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Background: Le Fort colpocleisis is an obliterative surgery for the treatment of pelvic organ prolapse (POP). In this study, we aimed to investigate the efficacy and safety of Le Fort colpocleisis in the treatment of patients with stage III-IV POP., Methods: The study was designed as a retrospective analysis of a single-center case series. Patients with stage III-IV POP treated with Le Fort colpocleisis were included. Perioperative indicators, subjective and objective outcomes and complications were assessed. The POP-Quantification (POP-Q) system was used for objective outcome evaluation. Pelvic Floor Distress Questionnaire (PFDI-20) and Pelvic Floor Impact Questionnaire (PFIQ-7) were used for subjective outcome evaluation., Results: A total of 54 patients with complete pre- and postoperative data completed follow-up and were included in our study. The mean ± standard deviation of operative time, intraoperative blood loss, recovery activity time, postoperative hospitalization time and total hospitalization time were 146.85 ± 37.01 min, 92.04 ± 68.31 ml, 2.81 ± 0.85 days, 6.5 ± 2.11 days and 13.52 ± 4.78 days, respectively. Within the median follow-up period of 38.5 months, the objective cure rate of Le Fort colpocleisis reached 98.15% (53/54), and the subjective cure rate reached 92.59% (50/54). No serious complications were reported during the perioperative period and follow-up period., Conclusion: Le Fort colpocleisis is an effective and safe procedure for the treatment of severe POP. Because of its lower operative risk, better subjective and objective outcomes, lower rates of prolapse recurrence and perioperative complications, Le Fort colpocleisis should be considered as the recommended procedure for elderly patients with severe POP (stage III-IV)., Competing Interests: Declarations. Ethics approval and consent to participate: All methods in this study were carried out in accordance with the Helsinki and STROBE guidelines. This study was approved by the Ethics Committee of the First Affiliated Hospital of Guangzhou Medical University, China. Written informed consent was obtained from participants. Given the design of the study, the Institutional Review Board of the First Affiliated Hospital of Guangzhou Medical University ruled that approval was not needed. Consent for publication: Not applicable. Compteting interests: The authors declare no competing interests., (© 2024. The Author(s).)

There are limited data on the effects of a high-fructose diet on the female reproductive system. Although metformin has some functional effects on female fertility, its reproductive outcome on high fructose diet-induced metabolic syndrome is unclear. The aim of the present study is to evaluate the impact of a high fructose diet on histomorphological and molecular parameters of the reproductive organs and vaginal microbiota as well as the treatment potential of metformin. Wistar albino rats were used in the study. The metabolic syndrome model was induced by a high-fructose diet in rats for 15 weeks. Metformin was orally administered once a day for the last 6 weeks. The high-fructose diet increased blood glucose, triglycerides, insulin, and ovarian testosterone levels; however, it reduced ovarian aromatase levels and follicle numbers and caused uterine inflammation. The high-fructose diet-induced molecular abnormalities on ovarian tissue were demonstrated by the downregulation of ovarian insulin signaling pathway proteins and dysregulation of ovarian mitogenic and apoptotic pathway proteins. A high-fructose diet caused vaginal dysbiosis, metformin increased probiotic bacteria in the vaginal microbiota. Our results revealed that metformin improves ovarian impairments by modulating hormonal balance, insulin level, mapk, and apoptotic signaling molecules, as well as regulating the vaginal microbiota., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Endometrial cancer (EC) rates are continuing to rise and it remains the most common gynecologic cancer in the US. Existing diagnostic methods are invasive and can cause pain and anxiety. Hence, there is a need for less invasive diagnostics for early EC detection. The study objective was to evaluate the utility of growth factors collected through minimally invasive cervicovaginal lavage (CVL) sampling as diagnostic and prognostic biomarkers for EC. CVL samples from 192 individuals undergoing hysterectomy for benign or malignant conditions were collected and used to quantify the concentrations of 19 growth and angiogenic factors using multiplex immunoassays. Patients were categorized based on disease groups: benign conditions (n = 108), endometrial hyperplasia (n = 18), and EC (n = 66). EC group was stratified into grade 1/2 endometrial endometrioid cancer (n = 53) and other EC subtypes (n = 13). Statistical associations were assessed using receiver operating characteristics, Spearman correlations and hierarchical clustering. Growth and angiogenic factors: angiopoietin-2, endoglin, fibroblast activation protein (FAP), melanoma inhibitory activity, and vascular endothelial growth factor-A (VEGF-A) were significantly (p < 0.0001) elevated in EC patients. A multivariate model combining 11 proteins with patient age and body mass index exhibited excellent discriminatory potential (area under curve = 0.918) for EC, with a specificity of 90.7% and a sensitivity of 87.8%. Moreover, angiopoietin-2, FAP and VEGF-A significantly (p < 0.05-0.001) associated with tumor grade, size, myometrial invasion, and mismatch repair status. Our results highlight the innovative use of growth and angiogenic factors collected through CVL sampling for the detecting endometrial cancer, showcasing not only their diagnostic potential but also their prognostic value., (© 2024. The Author(s).)

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.)

The antimicrobial activity of crude and purified L-glutaminase (EC 3.5.1.2), obtained from Lactobacillus gasseri, was evaluated against multidrug-resistant Pseudomonas aeruginosa in the in vivo vaginosis condition. The L-glutaminase possessed significant antimicrobial and anti-biofilm formation activity against multi-drug resistance P. aeruginosa, which were confirmed in the BALBc rat vaginosis model, together with its effects on the immunological and histopathological aspects. The untreated animals showed heavy vaginitis, characterized by sub-epithelial edema and infiltration of mononuclear leukocytes, perivascular heavy inflammatory cells infiltration in the vaginal tissue, and moderate stromal edema. However, the L-glutaminase treatment exhibited no changes in vaginal tissue structure with normal appearance of the epithelium and lamina propria with marked repair of the vaginal section when compared with normal, uninfected, control group A. The immunomodulatory actions of the L-glutaminase were confirmed by observance of higher concentrations of tumor necrosis factor-γ (TNF-γ), and interleukin -12 (IL-12) in treated animals, while the interleukin-10 (IL-10) was higher in the infected, untreated animals' sera samples. Therefore, the L-glutaminase showed corrective and healing actions, which were observed through histopathological observations of the vaginal tissue. The investigations led to imply that L-glutaminase may have the potential to be an effective antimicrobial agent for preventing and inhibiting bacterial growth, as well as inhibiting the biofilm formation in the P. aeruginosa-originated vaginosis. The observations may be of promising value for future clinical use., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The rectovaginal septum is an unusual location for neoplastic processes. The majority of these are extensions of tumors of the rectum or vagina. Masses arising primarily from the rectovaginal fascia are rare. Most primary rectovaginal malignant neoplasms are carcinomas that arise in the setting of endometriosis. Sarcomas in this location are exceedingly rare, with only few cases reported in the literature. We report a case of a 44-year-old lady who developed a high-grade sarcoma in the rectovaginal septum in the setting of endometriosis. We also discussed the differential diagnosis of this lady's challenging and unique lesion, which is most probably an extra-uterine "uterine-type" high-grade sarcoma that shows overlapping features of several entities. Moreover, we performed a literature review of sarcomas in this rare location. Given the fact that the rectovaginal septum is a common location for endometriosis, in the case of a rectovaginal neoplasm, a thorough sampling and a careful search for endometriotic lesions are important, as they may be a clue for the diagnosis. Although rare, sarcomas should always be considered in the differential diagnosis of rectovaginal neoplasms., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2024 by the International Society of Gynecological Pathologists.)

Adenoid cystic carcinoma (ACC) is a rare neoplasm most frequently observed in the salivary glands, that can occur in other organs, including the vulva and vagina. Oncogenic mechanisms involving MYB, NFIB , and MYB-NFIB rearrangements have been described, but evidence in the vulva and vagina remains scarce. Our aim is to report the clinicopathologic features, immunohistochemical, and molecular findings in a series of vulvar and vaginal ACCs. Five cases were included. Medical records and slides were reviewed. Formalin-fixed paraffin-embedded material was available in 4 cases, where additional immunohistochemical and molecular studies were carried out. Fluorescence in situ hybridization using MYB, MYBL1 , and NFIB bacterial artificial chromosome-clones break-apart and MYB::NFIB BAC-clones fusion probes was performed. The patients' mean age at diagnosis was 52 years. Tumor size ranged from 0.5 to 5 cm. Microscopic examination revealed tubular, cribriform, and solid patterns. Perineural invasion was seen in 4 cases. Patients were treated with surgery, some with adjuvant radiation therapy. During follow-up (mean: 11 yr), 4 patients developed local recurrences. Recently, one of these patients developed pulmonary disease. Cam 5.2, CK5/6, CD117, and DOG-1 were positive in all 4 cases and S100 and calponin were positive in 3 cases. MYB rearrangement was present in 3 cases, including one with concurrent MYB amplification. There were no MYBL1 or NFIB rearrangements and no MYB :: NFIB fusions. Our findings corroborate that the histologic, immunohistochemical, and oncogenic background is similar between ACCs of the lower female genital tract and ACCs elsewhere, although the canonical MYB::NFIB fusion seems to be a less common finding in this location., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 by the International Society of Gynecological Pathologists.)

