FZD3 regulates the viability, apoptosis, and extracellular matrix degradation of vaginal wall fibroblasts in pelvic organ prolapse via the Wnt signaling pathway.

The occurrence of pelvic organ prolapse (POP) seriously affects women's quality of life. However, the pathogenesis of POP remains unclear. We aimed to clarify the role of Frizzled class receptor 3 (FZD3) in POP. FZD3 expression in the vaginal wall tissues was detected using immunohistochemistry, real-time polymerase chain reaction, and western blot analysis. Then, vaginal wall fibroblasts (VWFs) were isolated from patients with POP and non-POP, and were identified. Cell viability and apoptosis were evaluated using Cell Counting Kit-8 and flow cytometry, respectively. Extracellular matrix (ECM) degradation was assessed by western blot analysis. The results illustrated that FZD3 was downregulated in POP. VWFs from POP had lower cell viability, ECM degradation, and higher apoptosis. Knockdown of FZD3 inhibited cell viability, ECM degradation, and promoted apoptosis of VWFs, whereas overexpression of FZD3 had opposite results. Moreover, IWP-4 (Wingless-type [Wnt] pathway inhibitor) reversed the role of FZD3 overexpression on biological behaviors. Taken together, FZD3 facilitates VWFs viability, ECM degradation, and inhibits apoptosis via the Wnt pathway in POP. The findings provide a potential target for the treatment of POP.

Early growth response 2, a novel target of pelvic organ prolapse, is highly expressed in anterior vaginal wall tissues with pelvic organ prolapse.

Pelvic organ prolapse (POP) is a common disorder among women that negatively affects women's quality of life. Early growth response 2 (EGR2) is a transcription factor that regulates cell growth. The present study aimed to explore the role of EGR2 in POP progression and provided a new target for the treatment and prevention of POP. Firstly, we extracted primary vaginal anterior wall fibroblasts from POP tissues and non-POP tissues and then constructed an EGR2-silencing lentivirus for further study. Immunoblotting, qPCR, TUNEL assay, CCK-8 assay, dual luciferase assay, and ELISA assay were carried out. EGR2 expression was much higher in POP tissues than in control tissues, and EGR2 expression positively correlated with cytokine signaling 3 (SOCS3) expression. Knockdown of EGR2 increased cell proliferation, upregulated PCNA expression, and reduced apoptosis in POP fibroblasts. Moreover, we found that the knockdown of EGR2 increased COL1A1, COL3A1, and Elastin expression and decreased MMP2 and MMP9 activities, and knockdown of EGR2 increased TGF-ß/Smad pathway activity in POP fibroblasts. Interestingly, the results of dual luciferase assay demonstrated that EGR2 was able to increase SOCS3 transcriptional activity. EGR2 knockdown alleviated the apoptosis of POP fibroblasts by reducing SOCS3 expression and improving the proliferation and collagen synthesis of POP fibroblasts. Overall, our study illustrated that EGR2 was highly expressed in POP tissues, and knockdown of EGR2 alleviated apoptosis and reduced matrix degradation in POP fibroblasts. This study might provide a new insight into the pathogenesis of POP.

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Pelvic floor ultrasound can clearly visualize the position and morphology of pelvic floor organs, observe the pelvic organ prolapse in real-time, and quantify and analyze the degree of the levator ani muscle injury, which is the most common imaging method to assess the morphology and function of the levator ani muscle to date. The different ultrasound imaging techniques provide a variety of indicators, each with its own advantages and limitations.Furthermore, two-dimensional ultrasound is the basis of imaging, but it fails to detect cross-sectional images of the pelvic floor; three-dimensional ultrasound can acquire the axial plane of the levator hiatus; tomographic ultrasound imaging allows real-time observation of the levator ani muscle injury; shear wave elastography can provide a quantitative assessment of the contractility and elastic characteristics of the levator ani muscle in real-time. It is of great significance to summarize the basic principles of various ultrasound imaging techniques, summarize the ultrasound image characteristics of levator ani muscle and its hiatus in different populations and different states, and explore the cut-off values and diagnostic criteria-related ultrasound parameters for improving the diagnostic efficiency of pelvic floor ultrasound for levator ani muscle injury, leading to reducing missed diagnosis and misdiagnosis of lesions.

Estrogen inhibits the differentiation of fibroblasts induced by high stiffness matrix by enhancing DNMT1 expression.

