Diagnostic accuracy of transvaginal ultrasound for non-invasive diagnosis of bowel endometriosis: systematic review and meta-analysis

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1 Ultrasound Obstet Gynecol 2011; 37: Published online in Wiley Online Library (wileyonlinelibrary.com). DOI: /uog.8858 Diagnostic accuracy of transvaginal ultrasound for non-invasive diagnosis of bowel endometriosis: systematic review and meta-analysis G. HUDELIST*, J. ENGLISH, A. E. THOMAS, A. TINELLI, C. F. SINGER** and J. KECKSTEIN *Department of Obstetrics and Gynaecology, Endometriosis and Pelvic Pain Clinic, Wilhelminen Hospital, Vienna, Austria; SEF, Stiftung Endometrioseforschung; Department of Obstetrics and Gynaecology, University of Brighton Medical School, Brighton, UK; Department of Methodological Research and Statistics, Institute of Psychology, Alpe Adria University Klagenfurt, Klagenfurt, Austria; Department of Obstetrics and Gynaecology, Lecce Hospital, Lecce, Italy; **Department of Obstetrics and Gynaecology, University of Vienna, Vienna, Austria; Department of Obstetrics and Gynaecology, Center for Endometriosis, Villach Hospital, Villach, Austria KEYWORDS: deep infiltrating endometriosis; presurgical diagnosis; transvaginal ultrasound ABSTRACT Objective To critically analyze the diagnostic value of transvaginal sonography (TVS) for non-invasive, presurgical detection of bowel endometriosis. Methods MEDLINE ( ) and EMBASE ( ) databases were searched for relevant studies investigating the diagnostic accuracy of TVS for diagnosing deep infiltrating endometriosis involving the bowel. Diagnosis was established by laparoscopy and/or histopathological analysis. Likelihood ratios (LRs) were recalculated in addition to traditional measures of effectiveness. Results Out of 188 papers, a total of 10 studies fulfilled predefined inclusion criteria involving 1106 patients with suspected endometriosis. The prevalence of bowel endometriosis varied from 24 to 73.3%. LR+ ranged from 4.8 to and LR ranged from 0.02 to 0.36, with wide confidence intervals. Pooled estimates of sensitivities and specificities were 91 and 98%; LR+ and LR were and 0.09; and positive and negative predictive values were 98 and 95%, respectively. Three of the studies used bowel preparations to enhance the visibility of the rectal wall; one study directly compared the use of water contrast vs. no prior bowel enema, for which the LR was 0.04 and 0.47, respectively. Conclusions TVS with or without the use of prior bowel preparation is an accurate test for non-invasive, presurgical detection of deep infiltrating endometriosis of the rectosigmoid. Copyright 2011 ISUOG. Published by John Wiley & Sons, Ltd. INTRODUCTION Over the past decade, the use of transvaginal sonography (TVS) has improved the quality of non-invasive assessment of patients with suspected pelvic pathologies. With respect to endometriosis TVS has been shown to be a highly sensitive tool for the detection of ovarian endometriomas 1 and is far superior to routine clinical examination alone 2,3. Moore et al. 1 systematically reviewed 67 papers on the validity of TVS for the detection of pelvic endometriosis, out of which seven fulfilled the inclusion criteria and focused on TVS imaging of ovarian endometriomas. The prevalence of the condition ranged between 13 and 38%. Sensitivities, specificities and positive (LR+) and negative likelihood ratios (LR )insix studies using gray-scale ultrasonography ranged between 64 and 89%, 89 and 100%, 7.6 and 29.8 and 0.1 and 0.4, respectively. The authors therefore concluded that TVS should be regarded as a useful test for identifying cystic ovarian endometriosis presurgically. Recent studies also suggest that TVS could be an accurate method for the detection of endometriosis in extra-ovarian locations, i.e. uterosacral ligament involvement, endometriosis of the rectovaginal space, the pouch of Douglas, the vagina, the urinary bladder and deep infiltrating endometriosis (DIE) of the rectosigmoid 3 8.Since TVS is a readily available, cost- and time-effective diagnostic instrument when compared to other radiological procedures such as computed tomography and magnetic resonance imaging (MRI) 9,10, several investigators have further examined the diagnostic value of TVS for the noninvasive detection of DIE infiltrating the bowel. The aim Correspondence to: Prof. G. Hudelist, Department of Obstetrics and Gynaecology, Endometriosis and Pelvic Pain Clinic, Wilhelminen General Hospital, Montlearstrasse 37, A-1160 Vienna, Austria ( gernot hudelist@yahoo.de) Accepted: 7 October 2010 Copyright 2011 ISUOG. Published by John Wiley & Sons, Ltd. SYSTEMATIC R E VIEW