Apart from bone marrow involvement, extranodal involvement of follicular lymphoma (FL) is rare. Gynecologic FL is seldom reported, among which the vagina is the rarest involved site. No vaginal involvement in advanced-staged FL was reported before. Here, we report a case of FL with systemic involvement including the vagina., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Stress urinary incontinence (SUI), characterized by involuntary urine leakage during increased abdominal pressure, remains poorly understood regarding its pathophysiology and treatment. In this study, we utilized single-cell sequencing to analyze the transcriptomic profiles of different cell types in anterior vaginal wall of SUI patients, aiming to explore the heterogeneity of the extracellular matrix (ECM) and immune microenvironment in SUI pathogenesis. Our results identified eleven cell types, including connective tissue cells, immune cells, and glial cells. Specifically, fibroblasts, smooth muscle cells, epithelial cells and T cells displayed transcriptional characteristics highly relevant to SUI pathogenesis. We observed that most cell types participate in ECM metabolism and immune-inflammatory responses, indicating a synergistic role of multiple vaginal cell types in SUI. Furthermore, altered intercellular communication, particularly between fibroblasts and T cells, was noted in SUI. This study provides novel single-cell insights into SUI and identifies potential biomarkers and therapeutic targets for future research., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Objective: To describe the incidence of uterovaginal anomalies and histologic findings in transgender and nonbinary (TGNB) patients seeking hysterectomies., Methods: All patients receiving gender-affirming hysterectomies between 2013 and 2023 were retrospectively reviewed. Primary outcomes included uterovaginal anomalies and histological findings. Multivariable logistic regressions were performed to evaluate relationships between variables of interest and whether they predict findings of uterovaginal anomalies, inactive endometrium, adenomyosis, leiomyoma, endometriosis, and cervical atrophy., Results: 278 patients received hysterectomies at an average age of 29.2 ± 8.3 years. Seven patients (2.5%) were found to have a developmental anomaly, including two bicornuate uterus (0.7%), two unicornuate uterus (0.7%), one septate uterus (0.4%), and two vaginal septum (0.7%). 60 patients (21.6%) were found to have inactive endometrium and 26 patients (9.4%) had cervical atrophy. Although 262 patients (94.2%) were on testosterone therapy, hormone duration was not a significant predictor of any uterine findings., Conclusion: This study describes uterovaginal anomalies in a large cohort of patients receiving gender-affirming hysterectomies. Although long-term testosterone use is commonly believed to be associated with endometrial and cervical atrophy, this study shows no such association., (© 2024 International Federation of Gynecology and Obstetrics.)

Regulatory T cells (Tregs) are well-known to mediate peripheral tolerance at homeostasis, and there is a growing appreciation for their role in modulating infectious disease immunity. Following acute and chronic infections, Tregs can restrict pathogen-specific T cell responses to limit immunopathology. However, it is unclear if Tregs mediate control of pathology and immunity in distal tissue sites during localized infections. We investigated the role of Tregs in immunity and disease in various tissue compartments in the context of "mild" vaginal Zika virus infection. We found that Tregs are critical to generating robust virus-specific CD8 T cell responses in the initial infection site. Further, Tregs limit inflammatory cytokines and immunopathology during localized infection; a dysregulated immune response in Treg-depleted mice leads to increased T cell infiltrates and immunopathology in both the vagina and the central nervous system (CNS). Importantly, these CNS infiltrates are not present at the same magnitude during infection of Treg-sufficient mice, in which there is no CNS immunopathology. Our data suggest that Tregs are necessary to generate a robust virus-specific response at the mucosal site of infection, while Treg-mediated restriction of bystander inflammation limits immunopathology both at the site of infection as well as distal tissue sites., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: Emerging evidence suggests that vaginal micro-environment disorder is closely related to the development of cervical lesions. Low-grade cervical intraepithelial neoplasia (CIN1), as an early stage of cervical lesions, exhibits a high risk of progressing to high-grade lesions or even cervical cancer. However, the effect of vaginal micro-environment on the malignant prognosis of CIN1 remains uncertain., Methods: A total of 504 patients diagnosed with CIN1 by pathology, who were from the population-based cohorts established in Shanxi Province, China, were enrolled and followed up for 2 years. Micro-environmental factors such as vaginal pH, cleanliness, hydrogen peroxide (H 2 O 2 ), β-glucuronidase (GUSB), leucocyte esterase (LE), and sialidase (SNA) were detected to evaluate their effect on the malignant prognosis of CIN1., Results: Abnormal vaginal pH (HR = 1.472, 95%CI 1.071-2.022), cleanliness (HR = 1.446, 95%CI 1.067-1.960), H 2 O 2 (HR = 1.525, 95%CI 1.155-2.013), GUSB (HR = 1.739, 95%CI 1.235-2.448), LE (HR = 1.434, 95%CI 1.038-1.981), and SNA (HR = 1.411, 95%CI 1.065-1.870) could promote a higher incidence of CIN1 malignant prognosis, and the combined effects of these micro-environmental factors resulted in a nearly twofold increased risk (HR = 2.492, 95%CI 1.773-3.504) compared to any single factor alone, especially under the high-risk human papillomavirus (HR-HPV) infection. Notably, the cumulative incidence of malignant prognosis for CIN1 gradually increased during the early follow-up period, reaching its peak at approximately 8 months, and then stabilizing., Conclusion: Vaginal micro-environment disorder could promote CIN1 malignant prognosis, particularly in HR-HPV-infected women. Taking micro-environmental factors as the breakthrough, our study provides a feasible vision for preventing early stage cervical lesions., (© 2024. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).)

Purpose: The present work seeks to develop, assess and refine a nanoethosomal vaginal in situ gel containing Berberine, aimed at enhancing its efficacy in treating Poly Cystic Ovary Syndrome (PCOS). This formulation aims to augment drug permeation, enable controlled release kinetics, and mitigate oral adverse effects commonly associated with Berberine administration., Method: Nanoethosomes formulated using diverse soya lecithin-ethanol concentrations within a 3 2 full-factorial-design, sought optimal formulations based on particle size and %entrapment-efficiency. Subsequent scrutiny involved PDI, Zeta potential and drug-content evaluation. TEM analysis authenticated morphology, while in vitro drug release from Nanoethosomes was examined. Pluronic F-127 concentrations (16%-21%w/v) were explored for the in situ gel, analyzing pH, gelation time and gelation temperature. The refined gel underwent evaluations for viscosity and in vitro diffusion. In vivo assessment covered pharmacokinetics, vaginal irritancy and Mifepristone-induced PCOS management, validated through histopathological and biochemical analysis, juxtaposing findings across normal, diseased, plain Berberine gel and standard metformin administered groups., Results: Optimized Nanoethosomal Formulation(F3) displayed particle size of 183.5 nm, 82.58 % as %entrapment-efficiency, PDI of 0.137, -50.34 mV as zeta potential and 81.64 ± 1.57 % drug-content. TEM analysis confirmed spherical, nano-sized particles. In vitro studies exhibited 80.45 % drug release over 24 h. The formulated gel with 18 % Pluronic F-127 showed viscosity ranging from 193.01 ± 0.16cps to 1817.08 ± 1.67cps with temperature changes from 25 ± 2.0 °C to 38 ± 2.0 °C. In vitro diffusion revealed 85.99 %drug release from optimized gel. In vivo animal studies demonstrated increased plasma drug concentration, non-irritating properties in vaginal tests, and efficacy in managing Mifepristone-induced PCOS compared to other treatments. Short-term stability evaluations confirmed thermodynamic stability at room-temperature., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Vulvovaginal atrophy, characterized by the thinning of vaginal mucosa typically resulting from reduced estrogen levels, is frequently exacerbated by oncogynecologic treatments such as chemotherapy, hormonal therapy, radiotherapy, or surgery. This condition significantly impacts the quality of life for cancer survivors, leading to persistent discomfort, heightened infection risk, and negative effects on sexual function and self-esteem. Despite being a relatively common complication, vulvovaginal atrophy is not always discussed before the start of treatment. Treatments typically mirror those used for natural menopause; however, efficacy and safety data specific to this population are limited due to the exclusion of these patients from clinical trials. A major safety concern is the risk of hormone-sensitive cancer recurrence associated with estrogen therapy, which drives a preference for non-hormonal alternatives. Newer treatments, such as laser therapy, radiofrequency, and vaginal injections, show promise with minimal side effects and hormone-independent mechanisms, though efficacy data varies, highlighting the need for further research. This narrative review explores the epidemiology, risk factors, diagnosis, and management of vulvovaginal atrophy after the treatment for oncogynecologic disorders.

Objectives: The aim of this study was to characterize the microbiome of multiple mucosal organs in cervical cancer (CC) patients., Methods: We collected oral, gut, urinary tract, and vaginal samples from enrolled study participants, as well as tumor tissue from CC patients. The microbiota of different mucosal organs was identified by 16S rDNA sequencing and correlated with clinical-pathological characteristics of cervical cancer cases., Results: Compared with controls, CC patients had reduced α-diversity of oral and gut microbiota (p Oral&#95;Sob < 0.001, p Oral&#95;Shannon = 0.049, p Oral&#95;Simpson = 0.013 p Fecal&#95;Sob = 0.030), although there was an opposite trend in the vaginal microbiota (p Vaginal&#95;Pielou = 0.028, p Vaginal&#95;Simpson = 0.006). There were also significant differences in the β-diversity of the microbiota at each site between cases and controls (p Oral = 0.002, p Fecal = 0.037, p Urine = 0.001, p Vaginal = 0.001). The uniformity of urine microbiota was lower in patients with cervical squamous cell carcinoma (p Urine = 0.036) and lymph node metastasis (p Urine&#95;Sob = 0.027, p Urine&#95;Pielou = 0.028, p Urine&#95;Simpson = 0.021, p Urine&#95;Shannon = 0.047). The composition of bacteria in urine also varied among patients with different ages (p = 0.002), tumor stages (p = 0.001) and lymph node metastasis (p = 0.002). In CC cases, Pseudomonas were significantly enriched in the oral, gut, and urinary tract samples. In addition, Gardnerella, Anaerococcus, and Prevotella were biomarkers of urinary tract microbiota; Abiotrophia and Lautropia were obviously enriched in the oral microbiota. The microbiota of tumor tissue correlated with other mucosal organs (except the gut), with a shift in the microflora between mucosal organs and tumors., Conclusions: Our study not only revealed differences in the composition and diversity of the vaginal and gut microflora between CC cases and controls, but also showed dysbiosis of the oral cavity and urethra in cervical cancer cases., (© 2024. The Author(s).)