INTRODUCTION AND HYPOTHESIS: Pelvic organ prolapse(POP) is a multifactorial connective tissue disorder caused by damage to the supporting structures of the pelvic floor. Evidence from several studies suggests that anterior vaginal wall stiffness is higher in patients with POP, but the mechanisms involved remain unknown. METHODS: Tissue from the anterior vaginal wall of patients with POP or other benign diseases was obtained. The modulus of elasticity of the anterior vaginal wall was measured using a microindenter. Cells were cultured in vitro on acrylamide gels of different stiffness and treated with DNMT1 inhibitor, microtubule polymerisation inhibitor and estrogen. Western blot or immunohistochemical staining was performed to detect DNA Methyltransferase 1, α-smooth muscle actin(α-SMA) expression, and connective tissue growth factor(CTGF) expression. CONCLUSION: Estrogen can inhibit high stiffness matrix-induced fibroblast differentiation, by enhancing DNMT1 expression. This study may help to elucidate the complex crosstalk between fibroblasts and their surrounding matrix under healthy and pathological conditions and provide new insights into the options for material-related therapeutic applications.

Morphological changes in the anterior vaginal wall caused by aging: a scanning electron microscopy study.

INTRODUCTION AND HYPOTHESIS: Collagen is a protein that confers robustness and resilience to several tissues. In the female reproductive system, collagen plays a critical role in maintaining the health and function of the vaginal walls. Aging leads to collagen reduction, which may cause vaginal dryness, irritation, and prolapse. We aim to analyze the structure and profile of collagen in the anterior vaginal wall of healthy pre-menopausal (pre-M) and post-menopausal (post-M) women under a scanning electron microscope (SEM). METHODS: Fragments of the anterior vaginal wall were collected and processed for light and scanning electron microscopy. Histological preparations were performed at first with Weigert's resorcin-fuchsin stain. Decellularized preparations were conducted, and the specimens were placed under an SEM to allow observation of the 3D organization of collagen. RESULTS: Decellularized preparations of the pre-M specimens showed a vaginal wall with an irregular subepithelial layer, organized with ECM projections. The subepithelium evidenced the network of collagen fibrils, which seemed to support the epithelium as a basal layer. In specimens of post-M, a fusion of a network of fibrils from different direction axes was evidenced, with plate formation observed in the subepithelial plane, disfiguring the structural organization of fibrils. CONCLUSIONS: Older specimens showed a remodeling of collagen organization in comparison with younger samples of the anterior vaginal wall.

Estrogen and Androgen Receptor Status in Uterosacral Ligaments of Women with Pelvic Organ Prolapse Stratified by the Pelvic Organ Prolapse Histology Quantification System.

Menopause is a significant risk factor for pelvic organ prolapse (POP), suggesting that ovarian sex steroids play a major role in the etiology of the condition. POP results from failure of the uterine-cervix-vagina support structures, including the uterosacral ligament (USL). We previously identified consistent degenerative USL phenotypes that occur in POP and used their characteristics to develop a standardized POP Histologic Quantification System (POP-HQ). In this study, POP and matched control USL tissue was first segregated into the unique POP-HQ phenotypes, and specimens were then compared for estrogen receptor (ER) alpha (ERα), ERbeta (ERß), the G-protein estrogen receptor (GPER), and androgen receptor (AR) content via immunohistochemical staining. ER and AR expression levels in the control USL tissues were indistinguishable from those observed in the POP-A phenotype, and partially overlapped with those of the POP-I phenotype. However, control-USL steroid receptor expression was statistically distinct from the POP-V phenotype. This difference was driven mainly by the increased expression of GPER and AR in smooth muscle, connective tissue, and endothelial cells, and increased expression of ERα in connective tissue. These findings support a multifactorial etiology for POP involving steroid signaling that contributes to altered smooth muscle, vasculature, and connective tissue content in the USL. Furthermore, these data support the concept that there are consistent and distinct degenerative processes that lead to POP and suggest that personalized approaches are needed that target specific cell and tissues in the pelvic floor to treat or prevent this complex condition.

Two-dimensional biomechanical finite element modeling of the pelvic floor and prolapse.

