Editorial. Assessment of pelvic organ prolapse: a review. K. L. SHEK* and H. P. DIETZ

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1 Ultrasound Obstet Gynecol 2016; 48: Published online in Wiley Online Library (wileyonlinelibrary.com). DOI: /uog Editorial Assessment of pelvic organ prolapse: a review K. L. SHEK* and H. P. DIETZ Department of Obstetrics and Gynaecology, Liverpool Hospital, Western Sydney University, Locked Bag 7103, Liverpool BC, NSW 1871, Australia; Department of Obstetrics and Gynaecology, Nepean Clinical School, University of Sydney, Sydney, Australia *Correspondence. ( shekkalai@yahoo.com.hk) Female pelvic organ prolapse (FPOP) is a common indication for gynecological surgery 1. It has been estimated that a woman s lifetime risk of FPOP surgery may be as high as 20% 2,3. In the USA it has been conservatively estimated that the prevalence of symptomatic FPOP will increase by 46% to reach 4.9 million women by Hence, FPOP is a major public health issue that will continue to grow due to the aging populations in developed countries. There is a pressing need to better understand FPOP, not only for its treatment but also for its prevention. Proper diagnosis is the first step towards achieving these goals. To date, pelvic organ support is generally quantified by clinical examination using the International Continence Society Pelvic Organ Prolapse Quantification (ICS POP-Q) system 5. The ICS POP-Q was introduced in 1996 with an aim of standardizing assessment. Although ICS POP-Q is widely used, the staging system derived from POP-Q is based on expert opinion rather than data. The system provides information on surface anatomy only and gives no information on underlying organs or functional anatomy. Staging of bladder, uterine, small bowel and rectal descent is identical under the quantification system, i.e. a uterus that descends to within 1 cm of the hymen is deemed to be as abnormal as descent of the anterior or posterior vaginal wall to the same level. This may not be appropriate 6. Furthermore, the ICS POP-Q system uses a moving structure, the hymen, as the reference point to quantify pelvic organ descent, which may not be optimal for this purpose. Most importantly, almost 20 years after the introduction of this assessment system, it still lacks a definition of normal. Significant FPOP is generally defined as ICS POP-Q stage 2 or above 7, and it is only very recently that information on the limits of normality have become available 6,8. Ultrasound is used increasingly in the evaluation of women with pelvic floor dysfunction 9. The technique is safe, simple, cheap and easily accessible to clinicians. Compared with transvaginal ultrasound imaging, the translabial approach is non-invasive and allows assessment of pelvic floor functional anatomy during maneuvers, such as the Valsalva maneuver. One of the main applications of translabial ultrasound imaging is in the quantification of FPOP, which is useful in both clinical audit and research. Figure 1 shows clinical findings and the corresponding ultrasound appearances on Valsalva maneuver of a cystocele, enterocele/vault prolapse and rectocele, respectively. One of the fundamental questions in the assessment of pelvic organ prolapse is what is significant pelvic organ descent?. In this Editorial, we focus on diagnosis, i.e. what is considered significant pelvic organ prolapse on clinical and translabial ultrasound examination, and discuss measures to avoid false-negative findings on FPOP assessment. FPOP: an abnormality of pelvic floor functional anatomy The etiology of FPOP is probably complex and multifactorial 10,11. A number of risk factors have been implicated in the pathogenesis of FPOP including aging, obesity, chronic increase in intra-abdominal pressure, genetics, ethnicity, connective tissue disorder, previous pelvic surgery and childbirth. Irrespective of the causes of the condition, FPOP can be considered as a form of hernia in which there is downward displacement of the bladder, uterine cervix, small bowel and/or rectal ampulla into the vagina through the levator hiatus. The levator hiatus is the space bounded by the puborectalis component of the levator ani muscle and the os pubis. It is the largest potential hernia portal in the human body. The size of the hiatus has been shown to be associated with both symptoms and signs of FPOP, in both asymptomatic and symptomatic populations 12,13. Hiatal dimensions vary widely in the general population 12,14 and between ethnic groups 15,16. Apart from congenital factors, lifestyle factors may also play a role 17. Pregnancy and childbirth appear to be the most important environmental factors affecting the size of the hiatus 18,19. Pregnancy may exert its influence through its hormonal and/or mechanical effects 18,and childbirth may cause enlargement of the hiatus, probably at the time of crowning of the fetal head 20,21, by either detaching the puborectalis muscle insertion from the os pubis, i.e. macrotrauma or levator avulsion, and/or by overstretching the pelvic floor muscle irreversibly, i.e. due to microtrauma 19,22. An abnormally distensible hiatus is a risk factor for FPOP development and recurrence after surgery 23,24. Prolapse repairs do not seem to reduce the hiatus back to normal, suggesting that the size of the hiatus has a primary role in the pathophysiological mechanism of FPOP development 25. The observation that maximum hiatal area is reached before maximum pelvic organ descent on Valsalva maneuver also supports this hypothesis 26. Copyright 2016 ISUOG. Published by John Wiley & Sons Ltd. EDITORIAL