The most commonly used animal models for evaluating the efficacy of HSV-2 candidate vaccines are mice and guinea pigs. While numerous HSV-2 vaccine candidates have been tested in these animals and were effective in reducing disease and mortality, these results did not predict the effectiveness of the vaccines in human trials. Infection of rhesus macaques rarely results in lesions or HSV-2 specific antibody responses. In seeking an animal model that better recapitulates human disease and that might be more predictive of the efficacy of prophylactic vaccines than mice and guinea pigs, we evaluated Cebus apella (C. apella), a New World primate, in an HSV-2 genital infection model. Infectious HSV-2 was cultured from vaginal swabs from all 4 animals for 9-14 days after intravaginal inoculation of HSV-2 seronegative monkeys. Two of 4 monkeys had vesicular lesions in the vagina or vulva. No neurological symptoms were noted. Recurrent lesions and HSV-2 DNA shedding after acute disease resolved was infrequent. UV irradiation of the genital area did not induce recurrent genital lesions or virus shedding. All 4 monkeys developed HSV-2 neutralizing antibodies as well as virus-specific CD4 and CD8 T cell responses. Reinfection of animals 15 to 19 months after primary infection did not result in lesions; animals had reduced virus shedding and a shorter duration of shedding compared with that during primary infection, suggesting that primary infection induced protective immunity. Primary fibroblasts from C. apella monkeys supported the growth of HSV-2 in vitro; in contrast, HSV-2 did not replicate above the titer of the input inoculum in fibroblasts from rhesus macaques. These observations suggest that the C. apella monkey has potential to serve as a model for evaluating the efficacy of prophylactic vaccines, antivirals, or monoclonal antibodies to HSV-2., Competing Interests: JIC has a Collaborative Research and Development Agreement with Sanofi Pasteur for a clinical trial of a replication-defective herpes simplex virus (HSV) vaccine. DMK has been a consultant for Curevo, MaxVax LLC, and Gilead concerning HSV or varicella-zoster virus infections, has received research funding from Sanofi related HSV vaccines, and has received royalties from his employer from the licensing of institutionally-owned patents concerning HSV vaccine candidates on which he is a co-inventor., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Objective: The aim of this study was to compare the efficacy of a non-hormone alternative, vaginal hyaluronic acid (HLA), to a standard-of-care therapy, vaginal estrogen, for the treatment of genitourinary syndrome of menopause (GSM)., Methods: This was a randomized, parallel arm pilot trial. Women with GSM were randomized to an HLA vaginal suppository or vaginal estrogen cream for 12 wk to compare the primary outcome, the vulvovaginal symptom questionnaire (VSQ) score. Secondary outcomes included the following: the female sexual function index (FSFI), the vaginal symptom index (VSI), visual analog scale (VAS) for dyspareunia, vaginal itching, and vaginal dryness, patient global impression of improvement (PGI-I) at follow-up, vaginal maturation index, and vaginal pH. Differences between treatment groups were estimated using the two-sided, two-sample t -test and 95% confidence intervals., Results: Forty-nine women were randomized and 45 participants (vaginal estrogen = 23, vaginal HLA = 22) provided data at week 12. Baseline characteristics were similar in both groups. On the VSQ, there was no observed difference in overall scores between the HLA and vaginal estrogen groups at 12 wk ( P = 0.81). Improvement was seen within both treatment groups on the VSQ after 12 wk. The VAS score, total VSI score, total FSFI score, and vaginal pH improved over time; however, improvement did not differ between study arms. Over 90% participants noted improvement on the PGI-I in both groups ( P = 0.61). No treatment-related serious adverse events occurred., Conclusions: There were no clinically meaningful differences between vaginal HLA and vaginal estrogen for the treatment of GSM after 12 wk. Vaginal HLA may be a promising non-hormone therapy for GSM., Competing Interests: Financial disclosure/conflicts of interest: Benjamin M. Brucker is an investigator, speaker, and advisor for AbbVie; advisor for Watkins Conti; investigator, speaker, and advisor for Urovant; advisor for Palette, funding from Myovant, ProPharma, Axonics, and Medtronic. Erinn M. Hale receives institutional funding from the National Institutes of Health, PCORI, and Educational Foundation of America, and is an editor for Reproductive, Female and Child Health Journal. Lila Nachtigall is chairman of the board of the Foundation for Woman's Wellness, which is a non-profit for which she receives no compensation. Christina Escobar receives institutional funding from Watkins Conti products. The other authors have nothing to disclose., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The Menopause Society.)

Objective: To compare patient satisfaction rate in postmenopausal women who chose dynamic quadripolar radiofrequency or topical estrogens as their preferred treatment for genitourinary syndrome of menopause., Methods: Patients were divided into two groups according to their preference: one was treated with estrogen therapy (ET) and the other with dynamic quadripolar radiofrequency treatment (RF). All patients included fulfilled a series of validated questionnaires, at baseline and at the 6-mo follow-up, in order to evaluate the discomfort degree associated with the presence of vulvovaginal atrophy and the impact of the reported symptoms on QoL and sexuality., Results: After propensity score matching, the proportion of women considering themselves satisfied with their genital health conditions was extremely small at study entry (5.2% of the RF group and 6.9% of the ET group), while at a 6-mo follow-up, it increased to 46.7% and 46.6%, respectively. No statistically significant between-group differences were found regarding mean numerical rating scale scores for dryness and dyspareunia at follow-up (5.6 ± 2.6 vs 5.3 ± 2.3, P = 0.5; and 2.9 ± 2.5 vs 3.0 ± 2.7, P = 0.46). At 6-mo follow-up, we observed no statistically significant differences between the two groups regarding the other items evaluated. RF treatment was overall well tolerated., Conclusion: The use of quadripolar radiofrequency devices seems effective, but it is not associated with better clinical outcomes compared with topical hormone treatment, which is a substantially cheaper and more convenient treatment for genitourinary syndrome of menopause. Therefore, we suggest limiting the use of dynamic quadripolar radiofrequency selectively when topical estrogens are not effective, not tolerated, or contraindicated., Competing Interests: Financial disclosure/conflicts of interest: EVA technology was provided to the Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, free of cost by Novavision Group SpA., Misinto, Monza-Brianza, Italy. None of the authors have anything to declare., (Copyright © 2024 by The Menopause Society.)

Background: Genitourinary syndrome of menopause (GSM) is a common condition, yet there is no defined, objective, and reproducible intervention with which to make a diagnosis. There are many different treatment options available, but without the correct diagnosis, affected women are unable to access the right therapy. This paper reports on the questionnaire arm of the VAN study (VAginal Health - What's N ormal? ) which aimed to evaluate the performance and acceptability of the methods of assessment of GSM, described below., Objectives: To determine the value of the Day-to-Day Impact of Vaginal Aging (DIVA) questionnaire: a multidimensional measure of the impact of vaginal symptoms on functioning and well-being in postmenopausal women, in a prospective, observational, feasibility study., Methods: 60 women were recruited to the study (20 premenopausal, asymptomatic women (control group) and 40 peri- and postmenopausal, symptomatic women). All women had a baseline assessment, using three different interventions, in addition to the DIVA questionnaire and symptomatic women were offered treatment, followed by a second assessment undertaken at 16 weeks, using the same interventions. This paper focusses on the outcomes for the questionnaire and specifically on the paired data sets, before and after treatment., Results: An improvement in the score for all four sections of DIVA (Activities of daily living, Emotions, Sexual Activity, and Feelings about yourself and your body (female embodiment)) was observed, following any treatment. Additional questions were added to DIVA, to assess patient preference in relation to the different diagnostic interventions. These included a speculum examination as part of the clinical assessment, a smear taken from the lateral vaginal wall to assess the vaginal maturation index, both undertaken by a clinician and a self-administered tampon to collect vaginal secretions, to determine the small molecule metabolite profile, using NMR spectroscopy, and to enable analysis of the vaginal microbiome. The medical standard tampon was the preferred intervention, before and after treatment, for women eligible for treatment., Conclusion: The VAN study demonstrates that DIVA, a previously tested questionnaire, is an easily accessible intervention, to assess the impact of urogenital symptoms on quality-of-life indicators in women in the United Kingdom with GSM and that women prefer to use a tampon themselves, rather than have a clinician performed vaginal speculum examination or a vaginal smear., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: To describe the incidence and management of vaginal stricture after uterus transplantation (UTx) in the US, to propose a grading system to classify stricture severity, and to identify risk factors for stricture formation., Design: Prospective cohort study., Setting: University Hospital., Patients: Recipients undergoing UTx from 2016-2023 at Baylor University Medical Center in Dallas, Cleveland Clinic, the University of Pennsylvania, and the University of Alabama at Birmingham were monitored postoperatively with regular pelvic examinations. Stricture was defined as vaginal narrowing of <3 cm in patients with graft survival of at least 7 days., Intervention: Demographic and surgery characteristics., Main Outcome Measures: Stricture development and severity (grade 1 for diameter 2-<3 cm, grade 2 for 1-<2 cm, or grade 3 for <1 cm)., Results: Of the 45 UTx from 2016-2023 (16 deceased donors and 29 living donors), 3 were excluded from the analysis because of graft loss within 7 days. Of the 42 remaining recipients, 39 (92.9%) had Mayer-Rokitansky-Küster-Hauser syndrome and 3 (7.1%) had a prior hysterectomy. Twenty-eight (66.7%) UTx recipients developed postoperative vaginal strictures with a median time to stricture of 33 days (interquartile range 19-53 days). Most strictures were of moderate severity, with 4 (14.3%) strictures categorized as grade 1, 19 (67.9%) as grade 2, and 5 (17.9%) as grade 3. History of Mayer-Rokitansky-Küster-Hauser syndrome and preoperative recipient vaginal length were significant risk factors for stricture, after adjustment for donor and recipient age and body mass index, anastomosis technique, total ischemia time, center, and year. Patients with longer preoperative vaginal length had a lower risk of stricture (hazard ratio 0.45, 0.29-0.70). The severity grading of the stricture was associated with the effectiveness of a nonoperative treatment approach (grade 1 vs. grade 3). No patients with grade 3 strictures improved with self-dilation alone; all required surgical repair and/or dilation under anesthesia. Conversely, for grade 1 or 2 strictures, self-dilation alone was successful in 47.8% (11/23), and no grade 1 strictures required surgical repair., Conclusions: Vaginal stricture is a common postoperative complication after UTx, affecting >65% of recipients. Short preoperative vaginal length and history of müllerian agenesis in the recipient are significant risk factors. Vaginal self-dilation was effective for some mild to moderate strictures, although dilation under anesthesia or surgical repair was required in most cases., Clinical Trial Registration Numbers: Dallas UtErus Transplant Study (DUETS) at Baylor University Medical Center (NCT02656550), Uterine transplantation for the treatment of uterine factor infertility at the Cleveland Clinic (NCT02573415), The University of Pennsylvania Uterus Transplant for Uterine Factor Infertility Trial (UNTIL) (NCT03307356)., Competing Interests: Declaration of Interests L.Z. has nothing to disclose. L.A.H. has nothing to disclose.P.M.P. G.T. has nothing to disclose. S.A. has nothing to disclose. J.R.W. has nothing to disclose. M.R. has nothing to disclose. C.A.F. has nothing to disclose. K.O. has nothing to disclose. E.G.R. has nothing to disclose., (Copyright © 2024 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Pelvic organ prolapse (POP), characterised by the downward displacement of pelvic organs, is a prevalent disorder that affects adult women. This study explored the therapeutic potential of PX-478, a selective hypoxia-inducible factor-1α (HIF-1α) inhibitor, in a murine POP model., Methods: A murine POP model was established through ovariectomy, mimicking oestrogen deprivation. Fifteen C57BL/6J mice were randomly assigned to control, POP, and PX-478 groups. PX-478, targeting HIF-1α, was administered intravaginally. The analysis of fibroblasts, macrophage and inflammation was performed through Masson staining, immunofluorescence, and ELISA. Collagen distribution was assessed using Sirius Red staining. Expression levels of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMP-1) were determined through immunohistochemistry and western blot. Fibroblast proliferation and apoptosis were evaluated by CCK-8 assay and flow cytometry., Results: PX-478 treatment significantly reduced vaginal length, indicating a therapeutic effect on POP severity. Masson staining revealed reduced fibrotic changes and collagen disruption in PX-478-treated mice. Immunofluorescence showed increased fibroblast markers (Vimentin, α-SMA) and collagen fibres by PX-478. Sirius Red staining indicated PX-478 mitigated damage to Type I and Type III collagen fibres. PX-478 significantly reduced MMP-2 and MMP-9 expression while increased TIMP-1. In macrophages, PX-478 decreased M1 and M2 markers (CD80, CD206) and IL-18 secretion. Fibroblasts exhibited increased proliferation, reduced apoptosis, and altered MMP/TIMP expression under PX-478 influence., Conclusion: PX-478 demonstrates a therapeutic potential in the mice POP model. It reduces vaginal length, attenuates fibrosis, and modulates collagen synthesis. Its immunomodulation is evident through reduced M1 and M2 macrophages and suppressed IL-18 secretion.

