Accepted Article
plane Coronal Ultrasound, 3D Neto Steven Lindheim +55(16)3633-0946; E-mail: E-mail: +55(16)3633-0946; Brazil; Country: Paulo; Sao State: Preto; Ribeirao Av. Bandeirantes Address: (DGO-FMRP-USP), Paulo of Sao Wilde London Hospital, London, United Kingdom. Kingdom. United London, Hospital, London College University 18) Italy, Florence, Florence, of University 17) Spain. Valencia, Infertilidad, de Valenciano Gynecology, Wright State University, Boonshoft School Medical Boston IsraelDeaconess Center, Radiology Beth Medical University Duke Obstetricsand Gynecology, 13)Division of Italy. University of Cagliari, Medicine, Houston, ofTX,Baylor College UnitedSt 10)Professor Germany. atthe University Medical Center University of Nepean, Sydney,NSW, Australia. Endo Pregnancy Advanced and Gynaecology,Early Acute Gynaecology, and 8)Obstetrics States. United MA, Brookline, School, Medical 7) Harvard Spain. Pamplona, Hernández University, Alicante, Spain. UniversityPaulo ofSao (DGO-FRMP-USP), RibeiraoPr Ribeirao Preto, Brazil. 4) Department of Obstetrics an Po Krakow, Center, Medical Private & Gynecology, Ludwin Authors: Authors: words: Key Title: Running University Medical School, Preto Ribeirao Gynecology, and of Obstetrics Department PMartins, Wellington *Corresponding author: author: *Corresponding Affiliations:
3 , Valeria M. , ValeriaLeitão 9 article as doi: 10.10 differencesbetween version lead to this may been through the copyediting, typesetting, pagination andproofreading process, which This article hasbeen accepted for publication andundergone full peer review but has not , Mark Hans Emanuel, Mark Congenital Uterine Malformation by Experts (CUM Experts by Malformation Uterine Congenital Artur Ludwin Mullerian ducts, Congenital Uterine Anomalies, Uterine septum, Agreement, Uterus, Ultrasound, Ultrasound, Uterus, septum,Agreement, Uterine Anomalies, CongenitalUterine ducts, Mullerian 1) Department of Gynecology and Oncology, Jagiellonian University, Krakow, Poland; 2) Ludwin 2) Ludwin Poland; Krakow, University, Jagiellonian Oncology, and of Gynecology 1)Department 15 Septate and normal/arcuate uterus Septate and , Antonio Pellicer 3 , Maribel , Maribel Acién 1,2 [email protected] , Wellington P. Martins WellingtonP. , 02/uog.18923 10 This article isprotectedby copyright. Allrights reserved. , William Gibbons 16 , Felice Petraglia Felice , normal/arcuate a normal/arcuate 6) Department of Obstetrics and Gynecology, University of Navarra, Navarra, of University Gynecology, and Obstetrics of Department 6) 5 , Juan L. Alcazar , Juan L. 11 , Stefano Guerriero Stefano , . * Postal code: 14048–900. Phone: +55(16)3602-2583; Fax: Fax: +55(16)3602-2583; Phone: 14048–900. Postal code: Reproductive Endocrinology and Infertility Department of of Department Infertility and Endocrinology Reproductive 3,4 17 Center, Durham, NC, United States. 14)Durham, Departmentof States. NC,UnitedCenter, , Carolina O.Nastri , Carolina , Ertan Saridogan , Ertan ates. 12) Department ofObstetrics and Gynecology, 9) Carl-von-Ossietzky-University Oldenburg, Oldenburg, d Gynaecology, Faculty of Me of d Gynaecology,Faculty nd septate nd septate uterus
of Medicine, Dayton, OH, United States. 16) Instituto 16) OH,United Instituto States. Dayton, of Medicine, surgery Nepean Unit, Hospital, SydneyMedical School and the Versionof Record. Please cite this 6 eto, Hospital/Miguel 5)SanJuanUniversityeto, Brazil. , MA, United States.15) Department of Obstetrics& ,Benacerraf Beryl land; 3) SEMEAR Fertilidade, Reproductive Medicine, 3) SEMEARFertilidade, Reproductive land; , 3900–8 andar - HCRP - Utrecht (NL) Utrecht and University Hospital (B).11) Ghent E): better criteria for distinguishing between distinguishing for criteria better E): 12 , William W.Hurd , William 18 . 4 , Inga , Inga Ludwin 7 , George Condous , George Campus Universitario; City: dicine of Ribeirão Preto, Preto, ofRibeirão dicine 1,2 13 , Marcela A. Coelho , Marcela A.Coelho , Deborah Levine 8 , Rudy-Leon De De , Rudy-Leon 14 ,
This articleisprotected bycopyright.Allrightsreserved. Accepted Article while those by ASRM underestimate this prevalence, leavin ASRMunderestimatethis whilethose by > 110% . reliable andwith the agreement in experts. opinion of depth indentation considering recommend We experts. by septate being off values for these measurements were: indentation depth depth indentation were: measurements these for off values ve standardwas reference usingCUMEas measurements 95%CI=0.90- (CCC=0.92, ratio andI:WT 95%CI=0.94-0.97) was 95%CI=0.98-0.99) (CCC=0.99, depth indentation the me Among three (kappa=0.93). was 98% agreement consider and (kappa=0.39), 87% septateCUME was and (kap 38% was andCUME ESHRE-ESGE between agreement The (gray-zone). be classified not would and13 uterus 90°) > angle < 10mm and (depth normal/arcuate 82 90°), < angle and > 15mm (depth 5septate in resulted criteria ASRM while 20 normal/arcuate, and septate82 normal/arcuate and uteri byCUME;ESHRE-ESGE Youden'sindex, considering the most voted option (CUME) asthereference standard. by thear test accuracywasassessed diagnostic the (CCC), coefficient correlation byconcordance assessed was reliability inter-rater the by kappa, wasassessed experts among agreement The ratio. (I:WT) towallthickness indentation and angle indentation ot Two relevant). isclinically indentation internal the by caused distortion of degree (the uterus septate or relevant) clinically not is indentation internal the by (norma normal/arcuate between tovote instructed were exper 15 to submitted and anonymized were indentation measurements suggested by recent guidelines, using the most voted option byexperts (CUME - ultrasound.We also aimto determine theinter-observer three-dimensional from view of coronal review from judgments subjective using uterus normal/arcuate U terine Conclusions: Conclusions:
Results: Results: Methods: Objectives: ABSTRACT M alformation by by alformation There was a good agreement among the impression the impression among agreement good There wasa Images of the coronal plane of the uterus from 100 women with suspected fundal internal internal fundal withsuspected women 100 from uterus the of plane coronal Imagesof the
Toassesswhetheragreement levelof among The suggested cut-off value by ESHRE-ESGE overestimates the prevalence of septate uterus uterus septate of prevalence the overestimates ESHRE-ESGE by value cut-off suggested The E xperts) as a reference standard. standard. reference asa xperts) ea underea ROC curve (AUROC) and the bestcut-off value wasassessed using her raters independently measured indentation depth, depth, indentation measured independently raters her ry good: AUROC between 0.96 and 1.00. The best cut- best The 1.00. and 0.96 AUROC between ry good: lmorphologyuterine ordegree ofdistortion caused ts (5 clinicians, 5 surgeons 5 ts (5clinicians, and5 surgeons sonologists). They pa=0.10); the agreement between ASRM criteria for criteria for theagreementbetween ASRM pa=0.10); better than both indentation angle (CCC=0.96, (CCC=0.96, angle indentation both than better 0.94). The diagnostic test accuracy of these three Thediagnostic accuracyofthesethree 0.94). test ing both septate and gray-zone as septate, the the septate, ingas bothseptate andgray-zone g in the gray zone most of gray zonemost the in g reliabilitydiagnosticand accuracy test of three ≥ criteria (I:WT ratio > 50%) resulted in 80 septate 80 septate 50%) resultedin (I:WT ratio> criteria 10 mm, indentation angle < 140°, and I:WT ratio ratio I:WT and 140°, < angle indentation mm, 10 asurements, the inter-rater reproducibility of of reproducibility inter-rater the asurements, experts indistinguishingbetween experts septate and of all experts (kappa = 0.62). There were 18 18 were There 0.62). = (kappa experts of all ≥ 10 mm as septate, since it is simple, simple, is it since septate, as mm 10 the uteri considered as as considered uteri the C ongenital