2 682 Shek and Dietz (b) Aa Ba Bp C D S B U A L Ap tvl (b) Aa Ba Bp D S B E R Ap tvl (b) Aa Ap Ba C Bp D tvl S B R A L Figure 1 Cystocele (a,b,c), enterocele/vault prolapse (d,e,f) and rectocele (g,h,i) on Valsalva maneuver: (a,d,g) clinical examination; (b,e,h) corresponding schematic representation on International Continence Society Pelvic Organ Prolapse Quantification system; and (c,f,i) corresponding ultrasound images in mid-sagittal plane. A, anus; Aa, anterior vaginal wall 3 cm proximal to the hymen; Ap, posterior vaginal wall 3 cm proximal to the hymen; B, bladder; Ba, most distal position of the remaining upper anterior vaginal wall; Bp, most distal position of the remaining upper posterior vaginal wall; C, most distal edge of cervix; D, posterior fornix; E, enterocele; L, levator ani muscle; R, rectal ampulla; S, symphysis pubis; tvl, total vaginal length; U, uterus. Reproduced with permission from Dietz 103. Other than hiatal area, integrity of the levator ani muscle is also important for pelvic organ support. A number of studies in different ethnic groups using magnetic resonance imaging or ultrasound have shown levator avulsion to be a strong risk factor for FPOP 27 30, especially in the anterior and central compartment 31. The condition is also associated with prolapse recurrence after surgery 24, A weaker muscle, increased pelvic floor muscle strain and abnormal distensibility of the levator hiatus 36 may be the underlying pathophysiological mechanisms. Based on current evidence, it is apparent that assessment of the pelvic floor, clinically and/or using imaging 37,38, should be an integral part of FPOP assessment. It is important not only in preoperative counseling but also in surgical planning, for example in the selection of patients for anterior mesh repair 24. Other factors apart from direct trauma to the pelvic floor muscle, e.g. nerve 39,40 and fascial injury, may also play a role in the pathogenesis of FPOP after childbirth. Although evidence of nerve function impairment is not uncommon in the postpartum period, causing temporary urinary or fecal incontinence and loss of sensation after a traumatic delivery, such impairment usually recovers with time. Permanent pudendal nerve neuropathy after childbirth seems to be rare 41.

3 Editorial 683 To date there is widespread disagreement regarding the existence of fascial structures, their importance in pelvic organ support, whether damage to those structures occurs, whether such damage is relevant in the pathogenesis of FPOP, whether there is an indication to repair such damage and how to perform such a repair. This is particularly evident with regards to the rectovaginal septum (RVS) Most posterior compartment repairs are performed by posterior colporrhaphy, without identification of or attention to the RVS. Some researchers actively dispute the existence of the RVS as a surgically useful structure 44.CullenRichardsonistobecredited with identifying the RVS as the primary structure in the pathogenesis of rectocele, and for designing surgical methods for its repair by reconstituting RVS integrity over the entire posterior vaginal wall 43. Although Richardson 43 described a number of different defects as the cause of rectocele, recent imaging data suggest that most rectoceles occur secondary to high transverse defects of the RVS. Such high transverse defects fully explain the appearance of a rectocele on X-ray or ultrasound as a diverticulum of the rectal ampulla into the vagina, defined by a clear distal margin that is formed by a transverse ridge at the upper margin of the perineal body (Figure 2). Childbirth may lead to the formation of rectoceles or may cause enlargement of a pre-existing rectocele 46 ; however, they may also be congenital and can be found in young nulliparous women 47. Body mass index seems to play a role in the pathogenesis of rectoceles with an increased risk associated with a higher body mass index 46,47. Attenuation or tears of the pubocervical fascia have been postulated as the underlying anatomical abnormality of cystocele formation. Two main types of pubocervical fascia defect, central and lateral paravaginal defects, have been hypothesized. In a recent study on women