{"paper_id":"838a3536-6d6a-4db8-81af-1a7c22b7e118","body_text":"~ 282 ~ \nInternational Journal of Clinical Obstetrics and Gynaecology 2020; 4(1): 282-286 \n \nISSN (P): 2522-6614 \nISSN (E): 2522-6622 \n© Gynaecology Journal \nwww.gynaecologyjournal.com \n2020; 4(1): 282-286 \nReceived: 07-11-2019 \nAccepted: 09-12-2019 \n \nDr. Meena Jain \nMS (Obstetrics & Gynaecology), \nMICOG, FIMS, Assistant \nProfessor, Department of \nObstetrics & Gynaecology, Sri \nShankaracharya Medical College, \nBhilai, Durg, Chhattisgarh, India \n \nDr. Preshit Chate \nMD (Obstetrics & Gynaecology), \nAssociate Professor, Department of \nObstetrics & Gynaecology, Sri \nShankaracharya Medical College, \nBhilai, Durg, Chhattisgarh, India \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \nCorresponding Author: \nDr. Preshit Chate \nMD (Obstetrics & Gynaecology), \nAssociate Professor, Department of \nObstetrics & Gynaecology, Sri \nShankaracharya Medical College, \nBhilai, Durg, Chhattisgarh, India \n \nTAS/TVS versus histopathological diagnosis in \nabnormal uterine bleeding: A comparative study \n \nDr. Meena Jain and Dr. Preshit Chate \n \nDOI: https://doi.org/10.33545/gynae.2020.v4.i1e.475 \n \nAbstract \nBackground: Any uterine bleeding outside the normal volume, duration, regularity or frequency is \nconsidered abnormal uterine bleeding. \nObjectives: This study was conducted to evaluate the efficacy of TAS /TVS and histopathological findings \nin AUB patients. \nMethods: A prospective study was done on 101 females of various age groups attending the Department of \nobstetrics a nd gynaecology over a period of 1  year with a clinical diagnosis of AUB. Each patient \nirrespective of the baseline investigations and sonography findings  were subjected to premenstrual \ndilatation and curettage as well as hysteroscopy a ccordingly hence endo metrial tissue obtained was \nsubjected to histopathological examination. \nResult: In our present study the most recurring  clinical uterine lesion noted was myoma  in about 34.16%, \nfollowed by Adenomyosi s in about 33.54% . Endometrial po lyp was noted at 21.11% and endometrial \ncarcinoma was in 8.69% . Cervical polyp a nd ce rvical carcinoma found in  1.24%. The se nsitivity and \nspecificity of sonography  for Diagnosing Polyp as compared to HPE was 52.77% and 98.46% while \npositive predictive value and negative predictive value were 95.00 % and 79.01% respectively. \nConclusion: Transabdominal or transvaginal  ultrasound is low cost primary modality for screen ing and \nshould include as a first line screening method. Though the investigation and management  of AUB among \nthe non-gravid women was confusing, histopathological diagnosis proved to be the gold standard. \n \nKeywords: Abnormal uterine bleeding (AUB), adenomyosis, endometrial polyp, myoma, non-gravid \n \n1. Introduction  \nInvestigation and management of a bnormal uterine bleed ing (AUB) among non -gravid women \nof reproductive age has been hampered both by confusing and inconsistently applied \nnomenclature and by the lack of standardized methods for investigation and categorization of the \nvarious potential etiologies [4, 5]. \nAcute AUB is an episode of bleeding in a woman of reproductive age, who is not pregnant, of \nsufficient quantity to require immediate intervention to prevent further blood loss. Chronic AUB \nis the bleeding from th e uterine corpus that is abno rmal in duration, volume,  and/or frequency \nand has been present for the majority in the last 6 months. \nPALM-COIEN classification in 2011, for the causes of AUB in non-gravid women of \nreproductive age was published in order to standardize terminology, diagn ostics and \ninvestigations [6]. There are 9 main categories, which are arranged according to the acronym \nPALM-COEIN (pronounced “pahm-koin”): polyp; Adenomyosis; leiomyomas; malignancy and \nhyperplasia; coagulopathy; ovulatory dysf unction; endometrial; iatro genic; and not yet \nclassified. In general, the components of the PALM group are discrete (structural) entities