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.

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.

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.

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.

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.

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 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.

Failed induction of labor in term nulliparous women with an unfavorable cervix: Comparison of cervical ripening by two forms of vaginal prostaglandins (slow-release pessary and vaginal gel).

OBJECTIVE: To compare the rate of failed induction after cervical ripening by two forms of vaginal prostaglandins. MATERIAL AND METHODS: This two-year retrospective study (January 1, 2016, through December 31, 2017) in two tertiary maternity units included nulliparous women with a singleton fetus in cephalic presentation and an unfavorable cervix requiring labor induction for prolonged pregnancy. The principal endpoint was the rate of failed induction, defined by the performance of a cesarean delivery before 6 cm of dilation. Cervical ripening was initiated by prostaglandins for 24 h, using a slow-release pessary (unit A) or a vaginal gel (unit B). The care protocol of the two groups after the first 24 h were similar. The women's individual characteristics were compared between the two units. The rates of failed induction were then compared between the two units, first by univariate and then by multivariable analysis adjusted for the characteristics that differed significantly between the units. RESULTS: Among the 17,217 women delivered in the two maternity units during the study period, 178 met our inclusion criteria (125 in unit A (slow-release pessary) and 53 in unit B (vaginal gel)). The rate of failed induction was similar: 21.6% in unit A (slow-release pessary) and 17.0% in unit B (vaginal gel) (P = 0.48). The multivariate analysis did not show any difference about failed induction, time from the onset of induction to delivery, and vaginal delivery rate within 24h. CONCLUSION: The rate of failed induction of labor did not differ between slow-release pessary and vaginal gel.

Prevention of recurrence of bacterial vaginosis using lactobacilli-containing vaginal tablets among women with HIV: a randomized, placebo-controlled, double-blinded phase IV trial.

OBJECTIVES: The effectiveness of lactobacilli-containing vaginal tablets (VT) in bacterial vaginosis (BV) recurrence prevention among women infected with HIV treated with standard oral metronidazole in Pune, India was studied. METHODS: Women infected with HIV with confirmed BV diagnosis (Nugent score ≥7 and Amsel criteria >3) were enrolled in a 12-month, double-blind, randomized, placebo-controlled, phase IV study between 2018 and 2021. After a standard course of oral metronidazole for 7 days (400 mg three times a day), women were randomly assigned to either lactobacilli-containing or placebo VT arms to receive VTs for 4 months. BV recurrence was assessed after the initial cure from BV. RESULTS: Of the 464 women infected with HIV, 80 women with confirmed BV were enrolled. The retention was affected due to the COVID-19 pandemic (6-month retention rates 78%). The cure was seen in 85% and 93.5% of participants from the treatment and placebo arms, respectively, after four VT cycles. BV recurrence was seen in 41.4% and 44.8% in the treatment and placebo arm, respectively, with no significant difference in the two groups. CONCLUSION: The lactobacilli-containing VT was acceptable and safe; however, the addition of VT over standard oral metronidazole did not show any additional benefit in the prevention of BV recurrence in women infected with HIV, indicating the need for long-term randomized trials among them. Registered at Clinical Trials Registry- India, (CTRI) Number: CTRI/2018/04/013298.

Preventive effect of metronidazole vaginal tablets on vaginal bacteria-related postoperative complications with total laparoscopic hysterectomy.

BACKGROUND: The use of total laparoscopic hysterectomy is increasing. However, as with conventional abdominal hysterectomy, vaginal bacteria-related postoperative complications need to be managed in total laparoscopic hysterectomy. Therefore, we started to combine metronidazole vaginal tablets with intravenous administration of cephem antibiotics immediately before starting surgery to reduce complications. To evaluate the effect of this combination, and to determine the risk factors for these complications, we retrospectively collected medical records from our hospital and performed a multivariate analysis. METHODS: We reviewed the medical records of 520 patients who underwent total laparoscopic hysterectomy from 1 January 2015 to 31 December 2021. Among these cases, we identified 16 cases as having vaginal bacteria-related postoperative complications, defined as needing more than one additional day for treatment of postoperative complications, namely postoperative infection (10 cases) and vaginal dehiscence (6 cases). First, we evaluate the effect of metronidazole vaginal tablets by dividing the patients into two groups according to whether metronidazole vaginal tablets were used, and comparing the vaginal bacteria-related postoperative complication rates and other indices. Second, we performed a multivariate logistic regression analysis to assess the influence of each of 17 representative factors, including patient characteristics and symptoms, uterus and leiomyoma sizes, concomitant procedures such as laparoscopic cystectomy and pelvic lymphadenectomy, and others. RESULTS: In the multivariate analysis of the 520 cases, we confirmed that the use of metronidazole vaginal tablets could reduce the vaginal bacteria-related postoperative complications rate by more than half (odds ratio, 0.36). In addition to metronidazole vaginal tablets use, concomitant laparoscopic cystectomy and blood transfusion were associated with significant increases in the vaginal bacteria-related postoperative complication rate. CONCLUSIONS: The effect of the addition of metronidazole vaginal tablets to pre- and postsurgical treatment on the reduction of vaginal bacteria-related postoperative complications was confirmed. This easy, safe, and low-cost method may improve the management of total laparoscopic hysterectomy.

The effect of 12 weeks of estriol cream on stress urinary incontinence post-menopause: A prospective multinational observational study.