before and after their first childbirth, vaginal delivery was found to be associated with a loss of tenting of the vaginal fornices, which was independently associated with increased cystocele descent, implying a role for such defects in the causation of anterior vaginal wall prolapse 48. It is interesting to see that levator avulsion, a likely cause of paravaginal defects, has been shown to be associated with Green Type 3 cystocele and urinary symptoms 49. In contrast to defect-specific repair, the results after anterior native tissue repair for a cystocele are less satisfactory, with a reported failure rate of 40 63% 32, Anterior mesh repair is associated with superior anatomical outcomes but the beneficial effect may largely be limited to women with levator avulsion 24. Symptoms of FPOP Female pelvic organ prolapse may give rise to a wide array of symptoms including bowel, sexual and/or lower urinary tract complaints. It can greatly affect women s daily activities and also impair women s body image perceptions 53. Seeing or feeling a vaginal bulge and/or a dragging sensation is the most common presentation of FPOP. The former seems to be the most specific symptom Herniation of the anterior vaginal wall is almost invariably due to a cystocele. Central compartment prolapse implies uterine prolapse, often with cervical elongation (probably due to hydrostatic edema of the cervix) or a small bowel hernia in women with previous hysterectomy, and this commonly presents as a bulge. Occasionally, a low cervix may become irritated by intermittent exteriorization and cause abnormal vaginal bleeding. Symptoms of obstructive defecation, i.e. straining at stool, incomplete bowel emptying and perineal, vaginal or anal digitation, have been shown to be associated with posterior compartment prolapse, in particular rectocele and rectal intussusception 55,57,58. Rectocele may also contribute to fecal incontinence 57 although this condition is clearly multifactorial 59. Symptoms of obstructive voiding may occur with anterior, apical and posterior compartment prolapse due to urethral kinking or external urethral compression (Figure 3). It is not surprising that advanced FPOP may mask stress urinary incontinence. A raised voiding residual can predispose women to recurrent urinary tract infections 64 and contribute to symptoms of overactive bladder. The relationship between irritative bladder symptoms such as urgency and urge urinary incontinence and FPOP is, however, less clear. It is hypothesized that women with obstructive voiding as a result of advanced FPOP may develop irritative bladder symptoms d d Figure 2 Measurement of depth (d) of a rectocele on defecation protography (a) and on translabial ultrasound (b).

4 684 Shek and Dietz Symphysis Bladder Bladder neck Bladder neck Bladder Symphysis Figure 3 Translabial ultrasound images in mid-sagittal plane at rest (a) and on Valsalva maneuver (b), showing a cystocele with urethral kinking. Reproduced with permission from Dietz 104. secondary to smooth muscle changes or recurrent urinary tract infections; evidence in the literature is, however, conflicting Women with FPOP may also complain of vaginal laxity or looseness 68. It is thought that vaginal laxity may result in loss of physical sensation and diminished sexual satisfaction 69. Apart from vaginal laxity, FPOP may cause sexual dysfunction through other mechanisms, e.g. physical narrowing of the vagina or obstruction by the presence of a lump. Assessment Pelvic organ prolapse assessment on clinical examination Over the years, a number of different systems have been described to quantify FPOP clinically, including those of Porges in , Baden and Walker in , Beecham in and the ICS POP-Q in These systems, however, share the same problem in that they are only a description of changes in surface anatomy. They provide no information as to the nature of the prolapse, e.g. a posterior compartment prolapse could be due to a true rectocele, perineal hypermobility (Figure S1), enterocele or rectal intussusception (Figure S2) 73, and none of those systems has been evaluated properly as a test for the prediction of symptoms of prolapse, nor have they been validated against imaging until recently. The ICS POP-Q is now commonly used by urogynecologists to quantify FPOP 74. It requires the maximal descent of six points on the vaginal surface to be measured relative to the hymenal remnant. In a joint report by the International Urogynecological Association and International Continence Society on the terminology for female pelvic floor dysfunction 75, FPOP is defined as the descent of one or more of the anterior vaginal wall, posterior vaginal wall, uterus (cervix) or apex of the vagina (vaginal vault or cuff scar after hysterectomy). The basic description of the technique reads as follows. All examinations for POP should be performed after bladder emptying (and if possible an empty rectum). An increasing bladder volume has been shown to restrict the degree of descent of the prolapse. The choice of the woman s position during examination, for example, left lateral (Sims), supine, standing or lithotomy, is that which can best demonstrate POP in that patient and which the woman can confirm, for example, by use of a mirror or digital palpation. 