{"paper_id":"e958ad79-eba9-40d9-a236-80192ce3767c","body_text":"Remedy Publications LLC., | http://clinicsinsurgery.com/\nClinics in Surgery\n2021 | Volume 6 | Article 31541\nInvolvement of Adenomyosis in Refractory Abnormal \nUterine Bleeding-Ovulatory Dysfunction: A Case Series\nOPEN ACCESS\n *Correspondence:\nDeng S, Department of Obstetrics and \nGynecology, Peking Union Medical \nCollege Hospital, Chinese Academy \nof Medical Sciences, National Clinical \nResearch Center for Obstetrical and \nGynecological Diseases, Beijing, \nChina,\nE-mail: ds_dengshan@163.com\nReceived Date: 22 Mar 2021\nAccepted Date: 15 Apr 2021\nPublished Date: 30 Apr 2021\nCitation: \nGui T, Deng S, He Y, Xue H. \nInvolvement of Adenomyosis in \nRefractory Abnormal Uterine Bleeding-\nOvulatory Dysfunction: A Case Series. \nClin Surg. 2021; 6: 3154.\nCopyright © 2021 Deng S. This is an \nopen access article distributed under \nthe Creative Commons Attribution \nLicense, which permits unrestricted \nuse, distribution, and reproduction in \nany medium, provided the original work \nis properly cited.\nCase Series\nPublished: 30 Apr, 2021\nAbstract\nObjective: To report six cases of refractory AUB-Ovulatory Dysfunction (AUB-O) diagnosed with \nadenomyosis and to emphasize the clinical significance of adenomyosis in AUB.\nMethods: This was a retrospective study conducted at the Peking Union Medical College Hospital. \nBetween September 2016 and July 2018, six patients with refractory AUB-O were admitted. \nRefractory AUB was defined as insensitivity to hormone therapy after exclusion of endometrial \nmalignancy. Ultrasound, curettage, and pelvic Magnetic Resonance Imaging (MRI) were performed.\nResults: According to MRI, the six patients with AUB-O were classified into either asymmetrical \ninternal adenomyosis or symmetrical internal adenomyosis. In the first group, a diagnosis of \nadenomyosis was made by ultrasonic images of thickened uterine walls with palisade echoes. \nMRI further revealed alveolate foci oppressing the endometrium and protruding into the uterine \ncavity (“Swiss cheese” signs). In the second group, ultrasound and pathological examination did \nnot provide positive findings after hysteroscopy, while MRI presented diffuse thickening of the \njunctional zone over 50% of the thickness of the myometrium, and the diagnosis of adenomyosis \nwas then established. In these cases, GnRHa was the only guaranteed drug to control acute vaginal \nbleeding.\nConclusion: When routine medications are ineffective in the treatment of AUB-O, adenomyosis is \nmost likely the underlying reason, even for patients without dysmenorrhea. Given that adenomyosis \nhas different subtypes, MRI is an optimal method to make a diagnosis and to guide individual \ntreatment, especially for cases in the early stages.\nKeywords: Refractory; Abnormal uterine bleeding; Ovulation dysfunction; Adenomyosis; \nUltrasound; MRI\nGui T1, Deng S1*, He Y2 and Xue H2\n1Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical \nSciences, National Clinical Research Center for Obstetrical and Gynecological Diseases, Beijing, China\n2Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, \nChina\nIntroduction\nAbnormal Uterine Bleeding (AUB) in non-pregnant women of reproductive age is the acute \nor chronic variation from the normal menstrual cycle, including changes in volume, regularity, \nduration, and/or frequency of bleeding [1-4]. AUB affects 9% to 14% of women of reproductive \nage [3]. The PALM-COEIN classification system proposed by the International Federation of \nGynecology and Obstetrics (FIGO) in 2011 is universally accepted to help clinicians and investigators \nin the evaluation, diagnosis, and management of AUB in non-pregnant women of reproductive age \n[1,5]. Structural causes include Polyp (AUB-P), Adenomyosis (AUB-A), Leiomyoma (AUB-L), and \nMalignancy (AUB-M) [6,7].