Comparison of two labor induction regimens with intravaginal misoprostol 25 µg and adverse perinatal outcomes.

OBJECTIVE: The aim of the study was to compare two labor induction regimens (4 and 6 h), to determine predictors of successful labor induction with intravaginal misoprostol 25 µg tablets, and to evaluate the association with adverse perinatal outcomes. METHODS: This was a retrospective cohort study that included singleton pregnancies undergoing induction of labor with an intravaginal misoprostol 25 µg tablet between 37 and 42 weeks of gestation. The pregnant women were divided into two groups: Group 1-intravaginal misoprostol 25 µg every 4 h and Group 2-intravaginal misoprostol 25 µg every 6 h. RESULTS: Pregnant women were divided into Group 1 (n=289) and Group 2 (n=278). Group 1 had a higher median number of intravaginal misoprostol 25 µg tablets (3.0 vs. 2.0 tablets, p<0.001), a lower prevalence of postpartum hemorrhage (7.6 vs. 32.7%, p<0.001), and a higher need for oxytocin (odds ratio [OR]: 2.1, 95%CI: 1.47-2.98, p<0.001) than Group 2. Models including intravaginal misoprostol 25 µg tablets every 4 and 6 h [x2(1)=23.7, OR: 4.35, p<0.0001], parity [x2(3)=39.4, OR: 0.59, p=0.031], and Bishop's score [x2(4)=10.8, OR: 0.77, p=0.019] were the best predictors of failure of labor induction. A statistically significant difference between groups was observed between the use of the first intravaginal misoprostol 25 µg tablet at the beginning (Breslow p<0.001) and the end of the active labor phase (Long Hank p=0.002). CONCLUSION: Pregnant women who used intravaginal misoprostol 25 µg every 4 h had a longer time from the labor induction to the beginning of the active phase of labor and higher rates of adverse perinatal outcomes than women who used intravaginal misoprostol 25 µg every 6 h.

Comparing the outcomes of in-vitro fertilization in patients receiving vaginal, subcutaneous, and intramuscular progesterone for luteal phase support: a three-armed randomized controlled trial.

BACKGROUND: The optimal approach to luteal-phase support in infertility treatment remains a subject of debate. This study was conducted to investigate the clinical outcomes, side effects, and patient satisfaction associated with vaginal, subcutaneous, and intramuscular progesterone administration in infertile women undergoing Frozen Embryo Transfer (FET). METHODS: This three-armed randomized clinical trial assigned infertile patients eligible for FET to three progesterone treatment groups: vaginal suppositories (400 mg twice daily; n = 100), subcutaneous injections (25 mg daily; n = 102), and intramuscular injections (50 mg daily; n = 108). The primary outcomes were chemical and clinical pregnancy rates per embryo transfer cycle, with chemical pregnancy defined as beta-human chorionic gonadotropin levels > 50 IU/mL two weeks post-transfer and clinical pregnancy confirmed by ultrasound four weeks later. Exploratory outcomes included progesterone-related adverse effects and participant satisfaction, assessed via a Likert-scale survey 12 weeks post-transfer. Statistical analyses included Chi-square tests for categorical data, one-way analysis of variances, and Kruskal-Wallis tests for continuous data. RESULTS: The intramuscular progesterone group had significantly higher chemical pregnancy rates compared to the vaginal and subcutaneous groups (41.7% vs. 26.0% and 27.5%, respectively; p = 0.026). Although the clinical pregnancy rate was also higher in the intramuscular group (32.4%) compared to the vaginal (23.0%) and subcutaneous groups (21.6%), this difference was not statistically significant (p = 0.148). Additionally, patient satisfaction was greater with vaginal and subcutaneous applications than with intramuscular injections (p < 0.001), likely due to a significantly higher incidence of side effects, such as pain and edema at the injection site, in the intramuscular group (p < 0.001). CONCLUSIONS: We found that intramuscular progesterone resulted in higher chemical pregnancy rates than vaginal or subcutaneous routes, but this did not translate into higher clinical pregnancy rates. Despite its effectiveness, intramuscular administration was associated with more adverse effects and lower patient satisfaction. Future research should explore optimizing progesterone regimens to balance efficacy and patient comfort. TRIAL REGISTRATION: The trial protocol was registered on December 6, 2020, in the Iranian Registry of Clinical Trials (IRCT), a primary registry in the World Health Organization (WHO) Registry Network, under the registration number IRCT20141217020351N12.