that \ncan be measured visually with imaging techniques and/or histopathology, whereas the COEIN \ngroup is related to entities that are not defined by imaging or histopathology (non-structural) [6]. \n Ultrasound is an appropriate screening tool and, in most instances, should be performed first or \nearly in the course of the investigation. Even in ideal circumstances, TVUS is not 100% \nsensitive because p olyps and other small lesions m ay elude detection, even in the context of a \nnormal study [7, 8]. However, if office hysteroscopy is available, there may be additional value \nshould polyps be identified because they could be removed in th e same setting. When  vaginal \naccess is difficult, as may be the case with adolescents and virgin women, TVUS, SIS and office \nhysteroscopy may not be feasible [6]. \n \n\n\nInternational Journal of Clinical Obstetrics and Gynaecology http://www.gynaecologyjournal.com \n~ 283 ~ \nEstimates of the prevalence of Adenomyosis vary widely, \nranging from 5% to 70%  [9] an observation that, at least in part, \nis p robably related to incons istencies in the histopathologic \ncriteria for diagnosis. Generally, these criteria have been based \non histopathologic evaluation of the depth of “endometrial” \ntissue beneath the endometrial  – myometrial in terface, as \ndetermined via hysterectomy. The histopa thologic criteria vary \nsubstantially9 and the requirement to diagnose adenomyosis \nsolely from specimens obtained at hysterectomy is an approach \nthat has limited value in a clinical classificatio n system. \nConsequently, and because there exist both sonographic [10] and \nmagnetic resonance imaging (MRI) based  [11, 12] diagnostic \ncriteria, Adenomyosis has been included in the classification \nsystem. \nEndometrial cancer is staged surgico-pathologically according to \nFIGO (International Fede ration of Gynecology and Obstetri cs) \ncriteria. Preoperative magnetic resonance imaging is performed \nto identify patients with deep myometrial invasion, enlarged \npelvic nodes, and extra uterine extension of disease, which alter \nthe extent of surgery. \nThe te rm “DUB,” which was previously us ed as a diagnosis \nwhen there was no systemic or locally definable structural cause \nfor AUB, is not included in the system and should be \nabandoned, per the agreement process [13, 14]. Women who fit this \ndescription generally  have one or a combination of \ncoagulopathy, disorder of ovulation, or primary endometrial \ndisorder the last of which is most often a primary or secondary \ndisturbance in local endometrial homeostasis. \nThis study was conducted to ass es sonography as a diagno stic \ninvestigation modality in patien ts of abnormal uterine bleeding \nand to correlate it with histopathological findings. \n \nMaterial and methods \nA prospective study was done on 101 females of various age \ngroups attending the Departm ent of obstetrics and gynecology \nover a period of 1year with a clinical diagnosis of AUB. \nPatients fulfilling the inclusion criteria were selected through \ndetailed clinical history, examination: general physical, \nsystemic, gynecological (per speculum, per vaginal) and all \ngeneral and specific investigation s were carried out. Written \ninformed consent (form attached) was taken from patient \ninterviewed, examined and investigated as per the predesigned \nproforma (attached).  All the patients were subjected to \npremenstrual dilatation and curettage and hysterosopic guided \nbiopsy accordingly. Tissue  obtained was subjected to \nhistopathological examination. \nAfter primary data collection, a master chart was prepared with \nthe help of Microsoft excel sheet and data entered into it was \nanalyzed according to the set objectives. \nNon-parametric (discrete) data was analyzed using chi -square \ntest. Mean, standard deviation and percentage was used for \nanalysis of parametric (continuous) data. A P value of <0.05 was \nconsidered statistically significant. \n \nResults \n \nTable 1: Age wise distribution of AUB cases \n \nAge group N (101) Percentage (%) \n31-40 17 16.83 \n41-50 63 62.38 \n51-60 11 10.89 \n61-70 8 7.92 \n>70 2 1.98 \n \nMost of the cases were found in 41-50 year age group i.e. 63 and \nleast case were found in 70<age group \n \nTable 2: Distribution of menstrual pattern in various age groups \n \nAge group (years) 31-40 41-50 51-60 61-70 >70 Total \nMenstrual pattern       \nHMB 9 25 1 1 0 36 \nHPMB 7 22 3 0 0 32 \nIMB 1 15 3 2 0 21 \nPMB 0 1 4 5 2 12 \nTotal 17 63 11 8 2 101 \n68 patients had menorrhagia as a prima ry complaint. Heavy Menstrual bleeding (HMB) in 36 (35.69%) and Heavy and Prolonged Menstrual \nBleeding (HPMB) in 32 (31.68%), 21(20.79%) patients have irregular menstrual bleeding patterns, while 12(11.88%) patients had post- Menopausal \nbleeding. \n \nTable 3: Tabulating the histopathological findings in all age group. \n \nPathology / Age group (years) 31-40 41-50 51-60 61-70 >70 Total \nMyoma 4 15 0 0 0 19 \nAdenomyosis 4 11 1 0 0 16 \nEndometrial polyp 1 3 1 0 0 5 \nCervical polyp 0 2 0 0 0 2 \nEndometrial carcinoma 0 1 2 4 1 8 \nCervical carcinoma 0 0 0 0 0 0 \nMyoma+ Adenomyosis 2 11 3 0 0 16 \nMyoma+ polyp 1 4 1 0 0 6 \nMyoma+ endometrial carcinoma 0 0 1 2 0 3 \nMyoma+ cervical carcinoma 1 0 0 0 1 2 \nPolyp+ Adenomyosis 3 8 1 0 0 12 \nPolyp+ endometrial carcinoma 0 1 0 1 0 2 \nAdenomyosis+ endometrial carcinoma 0 0 0 1 0 1 \nMyoma+ polyp+ Adenomyosis 1 7 1 0 0 9 \nTotal 17 63 11 8 2 101 \nHistopathological examination maximum number of patients were found having Myoma in 19 cases (18.81%) followed by Adenomyosis in 16 cases \n(15.84%) and Myoma+ Adenomyosis existed in 16 (15.84%) cases. Least frequently condition was myoma with endometrial carcinoma and 1 case \n(0.99%) of Adenomyosis with endometrial carcinoma. \n\nInternational Journal of Clinical Obstetrics and Gynaecology http://www.gynaecologyjournal.com \n~ 284 ~ \nTable 4: Correlation of various diagnostic modalities in AUB \n \nFindings USG HPE p value \nNormal 33 0 <0.0001 \nMyoma 18 19 0.97 \nEndometrial polyp 3 5 0.72 \nCervical polyp 0 2 0.36 \nAdenomyosis 10 16 0.44 \nEndometrial carcinoma 4 8 0.49 \nCervical carcinoma 0 0 0 \nMyoma+ Adenomyosis 14 16 0.83 \nMyoma+ polyp 3 6 0.53 \nMyoma+ Endometrial carcinoma 1 3 0.56 \nMyoma+ Cervical carcinoma 1 2 0.81 \nPolyp+ Adenomyosis 7 12 0.48 \nPolyp+ Endometrial carcinoma 1 2 0.81 \nAdenomyosis+ Endometrial carcinoma 0 1 0.60 \nMyoma+ polyp+ Adenomyosis 6 9 0.30 \n \nTable 5: Pathological findings in patients of AUB \n \nFindings Pathology n % \nTissue findings \nNormal Endometrium 20 16.53 \nEndometrial hyperplasia 27 22.31 \nProliferative phase 11 9.09 \nSecretary 17 14.04 \nMixed 3 2.47 \nAtrophic endometrium 3 2.47 \nEndometritis 1 0.83 \nEndometrial polyp 5 4.13 \nEndometrial Carcinoma 12 9.91 \nCervical Carcinoma 2 1.65 \nUterine Pathologies \nMyoma 55 34.16 \nAdenomyosis 54 33.54 \nEndometrial polyp 34 21.11 \nCervical polyp 2 1.24 \nEndometrial carcinoma 14 8.69 \nCervical carcinoma 2 1.24 \n \nIn our study dilatation and curettage findings 20 cases (16.53%) \nhad norma l endometrium . Highest number of patients . i.e. 27 \ncorresponding to 22.31% were detected as endometrial \nhyperplasia. secretary endometrium was detected in 17(14.04%), \nproliferative in 11(9.09%)  cases. 1 case (0.83%) had \nendometritis and 5 cases  (4.13%) had endometrial polyp while \n12 (9.91%) cases were diagnosed as endometrial carcinoma and \n2 (1.65%) had cervical carcinoma. \nIn our present study the most recurring cl inical uterine lesion \nnoted was myoma in about 34.16% followed by Adenomyosis in \nabout 33.54% of times. Endometrial polyp was noted at 21.11% \nof times and endometrial carcinoma was noted in 8.69% cases \nwhile cervical polyp and cervical carcinoma was noted at 1.24% \nof cases. \nIn our presen t study polyps was detected by USGs in 3 patients \nand HPE diagnosis of polyps was in 5 patients.2 cases of \nCervical polyp were missed by sonography. \n \nStatistic value \nSensitivity 52.77% \nSpecificity 98.46% \nPositive Predictive Value 95.00% \nNegative