2 258 Hudelist et al. of this work was to systematically analyze the published literature evaluating the role of TVS for the detection of DIE involving the rectosigmoid. METHODS The MEDLINE ( ) and EMBASE ( ) databases were searched using the following search strategy: 1. (pelvic or ovarian or deep infiltrating) near2 (mass or cyst * or tumo * r) 2. ENDOMETRIOSIS in MeSH or 1 or BOWEL ENDOMETRIOSIS 3. 2, not case reports, not review articles 4. with checktags female and human 5. with ULTRASOUND /all subheadings or TRANS- VAGINAL /all subheadings or SONOGRAPHY Abstracts of all studies identified were read and manuscripts were then fully reviewed. In addition, reference lists of all reviewed manuscripts were searched for additional data. Study selection and assessment of quality were performed independently by two reviewers (G. H. and J. E). Selection criteria All studies included in the present review had to be prospective and were required to involve both TVS examination and surgical exploration of the pelvis either by laparoscopy or by laparotomy (as stated by Moore et al. 1 ). Scientific publications including case reports, studies on adenomyosis or extrapelvic endometriotic disease as well as retrospective case series and review articles were excluded. Studies reporting on pregnant women, rectal ultrasound as the only examination and endoscopic sonography were also excluded from this review. Patients included in the studies presented with either subfertility or symptoms suggestive of endometriosis. According to the criteria of Moore et al. 1, studies were considered to be of good quality when information on recruitment of patients, blinding of ultrasound operators and surgeons and data on the technical equipment were provided. In order to define the stage and severity of disease (i.e. the final endpoint of diagnosis), studies had to describe the anatomical location of deep infiltrating disease combined with histological confirmation of endometriosis. Moore et al. 1 considered that studies missing one or two of these criteria were of moderate/poor quality. Data extraction and presentation of results As described by Moore et al. 1,2 2 tables were created to validate test results against surgical and histopathological findings aimed at defining whether DIE involving the rectosigmoid can be detected by TVS. In addition, QUADAS (quality assessment of diagnostic accuracy of studies) was used to assess the studies 11. As described previously, study quality is defined as high when 9 items out of 14 are met, moderate when 6 items are met and low when < 6 criteria are met 12.LR+, LR and test accuracy were calculated in studies lacking these data. Confidence intervals (CIs) were calculated as described previously 1 using CATMaker statistical software (Centre for Evidence-Based Medicine, Oxford, UK). In two cases raw data (true and false positive and negative rates) were obtained from the authors. Since heterogeneity is a common finding in diagnostic meta-analyses we calculated Cochran s Q and I 2 for all measures to assess the significance and magnitude of study heterogeneity 13. A forest plot was used to assess eventual outlier studies (data not shown). Potential sources of heterogeneity were explored by random-effects meta-regression. Number of subjects, year of publication, QUADAS scores and prevalence were used as study-level covariates that predicted the logarithm of diagnostic odds ratios (DORs). The studies were weighted by the inverse of variance of the DOR to consider the precision with which each study measured it. Relative DORs were calculated to compare the overall DOR with the adjusted DOR. When heterogeneity between studies is present, a random-effects model can be used to obtain pooled estimates 14. We applied random-effects models with the DerSirmonian Laird estimator in order to determine overall estimates of sensitivity, specificity, LR+, LR and DOR. For data with zero counts a continuity correction of 0.5 was added to every value in that study, thereby allowing the calculation of all LRs 15. For the assessment of publication bias Egger s test and Begg s test were conducted and funnel plots were investigated (data not shown). The tests for publication bias and funnel plots were performed with R statistical software version metafor package (R Development Core Team, Vienna, Austria) 16.All other analyses were performed with MetaDiSc statistical software version (Hospital Universitario, Madrid, Spain). RESULTS