Vaginal dinoprostone vs Foley catheter for induction of labor at term with an unfavorable cervix: an open-label randomized controlled trial.

BACKGROUND: Induction of labor (IOL) with mechanical methods or pharmacological agents is used in about 20% to 30% of all pregnant women. We specialized in comparing the effectiveness and safety of dinoprostone vs transcervical Foley catheter for IOL in term pregnant women with an unfavorable cervix with adequate samples. OBJECTIVE: To compare the effectiveness and safety of dinoprostone vs transcervical Foley catheter for IOL in term pregnant women with an unfavorable cervix. STUDY DESIGN: This is a parallel, open-label randomized controlled trial in two maternal centers in Shanghai, China between October 2019 and July 2022. Women with a singleton pregnancy in cephalic presentation at term and an unfavorable cervix (Bishop score <6) scheduled for IOL were eligible. A total of 1860 women were randomly allocated to cervical ripening with either a dinoprostone vaginal insert (10 mg) or a 60 cc Foley catheter for up to 24 hours. The primary outcomes were vaginal delivery rate and time to vaginal delivery. Secondary outcomes included time to delivery and maternal and neonatal morbidity. Analysis was done from an intention-to-treat perspective. The trial was registered with the China trial registry (CTR2000038435). RESULTS: The vaginal birth rates were 72.8% (677/930) vs 69.9% (650/930) in vaginal dinoprostone and Foley catheter, respectively (aRR 1.04, 95% confidence interval [CI] 0.98-1.10, risk difference: 0.03). Time to vaginal delivery was not significantly different between the two groups (sub-distribution hazard ratio 1.11, 95% CI 0.99-1.24). Vaginal dinoprostone was more likely complicated with hyperstimulation with fetal heart rate changes (5.8% vs 2.8%, aRR 2.09, 95% CI 1.32-3.31) and placenta abruption (0.9% vs 0.1%, aRR: 8.04, 95% CI 1.01-64.15), while Foley catheter was more likely complicated with suspected intrapartum infection (5.1% vs 8.2%, aRR: 0.62, 95% CI 0.44-0.88) and postpartum infection (1.4% vs 3.7%, aRR: 0.38, 95% CI 0.20-0.72). The composite of poor neonatal outcomes was not significantly different between the two groups (4.5% vs 3.8%, aRR 1.21, 95% CI 0.78-1.88), while more neonatal asphyxia occurred in the dinoprostone group (1.2% vs 0.2%, aRR 5.39, 95% CI 1.22-23.92). In a subgroup analysis, vaginal dinoprostone decreased vaginal birth rate slightly in multiparous women (90.6% vs 97.0%, aRR 0.93, 95% CI 0.88-0.99). CONCLUSIONS: In term pregnant women with an unfavorable cervix, IOL with vaginal dinoprostone or Foley catheter has similar effectiveness. Foley catheter leads to better safety for neonates, while it may result in a higher risk of maternal infection. Furthermore, Foley catheter should be preferred in multiparous women.

Gel instillation sonohysterography (GIS) using Endosgel versus ExEmgel, comparison of pain and image quality and cost benefit analysis: A double blind randomised controlled trial. GISPAIN trial.

INTRODUCTION: Pain experience, physical reaction, image quality and adverse events during Gel Instillation Sonohysterography (GIS) can differ using gels with different compositions. As a result, patient satisfaction can also be affected. The effect of two instillation gels, Endosgel versus ExEmgel, using both the Visual Analogue Scale (VAS) and a Continuous Pain Score Meter (CPSM) was therefore compared. METHODS: This single centre double blind randomised controlled trial included 80 women planned for outpatient GIS, diagnosed with abnormal intrauterine bleeding or fertility disorders and suspicion on an intrauterine abnormality. Patients were randomly allocated to the instillation of Endosgel containing chlorhexidine or ExEmgel without chlorhexidine. Primary outcome was reported pain during the procedure using VAS. Secondary outcomes included pain score measured using CPSM, satisfaction to the procedure and preference at 3 weeks and 3 months after the procedure and image quality. A cost benefit analysis was also performed. RESULTS: The reported median VAS concerning pain during gel instillation was comparable in the Endosgel and ExEmgel group, 2.50 (IQR 0.00-5.00) and 2.00 (IQR 0.00-5.75) respectively (p = 0.69). The median VAS of the entire procedure was also similar: both 2.00 (IQR 0.00-5.00) (p = 0.86). CPSM-scores were not significantly different either. Both groups were similar in image quality (p = 0.83) and patient's satisfaction (p = 0.36). CONCLUSION: Concerning the pain experienced during a GIS procedure and patients' satisfaction, the ExEmgel was not proven to be superior to the Endosgel. Our advice is to use the gel that is available at the lowest costs, as the image quality is the same for both Endosgel and ExEmgel.