Predictive Value 79.01% \n \nThe sensitivity and specificity of TAS for Diagnosing Polyp as \ncompared to HPE was 52.77% and 98.46% while positive \npredictive value and negative predictive value were 95.00 % and \n79.01% respectively. \nDiscussion \nUSG forms the baseline  imaging modality, Ultrasonography \n(USG) helps excludes organic pathology for AUB and is well \naccepted that  for various disease, pathology can be detected \naccurately by histopathological examination (HPE) [15]. \nA comprehensive history and physical examination , with focus \non the menstrual history and genitourinary exam was most \nhelpful in determining the diagnosis; however, based on the \nfindings, laboratory evaluation or imaging may be necessary  [16]. \nThus the demographic findings of our study were consistent with \nother studies. Higher number of patients found in the age group \nof 41-50 years. In the post-menopausal age group AUB was less, \nthus may be attributable to the increased rate of hysterectomy \nfor benign indications. \nMyoma was the most prevalent histopatholo gical finding during \nthe examination. In 19 (18.81%) patients while Adenomyosis \nexisted in 16 (15.84%) patients out of total findings dual \npathology of Myoma + Adenomyosis was found in again 16 \npatients i.e. 15.84. In va rious combinations, Myoma was \nobtained in maximum number of cases i.e in 55 patients in 54.46 \n% of the total his to pathological examination. \nAccording to a retrospective study conducted by Ghazala Rizvi \net al.  (2015) and published in 2013 Tilted “Histolog ical \ncorrelation of Adenomyosis and leiomyomas in hysterectomy \nspecimen as a cause of abnormal uterine bleeding.” 94 patients \ni.e. 51.08% were found to have Adenomyosis and 39.13 % were \nfound to have myoma while 9.78% of the patients have dual \npathology.17 \nThough the comparison of percentage in our study was favorable \nto other study but the other studies was retrospective and ours \nbeing prospective and since we have taken all the structural \ncauses of abnormal uterine bleeding the overall percentage has \ncome to lower studies. \nIn our study poly p with Adenomyosis existed in 12 patients as \nconfirmed by histological examination i.e. in 11.88%. While \nmyoma with polyp and Adenomyosis existed in 9 patient i.e \n8.91% of cases. Endometrial Carcinoma independently was \nfound in 8 cases i.e 7.92% while independently endometrial \npolypexisted in 5 cases while cervical polyp was found in 2 \ncases. Myoma with polypexisted in 6 cases. Similarly \nendometrial carcinoma existed with Myoma in 3 cases and \ncervical carcinoma was found in 2 cases. Endometrial carcinoma \nwith polyp was reported in 2 cases and endometrial carcinoma \nwith Adenomyosis was reported i n 1 cases. There was no \ncomparative study found for establish the correlation of our \nstudy. \n\nInternational Journal of Clinical Obstetrics and Gynaecology http://www.gynaecologyjournal.com \n~ 285 ~ \nMyoma and Adenomyosis existed in repro ductive and \nperimenopausal age group, while carcinomas mainly constituted \nthe post-menopausal age group. Maximum number of myo ma, \nAdenomyosis and the dual pathology existed in the age group of \n31-50 years. Polyp existed in the age group of 41 -60 years. \nEndometrial carcinomas were maximally seen in the ag e group \nof 61 -70 years of the 2 cases diagnosed as cervical carcinoma \none case was diagnosed at 38 years of age and other at 74 years \nof age this is in accordance with the bimodal distribution of the \ncervical carcinoma. \nThe pathological findings of Myoma and Adenomyosis are more \nconsistent with the menorrhagia while carcinomas are m ore \nconsistent with postmenopausal bleeding and inter -menstrual \nbleeding. \nIn our present study of 101 patients complaining of Abn ormal \nuterine bleeding 33 patients were declared N ormal as per trans \nabdominal sonographic findings and7 were having normal MRI  \nfinding While none of the Symptomatic patients were having \nnormal histopathological finding. Trans Abdominal