The initial implementation of the research strategy revealed 188 studies relating to endometriosis and/or adenomyosis and/or ovarian endometriosis diagnosed by laparoscopy or laparotomy and/or ultrasonography. Out of these only 51 papers specifically used TVS and surgical exploration to diagnose DIE. Of these 51 papers, seven were excluded because they were case reports or descriptive in nature. A further 18 papers did not meet the inclusion criteria due to the fact that they were review articles, despite the exclusion of this article type in the primary search process. Finally, three other publications included comments on publications and were also excluded from the final analysis, leaving 23 manuscripts for review 3 5,7,8, Out of these 23 papers, 13 publications were excluded due to methodological problems; three papers were purely retrospective in nature 18,27,28 ; four manuscripts

3 Transvaginal ultrasound in the diagnosis of bowel endometriosis 259 were excluded because they involved a group of patients already described in a previous publication by the same group of authors 5,7,25,29 and another four papers were not included in the analysis because insufficient information was provided on the presence or absence of bowel endometriosis within the group of women with endometriosis 22,30,32,34. Two papers were excluded due to the low number of cases with proven bowel endometriosis 24 or insufficient information on the anatomical localization of DIE affecting the bowel 35. Thus 10 papers fulfilled the inclusion criteria and were included in the final review. In addition to the quality criteria described by Moore et al. 1, the QUADAS scores were calculated for each of the studies. These ranged from 7 to 13, reflecting high methodological quality in eight cases and moderate quality in two cases. Out of these, four papers evaluated the diagnostic value of TVS for the detection of DIE infiltrating the rectosigmoid excluding other possible locations of DIE in the analysis 8,23,31,33. All other works also evaluated the potential of TVS for the visualization of other affected sites of deep infiltrating disease such as the vagina, rectovaginal space, uterosacral ligaments, bladder and pouch of Douglas. Two papers addressed the use of TVS to diagnose DIE involving the rectum, pouch of Douglas, vagina, rectovaginal space, uterosacral ligaments and bladder 3,26 using laparoscopic exploration and histological confirmation of endometriosis as the gold standard test. One work compared TVS with MRI to detect DIE preoperatively compared to the gold standard laparoscopy without histological confirmation 21. One paper assessed the diagnostic value of TVS vs. rectal endosonography 19 ; two papers compared TVS with MRI, digital examination 4 and rectal endosonography 20 to detect DIE presurgically. Data on the quality of these studies including number of patients and cases of bowel endometriosis, recruitment criteria, blinding, information and presence of diagnostic criteria and technical details, data on reference standards and assessment of the grade of study quality are provided in Table 1. Table 2 depicts prevalence rates, sensitivities, specificities, test accuracies, positive predictive values (PPVs), negative predictive values (NPVs) and positive and negative LRs with CIs of all studies included in the final analysis. The number of patients with proven DIE infiltrating the bowel undergoing preoperative TVS ranged from to Sensitivity and specificity varied from 67 to 98% and 92 to 100%, respectively. As further demonstrated in Table 2, PPVs and NPVs ranged from 87 to 100% and 75 to 99%, respectively. LR+ goes up to infinity in cases lacking false-positive findings and thus are not shown. LR+ of the remaining studies varied from 4.8 to and LR from 0.02 to Three studies used TVS combined with a bowel enema to provide a better visualization of rectal wall anatomy, specifically muscularis propria 4,23,33. Valenzano Menada et al. 33 directly compared whether adding water-contrast in the rectosigmoid (RWC-TVS) during TVS improves presurgical diagnosis of rectal DIE with TVS. The sensitivity of RWC-TVS vs. TVS in identifying rectal DIE was 97 vs. 56%, the specificity 100 vs. 92.5%, the PPV 100 vs. 72% and the NPV 99 vs. 86%. Due to the absence of false-positive cases in the RWC-TVS cohort, LR+ could not be calculated, and LR was 0.04 vs for TVS. Meta-analysis of all studies included in the final review yielded significant results of Cochran s Q for all measures except LR+ (sensitivity: P < 0.001, Q = , df = 9, I 2 = 76.7%; specificity: P = 0.037, Q = 17.8, df = 9, I 2 = 49.5%; LR+: P = 0.144, Q = 13.4, df = 9, I 2 = 33.0%; LR : P < 0.001, Q = 52.6, df = 9, I 2 = 82.9%; DOR: P = 0.001, Q = 27.6, df = 9, I 2 = 67.4%), indicating considerable heterogeneity between studies. Significant values for study heterogeneity were mainly caused by two studies 21,26 that were aberrant in respect to sensitivity, LR and DOR. However, meta-regression including sample size, prevalence, QUADAS and year of publication did not yield any significant results: number of subjects (P = 0.197, relative DOR = 1.02 (95% CI, )), prevalence (P = 0.568, relative DOR = 0.97 (95% CI, )), QUADAS score (P = 0.319, relative DOR = 1.44 (95% CI, )) and year of publication (P = 0.298, relative DOR = 1.35 (95% CI, )). This suggests that although there was relevant heterogeneity between the studies, the influence of the covariates was not systematic. To account for heterogeneity we used a random-effects model to perform pooled estimates and estimate the respective CIs (Table 3). As all studies were conducted with women who suffered from pain or infertility, the pooled prevalence of 47% refers to women with specific symptoms. Evaluation by both Egger s test (P = 0.221) and Begg s test (P = 0.293) did not show evidence of publication bias for logdor. This result was confirmed by inspection of the funnel plots, which were all symmetrical for the investigated diagnostic measures (sensitivity, specificity, PPV, NPV, LR+, LR and accuracy; data not shown). DISCUSSION Endometriosis infiltrating the rectosigmoid can be suspected in up to 9 22% of all women with proven endometriosis 36,37. Symptoms of DIE involving the bowel vary greatly, ranging from asymptomatic women with extensive rectal involvement to patients with severe dysmenorrhea and dyschezia 38. Treatment strategies include hormonal preparations or surgical excision of endometriotic nodules 37,39, but presurgical staging of DIE is crucial for planning surgical treatment options. The findings of our systematic review clearly suggest that TVS is a highly valuable tool for the non-invasive detection of DIE affecting the rectosigmoid. In addition to sensitivities, specificities, PPVs, NPVs and test accuracies, we recalculated all positive and negative LRs since these reflect the diagnostic accuracy and the clinical usefulness of a test independently of the prevalence of the study condition in the study population 1. The prevalence of

4 260 Hudelist et al. Table 1 Characteristics of the studies included in the analysis Study Diagnostic criteria stated; ultrasound criteria for diagnosis Study design Blinding Recruitment; cause for referral Patients with suspected endometriosis (n) Cases of rectal/sigmoidal endometriosis (n) Test method Reference standard Study quality according to Moore criteria (QUADAS score) Bazot et al. Yes; thickening of the (2003) 19 muscularis propria > 3 mm, which is hypoechoic and thin (< 3 mm) under normal circumstances Bazot et al. Prospective Sonographers (2004) 3 Yes; as above Prospective Sonographer Carbognin et al. (2006) 21 Not described Prospective Not stated Abrao et al. Yes; nodular, predominantly (2007) 4 solid, hypoechogenic lesion adhered to the wall of the intestinal loop Valenzano Menada et al. (2008) 33 Yes; rectovaginal hypoechoic mass adherent and/or penetrated into the intestinal wall thickening the muscularis mucosa Guerriero et al. Yes; presence of some thin (2008) 26 band-like echoes departing from the center of the mass as an Indian head dress. Piketty et al. Yes; irregular hypoechoic (2009) 31 Bazot et al. mass, with or without hypo/hyperechoic foci involving colon muscularis Prospective Sonographer Prospective Sonographers Prospective No information given Prospective Sonographer (2009) 20 Yes; as above Prospective Radiologists Hudelist et al. Yes; as above Prospective Sonographer not (2009) 8 to PV Goncalves et al. Prospective Sonographer Yes; long, nodular, (2010) 23 predominantly solid, hypoechogenic lesion adhered to the wall of the intestinal loop TVS, RES Histology Moderate (9) TVS Histology in 29 Moderate (8) TVS, MRI Laparoscopic visualization TVS, MRI, PV TVS, RWC-TVS Poor (7) Histology Moderate (10) Histology Good (12) TVS Histology Good (11) TVS Histology Good (12) TVS, MRI, PV, RES Histology in 54 Good (12) TVS, PV Histology Moderate (13) TVS Histology Good (12) MRI, magnetic resonance imaging; PV, per vaginam clinical examination; QUADAS, quality assessment of diagnostic accuracy of studies; RES, rectal endosonography; RWC, rectal water contrast; TVS, transvaginal sonography.