75 There are multiple problems with the document. The type of maneuver is not specified. Assessment during a cough is allowed, which is inappropriate. The duration of the Valsalva maneuver is not specified, despite this being a major factor due to the viscoelastic properties of support structures. It seems to require about 6 s for pelvic organs to reach 80% or more of maximal descent 26. There is no mention of other confounders such as levator coactivation, which is common, especially in younger women 76, and there is no definition of normality. Usually, prolapse is staged according to POP-Q coordinates 54, resulting in large proportions of the female population being diagnosed erroneously with asymptomatic prolapse (see below). Apart from assessing pelvic organ descent, assessment of the pelvic floor muscle should also be part of any evaluation for FPOP as explained above. Integrity of the puborectalis muscle can be palpated 37 by placing the index finger just lateral to the urethra, around 3 cm from the introitus on pelvic floor muscle contraction. The insertion of the puborectalis muscle should be felt on the lateral aspect of the examining finger. A widened gap between the urethra and the muscle insertion may suggest levator avulsion 37. To assess the size of the levator hiatus, the distance from the middle of the external urethral meatus to the center of the anus (genital hiatus (Gh) + perineal body (Pb)) can be measured (Figure 4). The sum of Gh and Pb has been shown to be associated with symptoms and signs of FPOP, and performs equally well in predicting significant prolapse on clinical examination as does hiatal area on Valsalva

5 Editorial 685 Symphysis pubis Pubic ramus Levator ani 1 D 6.67cm 2 D 4.96cm 3 A 26.25cm 2 C 19.12cm Figure 4 Clinical measurement of levator hiatal size by sum of measurements of genital hiatus and perineal body (a), and measurement of hiatal dimensions on four-dimensional translabial ultrasound on Valsalva maneuver in axial plane (b). Reproduced with permission from Gerges et al. 77. maneuver measured on imaging 77,78. Measurement of Gh + Pb may also help to identify women with levator avulsion 79. Pelvic organ prolapse assessment on translabial ultrasound The most basic requirement for quantification of FPOP using transperineal/translabial ultrasound is a small, portable real-time B-mode-capable system displaying two-dimensional (2D) grayscale images in real time. A curved-array transducer with a frequency of 3 8 MHz and a footprint of 5 8 cm is used for translabial or transperineal imaging. This method is non-invasive and by far the easiest, cheapest and most widely available technique used for pelvic floor imaging at present. The probe is covered with gel and either with a condom, a piece of Gladwrap or a powder-free glove for hygienic purposes, before it is covered with more gel and placed on the perineum. Imaging is commonly performed with the patient in the dorsal lithotomy position with the hips flexed and slightly abducted. The labia may have to be parted, especially if the woman is obese or hirsute. Sometimes, however, the examination may need to be repeated in the erect position, for instance when the patient is not able to perform a proper Valsalva maneuver in the supine position or when no significant pelvic organ descent can be detected to explain the patient s symptoms. Imaging in the standing position is expected to result in subtly different findings compared with the supine examination (Table S1). To assess pelvic organ descent, translabial ultrasound imaging is performed on maximal Valsalva maneuver 80. Using a horizontal line placed through the posteroinferior margin of the symphysis pubis as a reference, the most dependent part of the bladder is used to quantify prolapse of the bladder or cystocele, the leading edge of the cervix S C U R Figure 5 Translabial ultrasound image in mid-sagittal plane on maximal Valsalva maneuver, showing descent of cystocele (C), uterus (U) and rectal ampulla (R), relative to symphysis pubis (S). Reproduced with permission from Dietz 105. defines uterine prolapse and descent of the rectal ampulla defines posterior compartment prolapse (Figure 5). Enterocele is defined by measuring descent of abdominal contents such as omentum, small bowel, sigmoid or fluid-filled peritoneum. This may be apparent as anterior, central or posterior compartment descent on clinical examination. In order to allow the use of a reference line without a posterior anchoring point, the transducer must not be rotated around its transverse axis, i.e. the ovoid shape of the symphysis pubis must not be allowed to rotate on Valsalva maneuver as this would result in an increasingly large angle error with increasing distance of the measured structure from the symphysis pubis. In practice this is rarely an issue as demonstrated by the high repeatability that has been documented for the method 81. Levator integrity may be assessed in an oblique parasagittal view using a 2D ultrasound system 82.Levator avulsion is diagnosed when a discontinuity is seen between the hyperechogenic fibers of the puborectalis muscle and the pelvic sidewall, with the insertion being

