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Complications following surgical repair of pelvic organ prolapse (POP) with polypropylene mesh (PPM) are common. Recent data attributes complications, in part, to stiffness mismatches between the vagina and PPM. We developed a 3D printed elastomeric membrane (EM) from a softer polymer, polycarbonate urethane (PCU). EMs were manufactured with more material given the low inherent material strength of PCU. We hypothesized that the EMs would be associated with an improved host response as compared to PPM. A secondary goal was to optimize the material distribution (fiber width and device thickness) within EMs, in regards to the host response. EM constructs (2 × 1 cm 2 ) with varied polymer stiffness, fiber width, and device thickness were implanted onto the vagina of New Zealand white rabbits for 12 weeks and compared to similarly sized PPMs. Sham implanted animals served as controls. Mixed effects generalized linear models were used to compare the effect of construct type accounting for differences in independent variables. EMs had an overall superior host response compared to PPM as evidenced by preservation of vaginal smooth muscle morphology (p-values<0.01), decreased total cellular response to construct fibers (p-values<0.001), and a reduced percent of macrophages (p-values<0.02) independent of how the material was distributed. Both PPM and EMs negatively impacted vaginal contractility and glycosaminoglycan (GAG) content relative to Sham (all p-values<0.001) with EMs having less of an impact on GAGs (p-values<0.003). The results suggest that softer PCU EMs made with more material are well tolerated by the vagina and comprises a future material for POP repair devices. STATEMENT OF SIGNIFICANCE: Prolapse is a debilitating condition in which loss of support to the vagina causes it and the organs supported by it to descend from their normal position in the pelvis. Surgical solutions to rebuild support involves the use of polypropylene mesh which is orders of magnitude stiffer than the vagina. This mismatch results in complications including exposure of the mesh into the vagina and pain. To provide an innovative solution for women, we have developed an elastomeric membrane from a soft polymer that matches the stiffness of the vagina. Here, we show in a rabbit animal model that this device incorporates better into the vagina and is associated with an overall improved host response as compared to polypropylene mesh., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: We would like to draw the attention of the Editor to the following facts which may be considered as potential declaration of interests: Pamela Moalli reports equipment, drugs, or supplies was provided by Coloplast Corp. Katrina Knight reports financial support was provided by Magee-Womens Research Institute & Foundation. Pamela Moalli reports a relationship with Hologic Inc that includes board membership. However, there has been no significant financial support for this work that could have influenced its outcome. Additionally, Pamela Moalli is an Associate Editor for the following journals: Urogynecology and Female Urology (Frontiers in Urology)., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Pelvic organ prolapse (POP), a downward descent of the vagina and/or uterus through the vaginal canal, is a prevalent condition affecting up to 40% of women. Several risk factors of POP have been identified, including childbirth, connective tissue defects, and chronic intra-abdominal pressure; however, the underlying etiologies of POP development are not fully understood, leading to a high burden on patients and the healthcare systems. The uterosacral ligaments are key support structures of the uterus and upper vagina. Our previous work describes observed histopathological changes in uterosacral ligament (USL) tissue and demonstrates the presence of neutrophils in a subgroup of POP individuals. This presence of neutrophils prompted an examination for the presence of a broader spectrum of inflammatory cell types in the USL. Immunohistochemical staining was performed to identify neutrophils, lymphocytes, macrophages, and mast cells outside of the vasculature. All 4 inflammatory cell types were increased in the POP-HQ system-defined POP-Inflammatory (POP-I) phenotype USL tissue relative to the USL tissues of control or other POP-HQ phenotypes. Focal T-lymphocyte and macrophage co-accumulations were observed in the arterial walls from some patients of the POP-vascular (POP-V) phenotype suggesting previous arterial injury. In addition, 1 control and 2 POP-V subjects' USLs contained arterial wall foamy macrophages, evidence of atherosclerosis. These findings further support a complex etiology for POP and indicate that personalized approaches to preventing and treating the condition may be warranted., (© 2024. The Author(s).)

This study aimed to investigate the expression and significance of insulin-like growth factor binding protein 5 (IGFBP5) and extracellular matrix (ECM) related proteins in anterior vaginal wall tissues among aged pelvic organ prolapse (POP) patients. Tissues from the anterior vaginal wall were collected from 28 patients with POP and 20 patients without POP. The expression of protein and mRNA levels of IGFBP5 and ECM related proteins were evaluated in the vaginal wall tissues using immunohistochemistry, western blotting, and RT-qPCR techniques. The expression levels were then compared with clinical parameters. The expression levels of protein and mRNA of IGFBP5, collagen I, and collagen III were significantly lower in the POP group. Protein and mRNA expression levels of MMP2 were significantly higher in the POP group. IGFBP5 protein and mRNA expression levels were negatively correlated with age and significantly lower in older POP patients (≥ 65 years old) compared to younger POP patients (< 65 years old). IGFBP5 protein and mRNA expression levels were also significantly lower in POP-Q stage IV patients compared to POP-Q stage III patients. IGFBP5 expression level is negatively correlated with the age and severity of prolapse. The significant decrease in IGFBP5 expression may play a crucial part in the aging process and the occurrence of POP., (© 2024. The Author(s).)