This articleisprotected bycopyright.Allrightsreserved. Accepted Article distinguishing normal/arcuateuterus,criteriaobjectivehave and some been between septate proposed fundus, of theuterine distortion of level evaluate the women without reproductive failures aiming to improve reproductive outcomes outcomes reproductive improve to aiming failures reproductive without women uterus with septate women in metroplasty isconsidered malformations were described two centuries ago ago centuries two described were malformations recommended use to indentationan wallthicknessto (I:WT) ratio > 50%todiagnose septate uterus two uterinemorphologies these distinguish between th societies on important most the recently, More can be iatrogenic,can be with psychological consequences. for distinguishing of ‘congenital anomaly’ without consid surgery areassociated with risk iatrogenic of unnecessary for indications liberal and definitions, inconsistent uterus, septate and normal/arcuate between differentiation developed uterus was called the arcuate uterus uterus arcuate the was called uterus developed criteria of deformity degree degree deformity of criteria measurable without parts two into cavity uterine divided a with and fundus uterine single with uterus the justifications for surgical incision of internal fundal indentation in normal/arcuate uterus uterus normal/arcuate in indentation fundal of internal incision for surgical justifications indentation angle >90°,and uterus that does fitnot those wouldcriteria on beleft a gray zone an and mm 10 < depth indentation an both have should uterus normal/arcuate a while 90°; < angle indentation ASRM recommended considering asseptate when thereis anindentation both depth and an >15mm because of itis very hard toprovide a referencestandard for distinguishing between these two uterine probably accuracy, test diagnostic on based not were values cut-off suggested the Additionally, community. Distinguishing between normal uterus and congenital uterine anomalies and naming of specific specific of naming and anomalies uterine congenital and uterus normal between Distinguishing INTRODUCTION The coronal plane of the uterus, obtained bythree-di uterus, obtained planethe of The coronal The lack of universally accepted criteria is likely to to likely is criteria accepted universally lack of The 4-6 . An intermediate benign form of anomaly between septate and normally normally and septate between anomaly of form benign intermediate . An 1-3 . For years the term ‘uterus ‘uterus term the years . For 5 cause confusion for patients, care providers and scientific and scientific care providers patients, for confusion cause . Despite. lackevidence, the ofrobust hysteroscopic e field published their recommendations on how to and, aiming to improve the inter-observer variability of variabilityof inter-observer the improve to aiming and, using the coronal plane of the uterus: ESHRE-ESGE ESHRE-ESGE uterus: of the plane coronal the using associated with associated infertility in andeven or miscarriages, eration their relevance; especially the septate uterus uterus the septate especially relevance; their eration treatment. Indeed, misdiagnosis and defining criteria mensional ultrasound, provided an excellent tool to to tool excellent an provided ultrasound, mensional septate/uterine septum’ meant meant septum’ septate/uterine 6-9 ; however, there are no no are ; however, there 6, 10 6 . Difficulties in . 13, 14 , while , while 11, 12 11, .
This articleisprotected bycopyright.Allrightsreserved. Accepted Article distinguishing between normal/arcuate and septate ut and septate normal/arcuate between distinguishing in measurements used most the for values cut-off best and accuracy test diagnostic the assess to (iii) uterus; measurements reliability/agreement ofcurrentlyused ultrasound techniques assessing when the coronalplane of uterus; the (ii) to evaluate theinter-observer The secondary aims (i)were: tocompare the preference regarding image quality providedfour by different3D recent two to results these compare to and ultrasound, three-dimensional from view coronal of review from judgments subjective using uterus normal/arcuate and estimate bestthe cut-off values for such measurements. Indeed, reference the estimate standardis pivotal to standard. reference possible best bethe would test diagnostic optimal from uterus imagesof opinion using op voted themost assumed that we Thus, morphologies. Reliability and Agreement Studies (GRRAS) (GRRAS) Studies Agreement and Reliability Reporting for Guidelines the on based were report and design The study. the and project entire the approved an congenital tract genital female of classification three- and on two- project observational prospective Epidemiology (STROBE) statement statement (STROBE) Epidemiology Krakow, Poland), using a single 3D data-set of each uterus acquired by an experienced observer. Fifteen invited invited Fifteen observer. experienced an by acquired uterus ofeach 3Ddata-set a single using Poland), Krakow, Gynecology, &Ludwin (Ludwin center medical private in anomaly uterine suspected with Jul-2016 and Jun-2016 Our primary objective was to assess objective wasto Our primary This was a reliability/agreement and diagnostic test a diagnostic test and areliability/agreement This was design Study METHODS For this study, we planned to includeFor weplanned this data-setsstudy, to 3D fr
16 . Written informed consent was obtained from all patients. patients. all from obtained was consent informed Written . the level ofagreement amongexpert 15 and STrengthening the Reporting of OBservational studies in in studies OBservational of Reporting the andSTrengthening omalies (KBET/236/B/2013).omalies The local ethics committee erus using experts’ opinion as reference standard. standard. asreference opinion experts’ erus using om 100 different uteri consecutively evaluated between between evaluated consecutively uteri different 100 om the diagnostic test accuracy of measurements and to to and measurements accuracyof test diagnostic the dimensional ultrasound in screening, diagnostic and ly published guidelines fromESHRE-ESGE and ASRM. to distinguish between normal/arcuate and septate and septate to distinguishbetween normal/arcuate tion among several experts blinded to other expert’s expert’s other to blinded experts several among tion ccuracy study, performed as a part of an ongoing ongoing asapartofan performed study, ccuracy s in distinguishing between septate septate distinguishing s in between
