Systematic review and meta-analysis of the ultrasound diagnosis of pelvic organ prolapse (MUDPOP)

Our reference: GINE 101018 P-authorquery-v13 AUTHOR QUERY FORM Journal: GINE Please e-mail your responses and any corrections to: Article Number: 101018 E-mail: Dear Author, Please check your proof carefully and mark all corrections at the appropriate place in the proof (e.g., by using on-screen annotation in the PDF file) or compile them in a separate list. Note: if you opt to annotate the file with software other than Adobe Reader then please also highlight the appropriate place in the PDF file. To ensure fast publication of your paper please return your corrections within 48 hours. For correction or revision of any artwork, please consult http://www.elsevier.com/artworkinstructions. Any queries or remarks that have arisen during the processing of your manuscript are listed below and highlighted by flags in the proof. Click on the ‘Q’ link to go to the location in the proof. Location in Query / Remark: click on the Q link to go article Please insert your reply or correction at the corresponding line in the proof Q1 Please confirm that given name and surname are correctly identified. The different colors indicate whether tagged as first or last name. Please note that proper identification is key for correct indexing of the article. Q2 Please note that Refs. [9,25] and [13,27] were identical, and Ref. [25,27] have been deleted. The subsequent references have been renumbered. Please check this box or indicate your approval if you have no corrections to make to the PDF file Thank you for your assistance. ARTICLE IN PRESS +Model GINE 101018 1---12 Clínica e Investigación en Ginecología y Obstetricia xxx (xxxx) 101018 www.elsevier.es/gine clínica e investigación en ginecología y obstetricia REVIEW ARTICLE Systematic review and meta-analysis of the ultrasound diagnosis of pelvic organ prolapse (MUDPOP) J.A. García-Mejidoa,b,∗,F. Fernández-Palacínc,J.A. Sainz-Buenoa,b Q1 aDepartment of Obstetrics and Gynaecology, Valme University Hospital, Seville, Spain bDepartment of Surgery, Faculty of Medicine, University of Seville, Spain cDepartment of Statistics and Operational Research, University of Cadiz, Cadiz, Spain Received 2 October 2024; accepted 11 December 2024 KEYWORDS Systematic review; Meta-analysis; Pelvic floor; Ultrasonography; Pelvic organ prolapse Abstract We want to determine what the diagnostic criteria for pelvic organ prolapse (POP) should be for each pelvic compartment, establishing their diagnostic capability based on the current literature. This is a systematic review and meta-analysis of studies published until March 2024 that compared the diagnosis of POP between transperineal ultrasound and clinical POP-Q examination. The authors searched various databases including PubMed/MEDLINE, Scopus, Web of Science, CINAHL, The Cochrane Library and ClinicalTrials.gov. The Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool was used to assess study quality. Estimates of odds ratios, 95% confidence intervals and significance of sensitivity and specificity were obtained by aggregating all selected studies. All analyses were performed with R software. The search identified 2359 citations and after applying the inclusion and exclusion criteria, a total of 8 studies were finally included. All studies were considered to have low applicability concerns in terms of patient selection, index test, reference standard, flow and timing. The pooled sensitivity for ultrasound diagnosis of POP was 72.3% with a standard error of 3.1% (p< 0.001), tau of 0.11, I2of 97.1% (p< 0.001). The pooled specificity for ultrasound diagnosis of POP was 78.0% with a standard error of 4.4% (p< 0.001), tau of 0.16, I2of 98.6% (p< 0.001). The value of 10 mm is the cut-off point for the diagnosis of symptomatic cystocele (static measurement). A value of 15 mm is used for the diagnosis of symptomatic rectocele (static measurement) and for uterine prolapse (dynamic measurement). The current evidence is limited, so future research is needed to provide further confirmation. © 2024 Elsevier Espa˜ na, S.L.U. All rights are reserved, including those for text