We developed the pelvic floor model in physiological and pathological states to understand the changes of biomechanical axis and support that may occur from the normal physiological state to the prolapse pathological state of the pelvic floor. Based on the physiological state model of the pelvic floor, we model the uterus to the pathological state position by balancing intra-abdominal pressure (IAP) and uterine pathological position load. Under combined impairments, we compared the patterns of changes in pelvic floor biomechanics that may be induced by different uterine morphological characteristic positions under different IAP. The orientation of the uterine orifice gradually changes from the sacrococcygeal direction to the vertical downward of vaginal orifice, and a large downward prolapse displacement occurs, and the posterior vaginal wall shows "kneeling" profile with posterior wall bulging prolapse. When the abdominal pressure value was 148.1 cmH2O, the descent displacement of the cervix in the normal and pathological pelvic floor system was 11.94, 20, 21.83 and 19.06 mm in the healthy state, and 13.63, 21.67, 22.94 and 19.38 mm in the combined impairment, respectively. The above suggests a maximum cervical descent displacement of the uterus in the anomalous 90° position, with possible cervical-uterine prolapse as well as prolapse of the posterior vaginal wall. The combined forces of the pelvic floor point in the direction of vertical downward prolapse of the vaginal orifice, and the biomechanical support of the bladder and sacrococcygeal bone gradually diminishes, which may exacerbate the soft tissue impairments and biomechanical imbalances of the pelvic floor to occur of POP disease.

Total uterine prolapse: a rare cause of chronic obstructive uropathy associated with renal dysfunction (a case report).

Pelvic organ prolapse is rarely associated with severe bilateral ureteral hydronephrosis and renal dysfunction. The etiopathogenetic mechanism has not been fully elucidated. Contemporary imaging methods of the urinary tract play a decisive role in assessing the morphological function of the kidneys. In cases of moderate and severe pelvic organ prolapse, surgery appears to be the main choice of treatment. Our case concerns a post-menopausal patient with three vaginal deliveries in her obstetric history and with a history of bilateral hydronephrosis and impaired renal function who was referred to the outpatient clinic for a gynecological examination due to complete uterine prolapse. Bilateral hydroureteronephrosis due to prolapse was assessed as the main cause of renal dysfunction. A surgical intervention was decided to the pelvic floor and a vaginal hysterectomy was performed with simultaneous correction of the cystocele and rectocele. The postoperative course was uneventful. Three months later, re-examination of the urinary tract showed complete remediation of kidney morphology and function. The present case report emphasizes the significant degree of bilateral hydroureteronephrosis and deterioration of renal function rarely seen in patients with complete uterine prolapse. At the same time, it is pointed out that the exclusion of renal dysfunction related to complete uterine prolapse should be the main concern of the modern gynecologist even for complex cases with coexisting etiological factors for renal disease, in order to avoid permanent renal parenchymal damage and ensure the best health and quality of life of these patients.

scRNA-seq reveals aging-related immune cell types and regulators in vaginal wall from elderly women with pelvic organ prolapse.

Introduction: In the pathology of pelvic organ prolapse (POP), little is known about the contributing role of pelvic microenvironment. Also, the age-related differences in pelvic microenvironment of POP patients is always ignored. In the present study, we investigated the age-related differences in pelvic microenvironment between Young POP patients and Old POP patients, and the novel cell types and critical regulators which contributes to the age-related differences. Methods: Single-cell transcriptomic analyses were used to detect the changes in cell composition and gene expression from the pelvic microenvironment of control group (<60 years), Young POP group (<60 years) and Old POP group (>60 years). Then, immunohistochemistry and immunofluorescence were used to verify the novel cell types and critical regulators in the pelvic microenvironment. Furthermore, histopathological alteration and mechanical property alteration in POP with different ages were revealed by vaginal tissue histology and biomechanical testing. Results: The up-regulated biological process in Old women with POP is mainly related to chronic inflammation, while the up-regulated biological process in Young women with POP is mainly related to extracellular matrix metabolism. Meantime, CSF3+ endothelial cells and FOLR2+ macrophages were found to play a central role in inducing pelvic chronic inflammation. Furthermore, the collagen fiber and mechanical property of POP patients decreased with aging. Conclusions: Taken together, this work provides a valuable resource for deciphering the aging-related immune cell types and the critical regulators in pelvic microenvironment. With better understanding of normal and abnormal events in this pelvic microenvironment, we provided rationales of personalized medicine for POP patients with different ages.

A 3D finite element model of uterus support to evaluate mechanisms underlying uterine prolapse formation.

