3D finite element modeling of pelvic organ prolapse

Objectives: The purpose of this study is to develop a validated 3D finite element model of the pelvic floor system which can offer insights into the mechanics of anterior vaginal wall prolapse and have the ability to assess biomedical device treatment methods. The finite element results should accurately mimic the clinical findings of prolapse due to intra-abdominal pressure (IAP) and soft tissues impairment conditions. Methods: A 3D model of pelvic system was created in Creo Parametric 2.0 based on MRI Images, which included uterus, cervix, vagina, cardinal ligaments, uterosacral ligaments, and a simplified levator plate and rectum. The geometrical model was imported into ANSYS Workbench 14.5. Mechanical properties of soft tissues were based on experimental data of tensile test results from current literature. Studies were conducted for IAP loadings on the vaginal wall and uterus, increasing from lowest to extreme values. Results: Anterior vaginal wall collapse occurred at an IAP value corresponding to maximal valsalva and showed similar collapsed shape as clinical findings. Prolapse conditions exhibited high sensitivity to vaginal wall stiffness, whereas healthy tissues was found to support the vagina against prolapse. Ligament impairment was found to have only a secondary effect on prolapse.     

Tissue engineering in female pelvic floor reconstruction

Pelvic organ prolapse is a common and frequently occurring disease in middle‐aged and elderly women. Mesh implantation is an ideal surgical treatment. The polypropylene mesh commonly used in clinical practice has good mechanical properties, but there are long‐term complications. The application of tissue engineering technology in the treatment of pelvic organ prolapse disease can not only meet the mechanical requirements of pelvic floor support, but also be more biocompatible than traditional polypropylene mesh, and can promote tissue repair to a certain extent. In this paper, the progress of tissue engineering was summarized to understand the application of tissue engineering in the treatment of pelvic organ prolapse disease and will help in research.     

Expression of estrogen receptors in the pelvic floor of pre- and post-menopausal women presenting pelvic organ prolapse

The precise role of estrogen in the pathogenesis of pelvic organ prolapse (POP) is still unclear, while the results concerning the effect of selective estrogen receptor modulators on pelvic organ prolapse are contradictory. Our aim was to test whether alteration in the expression of estrogen receptors in the pelvic floor of pre- and post-menopausal women is related to genital prolapse status. The mRNA levels of ERα and ERβ in 60 biopsy specimens were measured. Significantly higher expression of ERα and higher ERα/ERβ ratio were demonstrated in post-menopausal women compared to pre-menopausal women. Higher expression of ERα and higher ERα/ERβ ratio were detected in all studied groups with POP, thus it did not reach significance in the post-menopausal group. Pre-menopausal and post-menopausal women presenting pelvic organ prolapse had no difference in the ERα expression. Our preliminary study may indicate that pelvic organ prolapse is associated with higher expression of ERα/ERβ in the pelvic floor of both pre- and post-menopausal women; thus not reaching statistical significance in the post-menopausal women was probably due to the group's size. We believe that the inevitable changes in the estrogen receptor expression over women's different lifetimes may affect the risk of genital prolapse progression, and might contribute to the further search for appropriate selective estrogen receptor modulators as a treatment for women with pelvic organ prolapse.     

A biomechanical model to assess the contribution of pelvic musculature weakness to the development of stress urinary incontinence

A biomechanical model of the female pelvic support system was developed to explore the contribution of pelvic floor muscle defect to the development of stress urinary incontinence (SUI). From a pool of 135 patients, clinical data of 26 patients with pelvic muscular defect were used in modelling. The model was employed to estimate the parameters that describe the stiffness properties of the vaginal wall and ligament tissues for individual patients. The parameters were then implemented into the model to evaluate for each patient the impact of pelvic muscular defect on the vaginal apex support and the bladder neck support, a factor that relates to the onset of SUI. For the modelling analysis, the compromise of pelvic muscular support was demonstrated to contribute to vaginal apex prolapse and bladder neck prolapse, a condition commonly seen in SUI patients, while simulated conditions of restored muscular support were shown to help re-establish both vaginal apex and bladder neck supports. The findings illustrate the significance of pelvic muscle strength to vaginal support and urinary continence; therefore, the clinical recommendation of pelvic muscle strengthening, such as Kegel exercises, has been shown to be an effective treatment for patients with SUI symptoms.     