and data mining, AI training, and similar technologies. ∗Corresponding author. E-mail address: [email protected] (J.A. García-Mejido). https://doi.org/10.1016/j.gine.2024.101018 0210-573X/© 2024 Elsevier Espa˜ na, S.L.U. All rights are reserved, including those for text and data mining, AI training, and similar technologies. Please cite this article as: J.A. García-Mejido, F. Fernández-Palacín and J.A. Sainz-Bueno, Systematic review and meta-analysis of the ultrasound diagnosis of pelvic organ prolapse (MUDPOP), Clínica e Investigación en Ginecología y Obstetricia, https://doi.org/10.1016/j.gine.2024.101018 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 ARTICLE IN PRESS +Model GINE 101018 1---12 J.A. García-Mejido, F. Fernández-Palacín and J.A. Sainz-Bueno Q1 PALABRAS CLAVE Revisión sistemática; Metaanálisis; Suelo pélvico; Ecografía; Prolapso de órganos pélvicos Revisión sistemática y metaanálisis del diagnóstico ecográfico del prolapso de órganos pélvicos (MUDPOP) Resumen Queremos determinar cuáles deben ser los criterios diagnósticos de prolapso de órganos pélvicos (POP) para cada compartimento pélvico, estableciendo su capacidad diagnóstica en función de la literatura actual. Se trata de una revisión sistemática y un metaanálisis de los estudios publicados hasta marzo de 2024, que compararon el diagnóstico de POP entre la ecografía transperineal y el examen clínico POP-Q. Los autores buscaron en varias bases de datos, incluidas PubMed/MEDLINE, Scopus, Web of Science, CINAHL, The Cochrane Library y ClinicalTrials.gov. Se utilizó la herramienta Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) para evaluar la calidad de los estudios. Se obtuvieron estimaciones de odds ratio, intervalos de confianza del 95% y significancia de la sensibilidad y especificidad agregando todos los estudios seleccionados. Todos los análisis se realizaron con el software R. La búsqueda identificó 2.359 citas y, tras aplicar los criterios de inclusión y exclusión, se incluyeron finalmente un total de 8 estudios. Se consideró que todos los estudios tenían problemas de aplicabilidad bajos en términos de selección de pacientes, prueba índice, estándar de referencia, flujo y tiempo. La sensibilidad combinada para el diagnóstico ecográfico de POP fue del 72,3% con un error estándar del 3,1% (p < 0,001), tau de 0,11, I2del 97,1% (p < 0,001). La especificidad combinada para el diagnóstico ecográfico de POP fue del 78,0% con un error estándar del 4,4% (p < 0,001), tau de 0,16, I2del 98,6% (p < 0,001). El valor de 10 mm es el punto de corte para el diagnóstico de cistocele sintomático (medición estática). Se utiliza un valor de 15 mm para el diagnóstico de rectocele sintomático (medición estática) y para prolapso uterino (medición dinámica). La evidencia actual es limitada, por lo que se necesita investigación futura para proporcionar una mayor confirmación. © 2024 Elsevier Espa˜ na, S.L.U. Se reservan todos los derechos, incluidos los de miner´ ıa de texto y datos, entrenamiento de IA y tecnolog´ ıas similares. Introduction Pelvic organ prolapse (POP) is defined as the descent of one or more pelvic organs from their usual anatomical position due to failure of the supporting structures, which can progress to different stages. Surgical treatment of POP is indicated when it is symptomatic and interferes with the patient’s quality of life, usually at stage II or above. It is estimated that a woman’s lifetime risk of undergoing surgery for POP or incontinence ranges between 11% and 19%.1,2 The Pelvic Organ Prolapse Quantification System (POPQ) has become the standard staging system for POP,3 selected by various scientific societies.3,4 The POP-Q system involves quantitative measurements of different vaginal sites describing the prolapse of each compartment, being an objective and specific method for describing and categorizing POP.5It has also demonstrated interand intra-observer reliability,6and has been established as the most widely used system in the medical literature.7,8 However, clinical assessment based on the POP-Q is an inaccurate tool for evaluating pelvic floor function and anatomy, since it focuses on the anatomy of the vaginal