Uterine prolapse (UP) seriously affects the quality of life and physical and mental health of elderly women, which can easily be caused by ligament injury or intra-abdominal pressure (IAP) increasing. The objective of this manuscript was to study the influence of IAP and ligament injury on uterus and its surrounding ligaments using the finite element method. First, the three-dimensional (3D) models of retroverted uterus and its surrounding ligaments were established, and loads and constraints were set in ABAQUS software, then the stress and deformation of uterine ligaments and uterine displacement were calculated. The study found that the uterine displacement and the stress and deformation of the ligaments increased when IAP and ligament injury increased alone or simultaneously. Then, the stress and sensitivity of the ligaments to the changes of IAP or ligament injury were in the order of uterosacral ligament (USL), broad ligament (BL), cardinal ligament (CL) and round ligament (RL), while the deformation and sensitivity the changes of the ligaments were in the order of BL > RL > USL > CL. Moreover, the ligament injury had a greater influence on the uterus and uterine ligaments than IAP. The results of this study can provide guidance for optimization of surgical scheme of uterus prolapsed in clinic and exploration of pathogenesis.

A 2D equivalent mechanical model of the whole pelvic floor and impairment simulation.

We developed a complete 2D equivalent mechanical model of the pelvic floor based on magnetic resonance imaging (MRI) images of a 35-year-old healthy woman. This model can simulate anterior vaginal prolapse (AVP) due to soft tissue impairment. Thus, we can study the mechanism of prolapse formation from a mechanical perspective and improve the assessment and treatment of the condition in clinical practice. Based on 2D MRI image parameter measurements and computer-aided design methods, the 2D equivalent mechanical model of the whole pelvic floor in the sagittal plane was accurately reconstructed, which includes all necessary tissues of the pelvic floor system. Material parameters were mainly from the literature. We simulated the impairment by reducing the tissue's mechanical properties, and numerical simulations predicted the mechanical response and morphological changes of the healthy and impaired pelvic floor in different states. In six intra-abdominal pressure (IAP) states (8.4-208.9 cmH2 O), the maximum cervical descent in the impaired pelvic floor was 0.3-18.521 mm, which was much greater than that in the healthy pelvic floor (0.14-6.55 mm). Once the impairment occurred (0%-25%), there was a significant increase in maximum displacement, stress, and cervical descent (30.9-36.5 mm, 0.56-1.12 MPa, 4.6-12.1 mm), and a clinically similar prolapse shape occurred. Simple supine and standing will not cause prolapse. The formation of prolapse is closely related to vaginal tissue impairment. In the standing position, the main forces on the healthy pelvic floor system are distributed horizontally posteriorly and inferiorly, reducing the burden in the vertically downward direction.

Research progress in pelvic floor ultrasound for assessing the morphology and function of levator ani muscle in women / 中南大学学报(医学版)

Pelvic floor ultrasound can clearly visualize the position and morphology of pelvic floor organs, observe the pelvic organ prolapse in real-time, and quantify and analyze the degree of the levator ani muscle injury, which is the most common imaging method to assess the morphology and function of the levator ani muscle to date. The different ultrasound imaging techniques provide a variety of indicators, each with its own advantages and limitations.Furthermore, two-dimensional ultrasound is the basis of imaging, but it fails to detect cross-sectional images of the pelvic floor; three-dimensional ultrasound can acquire the axial plane of the levator hiatus; tomographic ultrasound imaging allows real-time observation of the levator ani muscle injury; shear wave elastography can provide a quantitative assessment of the contractility and elastic characteristics of the levator ani muscle in real-time. It is of great significance to summarize the basic principles of various ultrasound imaging techniques, summarize the ultrasound image characteristics of levator ani muscle and its hiatus in different populations and different states, and explore the cut-off values and diagnostic criteria-related ultrasound parameters for improving the diagnostic efficiency of pelvic floor ultrasound for levator ani muscle injury, leading to reducing missed diagnosis and misdiagnosis of lesions.

Pelvic inclination correction system for magnetic resonance imaging analysis of pelvic organ prolapse in upright position.

INTRODUCTION AND HYPOTHESIS: Pelvic organ prolapse quantification by means of upright magnetic resonance imaging (MRI) is a promising research field. This study determines the angle for the pelvic inclination correction system (PICS) for upright patient position, which is hypothesized to deviate from the supine PICS angle. The necessity of different PICS angles for various patient positions will also be discussed. METHODS: Magnetic resonance scans of 113 women, acquired in an upright patient position, were used to determine the upright PICS angle, defined as the angle between the sacrococcygeal-inferior pubic point (SCIPP) line and the horizontal line. The difference and correlation between the upright and supine PICS angles were calculated using the paired Student's t-test and the Pearson's correlation coefficient (r) respectively. The effect of the difference between the upright and supine PICS angle on the measured pelvic organ extent was calculated using goniometry. RESULTS: The mean (interquartile range) PICS angles were 29° (26-35°) for the upright and 33° (30-37°) for the supine patient position. They were significantly different (p<0.001) and very strongly correlated (r = 0.914, p<0.001). The 4° difference between the average upright and supine PICS angle results in an average underestimation of the measured cervix height of approximately 0.5 cm for patients scanned in upright position. CONCLUSIONS: The PICS angle for the upright patient position is 29°. The use of a dedicated PICS angle for different patient positions allows for more accurate pelvic organ extent analysis in patients with prolapse.

Surgical anatomy of the mid-vagina.

AIM: The mid-vagina (MV) represents Level II of the vagina. The surgical anatomy of the MV has not been recently subject to a comprehensive examination and description. MV surgery involving anterior and posterior colporrhaphy represents a key part of surgery for a majority of pelvic organ prolapse (POP). METHODS: Literature review and surgical observations of many aspects of the MV were performed including MV length and width; MV shape; immediate relationships; histological analysis; anterior and posterior MV prolapse assessment and anterior MV surgical aspects. Unpublished pre- and postoperative quantitative data on 300 women undergoing posterior vaginal compartment repairs are presented. RESULTS: The MV runs from the lower limit of the vaginal vault (VV) to the hymen. Its length is a mean of 5 cm. Its shape in section overall is a compressed rectangle. Its longitudinal shape is created by its anterior and posterior walls being inverse trapezoid in shape. Histology comprises three layers: (i) mucosa; (ii) muscularis; (iii) adventitia. MV prolapse staging uses pelvic organ prolapse quantification (POP-Q). Anterior MV prolapse can be quantitatively assessed using POP-Q while posterior MV prolapse can be assessed with POP-Q or PR-Q. Around 50% of both cystocele and rectocele are due to VV defects. POP will increase anterior MV width and length. Native tissue anterior colporrhaphy is the current conventional repair with mesh disadvantages outweighing advantages. Posteriorly, Level II (MV) defects are far smaller (mean 1.3 cm) than Level I (mean 6.0 cm) and Level III (mean 2.9 cm). CONCLUSION: An understanding of the surgical anatomy of the MV can assist anterior and posterior colporrhaphy. In particular, if VV support is employed, the Level II component of a posterior repair should be relatively small.

Magnetic resonance imaging evaluation of the effectiveness of FemiCushion in pelvic organ prolapse.

AIMS: FemiCushion (FC) is a supportive device for pelvic organ prolapse (POP), but its effectiveness has not been evaluated with imaging studies. This study utilized magnetic resonance imaging (MRI) to evaluate the anatomic changes induced by FC use in patients with severe POP. METHODS: This prospective study examined patients with stage 3 or 4 POP who underwent treatment with FC and received a diagnostic MRI. Measurements were made in the midsagittal plane at rest and during straining with and without FC. The vertical distances from the lowest points of the anterior and posterior vaginal wall (A; P), uterine cervix or vaginal stump (C), and perineal body (PB) to the Pelvic Inclination Correction System line were measured, along with the lengths of the urogenital (UGH) and levator hiatus (LH). RESULTS: Twelve patients were included in the study. The median age was 72 (range, 56-84) years. All reference points were positioned significantly higher with the FC than without the FC (median ΔA: 11 mm, p = 0.005; ΔC: 14 mm, p = 0.011; ΔP: 6 mm, p = 0.008; ΔPB: 7 mm, p = 0.002). Median UGH and LH lengths during straining were significantly shorter with the FC than without the FC (UGH: 44 mm vs. 53 mm, p = 0.002; LH: 60 vs. 65 mm, p = 0.021). CONCLUSIONS: This is the first report on the use of MRI to measure the performance of FC. Our study demonstrates that FC effectively repositioned the organs involved in POP.

Role of Fibroblasts and Myofibroblasts on the Pathogenesis and Treatment of Pelvic Organ Prolapse.

Pelvic organ prolapse (POP) is a multifactorial connective tissue disorder caused by damage to the supportive structures of the pelvic floor, leading to the descent of pelvic organs in the vagina. In women with POP, fibroblast function is disturbed or altered, which causes impaired collagen metabolism that affects the mechanical properties of the tissue. Ideal surgical repair, either native tissue repair or POP surgery using an implant, aims to create a functional pelvic floor that is load-bearing, activating fibroblasts to regulate collagen metabolism without creating fibrotic tissue. Fibroblast function plays a crucial role in the pathophysiology of POP by directly affecting the connective tissue quality. On the other hand, fibroblasts determine the success of the POP treatment, as the fibroblast-to-(myo)fibroblast transition is the key event during wound healing and tissue repair. In this review, we aim to resolve the question of "cause and result" for the fibroblasts in the development and treatment of POP. This review may contribute to preventing the development and progress of anatomical abnormalities involved in POP and to optimizing surgical outcomes.

Multi-label classification of pelvic organ prolapse using stress magnetic resonance imaging with deep learning.

INTRODUCTION AND HYPOTHESIS: We aimed to develop a deep learning-based multi-label classification model to simultaneously diagnose three types of pelvic organ prolapse using stress magnetic resonance imaging (MRI). METHODS: Our dataset consisted of 213 midsagittal labeled MR images at maximum Valsalva. For each MR image, the two endpoints of the sacrococcygeal inferior-pubic point line were auto-localized. Based on this line, a region of interest was automatically selected as input to a modified deep learning model, ResNet-50, for diagnosis. An unlabeled MRI dataset, a public dataset, and a synthetic dataset were used along with the labeled image dataset to train the model through a novel training strategy. We conducted a fivefold cross-validation and evaluated the classification results using precision, recall, F1 score, and area under the curve (AUC). RESULTS: The average precision, recall, F1 score, and AUC of our proposed multi-label classification model for the three types of prolapse were 0.84, 0.72, 0.77, and 0.91 respectively, which were improved from 0.64, 0.53, 0.57, and 0.83 from the original ResNet-50. Classification took 0.18 s to diagnose one patient. CONCLUSIONS: The proposed deep learning-based model were demonstrated feasible and fast in simultaneously diagnosing three types of prolapse based on pelvic floor stress MRI, which could facilitate computer-aided prolapse diagnosis and treatment planning.

Dynamic magnetic resonance imaging evaluation before and after operation for pelvic organ prolapse.

PURPOSE: This study aimed to explore the value of dynamic magnetic resonance imaging (MRI) before and after operation for pelvic organ prolapse (POP). METHODS: Twenty-nine patients with POP (POP group) before and one month after surgery and 12 healthy women (control group) underwent static and dynamic MRI at rest and during straining (Valsalva maneuver). The preoperative MRI images of the POP and control groups were analyzed, and various measurements were recorded. Differences in measurements were compared between the POP and control groups; similarly, changes in measurements before and after operation were compared. RESULTS: In the POP group, MRI detected 29 anterior vaginal prolapses, 27 uterine prolapses, 1 rectoceles, and 14 pouch of Douglas hernias. In addition, 27 levator ani muscle defect and 15 pubocervical fascial defect cases were observed. The bladder-pubococcygeal line (B-PCL), uterus-pubococcygeal line (U-PCL), Douglas pouch-pubococcygeal line, the length of the hiatus, the descent of the levator plate, levator hiatus size, levator plate angle, iliococcygeus angle, and urethral inclination angle (UA) were larger in the POP group than in the control group. The pelvic organs' positions returned to normal postoperatively in 9 of 21 cases. The B-PCL, U-PCL, and UA were smaller post-surgery than pre-surgery. CONCLUSIONS: Static and dynamic MRI can comprehensively evaluate morphological and functional changes of the pelvic floor postoperatively.

Evaluation and Management of Pelvic Organ Prolapse.

Pelvic organ prolapse (POP) is a common clinical entity that can have a significant impact on a patient's quality of life secondary to symptoms of pelvic pressure, vaginal bulge, urinary and bowel dysfunction, or sexual dysfunction. It is highly prevalent, with roughly 13% of women undergoing surgery for prolapse in their lifetime. Vaginal prolapse is diagnosed by history and physical examination. Additional testing may be indicated for evaluation of bowel and bladder symptoms. On examination, prolapse can represent descent of the anterior vaginal wall, vaginal apex (cervix/uterus or vaginal cuff scar after hysterectomy), or posterior vaginal wall, although it represents a combination of these in many cases. Treatment options for POP include observation, pelvic floor physical therapy, pessary use, and surgery. In patients with asymptomatic POP, observation is typically used. In those not desiring or medically unfit for surgery, pessaries are an effective nonsurgical option. When it is indicated, surgery can be performed through transvaginal, laparoscopic/robotic, or open approaches, using either the patient's own tissue or mesh augmentation. Deciding between these is based on the compartments involved, extent of prolapse, medical and surgical comorbidities, differences in durability and risk between operations, and shared decision-making with the patient. Here, we review pertinent clinical considerations in the evaluation and management of POP.