Pelvic organ prolapse (POP) is a group of diseases caused by extracellular matrix (ECM) degradation in pelvic supportive tissues. Cysteine and serine rich nuclear protein 1 (CSRNP1) is involved in cell proliferation and survival regulation, and reportedly facilitates collagen breakdown in human chondrocytes. The present study aimed to probe the effect of CSRNP1 on collagen metabolism in human-derived vaginal fibroblasts. High expression of CSRNP1 was found in POP patient-derived vaginal fibroblasts in comparison to normal-derived vaginal fibroblasts. Following functional experiments revealed that CSRNP1 overexpression led to proliferation inhibition, apoptosis and collagen degradation in normal vaginal fibroblasts. In line with this, silencing of CSRNP1 inhibited hydrogen peroxide (H 2 O 2 )-triggered apoptosis, ROS generation and collagen loss in normal vaginal fibroblasts. Silencing of CSRNP1 also reduced the expression of cell senescence markers p21 and γ-H2Ax (the histone H2Ax phosphorylated at Ser139), as well as curbed collagen breakdown in normal vaginal fibroblasts caused by a DNA damage agent etoposide. Transcriptomic analysis of vaginal fibroblasts showed that differentially expressed genes affected by CSRNP1 overexpression were mainly enriched in the Wnt signaling pathway. Treatment with a Wnt pathway inhibitor DKK1 blocked CSRNP1 knockdown-caused collagen deposition. Mechanistically, CSRNP1 was identified to be a target of Snail family transcriptional repressor 2 (SNAI2). Forced expression of CSRNP1 reversed the anti-apoptotic, anti-senescent and anti-collagen loss effects of SNAI2 in normal vaginal fibroblasts exposed to H 2 O 2 or etoposide. Our study indicates that the SNAI2/CSRNP1 axis may be a key driver in POP progression, which provides a potential therapeutic strategy for POP., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: The pathogenesis of pelvic organ prolapse (POP), an age-related disease, has not been fully elucidated. Therapeutic targets of POP are limited. Silencing information regulator 2 related enzyme 1 (SIRT1), a gene considered capable of regulating oxidative stress and cellular senescence, has been widely demonstrated involved in aging and age-related diseases. The present study aimed to explore the role of SIRT1 in POP in vivo and in vitro., Methods: Expression levels of SIRT1 in uterosacral ligament (USL) tissues from patients with or without POP were measured using immunohistochemical assays. SRT1720, a SIRT1 agonist, was used to upregulate SIRT1, and hydrogen peroxide (H 2 O 2 ) was used to establish an oxidative stress model in human uterosacral ligament fibroblasts (hUSLFs). The effects of SIRT1 on cell viability, apoptosis, senescence, and reactive oxygen species (ROS) levels were detected, respectively. Western blot assays were used to examine expression levels of apoptosis- and senescence-associated biomarkers. Unpaired Student's t test, Mann-Whitney U test, χ 2 test, and one-way ANOVA were performed for determining statistically significant differences., Results: Compared to the control group, expression levels of SIRT1 were downregulated in USL tissues and hUSLFs from patients with POP, and associated with stage (p < 0.05). hUSLFs of patients with POP had lower growth rates (p < 0.0001) than those of the control group, which were improved by upregulating SIRT1 (p < 0.05). The senescent proportion was higher in the POP group than the control group (43.63 ± 10.62% vs. 4.84 ± 5.32%, p < 0.0001), which could be reduced by upregulating SIRT1 (p < 0.0001). High ROS levels in the POP group were also alleviated by SRT1720. H 2 O 2 exposure increased ROS levels, inhibited proliferation, and triggered apoptosis and senescence in hUSLFs of patients without POP in a concentration-dependent manner. Further, these damages were alleviated by pretreatment with SRT1720., Conclusions: SIRT1 is downregulated in patients with POP, and the development of SIRT1 activators or agonists may have applications in the treatment and prevention of POP through antioxidative stress and antisenescence effects., (© 2024 Wiley Periodicals LLC.)

Several 2-dimensional and 3-dimensional measurements have been used to assess changes in pelvic floor structures and shape. These include assessment of urogenital and levator hiatus dimensions, levator injury grade, levator bowl volume, and levator plate shape. We argue that each assessment reflects underlying changes in an individual aspect of the overall changes in muscle and fascial structures. Vaginal delivery, aging, and interindividual variations in anatomy combine to affect pelvic floor structures and their connections in different ways. To date, there is no unifying conceptual model that permits the evaluation of how these many measures relate to one another or that reflects overall pelvic floor structure and function. Therefore, this study aimed to describe a unified pelvic floor conceptual model to better understand how the aforementioned changes to the pelvic floor structures and their biomechanical interactions affect pelvic organ support with vaginal birth, prolapse, and age. In this model, the pelvic floor is composed of 5 key anatomic structures: the (1) pubovisceral, (2) puborectal, and (3) iliococcygeal muscles with their superficial and inferior fascia; (4) the perineal membrane or body; and (5) the anal sphincter complex. Schematically, these structures are considered to originate from pelvic sidewall structures and meet medially at important connection points that include the anal sphincter complex, perineal body, and anococcygeal raphe. The pubovisceral muscle contributes primarily to urogenital hiatus closure, whereas the puborectal muscle is mainly related to levator hiatus closure, although each muscle contributes to the other. Dorsally and laterally, the iliococcygeal muscle forms a shelflike structure in women with normal support that spans the remaining area between these medial muscles and attachments to the pelvic sidewall. Other features include the levator plate, bowl volume, and anorectal angle. The pelvic floor conceptual model integrates existing observations and points out evident knowledge gaps in how parturition, injury, disease, and aging can contribute to changes associated with pelvic floor function caused by the detachment of one or more important connection points or pubovisceral muscle failure., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

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., (© 2024 Wiley Periodicals LLC.)

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-β/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., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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 (ERβ), 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., (© 2023. The Author(s).)

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., Competing Interests: Conflict of Interest Statement We declare that we have no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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., (© 2023. The International Urogynecological Association.)

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.

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.

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 cmH 2 O, 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., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Miao, Wen, Wang, Wen, Cheng, Zhao and Wu.)

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 cmH 2 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., (© 2022 John Wiley & Sons Ltd.)

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., (© 2022. The Author(s).)

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., (© 2021. The International Urogynecological Association.)

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., (© 2022 The Authors. Neurourology and Urodynamics published by Wiley Periodicals LLC.)

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., (© 2022 The Authors. Journal of Obstetrics and Gynaecology Research published by John Wiley & Sons Australia, Ltd on behalf of Japan Society of Obstetrics and Gynecology.)

