \nshadowing; (E) echogenic subendometrial lines and buds; (F) translesional vascularity; (G) irregular junctional zone; (H) interrupted \njunctional zone; (I) enlarged uterus (not shown); and (J) heterogenous myometrial echotexture (not shown). \nAdapted with permission from Van den Bosch T, et al. Terms, definitions and measurements to describe sonographic features of myometrium and uterine masses: a consensus \nopinion from the Morphological Uterus Sonographic Assessment (MUSA) group. Ultrasound Obstet Gynecol. 2015;46:284-298. doi: 10.1002/uog.1480625\nA\nE\nC\nG\nB\nF\nD\nH\n\nmdedge.com/obgyn  Vol. 35  No. 8  |  August 2023  |  OBG Management   39\nthe treatment of localized lesions, although \nthat discussion is beyond the scope of  \nthis review.\nClinical presentation\nWhile many women who are later diagnosed \nwith adenomyosis are asymptomatic, the \ndisease can present with heavy menstrual \nbleeding and dysmenorrhea, which occur in \n50% and 30% of patients, respectively.28 Other \nsymptoms include dyspareunia and infer -\ntility. Symptoms were previously reported \nto develop between the ages of 40 and  \n50 years; however, this is biased by diagnosis \nat the time of hysterectomy and the fact that \nyounger patients are less likely to undergo \ndefinitive surgery. When using imaging crite-\nria for diagnosis, adenomyosis might be more \nresponsible for dysmenorrhea and chronic \npelvic pain in younger patients than previ -\nously appreciated.1,29 In a recent study review-\ning TVUS in 270 adolescents for any reason, \nadenomyosis was present in 5% of cases and \nthis increased up to 44% in the presence  \nof endometriosis.30\nAdenomyosis often co-exists and shares \nsimilar clinical presentations with other \ngynecologic pathologies such as endome -\ntriosis and fibroids, making diagnosis on \nsymptomatology alone challenging. Con -\ncurrent adenomyosis has been found in up \nto 73% and 57% of patients with suspected \nor diagnosed endometriosis and fibroids, \nrespectively.31,32 Accumulating evidence sug -\ngests that pelvic pain previously attributed \nto endometriosis may in fact be a result of \nadenomyosis; for example, persistent pelvic \npain after optimal resection of endometrio -\nsis may be confounded by the presence of \nadenomyosis.29 In one study of 155 patients \nwith complete resection of deep infiltrating \nendometriosis, persistent pelvic pain was \nsignificantly associated with the presence of \nadenomyosis on imaging.33\nAdenomyosis is increasingly being rec -\nognized at the time of infertility evalu -\nation with an estimated prevalence of  \nFIGURE 4  Ultrasound indications of adenomyosis25\nUltrasound images showing (A) myometrial cysts (arrows); (B) hyperechogenic islands (surrounded by dotted lines); and (C) echogenic \nspots (arrows). \nAdapted with permission from Van den Bosch T, et al. Terms, definitions and measurements to describe sonographic features of myometrium and uterine masses: a consensus \nopinion from the Morphological Uterus Sonographic Assessment (MUSA) group. Ultrasound Obstet Gynecol. 2015;46:284-298. doi: 10.1002/uog.1480625\nA C\nB\n\n40  OBG Management  |  August 2023  |  Vol. 35  No. 8  mdedge.com/obgyn\nAdenomyosis: Why we need to reassess our understanding \n30% in women with infertility. 