\nAdenomyosis a gynecologic condition characterized by the abnormal presence of endometrial \ntissue within the myometrium and is a structural cause of AUB [1,2,8]. Patients with adenomyosis \noften present with Heavy Menstrual Bleeding (HMB) and dysmenorrhea. Sammour et al. [9] reported \nthat menorrhagia and dysmenorrhea were found in 63% and 40% of patients with adenomyosis, \nrespectively. Nevertheless, in the presence of coexisting lesion such as uterine fibroids and/or \npolyps, the causal effect of adenomyosis in AUB is difficult to prove. Nevertheless, the conservative \npharmacological therapy for AUB-A is usually similar to that for AUB-O [10].\nTreatments aim at managing symptoms and preserving or improving fertility. After preliminary \nassessment, the first-line treatment for patients with AUB caused by ovulation dysfunction (AUB-O) \n\nDeng S, et al., Clinics in Surgery - Gynecological Surgery\nRemedy Publications LLC., | http://clinicsinsurgery.com/\n 2021 | Volume 6 | Article 31542\nis multi-dose oral contraceptives or high-dose progestogens [11-13]. \nNon-hormonal therapy, suitable for women who wish to conceive \nor avoid hormonal side effects, includes anti-fibrinolytics and non-\nsteroidal anti-inflammatory drugs and can reduce menstrual blood \nby up to 50% [8]. Oral or injection progestogens/progestins may be \nused to stop acute heavy bleeding, to manage irregular bleeding, or \nto control the timing of the onset of menstruation, although side \neffects may limit longer term use [8]. The Levonorgestrel releasing \nIntrauterine System (LNG-IUS) has been reported to be more \neffective than other first-line medical options in reducing the impact \nof heavy menstrual bleeding on quality of life [8]. Gonadotrophin \nReleasing Hormone analogs (GnRHa) are known to induce \namenorrhea in up to 90% of women, but side effects may significantly \naffect the quality of life, and clinical use is usually limited to 6 \nmonths. Surgical intervention is indicated when the pharmacological \ntherapy is unsatisfactory [14,15]. Hysteroscopy and histopathological \ndiagnosis are necessary to exclude structural causes [6,7]. In fact, \nthere are occasional cases of refractory AUB to medical treatments. \nUnexplained AUB may be persistent after Dilation and Curettage \n(D&C). It is therefore imperative to further explore the underlying \nreason, since adenomyosis as an underlying causing factor may be \nunderestimated or even ignored.\nTherefore, the aim of the present study was to review and analyze \nthe medical history of six patients with AUB-O, whose common \ncharacteristic was resistance to medical treatment of adequate \ndose. Aside ultrasound and hysteroscopic evaluation or D&C, we \nperformed pelvic Magnetic Resonance Imaging (MRI) in order to \nexplore for pathological clues.\nMaterials and Methods\nStudy design\nThis was a retrospective study conducted at the Peking Union \nMedical College Hospital (PUMCH). The study was approved by \nthe ethics committee of PUMCH. Since all data were de identified, \nwritten informed consent was not necessary due to the retrospective \nnature of the study.\nPatients\nBetween September 2016 and July 2018, six patients with \nrefractory AUB-O were admitted to the Department of Obstetrics and \nGynecology of PUMCH. The patients all presented a combination of \nunpredictable timing of bleeding and variable amount of blood flow \nthat resulted in HMB and anemia, with an average hemoglobin level \nof 70 g/l, ranging from 45 g/l to 109 g/l. Refractory AUB was defined \nas insensitivity to hormone therapy after exclusion of endometrial \nmalignancy [2,8].\nData collection\nPatient data, including age of onset, chief complaint, clinical \nfeatures, imaging findings, treatment modality, and clinical outcome, \nwere collected from the medical records and clinical database (Table \n1).