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., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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.

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., (Published by Elsevier Inc.)

Objective: To evaluate whether locally applied vaginal estrogen affects prolapse-associated complaints compared with placebo treatment in postmenopausal women prior to surgical prolapse repair., Design: Randomised, double-masked, placebo-controlled, multicentre study., Setting: Urogynaecology unit at the Medical University of Vienna and University Hospital of Tulln., Population: Postmenopausal women with symptomatic pelvic organ prolapse and planned surgical prolapse repair., Methods: Women were randomly assigned local estrogen cream or placebo cream 6 weeks preoperatively., Main Outcome Measures: The primary outcome was differences in subjective prolapse-associated complaints after 6 weeks of treatment prior to surgery, assessed with the comprehensive German pelvic floor questionnaire. Secondary outcomes included differences in other pelvic floor-associated complaints (bladder, bowel or sexual function)., Results: Out of 120 women randomised, 103 (86%) remained for the final analysis. After 6 weeks of treatment the prolapse domain score did not differ between the estrogen and the placebo groups (4.4 ± 0.19 versus 4.6 ± 0.19; mean difference, -0.21; 95% CI -0.74 to 0.33; P = 0.445). Multivariate analysis, including only women receiving the intervention, showed that none of the confounding factors modified the response to estradiol., Conclusions: These results demonstrate that preoperative locally applied estrogen does not ameliorate prolapse-associated symptoms in postmenopausal women with symptomatic pelvic organ prolapse., Tweetable Abstract: Preoperative local estrogen does not ameliorate prolapse-associated symptoms in postmenopausal women with pelvic organ prolapse., (© 2021 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

Objective: Cellular senescence, associated with aging, leads to impaired tissue regeneration. We hypothesize that vaginal injury initiates cell senescence, further propagated during aging resulting in pelvic organ prolapse (POP). Our objective was to employ a mouse model of POP (Fibulin-5 knockout mice, Fbln5 -/- ) to determine if vaginal distention leads to cellular senescence and POP., Methods: 6wk old females [wild-type (WT), n = 81; Fbln5 -/- , n = 47)] were assigned to control vs vaginal distention, which approximated vaginal delivery. Serial POP measurements were obtained until vagina were harvested from euthanized mice at 24, 48, 72 h and 1wk. Markers of cell senescence were quantified by immunofluorescence. DNA damage was assessed with γ-H2Ax., Results: WT distended mice showed decreased p53 (p = 0.0230) and γ-H2Ax (p = 0.0008) in vaginal stromal cells at 1wk compared to controls. In WT mice, SA-β-Gal activity increased 1wk after distention (p = 0.05). In Fbln5 -/- mice, p53 and γ-H2Ax did not decrease, but p16 decreased 72 h after distention (p = 0.0150). SA-β-Gal activity also increased in Fbln5 -/- , but at earlier time points and 1wk after distention (p < 0.0001). Fbln5 -/- mice developed POP after distention earlier than non distended animals (p = 0.0135)., Conclusions: Vaginal distention downregulates p53 and γ-H2Ax in WT mice, thereby promoting cell proliferation 1wk after injury. This was absent among Fbln5 -/- distention mice suggesting they do not escape senescence. These findings indicate a failure of cellular protection from senescence in animals predisposed to POP., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Pelvic organ prolapse (POP) is a common disorder in women, and it is characterized by weakening of pelvic supportive structure with extracellular matrix (ECM) degradation. Activating transcription factor 3 (ATF3) was upregulated in anterior vaginal wall tissues of POP patients. We hypothesized that upregulation of ATF3 might contribute to POP development. This study aims to unveil the role of ATF3 in the pathogenesis of POP using a H 2 O 2 -induced in vitro model. Vaginal fibroblasts were isolated from woman with POP-Q stage greater than II and asymptomatic women with normal pelvic floor support. Knockdown of ATF3 enhanced cell viability and decreased cell apoptosis. Flow cytometry and immunnofluorescence showed that ATF3 deficiency inhibited H 2 O 2 -induced ROS production and the expression of 8 OHdG and 4-HNE. Western blot and Real-time PCR analysis revealed that ATF3 deficiency attenuated ECM component degradation (increasing collagen I, collagen III and elastin) and MMPs/TIMPs imbalance (decreasing MMP2 and MMP9 and increasing TIMP2). Moreover, knockdown of ATF3 induced the activation of p38/Nrf2/HO-1 signaling pathway. Further treatment with p38 inhibitor SB203580 abolished the protection of ATF3 deficiency against H 2 O 2 -induced cell damage, which was reverted by Nrf2 activator TBHQ. Thus, ATF3 likely contributes to POP progression by inducing cell apoptosis, oxidative stress and ECM degradation via regulating p38/Nrf2 pathway, which provides a potential therapeutic target for POP., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Pelvic organ prolapse (POP) is a chronic disorder that affects quality of life in women. Several POP treatments may be accompanied by abrasion, constant infection, and severe pain. Therefore, new treatment methods and improvements in current treatments for POP are required. Non-thermal atmospheric-pressure plasma is a rising biomedical therapy that generates a mixed cocktail of reactive species by different mechanisms. In this study, we applied a cylinder-type dielectric barrier discharge plasma device to create a plasma-treated liquid (PTL). The PTL was added to primary cultured human uterosacral ligament fibroblast (hUSLF) cells from POP patients at each stage. Surprisingly, treatment with diluted PTL increased hUSLF cell viability but decreased ovarian cancer cell viability. PTL also decreased cell apoptosis in hUSLF cells but increased it in SKOV3 cells. Our results suggest that PTL protects hUSLF cells from cell apoptosis by controlling the p53 pathway and improves cell viability, implying that PTL is a promising application for POP therapy.