To accurately measure the vaginal mucosa thickness across different age groups using histopathologic techniques and investigate the factors that may influence the thickness changes. This study aims to provide clinicians with objective evidence of variations in vaginal mucosal thickness, facilitating personalized medical decisions for patients. A retrospective analysis was conducted on clinical data from 348 patients who underwent local vaginal wall resection at the West China Second University Hospital, Sichuan University, from January 2021 and May 2022. The thickness of vaginal mucosa, epithelium and lamina propria was measured precisely under the microscope. And the 10th, 25th, 50th, 75th, and 90th percentile values of vaginal mucosa thickness across different age groups were counted and charted a dot-line plot. The percentile values for vaginal mucosa thickness exhibited a decreasing trend with increasing age; vaginal mucosa thickness showed significant correlations with times of delivery (P = 0.031) and age (P < 0.001), both of which were negatively associated. And vaginal mucosa thickness demonstrated no significant correlation with body mass index (BMI) (P = 0.325), times of abortions (P = 0.511), times of gestation (P = 0.101), menstrual cycle (P = 0.533), or types of delivery (P = 0.056); epithelial thickness showed significant associations with age (P < 0.001) and types of delivery (P = 0.017), both of which were negative correlations. Moreover, BMI (P = 0.429), times of abortions (P = 0.764), delivery (P = 0.079), gestation (P = 0.475), and menstrual cycle (P = 0.950) were nonassociated with epithelial thickness; lamina propria thickness displayed a significant correlation only with age (P = 0.002), and there were no obvious correlations observed between lamina propria thickness and BMI (P = 0.374), times of abortion (P = 0.417), delivery (P = 0.053), gestation (P = 0.101), types of delivery (P = 0.132) and menstrual cycle (P = 0.495). Moreover, when the age segmentation was thresholded at 35 and 50 years, both epithelial thickness and vaginal mucosa thickness were significantly correlated with age (P < 0.05). Lamina propria thickness was associated with age when the age threshold was set at 35 years (P = 0.007), whereas it showed no strong link with age when the age threshold was 50 years (P = 0.072). This study has innovatively established percentile reference values for vaginal mucosa thickness based on histopathology, furnishing clinicians with objective evidence of variations in vaginal mucosal thickness to facilitate personalized medical decisions for patients. The findings demonstrated a strong link between vaginal mucosa thickness and age, with epithelium likely playing a predominant role, while the association with lamina propria appeared to be less significant. Further research involving a larger sample size is warranted to elucidate the potential relationship with the lamina propria., (© 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).)

Sexual violence is a global issue affecting individuals regardless of their relationship to the perpetrator or the setting. Microscopic examination of spermatozoa from vaginal swabs is crucial in investigating cases of sexual intercourse to determine the time of the crime. Factors such as vaginal pH and neutrophil count influence the motility and persistence of spermatozoa in the vagina, particularly in conditions like candidiasis, highlighting the need for further research in this area. This study aimed to determine the effect of pH and neutrophil count on the motility and persistence of spermatozoa in the vagina with candidiasis. An experimental study was conducted using white rats ( Rattus norvegicus ) of the Wistar strain, with four male rats providing spermatozoa samples and 32 female rats receiving treatment. The female rats were divided into two groups: the normal group and the candidiasis model group. In both groups, the female rats were given vaginal insemination of spermatozoa. Variables measured included pH, neutrophil count, motility, and persistence of spermatozoa in the vagina. Data were analyzed using the Mann-Whitney test, followed by the Spearman correlation test. The findings revealed that spermatozoa motility lasted up to three minutes in normal rats, whereas in the candidiasis model, it was reduced to two minutes. Additionally, spermatozoa persistence in the vagina lasted up to six days in the normal group compared to up to three days in the candidiasis model. There were significant differences in pH, neutrophil count, motility, and persistence of spermatozoa in the vagina between the normal group and the candidiasis model (all had p <0.001). There was a correlation between pH and neutrophil count with the motility and persistence of spermatozoa in the rat's vagina ( p <0.001). In conclusion, vaginal pH and neutrophil count influence the motility and persistence of spermatozoa in the vagina of candidiasis rat models., Competing Interests: All the authors declare that there are no conflicts of interest., (© 2024 The Author(s).)

Objective: The aim of the study was to investigate the effectiveness of intravaginal Er:YAG laser for treating atrophic vaginitis in postmenopausal women utilizing shear wave elastography., Methods: In this prospective randomized sham-controlled double-blind pilot study, 20 participants were included (laser group [n = 12] / sham-control group [n = 8]). A nonablative (Smooth mode) Er:YAG laser with a wavelength of 2,940 nm was used. Objective evaluation of laser treatment efficacy was conducted using a special ultrasonic technique: shear wave elastography. Ultrasonic velocity measurements were taken from the anterior and posterior vaginal walls. Mean elasticity (E mean ) was expressed in kilopascals (kPa). Additional outcome parameters were vaginal pH, Vaginal Health Index (VHI), Female Sexual Function Index (FSFI), and visual analog scale (VAS) scores for dyspareunia., Results: Baseline clinical characteristics, vaginal pH, VHI, VAS and FSFI scores, and E mean values were comparable between the laser and sham-control groups. Statistically significant differences were observed in the final E mean values of the anterior vaginal wall (13.1 ± 6.3 vs 20.0 ± 3.3 kPA, P = 0.01) and posterior vaginal wall (12.7 ± 10.3 vs 19.4 ± 6.9 kPA, P = 0.04) between the laser and sham-control group. Despite comparable baseline E mean values, significant differences in vaginal wall stiffness posttreatment indicated a notable increase in tissue elasticity following laser treatment. Statistically significant differences were also observed in final vaginal pH values, VHI, VAS scores, and FSFI score improvement in favor of laser treatment., Conclusions: Shear wave elastography may be considered as a reliable and objective technique for evaluating the efficacy of Er:YAG laser treatment in women with atrophic vaginitis. However, additional studies with larger sample sizes are necessary to establish conclusive evidence., Competing Interests: Financial disclosure/conflicts of interest: None reported., (Copyright © 2024 by The Menopause Society.)

Background: Despite the gold standard treatment for genitourinary syndrome of menopause (GSM) is based on the use of local or systemic estrogen-containing products, the typical long-term side effects of hormonal treatments and, most importantly, the contraindications in patients with history of breast and endometrial neoplasms do limit in some extent its use. As hyaluronic acid and some highly purified botanicals have clearly demonstrated their anti-inflammatory and mucosa-protecting properties, we have tested, in women with GSM, a class II vaginal medical device containing hyaluronate gel and a mucoadhesive active enriched with purified alkylamides from Zanthoxylum bungeanum, triterpenes from Centella asiatica and high molecular weight polysaccharides from Tamarindus indica., Methods: Our single-center, open-label, prospective and observational study was conducted on 50 menopausal women enrolled at the Department of Maternal-Fetal Medicine at Umberto I Polyclinic Hospital in Rome, Italy. Gel administration lasted 150 days and was performed daily for the first 12 days and every 48 hours for the remaining 138 days. Clinical evaluations were performed at baseline and after 12, 57 and 150 days. Besides product safety, main outcomes of our study were: 1) vaginal health (by Vaginal Health Index score [VHI]); 2) sexual quality of life (by Female Sexual Distress Scale [FSDS]); and 3) percentage of women declaring regular sexual activity., Results: The product was safe with no specific adverse events reported. It significantly improved VHI (about 5% after 57 days and 8% after 150 days), FSDS (about 7% after 57 days and 10% after 150 days), and sexual activity (about 20% after 150 days). It also reduced dryness, dyspareunia, burning, itching, and dysuria incidence, respectively by about 18%, 14%, 14%, 27% and 11% after 150 days., Conclusions: In women with GSM, the intravaginal administration of a hyaluronate-based gel enriched with purified botanical actives endowed with anti-inflammatory and mucosal-protecting properties, reduced painful sensation during sexual acts and increased regular sexual activity.