Bacteria-responsive drug release platform for the local treatment of bacterial vaginosis.

Bacterial vaginosis (BV) is a common vaginal infection affecting millions of women. Vaginal anaerobic dysbiosis occurs whenLactobacillusspp., the dominant flora in healthy vagina is replaced by certain overgrown anaerobes, resulting in unpleasant symptoms such as vaginal discharge and odor. With a high recurrence rate, BV also severely impacts the overall quality of life of childbearing women by inducing preterm delivery and increasing the risks of pelvic inflammatory disease and sexually transmitted infections. Among various BV-associated bacteria,Gardnerella vaginalis(G. vaginalis) has been identified as a primary pathogen since it has been isolated from almost all women carrying BV and exhibits higher virulence potential over other bacteria. When dealing with BV relapse, intravaginal drug delivery systems are superior to conventional oral antibiotic therapies in improving therapeutic efficacy owing to more effective drug dose, reduced drug resistance and minimized side effects such as stomach irritation. Traditional intravaginal drug administration generally involves solids, semi-solids and delivery devices inserted into the vaginal lumen to achieve sustained drug release. However, they are mostly designed for continuous drug release and are not preventative therapies, resulting in severe side effects caused by excess dosing. Stimuli-responsive systems that can release drug only when needed ('on-demand') can help diminish these negative side effects. Hence, we developed a bacteria-responsive liposomal platform for the prevention and treatment of BV. This platform demonstrated sustained drug release in the presence of vaginolysin, a toxin secreted specifically byG. vaginalis. We prepared four liposome formulations and evaluated their responsiveness toG. vaginalis. The results demonstrated that the liposome formulations could achieve cumulative drug release ranging from 46.7% to 51.8% over a 3-5 d period in response toG. vaginalisand hardly any drug release in the presence ofLactobacillus crispatus(L. crispatus), indicating the high specificity of the system. Overall, the bacteria-responsive drug release platform has great potential, since it will be the first time to realize sustained drug release stimulated by a specific pathogen for BV prevention and treatment. This on-demand therapy can potentially provide relief to the millions of women affected by BV.

Comparison of Misoprostol for Labor Induction: Vaginal Insert Versus Oral Application Concerning Efficiency and Safety.

BACKGROUND/AIM: The aim of the present retrospective study was to examine the efficiency and safety of the induction of labor with Misoprostol, administered either vaginally or orally. PATIENTS AND METHODS: This retrospective cohort study included pregnant women with a gestational age of ≥36 +0 weeks and a singleton pregnancy who underwent induction of labor with Misoprostol as vaginal insert or as tablet (oral) between January 2014 and January 2019 at the Department of Obstetrics and Gynecology of the University Hospital of Cologne. The objective of this study was to analyze the time until delivery and the maternal and neonatal outcomes. RESULTS: A total of 1,511 patients were included in this retrospective analysis, of whom 1,035 patients (68.5%) underwent induction of labor with a misoprostol vaginal insert (MVI) and 476 (31.5%) with tablets (oral misoprostol: OM). MVI significantly shortened the time from application to delivery (p<0.001) in comparison to OM, reduced the need for epidural anesthesia (EA) (p=0.018) without an increase in caesarean sections (CS) (p=1), ventouse deliveries (VD) (p=0.715), maternal birth injuries or a reduced neonatal outcome (APGAR-Score, umbilical cord pH). CONCLUSION: MVI is superior to OM in terms of efficiency (primary outcome: time from application to delivery) and is equally safe (primary outcome: CS rate). Our study, along with existing literature, highlights the need for further research, particularly regarding neonatal outcomes. Additionally, it underscores the importance of careful consideration when inducing labor and ensuring informed consent.

Innovative berberine nanoethosomal vaginal in situ gel: Unraveling polycystic ovary syndrome treatment on female Wistar rats.

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 32 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.

Use of vaginal dinoprostone for women with term prelabor rupture of membranes and an unfavorable cervix within 6 h versus within 6-24 h.