5 Transvaginal ultrasound in the diagnosis of bowel endometriosis 261 Table 2 Analysis of data in the included studies Specificity (n (%)) PPV (%) NPV (%) Accuracy (%) LR+ (95% CI) LR (95% CI) Sensitivity (n (%)) Prevalence of rectal/sigmoidal endometriosis (n (%)) Study Bazot et al. (2003) 19 22/30 (73) 21/22 (95) 8/8 (100) ( ) Bazot et al. (2004) 3 47/142 (33) 41/47 (87) 92/95 (97) ( ) 0.13 ( ) Carbognin et al. (2006) 21 17/32 (53) 12/17 (71) 15/15 (100) ( ) 0.29 ( ) Abrao et al. (2007) 4 54/104 (52) 53/54 (98) 50/50 (100) ( ) Valenzano Menada et al. (2008) 33 23/90 (26) 22/23 (96) 67/67 (100) ( ) Guerriero et al. (2008) 26 39/88 (44) 26/39 (67) 45/49 (92) ( ) 0.36 ( ) Piketty et al. (2009) 31 75/133 (56) 68/75 (91) 56/58 (97) ( ) 0.10 ( ) Bazot et al. (2009) 20 63/92 (68) 59/63 (94) 29/29 (100) ( ) Hudelist et al. (2009) 8 48/200 (24) 46/48 (96) 149/152 (98) ( ) 0.04 ( ) Goncalves et al. (2010) 23 81/194 (42) 79/81 (98) 113/113 (100) ( ) LR+, positive likelihood ratio; LR, negative likelihood ratio; NPV, negative predictive value; PPV, positive predictive value. Table 3 Overall analysis of all studies included in the final analysis using a random-effects model to perform pooled estimates of variables Variable Estimate (95% CI) Sensitivity (%) 91 ( ) Specificity (%) 98 ( ) LR ( ) LR 0.09 ( ) DOR ( ) Prevalence (%) 47 ( ) PPV (%) 98 ( ) NPV (%) 95 ( ) DOR, diagnostic odds ratio (values not adjusted); LR+, positive likelihood ratio (with continuity correction for studies with null-cells); LR, negative likelihood ratio; NPV, negative predictive value; PPV, positive predictive value. DIE involving the bowel ranged from 24 to 73%, which may be attributable to different referral patterns and the availability of tertiary referral centers providing sufficient expertise in the presurgical diagnosis and treatment of rectal DIE. LR+ ranged from to and LR from to The combined use of TVS with vaginal examination may further increase the diagnostic accuracy, with reported LR+ and LR and , respectively. In addition, it should be noted that LR+ went up to infinity in five studies (Table 2), suggesting highly accurate presurgical test results. Performance of a meta-analysis of all included studies by using a random-effects model to calculate pooled estimates revealed LR+ and LR of and 0.09, respectively. According to Altman 40, a very helpful test for establishing or excluding a condition is characterized by an LR+ > 10 and an LR < 0.1, while a test is regarded as moderately helpful with an LR+ between 5 and 10 and an LR between 0.1 and 0.2. As depicted in Table 3, the results of our meta-analysis clearly suggest that TVS is indeed very useful for sonographic diagnosis but also presurgical exclusion of bowel endometriosis. Two studies 21,26 were aberrant with respect to sensitivity, LR and DOR. This may be attributable to low sensitivity values in association with small patient numbers 21 or the use of tenderness guided transvaginal sonography 26, which may be less sensitive in cases of endometriotic involvement of the upper rectum/lower sigmoid, since these locations may not appear as painful sites when using this technique. The conclusions of this review are weakened by the fact that blinding of the surgeon was missing in all studies included in the final analysis, which might have a potential influence on the results of the gold standard test, i.e. surgery. On the other hand, information on the preoperative findings is essential for guiding the surgical technique and surgical diagnosis of endometriosis in everyday clinical practice. An additional variable in the accuracy of the gold standard test, i.e. laparoscopy, is the fact that several studies did not provide sufficient information about the

