BACKGROUND: Pelvic organ prolapse (POP) involves pelvic organ herniation into the vagina due to pelvic floor tissue laxity, and vaginal structure is an essential factor. In POP, the vaginal walls exhibit abnormal collagen distribution and decreased fibroblast levels and functions. The intricate etiology of POP and the prohibition of transvaginal meshes in pelvic reconstruction surgery present challenges in targeted therapy development. Human umbilical cord mesenchymal stromal cells (hucMSCs) present limitations, but their exosomes (hucMSC-Exo) are promising therapeutic tools for promoting fibroblast proliferation and extracellular matrix remodeling.
OBJECTIVE: To investigate the effects of hucMSC-Exo on the functions of primary vaginal fibroblasts and to elucidate the underlying mechanism involved.
METHODS: Human vaginal wall collagen content was assessed by Masson\'s trichrome and Sirius blue staining. Gene expression differences in fibroblasts from patients with and without POP were assessed via RNA sequencing (RNA-seq). The effects of hucMSC-Exo on fibroblasts were determined via functional experiments in vitro. RNA-seq data from fibroblasts exposed to hucMSC-Exo and microRNA (miRNA) sequencing data from hucMSC-Exo were jointly analyzed to identify effective molecules.
RESULTS: In POP, the vaginal wall exhibited abnormal collagen distribution and reduced fibroblast 1 quality and quantity. Treatment with 4 or 6 μg/mL hucMSC-Exo suppressed inflammation in POP group fibroblasts, stimulated primary fibroblast growth, and elevated collagen I (Col1) production in vitro. High-throughput RNA-seq of fibroblasts treated with hucMSC-Exo and miRNA sequencing of hucMSC-Exo revealed that abundant exosomal miRNAs downregulated matrix metalloproteinase 11 (MMP11) expression.
CONCLUSIONS: HucMSC-Exo normalized the growth and function of primary fibroblasts from patients with POP by promoting cell growth and Col1 expression in vitro. Abundant miRNAs in hucMSC-Exo targeted and downregulated MMP11 expression. HucMSC-Exo-based therapy may be ideal for safely and effectively treating POP.

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 (H2O2)-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 H2O2 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.

Exosomes derived from bone marrow-derived mesenchymal stem cells (BMSCs) can alleviate the symptoms of pelvic floor dysfunction (PFD) in rats. However, the potential therapeutical effects of exosomes derived from BMSCs treated with tumour necrosis factor (TNF)-α on the symptoms of PFD in rats are unknown. Exosomes extracted from BMSCs treated with or without TNF-α were applied to treat PFD rats. Our findings revealed a significant elevation in interleukin (IL)-6 and TNF-α, and matrix metalloproteinase-2 (MMP2) levels in the vaginal wall tissues of patients with pelvic organ prolapse (POP) compared with the control group. Daily administration of exosomes derived from BMSCs, treated either with or without TNF-α (referred to as Exo and TNF-Exo), resulted in increased void volume and bladder void pressure, along with reduced peak bladder pressure and leak point pressure in PFD rats. Notably, TNF-Exo treatment demonstrated superior efficacy in restoring void volume, bladder void pressure and the mentioned parameters compared with Exo treatment. Importantly, TNF-Exo exhibited greater potency than Exo in restoring the levels of multiple proteins (Elastin, Collagen I, Collagen III, IL-6, TNF-α and MMP2) in the anterior vaginal walls of PFD rats. The application of exosomes derived from TNF-α-treated BMSCs holds promise as a novel therapeutic approach for treating PFD.

OBJECTIVE: Lateral suspension is an abdominal prosthetic surgical procedure used to correct apical prolapse. The procedure involves the placement of a T-shaped mesh on the anterior vaginal wall and on the isthmus or uterine cervix that is suspended laterally and posteriorly to the abdominal wall. Since its description in the late 90s, modifications of the technique have been described. So far, no consensus on the correct indications, safety, advantages, and disadvantages of this emerging procedure has been reached.
METHODS: A modified Delphi process was used to build consensus within a group of 21 international surgeons who are experts in the performance of laparoscopic lateral suspension (LLS). The process was held with a first online round, where the experts expressed their level of agreement on 64 statements on indications, technical features, and other aspects of LLS. A subsequent re-discussion of statements where a threshold of agreement was not reached was held in presence.
RESULTS: The Delphi process allowed the identification of several aspects of LLS that represented areas of agreement by the experts. The experts agreed that LLS is a safe and effective technique to correct apical and anterior prolapse. The experts highlighted several key technical aspects of the procedure, including clinical indications and surgical steps.
CONCLUSIONS: This Delphi consensus provides valuable guidance and criteria for the use of LLS in the treatment of pelvic organ prolapse, based on expert opinion by large volume surgeons\' experts in the performance of this innovative procedure.