Abstract: This study aimed to know the distance of the cervicovaginal junction (CVJ) to the anterior peritoneal reflection (APR) as measured in surgical specimens, and assess the distance between the CVJ and APR to ensure safe anterior colpotomy for vaginal hysterectomy among Korean women.Patients who underwent vaginal hysterectomy were included in the analysis. According to the presence of pelvic organ prolapse or menopausal status, the distance from the CVJ to the APR was assessed preoperatively through transvaginal ultrasonography (TV-US), as well as intraoperatively using surgical specimens. The intraclass correlation coefficient was used to determine the reliability between 2 measurements.In total, 171 patients were included. The median distance from the CVJ to the APR measured on TV-US was 19.8 (3.3-41.3) mm. Meanwhile, the median distance from the CVJ to the APR measured using the surgical specimen was 26.0 (12.0-55.0) mm. The intraclass correlation coefficient for the absolute agreement between 2 measurements was 0.353 (95% confidence interval: 0.002-0.570; P < .001), which is indicative of poor reliability. The median distance from the CVJ to the APR measured using the surgical specimen did not differ significantly between the 2 groups according to pelvic organ prolapse (26.0 [12.0-55.0] vs 27.5 [17.0-55.0] mm, P = .076] and menopausal status (27.0 [15.0-55.0] vs 26.0 [12.0-55.0] mm, P = .237).TV-US does not an accurately measure the dissection plane length from the CVJ to the APR during anterior colpotomy. During vaginal hysterectomy, the median distance from the CVJ to the APR measured using the surgical specimen was 26 (12.0-55.0) mm, which can help decrease surgical complications., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Pelvic organ prolapse (POP) is common among older women who have delivered children vaginally. While the pathophysiology is not fully delineated, POP can occur in part from insufficient repair of disrupted elastic matrix fibers. Quantification of structural changes to elastic fibers has not been described previously for POP. The goal of this paper is to present a validated technique for morphometric analysis of elastic fibers in vaginal tissue cultures from lysyl oxidase like-1 knock out (LOXL1 KO) mice with POP. The effect of LOXL1 KO, effect of POP, effect of culture, and effect of elastogenic treatment on the changes in elastin fiber characteristics were tested using vaginal tissues from wild type multiparous (WT), LOXL1 KO multiparous prolapsed (POP) and LOXL1 KO multiparous non-prolapsed (NP) mice. Our results show significantly higher mean aspect ratio, maximum diameter and perimeter length in POP compared to NP after 3 weeks of tissue culture. Further, treatment of POP tissues in culture with growth factors with previously documented elastogenic effects caused a significant increase in the mean area and perimeter length of elastic fibers. This technique thus appears to be useful in quantifying structural changes and can be used to assess the pathophysiology of POP and the effect of elastogenic treatments with potential for POP., (© 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

Purpose: To evaluate COX-2 and Nrf2/GPx3 expressions in the lamina propria of the anterior vaginal wall tissues of women with and without pelvic organ prolapse (POP)., Methods: Tissue samples of anterior vaginal wall were examined using HE staining, immuohistochemical staining and Western blot for the expressions of COX-2/PGE2, Nrf2/GPx3, MMP2, TIMP1, collagen I and collagen III (n = 35, per group)., Results: Compared with control group, collagen fibers of the anterior vaginal wall were disorganized and discontinuous. Expressions of Nrf2, GPx3, TIMP1, collagen I and collagen III were found significantly lower in POP group (P < 0.05); while, expressions of COX-2, PGE2, and MMP2 were found significantly higher in POP group (P < 0.05). Statistically significant correlations of COX-2 and Nrf2/GPx3 were showed (P < 0.01)., Conclusion: We found that the interaction between inflammation and oxidative stress was closely related to the development of POP. This study demonstrates that COX-2 and Nrf2 pathways may be involved in pathogenesis of POP, as promising potential therapeutic targets and agents.

Morphometric and immunohistochemical examination of the vaginal mucosa before and 12 months after installation of polypropylene implants for the correction of stress urinary incontinence was performed in 20 patients with genital prolapse. The research results confirmed good biocompatibility of polypropylene and the formation of full-fledged connective tissue in the vaginal mucosa, but revealed the presence of a weak lymphocytic reaction to polypropylene 12 months after surgery. According to immunohistochemical study, increased contents of B lymphocytes and plasma cells responsible for the inductive and productive stages of the immune response were revealed in the vaginal mucosa around the implants 12 months after surgery. This reaction in the presences of provoking factors can lead to the development of inflammation and erosion, a type of mesh-associated complications.

Background: The collagen 3 alpha 1 (COL3A1) rs1800255 polymorphism has been reported to be associated with women pelvic organ prolapse (POP) susceptibility, but the results of these previous studies have been contradictory. The objective of current study is to explore whether COL3A1 rs1800255 polymorphism confers risk to POP., Methods: Relevant literatures were searched by searching databases including Pubmed, Embase, Google academic, the Cochrane library, China National Knowledge Infrastructure (CNKI). Search time is from database foundation to March 2021., Results: A total of seven literatures were enrolled in the present meta-analysis, including 1642 participants. Overall, no significant association was found by any genetic models. In subgroup analysis based on ethnicity, significant associations were demonstrated in Caucasians by allele contrast (A vs. G: OR = 1.34, 95%CI = 1.03-1.74,), homozygote comparison (AA vs. GG: OR = 3.25, 95%CI = 1.39-7.59), and recessive genetic model (AA vs. GG/GA: OR = 3.22, 95%CI = 1.40-7.42)., Conclusions: The present meta-analysis suggests that the COL3A1 is a candidate gene for POP susceptibility. Caucasian individuals with A allele and AA genotype have a higher risk of POP. The COL3A1 rs1800255 polymorphism may be risk factor for POP in Caucasian population., Competing Interests: The authors have declared that no competing interests exist.

Objectives: Mesh repair surgery for pelvic organ prolapse (POP) has been suspended in some countries owing to concerns about its associated complications. However, mesh repair has been shown to reduce the risk of prolapse recurrence after surgery. In view of this controversy, our aim was to assess the incidence of subjective and objective recurrence of POP following mesh repair surgery vs native-tissue repair in women with Stage-III or Stage-IV POP., Methods: This was a prospective observational study of women who presented with Stage-III or Stage-IV POP and received primary prolapse surgery between 2013 and 2018. Transperineal ultrasound was performed before the operation and volumes were analyzed offline to assess the presence of levator ani muscle (LAM) avulsion. All women were counseled on either mesh repair or native-tissue reconstruction. The mesh-repair group was followed up for up to 5 years and the native-tissue-repair group for up to 2 years after the operation. Prolapse symptoms and POP quantification (POP-Q) staging were assessed at follow-up. Subjective recurrence of POP was defined as symptoms of prolapse (vaginal bulge sensation or dragging sensation) reported by the patient. Objective recurrence was defined as POP-Q ≥ Stage II. The subjective and objective recurrences of prolapse were compared between women with and those without mesh use. Multivariate regression analysis was used to identify risk factors for the recurrence of POP., Results: A total of 154 Chinese women with Stage-III or Stage-IV prolapse were recruited. Of these, 104 (67.5%) underwent mesh repair (transabdominal in 57 women and transvaginal in 47 women) and 50 (32.5%) had native-tissue repair surgery. Ninety-five (61.7%) women had LAM avulsion. Both the subjective POP recurrence rate (4.8% vs 20.0%; P = 0.003) and the objective recurrence rate (20.2% vs 46.0%; P = 0.001) were significantly lower in the mesh-repair group than in the native-tissue-repair group. On multivariate logistic regression analysis, mesh repair was associated significantly with a reduced risk of subjective recurrence (odds ratio (OR), 0.20 (95% CI, 0.07-0.63)) and of objective recurrence (OR, 0.16 (95% CI, 0.07-0.55)) of prolapse. On subgroup analysis of women with LAM avulsion, mesh repair significantly reduced the risk of subjective recurrence (OR, 0.24 (95% CI, 0.07-0.87)) and objective recurrence (OR, 0.23 (95% CI, 0.09-0.57)) of POP. The incidence of mesh-related complications was low, and mesh exposure could be treated conservatively or by minor surgery., Conclusions: Mesh repair surgery, compared with native-tissue repair, was associated with a 5-fold reduction in the risk of subjective recurrence and a 6-fold reduction in the risk of objective recurrence of prolapse in women with Stage-III or Stage-IV POP. In women with concomitant LAM avulsion, mesh repair surgery was associated with a 4-fold reduction in both objective and subjective recurrence of POP. The rate of mesh-related complications was low, and mesh exposure could be treated conservatively or by minor surgery. The benefit of mesh surgery for these high-risk women appears to outweigh the risks of mesh complications, and it could be a treatment option for this group of women. © 2020 International Society of Ultrasound in Obstetrics and Gynecology., (© 2020 International Society of Ultrasound in Obstetrics and Gynecology.)

We evaluated the changes in the levels of TGF-β and SMAD gene and protein expression in the uterosacral ligament (USL) of patients with concomitant pelvic organ prolapse (POP) and urgency urinary incontinence (UUI) to illuminate the pathophysiology of UUI. The TGF-β pathway is involved in collagen synthesis and degradation. The Transforming Growth Family-β (TGF-β) superfamily has essential intracellular signaling components, such as newly identified SMAD family members. We evaluated the changes in the levels of TGF-β and SMAD gene and protein expression in the USL of patients with concomitant pelvic organ prolapse (POP) and UUI. This study included 10 patients who had been diagnosed with POP and UUI in the study group and 14 asymptomatic women without complaints of POP and UUI in the control group. Biopsy samples were collected from bilateral USL tissues during vaginal or abdominal hysterectomy. Total RNA was extracted from USL tissue and analyzed by qPCR. The protein expression levels were also analyzed with ELISA. In UUI patients, SMAD3 and TGF-ß1 gene expression levels significantly decreased compared to the control patients (p = 0.008 and p = 0.006, respectively). SMAD2 mRNA levels did not differ between the study and control groups (p = 0.139). No differences was found in the levels of SMAD2, SMAD3, and TGF-ß1 protein expression between the two groups. The reduction in the gene and protein expression levels of SMAD3 and TGF-ß1 in women with UUI and lax uterosacral ligaments may indicate a causal link.Clinical trial registration: NCT04525105.

Objectives: To evaluate the association between pessary use more than 1 year and change in prolapse severity., Methods: This is a secondary analysis of a previously published randomized controlled trial of women undergoing office management of pessaries for management of symptomatic pelvic organ prolapse and incontinence. Primary outcome was change in pelvic organ prolapse quantification measurement genital hiatus (GH). Secondary outcomes included change in prolapse stage, type of pessary, size of pessary, number of pessary changes, and duration of use. Baseline data were collected from the earliest documented examination within the hospital record before pessary placement and compared with their final study visit. Demographics were analyzed using descriptive statistics. Student t test and Mann-Whitney tests were used for categorical comparisons. Pearson and Spearman correlation coefficients were used to evaluate change over time., Results: The cohort was 132 predominantly non-Hispanic White (75%) women with symptomatic prolapse >stage 2 (70.5%). All were postmenopausal. Median duration of pessary use was 39.5 months (interquartile range, 17-64.5 months). Genital hiatus (P = 0.014) and prolapse stage (P = 0.001) decreased as duration of pessary use increased. Those with baseline stages ≥3 had a significant decrease in GH as duration of pessary use increased compared with stages <3 (-0.5 cm vs 0 cm, P < 0.001). There was no difference in change in GH when comparing women with baseline GH less than 3 to 3 cm or greater., Conclusions: Pessary use by women with pelvic organ prolapse causes a change in vaginal anatomy over time as seen by decreasing stage and point GH., Competing Interests: The authors have declared they have no conflicts of interest., (Copyright © 2020 American Urogynecologic Society. All rights reserved.)