Purpose: Tumors affecting the female genital tract and their treatments have the potential to induce adverse modifications in vaginal health and impact personal aspects of patient's lives. Vulvovaginal atrophy is one of the morphological changes observed in individuals with a history of gynecological cancer, influenced both by the biological environment of tumors and the main therapeutic modalities employed. Therefore, the purpose of this study was to identify approaches to treat vulvovaginal atrophy while assessing the impact on the emotional and sexual health of women diagnosed with gynecological cancers., Methods: To achieve this goal, a systematic review was conducted following the methodological guidelines outlined by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The databases used for literature research were PubMed and Web of Science., Results: Initially, 886 articles were obtained. After eliminating duplicates and applying inclusion/exclusion criteria, seven articles were selected for analysis. The period of highest publication activity spanned from 2017 to 2020, with the majority conducted in Italy. Five treatment modalities were identified and categorized as vaginal suppository, oral medication, surgical procedure, CO2 laser therapy, and vaginal dilator. Twenty-four outcomes related to vaginal health and 30 outcomes related to overall, sexual, and emotional quality of life were analyzed., Conclusion: In general, all interventions demonstrated the ability to improve vaginal health or, at the very least, the sexual health of patients. Thus, despite limitations, all treatments have the potential to address vulvovaginal atrophy in patients with a history of gynecological cancer., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: This TRIPLE study was aimed to evaluate the efficacy of polycarbophil vaginal gel (PCV) in treating symptoms of vaginal atrophy (VA) of peri- and post-menopausal women., Materials and Methods: Sexually active women in peri- (n = 29) and post-menopause (n = 54) suffering from VA, were progressively enrolled and treated for 30 days with PCV. Those wishing to continue (n = 73) were treated for additional 180 days. PCV was administered as one application twice a week. The vaginal health index (VHI; range 5 to 25) and the visual analogue score (VAS range for 0 to 100 mm for each item) for vaginal dryness, irritation, and pain at intercourse, along with the global symptoms score (GSS; range 1 to 15) and treatment safety, were evaluated at baseline and after 30 days. In those continuing the treatment an evaluation was performed after additional 180 days., Results: Women in peri and post-menopause were of 48.7 ± 3.3 years and 57.5 ± 5.7 years old., respectively. At baseline all outcomes were significantly worse (p<0.002) in postmenopausal group, except the VHI (p < 0.056). After 30 days VHI increased (p < 0.001) of 4.1 ± 0.5 (mean ± SE), and 5.1 ± 0.4 in peri- and post-menopausal women respectively. VAS of vaginal dryness decreased (p < 0.001) of -24.4 ± 3.6, and -52.7 ± 2.6 (p < 0.001), VAS of irritation decreased (p<0.001) of -18.6 ± 4.4 and -47.8 ± 3.2, VAS of pain decreased (p < 0.001) of -26.2 ± 4.3 and -55.6 ± 3.1 and the GSS decreased (p < 0.001) of -3.9 ± 0.3, and -4.9 ± 0.2, in peri and post-menopausal women, respectively. All the modifications were significantly greater (p < 0.001)(p < 0.032 for GSS) in postmenopausal women, and after 30 days all outcomes were similar in the two groups of women. In comparison to baseline, after 210 days of treatment VHI increased of 7.7 ± 0.3 (p < 0.001), VAS of vaginal dryness decreased of -53.6 ± 1.9 (p < 0.001) VAS of irritation of -42.6 ± 1.4 (p < 0.001) VAS of pain of -46.7 ± 2.3 (p < 0.001) and the GSS of -6.5 ± 0.2 ± 0.2 (p < 0.001). All outcomes improved (p < 0.001) over the values observed after 30 days of treatment (p < 0.001). No side effect was reported., Conclusions: In peri- and post-menopausal women PCV administration rapidly improves VA symptoms, and its prolongation up to 6 months further increases its efficacy., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Angelo Cagnacci received a fee as invited speaker for Italfarmaco, Shionogi, Bayer, Gedon-Richter, Theramex, MSD and Exeltis. Dionisio Franco Barattini is employed at Opera CRO, the Contract Research Organization that managed the study. Elena Casolati is a medical consultant for Italfarmaco SpA. Alberto Pecoroni and Mario Mangrella are employed at Italfarmaco SpA. Serban Marius Rosu and Liviu Cristian Patrascu certifies that there is no conflict of interest with any financial organization regarding the material discussed in the manuscript., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: The demand for effective and safe treatments of genitourinary syndrome (GSM) in post-menopausal women (PMW) is growing. Published data on the efficacy and safety of ospemifene (OSP) prompt an updated literature review to enlighten possible improvements in the GSM treatment., Area Covered: We searched articles published in English from 2010 to 2023 through Medline (PubMed) and Embase databases with Boolean terms: OSP, PMW, GSM, endometrium, breast cancer, cardiometabolic syndrome, bone metabolism, adherence to treatment, and patient satisfaction. We selected randomized controlled trials (RCTs) and observational and cross-sectional studies and completed the search manually., Expert Opinion: Of the 157 retrieved records, 25 primary studies met the inclusion criteria (15 regarding efficacy and safety, two for additional effects, and four for adherence and satisfaction with the OSP treatment). Seven RCTs involved nearly 5,000 patients, 10 out of 18 prospective observational studies 563, and six retrospective analyses 356,439. Evidence of OSP treatment in PMW with GSM relies on RCTs and remarkable real-world data. The 25 primary studies showcased the high clinical response to symptoms, the favorable safety profile of OSP with very few adverse events, a neutral impact on the endometrium, breast, bone, and thrombosis, and the possible improvement of cardiovascular risk factors.

Objective: Vaginal natural orifice transluminal endoscopic surgery (vNOTES) is an emerging surgical procedure that combines the advantages of the vaginal approach with laparoscopic vision and instrumentation. Shorter hospitalization and lesser postoperative pain associated with vNOTES may be explained by the advantages of this innovative surgical approach (e.g., absence of abdominal incisions, shorter operative time, and lower insufflation pressure). Ovarian tissue cryopreservation allows to preserve reproductive and endocrine functions in young women with oncological disease at risk of premature ovarian insufficiency (POI) caused by gonadotoxic treatments. Ovarian tissue biopsy for cryopreservation consists of a large biopsy of 1 or both ovaries that is usually performed by laparoscopy. Then, the removed ovarian tissue is cryopreserved for the future transplant after cancer remission. The volume of ovarian biopsy ranges from 50% of the ovary for women at moderate risk of POI to 70%-100% of it for those at high risk. The inclusion criteria for ovarian tissue cryopreservation are women aged <35 years who cannot delay start of oncological treatments for follicle cryopreservation, with a moderate or high risk of POI and good chance of 5-year survival. Ovarian tissue cryopreservation cannot be performed if tumor treatments include uterine irradiation or for tumors at risk of ovarian metastases (as in the case of ovarian cancer, leukemia, neuroblastoma, or Burkitt lymphoma). Despite widespread adoption of vNOTES in gynecology, ovarian biopsy for cryopreservation has never been performed using this route., Design: Step-by-step explanation of the procedure with descriptive text and narrated video footage., Setting: Tertiary-level referral academic center., Patient(s): A 27-year-old patient recently diagnosed with low-grade follicular non-Hodgkin lymphoma was referred to our center for ovarian tissue cryopreservation before chemotherapy. The patient included in this study gave informed consent for publication of the video and posting of the video online including social media, the journal website, scientific literature websites (e.g., PubMed, ScienceDirect, and Scopus), and other applicable sites. Because of the nature of the study, institutional review board approval was not required., Intervention(s): Access to the peritoneal cavity was created by a 3-cm posterior colpotomy. The peritoneum was then opened using cold scissors and temporarily fixed to the posterior vaginal wall. The GelPOINT Mini Advanced Access Platform (Applied Medical, Rancho Santa Margarita, CA), with 1 10-mm and 2 5-mm trocars, was used as the vNOTES port. The inner Alexis ring of the GelPOINT was inserted through the colpotomy into the pouch of Douglas. A hysterometer was placed into the uterine cavity to keep the uterus anteverted during the surgery. A pneumoperitoneum was created to a pressure of 8 mm Hg, and the operating table was tilted to a 20° Trendelenburg position. A 10-mm rigid 30° camera was inserted in the inferior and larger trocar, and both ovaries were visualized. Seventy percent of the left ovary was removed with cold scissors to minimize trauma on the surgical specimen. After removal of the GelPOINT cap, ovarian biopsy was immediately picked up by the biologist of our fertility center. The ovary was coagulated with a bipolar instrument. The hysterometer was then replaced by a uterine manipulator to perform tubal patency test, and blue dye passage through both salpinges was observed. Finally, the Alexis retractor and stich on the posterior peritoneum were removed, and the vagina was sutured using interrupted stiches. The total operative time was 25 minutes., Main Outcomes Measure(s): Ovarian tissue biopsy for cryopreservation by vNOTES., Result(s): No intraoperative and postoperative complications were reported, and the patient was discharged after 24 hours from surgery., Conclusion(s): Vaginal natural orifice transluminal endoscopic surgery may be a feasible alternative approach to laparoscopy for ovarian tissue cryopreservation: it allows an easy access to the ovaries and removal of different tissue volumes. Patients undergoing ovarian cryopreservation may benefit from the vNOTES approach because a rapid postoperative recovery is crucial to start chemotherapy in a short time. As for other vNOTES procedures, accurate selection of patients seems to be crucial for a successful ovarian tissue cryopreservation. We believe that the inclusion and exclusion criteria reported for other gynecologic procedures performed through vNOTES may also be valid for ovarian tissue cryopreservation by vNOTES. Women at high risk of pelvic adhesions (e.g., coexistent endometriosis, previous pelvic surgery, or inflammatory pelvic disease), those with an increased body mass index or enlarged uterus, and those with cervical, vaginal, or uterine cancer cannot be considered for this approach because all these factors are associated with failure of vNOTES. On the other hand, women with no history of surgery, endometriosis, and large myomas may benefit from the vNOTES approach, and these women represent most of patients who undergo ovarian tissue cryopreservation. Further and larger studies are needed to assess the efficacy and safety of this new approach., Competing Interests: Declaration of Interests R.S. has nothing to disclose. M.M. has nothing to disclose. E.P. has nothing to disclose. A.R. has nothing to disclose. R.V. has nothing to disclose. S.S. has nothing to disclose. V.B. has nothing to disclose. D.R. has nothing to disclose., (Copyright © 2024 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Abnormal cervical cytology is commonly observed in women with human immunodeficiency virus (WWH)., Methods: A cross-sectional study was conducted with 130 WWH and 147 age-matched healthy controls, who underwent gynecological examinations at Beijing Ditan Hospital. The presence of abnormal cervical cytology in WWH was predicted after performing a logistic regression analysis., Results: Multivariate logistic regression revealed 3 independent factors, among which CD4 cell count ≥350 cells/μL was the protective factor, while human papillomavirus infection and abnormal vaginal pH were the risk factors., Conclusions: Vaginal microecological disorders can increase the risk of abnormal cervical cytology in WWH., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To investigate the biological safety of commercially available natural rubber latex and synthetic polyurethane condoms., Methods: Natural rubber latex condom brands of A1 and A2 and polyurethane condom brands of B1 and B2 were purchased from large chain pharmacies in Chengdu, with three packages randomly selected for each brand. The study assessed the toxic effects of condom extracts on L-929 mouse fibroblasts according to GB/T standards. Gross observation and histopathological evaluation were conducted to assess the irritation reactions of condoms on the vagina and penis of rabbits (3 rabbits were used for each brand), as well as their sensitization effects on guinea pig skin. Additionally, the impact of continuous perfusion of condom extracts of the vaginas of SD rats for 30 days on their reproductive systems was evaluated, following GB/T standards (5 rats were used for each brand)., Results: Extracts from natural rubber latex condom brands A1 and A2, at concentrations of 100% and 50%, exhibited significant cytotoxicity, with optical density (OD) values being significantly lower than those of the blank control group and the polyurethane condom brands B1 and B2 ( P <0.01). There was no significant difference in cell morphology and OD values between the extracts of B1 and B2 and the blank control group ( P >0.05). Vaginal congestion was found in 3 rabbits from A1 group and 1 rabbit from the A2 group, while no obvious congestion was noted in rabbits from the B1 and the B2 groups. Histopathological examination showed scattered inflammatory cell infiltration in the vaginal tissue of 3 rabbits from the A1 group and 2 rabbits from the A2 group, and slight congestion in the blood vessels of the lamina propria. No obvious pathological changes were observed in the vaginal tissue of polyurethane brand rabbits. Two rabbits from the A1 group and 1 rabbit from the A2 group showed transient and mild erythema on the penis during the experiment. Histopathological examination showed that 1 rabbit from A1 group had small foci of pericapillary lymphocytes in the dermis of the penis, while no significant pathological changes were observed in the penile tissue of A2, B1, and B2 groups. After 30 days of continuous vaginal perfusion with condom extract, 3 rats in A1 group and 2 rats in the A2 group had uterine congestion, with the degree of congestion being lower in the A2 group. No significant congestion or pathological changes were observed in the vaginal and penile tissues of rabbits, or in the uterine tissues of rats from the polyurethane groups. None of the 4 groups of guinea pigs showed significant skin allergic reactions to the condom extracts., Conclusion: Significant differences in biosafety exist among condoms of various materials and brands. To ensure product safety, it is crucial to strengthen quality control and regulatory oversight after condoms become commercially available., Competing Interests: 利益冲突　所有作者均声明不存在利益冲突, (© 2024《四川大学学报（医学版）》编辑部 版权所有Copyright ©2024 Editorial Office of Journal of Sichuan University (Medical Sciences).)