6 686 Shek and Dietz replaced by a hypoechogenic zone representing the vaginal wall. This is, however, likely to be less repeatable than three/four-dimensional (3D/4D) imaging of the levator insertion in the axial plane due to the absence of a well-defined point of reference. To assess hiatal size on 2D imaging, the anteroposterior diameter of the hiatus can be measured in the mid-sagittal view, a parameter that is strongly associated with prolapse symptoms/pelvic organ descent 83. Using a 3D/4D ultrasound system, levator avulsion can be diagnosed by more reproducible means. This can be achieved via evaluation of rendered volumes or tomographic imaging 37. The latter has become a de-facto gold standard and is used by dozens of research groups around the world. Levator avulsion is diagnosed if the muscle insertion is clearly abnormal in slices at the plane of minimal hiatal dimensions and at 2.5 and 5 mm cranial to this (Figure 6) 84,85. With regards to hiatal area assessment, 3D/4D ultrasound equipment enables the use of at least three different methods: via a true axial plane after identification of the plane of minimal hiatal dimensions 12 (Figure S3); via a rendered volume of 1 2-cm thickness including this reference plane 86 ;orvia volume contrast imaging 87.The use of rendered volumes of 1 2-cm thickness may be more valid than single-plane techniques as the plane of minimal hiatal dimensions is non-euclidean, i.e. warped 86. Sonographic techniques for determination of pelvic organ descent, levator hiatal biometry and morphological integrity have been shown to be highly repeatable, with regards to both ultrasound volume data acquisition and offline assessment of ultrasound parameters 81,88,89.Ithas been shown that one may learn to perform transperineal ultrasound examination after a few weeks of teaching 88 and that postprocessing analysis of ultrasound parameters can be taught to an acceptable standard within 1 week 89. Potential confounders of pelvic organ descent Discrepancies between preoperative FPOP assessment and intraoperative findings are not uncommon in clinical practice. This is probably due to false-negative results on clinical examination, and a number of different factors, usually unrecognized, may lead to an underestimation of pelvic organ descent. This is most likely for the central compartment, where significant uterine descent is frequently missed on clinical examination 90. It is important for clinicians to be aware of these confounders, to observe and control for them so that false-negative results can be avoided to allow proper counseling and management. Levator coactivation Levator coactivation, the triggering of a pelvic floor muscle contraction when asked to perform a Valsalva maneuver, is an important confounder of prolapse assessment and is common in young nulliparous women 76. Assessment of pelvic organ descent, both clinically and on imaging, is undertaken based on the assumption of a subject s best (correctly performed) Valsalva maneuver. A properly performed Valsalva maneuver for FPOP assessment involves forced expiration against a closed glottis, together with contraction of the diaphragm and abdominal muscles, in order to markedly increase intra-abdominal pressure while relaxing the levator ani muscle. Performing a Valsalva maneuver with a relaxed pelvic floor can, however, be embarrassing for the patient as it may lead to the involuntary passage of urine, bowel gas or even stool. As a consequence, it is not uncommon for subjects to voluntarily or involuntarily contract the levator ani muscle during a Valsalva maneuver, impeding full development of pelvic organ descent. Prolapse assessment by imaging techniques facilitates the detection of levator coactivation, evident as a decrease in the mid-sagittal hiatal diameter on Valsalva maneuver (Figure 7). Visual biofeedback using real-time ultrasound as a tool together with repeated instruction may help eliminate levator coactivation 76. However, in a minority of cases, especially in nulliparae, it may be necessary to repeat imaging in the standing position. Figure 6 Right levator avulsion ( ) seen through large vaginal tear observed in delivery suite (a), on translabial ultrasound in rendered volume (b) and on tomographic ultrasound imaging (c).