\nUltrasound\nTransvaginal ultrasound was performed using color Doppler \nultrasound diagnosis systems and a 5 MHz to 9 MHz transvaginal \nprobe (iU22, Philips, Best, The Netherlands; Logiq 9, GE Healthcare, \nWaukesha, WI, USA) by experienced ultrasound radiologists. \nGroup No. Age Years of \nAUB-O Hb (g/l) Medical treatment Ultrasound MRI Surgery\nGroup 1- \nasymmetrical \nintrinsic \nadenomyosis\n1 41 6 50\nMenstruation was regular during medication \nwith COCs or progestins, but period still lasted \nfor 7-14 days with HMB. Even with LNG-IUS, \nmonthly bleeding like normal menstruation \ncontinued till 6 months. Fortunately, anemia has \nimproved.\nthickening of uterine \nwalls (1.7/3.9 cm), \nand thickening of \nendometrium 2.3 cm\nThickening of \njunctional zone 1.2 \ncm, thickening of \nposterior uterine \nwall, Swiss Cheese \nSign\nD&C (-)\n2 34 4 51\nMultiple-dose COCs could control the irregular \nvaginal bleeding, but breakthrough bleeding \nrecurred when the drug dose reduced to one \npill per day. Now the patient is receiving the \ntreatment of GnRHa.\nthickening of uterine \nwalls (2.3/2.4 cm)\nthickening of \njunctional zone, \npartially protruding \ninto the uterine \ncavity, Swiss \nCheese sign \npossibly\nD&C (-)\n3 39 0.5 78\nGnRHa is the only guaranteed drug to control \nher vaginal bleeding COCs and Norplant were \nboth ineffective. LNG-IUS shed out along \nwith persistent heavy bleeding for the first \ntime. Hysteroscopic lesion resection. followed \nby second insertion of LNG-IUS achieved \npreliminary effect, uterine bleeding stopped by \nsix months later\nthickening of uterine \nwalls (1.4/4.2 cm)\nthickening of \njunctional zone\nD&C (-)\nHys: partial \nresection of \nAM\nGroup 2- \nsymmetrical \nintrinsic \nadenomyosis\n4 41 1 80\nCOCs and norethindrone (15 mg/d) could not \ncontrol the irregular bleeding, until the use of \nGnRHa for 2 cycles. Now the patient is treated \nby the LNG-IUS.\nthickening of \nendometrium 1.7 cm \nwith echo heterogeneity\nthickening \nof junctional \nzone over 1/2 \nmyometrium\nD&C (-)\nHys: polypoid \nhyperplasia\n5 53 1 65\nMedroxyprogesterone (40 mg/d) could not \ncontrol the irregular vaginal bleeding. A \nlaparoscopic hysterectomy was performed after \nhemostasis with GnRHa.\nthickening of \nendometrium 1.1 cm \nto 1.5 cm with echo \nheterogeneity, and intra-\nuterine occupation 3 cm \n× 2 cm\nthickening of \njunctional zone \nabout 3cm\nD&C (-)\nLH after \nclarification \nof AM\n6 49 1 88\nMedroxyprogesterone (40 mg/d) could not \ncontrol the irregular vaginal bleeding. Now the \npatient is receiving the treatment of GnRHa.\nthickening of \nendometrium 2.5 cm \nwith echo heterogeneity, \nand intra-uterine \noccupation 1.2 cm × \n0.8 cm\nthickening of \njunctional zone \nand signal \nheterogeneity of \nmyometrium\nD&C (-)\nTable 1: Clinical information of 6 patients with refractory AUB.\n\nDeng S, et al., Clinics in Surgery - Gynecological Surgery\nRemedy Publications LLC., | http://clinicsinsurgery.com/\n 2021 | Volume 6 | Article 31543\nUltrasound characteristics, including the size of the uterus, the \nthickness of the endometrium, anterior and posterior walls, and \nwhether there were cystic spaces or heterogeneous zones in the \nmyometrium, were detected in the sagittal and transverse planes. \nMRI was performed by radiologists.\nMagnetic resonance imaging\nWho were experienced in gynecology and using 3T scanners \n(Sigma, GE Healthcare, Waukesha, WI, USA; Ingenia 3.0T CX; \nPhilips, Best, the Netherlands). As per routine practice, 4-mm slices \nwith 1-mm spacing were acquired in the sagittal, coronal, and axial \nplanes relative to the orientation of the body using T2-weighted fast \n(turbo) spin echo sequences (TR/TE, 3500 to 4000 ms/90 ms, echo \ntrain length 16) in all three planes. Phase array pelvic coils were used \nfor data acquisition. The examination was completed in 20 min. \nJunctional zone thickness >12 mm and high-signal spots seen in the \nmyometrium indicated adenomyosis [16-18].