This articleisprotected bycopyright.Allrightsreserved. Accepted Article uterine surgeries uterine surgeries The exclusion criteria were unknown pregnancy, menopaus data-sets. 3D the using measurements the performed 2 observers experts wereincluded toperform subjective judgements, either normal/arcuate or partially septate were not included in this study study this in included not were septate partially or normal/arcuate either rendered mode (OmniView with VCI), and a curved rendered mode using HD-Live. Each one of these observers observers of these one Each HD-Live. using mode rendered curved a and VCI), with (OmniView mode rendered approximate angle between approximate the ultrasound obtain 120° after of sweep angle maximum acquisition. A volume 3D during moving from refrain and breath their hold to asked were patients The menstruation. hormonalon contraceptionexamined were regardle regula with women in cycle menstrual the 25) of 17 and days (between phase luteal in the (I.L) examiner byanexperienced manner in a standardized were performed USA) with intr WI, Milwaukee, volumetric Ultrasound, uterusinternalindentation with were not excluded. and asymmetrical T-shape uteri). the On contrary, septate andcomplete didelphys bicornuate, unicornuate, volume of the uterus of each woman was was recorded,volume woman oftheuterus each of an multiplanar view (MP) (MP) view multiplanar from plane coronal standard techniques: ultrasound different four using experts, for view coronal of images the prepared who 3D-ultrasound) with experience of 3 years with both VML, and (MACN institution another from 3D data-sets of uteri were obtained from non-pregnant women in reproductive age (>18 and < 45 years). <45years). and (>18 age reproductive in women non-pregnant from obtained were ofuteri data-sets 3D The 3D data-sets were acquiredultrasoundan using3D data-sets The scanning Ultrasound We included 3D datasetswomenWe includedofsusp consecutive with Subject selection and preparation 17, 18 . Moreover obvious uterine anomalies that were completely impossible to classify as as classify thatwere impossibleto anomalies completely uterine obvious Moreover . 19
, a rendered view of the coronal plane (volume contrast imaging, VCI), a curved curved a VCI), imaging, contrast (volume plane thecoronal of view , a rendered
beam and the uterine axis was 90°. was theuterineaxis and beam onymized, numbered, stored stored numbered, onymized, r cycles. Women withr cycles.irregular Women cycles, amenorrheaand avaginal probes (GE RIC 5–9 MHz). Ultrasound scans Ultrasound 5–9MHz). (GE scans probes RIC avaginal ssof the day of the cycle outside the periodof inga sagittal viewof the uteruswas adopted andthe 2 observers prepared the im2 observerspreparedthe system (Voluson E8 Expert BT13, GE Healthcare Healthcare GE BT13, Expert E8 (Voluson system e, malignante, lesions, neoplasms, specificbenign and icion of uterine internal indentation. A single 3D Asingle internalindentation. uterine of icion 5 (namely uterine agenesia, agenesia, uterine (namely and sent to observerstwo ages for the experts, and and experts, the for ages
This articleisprotected bycopyright.Allrightsreserved. Accepted Article experts. experts. other of the opinion the and measurements of results the to blinded were experts the bias avoid To field. same the for representative was who list, supplemental from expert another invited consecutively we participation, If experts. to sent consecutively were invitations of field in the 50 publications least at have should well-knownfields experts inthese publicat duetotheir Executive Committ of Presidents or Members (ii) Surgery; Gyneco fields: the in impact highest the with journals of Board Editorial of Editors/Members Chief/Deputy in Editors (i) following: were criteria inclusion and process clinicians,5 surgeons5 sonologistsand/or and radiolog malfor uterine congenital for criteria measurable the for field) should provide a better representati better a provide field) should for size to obtain sufficiently precise estimation ofre estimation precise sufficiently obtain size to uterus combinedinto were im a single were re images all the and images ofthe prepared half the effort effort the thepr in that increase argue authors additionally, some rarely worth of attempts to reach to attempts worth of rarely andthe W.P.M), (A.L., created were field) per experts list(2 andsupplemental experts of 15 list An initial rnilsfrteslcino xet th around experts 15 independent include to We intended Principles for the selectionof experts We planned toinclude100 because datafrom subjects, Sample size 23, 24 . The samplesize ofraters(exp more precisereliability coefficients more age and submitted to the 15 experts. experts.15 age and the submitted to on of medical community in the study subject. subject. study the in community on of medical erts) was arbitrarily chosen; although, more than threeraters is Obs/Gyn/Surg/Imaging; and (v) consent to participate. participate. to consent (v) and Obs/Gyn/Surg/Imaging; liability coefficients based on available guidelines available guidelines on based liability coefficients somebody from the initial list did not agreed on the from initialsomebody the listdidnotagreedonthe logy andReproductiveMedi mations without known personal conflict of interest: 5 mations withoutknownpersonalof interest: conflict ecision gained from sample > 50 subjects is rarely worth is rarelyworth 50 subjects sample> from ecision gained viewed by the two observers. The four images for each each for images four The observers. two viewed bythe ions about uterine anomalies; and (iv) invited experts (iv)invitedexperts anomalies; and uterine ions about ist specialized ingynecologi specialized ist ee of the targeted societies in the field; (iii) globally (iii) in globally field; the targetedsocieties ee ofthe this is considered as the minimum sufficient sample sample minimum sufficient the as is considered this e world not involved in previous consensuses on on consensuses previous in involved not e world 25 , we assumed that15raters(5raters cine/Imaging/Gynecological cine/Imaging/Gynecological cal imaging. The selection The cal imaging. 20-22 ;
This articleisprotected bycopyright.Allrightsreserved. Accepted Article ( dichotomous responses; and(ii) imagin ( voting quality image for datasets 100 the among 1-100) between numbers unique 15 of set 1 generate random online an (using chosen randomly examples each end techniqueof inthe questionnaire,the using for vote one only providing experts by rated were mode render HD-Live (iv) and VCI, with (iii) OmniView (VCI), values of patients, unbiased relative toavailable definitions, indentation is clinically relevant. Thesedefinitions we ut septate (ii) and relevant; clinically isnot indentation internal the by caused distortion of degree or morphology uterine = normal normal/arcuate (i) definitions: https://goo.gl/forms/XU51vdDe79Fw2RDE2 Supplemental Figure1 An online form was created and the link was submitted to the participating the experts to linkwas submitted theonlineformandAncreated was Rating process (i) techniques: imaging four of the quality The image quality Imaging Experts were asked to distinguish between normal/arcuate and septate uterus using the following following the using uterus septate and normal/arcuate between distinguish to asked were Experts definitions forClinical experts 6, 6, 11, 14, 26 . ). g quality using a multipoint scale. scale. multipoint a using quality g ). The experts were asked about: (i) uterine morphology using using morphology uterine (i) askedabout: were experts ). The re constructed as potentially important for management management for important aspotentially constructed re without any hint relative to other measurable cut-off cut-off other measurable to relative anyhint without an 11-pointan numericprovided scale(0-10).fifteen We erus = the degree of distortion caused by the internal internal the by caused distortion of degree =the erus numbers generator; https://www.randomizer.org/ to to https://www.randomizer.org/ generator; numbers standard coronal view, (ii) volume contrast imaging imaging contrast (ii) volume view, coronal standard