6 262 Hudelist et al. surgical exploration of the patients with DIE 3,20,21,26 since complete cul-de-sac obliteration secondary to endometriosis was reported but could not necessarily be surgically cleared. This may, in cases of DIE affecting the non-visible, occluded lower rectum, lead to misinterpretation and observation bias of the gold standard test and consequently negatively affect the validation of the index test, i.e. TVS. Hence, full surgical exploration of patients with an occluded pouch of Douglas is important for the final and accurate diagnosis of bowel endometriosis since DIE may be missed at the time of laparoscopy, thereby questioning the quality of laparoscopic visualization of the pelvis as the gold standard test for the diagnosis of endometriosis. Another limiting factor to the results of this systematic review is the heterogeneity of populations included in the studies. Some authors failed to provide sufficient data on the selection criteria and referral patterns of centers where studies were conducted. Due to the fact that most patients were treated in tertiary referral centers, it is conceivable that the study populations represent an already preselected patient cohort with a high prevalence of bowel endometriosis. As a consequence, the conclusions of this review may therefore only be applicable to a tertiary referral setting and patients with a high risk for DIE. In clinical everyday practice, exclusion of DIE is of critical importance since extensive bowel involvement warrants an interdisciplinary approach and referral to a tertiary center. In conclusion, the majority of the published evidence suggests that TVS is a highly useful and easy accessible test for the preoperative detection of DIE infiltrating the rectosigmoid. Whether the widespread use of TVS and the inclusion of TVS in specialist training programs lead to a reduction in the diagnostic delay of patients with endometriosis remains to be seen. ACKNOWLEDGMENTS The authors want to thank Dr Simone Ferrero and MMag Nadja Fritzer for their support and helpful advice. This work was supported by the OEGEO, Österreichische Gesellschaft für Endokrinologische Onkologie. REFERENCES 1. Moore J, Copley S, Morris J, Lindsell D, Golding S, Kennedy S. A systematic review of the accuracy of ultrasound in the diagnosis of endometriosis. Ultrasound Obstet Gynecol 2002; 20: Nezhat C, Santolaya J, Nezhat FR. Comparison of transvaginal sonography and bimanual pelvic examination in patients with laparoscopically confirmed endometriosis. J Am Assoc Gynecol Laparosc 1994; 1: Bazot M, Thomassin I, Hourani R, Cortez A, Darai E. Diagnostic accuracy of transvaginal sonography for deep pelvic endometriosis. Ultrasound Obstet Gynecol 2004; 24: Abrao MS, Goncalves MO, Dias JA Jr, Podgaec S, Chamie LP, Blasbalg R. Comparison between clinical examination, transvaginal sonography and magnetic resonance imaging for the diagnosis of deep endometriosis. Hum Reprod 2007; 22: Bazot M, Malzy P, Cortez A, Roseau G, Amouyal P, Darai E. Accuracy of transvaginal sonography and rectal endoscopic sonography in the diagnosis of deep infiltrating endometriosis. Ultrasound Obstet Gynecol 2007; 30: Hudelist G, Keckstein J. The