\nClassification method\nThe MRI classification of adenomyosis suggested by Bazot was \nused for reference [19]. This classification is based on the morphology \nand location of adenomyosis; the two subtypes are mainly internal \nadenomyosis and external adenomyosis. According to MRI, the \nsix patients were all diagnosed with internal adenomyosis. They \nwere further classified into two groups: Asymmetrical internal \nadenomyosis and symmetrical internal adenomyosis.\nStatistical analysis\nOnly descriptive statistics were used.\nResults\nAccording to the imaging characteristics of MRI, the six patients \nwere classified into two groups: Asymmetrical internal adenomyosis \ngroup and symmetrical internal adenomyosis group.\nIn the first group, the three patients were complaining of an \nirregular menstrual cycle and HMB. They all received medical \ntreatment with oral contraceptives and progestins in the early stage. \nThe common characteristic was resistance to single-dose COCs. Only \na multidose strategy (≥ 3 tablets each day) could control the bleeding \ntemporarily, but irregular bleeding recurred once the drugs were \nreduced to a single dose. GnRHa was prescribed to all three patients \nbecause of moderate-to-severe anemia due to refractory bleeding. \nUltrasound in all three patients suggested adenomyosis given the \nimage of myometrial wall thickness with palisade echoes, but the \ninitial diagnosis was not adenomyosis. Patients #1 (Figure 1a, 1e) and \n#2 (Figure 1b, 1f) had the “Swiss-cheese sign”, indicating the presence \nof a large area of endometrium folded inward. Even after insertion of \nthe levonorgestrel intrauterine system (LNG-IUS, Mirena), periodic \nbleeding resembling normal menstruation lasted for nearly one year \nin patient #1. Given her reluctance to have her uterus removed, \nshe was satisfied with the current situation. Specifically, patient #3 \ntried to use the LNG-IUS and Norplant implantation, but the LNG-\nIUS eventually shed out with persistent heavy bleeding, and the \nNorplant implantation also failed to stop the uterine bleeding. The \npatient’s condition of adenomyosis was well-known according to her \nmedical history, since multiple ultrasound examination indicated \necho heterogeneity of the myometrium as well as thickening of \nboth the anterior and posterior walls of uterus (1.4 cm and 4.2 cm, \nrespectively). In addition, recent MRI imaging revealed for the first \ntime that the junctional zone of the uterus was obscure, and that an \nadenomyoma protruded from the posterior wall of the uterus into the \nuterine cavity (Figure 1c, 1g). LNG-IUS was successfully placed after \nhysteroscopic resection of the protruding lesion in the uterine cavity. \nAlthough the location of the IUS later declined to the lower part of \nthe uterine cavity, the bleeding symptoms have been controlled up \nto now. The drawback was that irregular spotting has been ongoing \nfor up to a year. We classified this type as “asymmetrical internal \nadenomyosis” according to the infiltration degree in myometrium in \nthe anterior, posterior, or lateral walls of the uterus.\nIn the second group, the three patients also complained of \nan irregular menstrual cycle and HMB and took multidose oral \ncontraceptives or progestins. Nonetheless, AUB could not be \neffectively controlled until GnRHa or LNG-IUS was used. The \ncommon ultrasound feature was thickening of the endometrium, \nbut no positive pathological findings were observed even after D&C \nassisted by hysteroscope. Additional MRI showed thickening of the \njunctional zone over 50% of the myometrium layer, indicating that \nadenomyosis played a role in causing the persistent vaginal bleeding. \nIt is worth mentioning that patient #5 finally received hysterectomy \nbecause she was 53 years old, which was different from the other \ntwo patients (Figure 2). Hysterectomy was performed and gross \npathological examination confirmed the diagnosis of  adenomyosis \nFigure 1: Ultrasound and MRI images for asymmetrical intrinsic adenomyosis \nin refractory abnormal uterine bleeding.