This articleisprotected bycopyright.Allrightsreserved. Accepted Article using the most voted option of the experts as reference standard. standard. reference as experts of the option voted most using the th assess testaccuracyof thediagnostic ASRM), to and two observers classify wereusedto uterine of morpho assessment easierOmniviewthan both use and HDlive to it and is it because VCI using wepreferred methods imaging the Among ratio. (I:WT) thickness wall to indentation ( thickness wall fundal uterine and angle, the followingmeasurements blinded toeach otherresults using VCIindentation mode: depth, indentation of parts intramural visible the identify to aiming plane contour contour uterine external the and line intercornual internal the between distance asthe measured and was defined indentation angle was measured tracing two lines close to the indentation apex indentation the closeto lines two tracing was measured angle indentation refl not would asreference line using this isso line interostial the cases. Additionally, measurable ( view MP standard using the internalindentation/partition in lower the partuterus of the connecting the highestpoint of the endometrialcavity in each side of the uterus)and thelowest point of the authors suggest usingauthors suggest interostial the line These measurements were used tocalculateinter-obse Two observers using theTwo sameinitial independ data-set, Measurements Thedepth indentationwasmeasured distance between internal asthe intercornual the the (lineline 14 . 27 . Supplemental1 Figure 14 ect the total indentation in these cases ( cases these in indentation the total ect , the position of the tubal ostia is frequently not so clear, particularly particularly soclear, not ostia is frequently tubal positionofthe , the Supplemental Figure 2 Figure Supplemental ); using this lineasreference would in result several non- both Fallopian tubes (mid-coronal plane) and performed (mid-coronal performed plane) Fallopiantubes and both e measurements and to determine the best cut-off values values cut-off best the determine to and e measurements metimes placed below the internal intercornual line, and and line, intercornual internal the below placed metimes logy as suggested byprevious guidelines (ESHRE-ESGE is the suggested imaging technique for myometrial formyometrial technique imaging suggested isthe rver reliability; and the average values between the the between values average the and reliability; rver ently manipulatedently theuterus toobtainthe coronal 6, 14 ); the latter was used tocalculated the ( Supplemental 2 Figure 6, 11 Supplemental3 Figure . The uterine wall thickness . The uterine wall thickness ). Although some ). Although ). The ). The
This articleisprotected bycopyright.Allrightsreserved. Accepted Article proportion of proportion agreement (p assessing each group of experts with Agreem test. Friedman with performed groups across agreement between ESGE-ESHRE, ASRM and CUME (the most voted option by experts: experts: by option voted most (the CUME and ASRM ESGE-ESHRE, between agreement express to used were (FN) negative false and (FP) positive false of proportion and kappa, agreement, observed M ESHRE-ESGE andASRM ESHRE-ESGE relative CUME. to probabilityof the estimate diagnosis the to calculated using assessed was value best cut-off very good, >0.99 >0.99 very good, and 0.95-0.99; good, 0.90-0.95; moderate, 0.70-0.90, = poor 0.70; < very poor, following: as interpreted were (LoA). CCC values of andlimits agreement (CCC) coefficient correlation concordance by assessed ratio were I:WT re Inter-observer 0.81–1.00. good, almostperfect/very 0.21–0.40; fair, <0.20; poor, follows: as agreement were presentednumbersas and of percentages. subjects values median as presented were variables continuous other The deviation. distribution wereasmean± presented with standard normal Variables normality test. USA). Continuousvariables wereanalyzedfor normal distribution usingD'Agostinothe &Pearson omnibus and USA), NY, Corp.,Armonk, (IBM 22 Statistics SPSS IBM alformation by
Results of the imaging quality rating summarized as quality Results imaging ofthe USA), CA, Diego, San Inc., Software 6 (GraphPad version Prism using GraphPad out carried were Analyses Statisticalanalysis E xperts). Diagnostic accuracy wastest assesse 22 ; limits of agreement were assessed to ; limitsofassessed were estima to agreement o ). The The ). κ -value was interpreted withreportingregard to thereliability/strength of respect to area of expertise) wa of expertise) area respectto Youden's index. The relative risk (RR) with 95% CI, and P value were were value P and CI, 95% with (RR) risk relative The index. Youden's moderate, 0.41–0.60; substantial/good, 0.61–0.80; and and 0.61–0.80; substantial/good, 0.41–0.60; moderate, septate uterus using ESHRE-ESGE relative to ASRM, and and ASRM, to relative ESHRE-ESGE using uterus septate liability and agreement of indentation depth, angle and and depth,of indentation angle agreement and liability median and interquartile range (IQR), and comparison comparison and (IQR), range and interquartile median with lower and upper quartiles. Categorical variables variables Categorical upper quartiles. and lower with ent across experts (assessing all experts, and then andthen allexperts, (assessing across experts ent Stata version 13.0 (StataCorp LP, College Station, TX, TX, CollegeStation, (StataCorp LP, 13.0 version Stata d by the area under ROC curve (AUROC) and the the and (AUROC) ROCcurve under area the by d te the margins The ofvariability/error. te the margins s assessed by kappa statistics and C ongenital U terine
This articleisprotected bycopyright.Allrightsreserved. Accepted Article = 25%; kappa = 0.56, 95%CI = 0.41-0.68; p 0.41-0.68; = 95%CI 25%; kappa =0.56, = angle,wall thickness) anduterine fo the study and analyzed as planned. Theresults forindividual measurements (indentation depth, indentation uterus septate complete 1, = uterus dydelphys 6, = cleft 2, Mayer-Rokitansky-Küster-Hauser syndrome = 2, unicornua because of following the reasons: unknown pregnancy = 1,myomas8,Asherman= surgeries11, = syndrome = Four women eligibility. for examined of themwere in 5 are presented surgeons) th of Details planned. as same the exactly were (N=100) (septate uterus = 92/500 = 18%; kappa = 0.74, 95%CI = 0.64-0.82; p 95%CI = 0.64-0.82; =0.74, =18%; kappa 92/500 = uterus (septate agreement inter-observer better a had and normal being as uteri the consider to likely weremore sonologists uterus = 138/500 = 28%; kappa = 0.53, 95%CI = 0.37-0.66; p 0.37-0.66; = 95%CI 0.53, = kappa 28%; = 138/500 = uterus agreement (kappa = 0.62, 95%CI = 0.48-0.73; p 0.48-0.73; = 95%CI 0.62, = (kappa agreement septate, 82 normal/arcuate and 13uteri would not be classified (gray-zone) ( 5 in resulted criteria ASRM while normal/arcuate, 20 only and septate 80 in resulted criteria ESHRE-ESGE voted most the using uteri 82 normal/arcuate and septate 0.10, 95%CI = -0.10 to 0.29); the agreement between ASRM criteria for septate and the opinion of experts was was of experts opinion the and for septate ASRM criteria between agreement the 0.29); to -0.10 95%CI= 0.10, 3D datasets were from143selected women who were subjects/uteri and (N=2), measurements for (N=15), assessment forsubjective experts of number actual The RESULTS Agreement between ESHRE/ESGE and ASRM criteria and with the exp the with and criteria ASRM ESHRE/ESGEand between Agreement Considering all the experts, 357/1500 (24%) thevo (24%) of 357/1500 all theexperts, Considering Agreement among experts The agreement between ESHRE-ESGE and the opinion of experts was only 38% (FP=62%, FN=0%, kappa = kappa FN=0%, (FP=62%, 38% was only experts of opinion the and ESHRE-ESGE between agreement The