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.)

Purpose: Endometrial cancer is highly prevalent and lacking noninvasive diagnostic techniques. Diagnosis depends on histological investigation of biopsy samples. Serum biomarkers for endometrial cancer have lacked sensitivity and specificity. The objective of this study was to investigate the cervicovaginal environment to improve the understanding of metabolic reprogramming related to endometrial cancer and identify potential biomarker candidates for noninvasive diagnostic and prognostic tests., Experimental Design: Cervicovaginal lavages were collected from 192 participants with endometrial cancer (n = 66) and non-malignant conditions (n = 108), and global untargeted metabolomics was performed. Using the metabolite data (n = 920), we completed a multivariate biomarker discovery analysis., Results: We analyzed grade 1/2 endometrioid carcinoma (n = 53) and other endometrial cancer subtypes (n = 13) to identify shared and unique metabolic signatures between the subtypes. When compared to non-malignant conditions, downregulation of proline (P < 0.0001), tryptophan (P < 0.0001), and glutamate (P < 0.0001) was found among both endometrial cancer groups, relating to key hallmarks of cancer including immune suppression and redox balance. Upregulation (q < 0.05) of sphingolipids, fatty acids, and glycerophospholipids was observed in endometrial cancer in a type-specific manner. Furthermore, cervicovaginal metabolites related to tumor characteristics, including tumor size and myometrial invasion., Conclusions: Our findings provide insights into understanding the endometrial cancer metabolic landscape and improvement in diagnosis. The metabolic dysregulation described in this article linked specific metabolites and pathophysiological mechanisms including cellular proliferation, energy supply, and invasion of neighboring tissues. Furthermore, cervicovaginal metabolite levels related to tumor characteristics, which are used for risk stratification. Overall, development of noninvasive diagnostics can improve both the acceptability and accessibility of diagnosis., (©2024 The Authors; Published by the American Association for Cancer Research.)

Background: Sex reassignment surgery (SRS) is a necessary step in transitioning into the desired gender for male-to-female transgender individuals. This study focuses on a rare complication developed following SRS, aiming to highlight potential complications associated with this procedure., Case Presentation: This report describes a 49-year-old transgender woman with a history of SRS who developed bloody diarrhea and neovaginal bleeding 10 years later. A colonoscopy revealed features compatible with ulcerative colitis, which was confirmed by a biopsy., Conclusions: The unpredictable clinical course of this phenomenon may prompt surgeons to reconsider the use of a rectosigmoid colon to create a neovagina. This case report underscores the necessity of long-term monitoring for gastrointestinal complications in transgender women post-SRS when a rectosigmoid colon segment is utilized for neovaginal construction., (© 2024. The Author(s).)

Background: Endometriosis, a complex gynecological condition, involves inflammation and immune dysregulation. The vaginal microbiota, characterized by its diversity, is an integral part of the vaginal microecology-interacting with vaginal anatomy, the endocrine system, and local mucosal immunity. Imbalances in this microecology are known to precipitate various inflammatory diseases. Despite extensive research, the connection between vaginal microbiota dysbiosis and endometriosis remains a subject of debate. Our study assesses the association between vaginal microecology dysbiosis and endometriosis., Methods: We systematically searched major electronic databases in English, including Embase, PubMed, The Cochrane Library, MEDLINE (Ovid), BIOSIS (Ovid), China National Knowledge Infrastructure (CNKI), and Wanfang, up to August 15, 2023. Selected articles underwent screening based on predefined inclusion and exclusion criteria. Normal vaginal microecology was defined as a negative Amsel/Spiegel test or Nugent score of 0-3, or Lactobacillus predominance determined by 16S rRNA gene amplification sequencing. Deviations from this norm were classified as dysbiosis, further categorized into bacterial vaginosis (BV) and intermediate BV. Data analysis utilized Revman 5.4, with effect sizes presented as Odds Ratios (OR) and 95% Confidence Intervals (CI)., Results: Out of 1081 articles, eight met the inclusion criteria. Utilizing fixed-effect models due to low heterogeneity, the analysis revealed a positive association between dysbiosis and endometriosis (OR = 1.17, 95% CI 0.81-1.70; I2 = 0%), but showed a slight negative association between normal vaginal microecology with endometriosis (OR = 0.90, 95% CI 0.55-1.46; I2 = 29%). However, the association was not significant. Subgroup and sensitivity analyses corroborated the stability of these associations., Conclusion: A positive correlation exists between vaginal microecology dysbiosis and endometriosis, notably with intermediate BV. However, the mechanisms underpinning this relationship remain elusive, highlighting the need for further research to overcome limitations., Trial Registration: Registration number: CRD42023445163., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Qing et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Rationale and Objectives: This study aimed to determine the feasibility of using the deep learning (DL) method to determine the degree (whether myometrial invasion [MI] >50%) of MI in patients with endometrial cancer (EC) based on ultrasound (US) images., Materials and Methods: From September 2017 to April 2023, 1289 US images of 604 patients with EC who underwent surgical resection at center 1, center 2 or center 3 were obtained and divided into a training set and an internal validation set. Ninety-five patients from center 4 and center 5 were randomly selected as the external testing set according to the same criteria as those for the primary cohort. This study evaluated three DL models trained on the training set and tested them on the validation and testing sets. The models' performance was analyzed based on accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve (AUC), and the performance of the models was subsequently compared with that of 15 radiologists., Results: In the final clinical diagnosis of MI in patients with EC, EfficientNet-B6 showed the best performance in the testing set in terms of area under the curve (AUC) [0.814, 95% CI (0.746-0.882]; accuracy [0.802, 95% CI (0.733-0.855]; sensitivity [0.623]; specificity [0.879]; positive likelihood ratio (PLR) [6.750]; and negative likelihood ratio (NLR) [0.389]. The diagnostic efficacy of EfficientNet-B6 was significantly better than that of the 15 radiologists, with an average diagnostic accuracy of 0.681, average AUC of 0.678, AUC of the best performance of 0.739, accuracy of 0.716, sensitivity of 0.806, specificity 0.672, PLR2.457, and NLR 0.289., Conclusion: Based on the preoperative US images of patients with EC, the DL model can accurately determine the degree of endometrial MI; the performance of this model is significantly better than that of radiologists, and it can effectively assist in clinical treatment decisions., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Xiachuan Qin reports financial support was provided by the Nanchong school science and technology strategic cooperation project (19SXHZ0165), Science and Technology Plan Project of Nanchong City (22JCYJPT0004) and Xiaoling Liu reports financial support was provided by the Nanchong Social Science Federation 14th Five-Year planning project (NC23B001)., (Copyright © 2024 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Objective: To test the diagnostic concordance between microscopic (MI) and digital (DG) observation of cervico-vaginal (CV) cytology in a validation study of the technique., Methods: Five cytotechnologists (CT) reviewed 888 routine CV cytology cases from the Cervical Pathology Unit of our center over a 2-week period of time. The cases were first observed by MI and at the end of the day the cases were observed by DG., Statistical Analysis Used: Agreement calculated using the Kappa index., Results: Most of the diagnoses corresponded to benign (64%) or inflammatory conditions (14%) and 24% corresponded to the intraepithelial lesion or malignancy (ILM) category. The overall kappa coefficient of concordance was strong (0.87). Among the different CTs it was almost perfect in two, strong in two and moderate in one. In 18 cases (10%) there were discrepancies between techniques in the category of ILM. In 10 (56%) cases there was an overdiagnosis in DG and in 8 (44%) an overdiagnosis in MI. Only in two cases, the diagnostic discrepancy exceeded one degree of difference between lesions, and they were ASCUS or AGUS for DG and CIN 2 for MI., Conclusions: In this validation test in which routine cases during a two-week period have been used, observing the cases with both techniques on the same day, we have obtained a strong degree of concordance. The discordances obtained have not been considered relevant., (Copyright © 2024 Sociedad Española de Anatomía Patológica. Publicado por Elsevier España, S.L.U. All rights reserved.)

Problem: Vulvovaginal candidiasis (VVC) is a common mucosal fungal infection, and Candida albicans is the main causative agent. The NLRP3 inflammasome plays an important role in VVC, but the underlying mechanism is unknown., Method of Study: Vaginal epithelial cells were divided into three groups: control, C. albicans strain SC5314 (wild-type, WT), and WT+ Matt Cooper Compound 950 (MCC950, a specific NLRP3 inhibitor). After human vaginal epithelial cells were pretreated with 1 µmol/L MCC950 for 2 h, C. albicans (MOI = 1) was cocultured with the human vaginal epithelial cells for 12 h. The cell supernatants were collected, LDH was detected, and the IL-1β and IL-18 levels were determined by ELISA. The expression of the pyroptosis-related proteins NLRP3, Caspase-1 p20 and GSDMD was measured by Western blotting analysis. The protein expression of the pyroptosis-related N-terminus of GSDMD (GSDMD-N) was detected by immunofluorescence., Results: In this study, we showed that the WT C. albicans strain induced pyroptosis in vaginal epithelial cells, as indicated by the LDH and proinflammatory cytokine levels and the upregulated levels of the pyroptosis-related proteins NLRP3, Caspase-1 p20, and GSDMD-N. MCC950 reversed the changes in the expression of these proteins and proinflammatory cytokines in vaginal epithelial cells., Conclusion: C. albicans activated the NLRP3 inflammasome to induce vaginal epithelial cell pyroptosis. MCC950 inhibited the NLRP3 inflammasome, reduced vaginal epithelial cell pyroptosis, and decreased the release of inflammatory cytokines., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: The efficacy and tolerability of a non-hormonal pessary (that forms an oil-in-water emollient with the vaginal fluid) were assessed for the treatment of symptoms of vaginal dryness associated with menopause., Study Design: Seventy-nine postmenopausal women (mean age 60.8 ± 6.5 years) with mild to moderate symptoms of vaginal dryness (including dyspareunia) were enrolled in this open-label, prospective, post-market clinical follow-up trial, conducted in 2022 by one research center in Germany. The investigational pessary was applied for the first 7 days once daily and the subsequent 31 days twice a week, at bedtime. A treatment-free period of 6 days completed the trial., Main Outcome Measures: During the trial, participants filled out questionnaires that enabled the calculation of a total severity score for subjective symptoms of atrophy-related vaginal dryness and impairment of daily as well as sexual life. Furthermore, vaginal health index and safety were studied., Results: A rapid and significant reduction in the severity scores for symptoms was observed over the 38-day course of treatment and beyond. Quality of life assessed by DIVA (day-to-day impact of vaginal aging) questionnaire, dyspareunia and vaginal health index also clearly improved. The tolerability was mainly rated as "good to very good" by the investigator and 94.9 % of participants. The vast majority were very satisfied with the simple and pleasant handling. No serious adverse events occurred., Conclusion: Overall, the presented data suggest that the investigated non-hormonal pessary is an effective and well tolerated treatment option for vaginal symptoms associated with dryness, thus improving quality of life for women, even those who are sexually active., Clinicaltrials: gov identifier NCT05211505., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: all authors are employees of Dr. August Wolff GmbH & Co. KG Arzneimittel, 33611 Bielefeld, Germany., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Studies on the changes of extracellular matrix (ECM) in pelvic organ prolapse (POP) are still controversial., Objective: To identify the changes in the ECM in POP patients., Search Strategy: Comprehensive searching in Embase, PubMed, Web of Science and the Cochrane Library was carried out until 23 February 2023., Selection Criteria: Studies comparing the protein levels of ECM-related components between women with and without POP., Data Collection and Analysis: Quality and risk of bias were assessed using the Agency for Healthcare Research and Quality assessment. Indicators were pooled with random or fixed effect meta-analysis based on heterogeneity and sub-grouped analysed by the biopsy site., Main Results: Thirty cross-sectional studies were included, comprising 840 POP cases and 755 controls. Overall results showed that the expression of type III collagen (COLIII) and several matrix metalloproteinases (MMP-1, -2 and -9) were increased, whereas those of type I collagen (COLI), and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) were decreased in patients with POP. Subgroup analysis showed that the expression of COLIII in the anterior vaginal wall (AVW) and COLIII, MMP-2 and -9 in the uterosacral ligament (USL) were consistent with the overall results. However, the expression of COLI and MMP-1 in the AVW showed no difference and the expression of COLI and MMP-1 in the USL is still controversial based on current studies., Conclusions: Patients with POP have lower expression of COLI and TIMP-1 and higher expression of COLIII and MMPs compared with non-POP cases, but further studies are required to investigate in specified anatomical sites., (© 2024 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

Objective: Vaginal dryness is an important factor influencing sexual function in women with primary Sjögren syndrome (pSS). Previous studies showed a higher degree of inflammation in vaginal biopsies from patients with pSS compared to non-pSS controls. However, the molecular pathways that drive this inflammation remain unclear. Therefore, the aim of this study was to investigate inflammatory pathway activity in the vaginal tissue of patients with pSS., Methods: Vaginal biopsies of 8 premenopausal patients with pSS experiencing vaginal dryness and 7 age-matched non-pSS controls were included. Expression of genes involved in inflammation and tissue homeostasis was measured using NanoString technology and validated using TaqMan Real-Time PCR. Vaginal tissue sections were stained by immunohistochemistry for myxovirus resistance protein 1 (MxA) and CD123 (plasmacytoid dendritic cells [pDCs])., Results: The most enriched pathway in vaginal biopsies from patients with pSS compared to non-pSS controls was the interferon (IFN) signaling pathway ( P < 0.01). Pathway scores for Janus kinase and signal transducer and activator of transcription (JAK-STAT) and Notch signaling were also higher ( P < 0.01 for both pathways). Conversely, transforming growth factor-β signaling and angiogenesis pathway scores were lower in pSS ( P = 0.02 and P = 0.04, respectively). Differences in IFN signaling between patients with pSS and non-pSS controls were confirmed by PCR and MxA tissue staining. No CD123+ pDCs were detected in vaginal biopsies. IFN-stimulated gene expression levels correlated positively with CD45+ cell numbers in vaginal biopsies and serum anti-SSA/Ro positivity., Conclusion: Upregulation of IFN signaling in vaginal tissue of women with pSS, along with its association with tissue pathology, suggests that IFNs contribute to inflammation of the vaginal wall and potentially also to clinical symptomatology (ie, vaginal dryness)., (Copyright © 2024 by the Journal of Rheumatology.)

Background: There are varying reports of immunohistochemically detected prostatic marker protein distribution in glands associated with the female urethra that may be related to tissue integrity at the time of fixation., Aim: In this study we used tissue derived from rapid autopsies of female patients to determine the distribution of glandular structures expressing prostate-specific antigen (PSA) and prostate-specific acid phosphatase (PSAP) along the female urethra and in surrounding tissues, including the anterior vaginal wall (AVW)., Methods: Tissue blocks from 7 donors that contained the entire urethra and adjacent AVW were analyzed. These tissue samples were fixed within 4-12 hours of death and divided into 5-mm transverse slices that were paraffin embedded. Sections cut from each slice were immunolabeled for PSA or PSAP and a neighboring section was stained with hematoxylin and eosin. The sections were reviewed by light microscopy and analyzed using QuPath software., Observations: In tissue from all donors, glandular structures expressing PSA and/or PSAP were located within the wall of the urethra and were present along its whole length., Results: In the proximal half of the urethra from all donors, small glands expressing PSAP, but not PSA, were observed adjacent to the and emptying into the lumen. In the distal half of the urethra from 5 of the 7 donors, tubuloacinar structures lined by a glandular epithelium expressed both PSA and PSAP. In addition, columnar cells at the surface of structures with a multilayered transitional epithelium in the distal half of the urethra from all donors expressed PSAP. No glands expressing PSA or PSAP were found in tissues surrounding the urethra, including the AVW., Clinical Implications: Greater understanding of the distribution of urethral glands expressing prostatic proteins in female patients is important because these glands are reported to contribute to the female sexual response and to urethral pathology, including urethral cysts, diverticula, and adenocarcinoma., Strengths and Limitations: Strengths of the present study include the use of rapid autopsy to minimize protein degradation and autolysis, and the preparation of large tissue sections to demonstrate precise anatomical relations within all the tissues surrounding the urethral lumen. Limitations include the sample size and that all donors had advanced malignancy and had undergone previous therapy which may have had unknown tissue effects., Conclusion: Proximal and distal glands expressing prostate-specific proteins were observed in tissue from all donors, and these glands were located only within the wall of the urethra., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society of Sexual Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background and Objectives: Postmenopausal vaginal discomfort is often attributed to vulvovaginal atrophy (VVA). Women with VVA experience symptoms such as vaginal dryness, itching, burning, irritation, and dyspareunia. Materials and Methods: This pilot study was conducted to assess the effects of a micro-ablative fractional CO 2 laser on the clinical symptoms of VVA, as well as concordant sexual function. The severity of VVA symptoms was evaluated by a visual analogue scale (VAS), while the condition of the vaginal mucosa was evaluated using the Vaginal Health Index Score (VHSI). Sexual function was evaluated using the Female Sexual Function Index (FSFI) Questionnaire. Results: Our cohort included 84 sexually active postmenopausal women with bothersome VVA, leading to sexual health complaints. The mean age of the participants in our study was 55.2 ± 5.4 years, with an average postmenopausal period of 6 ± 4.8 years. The age of our patients and the length of their postmenopausal period exhibited a significant negative correlation with VHSI scores, while a longer postmenopausal period was associated with increased severity of vaginal dryness and dyspareunia. Baseline VHSI values showed that 65% of patients had atrophic vaginitis with pronounced VVA symptoms (70.2% experienced vaginal itching, 73.8% reported vaginal burning, 95.3% had vaginal dryness, and 86.1% suffered from dyspareunia). Lower VHSI values significantly correlated with lower FSFI scores, while more severe VVA symptoms scores correlated with lower FSFI scores. VVA symptoms were significantly less severe after treatment. VHIS regained high non-atrophic values in 98.8% of patients post-treatment ( p < 0.001). FSFI total and domain scores were significantly higher after treatment ( p < 0.001). Conclusions: Our study revealed that fractional CO 2 laser is a useful treatment option to alleviate VVA symptoms and improve vaginal health and sexual functioning in postmenopausal women.