\n(a-c) Ultrasound images from three patients (#1-3) suggesting enlargement \nof the uterus at different degrees, thickening of the uterine wall, and echo \nheterogeneity of the myometrium layer. Sagittal T2-weighted MRI images \nproviding more detailed information. (d) Patient #1: Thickening of the \njunctional zone in the posterior wall of the uterus, with an alveolate focus \nprotruding into the cavity. (e) Patients #2: Thickening of both the anterior and \nposterior walls of the uterus, with alveolate foci pressing on the endometrium \nlayer. (f) Patient #3: A focus-like adenomyoma in the posterior wall of the \nuterus causing deformity of the uterine cavity. The white arrows indicate the \n“Swiss cheese” sign.\n\nDeng S, et al., Clinics in Surgery - Gynecological Surgery\nRemedy Publications LLC., | http://clinicsinsurgery.com/\n 2021 | Volume 6 | Article 31544\nwith diffuse and dense thickening of the myometrium. We classified \nthis type as “symmetrical internal adenomyosis” according to the \ninfiltration degree in myometrium in the anterior, posterior, or lateral \nwalls of the uterus.\nDiscussion\nSome patients with AUB are refractory to medical treatment. \nAdenomyosis could be involved in those cases. Therefore, the \naim of the present study was to report six cases of refractory \nAUB-O diagnosed with adenomyosis and to emphasize the clinical \nsignificance of adenomyosis in AUB. The results suggest that routine \nmedications are ineffective in the treatment of AUB-O. Adenomyosis \nis most likely the underlying reason, even for patients without \ndysmenorrhea. Given that adenomyosis has different subtypes, \nMRI is an optimal method to make a diagnosis and guide individual \ntreatment, especially for cases in the early stages.\nIt is well-known that dysmenorrhea is the main clinical feature \nof adenomyosis. Nevertheless, the role of adenomyosis in AUB \nwith no pain is usually neglected or underestimated. According to \nour experience, dysmenorrhea is not an indispensable “signature \nsymptom” of adenomyosis, and adenomyosis is an important \ncontributor to AUB refractory to routine medications. The complex \npathogenesis and manifestation of adenomyosis make it one of the \nmost difficult AUB types to diagnose and treat according to the \nFIGO PALM-COEIN system [1]. The incidence of adenomyosis as \nan isolated pathology is not clear. Approximately 30% patients with \nadenomyosis are asymptomatic, and the incidence of dysmenorrhea \nhas been reported to be 50% to 93.4% [11,17,20,21]. Meanwhile, in \nthe absence of concomitant pathology, adenomyosis could cause \nAUB in 27% to 65% of patients [11,17,20,21]. For patients with HMB \nthat is significant enough to cause anemia, adenomyosis should be \ngiven particular attention, especially in nulliparous women [9].\nAdenomyosis varies widely in the extent and location of its \ninvasion within the uterus [20,22]. Although noninvasive diagnosis \nmethods such as transvaginal ultrasound and MRI are recognized \nas being highly accurate, histological examination remains the gold \nstandard for diagnosis [23]. Nevertheless, noninvasive imaging \ntechniques such as TVUS and MRI can both be used to strongly \nsuggest the diagnosis of adenomyosis, guide treatment options, and \nmonitor the responses to treatment [21,24]. By virtue of its ability \nto objectively differentiate between different types of soft tissue, MRI \nprovides slightly better diagnostic capability compared to TVUS \n[19,25]. Our experience confirmed that MRI could provide more \nspecific details about important parameters to be included in the \nclassification system of adenomyosis, such as the affected area (inner \nor outer myometrium), localization (anterior or posterior or fundus), \npattern (diffuse or focal), type (muscular or cystic), and volume or \nsize, in the form of objective images from different angles, especially \nfor the symmetrical internal subtype [25]. This is very helpful in \nmaking clinical decisions of management.