surface rather than on actual structural abnormalities9and uses a variable reference point; the hymen.5In addition, POP-Q does not allow for the recognition of certain aspects that may influence the diagnosis of POP, such as the determination of bladder volume,10 the coactivation of the levator ani muscle during Valsalva,11 or the Valsalva time required for complete descent of the POP.12 In fact, it has been shown that intraoperative assessment of POP may exhibit significant differences compared to preoperative assessment.13 Nevertheless, the use of ultrasound in the diagnosis of POP has become part of our routine management in recent years. The introduction of transperineal ultrasound in POP has allowed us to evaluate and control the various confounding factors present in the clinical assessment of POP.14 Actually, it has allowed us to obtain better diagnostic rates of surgical prolapse compared to POP-Q.15 The current literature on the ultrasound diagnosis of POP is becoming increasingly extensive, making it necessary to establish definitive diagnostic criteria. Therefore, we proposed this systematic review and meta-analysis with the aim of determining what the diagnostic criteria for POP of each compartment should be, establishing their diagnostic capacity based on the current literature. Materials and methods Protocol and registry These systematic review and meta-analysis were conducted according to the PRISMA 2020 guidelines. The methodology was registered with PROSPERO (registration number: CRD42024535429) before the start of the study (unchanged 2 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 ARTICLE IN PRESS +Model GINE 101018 1---12 Clínica e Investigación en Ginecología y Obstetricia xxx (xxxx) 101018 after registration). Due to the methodology used, this work did not require the approval of a research ethics committee. The different authors of this paper searched several databases: PubMed/MEDLINE, Scopus, Web of Science, CINAHL, The Cochrane Library and ClinicalTrials.gov. The search was performed using the following terms and Boolean operators (‘pelvic organ prolapse’ OR ‘pelvic organ prolapse/diagnostic imaging’ OR ‘pelvic floor disorders/diagnostic imaging’ OR ‘uterine prolapse’ OR ‘cystocele/diagnostic imaging’ OR ‘rectal prolapse/diagnostic imaging’) AND (ultrasound OR ‘ultrasound/methods’), for papers published until March 2024. Inclusion and exclusion criteria Studies that met the following criteria were considered for inclusion: •Studies in women. •Cross-sectional, prospective or retrospective design. •Studies referring to the use of transperineal ultrasound as a diagnostic method for POP. •Studies comparing the diagnosis of POP between transperineal ultrasound and clinical examination with POP-Q. •Studies that used a fixed point (e.g. the pubis) as a reference for the ultrasound diagnosis of POP. Studies were excluded when: •They counted with less than 30 women (sample size set arbitrarily). •They did not provide data on sensitivity or specificity of transperineal ultrasound diagnosis compared to POP-Q. •The aim of the study was not to determine an ultrasound measurement to diagnose POP as defined by POP-Q. Study selection procedure Initially, the authors examined the titles of the articles identified in the research, finally excluding those of no relevance, clinical cases, reviews, meta-analyses, comments or letters to the editor. Subsequently, after having read the abstracts, some additional articles were excluded using the same systematic approach as described above. The remaining studies were examined in full text and afterwards the inclusion and exclusion criteria were applied. As mentioned in the section above, we excluded case reports and studies with a sample size < 30, studies that did not use POP-Q as the gold standard, and those that did not use transperineal ultrasound to diagnose POP. We also excluded studies that did not consider the pubic bone as the reference point for the ultrasound diagnosis of POP, and those in respect of which the paper did not provide sensitivity and specificity values. Data collected from the studies The following data were extracted from each included