Sonography \nmissed t he diagnosis of Adenomyosis in about 23 cases and \nincorrectly diagnosed 2 cases as Adenomyosis. \nHistopathology diagnosed a tota l of 36 cases of polyp in which \n30 cases were correctly diagnosed by MRI while 3 cases were \nincorrectly diagnosed as polyp by MRI . Transabdominal \nsonography diagnosed only 19 case s and missed 17 cases \nmoreover wrongly diagnosed 1 case as polyp. Transabdomi nal \nsonography was not able to diagnose cervical carcinoma cases. \nTransabdominal sonography diagnosed only 4 cases of \nendometrial carcinoma while of total 8 cases diagnosed by \nhistopathology. \nThe p value was found to be highly significant for diagnosing \nnormal findings in symptomatic patients and for preoperative \nevaluation, counseling, and planning of surgical management. \nIn diagno sing other uterine lesions, the p value was not fou nd \nsignificant. And thus, this preoperative imaging modality plays \nrole in dia gnosis and management of uterine pathologies in \npatients complaining of abnormal uterine bleeding. \nIn our study, all the patien ts were subjected to dilatation and \ncurettage so as to get endometrial tissue for histopathological \nexamination before proceeding and deciding for surgical \nmanagement. \nDilatation and curettage findings of 20 patients were normal  \nendometrium for the menstrual day and they were excluded from \nthe study and man aged conservatively . highest number of \npatients. i.e. 27 corresponding to 22.31% were having \nendometrial hyperplasia, secretary endomctrium was found in 18 \npatients proliferati ve in 11 patients 1 patient had endometritis \nand 5 patients had endometrial poly p while 12 patients were \ndetected to have endometrial carcinoma and 2 had cervical \ncarcinoma. \nIn a study conducted by Sujith K et al. (2014) titled “Study of \nhistopathological p atterns of endometrium in a bnormal uterine \nbleeding” Endometrial hyperplasia wa s the most common \nhistopathological findings in 25% of the patients followed by \nsecretary endometrium in 16.7%patients and proliferative phase \nin 12.2%. Malignancy was detected in 6.4% of cases and \nendometrial carcinoma was most common malignancy in \n4.5%.19 \nWhere as in a study conducted by Saraswath Doraiswami et al. \n(2011); in “study of endometrial pathology in abnormal uterine \nbleeding” normal cyclical endometrium was found in 2 8.4% \nproliferative pattern was seen in 20.5%. Endometrial hyperplasia \nin only 6.1%. carcinoma in 4.4% and endometritis in 4.2%, 20 \nThus, our findings of study were consistent to other studies. \nIn our present study the most recurring uterine lesion noted is \nmyoma found in about 34.16 % of circumstances, followed by \nAdenomyosis in about 33.54% of times. Endometrial polyp was \nnoted at 21.11% of times and endometrial carcinoma was noted \nin 8.69% of times while cervical polyp and cervical carcinoma \nwas noted at 1.24% of times. \nIn a study c onducted by Bharat Talukdar et al. histopathologic \nally myoma was seen in about 44.66% of cases and \nAdenomyosis was seen in 20.39% of cases. The findings are \nconsistent with our study.21 \nSimilarly, in a study conducted by N Bhavani et al.  (2015), \namong the  causes of abnormal uterine bleeding, Structural \ncauses accounted for 54.5% of cases. 45.5% of them had \nnonstructural causes of abnormal uterine bleeding. Myoma in \n38.5% is the commonest Cause of abnormal uterine bleeding, \nfollowed by hyperplasia and malig nancy 7.5%, adenomyosis in \n6%, polyp in 2.5%. 