OBJECTIVE: To develop an algorithm for the automated localization and measurement of levator hiatus (LH) dimensions (AI-LH) using 3-D pelvic floor ultrasound.
METHODS: The AI-LH included a 3-D plane regression model and a 2-D segmentation model, which first achieved automated localization of the minimal LH dimension plane (C-plane) and measurement of the hiatal area (HA) on maximum Valsalva on the rendered LH images, but not on the C-plane. The dataset included 600 volumetric data. We compared AI-LH with sonographer difference (ASD) as well as the inter-sonographer differences (IESD) in the testing dataset (n = 240). The assessment encompassed the mean absolute error (MAE) for the angle and center point distance of the C-plane, along with the Dice coefficient, MAE, and intra-class correlation coefficient (ICC) for HA, and included the time consumption.
RESULTS: The MAE of the C-plane of ASD was 4.81 ± 2.47° with 1.92 ± 1.54 mm. AI-LH achieved a mean Dice coefficient of 0.93 for LH segmentation. The MAE on HA of ASD (1.44 ± 1.12 mm²) was lower than that of IESD (1.63 ± 1.58 mm²). The ICC on HA of ASD (0.964) was higher than that of IESD (0.949). The average time costs of AI-LH and manual measurement were 2.00 ± 0.22 s and 59.60 ± 2.63 s (t = 18.87, p < 0.01), respectively.
CONCLUSIONS: AI-LH is accurate, reliable, and robust in the localization and measurement of LH dimensions, which can shorten the time cost, simplify the operation process, and have good value in clinical applications.

OBJECTIVE: To investigate the superiority of transrectal high-frequency ultrasound (TRUS) in precise assessment of middle compartment prolapse in comparison with routine transperineal ultrasound (TPUS).
METHODS: Prospectively analyzed and compared detection rates of entire cervical length and uterine descent on TPUS and TRUS in 101 patients with pelvic organ prolapse (POP).
RESULTS: Detection rates of entire cervix on TRUS were significantly higher than those on TPUS both at rest and during Valsalva maneuver (90.10% VS 49.50%, 92.08% VS 9.90% respectively, both p < 0.05). Uterine descent was able to be evaluated in 92.08% of patients by TRUS and in 5.94% of patients by TPUS, which was statistically significant (p < 0.05). The interobserver repeatability for the measurements of anterior lip, cervical canal and posterior lip on TRUS was excellent. The mean lengths of anterior lip, cervical canal and posterior lip were significantly increased during Valsalva maneuver than those measured at rest (p < 0.05). And mean length of anterior lip was longer than posterior lip both at rest and during Valsalva (p < 0.05).
CONCLUSIONS: TRUS can significantly raise detection rates of entire cervix, and make the direct evaluation of uterine descent feasible. TRUS can be used as a complementary method to TPUS to attain more comprehensive and accurate presurgical imaging information in middle compartment prolapse patients.

UNASSIGNED: Colpocleisis is one of traditional surgical procedures for elderly and frail women with advanced pelvic organ prolapse. The occurrence of de novo urinary incontinence following colpocleisis was considered to impair the postoperative quality of life. The incidence of de novo urinary incontinence after colpocleisis has been reported to be ranging from 6.6 % to 27 %. There was an absence of prospective large-sample study to investigate the accurate incidence of de novo urinary incontinence following colpocleisis and the impact on the quality of life till now.
UNASSIGNED: s The primary objective was to report the incidence of de novo urinary incontinence after colpocleisis. The second objectives were to evaluate the long-term quality of life in patients with de novo urinary incontinence, and to conduct detailed pre- and post-operative evaluations of lower urinary tract symptoms.
UNASSIGNED: This prospective study included 253 patients with symptomatic pelvic organ prolapse who underwent colpocleisis between 2009 and 2021. De novo urinary incontinence was defined as the occurrence of urinary incontinence 3 months postoperatively. All patients were required to complete the Urinary Distress Inventory questionnaire and the Urinary Impact Questionnaire for the evaluation of patients\' quality of life, and the Patient Global Impression of Improvement questionnaire for the evaluation of patients\' satisfaction.
UNASSIGNED: 245 patients (245/253, 96·8 %) completed the 3-month follow-up, and were included in the final analysis. The incidence of de novo urinary incontinence was 5.4 % (10/185). There was no significant difference in the Urinary Distress Inventory -6 scores (22.50 vs. 10.30, P = 0.276) or the subjective satisfaction rate (100 % vs. 98.9 %, P = 0.250) between the patients with or without de novo urinary incontinence at the long-term follow-up. The incidence of voiding difficulty was significantly reduced after colpocleisis (27.8 % vs. 0.0 %, P < 0.001). The patients\' quality of life indicated by Urinary Distress Inventory-6 and Urinary Impact Questionnaire-7 scores were significantly improved postoperatively (26.27 vs. 13.39, and 19.13 vs. 6.05, P < 0.05).
UNASSIGNED: The incidence of de novo urinary incontinence after colpocleisis was very low. Patients\' quality of life, and low urinary tract symptoms were significantly improved after colpocleisis.