use of transvaginal sonography (TVS) for preoperative diagnosis of pelvic endometriosis. Praxis (Bern 1994) 2009; 98: Hudelist G, Oberwinkler KH, Singer CF, Tuttlies F, Rauter G, Ritter O, Keckstein J. Combination of transvaginal sonography and clinical examination for preoperative diagnosis of pelvic endometriosis. Hum Reprod 2009; 24: Hudelist G, Tuttlies F, Rauter G, Pucher S, Keckstein J. Can transvaginal sonography predict infiltration depth in patients with deep infiltrating endometriosis of the rectum? Hum Reprod 2009; 24: Kinkel K, Frei KA, Balleyguier C, Chapron C. Diagnosis of endometriosis with imaging: a review. Eur Radiol 2006; 16: Brosens I, Puttemans P, Campo R, Gordts S, Kinkel K. Diagnosis of endometriosis: pelvic endoscopy and imaging techniques. Best Pract Res Clin Obstet Gynaecol 2004; 18: Whiting P, Rutjes AW, Reitsma JB, Bossuyt PM, Kleijnen J. The development of QUADAS: a tool for the quality assessment of studies of diagnostic accuracy included in systematic reviews. BMC Med Res Methodol 2003; 3: Meredith SM, Sanchez-Ramos L, Kaunitz AM. Diagnostic accuracy of transvaginal sonography for the diagnosis of adenomyosis: systematic review and metaanalysis. Am J Obstet Gynecol 2009; 201: 107.e Sidik K, Jonkman JN. Simple heterogeneity variance estimation in meta-analysis. J R Stat Soc [Ser C] 2005; 54: Devillé W, Buntix F, Bouter LM, Montori VM, de Vet HC, van der Windt DA, Bezemer PD. Conductiong systematic reviews of diagnostic studies: didactic guidelines. BMC Med Res Methodol 2002; 2: Goodacre S, Sampson F, Thomas S, van Beek E, Sutton A. Systematic review and meta-analysis of the diagnostic accuracy of ultrasonography for deep vein thrombosis. BMC Med Imaging 2005; 5: Viechtbauer W. Conducting meta-analysis in R with the metaphor package. J Stat Softw 2010; 36: Zamora J, Abraira V, Muriel A, Khan K. Coomarasamy Meta- DiSc: a software for meta-analysis of test accuracy data. BMC Med Res Methodol 2006; 6: Balleyguier C, Chapron C, Dubuisson JB, Kinkel K, Fauconnier A, Vieira M, Hélénon O, Menu Y. Comparison of magnetic resonance imaging and transvaginal ultrasonography in diagnosing bladder endometriosis. J Am Assoc Gynecol Laparosc 2002; 9: Bazot M, Detchev R, Cortez A, Amouyal P, Uzan S, Darai E. Transvaginal sonography and rectal endoscopic sonography for the assessment of pelvic endometriosis: a preliminary comparison. Hum Reprod 2003; 18: Bazot M, Lafont C, Rouzier R, Roseau G, Thomassin-Naggara I, Darai E. Diagnostic accuracy of physical examination, transvaginal sonography, rectal endoscopic sonography, and magnetic resonance imaging to diagnose deep infiltrating endometriosis. Fertil Steril 2009; 92: Carbognin G, Girardi V, Pinali L, Raffaelli R, Bergamini V, Pozzi Mucelli R. Assessment of pelvic endometriosis: correlation of US and MRI with laparoscopic findings. Radiol Med 2006; 111: Eskenazi B, Warner M, Bonsignore L, Olive D, Samuels S, Vercellini P. Validation study of nonsurgical diagnosis of endometriosis. Fertil Steril 2001; 76: Goncalves MO, Podgaec S, Dias JA Jr, Gonzalez M, Abrao MS. Transvaginal ultrasonography with bowel preparation is able to predict the number of lesions and rectosigmoid layers affected in cases of deep endometriosis, defining surgical strategy. Hum Reprod 2010; 25:

