Lubricating gel influence on vaginal microbiome sampling.

Gel lubrication is routinely used during gynecological examination to prevent or reduce pain, yet its impact on microbial composition during sampling remains unclear. This study aimed to investigate whether lubricating gel affects the microbial composition of vaginal samples. We included 31 pregnant women presenting during their third trimester to clinics or emergency room and collected 143 unique vaginal samples for 16S amplicon microbial analysis. Vaginal samples were obtained using sterile swabs under various conditions: without gel-immediately frozen (n = 30), with gel-immediately frozen, without gel-at room temperature (RT) for 5 h before freezing, with gel-at RT for 5 h before freezing, and additional sampling after 24 h without gel-immediate freezing. We found that sample collection with gel lubrication influenced specimen quality-half of the gel samples failing to meet processing limitation compared to those without gel. The effect of gel on testing quality dissipated after 24 h. However, when samples met post-sequencing filters, gel lubrication did not alter the microbial composition, individual taxa abundance or alpha and beta diversity. We recommend sampling either before gel exposure or 24 h after. These findings underscore the importance of considering sample collection methodologies in vaginal microbiome studies to ensure high-quality microbial data for accurate analysis.

Short and long-term effect of polycarbophil vaginal gel on vaginal atrophy of peri- and post-menopausal women. The TRIPLE study.

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.

Fractional and Microablative CO2 LASER and Radiofrequency in the Treatment of Genitourinary Syndrome of Menopause: A Descriptive Study.

Objectives: This study aimed to evaluate the vagina clinically, cytologically, and histologically before and after treating genitourinary syndrome of menopause (GSM) with fractional microablative carbon dioxide LASER (CO2L), radiofrequency (RF), and estrogen vaginal cream (CT). Methods: Women with moderate-to-severe symptoms of GSM, denoted by a GSM Visual analog scale (VAS) score of >4, were eligible for this study. The patients were randomized into treatment groups. In the energy groups, three vulvovaginal applications were administered monthly. The CT group used 0.5 mg vaginal estriol cream for 14 consecutive days, followed by twice a week for 4 months. The follow-up visits occurred 120 days after the beginning of the treatments. The same parameters obtained at the first visit were re-evaluated: GSM VAS score, Incontinence Quality of Life Questionnaire (I-QOL), gynecological examination determining Vaginal Health Index (VHI), vaginal smear for Vaginal Maturation Value (VMV), and vaginal biopsy. Results: Seventy-one women were included, 48 completed the study and provided adequate samples for analysis (CO2L [21 patients], RF [15 patients], and CT [12 patients]). GSM symptoms, I-QOL, and VHI significantly improved after all proposed treatments, with no significant differences between them. VMV did not change after any treatment; however, only 22.9% of the patients presented with cytological atrophy before treatment. Histological vaginal atrophy was identified in 6 (12.5%) pretreated vaginal samples. After the intervention, all histological parameters were normalized, no tissue damage was observed, and no major clinical complications were observed. Conclusion: CO2L and RF seem to be good alternatives to CT for GSM treatment, with no tissue damage.

Safety of carrageenan-based gels as preventive microbicides: a narrative review.

BACKGROUND: Carrageenan-containing gels researched for the prevention of sexually transmitted infections (STIs) have shown promising results for human papillomavirus prevention in women, but not in men. We conducted a narrative review to assess the safety of these gels for genital use. METHODS: We searched PubMed using MeSH terms and keywords on 5 November 2023. Title/abstract of articles were screened to identify relevant ones. Full-text screening determined eligibility: empirical study evaluating safety of carrageenan-containing gel(s) for genital use. RESULTS: Of the 125 identified records, 15 were eligible, comprising 14 (10 randomised controlled trials and 4 cohorts) unique study populations. Studies included women only (n=11), men only (n=1) or both (n=3); number of participants ranged from 4 to 6202. Safety was assessed for vaginal (n=13), penile (n=3) and anal use (n=2). Most studies assessed safety of Carraguard (53%), followed by Divine9 (14%), and one each of iota-carrageenan gel, lambda-carrageenan gel, Carvir, PC-6500 (griffithsin and carrageenan) and PC-1005 (MIV-150/zinc acetate/carrageenan). Safety assessment relied on self-report (80.0%), testing for STIs (53.3%), investigator-identified genital findings (93.3%) and/or testing for changes in genital flora (60.0%). Adverse events (AEs) were described by investigators as mostly mild, (mostly) comparable between groups, not observed and/or not significant for vaginal and penile use. Only one study, assessing anal use of carrageenan, reported a significantly higher proportion of AEs in the carrageenan compared with placebo group. CONCLUSIONS: Carrageenan-based gels are generally well tolerated for vaginal and penile, but not anal use. Studies on carrageenan gel's safety for anal use are scarce.