OBJECTIVE: To quantitate the changes in stress urinary incontinence (SUI) outcome measures after 12 weeks of vaginal estriol cream in women with stress incontinence. METHODS: A prospective multicentre observational study conducted in tertiary urogynaecology centers. Postmenopausal women with pure SUI or stress predominant mixed urinary incontinence (MUI), not receiving any other treatment for their incontinence were given written instructions regarding digital application of a standard dose of vaginal estriol cream. Outcomes were measured at baseline and 12 weeks. The primary objective outcome was vaginal pH. The primary subjective outcome was the stress domain of the Urogenital Distress Inventory-6 (UDI-6). The secondary objective outcome used was the erect cough stress test. Two quality of life questionnaires and two patient reported outcomes were also included. RESULTS: The 46 postmenopausal recruits had a median age of 62.1 interquartile range (IQR 56.2-65.4). At follow up, the primary subjective outcome SUI domain [UDI-6] significantly improved from 83.3 (IQR 50-100) to 33.3 (33.3-66.7, p ≤ 0.001) as did vaginal pH [from 5.1 (4.9-5.9) to 4.9 (4.6-5.0] p ≤ 0.001; 18/43 patients (42%) were dry on cough stress test. CONCLUSIONS: Twelve weeks of vaginal estriol cream significantly reduced symptoms of stress urinary incontinence in this sample of postmenopausal women.

Improved treatment of vulvovaginal candidiasis with Clotrimazole plus probiotic Lacidophilin Vaginal Capsules: A prospective, real-world study.

BACKGROUND: Clotrimazole has long been used to treat vulvovaginal candidiasis (VVC), yet the antibiotic resistance, adverse effects and recurrences still bring about a great challenge for the clinicians. To explore the effect of probiotic Lacidophilin Vaginal Capsules plus Clotrimazole Vaginal Tablets (500mg) in the treatment of uncomplicated VVC, a self-controlled real-world study was conducted. METHODS: Twenty-seven women with a normal vaginal flora and 15 women with uncomplicated VVC were recruited. The patients were treated with the single dose of Clotrimazole Vaginal Tablets (500mg) supplemented with 2 Lacidophilin Vaginal Capsules for the following 7 days. The patients were prospectively examined 4 times and the time points were at m0 (the first visit), m1 (8-10 days after the first visit), m2 (30 days after the second visit) and m3 (30 days after the third visit). However, women in the healthy normal control group were examined just once at the first visit. The obtained vaginal secretions were examined by high-throughput sequencing. RESULTS: The mean age in healthy control group and case group was 28.63 ± 5.40y and 27.67 ± 3.33y, respectively. Finally, 46.67% (7/15) of patients were cured at the second visit, 61.54% (8/13) were cured at the third visit and eventually 72.73% (8/11) were cured. A total of 81 samples were sequenced, generating 1668 operation taxonomy units among all the samples. The bacterial composition of women in the healthy control group was exceedingly abundant and dominated by Lactobacillus, especially by Lactobacillus. crispatus, and followed by Lactobacillus. iners, Lactobacillus. jensenii and Gardneralla. On the contrary, the bacterial composition of women with VVC was relatively few and dominated by Lactobacillus. iners. During the process of treatment, the bacterial abundance of VVC patients was increased gradually. At the final visit, the abundance of vaginal flora was augmented further with the dominant bacteria being Lactobacillus. crispatus, followed by Lactobacillus. iners. CONCLUSION: Clotrimazole Vaginal Tablets plus probiotic Lacidophilin Vaginal Capsules could improve the effect in treating uncomplicated VVC. This improved effect was achieved perhaps through improving the composition of vaginal flora and restoring vaginal microecology.

Evaluation of the safety and efficacy of wormwood vaginal gel in improving sexual function and sexual satisfaction in women of reproductive age: A randomized, triple-blinds, placebo-controlled clinical trial.

INTRODUCTION: All aspects of sexual function are related to sexual satisfaction, and not paying attention to sexual problems leads to sexual dissatisfaction. According to studies, sexual satisfaction is a key factor in a couple's quality of life. The aim of this study was to evaluate the safety and efficacy of wormwood vaginal gel in improving sexual function and sexual satisfaction in women of reproductive age. METHODS: This study was a randomized, triple-blinds, parallel-groups clinical trial performed on 76 women of reproductive age (18-45 years) referred to the gynecological clinic of Ghaem Hospital in Mashhad who had sexual dysfunction and low sexual satisfaction. 76 women were assigned to the wormwood gel (n = 38) and placebo (n = 38) groups using random permuted blocks of sizes 4 or 6 and an allocation ratio of 1:1. Wormwood gel or placebo was used for 4 weeks and 3 times a week for 4 weeks from22 May to 23 October 2021. The main data collection tools were the Female Sexual Function Index (FSFI) and Larson Sexual Satisfaction Questionnaire (LSSQ) to access changes in sexual function and sexual satisfaction at baseline and after 4 weeks. RESULTS: The Mean and Standard Deviation of the age of the studied women was 36.8 ± 5.9 years in the intervention group and 37.1 ± 7.3 years in the placebo group. Before the intervention, the Mean and Standard Deviation of the total score of sexual function and sexual satisfaction in the studied women were 17.70 ± 3.66 and 72.20 ± 6.56 in the intervention group and in the placebo group were 18.23 ± 3.84 and 73.26 ± 5.86, respectively. At the end of the intervention, the Mean and Standard Deviation of the total score of female sexual function and sexual satisfaction in the intervention group were 32.11 ± 2.03 and 96.91 ± 7.93 and in the placebo group were 21.07 ± 3.22 and 75.91 ± 8.87, respectively. sexual function and satisfaction improved significantly in the wormwood gel compared to the control group(p < 0.0001). CONCLUSIONS: Based on the findings of this trial, it seems that the wormwood vaginal gel can be used as a topical supplement to improve sexual function and sexual satisfaction in women of reproductive age who have sexual dysfunction and low sexual satisfaction.