7 Transvaginal ultrasound in the diagnosis of bowel endometriosis Grasso RF, Di Giacomo V, Sedati P, Sizzi O, Florio G, Faiella E, Rossetti A, Del Vescovo R, Zobel BB. Diagnosis of deep infiltrating endometriosis: accuracy of magnetic resonance imaging and transvaginal 3D ultrasonography. Abdom Imaging 2009; 35: Guerriero S, Ajossa S, Gerada M, D Aquila M, Piras B, Melis GB. Tenderness-guided transvaginal ultrasonography: a new method for the detection of deep endometriosis in patients with chronic pelvic pain. Fertil Steril 2007; 88: Guerriero S, Ajossa S, Gerada M, Virgilio B, Angioni S, Melis GB. Diagnostic value of transvaginal tendernessguided ultrasonography for the prediction of location of deep endometriosis. Hum Reprod 2008; 23: Hensen JH, Puylaert JB. Endometriosis of the posterior culde-sac: clinical presentation and findings at transvaginal ultrasound. AJR Am J Roentgenol 2009; 192: Koga K, Osuga Y, Yano T, Momoeda M, Yoshino O, Hirota Y, Kugu K, Nishii O, Tsutsumi O, Taketani Y. Characteristic images of deeply infiltrating rectosigmoid endometriosis on transvaginal and transrectal ultrasonography. Hum Reprod 2003; 18: Menada MV, Remorgida V, Abbamonte LH, Fulcheri E, Ragni N, Ferrero S. Transvaginal ultrasonography combined with water-contrast in the rectum in the diagnosis of rectovaginal endometriosis infiltrating the bowel. Fertil Steril 2008; 89: Okaro E, Condous G, Khalid A, Timmerman D, Ameye L, Huffel SV, Bourne T. The use of ultrasound-based soft markers for the prediction of pelvic pathology in women with chronic pelvic pain can we reduce the need for laparoscopy? BJOG 2006; 113: Piketty M, Chopin N, Dousset B, Millischer-Bellaische AE, Roseau G, Leconte M, Borghese B, Chapron C. Preoperative work-up for patients with deeply infiltrating endometriosis: transvaginal ultrasonography must definitely be the first-line imaging examination. Hum Reprod 2009; 24: Savelli L, Manuzzi L, Pollastri P, Mabrouk M, Seracchioli R, Venturoli S. Diagnostic accuracy and potential limitations of transvaginal sonography for bladder endometriosis. Ultrasound Obstet Gynecol 2009; 34: Valenzano Menada M, Remorgida V, Abbamonte LH, Nicoletti A, Ragni N, Ferrero S. Does transvaginal ultrasonography combined with water-contrast in the rectum aid in the diagnosis of rectovaginal endometriosis infiltrating the bowel? Hum Reprod 2008; 23: Yazbek J, Helmy S, Ben-Nagi J, Holland T, Sawyer E, Jurkovic D. Value of preoperative ultrasound examination in the selection of women with adnexal masses for laparoscopic surgery. Ultrasound Obstet Gynecol 2007; 30: Holland TK, Yazbek J, Cutner A, Saridogan E, Hoo WL, Jurkovic D. Value of transvaginal ultrasound in assessing the severity of pelvic endometriosis. Ultrasound Obstet Gynecol 2010; 36: Chapron C, Chopin N, Borghese B, Foulot H, Dousset B, Vacher-Lavenu MC, Vieira M, Hasan W, Bricou A. Deeply infiltrating endometriosis: pathogenetic implications of the anatomical distribution. Hum Reprod 2006; 21: Chapron C, Fauconnier A, Vieira M, Barakat H, Dousset B, Pansini V, Vacher-Lavenu MC, Dubuisson JB. Anatomical distribution of deeply infiltrating endometriosis: surgical implications and proposition for a classification. Hum Reprod 2003; 18: Ballard K, Lane H, Hudelist G, Banerjee S, Wright J. Can specific pain symptoms help in the diagnosis of endometriosis? A cohort study of women with chronic pelvic pain. Fertil Steril 2010; 94: Keckstein J, Ulrich U, Kandolf O, Wiesinger H, Wustlich M. Laparoscopic therapy of intestinal endometriosis and the ranking of drug treatment. Zentralbl Gynakol 2003; 125: Altman DG. Statistics in medical journals: developments in the 1980s. Stat Med 1991; 10: