BACKGROUND: Fibrosis of the connective tissue in the vaginal wall predominates in pelvic organ prolapse (POP), which is characterized by excessive fibroblast-to-myofibroblast differentiation and abnormal deposition of the extracellular matrix (ECM). Our study aimed to investigate the effect of ECM stiffness on vaginal fibroblasts and to explore the role of methyltransferase 3 (METTL3) in the development of POP. METHODS: Polyacrylamide hydrogels were applied to create an ECM microenvironment with variable stiffness to evaluate the effects of ECM stiffness on the proliferation, differentiation, and expression of ECM components in vaginal fibroblasts. METTL3 small interfering RNA and an overexpression vector were transfected into vaginal fibroblasts to evaluate the effects of METTL3 silencing and overexpression on matrix stiffness-induced vaginal fibroblast-to-myofibroblast differentiation and abnormal modulation of the ECM. Both procedures were detected by 5-ethynyl-2'-deoxyuridine (EdU) staining, Western blotting (WB), quantitative real-time polymerase chain reaction (RT-qPCR), and immunofluorescence (IF). RESULTS: Vaginal fibroblasts from POP patients exhibited increased proliferation ability, increased expression of α-smooth muscle actin (α-SMA), decreased expression of collagen I/III, and significantly decreased expression of tissue inhibitors of matrix metalloproteinases (TIMPs) in the stiff matrix ( P <0.05). Compared with those from non-POP patients, vaginal wall tissues from POP patients demonstrated a significant increase in METTL3 content ( P <0.05). However, silencing METTL3 expression in vaginal fibroblasts with high ECM stiffness resulted in decreased proliferation ability, decreased α-SMA expression, an increased ratio of collagen I/III, and increased TIMP1 and TIMP2 expression. Conversely, METTL3 overexpression significantly promoted the process of increased proliferation ability, increased α-SMA expression, decreased ratio of collagen I/III and decreased TIMP1 and TIMP2 expression in the soft matrix ( P <0.05). CONCLUSIONS Elevated ECM stiffness can promote excessive proliferation, differentiation, and abnormal ECM modulation, and the expression of METTL3 plays an important role in alleviating or aggravating matrix stiffness-induced vaginal fibroblast-to-myofibroblast differentiation and abnormal ECM modulation.
Humans ; Female ; Extracellular Matrix/metabolism* ; Cell Differentiation/genetics* ; Methyltransferases/metabolism* ; Pelvic Organ Prolapse/pathology* ; Fibroblasts/metabolism* ; Myofibroblasts/metabolism* ; Vagina/metabolism* ; Cell Proliferation/physiology* ; Cells, Cultured ; Middle Aged

Pelvic organ prolapse (POP), whose etiology is influenced by genetic and clinical risk factors, considerably impacts women's quality of life. However, the genetic underpinnings in non-European populations and comprehensive risk models integrating genetic and clinical factors remain underexplored. This study constructed the first polygenic risk score (PRS) for POP in the Chinese population by utilizing 20 disease-associated variants from the largest existing genome-wide association study. We analyzed a discovery cohort of 576 cases and 623 controls and a validation cohort of 264 cases and 200 controls. Results showed that the case group exhibited a significantly higher PRS than the control group. Moreover, the odds ratio of the top 10% risk group was 2.6 times higher than that of the bottom 10%. A high PRS was significantly correlated with POP occurrence in women older than 50 years old and in those with one or no childbirths. As far as we know, the integrated prediction model, which combined PRS and clinical risk factors, demonstrated better predictive accuracy than other existing PRS models. This combined risk assessment model serves as a robust tool for POP risk prediction and stratification, thereby offering insights into individualized preventive measures and treatment strategies in future clinical practice.
Humans ; Female ; Pelvic Organ Prolapse/epidemiology* ; Middle Aged ; Risk Assessment/methods* ; China/epidemiology* ; Multifactorial Inheritance ; Aged ; Risk Factors ; Genome-Wide Association Study ; Genetic Predisposition to Disease ; Case-Control Studies ; Adult ; Polymorphism, Single Nucleotide ; Genetic Risk Score ; East Asian People

Background: Pelvic organ prolapse (POP) is an inconvenience that can affect a woman’s well-being. Reconstructive pelvic floor surgery involves repairing defects in the endopelvic fascia and pelvic floor musculature as close to the physiologic and anatomic norm. The cornerstone of successful prolapse repair is a strong apical support. Objective: The aim of the study is to determine the outcomes of abdominal sacrocolpopexy (ASC) and abdominal sacrohysteropexy (ASH) in the Philippines. Methods: The study utilized a descriptive study design to compare the pre-operative and post-operative Pelvic Organ Prolapse Quantification Score (POP-Q Score), presence of mesh complications, and urinary/bowel symptoms in patients operated within 2010-2016 in a Philippine tertiary training hospital. Based on recovered charts and inclusion/ exclusion criteria, this study sampled 34 of 50 patient records. Statistical measures of median and range were used to describe pre-operative and post-operative POP-Q scores in any two follow-ups within 6-, 12-, 18-, and 24-month interval. The objective success rate and incidence of urinary/bowel symptoms were described using frequencies and percentages. Presence of any mesh erosion was noted for each follow-up. McNemar's test was applied to assess the comparative occurrence of each symptom comparing between the pre-operative and first follow-up periods. Results: ASC had a success rate of 73.7% at six months and 56.3% at 12 months post-surgery. ASH showed an 84.6% success rate at six months and 71.4% at 12 months. Apical support has a 97% success rate without affecting the anterior or posterior compartments. Out of 20 ASC patients, 5 (25%) exhibited anterior compartment descent, whereas two out of 14 ASH patients (14.2%) had the same condition. It is observed that the anterior vaginal wall has the higher tendency to descend after reconstructive surgery, independent of route or technique. In addition, not all patients with surgical prolapse beyond -1 experienced symptomatic vaginal bulges. Overall, a notable decrease in the occurrence of urine symptoms was seen after the surgery. No mesh erosion was seen within the initial two years of followup but there was a single reported instance of abdominal hernia, an uncommon consequence. Conclusion This study demonstrated that ASC and ASH have good success rate in apical support; however, descent of the anterior or posterior compartment diminishes the overall success rate in terms of over-all objective POP-Q score. Both resulted to improvement in symptoms with minimal complications.
Pelvic Organ Prolapse

OBJECTIVES: Pelvic organ prolapse (POP) is a common condition in postmenopausal women, with an increasing prevalence due to aging. Some women experience POP recurrence after surgical treatment, significantly affecting their physical and mental health. The uterosacral ligament is a critical pelvic support structure. This study aims to investigate the molecular pathological changes in the uterosacral ligament of postmenopausal women with recurrent POP using transcriptomic analysis. METHODS: Transcriptomic data of uterosacral ligament tissues were obtained from the public dataset GSE28660, which includes samples from 4 postmenopausal women with recurrent POP, 4 with primary POP, and 4 without POP. Differentially expressed genes (DEGs) were identified between recurrent POP and both primary and non-POP groups. Further analysis included intersection analysis of DEGs, gene ontology enrichment, protein-protein interaction (PPI) network construction, gene set enrichment analysis (GSEA), single-sample GSEA, and xCell immune cell infiltration analysis to explore molecular pathological changes in recurrent POP. Additionally, histological and molecular differences in the uterosacral ligament were compared between simulated vaginal delivery (SVD) rat models with and without ovariectomy. RESULTS: Compared with primary POP and non-POP groups, recurrent POP exhibited activation of adipogenesis and inflammation-related pathways, while pathways related to muscle proliferation and contraction were downregulated in the uterosacral ligament. Nine key DEGs (ADIPOQ, FABP4, IL-6, LIPE, LPL, PCK1, PLIN1, PPARG, and CD36) were identified, with most enriched in the peroxisome proliferator-activated receptor (PPAR) signaling pathway. These genes were significantly correlated with lipid accumulation, monocyte infiltration, and neutrophil infiltration in the uterosacral ligament. Urodynamic testing revealed that the bladder leak point pressure was significantly higher in ovariectomized SVD rats, both of which had higher values than the sham group. Masson staining showed pronounced adipogenesis in the uterosacral ligament of ovariectomized SVD rats, along with reduced collagen and muscle fibers compared to the sham and non-ovariectomized SVD groups. Furthermore, real-time RT-PCR confirmed significantly elevated expression of key DEGs, including ADIPOQ, IL-6, PCK1, and PLIN1, in the uterosacral ligaments of ovariectomized SVD rats. CONCLUSIONS Adipogenesis and inflammation in the uterosacral ligament may contribute to its reduced supportive function, potentially leading to recurrence POP in postmenopausal women.
Female ; Humans ; Ligaments/pathology* ; Pelvic Organ Prolapse/metabolism* ; Postmenopause ; Animals ; Rats ; Adipogenesis/genetics* ; Recurrence ; Gene Expression Profiling ; Transcriptome ; Middle Aged ; Ovariectomy ; Protein Interaction Maps ; Aged ; Rats, Sprague-Dawley ; Uterus