7 Editorial 687 Symphysis pubis Bladder Bladder neck LA Cranial Rest First Valsalva Optimal Valsalva Figure 7 Translabial ultrasound images of female pelvic floor in mid-sagittal plane (a c) and axial plane (d f) at rest (a,d), on Valsalva maneuver (b,e), showing levator coactivation as shortening in anteroposterior diameter of levator hiatus (vertical line), and on optimal Valsalva maneuver after proper coaching (c,f), showing no levator coactivation. LA, levator ani. Adequacy of Valsalva maneuver Intra-abdominal pressure and the duration of a Valsalva maneuver are two other factors that determine the adequacy of prolapse assessment. Attempts have been made to standardize Valsalva maneuver pressure non-invasively, using a modified sphygmomanometer and a valsalvometer 91 93, asking patients to blow into a flow restriction tube. The pressures that can be obtained in this way are in the range of cm H 2 O, much lower than the cm H 2 O reported by other researchers for usual Valsalva pressures However, it has recently been found that standardization of Valsalva maneuver pressure for prolapse assessment may not be necessary as all patients were able to generate intra-abdominal pressure resulting in 80% of maximal pelvic organ descent 96. Standardization of pressure does not seem to be necessary provided proper coaching or biofeedback is undertaken, but duration of Valsalva maneuver does seem to need standardization. This obvious confounder of prolapse assessment is often overlooked. Orejuela et al. have shown that, on average, a Valsalva maneuver lasting 9 s was required to reach maximum pelvic organ descent, and a minimum of 6 s was needed to achieve 80% of maximum descent 26. A short push for 1 or 2 s, or a cough, not uncommonly performed for prolapse assessment in clinical practice, is obviously insufficient. Pelvic organ prolapse in other compartments If we consider FPOP to be a form of hernia through the levator hiatus, it becomes immediately apparent that there is competition for space between various pelvic organs. It is then not difficult to understand how FPOP in one compartment may mask prolapse development in another. This may explain why prolapse recurrence may develop in an untreated compartment after surgery. Uterine prolapse, although more commonly missed due to slower organ descent during Valsalva maneuver 90,is a particularly interesting confounder for the diagnosis of posterior compartment descent due to a defect of the RVS. Significant uterine prolapse may occlude a rectovaginal septal defect and hence mask the existence of a rectocele by preventing the pressure differential between the rectal ampulla and the lower vagina from exploiting an RVS defect. In effect, a low cervix can splint the posterior vaginal wall and prevent development of a rectocele or rectoenterocele, which will inevitably become apparent once the uterus is removed or elevated. In fact, a rectocele may be observed during the early stages of a Valsalva maneuver, before the uterus descends to occlude the RVS defect. Of course, proper clinical examination by reducing the

8 688 Shek and Dietz uterine prolapse during assessment for posterior compartment descent may also help to avoid false-negative results, provided the Valsalva maneuver is sufficiently prolonged. Bladder and rectal filling For a similar reason, i.e. competition for space between various pelvic organs above and within the levator hiatus, a full bladder and/or a loaded rectum are potential confounders that may stop full development of pelvic organ descent 97. Prolapse assessment should therefore be performed after bladder and (if possible) rectal emptying. Sometimes this may require a repeat assessment after laxatives or an enema, or at another time. High residuals should be emptied by catheterization prior to prolapse assessment. Defining limits of normality for functional anatomy Mild degrees of pelvic organ descent are common, even in young nulliparous women 98. In fact, normality of pelvic organ descent has, to date, not been considered in standardization documents and guidelines, a remarkable omission. The staging used on the basis of the POP-Q system is clearly inappropriate and may be regarded as a form of disease mongering 99. Using the ICS POP-Q system, 45%, 48% and 3% of women seen for annual gynecological examinations were found to have Stage I, II and III pelvic organ descent, respectively 54. One of the fundamental questions is therefore What is significant pelvic organ descent, i.e. what is organ descent that is likely to cause symptoms of prolapse?. As FPOP is a relative indication for surgery, it is important to determine whether a certain degree of organ descent is relevant, whether the symptoms reported by the patient are sufficiently explained by the examination findings, and to determine which compartment is most likely to be responsible for the patient s symptoms. Determining cut-offs is essential to define significant FPOP prior to surgical treatment. It will also be useful when a dichotomous variable is required in clinical practice or research. There are two primary mathematical approaches to defining normality: determining the 95 th centile in a young nulliparous population (or mean + 2 SD) or, alternatively, using receiver operating characteristics (ROC) statistics to define cut-offs with optimal sensitivity and specificity for distinguishing symptomatic individuals from those who are symptom-free. Both approaches have been used to define significant pelvic organ descent and ballooning on translabial ultrasound and/or clinical examination, and will be