3 Among \nwomen with infertility, adenomyosis has been \nassociated with a lower clinical pregnancy \nrate, higher miscarriage rate, and lower live \nbirth rate, as well as obstetric complications \nsuch as abnormal placentation.34-36 A study of  \n37 baboons found the histologic diagnosis \nof adenomyosis alone at necropsy was asso -\nciated with a 20-fold increased risk of life -\nlong infertility (odds ratio [OR], 20.1; 95% CI,  \n2.1-921), whereas presence of endometriosis \nwas associated with a nonsignificant 3-fold \nrisk of lifelong infertility (OR, 3.6; 95% CI,  \n0.9-15.8).37 \nIn women with endometriosis and  \ninfertility, co-existing adenomyosis portends \nworse fertility outcomes. In a retrospective \nstudy of 244 women who underwent endo -\nmetriosis surgery, more than five features \nof adenomyosis on imaging was associated \nwith higher rates of infertility, in vitro fer -\ntilization treatments, and a higher number \nof in vitro fertilization cycles. 31 Moreover, \nin women who underwent surgery for deep \ninfiltrating endometriosis, the presence of \nadenomyosis on imaging was associated \nwith a 68% reduction in likelihood of preg -\nnancy after surgery. 38\nConclusion\nAs we begin to learn about adenomyosis, our \nmisconceptions become more evident. The \nnotion that it largely affects women at the \nend of their reproductive lives is biased by \nusing histopathology at hysterectomy as the \ngold standard for diagnosis. Lack of defini -\ntive histologic or imaging criteria and biopsy \ntechniques add to the diagnostic challenge. \nThis in turn leads to inaccurate estimates \nof incidence and prevalence, as we assume \npatients’ symptoms must be attributable to \nwhat we can see at the time of surgery (for \nexample, Stage I or II endometriosis), rather \nthan what we cannot see. We now know that \nadenomyosis is present in women of all ages, \nincluding adolescents, and can significantly \ncontribute to reduced fertility and quality of \nlife. We owe it to our patients to consider this \ncondition in the differential diagnosis of dys -\nmenorrhea, heavy menstrual bleeding, dys -\npareunia, and infertility.\nCASE Resolved\nThe patient underwent targeted hysteroscopic \nresection of adenomyosis ( FIGURE 5 ) and con-\nceived spontaneously the following year. ●\nReferences\n1. Exacoustos C, Lazzeri L, Martire FG, et al. Ultrasound \nfindings of adenomyosis in adolescents: type and grade of the \ndisease. J Minim Invasive Gynecol. 2021;29:291.e1-299.e1.  \ndoi: 10.1016/j.jmig.2021.08.023\n2. Loring M, Chen TY, Isaacson KB. A systematic review of \nadenomyosis: it is time to reassess what we thought we knew \nabout the disease.  J Minim Invasive Gynecol.  2021;28:644-\n655. doi: 10.1016/j.jmig.2020.10.012\n3. Bourdon M, Santulli P , Oliveira J, et al. Focal adenomyosis \nis associated with primary infertility. Fertil Steril. \n2020;114:1271-1277. doi: 10.1016/j.fertnstert.2020.06.018\n4. Lan J, Wu Y, Wu Z, et al. Ultra-long GnRH agonist protocol \nduring IVF/ICSI improves pregnancy outcomes in women \nwith adenomyosis: a retrospective cohort study. Front \nFIGURE 5 Hysteroscopic resection of adenomyosis\nStill image from hysteroscopic resection of adenomyosis. Yellow circles \nhighlight foci of adenomyosis as characterized by glandular tissue within  \nthe myometrium.\nImage courtesy of Dr. Keith B. Isaacson\n\nmdedge.com/obgyn  Vol. 35  No. 8  |  August 2023  |  OBG Management   41\nEndocrinol (Lausanne). 2021;12:609771. doi: 10.3389  \n/fendo.2021.609771\n5. Gnecco JS, Brown AT , Kan EL, et al. Physiomimetic models \nof adenomyosis.  Semin Reprod Med.  2020;38:179-196.  \ndoi: 10.1055/s-0040-1719084\n6. Harmsen MJ, Trommelen LM, de Leeuw RA, et al. Uterine \njunctional zone and adenomyosis: comparison of MRI, \ntransvaginal ultrasound and histology. Ultrasound Obstet \nGynecol. 2023;62:42-60. doi: 10.1002/uog.26117\n7. Xie T , Xu X, Yang Y, et al. The role of abnormal uterine junction \nzone in the occurrence and development of adenomyosis. \nReprod Sci. 2022;29:2719-2730. doi: 10.1007/s43032-021  \n-00684-2\n8. Lazzeri L, Morosetti G, Centini G, et al. A sonographic \nclassification of adenomyosis: interobserver reproducibility \nin the evaluation of type and degree of the myometrial \ninvolvement. Fertil Steril. 2018;110:1154-1161.e3. doi: 10.1016 \n/j.fertnstert.2018.06.031\n9. Tahlan A, Nanda A, Mohan H. Uterine adenomyoma: \na clinicopathologic review of 26 cases and a review of \nthe literature. Int J Gynecol Pathol . 2006;25:361-365. doi: \n10.1097/01.pgp.0000209570.08716.b3\n10. Chung K, Wallace J, Kim S- Y, et al. Structural and molecular \ninterrogation of intact biological systems. Nature. \n2013;497:332-337. doi: 10.1038/nature12107\n11. Yamaguchi M, Yoshihara K, Suda K, et al. Three-dimensional \nunderstanding of the morphological complexity of the \nhuman uterine endometrium. iScience. 2021;24:102258.  \ndoi: 10.1016/j.isci.2021.102258\n12. Vannuccini S, Tosti C, Carmona F , et al. Pathogenesis \nof adenomyosis: an update on molecular mechanisms. \nReprod Biomed Online . 2017;35:592-601. doi: 10.1016  \n/j.rbmo.2017.06.016\n13. Zhai J, Vannuccini S, Petraglia F , et al. Adenomyosis: \nmechanisms and pathogenesis. Semin Reprod Med . \n2020;38:129-143. doi: 10.1055/s-0040-1716687\n14. Munro MG. Uterine polyps, adenomyosis, leiomyomas, \nand endometrial receptivity. Fertil Steril. 2019;111:629-640.  \ndoi: 10.1016/j.fertnstert.2019.02.008\n15. Kay N, Huang C- Y, Shiu L- Y, et al. TGF- β1 neutralization \nimproves pregnancy outcomes by restoring endometrial \nreceptivity in mice with adenomyosis. Reprod Sci . \n2021;28:877-887. doi: 10.1007/s43032-020-00308-1\n16. Habiba M, Benagiano G. Classifying adenomyosis: \nprogress and challenges. Int J Environ Res Public Health . \n2021;18:12386. doi: 10.3390/ijerph182312386\n17. Movilla P , Morris S, Isaacson K. A systematic review of tissue \nsampling techniques for the diagnosis of adenomyosis.  \nJ Minim Invasive Gynecol . 2020;27:344-351. doi: 10.1016  \n/j.jmig.2019.09.001\n18. Agostinho L, Cruz R, Osório F , et al. MRI for adenomyosis: \na pictorial review. Insights Imaging . 2017;8:549-556.  \ndoi: 10.1007/s13244-017-0576-z\n19. Bazot M, Cortez A, Darai E, et al. Ultrasonography compared \nwith magnetic resonance imaging for the diagnosis of \nadenomyosis: correlation with histopathology. Hum Reprod. \n2001;16:2427-2433. doi: 10.1093/humrep/16.11.2427\n20. Reinhold C, Tafazoli F , Mehio A, et al. Uterine adenomyosis: \nendovaginal US and MR imaging features with histopathologic \ncorrelation. Radiographics. 1999;19:S147-S160. doi: 10.1148  \n/radiographics.19.suppl_1.g99oc13s147\n21. Rees CO, Nederend J, Mischi M, et al. Objective measures \nof adenomyosis on MRI and their diagnostic accuracy—a \nsystematic review & meta-analysis. Acta Obstet Gynecol \nScand. 2021;100:1377-1391.\n22. Chapron C, Vannuccini S, Santulli P , et al. Diagnosing \nadenomyosis: an integrated clinical and imaging approach. \nHum Reprod Update.  