Hypotonic, gel-forming delivery system for vaginal drug administration.

Vaginal drug delivery is often preferred over systemic delivery to reduce side effects and increase efficacy in treating diseases and conditions of the female reproductive tract (FRT). Current vaginal products have drawbacks, including spontaneous ejection of drug-eluting rings and unpleasant discharge from vaginal creams. Here, we describe the development and characterization of a hypotonic, gel-forming, Pluronic-based delivery system for vaginal drug administration. The rheological properties were characterized with and without common hydrogel polymers to demonstrate the versatility. Both qualitative and quantitative approaches were used to determine the Pluronic F127 concentration below the critical gel concentration (CGC) that was sufficient to achieve gelation when formulated to be hypotonic to the mouse vagina. The hypotonic, gel-forming formulation was found to form a thin, uniform gel layer along the vaginal epithelium in mice, in contrast to the rapidly forming conventional gelling formulation containing polymer above the CGC. When the hypotonic, gel-forming vehicle was formulated in combination with a progesterone nanosuspension (ProGel), equivalent efficacy was observed in the prevention of chemically-induced preterm birth (PTB) compared to commercial Crinone® vaginal cream. Further, ProGel showed marked benefits in reducing unpleasant discharge, reducing product-related toxicity, and improving compatibility with vaginal bacteria in vitro. A hypotonic, gel-forming delivery system may be a viable option for therapeutic delivery to the FRT.

Three-year outcomes of a randomized clinical trial of perioperative vaginal estrogen as adjunct to native tissue vaginal apical prolapse repair.

BACKGROUND: As the muscular and connective tissue components of the vagina are estrogen responsive, clinicians may recommend vaginal estrogen to optimize tissues preoperatively and as a possible means to reduce prolapse recurrence, but long-term effects of perioperative intravaginal estrogen on surgical prolapse management are uncertain. OBJECTIVE: This study aimed to compare the efficacy of perioperative vaginal estrogen vs placebo cream in reducing composite surgical treatment failure 36 months after native tissue transvaginal prolapse repair. STUDY DESIGN: This was an extended follow-up of a randomized superiority trial conducted at 3 tertiary US sites. Postmenopausal patients with bothersome anterior or apical vaginal prolapse were randomized 1:1 to 1-g conjugated estrogen cream (0.625 mg/g) or placebo, inserted vaginally twice weekly for ≥5 weeks preoperatively and continued twice weekly for 12 months postoperatively. All participants underwent vaginal hysterectomy (if the uterus was present) and standardized uterosacral or sacrospinous ligament suspension at the surgeon's discretion. The primary report's outcome was time to failure by 12 months postoperatively, defined by a composite outcome of objective prolapse of the anterior or posterior walls beyond the hymen or the vaginal apex descending below one-third the total vaginal length, subjective bulge symptoms, and/or retreatment. After 12 months, participants could choose to use-or not use-vaginal estrogen for atrophy symptom bother. The secondary outcomes included Pelvic Organ Prolapse Quantification points, subjective prolapse symptom severity using the Patient Global Impression of Severity and the Patient Global Impression of Improvement, and prolapse-specific subscales of the 20-Item Pelvic Floor Distress Inventory and the Pelvic Floor Impact Questionnaire-Short Form 7. Data were analyzed as intent to treat and "per protocol" (ie, ≥50% of expected cream use per medication diary). RESULTS: Of 206 postmenopausal patients, 199 were randomized, and 186 underwent surgery. Moreover, 164 postmenopausal patients (88.2%) provided 36-month data. The mean age was 65.0 years (standard deviation, 6.7). The characteristics were similar at baseline between the groups. Composite surgical failure rates were not significantly different between the estrogen group and the placebo group through 36 months, with model-estimated failure rates of 32.6% (95% confidence interval, 21.6%-42.0%) and 26.8% (95% confidence interval, 15.8%-36.3%), respectively (adjusted hazard ratio, 1.55; 95% confidence interval, 0.90-2.66; P=.11). The results were similar for the per-protocol analysis. Objective failures were more common than subjective failures, combined objective and subjective failures, or retreatment. Using the Patient Global Impression of Improvement, 75 of 80 estrogen participants (94%) and 72 of 76 placebo participants (95%) providing 36-month data reported that they were much or very much better 36 months after surgery (P>.99). These data included reports from 51 of 55 "surgical failures." Pelvic Organ Prolapse Quantification measurements, Patient Global Impression of Severity scores, and prolapse subscale scores of the 20-Item Pelvic Floor Distress Inventory and Pelvic Floor Impact Questionnaire-Short Form 7 all significantly improved for both the estrogen and placebo groups from baseline to 36 months postoperatively without differences between the groups. Of the 160 participants providing data on vaginal estrogen usage at 36 months postoperatively, 40 of 82 participants (49%) originally assigned to the estrogen group were using prescribed vaginal estrogen, and 47 of 78 participants (60%) assigned to the placebo group were using vaginal estrogen (P=.15). CONCLUSION: Adjunctive perioperative vaginal estrogen applied ≥5 weeks preoperatively and 12 months postoperatively did not improve surgical success rates 36 months after uterosacral or sacrospinous ligament suspension prolapse repair. Patient perception of improvement remained very high at 36 months.

Development and verification of mechanistic vaginal absorption and metabolism model to predict systemic exposure after vaginal ring and gel application.

AIMS: The current work describes the development of mechanistic vaginal absorption and metabolism model within Simcyp Simulator to predict systemic concentrations following vaginal application of ring and gel formulations. METHODS: Vaginal and cervix physiology parameters were incorporated in the model development. The study highlights the model assumptions including simulation results comparing systemic concentrations of 5 different compounds, namely, dapivirine, tenofovir, lidocaine, ethinylestradiol and etonogestrel, administered as vaginal ring or gel. Due to lack of data, the vaginal absorption parameters were calculated based on assumptions or optimized. The model uses release rate/in vitro release profiles with formulation characteristics to predict drug mass transfer across vaginal tissue into the systemic circulation. RESULTS: For lidocaine and tenofovir vaginal gel, the predicted to observed AUC0-t and Cmax ratios were well within 2-fold error limits. The average fold error (AFE) and absolute AFE indicating bias and precision of predictions range from 0.62 to 1.61. For dapivirine, the pharmacokinetic parameters are under and overpredicted in some studies due to lack of formulation composition details and relevance of release rate used in ring model. The predicted to observed AUC0-t and Cmax ratios were well within 2-fold error limits for etonogestrel and ethinylestradiol vaginal ring (AFEs and absolute AFEs from 0.84 to 1.83). CONCLUSION: The current study provides first of its kind physiologically based pharmacokinetic framework integrating physiology, population and formulation data to carry out in silico mechanistic vaginal absorption studies, with the potential for virtual bioequivalence assessment in the future.

The Effect of Citrus Aurantium Vaginal Cream on Vaginal Atrophy in Postmenopausal Women: A Quasi-experimental Study.

Background: Vulvovaginal atrophy (VVA) is a common condition and a silent epidemic affecting many postmenopausal women who suffer from it in silence. This study aimed to evaluate the effect of Citrus aurantium vaginal cream on vaginal atrophy in postmenopausal women. Methods: This single-group pretest-posttest quasi-experimental study was conducted on 30 postmenopausal women who were referred to the Gynecology Clinic of Imam Khomeini Hospital in the city of Noor, Iran, from June to November 2020. Citrus aurantium vaginal cream was administered to women diagnosed with vaginal atrophy (based on subjective symptoms of atrophy, descriptive evaluation of the vagina, vaginal pH measurement, and degree of vaginal maturation determined by vaginal smear) every night in the first two weeks and every other night for the second two weeks. Data were collected using the scale of subjective symptoms of vaginal atrophy; descriptive evaluation checklist of vaginal mucosa; laboratory results registration form (vaginal maturation index, vaginal maturation value, and vaginal pH) before the intervention and two and four weeks after the intervention. Data were analyzed using SPSS software (version 24) through the analysis of variance with repeated measurements, and LSD post-hoc test. A P value less than 0.05 (P<0.05) was considered statistically significant. Results: Citrus aurantium vaginal cream improved subjective symptoms of vaginal atrophy (P<0.001), reduced the score of descriptive evaluation of vaginal mucosa (P<0.001), decreased vaginal pH (P<0.001), and increased vaginal maturity (P<0.001). Conclusions: The results showed that citrus aurantium vaginal cream could improve the symptoms of vaginal atrophy without causing serious complications. However, further studies with a control group are suggested to confirm the findings of this study.Trial Registration Number: IRCT20200215046494N.

Twice-daily versus once-daily vaginal dinoprostone gel for induction of labor at term: A randomized controlled trial.

OBJECTIVE: The aim of this study was to compare twice-daily versus once-daily administration of intravaginal PGE2 for induction of labor at term. Efficacy, safety, and patient satisfaction were evaluated. STUDY DESIGN: For this single-center, randomized, comparative, open-label, two-arm, and parallel study, pregnant women with term singleton live pregnancies ≥ 37 weeks of gestation, medical indications for induction of labor, and Bishop score ≤ 6 were randomized to either the control group (induction of labor with PGE2 gel with repeat dose after 24 h) or the experimental group (repeat dose after 12 h). The primary outcome was induction-to-delivery interval time. Secondary outcomes were maternal and neonatal outcomes and patient satisfaction. RESULTS: In total, 246 women were randomized to the control (n = 121) or experimental groups (n = 125). The mean time for initiation of induction to delivery was 9.4 h shorter in the experimental group compared to controls (p = 0.007). For control vs experimental, there were no differences in tachysystole (19/121, 15.7 % vs 21/124, 16.9 %, respectively; p = 0.79), cesarean section rate (18/121, 14.9 % vs 28/124, 22.6 % respectively; p = 0.12), or other main obstetrical or neonatal outcomes. Patients in the experimental group reported higher satisfaction with their induction (48/96, 50 % with once-daily vs 60/86, 69.8 % with twice-daily; p = 0.010). CONCLUSION: Among women admitted for induction of labor at term, closer interval of vaginal PGE2 administration was associated with a significantly shorter induction-to-delivery time without increasing maternal or neonatal morbidity. Furthermore, the reduction in induction time was associated with improved patient experience of delivery.

Berberine-fluconazole microparticle-based combination therapy to treat candidiasis infections.

AIM: This study aims to incorporate alginate microparticles containing berberine and fluconazole into two different types of pharmaceutical formulations, to subsequently evaluate the antifungal activity against Candida albicans. METHODS AND RESULTS: Alginate microparticles containing BBR (berberine) and FLU (fluconazole) were produced by the spray-drying technique, characterized and incorporated in two pharmaceutical formulations, a vaginal cream and artificial saliva. Broth microdilution, checkerboard, time-kill curve, and scanning electron microscopy were carried out to determine the antifungal effects of BBR and FLU against C. albicans. The minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) values of free BBR were 125 µg ml-1. Synergism between BBR and FLU was demonstrated by a fractional inhibitory concentration index (FICI) = 0.0762. The time-kill curve for the combination BBR + FLU showed a more pronounced decrease in fungal growth in comparison to free drugs, and an antibiofilm effect of BBR occurred in the formation and preformed biofilm. CONCLUSION: Alginate microparticles containing BBR and FLU were obtained and incorporated in a vaginal cream and artificial saliva. Both formulations showed good stability, antifungal effects, and organoleptic characteristics, which suggest that BBR-FLU microparticles in formulations have potential as antifungal therapy.

ROS mediated anticandidal efficacy of 3-Bromopyruvate prevents vulvovaginal candidiasis in mice model.

Candidal infections, particularly vulvovaginal candidiasis (VVC), necessitate effective therapeutic interventions in clinical settings owing to their intricate clinical nature and elusive understanding of their etiological mechanisms. Given the challenges in developing effective antifungal therapies, the strategy of repurposing existing pharmaceuticals has emerged as a promising approach to combat drug-resistant fungi. In this regard, the current study investigates molecular insights on the anti-candidal efficacy of a well-proven anticancer small molecule -3-bromopyruvate (3BP) against three clinically significant VVC causing Candida species viz., C. albicans, C. tropicalis and C. glabrata. Furthermore, the study validates 3BP's therapeutic application by developing it as a vaginal cream for the treatment of VVC. 3BP exhibited phenomenal antifungal efficacy (killing >99%) with minimum inhibitory concentrations (MIC) and minimum fungicidal concentrations (MFC) of 256 µg/mL against all tested Candida spp. Time killing kinetics experiment revealed 20 min as the minimum time required for 3BP at 2XMIC to achieve complete-killing (99.9%) in all Candida strains. Moreover, the ergosterol or sorbitol experiment explicated that the antifungal activity of 3BP does not stem from targeting the cell wall or the membrane component ergosterol. Instead, 3BP was observed to instigate a sequence of pre-apoptotic cascade events, such as phosphatidylserine (PS) externalization, nuclear condensation and ROS accumulations, as evidenced by PI, DAPI and DCFH-DA staining methods. Furthermore, 3BP demonstrated a remarkable efficacy in eradicating mature biofilms of Candida spp., achieving a maximum eradication level of 90%. Toxicity/safety profiling in both in vitro erythrocyte lysis and in vivo Galleria mellonella survival assay authenticated the non-toxic nature of 3BP up to 512 µg/mL. Finally, a vaginal cream formulated with 3BP was found to be effective in VVC-induced female mice model, as it significantly decreasing fungal load and protecting vaginal mucosa. Concomitantly, the present study serves as a clear demonstration of antifungal mechanistic action of anticancer drug -3BP, against Candida species. This finding holds significant potential for mitigating candidal infections, particularly VVC, within healthcare environments.

Vaginal health and quality of sexual life of postmenopausal women on hyaluronic acid and Biosaccharide Gum-1 vaginal gel.

OBJECTIVE: To evaluate the efficacy of daily vaginal gel containing hyaluronic acid (HA) and Biosaccharide Gum-1 (BG-1) on vulvovaginal atrophy (VVA) and on sexual function and quality of life (QoL). MATERIALS AND METHODS: One hundred-four postmenopausal women with VVA were enrolled in the nonrandomized comparison cohort study. Of them, 50 women on HA/BG-1 participated in the study group and 54 women on lubricants/moisturizers on-demand as a control group. The primary endpoint was the efficacy of the vaginal gel on VVA evaluated by the Vaginal Health Index (VHI) score. Secondary endpoints included sexual behavior by the self-administered female sexual function index (FSFI) questionnaire, and quality of life (QoL), by the Short Form-36 questionnaire (SF-36). RESULTS: All symptoms of AVV improved after 12 weeks of treatment in women on HA/BG-1. The VMI, although improved at the 12-week follow-up compared to baseline, it connoted a low estrogenic stimulation value. Sexual function improved significantly in women on HA/BG-1. Moreover, women reported a significant improvement in the somatic aspects of QoL. No benefits were obtained by the women in the control group. CONCLUSIONS: Treatment with HA/BG-1 could have used in postmenopausal women who complain of vaginal dryness. The amelioration of VVA-related signs could improve sexual function and QoL.

Development of Dispersible Vaginal Tablets of Tenofovir Loaded Mucoadhesive Chitosan Microparticles for Anti-HIV Pre-Exposure Prophylaxis.

Tenofovir disoproxil fumarate (TDF)-loaded bioadhesive chitosan microparticles (CM) were developed by an emulsification internal gelation technique. Among different batches produced, ECH-4 was found to display a high % entrapment efficiency (68.93 ± 1.76%) and sustained drug release of 88.05 ± 0.38% at 24 h. Solid state characterization of ECH-4 employing DSC and PXRD indicated that the TDF existed in an amorphous state as a solid-solid solution in chitosan. Scanning electron microscopy revealed CM of ECH-4 was spherical in shape with a rough surface topography. Laser scattering analysis using Malvern Master sizer indicated that particle size of ECH-4 was in the range of 0.52 ± 0.10 µm to 284.79 ± 21.42 µm with a surface-mean diameter of 12.41 ± 0.06 µm. Ex vivo mucoadhesion studies using rabbit mucosa as a substrate indicated that 10.34 ± 2.08% of CM of ECH-4 was retained at the end of 24 h. The microparticles of ECH-4 were incorporated into dispersible tablets (DT-TCM) intended for intravaginal administration, in view to arrest the pre-exposure transmission of HIV during sexual intercourse. In vitro release from the dispersible tablet (F3) into simulated vaginal fluid (pH 4.5) displayed a sustained release profile of TDF as 89.98 ± 1.61% of TDF was released at 24 h. The in vitro dissolution profile of the DT-TCM was found to be similar to that of TDF loaded CM with the values of f1 (difference factor) and f2 (similarity factor) being 1.52 and 78.02, respectively. Therefore, DT-TCM would be a promising novel drug delivery platform for pre-exposure prophylaxis against HIV.

Perioperative Vaginal Estrogen as Adjunct to Native Tissue Vaginal Apical Prolapse Repair: A Randomized Clinical Trial.

Importance: Surgical repairs of apical/uterovaginal prolapse are commonly performed using native tissue pelvic ligaments as the point of attachment for the vaginal cuff after a hysterectomy. Clinicians may recommend vaginal estrogen in an effort to reduce prolapse recurrence, but the effects of intravaginal estrogen on surgical prolapse management are uncertain. Objective: To compare the efficacy of perioperative vaginal estrogen vs placebo cream on prolapse recurrence following native tissue surgical prolapse repair. Design, Setting, and Participants: This randomized superiority clinical trial was conducted at 3 tertiary US clinical sites (Texas, Alabama, Rhode Island). Postmenopausal women (N = 206) with bothersome anterior and apical vaginal prolapse interested in surgical repair were enrolled in urogynecology clinics between December 2016 and February 2020. Interventions: The intervention was 1 g of conjugated estrogen cream (0.625 mg/g) or placebo, inserted vaginally nightly for 2 weeks and then twice weekly to complete at least 5 weeks of application preoperatively; this continued twice weekly for 12 months postoperatively. Participants underwent a vaginal hysterectomy (if uterus present) and standardized apical fixation (either uterosacral or sacrospinous ligament fixation). Main Outcomes and Measures: The primary outcome was time to failure of prolapse repair by 12 months after surgery defined by at least 1 of the following 3 outcomes: anatomical/objective prolapse of the anterior or posterior walls beyond the hymen or the apex descending more than one-third of the vaginal length, subjective vaginal bulge symptoms, or repeated prolapse treatment. Secondary outcomes included measures of urinary and sexual function, symptoms and signs of urogenital atrophy, and adverse events. Results: Of 206 postmenopausal women, 199 were randomized and 186 underwent surgery. The mean (SD) age of participants was 65 (6.7) years. The primary outcome was not significantly different for women receiving vaginal estrogen vs placebo through 12 months: 12-month failure incidence of 19% (n = 20) for vaginal estrogen vs 9% (n = 10) for placebo (adjusted hazard ratio, 1.97 [95% CI, 0.92-4.22]), with the anatomic recurrence component being most common, rather than vaginal bulge symptoms or prolapse repeated treatment. Masked surgeon assessment of vaginal tissue quality and estrogenization was significantly better in the vaginal estrogen group at the time of the operation. In the subset of participants with at least moderately bothersome vaginal atrophy symptoms at baseline (n = 109), the vaginal atrophy score for most bothersome symptom was significantly better at 12 months with vaginal estrogen. Conclusions and Relevance: Adjunctive perioperative vaginal estrogen application did not improve surgical success rates after native tissue transvaginal prolapse repair. Trial Registration: ClinicalTrials.gov Identifier: NCT02431897.

Comparison of fetal safety of vaginal Misoprostol tablet and Dinoprostone gel for induction of labor: An open-label randomized control trial.

AIM: In modern obstetrics, need of labor induction is increasing along with increased caesarean deliveries. Major contributions for these operative deliveries are due to induction failure. This demands a potent labor-inducing agent. Dinoprostone gel is an established method but having some drawbacks. Misoprostol could be an effective alternative to Dinoprostone, but its fetal safety is not yet well established. This study aimed to evaluate the fetal safety of vaginal Misoprostol tablet by measuring fetal heart rate changes during induction of labor. METHODS: This was a single-center randomized controlled trial incorporating 140 term women, equally randomized to get either tablet Misoprostol or Dinoprostone gel. Fetal heart rate patterns were compared in both the groups by continuous cardiotocographic tracing. All the data were analyzed on an intention-to-treat basis. RESULTS: There were no statistically significant changes in fetal heart rate pattern in both Misoprostol and Dinoprostone groups. Vaginal deliveries were statistically higher in Misoprostol group. Neonatal parameters like 1 min Appearance, Pulse, Grimace, Activity, and Respiration score and neonatal intensive care unit admission were comparable, and there was no significant difference in terms of major adverse events and side effects. CONCLUSIONS: Misoprostol is a safe alternative to Dinoprostone gel for induction of labor and found to be more effective labor-inducing agent. In the background of higher caesarean rate, vaginal Misoprostol can be a potential labor-inducing agent especially in a resource poor setting.

Effects of two different types of luteal support on pregnancy outcomes following antagonist fresh embryo transfer: a retrospective study.

BACKGROUND: Only a small number of studies have reported the use of progesterone vaginal gel in combination with dydrogesterone as part of the antagonist protocol for fresh embryo transfer. Therefore, this study aimed to compare the effects of two types of luteal support on pregnancy outcomes following the antagonist protocol for fresh embryo transfer. METHODS: We performed a retrospective analysis of clinical data from infertile patients who underwent fresh embryo transfer via the antagonist protocol (2785 cycles) between February and July 2019 and between February and July 2021 at the Peking University Third Hospital Reproductive Medicine Centre. According to the luteal support received, the cycle groups were divided into the progesterone vaginal gel group (single medication or VP group; 1170 cycles) and the progesterone vaginal gel plus dydrogesterone group (combination medication or DYD + VP group; 1615 cycles). After propensity score matching, the clinical pregnancy, ongoing pregnancy, early miscarriage, and ectopic pregnancy rates were compared between the two groups. RESULTS: In total, 1057 pairs of cycles were successfully matched via propensity scores. The clinical and ongoing pregnancy rates in the combination medication group were significantly higher than those in the single medication group (P < 0.05), whereas no significant differences were noted in the early miscarriage and ectopic pregnancy rates between the two groups (both P > 0.05). CONCLUSIONS: Combined luteal support after the antagonist protocol is preferred for patients undergoing fresh cycle embryo transfer.

Acceptability of Single-dose Clindamycin Gel for Bacterial Vaginosis: A Randomized Controlled Trial.

PURPOSE: The goal of this study was to assess the acceptability of a single-dose bioadhesive 2% clindamycin vaginal gel for bacterial vaginosis (BV). METHODS: This double-blind, placebo-controlled, randomized study compared a new clindamycin gel with placebo gel (2:1 ratio). The primary objective was efficacy; secondary objectives were safety and acceptability. Subjects were evaluated at screening, days 7 to 14 (Day 7-14), and days 21 to 30 (test-of-cure [TOC]). An acceptability questionnaire with 9 questions was administered at the Day 7-14 visit, and a subset of questions (#7-#9) was asked again at the TOC visit. At Visit 1, subjects were provided with a daily electronic diary (e-Diary) to collect information regarding study drug administration, vaginal discharge, odor, itching, and any other treatments used. Study site staff reviewed e-Diaries at the Day 7-14 and TOC visits. FINDINGS: A total of 307 women with BV were randomized to treatment (204 to the clindamycin gel group and 103 to the placebo gel group). Most (88.3%) reported at least one previously diagnosed BV episode, and more than one half (55.4%) had experience with other vaginal treatments for BV. At the TOC visit, almost all (91.1%) of the clindamycin gel subjects described their overall experience with the study drug as "satisfied" or "very satisfied," 95.8% indicated that they would be "likely" or "very likely" to use the product again if it became available after the study and they had BV again, and 93.7% would be "likely" or "very likely" to recommend their treatment to a friend who had BV. Almost all (90.2%) clindamycin-treated subjects responded that application was "clean" or "fairly clean," as opposed to "neither clean nor messy," "fairly messy," or "messy." Although 55.4% experienced leakage in the days after application, only 26.9% of those indicated that it was bothersome. Subjects receiving clindamycin gel also reported improvement in both odor and discharge, commencing shortly after dosing and continuing through the assessment period, regardless of whether they met the critical cure criteria. IMPLICATIONS: A single dose of a new bioadhesive 2% clindamycin vaginal gel showed rapid resolution of symptoms and was highly acceptable as a treatment for bacterial vaginosis. CLINICALTRIALS: gov identifier: NCT04370548.

The efficacy of complementary treatment with marshmallow (Althaea officinalis L.) on vulvovaginal candidiasis: A randomized double-blinded controlled clinical trial.

BACKGROUND: Vulvovaginal candidiasis is a common gynecologic infection, and recurring cases are yet incurable. This trial was based on Persian medicine to compare how effective marshmallow aqueous extract 4% plus clotrimazole 1% (CLOT-M) is compared to clotrimazole 1% vaginal creams on VVC. METHODS: This study randomly assigned 100 women with VVC into two groups. The target group (n = 50) was treated with CLOT-M while controls (n = 50) with clotrimazole vaginal creams for seven consecutive nights. Different VVC symptoms and signs, and yeast culture from vaginal discharge were evaluated as the outcome measures before the intervention and 7 and 30 days after. RESULTS: The efficacy of CLOT-M vaginal cream was assessed during the 1st and 2nd follow-ups, indicating a significant decrease in mean itching (P = 0.001 for both comparisons) and dyspareunia score (P = 0.001 and P = 0.04, respectively) as compared to treatment with clotrimazole vaginal cream. Moreover, after 7 days of the intervention, patients in the CLOT-M group experienced significant improvement in mean dysuria score compared to those in the control group (P = 0.001). Neither cream caused any significant adverse events. CONCLUSION: It seems that CLOT-M vaginal cream had a significant effect on the VVC symptoms improvement, without any significant side effects. However, larger sample-sized trials are needed for more evidence-based judgment.