OBJECTIVE: We hypothesized that some metabolic factors, lifestyle factors, and socioeconomic factors may have a causal effect on pelvic organ prolapse (POP).
METHODS: We selected instruments from corresponding genome-wide association studies (GWAS), which identified independent single nucleotide polymorphisms strongly associated with 12 potential risk factors. Summary statistics for POP were derived from two GWAS datasets, serving for discovery and replication stage. The primary analysis involved the use of the inverse-variance weighting mendelian randomization (MR) method, with additional sensitivity MR analyses conducted.
RESULTS: The univariable mendelian randomization (UVMR) analysis in both the discovery and replication stage provided evidence for significant causal effects between higher waist-to-hip ratio adjusted for body mass index (WHRadjBMI) levels, lower high-density lipoprotein cholesterol (HDL-C) levels, and lower educational attainment and higher POP risk, as well as a suggestive positive causal effect between triglycerides and POP. The multivariable mendelian randomization (MVMR) analysis showed that only HDL-C among the three blood lipid fractions could reduce the risk of POP. Mediation analysis indicated that HDL-C may partially mediate the effect of WHRadjBMI on POP risk, and the causal effect between educational attainment and POP may be mediated through WHRadjBMI and HDL-C.
CONCLUSIONS: Our study\'s evidence supported a causal relationship between WHRadjBMI, triglycerides, HDL-C, educational attainment, and POP risk. This highlights that clinicians may guide the general female population to control obesity and blood lipid levels to reduce the risk of POP.

OBJECTIVE: The study was aimed at systematically analyzing the research status and trends of pelvic organ prolapse (POP) using bibliometrics.
METHODS: We retrieved documents published between 1975 and 2022 from the Web of Science Core Collection (WoSCC) database, and manually selected them for bibliometric analyses of country, institution, journal, highly locally cited documents and research trends based on co-citation clustering and keywords using the R Bibliometricx package and CiteSpace software.
RESULTS: A total of 5,703 publications were included. Although the number of annual publications on POP increased, the trend of annual publication reached an obvious plateau in the first half of the 2010s. The USA, China, the UK, the University of Michigan, the University of Pittsburgh, and the University of Sydney were the top three countries and institutions with the most publications respectively. International Urogynecology Journal, American Journal of Obstetrics and Gynecology, and Obstetrics and Gynecology were the journals with the most extensive academic influence on the field of POP research. The international cooperation was lacking and the highly cited documents focused on high-level, evidence-based studies. Epidemiological studies and surgical treatment have achieved a plateau or decline. Recent studies have focused on conservative treatment, physical therapy, and minimally invasive surgery. In addition to evidence-based medicine studies, tissue engineering is the future direction of POP.
CONCLUSIONS: This study used bibliometric analyses to provide insights into the status and potential research directions of POP. More high-quality, evidence-based medicine studies and in-depth tissue engineering research should be propelled forward.

OBJECTIVE: Utilize magnetic resonance defecography (MRD) to analyze the primary pelvic floor dysfunctions in patients with stress urinary incontinence (SUI) associated with pelvic organ prolapse (POP), and in SUI patients with asymptomatic POP.
METHODS: We performed MRD in both SUI and POP subjects. As a primary analysis, the functional MR parameters were compared between the isolated POP and POP combined SUI groups. As a secondary analysis, the functional MR data were compared between the POP combined SUI and the SUI with asymptomatic POP (isolated SUI) groups.
RESULTS: MRD noted the main characteristics of SUI combined moderate or severe POP, including the shorter closed urethra length (1.87 cm vs. 2.50 cm, p < 0.001), more prevalent urethral hypermobility (112.31° vs. 85.67°, p = 0.003), bladder neck funneling (48.28% vs. 20.51%, p = 0.020), lower position of vesicourethral junction (2.11 cm vs. 1.67 cm, p = 0.030), and more severe prolapse of the posterior bladder wall (6.26 cm vs. 4.35 cm, p = 0.008). The isolated SUI patients showed the shortest length of the closed urethra (1.56 cm vs. 1.87 cm, p = 0.029), a larger vesicourethral angle (153.80° vs. 107.58°, p < 0.001), the more positive bladder funneling (84.85% vs. 48.28%, p = 0.002) and a special urethral opening sign (45.45% vs. 3.45%, p < 0.001).
CONCLUSIONS: Patients with SUI accompanying POP primarily exhibit excessive urethral mobility and a shortened urethral closure. SUI patients with asymptomatic POP mainly show dysfunction of the urethra and bladder neck, characterized by the opening of the urethra and bladder neck and a shortened urethral closure.