Endometrial mesenchymal stem cells as a cell based therapy for pelvic organ prolapse

Pelvic organ prolapse(POP) occurs when the pelvic organs(bladder, bowel or uterus) herniate into the vagina, causing incontinence, voiding, bowel and sexual dysfunction, negatively impacting upon a woman's quality of life. POP affects 25% of all women and results from childbirth injury. For 19% of all women, surgical reconstructive surgery is required for treatment, often augmented with surgical mesh. The surgical treatment fails in up to 30% of cases or results in adverse effects, such as pain and mesh erosion into the bladder, bowel or vagina. Due to these complications the Food and Drug Administration cautioned against the use of vaginal mesh and several major brands have been recently been withdrawn from market. In this review we will discuss new cell-based approaches being developed for the treatment of POP. Several cell types have been investigated in animal models, including a new source of mesenchymal stem/stromal cells(MSC) derived from human endometrium. The unique characteristics of endometrial MSC, methods for their isolation and purification and steps towards their development for good manufacturing practice production will be described. Animal models that could be used to examine the potential for this approach will also be discussed as will a rodent model showing promise in developing an endometrial MSC-based therapy for POP. The development of a preclinical large animal model for assessing tissue engineering constructs for treating POP will also be mentioned.     

Modeling leaflet correction techniques in aortic valve repair: A finite element study

In aortic valve sparing surgery, cusp prolapse is a common cause of residual aortic insufficiency. To correct cusp pathology, native leaflets of the valve frequently require adjustment which can be performed using a variety of described correction techniques, such as central or commissural plication, or resuspension of the leaflet free margin. The practical question then arises of determining which surgical technique provides the best valve performance with the most physiologic coaptation. To answer this question, we created a new finite element model with the ability to simulate physiologic function in normal valves, and aortic insufficiency due to leaflet prolapse in asymmetric, diseased or sub-optimally repaired valves. The existing leaflet correction techniques were simulated in a controlled situation, and the performance of the repaired valve was quantified in terms of maximum leaflets stress, valve orifice area, valve opening and closing characteristics as well as total coaptation area in diastole. On the one hand, the existing leaflet correction techniques were shown not to adversely affect the dynamic properties of the repaired valves. On the other hand, leaflet resuspension appeared as the best technique compared to central or commissural leaflet plication. It was the only method able to achieve symmetric competence and fix an individual leaflet prolapse while simultaneously restoring normal values for mechanical stress, valve orifice area and coaptation area.     

A Retrospective Analysis of the Effectiveness of a Modified Abdominal High Uterosacral Colpopexy in the Treatment of Uterine Prolapse

To evaluate the clinical value of a novel method for high uterosacral colpopexy in the treatment of uterine prolapse. Thirty-one cases with severe pelvic organ prolapse diagnosed by pelvic organ prolapse quantification (POP-Q) system received a novel high sacral colpopexy method. Clinical parameters associated perioperative period and 12?months after surgery and complications were analyzed. A questionnaire survey on pelvic floor distress inventory and pelvic organ prolapse/urinary incontinence and sexual function was implemented. Between January 2007 and June 2008, 31 patients successfully received a Modified Abdominal High Uterosacral Colpopexy. The mean operation time was 50?±?15?min, and the average blood loss was 100?±?20?mls. 28 Patients returned for a 1-year follow-up, and the average follow-up period was 14?±?6?months. According to POP-Q system evaluation, the rate of operational success reached 100?%. There were no significant intraoperative and postoperative complications. A total of 31 responses on pelvic floor distress inventory short form questionnaire and 24 responses on pelvic organ prolapse/urinary incontinence sexual questionnaire showed that there was statistical significant difference before and after the procedure. This novel, high uterosacral colpopexy method is a safe and effective method for the treatment of uterine prolapse.     