discussed in detail below. What is significant pelvic organ descent on clinical examination? In a study using ROC statistics to define optimal cut-offs for ICS POP-Q coordinates in a group of 764 symptomatic individuals, a value of 0.5 cm (0.5 cm above the hymen) seemed to be most appropriate for the anterior and posterior compartments. Surprisingly, however, the corresponding value for significant uterine descent was 5 cm (5 cm above the hymen) 6 (Figure 8). This implies that a given degree of uterine descent is much more likely to be symptomatic as compared with the anterior and posterior compartment, and this finding concurs with previously published imaging studies 8,100. Clearly, the currently used prolapse quantification system needs to be revised and staging of uterine prolapse should be different from staging of other compartments. What is abnormal distensibility of the levator hiatus or ballooning on clinical examination? As mentioned above, hiatal dimensions are likely to be of importance for the pathophysiology of prolapse; hence, their assessment should form part of a full clinical examination for FPOP. DeLancey and Hurd reported (a) 1.0 (b) 1.0 (c) Sensitivity Sensitivity Sensitivity Specificity Specificity Specificity Figure 8 Receiver operating characteristics (ROC) curves to define optimal cut-off values for bladder (a), uterine (b) and rectal (c) descent using International Continence Society Pelvic Organ Prolapse Quantification system. Optimal cut-off values were: (a) 0.5 cm for downward displacement of anterior vaginal wall (n = 557), with area under the ROC curve (AUC) of 0.768; (b) 5.0 cm for maximal downward displacement of cervix (n = 363) with AUC of 0.724; and (c) 0.5 cm for maximum downward displacement of posterior vaginal wall (n = 486) with AUC of Reproduced with permission.

9 Editorial 689 that the anteroposterior diameter of the urogenital hiatus measured clinically (Gh) was associated with pelvic organ prolapse and surgical failure 101. In previous studies, Gh + Pb was demonstrated to be strongly associated with symptoms and signs of FPOP 77,78. The sum of Gh + Pb seems to be the closest equivalent to levator hiatal dimensions that can be measured clinically. Using ROC statistics, 7 cm was shown to be the optimal cut-off for distinguishing between women with symptoms of prolapse and those without, with an area under the ROC curve (AUC) of (95% CI, ) and an AUC of 0.89 (95% CI, ) for predicting objective FPOP (POP-Q stage 2) 77. A measurement of 8.5 cm may help to identify women with levator avulsion (AUC, (95% CI, )) 79. What is significant pelvic organ descent on translabial ultrasound? In a study on 118 young nulliparous Caucasian women, cut-offs using the 95 th centile definition (mean + 2 SD) were determined for bladder, uterine and rectal descent as follows (with negative values signifying descent below the symphysis pubis): bladder, 6 mm (mean, +14 mm; SD, 10 mm; range, +30 to 10 mm); uterus, +5mm (mean, +31 mm; SD, 13 mm; range, +59 to 0 mm); and rectal ampulla, 24 mm (mean, 8 mm; SD, 16 mm; range, +54 to 22 mm), respectively 98 (Table 1). In two other studies that used ROC statistics to determine optimal cut-offs for significant prolapse in a group of symptomatic subjects, corresponding values for bladder, uterine and rectal descent were: 10 mm (AUC, 0.857), +15 mm (AUC, 0.68) and 15 mm (AUC, 0.821), respectively (Figure 9) 8,100. It is not surprising that different cut-offs were obtained in these studies as different definitions of significant pelvic organ descent were used; in fact, the values never vary by more than 10 mm. A definition obtained in symptomatic older women rather than in asymptomatic young nulliparae may be more appropriate and more relevant to clinicians, as treatment decisions will of course be necessary in this population rather than in young nulliparae. Table 1 Cut-offs for defining significant female pelvic organ prolapse (FPOP) by translabial ultrasound (US) assessment and by the International Continence Society Pelvic Organ Prolapse Quantification (ICS POP-Q) system, and association between significant pelvic organ descent on US and on ICS POP-Q Cut-off value for: Parameter Mathematical 95 th centile definition for US measurements 98 ROC definition using symptoms of FPOP for US measurements 8,100 ROC definition using symptoms of FPOP for ICS POP-Q 6 Equivalent cut-offs for US and ICS POP-Q values 102 Bladder descent 6mm 10 mm Ba 0.5 cm Bladder 10 mm = Ba 0.5 cm Uterine descent +5 mm +15 mm C 5.0 cm Uterus +15 mm= C 4.5 cm Rectal descent 24 mm 15 mm Bp 0.5 cm Rectum 15 mm= Bp 0.5 cm A negative value signifies a position below the posterior inferior margin of the symphysis pubis on US or above the hymen on ICS POP-Q assessment. Ba, most distal position of the remaining upper anterior vaginal wall; Bp, most distal position of the remaining upper posterior vaginal wall; C, most distal edge of cervix. ROC, receiver operating characteristics. (a) 1.0 (b) mm 20 mm 15 mm mm mm 10 mm (c) mm Sensitivity Sensitivity Sensitivity Specificity Specificity 1 Specificity Figure 9 Receiver operating characteristics (ROC) curves to define optimal cut-off values (indicated) for: (a) cystocele, with optimal cut-off of 10 mm (area under ROC curve = 0.857); (b) rectocele, with optimal cut-off of 15 mm (area under ROC curve = 0.821) (both n = 655; reproduced with permission from Dietz and Lekskulchai 8 ); and (c) uterine prolapse, with optimal cut-off of +15mm (15 mm above symphysis pubis) (area under ROC curve = 0.678; n = 538; reproduced with permission from Shek and Dietz 100 ).