Supplemental Table 1 ( Table 2 r each observer are presented on presented are observer r each )
o =83.2%). o (field, years of experience, country of residence). ofresidence). country experience, of years (field, = 86.3%). Considering the three groupsseparately, the declined for participate and39 women for participate were excluded declined e included fifteen experts clinicians,(5 imaging,5 and = 5. = Finally, datasetsof potentially eligible with suspected anomaly and all all and anomaly eligiblewithsuspected potentially option of all the 15 expe o tes were for septate uterus with a good overall overall a good with tes forseptateuterus were =81.2%) andsurgeons (septate uterus = 127/500 te uterus = 3, bicornuate or uterus with external external with or uterus bicornuate 3, = te uterus o = 92.2%) than (septate= 92.2%) both than clinicians erts’ opinion erts’ Supplemental Table2 Supplemental Table 1 100 women were included in in included were 100 women ). rts as reference standard. rts asreference standard. ( Table 3 )
. There18 were
This articleisprotected bycopyright.Allrightsreserved. Accepted Article = 8 (7.5-9.5), and HDlive=8 (7.5-9.5), =8 (8-9.5); (8-10); (6 7 = MP quality: imaging worse providing as considered I:WT ratio = -75% to to +96%. I:WT ratio =-75% were: indentation0.94, moderate). TheLoA depth = -1.7 95%CI angle(CCC=0.96, indentation both than better 0.01), and significantly lower if 0.01), and significantly usingtheASRM if higher be significantly would uteri ofseptate proportion Inco P <0.01). 5.9-32.7, CI 13.9, (RR ASRM criteria FN=1 (FP=1%, 98% was agreement the septate, 0. to 0.21 = 95%CI 0.39, = kappa FN=13%, (FP=0%, 87% experts’ opinion are presented on on presented are opinion experts’ and I:WT ratio > 111%. 111%. > ratio I:WT and by determined values cut-off best indentationdepth, 95%CI=0.96-1.00/0.90-0.99/0.94-1.00; Diagnostic test accuracy and best best and testaccuracy Diagnostic good) was significantly very 95%CI=0.98-0.99, (CCC=0.99, indentation inter-raterdepth of reliability The The proportion of septate uteri if using the ESHRE-ESGE criteria would be much higher than if using the using the if than higher be much would criteria ESHRE-ESGE the uteri if using septate of The proportion c different using uteri septate of proportion the in Difference Considering the opinion of all fifteen experts, thest fifteen ofall opinion the Considering quality image and techniques 3D Septate uterus by best cut-off values for currentl for values cut-off best by uterus Septate AUROC=1.00/0.96/0.99, good: wasvery measurements three ofthe accuracy test diagnostic The measurem used currently of reliability/agreement Inter-observer P =0.002. Considering only thefive clinicians the re Youden’s Indexwere:indentation depth Supplemental Table 3. P cut-off values for currently currently for values cut-off = 0.39. Considering only the five surgeons, the results were: MP = 7 (5- 7 MP = were: results the five surgeons, the only Considering 0.39. = %, kappa = 0.93, 95%CI = 0.90 to 0.95). 0.95). 0.90 to = 95%CI 0.93, = %, kappa criteria (RR 0.3, CI 0.1-0.8, P = 0.01). 0.01). P= 0.1-0.8, (RR0.3, CI criteria =0.94-0.97, good) and I:WT ratio (CCC=0.92, 95%CI=0.90- (CCC=0.92, ratio and good) I:WT =0.94-0.97, mparison withthemost vote y used measurements and their agreement with the with agreement the andtheir y usedmeasurements andard coronal plane from multiplanar view (MP) was was (MP) view multiplanar from plane coronal andard mm to +2.1mm; indentation angle = -17° to +16°; and and indentation anglemm to+2.1mm; = -17° to +16°;
-9),VCI=8 (8-10), Omniview =8 (8-9), and HDlive =9 55), and considering septate both and gray zone as using the ESHRE-ESGE criteria (RR 4.5, CI 2.9-6.8, P < < P 2.9-6.8, (RR 4.5, CI criteria using theESHRE-ESGE sults were: MP=7 (5-9.5), VCI = 8 (7.5-9.5), Omniview Omniview =8(7.5-9.5), VCI (5-9.5), MP=7 sults were: indentation angle and I:WTratio respectively. The riteria riteria used measurements ents ( Table 4, Figure 1 ≥ 10 mm, indentation angle 10 ( d option by experts, the d optionbyexperts,the Table 5 )
) ≤ 136°, 136°,
This articleisprotected bycopyright.Allrightsreserved. Accepted Article anomalies by caused internal fundalindentation were: of uterine classification the for standard reference the as deformity uterine of relevance clinical on judgments P=0.07. (9-10); 10 = HDlive and (8.5-9.5), 9 = Omniview (7.5-10), 8 = VCI (6-8.5), 7 = MP were: results the sonologists, five the only Considering P=0.14. = 8(8-9.5); and HDlive = 8(7.5-9.5), Omniview VCI= 8 (7.5-9.5), 9.5), values suggested by ESHRE-ESGE ASRMand definitions ( an indentation for study this by values cut-off suggested the using when accuracy test diagnostic a good have septate); nor normal/arcuate (neither proportion ofseptate uteri, leaving a large proportion uteriof septate byexperts’ opinion in thegray zone of septat proportion higher a much in result definition 136° (or < 140° for rounding), and I:WT ratio > 111% (or > 110% for rounding) ( rounding) for 110% (or > > 111% ratio and I:WT rounding), for 140° (or < 136° clinical relevance: appropriateness of our reference standard criteria for patient management should be be should management patient for criteria standard reference our of appropriateness relevance: clinical view. coronal it and agreement) very good of level Thefindings mostimportant this of study, usingvoted most the among independent option expert’s DISCUSSION - The three measurements suggested by those criteria (indentation depth, indentation angle and I:WT ratio) ratio) I:WT and angle indentation depth, (indentation criteria those by suggested measurements three - The poor: is opinion experts’ ESHRE-ESGE the with and criteria ESHRE-ESGE ASRM between agreement The - coronal using experts among ofagreement - Thelevel The most important limitation of this study is that ou isthat study limitation ofthis important The most ofuterine in visualization orHDlive) VCI with Omniview (VCI, modes rendered preferred had experts The - theindentation three - From these measurements, - The best cut-off values for defining septate uterus are: indentation depth depth indentation are: uterus septate defining for values cut-off best - The is the simplest to beperformed. experts’ opinion as the reference standard, however the the however standard, reference asthe opinion experts’ depth has the best inter-observer reliability inter-observer best has the depth
e uteri, and the ASRM criteria result in a much lower lower amuch resultcriteria in e theASRM and uteri, Table 6 gle andI:WTratiosubstantially are different from the r reference standard might not be good for assessing assessing begood for not might standard r reference view of uterus from 3D ultrasound is good; is 3Dgood; of uterus from view ultrasound ). Figure 2 ≥ 10 mm, indentation angle angle indentation 10mm, );
(CCC=0.99; (CCC=0.99; ≤
This articleisprotected bycopyright.Allrightsreserved. Accepted Article International multi-rater agreement study without any any without study agreement multi-rater International wall thickness by the study results(sep sources of variability sources of variability data-set beforemeasurements, believe andsuch we manipulation that is probably one mostimportant ofthe 3D the manipulate independently to had raters the hand, other the On for measurements. dataset 3D single si overestimated somewhat be might accuracy diagnostic and reliability/agreement of estimates the Additionally, all miscarriage. and infertility risk of high and low at uterus distinguishing for appropriate are values cut-off such using whether assessing studies by confirmed agreementAlthough among limitat raters. other study other study indentation as normal uterus depending on the uterine wall thickness thickness wall uterine on the depending uterus as normal indentation the angle, and uterine wall thickness thickness wall uterine and angle, the of measurements of thereliability that confirm ultrasound proposed bynew results studies interpretationof these without truewithout measurements is unreliable the planeis( anglethe coronal obtained that definitions of uterine anomalies, particularly the most used one one used most the particularly anomalies, uterine of definitions distinguishing between normal/arcuate and septate uterus in borderline cases: all most the important for standard reference the be usedas not should judgments subjective with hysteroscopy that indicate earlier highlighted was shape cavity uterine regarding deformity) from independent is that parameter variable (a wall uterine of the uterus for distinguishing anomalies and hysteros and anomalies for distinguishing uterus of the endoscopy is anexpensive and invasive to Reliability of currently used measurements ma ESHRE/ESGE consensus wrote that endoscopy shou endoscopy that wrote consensus ESHRE/ESGE 29 , with and without criteria and hysteroscopic vi hysteroscopic and criteria without and , with 34 17 : a small internal indentation mayrecognizedbe asseptate uterus, and larger internal as the same uterus in the same data-set 22 tate when I:WT > 110%) showed that I:WT can be accurate in diagnosis, diagnosis, in accurate be I:WTcan that showed 110%) > when I:WT tate . Moreover, the problem with the paradox of use the index based on on based ofusetheindex paradox with the problem the . Moreover, ions of these estimations were shown ol when used in the diagnostic setting setting the diagnostic used in ol when 28, 29 Supplemental Figure 4 Supplemental Figure , and reliability of laparoscopy have not been tested yet. yet. tested been not have oflaparoscopy reliability and , y be compared with four available studies withfour be compared y copy/laparoscopy does not provide such an image. image. an such provide not does copy/laparoscopy criteria for septate, arcuate and normal uterus uterus normal and arcuate septate, for criteria ld be used in debata in ld be used nce it was performed by highly trained raters using a a raters highly trained using by was performed it nce internal indentationisdepth significantly than better cut-offs for assessment of the level of reliability in in level ofreliability the of assessment for cut-offs 5 deos show assubjects, might providedifferent on imagesdepending , use patternrecognition of the coronal plane ). ). 18, 33, 33, 35 18, . Suggested cut-offs for uterine for uterine . cut-offs Suggested ble casesof anomalies 30, 31 6 , moreover hysteroscopy , moreoverhysteroscopy , two these studies may ed poor to moderate 11, 17, 32, 17, 33 11, . Revised 28 14 , and , and , but
This articleisprotected bycopyright.Allrightsreserved. Accepted Article another observer) indicate problems by measurement the repeating by just 80% ± (approximately benchmark this for error of margin wide but most reliable measurement of these three. ofthesethree. reliable measurement most indentation depth of 1 cm, but our findings could be helpour findingscould but be 1 cm, of depth indentation study protocol are twoongoing trialsnoneandof them contain areliable/accuratedefinition of septateregistered uterusin the indentation depth indentation depth in withagreement thebestcut-off considerin values (>50% ratio I:WT for and ASRM) by angle(<90° indentation for values cut-off suggested the however, uterus; septate and normal/arcuate between distinguishing for accuracy test diagnostic havegood ratio I:WT and angle indentation depth, Indentation zone. gray the in them of most leaving uteri, ofseptate prevalence the ASRMunderestimates by definition the while uterus, as areferencestandard, suggeste the opinion expert Using ultrasound. 3D by obtained uterus the of plane coronal the assessing just by uterus septate uterus. Experts, particularly sonologists, have a good
Currently, there is no evidence to support any surgical procedure for women with septate uterus uterus septate with women for procedure surgical any support to evidence isno there Currently, Experts showed a preference for rendered imaging techniques when assessing the coronal plane of the of plane the imaging when the techniques coronal rendered assessing afor preference showed Experts CONCLUSIONS 36, 37 ≥ ≥ 10 mmtodistinguish betweennormal/arcuate andsimplest septate,asitisthe and the . Our study should not be used as be a suppor used not should study . Our 10 mm, indentation angle <140°, and I:WT andI:WT <140°, angle indentation mm, 10 of its use in clinical practice. practice. clinical in use its of d cut-off by ESHRE-ESGE greatly overestimates the prevalence of septate septate of prevalence the overestimates greatly ESHRE-ESGE by cut-off d agreement inagreement distinguishing between normal/arcuate and g the experts’ opinion as the reference standard: standard: reference the as opinion experts’ the g ful for future ful forfuture studies to defi by ESHRE-ESGE) should be revised, as they are not not are asthey revised, be should ESHRE-ESGE) by ratio >110%. We suggest using the internal using theinternal Wesuggest >110%. ratio t for metroplasty in women with internal with in internal women formetroplasty t ne the eligibility criteria. criteria. theeligibility ne 9 . There . There
This articleisprotected bycopyright.Allrightsreserved. Accepted Article de Infertilidad, Valencia, Spain) for their help in data management. data in help their for Spain) Valencia, de Infertilidad, Po Krakow, Gynecology, Ludwin & (Ludwin Stryjak Marzena both thank to we want additionally expert; an as study this in participation his for USA) Ohio, Cleveland, Clinic,
The authors haveno conflict CONFLICTS OFINTEREST K/ZDS/005568). no. (grant University Jagiellonian by was supported This study FUNDING We want to thank Professor T. Falcone (Obstetrics, (Obstetrics, T.Falcone Professor to thank We want ACKNOWLEDGMENTS
s of interesttodeclare. Gynecology, andWomen'sHealth Cleveland Institute, land) and Doctor Fabio Cruz (Instituto Valenciano Valenciano (Instituto Cruz Fabio Doctor and land)
This articleisprotected bycopyright.Allrightsreserved. Accepted Article 10. 9. 12. 11. 8. 3. 2. 1. 18. 17. 16. 15. 14. 13. 7. 6. 5. 4. 19.