Objective: The vaginal microbiota dysbiosis induces inflammation in the uterus that triggers tissue damage and is associated with preterm birth. Progesterone is used to prevent labor in pregnant women at risk of preterm birth. However, the mechanism of action of progesterone still needs to be clarified. We aimed to show the immunomodulatory effect of progesterone on the inflammation of uterine tissue triggered by dysbiotic vaginal microbiota in a pregnant mouse model., Methods: Healthy (n = 6) and dysbiotic (n = 7) vaginal microbiota samples isolated from pregnant women were transferred to control (n = 10) and dysbiotic (n = 14) pregnant mouse groups. The dysbiotic microbiota transferred group was treated with 1 mg progesterone (n = 7). Flow cytometry and immunohistochemistry analyses were used to evaluate inflammatory processes. Vaginal microbiota samples were analyzed by 16 S rRNA sequencing., Results: Vaginal exposure to dysbiotic microbiota resulted in macrophage accumulation in the uterus and cellular damage in the placenta. Even though TNF and IL-6 elevations were not significant after dysbiotic microbiota transplantation, progesterone treatment decreased TNF and IL-6 expressions from 49.085 to 31.274% (p = 0.0313) and 29.279-21.216% (p = 0.0167), respectively. Besides, the macrophage density in the uterus was reduced, and less cellular damage in the placenta was observed., Conclusion: Analyzing the vaginal microbiota before or during pregnancy may support the decision for initiation of progesterone therapy. Our results also guide the development of new strategies for preventing preterm birth., (© 2024. The Author(s).)

Objective: This study aimed to establish the dose-response relationship between volume base dose and tumor local control for vaginal cancer, including primary vaginal cancer and recurrent gynecologic malignancies in the vagina., Materials and Methods: We identified studies that reported volume base dose and local control by searching the PubMed, the Web of Science, and the Cochrane Library Database through August 12, 2023. The regression analyses were performed using probit model between volume based dose versus clinical outcomes. Subgroup analyses were performed according to stratification: publication year, country, inclusion time of patients, patients with prior radiotherapy, age, primaries or recurrent, tumor size, concurrent chemoradiotherapy proportion, dose rate, image modality for planning, and interstitial proportion., Results: A total of 879 patients with vaginal cancer were identified from 18 studies. Among them, 293 cases were primary vaginal cancer, 573 cases were recurrent cancer in the vagina, and 13 cases were unknown. The probit model showed a significant relationship between the HR-CTV (or CTV) D90 versus the 2-year and 3-year local control, P values were 0.013 and 0.014, respectively. The D90 corresponding to probabilities of 90% 2-year local control were 79.0 Gy EQD2,10 (95% CI: 75.3-96.6 Gy EQD2,10 )., Conclusions: A significant dependence of 2-year or 3-year local control on HR-CTV (or CTV) D90 was found. Our research findings encourage further validation of the dose-response relationship of radical radiotherapy for vaginal cancer through protocol based multicenter clinical trials., (© 2024. The Author(s).)

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., (© 2024 The Author(s). Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Objective: The aim of this study was to demonstrate whether lasofoxifene improves vaginal signs/symptoms of genitourinary syndrome of menopause., Methods: Two identical, phase 3 trials randomized postmenopausal women with moderate to severe vaginal symptoms to oral lasofoxifene 0.25 or 0.5 mg/d, or placebo, for 12 week. Changes from baseline to week 12 in most bothersome symptom, vaginal pH, and percentages of vaginal parabasal and superficial cells were evaluated. These coprimary endpoints were analyzed using analysis of covariance, except superficial cells, which were analyzed by the nonparametric, rank-based Kruskal-Wallis test., Results: The two studies enrolled 444 and 445 women (mean age, ~60 y), respectively. Coprimary endpoints at week 12 improved with lasofoxifene 0.25 and 0.5 mg/d greater than with placebo ( P < 0.0125 for all). Study 1: most bothersome symptom (least square mean difference from placebo: -0.4 and -0.5 for 0.25 and 0.5 mg/d, respectively), vaginal pH (-0.65, -0.58), and vaginal superficial (5.2%, 5.4%), and parabasal (-39.9%, -34.9%) cells; study 2: most bothersome symptom (-0.4, -0.5), vaginal pH (-0.57, -0.67), and vaginal superficial (3.5%, 2.2%) and parabasal (-34.1%, -33.5%) cells. Some improvements occurred as early as week 2. Most treatment-emergent adverse events were mild or moderate and hot flushes were most frequently reported (lasofoxifene vs placebo: 13%-23% vs 9%-11%). Serious adverse events were infrequent and no deaths occurred., Conclusions: In two phase 3 trials, oral lasofoxifene 0.25 and 0.5 mg/d provided significant and clinically meaningful improvements in vaginal signs/symptoms with a favorable safety profile, suggesting beneficial effects of lasofoxifene on genitourinary syndrome of menopause., Competing Interests: Financial disclosures/conflicts of interest: R.K. has been a consultant for Astellas, Amgen (no longer active), Pfizer, and TherapeuticsMD (no longer active); has been on the advisory board for Astellas, Pfizer, and Pharmavite (no longer active); has been on speaker's bureau for Astellas, Pfizer, and TherapeuticsMD (no longer active); has been a medical advisor for Carrot Fertility and Lisa Health; and Data Monitoring Committee for Astellas. J.A.S. receives grant/research support from AbbVie, Bayer Healthcare, Daré Bioscience, Enteris BioPharma, ylan/Viatris, Myovant Sciences, ObsEva, Pfizer, Inc, and Viveve Medical; serves on consulting/advisory boards of Bayer Healthcare, Besins Healthcare, California Institute of Integral Studies (CIIS), Daré Bioscience, DEKA M.E.L.A S.r.l., Femasys, KaNDy/NeRRe Therapeutics, Khyria, Madorra, Mitsubishi Tanabe Pharma Development America, Pfizer, Inc, QUE Oncology, Scynexis Inc, Sprout Pharmaceuticals, and Vella Bioscience; serves on speaker's bureaus of: Ascend Therapeutics, Astellas Pharma, Inc, Mayne Pharma, Myovant Sciences, Pfizer, Pharmavite, and Scynexis; is a stockholder (direct purchase) in Sermonix Pharmaceuticals. Dr. Goldstein was a consultant for Astellas, Bayer, Cook OB/GYN, Cooper Surgical, Mylan, and Pfizer. B.S.K. and S.N.J. are consultants for Sermonix. D.J.P. is an employee and stockholder of Sermonix; his spouse is also an employee and stockholder of Sermonix., (Copyright © 2024 by The Menopause Society.)

Background: Vulvovaginal atrophy (VVA) includes a wide range of conditions affecting the reproductive and urinary systems, often requiring careful evaluation and management for optimal health., Aims: This study aims to evaluate the symptom management effects of a real time temperature-monitored non-ablative RF device for the treatment of postmenopausal Chinese women with VVA symptoms., Methods: This pilot study involved 24 postmenopausal Chinese women with one or more VVA symptoms, who wished to remain sexually active. VHIS, VAS, and FSFI were used to track and evaluate various aspects of the patient's condition. Analyses were conducted at the end of the study to verify the statistical significance of the treatment's results., Results: All patients reported substantial, statistically significant, improvements on every VVA symptom tracked. Approximately 80% of the patients reported total symptom reversal at 12-week post-treatment follow-up., Conclusion: This pilot study demonstrated that non-ablative, monopolar RF technology equipped with real time temperature monitoring is feasible and safe in the treatment of postmenopausal women with VVA symptoms, and efficacious at up to 12 weeks post-treatment., (© 2024 The Authors. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Vaginoplasty using sigmoid colon is a common technique used for the creation of a neovagina. However, the risk of adverse neovaginal bowel events is a common mentioned disadvantage. We report the case of a woman submitted to intestinal vaginoplasty for Mayer-Rokitansky-Küster-Hauser (MRKH) Syndrome at the age of 24 years who, with the onset of menopause, developed blood-stained vaginal discharge. Almost simultaneously, the patients complained chronic abdominal pain in lower left quadrant and prolonged diarrhea. General exams, Pap smear test, microbiological tests and viral test for HPV were negative. Neovaginal biopsies were suggestive for inflammatory bowel disease (IBD) of moderate activity and colonic biopsies were suggestive for ulcerative colitis (UC). The development of UC in the sigmoid neovagina and, almost simultaneously, in the remaining colon with onset of menopause raises important questions about etiology and pathogenesis of these diseases. Our case suggests that menopause may consider a trigger for the development of UC, due to the changes in the colon surface permeability related to menopause.