study: name of first author, year of publication, study design (prospective or retrospective cohort), type of compartment studied (anterior, middle, posterior), type of POP analyzed (cystocele, uterine prolapse, rectocele), population included in the study and population affected by the POP studied. We also screened for information on the ultrasound methodology, such as the fixed reference point used in the ultrasound assessment, the organ and the reference point of the organ to which the measurement is applied, the type of measurement (isolated or dynamic; where resting and Valsalva measurements are compared), the test used as a gold standard, the cut-off point of the measurement for the ultrasound diagnosis of POP, and the sensitivity and specificity of this cut-off point. Risk of bias assessment The QUADAS-2 tool was used in this meta-analysis to assess the risk of bias of the different studies. This tool consists of four key domains: patient selection, index test, reference standard, and flow and timing. For each domain, the risk of bias and concerns regarding applicability were classified as high, low or unclear.16 Disagreements between authors were resolved by discussion to reach consensus. The assessment of the ‘‘patient selection’’ domain was based on the inclusion and exclusion criteria of the studies. In the ‘‘index test’’ domain, it was determined that the measurement criteria for the diagnosis of POP had to be clear, so they could be reproduced in different studies. The ‘‘reference standard’’ domain was the clinical examination with the POP-Q score (gold standard for POP diagnosis3). For the ‘‘flow and time’’ domain, the studies had to report that the clinical examination and the ultrasound examination were performed in the same act. The transperineal ultrasound diagnostic performance data evaluated in this meta-analysis were extracted from the included studies, comparing clinical examination by POP-Q and ultrasound measurements from a fixed reference point, the pubis. Statistical analysis Statistical analyses were performed using R software. The meta-analysis consisted of two stages: a first stage in which the results of each study were estimated using an odds ratio estimate and 95% confidence intervals for sensitivity and specificity, and a second stage including Chi-squared tests to compare sensitivity and specificity between the primary studies. The diagnostic odds ratio (OR) and confidence intervals (95%), as well as positive and negative likelihood ratios, were calculated for each selected study. The following univariate measures of overall diagnostic accuracy were calculated: (1) the DSL estimator for weighted estimates of the likelihood ratios observed in the primary studies, (2) the statistics ␶au (), 2(2), and (3) the I2statistic (to examine the methodological heterogeneity of the studies in the review). The threshold effect was assessed numerically using Spearman’s rho statistic and graphically using ROC curve plots. Publication bias was assessed using the Fail-Safe N analysis calculated from Rosenthal’s approximation. Forest plots 3 111 112 113 114 115 116 117 118 119 120 121 122 123 124 125 126 127 128 129 130 131 132 133 134 135 136 137 138 139 140 141 142 143 144 145 146 147 148 149 150 151 152 153 154 155 156 157 158 159 160 161 162 163 164 165 166 167 168 169 170 171 172 173 174 175 176 177 178 179 180 181 182 183 184 185 186 187 188 189 190 191 192 193 194 195 196 197 198 199 200 201 202 203 204 205 206 207 208 209 210 211 212 213 214 215 216 217 218 ARTICLE IN PRESS +Model GINE 101018 1---12 J.A. García-Mejido, F. Fernández-Palacín and J.A. Sainz-Bueno Q1 were included to supplement study heterogeneity and funnel plots were drawn to conduct bias studies. The results of the studies were aggregated using a random effects model (after comparing their adequacy). In this step, we obtained the OR value, 95% confidence intervals and significance of sensitivity and specificity by integrating all selected studies. All analyses were performed with R software.17 Results Search results A flow chart summarizing the literature identification and study selection is shown in Fig. 1. The electronic