18 Thus findings in our study are consistent \nwith other study. \nIn our study total no of cases diagnosed as myoma in MRI is 55 \nand in Histopathological Specimen who underwent Surg ical \ntreatment also diagnosed myoma as a total in 55 patients. \nOne case of endometrial polyp was diagnosed as myoma by \nTAS and one case of small myoma \n<1cm was diagnosed on Histopathological examination. Thus, \nthe positive predictive value and Sensitivity o f TAS in \ncorrelation to HPE for myoma was 98.18% while negative \npredictive value and sp ecificity was calculated as 97.83%, in \nwhich both were high. Thus, in our study sensitivity came out to \nbe 87.04% specificity was found to be 95.74 % positive \npredictive value 95.92 % and negative predictive value 86.54 %. \nIn our present study transabdomina l ultrasonography diagnosed \na total of 35 patients as having Adenomyosis while \nhistopathology detected a total of 54 patients as Adenomyosis \nTAS missed 19 cases as Adeno myosis and diagnosed 2 other  \nlesions as Adenomyosis. \nThus, in our study statistical value s of TAS with respect to HPE \nfor adenomyotic lesions are; sensitivity came out to be 64.81%, \nspecificity was found to be 95.74 % positive predictive \nvalue94.59% and negative predictive value 29.68 %. \nIn a study conducted by Devimeenal Jaganathan et al.  (2016) \nand published in 2017 titled as ‘ Comparison of the Diagnostic \naccuracy of Magnetic Resonance Imaginary (MRI) Trans \nabdominal ultrasonography (TAS), Trans Vaginal \nUltrasonography (TVS)in characte rizing the uterine mass \nlesion,”22 Thus the findings in ou r study are consistent with \nother studies. \nKang S et al.  study on specificity of 5mm as the maximum \nnormal uterine JZ thickness in detecting Adenomyosis \nconcluded that if a diagnosis of Adenomyosis is based solely on \nJZ thickness of 5mm as upper limit of n ormal may result in a \nhigh false positive rate.23 \nOur study has showed 12 mm as minimal thickness in positive \ncases of adenomyosis and p value is found to be highly \nsignificant. \nIn our present study polyps was diagnosed by TAS in 19 patients \nand HPE diagno sis of polyps was in 36 patients TAS labeled 1 \nother cases as polyp while HPE diagnosed a total of 36 cases \ni.e. as a whole 17 cases of polyp was missed by TAS. The \nsensitivity and specificity of TA S for Diagnosing Polyp as \ncompared to HPE was 52.77% and 9 8.46% while positive \npredictive value and negative predictive value were 95.00% and \n79.01% respectively. While negative predictive value comes out \nto be 96.67%. Thus, the sensitivity and specificity  of our study \nin diagnosing endometrial carcinoma is comp arable to other \n\nInternational Journal of Clinical Obstetrics and Gynaecology http://www.gynaecologyjournal.com \n~ 286 ~ \nstudies. \nThe total cases diagnosed as endometrial carcinoma by trans -\nabdominal sono graphy is only 4, while HPE diagnosed all 14 \ncases, thus the sensitivity of TAS against MRI in diagn osing \nendometrial carcinoma is 28.57% and specificity is 97.70%. all \nthe results were consistent with few previous studies.18,21,22 \n \nConclusion \nWe can concl ude from our discussion that AU B Abnormal \nuterine bleeding iscommon during the perimenopausal age group \nof 40-51 years while the causes ranged from medical d isorders \nto simple pathologies like myoma to malignancy. \nAUB existed among the parity -2 with chroni c onset and \nassociated with hypothyroidism being most common symptoms \nranged from heavy menstrual bl eeding to the post -menopausal \nbleeding. Endometrial biops y sample revealed a wide range of \nfindings from normal to endometrial carcinoma. Maximum \nhistopathological finding detected in our study was of myoma \nand Adenomyosis. \nSensitivity and specificity for detecting myoma in respect to \nHPE was found high. Transab dominal ultrasound is low cost \nprimary modality for screening and should include as a first line \nscreening method. Though the investigation and management of \nAUB among the non - gravid women was confu sing, \nhistopathological diagnosis proved to be the gold standard. \n \nReferences \n1. Grimbizis GF, Tsolakidis D, Mikes T et a l. A prospective \ncomparison of transvaginal ultrasound, saline infusion \nsonohysterography, and diagnostic hysteroscopy in the \nevaluation of endometrial pathology. Fertil Steril. 2010; \n94:2720-5. \n2. Espindola D, Kennedy KA, Fischer EG. Management of \nabnormal uterine bleeding and the pathology of endometrial \nhyperplasia. 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