References References 29 studies. comparative of meta-analysis a anomalies: uterine congenital of implications Clinical GF. BC,Grimbizis Tarlatzis S, Gordts R, SP, Campo Papadopoulos Venetis CA, CD008576. CD008576. resection forwomen of reproducti M. Septum Goddijn M, van Wely F, Veen der Van BW, Mol MH, Emanuel CR, Kowalik JF, Rikken septate and bicornuate uterus. bicornuate uterus. and septate arcuate, of diagnosis in hysteroscopy diagnostic and hysterosalpingography sonohysterography, Ludwin A, Ludwin I, Banas T, Knafel A, Miedzyblocki M, Basta A. Diagnostic accuracy of of accuracy Diagnostic A. Basta M, Miedzyblocki A, T,Knafel Banas I, A,Ludwin Ludwin anomalies. uterine congenital of diagnosis ultrasound three-dimensional of Reproducibility D. Jurkovic L, Regan M, B,Backos Woelfer R, Salim uterus. for wo management versus expectant Metroplasty BongersMY,M, Goddijn MH, Kowalik CR, Emanuel Gynecol Minim Invasive tubal pregnancies, mullerian anomalies and intrauterine adhesions. adhesions. intrauterine and anomalies mullerian pregnancies, tubal ligation, totubal secondary occlusion tubal occlusion, tubal distal adhesions, adnexal of classifications the 100th anniversary of Rokitansky's death]. death]. Rokitansky's of the anniversary 100th Rudo Rokitansky, v. Carl Cruveilhier, W.[Jean Doerr J. Cruveilhier updated system. Acienof P,Acienfemale history The genital MI. trac anomalies in everyday practice. practice. in everyday anomalies duct Mullerian of classifications ASRM and the of ESHRE-ESGE Comparison I. A,Ludwin Ludwin dimensional ultrasonography. ultrasonography. dimensional for Medicine systems classification Reproductive Gynaecol for Society Embryology/European and Ludwin A,Ludwin I, Kudla M, Kottner J. 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Hysteroscopic metroplasty for metroplasty Hysteroscopic GE. Ekpo RF, Valle UterineASRM. septum: a guideline. Buttram Gomel VCJ, V,SieglerA, Gi A,DeCherney cases). Buttram VC, Jr., GibbonsWE. Mullerian anomalies: aproposed classification. (Ananalysis of144 Ultrasound Obstet Gynecol SP, Ferriani WP, Raine-Fenning NJ, Leite Martins technique may improve the reliability of measur of the reliability improve may technique : 665-683. : 665-683. 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bicornuate, and arcuate uteri. sonohysterography versus hysteroscopy withlaparoscopy in the differential diagnosis of septate, and ultrasonography three-dimensional and Two- A. T,Knafel Banas I, Ludwin K, A,Pitynski Ludwin results. new and review study: reliability of design for the requirements size Sample A. M, Donner M, Asyali Shoukri 700. 700. Cicchetti DV. The precision DV.Theprecision ofCicchetti re clinical and statistical significance of sample size requirements. requirements. size ofsample significance statistical and clinical solutions. proposed and diagnosis of the septate uterus: a randomized controlled trial. trial. controlled a randomized uterus: septate the of diagnosis hysteroscopic the of reproducibility the on criteria diagnostic of impact The FJ. Broekmans M, Vleugels MH, Emanuel M, Bongers MJ, Eijkemans HL, JC,Torrance Kasius MolBW, S, JG, Overdijkink Smit patients. infertile in uterus atoffice hysteroscopy septate of the the on diagnosis study agreement The international FJ. Broekmans R, Campo EJ, van Santbrink HM, S, Fatemi MJ, Veersema Eijkemans JC, Kasius JG, Smit group. (MUSA) Assessment Sonographic Uterus Morphological the from opinion consensus a masses: uterine and myometrium of features sonographic describe to measurements and definitions Terms, D. Timmerman T, Bourne E, Epstein S, Goldstein H, Brolmann Landolfo C, Installe AJ, Guerriero S, Exacoustos C,Gordts S, Benacerraf B, D'HoogheT, De Moor B, D, Van Schoubroeck A, CK,Votino Rasmussen L, Valentin FP, Leone M, T,Dueholm Bosch den Van 284-298. 284-298. Cocchetti DV. Sample size requireme size DV.Sample Cocchetti Obstet Gynecol measurements. ultrasound for results reproducibility Interpreting CO. Nastri WP, Martins Gynecol reviewsystematic (TRUST): in and of reliabilitystudies obstetrics gynecology. Techniques UltraSound of Reproducibility True WP. Martins CO, Nastri P, Roncato MA, Neto Coelho interobserver agreement studies with a fo size requirements MA. Sample A, Rotondi Donner Article 31. Prior M. Pilot randomised controlled trial of hysteroscopic septal resection. ISRCTN28960271 of septate, arcuate and normal normal and arcuate septate, of diagnosis hysteroscopy-based of Reliability Reply: FJ. Broekmans MJ, Eijkemans HL, Torrance JG, Smit estimate or guestimate? estimate orguestimate? uterus: normal and arcuate septate, of diagnosis hysteroscopy-based of Reliability I. A,Ludwin Ludwin dimensional ultrasound and implications for clinical practice. practice. forclinical implications and ultrasound dimensional Saravelos SH, Li TC. Intra- and inter-observer va inter-observer and Li Intra- SH, TC. Saravelos metroplasty. septumin the prediction and prevention of abnormal healing outcomesafter hysteroscopic uterine ofthe characteristics morphologic of Role R. Jach T, Banas K, I, Pitynski A, Ludwin Ludwin 564. 564. Ludwin A, Ludwin I, Pitynski K, Jach R, Banas T. Ar T. Banas R, Jach K, appropriate? uterus of septate diagnosis for Pitynski I, Ludwin A, Ludwin Obstet Gynecol Gynecol Obstet naked? is Emperor the seethat not we do why malformations: uterine othercommon and uterus septate for classification ESHRE-ESGE the of accuracy and rate Diagnostic I. Ludwin A, Ludwin Mol BWJ, Rikken JFW. The Randomised Uter RikkenRandomised The JFW. Mol BWJ, http://www.trialregister.nl/tria 2015; 2015; Hum Reprod Reprod Hum 46 2014; 2014; 2015; 2015; Stat Methods Med Res Med Methods Stat : 14-20. 14-20. : : Fertil Steril Steril Fertil http://www.isrctn.com/ISRCTN28960271 43 46 : 479-480. : 479-480. : 634-636. : 634-636. J Clin Exp Neuropsychol Neuropsychol Exp Clin J Hum Reprod 2014; 2013; J Minim Invasive Gynecol lreg/admin/rctview.asp?TC=1676 uterus: estimateuterus: orguestimate? 