search identified 2359 citations (1481 in PubMed/MEDLINE, 38 in Scopus, 817 in Web of Science, 19 in CINAHL, 1 in The Cochrane Library, 3 in ClinicalTrials.gov). We excluded 293 trials that were duplicated or that had not been conducted in women. Of the remaining 2066 studies, 1256 were excluded after title screening (992 not relevant, 130 case reports, 120 reviews, 2 systematic reviews, 7 meta-analyses, 5 comments or letters to the editor). Of the remaining 810 studies, we performed a second screening by reviewing the abstracts, and 743 papers were excluded (700 not relevant, 26 case reports, 12 reviews, 5 comments or letters to the editor). We reviewed the full text of the remaining 67 papers, excluding 59 for the following reasons: case reports (n= 2), sample size < 30 (n= 1), POP-Q not used as gold standard (n= 40), transperineal ultrasound not used as diagnostic method for POP (n= 3), pubis not used as reference point for ultrasound diagnosis of POP (n= 6) and others not providing sensitivity or specificity (n= 7). Finally, we included a total of 8 studies in the review,15,18---24 of which 3 examined the anterior compartment,18---20 6 the middle compartment15,19,21---24 and 2 the posterior compartment.18,19 Characteristics of included studies The characteristics of the included studies are listed in Table 1. The selected studies were published between 2007 and 2024 and included a total of 4481 patients, 1454 of whom were diagnosed with POP using the POP-Q clinical score. The 2 studies based on the anterior and posterior compartments18,19 were retrospective and 1 prospective20 focused on cystocele and rectocele, respectively. Of the papers examining the middle compartment,15,19,21---24 2 were retrospective19,21 and 4 prospective.15,22---24 The fixed reference point for ultrasound examination of POP was the pubic bone in all studies,15,18---24 more specifically the posterior---inferior border of the symphysis pubis. In relation to the anterior compartment, the ultrasound diagnosis of cystocele was based on a static Valsalva measurement from the posterior---inferior border of the pubic symphysis to the most descended part of the bladder, with a cut-off point of at least 10 mm.18---20 Regarding the middle compartment, 3 articles19,21,23 based the ultrasound diagnosis of uterine prolapse on a static Valsalva measurement from the posterior---inferior border of the pubic symphysis to the most descended part of the uterine cervix, with a cut-off point of 15 mm. In 3 of the relevant articles15,22,24 this ultrasound diagnosis was defined as a dynamic measurement (difference between rest and Valsalva) from the posterior---inferior border of the pubic symphysis to the uterine fundus, with a cut-off point of 15 mm. In respect of the posterior compartment, 2 articles18,19 defined the ultrasound diagnosis of rectocele as a static Valsalva measurement from the posterior---inferior border of the pubic symphysis to the most descending part of the rectum, with a cut-off point of 15 mm. All studies used the POP-Q clinical assessment as the gold standard for the diagnosis of POP. The sensitivity and specificity of transperineal ultrasound for diagnosing POP in the anterior compartment range from 55.9% to 89.9% and from 56.0% to 82%, respectively.18---20 For the middle compartment, the sensitivity and specificity of transperineal ultrasound for diagnosing POP vary from 60.2% to 81.2% and from 64% to 95%, respectively.15,19,21---24 For the posterior compartment, the sensitivity and specificity of transperineal ultrasound for diagnosing POP fluctuate from 70.8% to 93.1% and from 47.1% to 78%, respectively.18,19 Qualitative synthesis Table 2 shows the assessment of risk of bias and concerns about applicability of the included studies according to the QUADAS-2 tool. All studies had a low risk of patient selection bias, as they were retrospective or prospective studies that included patients with pelvic organ prolapse diagnosed at clinical examination. For the index test domain, the included studies were considered to have a low risk of bias as they used a fixed ultrasound reference point (posterior---inferior border of the pubic symphysis) and