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.
Humans ; Female ; Pelvic Floor/pathology* ; Pelvic Organ Prolapse/pathology* ; Ultrasonography/methods* ; Imaging, Three-Dimensional

Humans ; Matrix Metalloproteinase 9 ; Collagen Type I ; Pelvic Organ Prolapse/metabolism*

Surgery is currently the only cure for rectal prolapse. Standardized preoperative evaluation and appropriate selection of surgical methods are crucial to the outcome of rectal prolapse surgery. With the development of a series of clinical studies in China and abroad, transabdominal surgery (such as ventral mesh fixation) and transperineal (anal) surgery (such as Altemeier surgery) have been widely recognized. Precise preoperative assessment of rectal prolapse and appropriate selection of surgical approaches has important clinical value in reducing postoperative recurrence rates and surgical-related complications. However, the current rectal prolapse assessment system needs to be improved, and the choice of surgical procedures remains controversal. To guide the diagnosis and surgical treatment of patients with rectal prolapse in China, nationwide specialists of colorectal and pelvic floor surgery have been organized by the of Chinese Medical Doctor Association Anorectal Branch, the Pelvic Floor Surgery Committee, and Clinical Guidelines Committee. Experts have conducted rounds of discussions on the core content of standardized diagnosis and surgical treatment for rectal prolapse, and jointly formulated the "Chinese expert consensus on the diagnosis and surgical treatment of rectal prolapse (2022)". We hope that this consensus will provide useful resources for the colorectal and pelvic floor surgeons, and promote the standardization of diagnosis and surgical treatment for the rectal prolapse in China.
Humans ; Rectal Prolapse/complications* ; Consensus ; East Asian People ; Treatment Outcome ; Colorectal Neoplasms/complications* ; Surgical Mesh/adverse effects*

Background: The rate of prolapse recurrence after vaginal hysterectomy ranges from 6% to 12%. Vaginal vault fixation procedures like the iliococcygeus fixation and the cul-de-sac obliteration (McCall culdoplasty) have been used to address the loss of apical support in patients with advanced-stage prolapse to prevent this recurrence. Objectives: This study aims to assess the rate of prolapse recurrence and risk factors for recurrence as well as urinary, bowel, and sexual symptoms in women who have undergone vaginal hysterectomy with and without vaginal vault fixation for pelvic organ prolapse stage 2 or higher. Methods: This study is a retrospective study that included patients with pelvic organ prolapse stage 2 or greater who underwent vaginal hysterectomy with and without vaginal vault fixation from 2009 to 2014 seen at the urogynecology clinic of a Philippine tertiary referral center. The cohorts were divided into those with iliococcygeal fixation (n=171) and those without (n=83). The Z test of mean difference was used in comparing average values between the two groups. Chi-square test of independence was used in comparing the proportion of patients as stratified by various variables and their corresponding groups, while some variables were adjusted for 2x2 Fischer Exact test. Any associated p-value less than 0.05 alpha were considered statistically significant. Results: Of the 876 patients operated on for prolapse between 2009 to 2014, 254 were included in the study. They were divided into those with iliococcygeal fixation (n=171) and those without (n=83). Recurrence was significantly lower in the group who underwent iliococcygeal fixation (23.39% vs 36.14%, p=0.037) after a median follow-up of 28.98 months for those with fixation and 31.08 for those without. The posterior compartment prolapse recurrence rate is higher in those without fixation (16.87% vs 6.43%, p=0.013). Longer duration of menopause (16.96 ± 7.16 vs 13.37 ± 7.1, p=0.001), unemployment (52.85% vs 36.41%, p=0.22) and longer time from surgery (37.84 ± 15.69 vs 26.55 ± 12.59, p=0.000) were significantly associated with recurrence. Moreover, higher pre- (6.24 ± 1.41 vs 5.78 ± 0.95, p=0.003) and post-operative genital hiatus (4.53 ± 0.97 vs 4.23 ± 0.54, p=0.002) and shorter pre-operative perineal body (1.86 ± 0.35 vs 1.97 ± 0.35, p=0.025) measurements were also significantly associated with recurrence. Both groups have no significant difference in urinary, sexual or bowel symptoms. Conclusion Iliococcygeus fixation is an effective method of preventing prolapse recurrence. Increased duration of menopause, longer time from surgery, longer genital hiatus, and shorter perineal body all contribute to recurrence. Moreover, urinary, sexual and bowel symptoms do not differ significantly between those with and without iliococcygeus fixation. Thus performing prophylactic vaginal vault fixation should be contemplated in patients undergoing prolapse surgery, with careful consideration of patient factors and potential morbidities.
Pelvic Organ Prolapse ; Recurrence ; Hysterectomy, Vaginal