2020;26:392-411. doi: 10.1093  \n/humupd/dmz049\n23. Liu L, Li W, Leonardi M, et al. Diagnostic accuracy of \ntransvaginal ultrasound and magnetic resonance imaging \nfor adenomyosis: systematic review and meta-analysis and \nreview of sonographic diagnostic criteria. J Ultrasound Med. \n2021;40:2289-2306. doi: 10.1002/jum.15635\n24. Bazot M, Daraï E. Role of transvaginal sonography and \nmagnetic resonance imaging in the diagnosis of uterine \nadenomyosis. Fertil Steril . 2018;109:389-397. doi: 10.1016  \n/j.fertnstert.2018.01.024\n25. Van den Bosch T , Dueholm M, Leone FPG, et al. Terms, \ndefinitions and measurements to describe sonographic \nfeatures of myometrium and uterine masses: a consensus \nopinion from the Morphological Uterus Sonographic \nAssessment (MUSA) group. Ultrasound Obstet Gynecol . \n2015;46:284-298. doi: 10.1002/uog.14806\n26. Săsăran V , Turdean S, Gliga M, et al. Value of strain-\nratio elastography in the diagnosis and differentiation of \nuterine fibroids and adenomyosis. J Pers Med . 2021;11:824.  \ndoi: 10.3390/jpm11080824\n27. Di Spiezio Sardo A, Calagna G, Santangelo F , et al. The \nrole of hysteroscopy in the diagnosis and treatment \nof adenomyosis. Biomed Res Int . 2017;2017:2518396.  \ndoi: 10.1155/2017/2518396\n28. Azzi R. Adenomyosis: current perspectives. Obstet Gynecol \nClin North Am. 1989;16:221-235.\n29. Parker JD, Leondires M, Sinaii N, et al. Persistence of \ndysmenorrhea and nonmenstrual pain after optimal \nendometriosis surgery may indicate adenomyosis. Fertil \nSteril. 2006;86:711-715. doi: 10.1016/j.fertnstert.2006.01.030\n30. Martire FG, Lazzeri L, Conway F , et al. Adolescence and \nendometriosis: symptoms, ultrasound signs and early \ndiagnosis. Fertil Steril . 2020;114:1049-1057. doi: 10.1016  \n/j.fertnstert.2020.06.012\n31. Decter D, Arbib N, Markovitz H, et al. Sonographic signs of \nadenomyosis in women with endometriosis are associated \nwith infertility. J Clin Med.  2021;10:2355. doi: 10.3390  \n/jcm10112355\n32. Brucker SY, Huebner M, Wallwiener M, et al. Clinical \ncharacteristics indicating adenomyosis coexisting with \nleiomyomas: a retrospective, questionnaire-based \nstudy. Fertil Steril . 2014;101:237-241.e1. doi: 10.1016  \n/j.fertnstert.2013.09.038\n33. Perelló MF , Martínez-Zamora MÁ, Torres X, et al. \nEndometriotic pain is associated with adenomyosis but \nnot with the compartments affected by deep infiltrating \nendometriosis. Gynecol Obstet Invest . 2017;82:240-246.  \ndoi: 10.1159/000447633\n34. Younes G, Tulandi T . Effects of adenomyosis on \nin vitro fertilization treatment outcomes: a meta-\nanalysis. Fertil Steril . 2017;108:483-490.e3. doi: 10.1016  \n/j.fertnstert.2017.06.025\n35. Nirgianakis K, Kalaitzopoulos DR, Schwartz ASK, et al. \nFertility, pregnancy and neonatal outcomes of patients \nwith adenomyosis: a systematic review and meta-analysis. \nReprod BioMed Online . 2021;42:185-206. doi: 10.1016  \n/j.rbmo.2020.09.023\n36. Ono Y, Ota H, Takimoto K, et al. Perinatal outcomes \nassociated with the positional relationship between the \nplacenta and the adenomyosis lesion. J Gynecol Obstet Hum \nReprod. 2021;50:102114. doi: 10.1016/j.jogoh.2021.102114\n37. Barrier BF , Malinowski MJ, Dick EJ Jr, et al. Adenomyosis \nin the baboon is associated with primary infertility. \nFertil Steril . 2004;82(suppl 3):1091-1094. doi: 10.1016  \n/j.fertnstert.2003.11.065\n38. Vercellini P , Consonni D, Barbara G, et al. Adenomyosis and \nreproductive performance after surgery for rectovaginal \nand colorectal endometriosis: a systematic review and \nmeta-analysis. Reprod Biomed Online . 2014;28:704-713.  \ndoi: 10.1016/j.rbmo.2014.02.006","source_license":"CC0","license_restricted":false}