clear measurements applied to the compartments. In the reference standard area, there are two papers where the risk of bias is unclear due to the lack of definition of the prolapse stages included, based on the POP-Q. The risk of bias for flow and timing is low in all included articles, given that the ultrasound assessment was performed after the clinical examination. All studies were considered to have low applicability concerns in terms of patient selection, index test, reference standard, flow and timing. Quantitative synthesis The diagnostic OR estimates, confidence intervals (95%), and positive and negative likelihood ratios for each selected study are shown in Table 3. Forest plots are presented in Figs. 2 and 3. The pooled sensitivity for the ultrasound diagnosis of POP was 72.3% with a standard error of 3.1% (p< 0.001), tau of 0.11, I2of 97.1% (p< 0.001) (Table 4). A funnel plot of sensitivity for the diagnosis of POP using transperineal ultrasound is shown in Fig. 4. The pooled specificity for ultrasound diagnosis of POP was 78.0% with a standard error of 4.4% (p< 0.001), tau of 0.16, I2of 98.6% (p< 0.001) (Table 4). A 4 219 220 221 222 223 224 225 226 227 228 229 230 231 232 233 234 235 236 237 238 239 240 241 242 243 244 245 246 247 248 249 250 251 252 253 254 255 256 257 258 259 260 261 262 263 264 265 266 267 268 269 270 271 272 273 274 275 276 277 278 279 280 281 282 283 284 285 286 287 288 289 290 291 292 293 294 295 296 297 298 299 300 301 302 303 304 305 306 307 308 309 310 311 312 313 314 315 316 317 318 319 320 321 322 323 324 325 326 327 328 329 330 ARTICLE IN PRESS +Model GINE 101018 1---12 Clínica e Investigación en Ginecología y Obstetricia xxx (xxxx) 101018 Table 1 Characteristics of the included studies. Study Compartment Organ prolapse Study design Patients (n) Patient with prolapse (n) Reference point Organ of reference Type of measure Cut point Gold standard Sensitivity Sensitivity (95% CI) Specificity Specificity (95% CI) Dietz 200718 Anterior Cystocele Retro 735 56 Pubic symphysis Urinary bladder Static 10 mm POP-Q 71.4% 58.5%; 81.6% 82.0% 79.0%; 84.7% Dietz 201619 Anterior Cystocele Retro 825 477 Pubic symphysis Urinary bladder Static 10 mm POP-Q 89.9% 86.9%; 92.3% 64.1% 58.9%; 68.9% Wu 202220 Anterior Cystocele Prosp 674 440 Pubic symphysis Urinary bladder Static 10 mm POP-Q (stage II) 55.9% 51.2%; 60.5% 56.0% 49.6%; 62.2% Shek 201521 Medium Uterine prolapse Retro 538 63 Pubic symphysis Uterine cervix Static 15 mm POP-Q (stage II) 69.8% 57.6%; 79.8% 64.0% 59.6%; 68.2% Dietz 201619 Medium Uterine prolapse Retro 568 221 Pubic symphysis Uterine cervix Static 15 mm POP-Q 60.2% 53.6%; 66.4% 76.9% 72.2%; 81.1% GarcíaMejido 202122 Medium Uterine prolapse Prosp 60 40 Pubic symphysis Uterine fundus Dynamic 15 mm POP-Q (stage II) 75.0% 59.8%; 85.8% 95.0% 76.4%; 99.1% Wu 202123 Medium Uterine prolapse Prosp 534 274 Pubic symphysis Uterine cervix Static 15 mm POP-Q (stage II) 63.9% 58.0%; 69.3% 93.1% 89.3%; 95.6% GarcíaMejido 202315 Medium Uterine prolapse Prosp 52 16 Pubic symphysis Uterine fundus Dynamic 15 mm POP-Q (stage II) and surgical criteria 81.2% 57.0%; 93.4% 91.7% 78.2%; 97.1% GarcíaMejido 202424 Medium Uterine prolapse Prosp 143 69 Pubic symphysis Uterine fundus Dynamic 15 mm POP-Q (estadio II) General 68.1% 56.4%; 77.9% 89.2% 80.1%; 94.4% POP-Q (estadio II) Premenopausal 76.8% 65.6%; 85.2% 91.9% 83.4%; 96.2% POP-Q (estadio II) Postmenopausal 66.7% 54.9%; 76.6% 86.5% 76.9%; 92.5% Dietz 200718 Posterior Rectocele Retro 735 48 Pubic symphysis Rectum Static 15 mm POP-Q 70.8% 56.8%; 81.8% 78.0% 74.8%; 81.0% Dietz 201619 Posterior Rectocele Retro 825 464 Pubic symphysis Rectum Static 15 mm POP-Q 93.1% 90.4%; 95.1% 47.1% 42.0%; 52.2% 5 ARTICLE IN PRESS +Model GINE 101018 1---12 J.A. García-Mejido, F. Fernández-Palacín and J.A. Sainz-Bueno Q1 Table 2 Evaluation of bias risk and concerns regarding the applicability of studies included according to the QUADAS-2 tool. Risk of bias Applicability concerns Index test Index test Study Patient selection Cystocele Uterine prolapse Rectocele Reference standard Flow and timing Patient selection Cystocele Uterine prolapse Rectocele Reference standard