The effect of nettle vaginal cream on subjective symptoms of vaginal atrophy in postmenopausal women.

BACKGROUND AND OBJECTIVE: Vaginal atrophy is a condition where the vaginal epithelium gets thinner and includes symptoms, such as vaginal dryness, abnormal vaginal discharge, vaginal bleeding, dyspareunia, and sexual problems. Hormone therapy is associated with some problems and some women prefer herbal medicine to reduce vaginal atrophy. Considering the phytoestrogenic compounds present in the nettle, this study aimed to investigate the effect of the nettle vaginal cream on subjective symptoms of vaginal atrophy in postmenopausal women. MATERIALS AND METHODS: This triple-blind randomized placebo-controlled clinical trial study was conducted on 84 eligible postmenopausal women aged 45-60 years, who referred to comprehensive health service centers in Aliabad Katul in 2021-2022. Women eligible for the study received 5% nettle vaginal cream and placebo for 8 weeks. Subjective symptoms of vaginal atrophy were assessed before, four and eight weeks after the intervention. Data collection tools included a checklist for research unit selection, individual and midwifery characteristics questionnaire, vaginal assessment scale (VAS), vaginal pH, laboratory results of the vaginal maturation value (VMV). Data analysis was performed using SPSS software (version 21) and independent t-test, Mann-Whitney, chi-square, Two-way analysis of variance and analysis of covariance. P value less than 0.05 was considered significant. RESULTS: Subjective symptoms of vaginal atrophy decreased significantly after the intervention compared to before the intervention in both the nettle and placebo groups (p < 0.001), but in the comparison between groups four weeks and eight weeks after the intervention, the subjective symptoms of vaginal atrophy in nettle group decreased significantly (p < 0.001). In the nettle group, the scores of vaginal burning, vaginal dryness, vaginal itching and dyspareunia significantly improved after the intervention compared to before the intervention (p < 0.001). Also, in the nettle group compared to the placebo group, after the intervention, vaginal burning and vaginal dryness score (p < 0.001) and vaginal itching score (0.004) improved significantly. CONCLUSION: Based on the results of the present study, Nettle vaginal cream reduced subjective symptoms of vaginal atrophy, including vaginal burning, vaginal dryness, vaginal itching, and dyspareunia in postmenopausal women, so it is a cost-effective, available and do not have the side effects product that can be useful for menopausal women.

Comparing the effects of two different progesterone vaginal gels, Progeson™ and Crinone™, from pharmacokinetics study to clinical applications in patients undergone fresh embryo transfer and frozen-thawed embryo transfer via natural cycle endometrial preparation protocol.

OBJECTIVE: The pharmacokinetics performance and clinical pregnancy rate of two vaginal progesterone gel, Progeson™ and Crinone™, were compared in this study. MATERIALS AND METHODS: In the pharmacokinetics performance, Progeson showed similar long-term dissolution rate as Crinone. In the clinical study, 141 subjects undergone in vitro fertilization (IVF) treatments were included to compare serum progesterone level and clinical pregnancy rates. RESULTS: Among the subjects, 78 subjects received fresh embryo transfer and 63 subjects received frozen embryo transfer via natural cycle endometrial preparation protocol. In each group, subjects were given either Crinone™ or Progeson™ for luteal phase support without combination with other progesterone products. The study showed that Crinone™ group led to higher estrogen level at mid-luteal phase in the fresh embryo transfer group, and Progeson™ group led to higher progesterone level at mid-luteal phase and pregnancy test day in the frozen-thawed embryo transfer group. CONCLUSION: Subjects received Crinone™ or Progeson™ had similar rate of pregnancy, live birth, and stillbirth in both fresh embryo transfer and frozen-thawed embryo transfer group. Thus, Progeson™ might be a suitable substitute for Crinone™ in assisted reproductive therapy.