\nThere has been a call for a classification system for adenomyosis to \nassist clinicians in making a diagnosis and for planning management \n[16]. While there are several proposed classification systems, none \nhave been universally adopted. This is problematic at both clinical \nand research levels. Comprehensively, there are mainly two forms \nof adenomyosis: diffuse and focal [17,26-29]. For the diffuse type, \nextensive disease with endometrial mucosa includes glands and \nstroma scattered throughout the uterine muscular layer. For the \nfocal type, also named adenomyoma, a hypertrophic and distorted \nendometrium is found in the myometrium with a circumscribed \nmass. Unusual types of adenomyosis include adenomyotic polyp, \nadenomyotic cyst, and Swiss cheese appearance of adenomyosis [18]. \nIn recent years, the classification strategy based on MRI features \n(internal, external and intramural adenomyosis subtypes), which \nwas first proposed by Kishi et al. in 2012 [27], has received increasing \nattention. The classification system further refined by Bazot et al. has \nthe greatest potential to help make a therapeutic strategy and reflect \nthe pathogenesis of adenomyosis [19,25]. Internal adenomyosis \ndevelops in direct connection to the thickened junctional zone and \nhealthy myometrium is preserved outside the adenomyosis. External \nadenomyosis is located in the outer shell of the uterus, the junctional \nzone is kept intact without aberrancy, and healthy muscular structures \nare preserved in between the adenomyosis and the junctional zone. \nAmong them, internal adenomyosis comprised focal or multifocal, \nsuperficial asymmetric or symmetric, and diffuse asymmetric or \nsymmetric subtypes. Our initial clinical impression was that the \ninternal subtype presented more severe bleeding, while the external \nsubtype presented more serious dysmenorrhea. In addition, focal, \nsuperficial and symmetric lesions, namely, internal adenomyosis of \nan early stage are not easily detected by transvaginal ultrasound.\nIn our second series, adenomyosis was neglected mostly because \nthe patients did not complain of dysmenorrhea, although ultrasound \nsuggested thickening of the endometrium, but MRI examination \nprovided more information. For mild internal adenomyosis (focal or \nsuperficial lesion), ultrasound is presumed to be less sensitive than \nFigure 2: Ultrasound, MRI images, and gross specimen of symmetrical \nintrinsic adenomyosis in refractory abnormal uterine bleeding in patient #5.\nA 53-year-old, complaining of irregularity of the menstrual cycle and heavy \nmenstrual bleeding for 1 year, with a minimum hemoglobin level of 65 g/l. \nMedroxyprogesterone (40 mg/d) could not control the irregular vaginal \nbleeding. A laparoscopic hysterectomy was performed after hemostasis with \nGnRHa. (a) Ultrasound image indicated enlargement of the uterus, thickening \nof the endometrium (1.1 cm), echo heterogeneity of the myometrium, and \nlow-echo focus in the anterior wall (1.9 cm × 1.8 cm). (b) Sagittal T2-weighted \nMRI image presented diffuse thickening of the junctional zone (single layer, \n2.5 cm). (c-d) Gross pathological examination suggested adenomyosis. It \nwas observed that the uterine wall was diffusely and densely thickened, while \nonly the outer 5 mm near the serosa was normal in texture.