29 liability and validity estimates re estimates liability andvalidity : 1420-1431. : 1420-1431. 99 nts for increasing theprecision of : 2108-2113 e2102. 2016; 2016; 2004; binary outcome andmultiple raters. 31 Hum Reprod Hum ine Transsection Septum Trial (TRUST). 13 : 1376-1377. e ESHRE/ESGEthe criteria of female anomalies genital 1999; 1999; : 251-271. : 251-271. riability of uterine me uterine of riability r interval estimation ofthe kappa statistic for 21 2013; 2013; : 567-570. 567-570. : 2014; 2014; . 20 Hum Reprod Reprod Biomed Online Online Biomed Reprod J Clin Exp Neuropsychol Neuropsychol Exp J Clin Ultrasound Obstet Gynecol Gynecol Obstet Ultrasound 29 Hum Reprod . : 90-99. : 90-99. : 867-868. : 867-868. -visited: distinguishing between between -visited: distinguishing reliability estimates: problems estimates: reliability problems 2015; asurements 2016; Int JBiostat Int 30 Ultrasound Obstet Obstet Ultrasound 31 : 1323-1330. NTR1676 : 1377-1378. 1377-1378. : 2015; 2015; ISRCTN ISRCTN 2001; 2001; with three-with Ultrasound Ultrasound Ultrasound Ultrasound 2015; 31 2010; 2010; 23 : 557- : 695- 2009; 2009; 2015; 46 6 : :
This articleisprotected bycopyright.Allrightsreserved. Accepted Article Table 1 or normal/arcuate. septate either as to beclassified indent AND >15mm depth =indentation 90°; septate > angle * septate =indentation wallthickness to ** ratio >50%; other previously suggested cut-offs, and the most voted option by experts (CUME) (CUME) experts by option voted most the and cut-offs, suggested previously other CUME ASRM** ESHRE-ESGE*
Diagnosticnormal/arcuate rateof uter andseptate 21 5 18 0 82 80 13 82 0 20 omlAcaeGa oe Septate Normal/Arcuate Gray Zone normal = indentation depth < 10 mm AND indentation indentation AND 10 mm < depth indentation = normal us according to the original ESHRE-ESGE, ASRM and and ASRM ESHRE-ESGE, totheoriginal according us ation angle < 90°; Gray zone = not have the criteria havethecriteria 90°; Grayzone=not ation angle<
This articleisprotected bycopyright.Allrightsreserved. Accepted Article caused by the internal indentation is clinically relevant). relevant). isclinically indentation internal bythe caused internalofc the distortionby causedindentationisnot Table 2
oe o ett kpa 5 I Proportion of agreement 95% CI kappa Votes for septate Overall Surgeons Sonologists Clinicians Agreement among experts on voting between normal/arcuate (normal uterine morphology or degree ordegree morphology uterine (normal normal/arcuate between onvoting experts among Agreement 357/1500 (24%) 0.62 0.48-0.73 86.3% 86.3% 83.2% 92.2% 0.48-0.73 0.41-0.68 81.2% 0.64-0.82 0.62 0.56 0.37-0.66 0.74 0.53 (24%) 357/1500 (25%) 127/500 92/500 (18%) 138/500 (28%) linically relevant) or septate (the degree of distortion distortion of degree (the septate or relevant) linically
This articleisprotected bycopyright.Allrightsreserved. Accepted Article Table 3 negative;= true TPpositi false = FN positive; false = FP 90°; < angle indentation OR 10 mm > depth indentation = ***septate 90°; < angle * septate =indentationwall thickness to **50%; septate ratio=> indentation depth 15indentation > mmAND
ASRM septate and gray-zone*** septate** only ASRM ESHRE-ESGE* Agreement between ESHRE-ESGE and ASRM criteria with the experts’ opinion (reference standard) standard) (reference opinion experts’ the with ASRMcriteria and ESHRE-ESGE between Agreement ve;= TNtrue negative. ett gemn PT P N kappa 95% FN CI TP TN AgreementSeptate FP 7 201 0.39 13 0.21 0.10 0 -0.10 to to 0 82 81 5 62 17 1 0.93 20 0.550.90 98% 18 18 5 87% to 0.95 80 38%
0.29 0.29
This articleisprotected bycopyright.Allrightsreserved. Accepted Article Table 4 to wall thickness.indentation interval; I:WT= SD =standard deviation;=limitsLoA of agreement; CCC ifrnebtenosres Differencebetween observers I:WT ratio (%) angle (°) Indentation thickness wall Uterine (mm) (mm) depth Indentation Mean SD LoA CCC 95% CI Inter observeragreement and reliability reliability of themeasurements. .201 17210.987 0.982 0.991 2.1 0.922 0.903 0.938 95.5 -74.8 43.4 -1.7 0.864 0.817 0.905 2.0 10.4 -1.9 0.10 0.98 0.03 0.02 03 . -68 61 0.960 0.941 0.973 16.1 -16.8 8.4 -0.3 = concordance correlation coefficient; CI = confidence =confidence CI coefficient; correlation =concordance
This articleisprotected bycopyright.Allrightsreserved. Accepted Article reference standard. standard. reference Table 5 interval. = CI confidence ROCcurve; under AUROC =area AUROC AUROC 95%CI Best cut-off Sensitivity Specificity I:WT ratio angle Indentation depth Indentation Diagnostic test accuracy of the measurements considering the most voted option by experts as the the as by experts option voted most the considering measurements of the accuracy test Diagnostic .909-.0 1% 0% 96% > 0.99 0.94-1.00 100% 0.96 0.90-0.99 111% 0.96-1.00 1.00 ≥ ≤ 1 m10 99% 100% 10 mm 136° 94% 91% 91% 94% 136°
This articleisprotected bycopyright.Allrightsreserved. Accepted Article and suggested cut-off values according this study results. study this according values cut-off and suggested Table 6
Septate Normal/arcuate Suggested Septate Normal/arcuate by Suggested ESHRE-ESGE, ASRM and CUME definitions of internal indentation for normal/arcuate and septate uterus uterus septate and normal/arcuate for indentation internal of definitions CUME and ASRM ESHRE-ESGE, I:WT I:WT SR-SE SM ASRM ASRM ESHRE-ESGE I:WT > 50 % Angle < 90° Depth > 15 mm Clinically relevant relevant Clinically relevant clinically Not 15 mm > Depth 10 10 mm This articleisprotected bycopyright.Allrightsreserved. Accepted Article Figure 1 Bland-Altman plots for the absolute difference ob difference absolute Bland-Altmanplotsforthe served between measurements of the twoobservers. This articleisprotected bycopyright.Allrightsreserved. Accepted Article Indentation depth had highestthe inter-observer reliability andit is the simplest tobe performed. Figure 2 Criteria and the best cut-offs for distinguishing between normal/arcuate and septate uterus. uterus. septate and normal/arcuate between distinguishing for cut-offs best the and Criteria