10 690 Shek and Dietz (a) 3 POP-Q coordinate Bladder descent on US (mm) (b) 5 POP-Q coordinate Uterine descent on US (mm) (c) POP-Q coordinate Rectoentercoele descent on US (mm) Figure 10 ANOVA graphs showing association between pelvic organ descent on translabial ultrasound (US) and coordinates. (a) Maximum downward displacement of anterior vaginal wall (Ba), (b) maximum downward displacement of cervix (C) and (c) maximum downward displacement of posterior vaginal wall (Bp) on International Continence Society Pelvic Organ Prolapse Quantification (ICS POP-Q) assessment (n = 825). For significant bladder descent on US, 10 mm corresponds to 0.5 cm on ICS POP-Q; for significant uterine descent on US, +15 mm corresponds to 4.5 cm on ICS POP-Q; and for significant rectoenterocele descent on US, 15 mm corresponds to 0.5 cm on ICS POP-Q 102. What is abnormal distensibility of the levator hiatus or ballooning on ultrasound? The simplest way to measure levator hiatal dimensions on imaging is to determine the anteroposterior diameter of the hiatus on Valsalva maneuver in the mid-sagittal view, using a 2D ultrasound system. This measurementis strongly associated with prolapse symptoms/pelvic organ descent 83. If a 3D/4D ultrasound system is available, hiatal area can be determined, and the strongest correlations with symptoms and signs of pelvic organ descent are consistently obtained for hiatal area on Valsalva maneuver 12,13. Using ROC statistics, a cut-off of 25 cm 2 yielded an AUC of 0.71 (95% CI, ; sensitivity, 0.55; specificity, 0.77) for detecting prolapse symptoms 13. Coincidentally, in a prospective observational study on 52 young nulligravid female Caucasians, the 95 th centile for hiatal area on Valsalva maneuver was also found to be 25 cm 2 (mean ± SD, ± 5.87 cm 2 ) 12. Based on these findings, a hiatal area on Valsalva maneuver of 25 cm 2 is used to define ballooning or abnormal distensibility of the levator hiatus on translabial ultrasound. Subclassifying ballooning into mild ( cm 2 ), moderate ( cm 2 ), marked ( cm 2 ) and severe ( 40 cm 2 ) has been demonstrated to show a progressively stronger association with FPOP for those subgroups 13. Association between POP-Q coordinates and translabial ultrasound findings Translabial ultrasound measures of pelvic organ descent are strongly associated with symptoms of FPOP 8. However, the association between POP-Q and ultrasound findings has not been investigated in detail until recently 102. This is relevant, not least in the light of the abovementioned need to define normality. Figure 10 shows ANOVA graphs of the POP-Q coordinates Ba, C and Bp, and their association with corresponding translabial ultrasound findings. The proposed cut-offs for significant prolapse on ultrasound and POP-Q using ROC statistics 8,100 are mutually compatible and consistent with the literature 6 (Table 1). Conclusion A proper diagnosis is a precondition for appropriate management of any clinical condition. The best surgical treatment, even in the hands of the best surgeon, is likely to fail if it is performed for the wrong indication or on the wrong patient. Over the last 10 years, imaging has helped us make significant progress in the assessment of FPOP, not least by defining limits of normality, another essential precondition for effective and appropriate treatment. Imaging, especially translabial ultrasound, complements clinical examination findings in determining the nature and severity of the condition, and in identifying different underlying anatomical abnormalities that are impossible to distinguish clinically as they result in similar changes to surface anatomy. 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