BACKGROUND: It has been a global trend that increasing complications related to pelvic floor surgeries have been reported over time. The current study aimed to outline the development of Chinese pelvic floor surgeries related to pelvic organ prolapse (POP) over the past 14 years and investigate the potential influence of enhanced monitoring conducted by the Chinese Association of Urogynecology since 2011. METHODS: A total of 44,594 women with POP who underwent pelvic floor surgeries between October 1, 2004 and September 30, 2018 were included from 22 tertiary academic medical centers. The data were reported voluntarily and obtained from a database. We compared the proportion of each procedure in the 7 years before and 7 years after September 30, 2011. The data were analyzed by performing Z test (one-sided). RESULTS: The number of different procedures during October 1, 2011-September 30, 2018 was more than twice that during October 1, 2004-September 30, 2011. Regarding pelvic floor surgeries related to POP, the rate of synthetic mesh procedures increased from 38.1% (5298/13,906) during October 1, 2004-September 30, 2011 to 46.0% (14,107/30,688) during October 1, 2011-September 30, 2018, whereas the rate of non-mesh procedures decreased from 61.9% (8608/13,906) to 54.0% (16,581/30,688) (Z = 15.53, P < 0.001). Regarding synthetic mesh surgeries related to POP, the rates of transvaginal placement of surgical mesh (TVM) procedures decreased from 94.1% (4983/5298) to 82.2% (11,603/14,107) (Z = 20.79, P < 0.001), but the rate of laparoscopic sacrocolpopexy (LSC) procedures increased from 5.9% (315/5298) to 17.8% (2504/14,107). CONCLUSIONS: The rate of synthetic mesh procedures increased while that of non-mesh procedures decreased significantly. The rate of TVM procedures decreased while the rate of LSC procedures increased significantly. TRIAL REGISTRATION NUMBER NCT03620565, https://register.clinicaltrials.gov.
China ; Female ; Gynecologic Surgical Procedures/adverse effects* ; Humans ; Pelvic Floor/surgery* ; Pelvic Organ Prolapse/surgery* ; Surgical Mesh/adverse effects* ; Treatment Outcome ; Vagina

The pelvic floor disorder disease (PFDD) typically originates from supportive tissue defects or injuries in the pelvic floor with a wide spectrum of symptoms such as urinary incontinence, pelvic organ prolapse, sexual dysfunction, fecal incontinence and chronic pelvic pain. But its etiology is complex, involving multiple systems and organs. So the best management of PFDD requires the implementation of multidisciplinary team (MDT). Pelvic floor centers have been developed abroad to provide pelvic floor services. In the setting of PFDD, the concept of MDT starts lately and develops slowly in China. The MDT approach was demonstrated to improve general rehabilitation, psychological state and quality of life. However, there is no unified standardization for MDT diagnosis and treatment of PFDD at home and abroad. Meanwhile, the personnel composition, responsibilities, training, and operation mode of the MDT need to be further developed. Perfecting the management mode of MDT team members, establishing standardized training programs and assessment criteria play crucial role in the future development of MDT in PFDD.
China ; Fecal Incontinence ; Humans ; Pelvic Floor ; Pelvic Floor Disorders/therapy* ; Pelvic Organ Prolapse/therapy* ; Quality of Life ; Urinary Incontinence