Objective: To study the anatomical relationship among uterosacral ligament and ureter or rectum by using MRI three-dimensional reconstruction model in pelvic organ prolapse (POP) patients. Methods: According to the research standard, 67 POP patients were enrolled, who accepted pelvic MRI before surgery in Nanfang Hospital, Southern Medical University during May 2015 to March 2020. Three-dimensional model of uterosacral ligament was reconstructed. The intersection point of the fitting curve of uterosacral ligament and ischial spine level marked point P0, every 1 cm increasing from P0 towards the sacrum marked points P1, P2, and P3. Distances were measured between rectum or ureter to uterosacral ligament respectively at the P0-P3 horizontal levels. Results: (1) The distances between the left ureter and the left uterosacral ligament were (15.45±7.46) to (19.31±11.38) mm, and the distances between the right ureter and the right uterosacral ligament were (13.77±8.16) to (14.78±9.18) mm. At the P1 horizontal level ureters were the closest to uterosacral ligaments, and the right ureter was the closest to right uterosacral ligament [(13.45±9.34) mm] at P2 horizontal level in severe POP group. The farthest distance presented at the P3 horizontal level between bilateral ureters and uterosacral ligaments. (2) At the P0 horizontal level, the rectum was the closest to the bilateral uterosacral ligaments [left: (20.62±9.99) mm, right: (16.82±9.63) mm; P =0.026], and the rectum was closer to the right uterosacral ligament. There were no significant differences in the distance between rectum and bilateral uterosacral ligaments in mild POP group ( P >0.05), and the results of severe POP group also showed the rectum was closer to the right uterosacral ligament [(15.64±10.31) mm at P0 horizontal level]. Conclusions: Right ureter and rectum are closer to the right uterosacral ligament. Gynecologists should pay more attention to avoid damaging the right ureter and rectum during the operation of the right uterosacral ligament in POP patients.

Anterior vaginal prolapse (AVP) is the most common form of pelvic organ prolapse (POP) and has deleterious effects on women's health. Despite recent advances in AVP diagnosis and treatment, a cell atlas of the vaginal wall in AVP has not been constructed. Here, we employ single-cell RNA-seq to construct a transcriptomic atlas of 81,026 individual cells in the vaginal wall from AVP and control samples and identify 11 cell types. We reveal aberrant gene expression in diverse cell types in AVP. Extracellular matrix (ECM) dysregulation and immune reactions involvement are identified in both non-immune and immune cell types. In addition, we find that several transcription factors associated with ECM and immune regulation are activated in AVP. Furthermore, we reveal dysregulated cell-cell communication patterns in AVP. Taken together, this work provides a valuable resource for deciphering the cellular heterogeneity and the molecular mechanisms underlying severe AVP.

Study Objective: To determine the objective and subjective outcomes of pelvic organ prolapse (POP) surgery using a modified Surelift system (Neomedic International, Barcelona, Spain) and to evaluate surgical complications and postoperative impact on quality of life (QOL) and lower urinary tract symptoms., Design: Retrospective cohort study., Setting: Tertiary-care university hospital., Patients: Patients with symptomatic anterior or apical POP stage III and above., Interventions: All patients underwent pelvic reconstructive surgery with a modified Surelift transvaginal mesh kit., Measurements and Main Results: Eighty-three women who underwent pelvic reconstructive surgery with a modified Surelift for symptomatic anterior or apical prolapse stage III and above from April 2018 to January 2019 were reviewed retrospectively. All completed a 72-hour voiding diary, urodynamic study, and multiple validated QOL questionnaires at baseline and at between 6 and 12 months postoperatively. Descriptive statistics were used for demographics and perioperative data. Paired-samples t test and the McNemar test were applied for comparison of pre- and postoperative continuous and categoric data, respectively. The primary outcomes were the objective cure of POP, defined as anterior and apical prolapse Pelvic Organ Prolapse Quantification System ≤ stage I, and subjective cure on the basis of negative answers to Pelvic Organ Prolapse Distress Inventory 6. The objective and subjective cure rates at 1 year were 97.6% and 92.8%, respectively. There were significant improvements in QOL scores postoperatively. Although bladder outlet obstruction improved, de novo urodynamic stress incontinence and stress urinary incontinence were increased at 18.9% and 21.6%, respectively, at 1-year follow-up. The mesh extrusion rate was 4.8%., Conclusion: A modified Surelift has good objective and subjective cure rates at 1 year postoperatively with 4.8% mesh extrusion rate. There was significant improvement in lower urinary tract symptoms and QOL. De novo urodynamic stress incontinence at 6 months to 12 months was increased, but it was not sufficiently bothersome to warrant surgery., (Copyright © 2020 AAGL. Published by Elsevier Inc. All rights reserved.)

Objective: Relationships between pelvic organ prolapse (POP) staging and lower urinary tract symptoms (LUTS) are controversial. In this study, we evaluated correlations of POP staging with LUTS in different compartments., Materials and Methods: From January 2016 to December 2017, 250 consecutive patients with urogynecologic complaints who were referred to our urodynamic unit were recruited into this study. Different stages of different compartments (anterior, central and posterior) of POPs according to IUGA and ICS terminology were re-grouped into four categories as stage 0, 1, 2, and 3 (including stage 4 because of a limited number of patients in stage 4). Pearson correlation coefficient and general linear regression were used for correlations of POP staging in different compartments and LUTS (stress urinary incontinence, overactive bladder and voiding symptoms) as well as their associated factors., Results: Only OAB had a moderate correlation with different compartments of POP (anterior vaginal wall: -0.3116; cervix: -0.2954 and posterior vaginal wall: -0.3779; all p < 0.05). Stage 1 AVWP significantly increased (39.6%) the occurrence of OAB compared to no prolapse. Posterior compartment (stage 1-3) prolapse reduced the occurrence of OAB., Conclusion: Only stage 1 AVWP is associated with an increase in OAB, and posterior compartment prolapse may reduce the occurrence of OAB., Competing Interests: Declaration of competing interest The authors have declared that no competing interests exist., (Copyright © 2021. Published by Elsevier B.V.)

Female urinary incontinence mainly relates to damage of female urethra supporting structures, while its anatomy and function specially in which the connective tissue part are still unclear and controversial. We study it based on 4 thin-sectional, high-resolution, transverse sectional anatomical images [Chinese Visible Human (CVH) images] and 10 high-resolution MRI images from volunteers. The female urethral supporting structures and its adjacent structures were segmented and three-dimensional (3D) reconstructed with Amira software. The urethral supporting structures include muscular and connective tissue supporting structures. Muscular supporting structures are composed of levator ani muslce and striated urethral sphincter, the connective tissue supporting structures are composed of anterior vaginal wall, pubovesical muscle, pubovesical ligament, lateral vesical ligament, and tendinous arch of pelvic fascia (TAPF). The anterior vaginal wall includes tight and loose connections between urethral, bladder, and vagina. The lateral vesical ligament connects the proximal part of the urethra to the TAPF. The pubovesical muscle is crescent shaped and continues with the detrusor of the bladder superior and directly connects the TAPF laterally. The TAPF is an obvious fibrous structure that originates at the middle-posterior surface of the pubis, travels onto the parietal pelvic fascia, and inserts posteriorly onto the ischial spine. The anterior vaginal wall, the pubovesical muscle, the lateral vesical ligament, and the TAPF create the "hammock" structure and supplement DeLancey's theory. Its support to the proximal urethra and neck of bladder is crucial to maintain stability and urinary continence during increased abdominal pressure.

Study Objective: Recently, there has been a paradigm shift toward uterine conservation during the surgical management of pelvic organ prolapse (POP), specifically uterine prolapse. There are few reports on transvaginal uterosacral ligament hysteropexy (TULH). This study aimed to describe our surgical technique and outcomes., Design: Retrospective review and description of surgical technique. Anatomic outcome has been reported using the POP quantification system. Complications were segregated. A comparison of parametric continuous variables was performed using paired t test. Categoric variables were evaluated using the Pearson χ 2 test and the Fisher exact test. A p-value <.05 was considered significant., Setting: Teaching hospital., Patients: Forty patients who underwent TULH from 2009 to 2017., Interventions: TULH., Measurements and Main Results: A total of 40 patients met the inclusion criteria. Of these, 56.1% had preoperative stage 3 prolapse. The median operative time was 116 minutes. The mean estimated blood loss was 158.5 mL. Transient ureteral obstruction occurred in 2 patients. The mean follow-up time was 17.2 months, and all patients had significant improvement of prolapse (p <.001). There was also an improvement in urinary incontinence and bladder storage symptoms (p <.001). None of the patients were reoperated on for recurrent POP., Conclusion: TULH is an effective uterus-preserving surgical alternative for the treatment of uterovaginal prolapse and provides good apical support. It is also associated with a low short-term recurrence and incidence of reoperation. TULH is a viable option for suitable patients with uterovaginal prolapse who desire uterine conservation., (Copyright © 2020 AAGL. Published by Elsevier Inc. All rights reserved.)

Objective: To assess the effects of 17β-estradiol (E2) on proliferation, apoptosis, and protein expressions of fibroblasts at different concentrations and time intervals to reveal the mechanism of E2 in the treatment of pelvic organ prolapse (POP)., Study Design: The uterosacral ligament fibroblasts were collected from seven POP patients for primary culture of fibroblasts. The culture media containing 0, 10 -6 , 10 -7 , 10 -8 , and 10 -9 mol/L E2 were used for 24, 48, 72, and 96 h., Main Outcome Measures: The cells were collected for cell counting kit-8 (CCK-8), apoptosis, quantitative reverse transcription polymerase chain reaction (qRT-PCR), and Western blotting assays., Results: Compared with the control group, in the values of fibroblasts cultured in 10 -8 mol/L E2 for 72 h, the proliferation, mRNA and protein expression of Mitofusin-2 (Mfn2) separately increased (P < 0.05), decreased (P<0.001) and decreased (P<0.001). However, the expression level of procollagen 1A1/1A2/3A1 and cyclinD1 markedly increased (P<0.001, all), which was consistent with the results of protein level. What's more, the expression of estrogen receptor α(ERα), estrogen receptor β(ERβ) and G protein-coupled receptor 30(GPR30) were significantly increased in 10 -8 mol/L E2 group., Conclusions: E2 can inhibit the progress of POP by inhibiting the expression level of Mfn2, as well as promoting expression of procollagens and proliferation of fibroblasts. This effect is time- and concentration-dependent. Only when the estrogen concentration reaches 10 -8 mol/L, the therapeutic effect is the greatest after 72 h., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Wang, He, Xiao and Lu.)

Pelvic organ prolapse (POP) occurs when the pelvic organs (bladder, bowel or uterus) herniate into the vagina, causing incontinence, voiding, and bowel and sexual dysfunction, negatively impacting upon a woman's quality of life. Intermediate intermolecular cross-links and advanced glycation cross-links increase in prolapsed tissue. Stem cells are able to participate in tissue repair due to their ability to differentiate into multiple lineages, and thus into various types of connective tissue cells, so they therefore hold great promise for treating pelvic floor dysfunction. The current study found that advanced glycation end products (AGEs) inhibited the viability and proliferation of human vaginal wall fibroblasts (VWFs), were cytotoxic to VWFs, and also induced the apoptosis of VWFs. In contrast, umbilical cord-derived mesenchymal stem cells (UCMSCs) secreted anti-inflammation cytokines to protect against the cytotoxic effects of fibroblasts induced by AGEs and attenuated the cytotoxic effect of AGE on fibroblasts by activation of the PI3K/Akt-PTEN pathway. This study demonstrated that UCMSCs inhibited the cytotoxic effect of AGE in cells from patients with POP by inducing an anti-inflammatory reaction and activating the PI3K/AKT/PTEN signaling pathway. The current results provide important insights into use of stem cells to treat POP.