\n\nDeng S, et al., Clinics in Surgery - Gynecological Surgery\nRemedy Publications LLC., | http://clinicsinsurgery.com/\n 2021 | Volume 6 | Article 31545\nMRI. In terms of ultrasound features of adenomyosis, asymmetrical \nmyometrial thickening, myometrial cysts, linear striations, and \nhyperechoic islands are common signs. Nevertheless, the “irregular \nand thickened endometrial-myometrial junction zone” on either 2D \nor 3D imaging, which corresponds to the junction zone in MRI, seems \nto be less reliable and inevitably depends on the performance of the \nMRI system as well as on the experience of the physicians, though a \nnew scoring system for uterine adenomyosis was published recently \n[30]. For adenomyosis, where the uterine volume is not significantly \nenlarged and only the superficial muscle layer is involved, ultrasound \ntends to miss the diagnosis of adenomyosis.\nFor three other patients, although the ultrasound examinations \nprovided a diagnosis of adenomyosis given the thickening of both \nanterior and posterior walls of the uterus with palisade echoes, \nMRI helped in clarifying the classification as internal adenomyosis \nwith characteristic features of “Swiss cheese” and submucosal \nadenomyoma, respectively. This imaging information is very helpful \nfor analyzing the cause of drug resistance and formulating the \nsubsequent treatment plan.\nIn view of the above analysis, transvaginal ultrasound is the first-\nline imaging technique currently used for the noninvasive diagnosis \nof adenomyosis. Although adenomyosis may by successfully manage \nin many patients, some patients still have symptoms. Therefore, MRI \nmay be needed for proper patient management.\nFor patients with refractory AUB due to adenomyosis and \nwithout fertility requirements, hysterectomy is the most cost-effective \ntreatment, as shown with patient #5 and #6 in the present study \n[4,31]. For patients unwilling to lose their uterus, GnRHa followed \nby LNG-IUS insertion may be the most promising strategy [32,33]. \nMeanwhile, physicians have to foresee the possibility of prolonged \nbreakthrough bleeding during IUS on-site, as demonstrated by \npatient’s #1-4 in the present study. If the lesions invade the uterine \ncavity, appropriate hysteroscopic surgery may improve the prognosis \nof IUS therapy, which was shown in patient #3 [34]. On the other \nhand, there is still a lack of experience regarding patients with \nfertility requirements. Nevertheless, MRI is essential to make an early \ndiagnosis and classification. On the other hand, for simultaneous \nAUB-O, conscious and comprehensive interventions, including \nlifestyle and body weight control combined with drug therapy, have \nthe potential to ultimately improve reproductive prognosis.\nThis study has limitations. As a retrospective analysis on a series \nof very specific patients, this study was limited by a small sample size. \nIn addition, available data were limited to those available in the charts. \nNevertheless, the whole process of clinical treatment and follow-up \nallowed us to accumulate more experience, which we think should \nbe share with our colleagues. These cases could be the beginning of \na study that investigates how MRI plays a role in the diagnosis and \nsub-classification of adenomyosis in AUB, and how this can aid in \ntreatment decision-making and improve outcomes.\nConclusion\nThe present study suggests that when routine medical treatment \nis ineffective in the treatment of AUB-O and that endometrial \nmalignancy is excluded, adenomyosis is most likely the underlying \ncause of AUB, even for patients who do not complain of dysmenorrhea. \nGiven that adenomyosis has different phenotypes, transvaginal \nultrasound is the first-line imaging technique, but MRI can facilitate \nclinical decision making in patients with early stage or atypical cases.\nAuthor Contributions\nGui T: data curation, formal analysis, investigation, methodology, \nwriting-original draft preparation; Deng S: conceptualization, \ninvestigation, methodology, project administration, supervision; He \nY: data curation, resources; Xue H: data curation, resources.\nReferences\n1. 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