Flow and timing Dietz 200718 Low Low --- Low Unclear Low Low Low --- Low Low Low Dietz 201619 Low Low Low Low Unclear Low Low Low Low Low Low Low Wu 202220 Low Low --- --- Low Low Low Low --- --- Low Low Shek 201521 Low --- Low --- Unclear Low Low --- Low --- Low Low GarcíaMejido 202122 Low --- Low --- Low Low Low --- Low --- Low Low Wu 202123 Low --- Low --- Low Low Low --- Low --- Low Low GarcíaMejido 202315 Low --- Low --- Low Low Low --- Low --- Low Low GarcíaMejido 202424 Low --- Low --- Low Low Low --- Low --- Low Low 6 ARTICLE IN PRESS +Model GINE 101018 1---12 Clínica e Investigación en Ginecología y Obstetricia xxx (xxxx) 101018 Figure 1 A flowchart summarizing literature identification and selection of studies. funnel plot of the specificity for the diagnosis of POP by transperineal ultrasound is represented in Fig. 5. The ROC curve resulting from the several included studies is shown in Fig. 6. An attempt was made to perform a subgroup analysis according to the compartment affected by POP. However, this was not possible due to the small number of studies evaluating the anterior and posterior compartments. Therefore, the analysis was finally based on the study that included all three compartments. Discussion Summary of the evidence According to our results, the diagnosis of POP by transperineal ultrasound has a moderate sensitivity (72.3%) and specificity (78.0%). Due to the limited number of publications referring to the anterior and posterior compartments, we were not able to determine the diagnostic capacity of ultrasound for POP according to each compartment. 7 331 332 333 334 335 336 337 338 339 340 341 342 343 344 345 346 347 348 ARTICLE IN PRESS +Model GINE 101018 1---12 J.A. García-Mejido, F. Fernández-Palacín and J.A. Sainz-Bueno Q1 Table 3 The point estimates and confidence intervals (95%) of the diagnostic ORs, and likelihood ratios of a positive result and a negative result for each selected study. Study DOR DOR (95% CI) POSLR POSLR (95% CI) NEGLR NEGLR (95% CI) Dietz 200718 11.4 6.2; 21.0 3.9 3.2; 5.0 0.3 0.2; 0.5 Dietz 201619 15.9 11.9; 23.1 2.5 2.2; 2.9 0.2 0.1; 0.2 Wu 202220 1.6 1.2; 2.2 1.3 1.1;1.5 0.8 0.7; 0.9 Shek 201521 4.1 2.3; 7.3 1.9 1.6; 2.4 0.5 0.3; 0.7 Dietz 201619 5.0 3.5; 7.3 2.6 2.1; 23.2 0.5 0.4; 0.6 García-Mejido 202122 57.0 6.7; 481.8 15.0 2.2; 102.2 0.3 0.2; 0.5 Wu 202123 23.8 13.9; 40.7 9.2 5.9; 14.5 0.4 0.3; 0.5 García-Mejido 202315 47.7 8.5; 267.3 9.8 3.2; 29.5 0.2 0.1; 0.6 García-Mejido 202424 General 17.6 7.2; 42.9 6.3 3.2; 12.4 0.4 0.3; 0.5 García-Mejido 202424 Premenopausal 37.5 13.7; 102.5 9.5 4.4; 20.6 0.3 0.2; 0.4 García-Mejido 202424Postmenopausal 12.8 5.6; 29.5 4.9 2.7; 8.9 0.4 0.3; 0.6 Dietz 200718 8.6 4.5; 16.5 3.2 2.6; 4.1 0.4 0.2; 0.6 Dietz 201619 12.0 7.9; 18.2 1.8 1.8; 1.6 0.1 0.1; 0.2 DOR: diagnostic odds ratio. POSLR: positive likelihood ratio. NEGSLR: negative likelihood ratio. Table 4 Global precision diagnosis with the DSL estimator to estimate in a weighted way the likelihood ratios observed in the primary studies and the statistics ␶au (), 2(2), as well as the I2statistic (for the study of the heterogeneity of the methodology of the studies in the review). Estimate Standard error p(95% CI) Tau Tau2I2p Sensitivity 72.3% 3.1% <0.001 66.2%; 78.3% 0.11 0.01 (SE = 0.005) 97.1% <0.001 Specificity 78.0% 4.4% <0.001 69.5%; 86.6% 0.16 0.024 (SE = 0.01) 98.6% <0.001 Figure 2 Forest plots of sensitivity in the diagnosis of POP using transperineal ultrasound. Only first author of each study is given. Interpretation of the results Currently, the diagnosis of POP is made clinically based on the POP-Q score.5Ultrasonography has emerged as a complementary test that can aid in the diagnosis of symptomatic Figure 3 Forest plots of specificity in the diagnosis of POP by transperineal ultrasound. Only first author of each study is given. POP. However, the number of studies comparing ultrasound diagnosis with clinical POP-Q assessment is limited.15,18---24 Nevertheless, all these studies show sensitivities between 55% and 93% for the diagnosis of the various POPs in different compartments. However, specificities range from 56% to 8 349 350 351 352 353 354 355 356 357