The growing number of female reproductive system disorders creates a need for novel treatment methods. Tissue engineering brings hope for patients, which enables damaged tissue reconstruction. For this purpose, epithelial cells are cultured on three-dimensional scaffolds. One of the most promising materials is chitosan, which is known for its biocompatibility and biodegradability. The aim of the following study was to verify the potential of chitosan-based biomaterials for pelvic organ prolapse regeneration. The scaffolds were obtained under microwave-assisted conditions in crosslinking reactions, using dicarboxylic acids and aminoacid as crosslinkers, including l-glutamic acid, adipic acid, malonic acid, and levulinic acid. The products were characterized over their physicochemical and biological properties. FT-IR analysis confirmed formation of amide bonds. The scaffolds had a highly porous structure, which was confirmed by SEM analysis. Their porosity was above 90%. The biomaterials had excellent swelling abilities and very good antioxidant properties. The cytotoxicity study was performed on vaginal epithelial VK2/E6E7 and human colon cancer HCT116 cell lines. The results showed that after certain modifications, the proposed scaffolds could be used in pelvic organ prolapse (POP) treatment.

Pelvic organ prolapse (POP) is a common symptom of pelvic floor disorders which is characterized by the descent of the uterus, bladder or bowel from their normal anatomical position towards or through the vagina. Among the older population, the incidence of POP increases with age. It is becoming necessary to recognize that POP is a degenerative disease that is correlated with age. In recent years, studies have been performed to improve understanding of the cellular and molecular mechanisms concerning senescent fibroblasts in pelvic tissues, which contribute to the loss of structure supporting the pelvic organs. These mechanisms can be classified into gene and mitochondrial dysfunctions, intrinsic senescence processes, protein imbalance and alterations in stem cells. The present review provides an integrated overview of the current research and concepts regarding POP, in addition to discussing how fibroblasts can be targeted to evade the negative impact of senescence on POP. However, it is probable that other mechanisms that can also cause POP exist during cell senescence, which necessitates further research and provides new directions in the development of novel medical treatment, stem cell therapy and non‑surgical interventions for POP.

Introduction and Hypothesis: Treatment of anterior vaginal and/or apical prolapse by sacrocolpopexy is most often performed by systematic placement of two non-resorbable meshes, anterior and posterior, whether or not there is an associated posterior vaginal prolapse. We believe that isolated correction of an anterior vaginal and/or apical prolapse in the absence of posterior vaginal prolapse is not associated with a higher rate of de novo posterior vaginal prolapse., Method: A prospective, observational, monocenter study performed in the Gynecology unit of the Conception UHC in Marseille from May 2011 to October 2014. Patients over 18 years of age exhibiting an anterior vaginal and/or apical prolapse of stage ≥ 2 of the POP-Q classification resulting in functional impairment with alteration of the quality of life, without an associated posterior vaginal prolapse were included and underwent a laparoscopic anterior sacrocolpopexy (ASP). They were seen again in consultation one year from the intervention. Validated quality of life questionnaires were completed pre- and one year postoperatively., Results: 50 patients were included. The rate of de novo posterior vaginal prolapse was 8/50 (16 %). At one year, there was a significant improvement in terms of the SPDI-20 and SPIQ-7 (p < 0.0001) questionnaire, without significant improvement in the quality of sexual function (PISQ-12 questionnaire) (p = 0.073)., Conclusion: The risk of de novo posterior vaginal prolapse at one year is low when an ASP is carried out., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Study Objective: To evaluate the postoperative anatomic and functional outcomes of patients who underwent laparoscopic nerve-sparing sacrocolpopexy or sacrocervicopexy for pelvic organ prolapse (POP) POP-Q stage III and IV apical prolapse, and to delineate the contributing factors for recurrence., Study Design and Classification: The file records of patients who underwent sacropexy in the last five years were reviewed retrospectively and compared in terms of preoperative and postoperative anatomic findings and symptoms., Patients: Patients who underwent laparoscopic nerve-sparing surgery for treatment of POP-Q Stage III and IV/prolapse of uterine or vaginal cuff were included., Interventions: Postoperative anatomic and functional outcomes were evaluated using POP-Q classification and urinary/anal function by questioning during visits., Results: The mean follow-up duration was 24.2 ± 17.6 months. Anatomic recovery was achieved in 104 (90.4 %) cases. Advanced age (≥70 years), longer duration of symptoms, and low body mass index were determined as parameters related to recurrence risk., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Fibroblast to myofibroblast differentiation is a key feature of wound-healing in soft tissues, including the vagina. Vaginal fibroblasts maintain the integrity of the vaginal wall tissues, essential to keep pelvic organs in place and avoid pelvic organ prolapse (POP). The micro-environment of vaginal tissues in POP patients is stiffer and has different extracellular matrix (ECM) composition than healthy vaginal tissues. In this study, we employed a series of matrices with known stiffnesses, as well as vaginal ECMs, in combination with vaginal fibroblasts from POP and healthy tissues to investigate how matrix stiffness and composition regulate myofibroblast differentiation in vaginal fibroblasts. Stiffness was positively correlated to production of α-smooth muscle actin (α-SMA). Vaginal ECMs induced myofibroblast differentiation as both α-SMA and collagen gene expressions were increased. This differentiation was more pronounced in cells seeded on POP-ECMs that were stiffer than those derived from healthy tissues and had higher collagen and elastin protein content. We showed that stiffness and ECM content regulate vaginal myofibroblast differentiation. We provide preliminary evidence that vaginal fibroblasts might recognize POP-ECMs as scar tissues that need to be remodeled. This is fundamentally important for tissue repair, and provides a rational basis for POP disease modelling and therapeutic innovations in vaginal reconstruction.