Two parallel,pragmatic, UK multicentre,randomised controlled trials comparing surgical options for upper compartment (vault or uterine) pelvic organ prolapse (the VUE Study): study protocol for a randomised controlled trial

BackgroundOne in three women who have a prolapse operation will go on to have another operation, though not necessarily in the same compartment. Surgery can result in greater impairment of quality of life than the original prolapse itself (such as the development of new-onset urinary incontinence, or prolapse at a different site). Anterior and posterior prolapse surgery is most common (90 % of operations), but around 43 % of women also have a uterine (34 %) or vault (9 %) procedure at the same time. There is not enough evidence from randomised controlled trials (RCTs) to guide management of vault or uterine prolapse. The Vault or Uterine prolapse surgery Evaluation (VUE) study aims to assess the surgical management of upper compartment pelvic organ prolapse (POP) in terms of clinical effectiveness, cost-effectiveness and adverse events.Methods/designVUE is two parallel, pragmatic, UK multicentre, RCTs (Uterine Trial and Vault Trial). Eligible for inclusion are women with vault or uterine prolapse: requiring a surgical procedure, suitable for randomisation and willing to be randomised. Randomisation will be computer-allocated separately for each trial, minimised on: requiring concomitant anterior and/or posterior POP surgery or not, concomitant incontinence surgery or not, age (under 60 years or 60 years and older) and surgeon. Participants will be randomly assigned, with equal probability to intervention or control arms in either the Uterine Trial or the Vault Trial. Uterine Trial participants will receive either a vaginal hysterectomy or a uterine preservation procedure. Vault Trial participants will receive either a vaginal sacrospinous fixation or an abdominal sacrocolpopexy. Participants will be followed up by postal questionnaires (6 months post surgery and 12 months post randomisation) and also reviewed in clinic 12 months post surgery. The primary outcome is the participant-reported Pelvic Organ Prolapse Symptom Score (POP-SS) at 12 months post randomisation.DiscussionDemonstrating the efficacy of vault and uterine prolapse surgeries is relevant not only to patients and clinicians but also to health care providers, both in the UK and globally.

Trial registration

Current controlled trials ISRCTN86784244 (assigned 19 October 2012), and the first subject was randomly assigned on 1 May 2013 

Electronic supplementary material

The online version of this article (doi:10.1186/s13063-016-1576-x) contains supplementary material, which is available to authorized users.     

Measuring morphological parameters of the pelvic floor for finite element modelling purposes

The goal of this study was to obtain a complete data set needed for studying the complex biomechanical behaviour of the pelvic floor muscles using a computer model based on the finite element (FE) theory. The model should be able to predict the effect of surgical interventions and give insight into the function of pelvic floor muscles. Because there was a lack of any information concerning morphological parameters of the pelvic floor muscle structures, we performed an experimental measurement to uncover those morphological parameters. Geometric parameters as well as muscle parameters of the pelvic floor muscles were measured on an embalmed female cadaver. A three-dimensional (3D) geometric data set of the pelvic floor including muscle fibre directions was obtained using a palpator device. A 3D surface model based on the experimental data, needed for mathematical modelling of the pelvic floor, was created. For all parts of the diaphragma pelvis, the optimal muscle fibre length was determined by laser diffraction measurements of the sarcomere length. In addition, other muscle parameters such as physiological cross-sectional area and total muscle fibre length were determined. Apart from these measurements we obtained a data set of the pelvic floor structures based on nuclear magnetic resonance imaging (MRI) on the same cadaver specimen. The purpose of this experiment was to discover the relationship between the MRI morphology and geometrical parameters obtained from the previous measurements. The produced data set is not only important for biomechanical modelling of the pelvic floor muscles, but it also describes the geometry of muscle fibres and is useful for functional analysis of the pelvic floor in general. By the use of many reference landmarks all these morphologic data concerning fibre directions and optimal fibre length can be morphed to the geometrical data based on segmentation from MRI scans.These data can be directly used as an input for building a mathematical model based on FE theory.     

Expression of matrix metalloproteinase-1 in uterosacral ligaments tissue of women with genital prolapse

Collagen metabolism is altered in the pelvic organ tissues of women with genital prolapse. The aim of this study was to compare collagen metabolism by measuring matrix metalloproteinase-1 (MMP-1) expression in uterosacral ligament tissues of postmenopausal women with and without genital prolapse. Uterosacral ligament tissues were obtained at the time of abdominal or vaginal surgery from twenty-four patients with pelvic organ prolapse (POP) and 21 women who underwent gynecologic surgery for benign indications. The tissue samples were analyzed by immunohistochemistry. There were no differences in age, BMI and parity between two groups. The patients with genital prolapse demonstrated significantly higher occurences of MMP-1 expression compared to controls. These findings indicate that increased MMP-1 expression in uterosacral ligaments is associated with genital prolapse. Our data are consistent with the theory that increased collagen breakdown may play an important role in the onset and development of pelvic organ prolapse (POP).     

The controversies regarding the role of estrogens in urogynecology

Estrogens are crucial for the proper functioning of genitourinary tract. Hypoestrogenism related to menopause could be linked to numerous disturbances of lower urinary tract. However, the results of most well designed clinical studies do not support use of estrogen or hormone replacement therapy for the treatment of genitourinary symptoms. According to evidence base medicine stress urinary incontinence, overactive bladder syndrome or pelvic organ prolapse are best treated by the surgery or non-hormonal drug therapy.     

Personalized Computational Modeling of Mitral Valve Prolapse: Virtual Leaflet Resection

Posterior leaflet prolapse following chordal elongation or rupture is one of the primary valvular diseases in patients with degenerative mitral valves (MVs). Quadrangular resection followed by ring annuloplasty is a reliable and reproducible surgical repair technique for treatment of posterior leaflet prolapse. Virtual MV repair simulation of leaflet resection in association with patient-specific 3D echocardiographic data can provide quantitative biomechanical and physiologic characteristics of pre- and post-resection MV function. We have developed a solid personalized computational simulation protocol to perform virtual MV repair using standard clinical guidelines of posterior leaflet resection with annuloplasty ring implantation. A virtual MV model was created using 3D echocardiographic data of a patient with posterior chordal rupture and severe mitral regurgitation. A quadrangle-shaped leaflet portion in the prolapsed posterior leaflet was removed, and virtual plication and suturing were performed. An annuloplasty ring of proper size was reconstructed and virtual ring annuloplasty was performed by superimposing the ring and the mitral annulus. Following the quadrangular resection and ring annuloplasty simulations, patient-specific annular motion and physiologic transvalvular pressure gradient were implemented and dynamic finite element simulation of MV function was performed. The pre-resection MV demonstrated a substantial lack of leaflet coaptation which directly correlated with the severe mitral regurgitation. Excessive stress concentration was found along the free marginal edge of the posterior leaflet involving the chordal rupture. Following the virtual resection and ring annuloplasty, the severity of the posterior leaflet prolapse markedly decreased. Excessive stress concentration disappeared over both anterior and posterior leaflets, and complete leaflet coaptation was effectively restored. This novel personalized virtual MV repair strategy has great potential to help with preoperative selection of the patient-specific optimal MV repair techniques, allow innovative surgical planning to expect improved efficacy of MV repair with more predictable outcomes, and ultimately provide more effective medical care for the patient.     

Surgery Issue: Solving the Puzzle of Chronic Ischemic Mitral Regurgitation

Chronic ischemic mitral regurgitation is a prevalent problem among patients following a myocardial infarction. Until recently, the pathophysiology was poorly understood, resulting in surgical strategies with suboptimal results and limited durability. The surgical approach has evolved from revascularization alone to an additional mitral valve procedure, replacement, or repair. When the valve was repaired, isolated annuloplasty was performed. The dilemma that surgeons had when repairing a mitral valve was which type of ring to use and what size. In all series with annuloplasty alone, the results were poor with very high recurrence rates. The primary feature of ischemic mitral regurgitation is a prolapse of the anterior leaflet at A3 ± A2. This prolapse can be caused by fibrotic elongation of the papillary muscle supporting A3 ± A2 or tethering of P3 by a ballooning posterior left ventricular wall. Using a technique that corrects this prolapse with Gore-Tex neochords, we have achieved excellent results with effective and durable correction of the ischemic mitral regurgitation.     

Quantification of pelvic organ prolapse in mice: vaginal protease activity precedes increased MOPQ scores in fibulin 5 knockout mice

Two mouse models of pelvic organ prolapse have been generated recently, both of which have null mutations in genes involved in elastic fiber synthesis and assembly (fibulin 5 and lysyl oxidase-like 1). Interestingly, although these mice exhibit elastinopathies early in life, pelvic organ prolapse does not develop until later in life. In this investigation we developed and validated a tool to quantify the severity of pelvic organ prolapse in mice, and we used this tool prospectively to study the role of fibulin 5, aging, and vaginal proteases in the development of pelvic organ prolapse. The results indicate that >90% of Fbln5(-/-) mice develop prolapse by 6 mo of age, even in the absence of vaginal delivery, and that increased vaginal protease activity precedes the development of prolapse.     

Quantitative analysis of 17 amino acids in the connective tissue of patients with pelvic organ prolapse using capillary electrophoresis-tandem mass spectrometry

The simultaneous determination of 17 amino acids in connective tissue using capillary electrophoresis is described in this study. Separation was carried out on a fused silica capillary column (80 cm x 50 mm i.d.) with 1M formic acid as the running electrolyte. The detection was conducted on a mass spectrometer by selective reaction monitoring (SRM) mode via an electrospray ionization source. Tissue samples were prepared by reduction and acid hydrolysis to extract amino acids; over 84.3% recovery was seen for all compounds. The method allowed for sensitive, reproducible, and reliable quantification, and all 17 amino acids were separated using this method. Good linearity over the investigated concentration ranges was observed, with values of R higher than 0.993 for all the analytes. Precision and accuracy examined at three concentration levels ranged from 0.2% to 19.5% and 84.1% to 120.0%, respectively. Matrix effects were also tested and ranged from -9.1% to 15.4%. The validated method was applied to the quantitation of 17 amino acids in pelvic connective tissue of pelvic organ prolapsed patients. Methionine, glutamine, and histidine were significantly higher in the experimental patients compared to the controls. This suggests that changes in the amino acid concentrations within the connective tissue could be a factor in the genesis of pelvic organ prolapse. Therefore, this method is potentially applicable for amino acid analysis in tissue, providing a more complete understanding of pelvic organ prolapse.     

子宫托对阴道微生态的影响以及应用雌激素的作用

通常将阴道前后壁、膀胱或直肠等盆腔脏器突入阴道内,称为盆腔脏器脱垂,常发生于老年女性。盆腔脏器脱垂及其引起的排尿相关症状严重影响患者的生活质量。目前临床上治疗盆腔脏器脱垂最常用的方法为佩戴子宫托。子宫托治疗盆腔脏器脱垂已有久远的历史。使用子宫托可明显改善盆腔脏器脱垂患者的临床症状,提高患者的生活质量。然而研究显示,对于机体而言,阴道内放置子宫托可在一定程度上影响阴道微生态环境平衡,从而使佩戴子宫托患者的细菌性阴道病患病率增加4.37倍。同时使用雌激素可明显减少由使用子宫托引起的阴道微环境改变、出血、溃疡等症状的发生。现就子宫托对阴道微生态的影响以及应用雌激素的作用做一简要综述。     

Pelvic Organ Support in Animals with Partial Loss of Fibulin-5 in the Vaginal Wall

Compromise of elastic fiber integrity in connective tissues of the pelvic floor is most likely acquired through aging, childbirth-associated injury, and genetic susceptibility. Mouse models of pelvic organ prolapse demonstrate systemic deficiencies in proteins that affect elastogenesis. Prolapse, however, does not occur until several months after birth and is thereby acquired with age or after parturition. To determine the impact of compromised levels of fibulin-5 (Fbln5) during adulthood on pelvic organ support after parturition and elastase-induced injury, tissue-specific conditional knockout (cKO) mice were generated in which doxycycline (dox) treatment results in deletion of Fbln5 in cells that utilize the smooth muscle α actin promoter-driven reverse tetracycline transactivator and tetracycline responsive element-Cre recombinase (i.e., Fbln5^f/f/SMA⁺⁺-rtTA/Cre⁺, cKO). Fbln5 was decreased significantly in the vagina of cKO mice compared with dox-treated wild type or controls (Fbln5^f/f/SMA⁺⁺-rtTA/Cre^-/-). In controls, perineal body length (PBL) and bulge increased significantly after delivery but declined to baseline values within 6–8 weeks. Although overt prolapse did not occur in cKO animals, these transient increases in PBL postpartum were amplified and, unlike controls, parturition-induced increases in PBL (and bulge) did not recover to baseline but remained significantly increased for 12 wks. This lack of recovery from parturition was associated with increased MMP-9 and nondetectable levels of Fbln5 in the postpartum vagina. This predisposition to prolapse was accentuated by injection of elastase into the vaginal wall in which overt prolapse occurred in cKO animals, but rarely in controls. Taken together, our model system in which Fbln5 is conditionally knock-downed in stromal cells of the pelvic floor results in animals that undergo normal elastogenesis during development but lose Fbln5 as adults. The results indicate that vaginal fibulin-5 during development is crucial for baseline pelvic organ support and is also important for protection and recovery from parturition- and elastase-induced prolapse.     

Changes in Muscularis Propria of Anterior Vaginal Wall in Women with Pelvic Organ Prolapse

The objective of this study was to evaluate the morphological and immunohistochemical alterations of tissue removed from the upper third of anterior vaginal wall in a sample group of the female population presenting homogenous risk factors associated with pelvic organ prolapse (POP). The case study consisted of 14 patients with POP and there were 10 patients in the control group. Patient selection was carried on the basis of specific criteria and all of the patients involved in the study presented one or more of the recognized POP risk factors. Samples were taken from POP patients during vaginal plastic surgery following colpohysterectomy, and from control patients during closure of the posterior fornix following hysterectomy. Samples were processed for histological and immunohistochemical analyses for Collagen I and Collagen III, α-Smooth Muscle Actin (α-SMA), Platelet-Derived-Growth-Factor (PDGF), matrix metalloproteinase 3 (MMP3), tissue inhibitors metalloproteinase 1 (TIMP1), Caspase3. Immunofluorescence analyses for Collagen I and III and PDGF were also carried out. In prolapsed specimens our results show a disorganization of smooth muscle cells that appeared to have been displaced by an increased collagen III deposition resulting in rearrangement of the muscularis propria architecture. These findings suggest that the increase in the expression of collagen fibers in muscularis could probably be due to a phenotypic switch resulting in the dedifferentiation of smooth muscle cells into myofibroblasts. These alterations could be responsible for the compromising of the dynamic functionality of the pelvic floor.Key words: Pelvic organ prolapse, immunohistochemistry, smooth muscle cells, collagen, PDGF     

How Accurate Is Preoperative Evaluation of Pelvic Organ Prolapse in Women Undergoing Vaginal Reconstruction Surgery?

Objective

To evaluate the differences between the in-office and intraoperative techniques used to evaluate pelvic organ prolapse.

Materials and Methods

A prospective study included 25 women undergoing vaginal reconstruction surgery including vaginal hysterectomy for pelvic organ prolapse. The outpatient pelvic and site-specific vaginal examination was performed in the lithotomy position with the Valsalva maneuver. Repeated intraoperative examination was performed under general anesthesia with standard mild cervical traction. The Pelvic Organ Prolapse Quantification system (POPQ) was used for both measurements and staging. The values found under the two conditions were compared.

Results

The intraoperative POPQ-measurements values were significantly higher than the outpatient values for apical wall prolapse in 17/25 (68%) women and for anterior wall prolapse in 8/25 (32%) women. There was not a significant difference in the posterior wall where increase in staging was shown in 3/25 (12%) patients.

Conclusions

Clinicians and patients should be alert to the possibility that pelvic organ measurements performed under general anesthesia with mild traction may be different from preoperative evaluation.     

经利用网片的前盆底重建术治疗重度盆腔器官脱垂的临床疗效

目的:探讨经利用网片的前盆底重建术治疗重度盆腔器官脱垂的临床效果。方法:选取2013年1月-2015年3月我院妇科收治的以前中盆腔联合缺陷为主的盆底障碍性疾病患者39例(POP-Q分度III-IV度)。实施经阴道Avaulta前盆腔重建术,24例切除子宫,9例保留子宫,其中6例因中盆腔重度脱垂联合行阴道残端骶棘韧带固定术,2例合并尿失禁同时行经尿道无张力悬吊术。术后随访12-25月,根据盆腔脏器脱垂评分(POP-Q)测量及PFIQ-7评分进行客观评价及主观感受评价进行中短期的临床效果分析。结果:39例患者手术过程顺利,术后无严重并发症,POP-Q评分均较术前显著降低,客观疗效理想。术后阴道前壁及子宫、阴道穹窿脱垂等症状显著改善;到目前为止无一例复发。结论:经阴道前盆腔重建术治疗前盆腔重度盆腔脱垂为主以及合并尿失禁等复杂情况的并发症少,治愈率高,复发率低,临床效果好。