BACKGROUND: Most guidelines propose inducing labor within 24 h following term (37 or more weeks of gestation) prelabor rupture of membranes (PROM). However, the exact timing for initiating induction within the 24 h period remains unknown. This study aims to comparatively assess the efficacy and safety of the use of vaginal dinoprostone within 6 h versus within 6-24 h for singleton pregnancies with PROM and an unfavorable cervix (Bishop score < 6). METHODS: This was a retrospective cohort study including singleton pregnancies with PROM and an unfavorable cervix (Bishop score < 6) in which labor was induced using vaginal dinoprostone. Women were divided into two groups according to the timing of the use of induction (within 6 h versus within 6-24 h after PROM). Baseline maternal data, maternal and neonatal outcomes were recorded for statistical analysis. RESULTS: 450 women were included, 146 (32.4%) of whom were induced within 6 h of PROM and 304 (67.6%) were induced within 6-24 h. Cesarean delivery rate (15.8% versus 29.3%, p = 0.002) and nonreassuring fetal heart rate tracing (4.8% versus 10.5%, p = 0.043) in group with vaginal dinoprostone within 6 h were significantly lower than those in group with vaginal dinoprostone within 6-24 h. There was no significant differences in terms of duration from IOL to vaginal delivery. CONCLUSION: Induction of labor within 6 h with vaginal dinoprostone after PROM for singleton pregnancies with an unfavorable cervix (Bishop score < 6) significantly associated with less cesarean section, less nonreassuring fetal heart rate tracing, compared to induction of labor within 6-24 h after PROM.

Comparison of two intravaginal progesterone-releasing devices in lactating Holstein cows synchronized with a 5-d GnRH-based timed-AI protocol.

The objective of the study was to compare the effectiveness of CIDR vs. PRID-Delta devices for use in a 5-day Ovsynch protocol for TAI in lactating Holstein cows that were either not in estrus after the end of the voluntary waiting period or non-pregnant and not returning to estrus following the previous AI. Cows fitted with a collar-mounted automated activity monitoring system (Alta Cow Watch) were subjected to a standard 5-d Ovsynch protocol [100 µg of gonadorelin (GnRH) on Day 0 and 500 µg of cloprostenol on Days 5 and 6] and allocated randomly to receive either an intravaginal device containing 1.35 g (CIDR; n = 304) or 1.55 g (PRID ® DELTA; n = 304) of progesterone between Day 0 and 5. All cows received a second administration of GnRH at approximately 56 h and timed-AI (TAI) 72 h after intravaginal device removal. Inseminations were done using conventional frozen-thawed semen. Estrus events prior to TAI were recorded and transrectal ultrasonography was done on Day 0 to determine presence of a corpus luteum (CL) and 33 and 61 d post-TAI, respectively, to diagnose and confirm pregnancy. Cows had an average of 2.2 lactations, 124.3 days in milk, and a milk yield of 43.6 kg/d at enrollment. The overall percentage of cows with a CL at initiation of treatment was 68.8 % and did not differ between treatment groups. Cows with a CL had greater pregnancy per AI (P/AI) at 33 and 61 d post-TAI than cows without a CL (P < 0.01; 46.9 and 42.3 % vs. 32.1 and 27.4 %, respectively). The overall percentage of cows that expressed estrus prior to TAI was 24.8 % and did not differ between treatment groups; however, estrus expression prior to TAI affected P/AI at 33 and 61 d post-TAI (P < 0.01; 53.6 and 49.0 % vs. 38.5 and 33.9 % for those expressing or not expressing estrus, respectively). Pregnancy per AI at 33 d post-TAI tended to differ between treatment groups (P = 0.08; 46.1 vs. 38.5 % for PRID and CIDR groups, respectively) and P/AI at 61 d post-TAI was greater (P < 0.01) for PRID-treated cows (43.8 %) compared to CIDR-treated cows (31.6 %). Thus, PRID-treated cows had lower pregnancy loss than CIDR-treated cows (P < 0.01; 5.0 vs. 17.9 %). Also, treatment with a PRID tended (P = 0.08) to result in fewer twin pregnancies (7.9 vs. 14.5 % for PRID and CIDR treated cows, respectively). In conclusion, lactating dairy cows subjected to a 5-d Ovsynch TAI protocol plus a PRID-Delta had greater P/AI at 61 d post-TAI, lower pregnancy loss between 33 and 61 d post-TAI, and fewer twin pregnancies compared to cows subjected to a 5-d Ovsynch protocol plus a CIDR.

Effect of acidic vaginal pH on the efficacy of dinoprostone (PGE2) vaginal tablet for labor induction in full term pregnant women: a randomized controlled trial.

OBJECTIVES: There is controversial evidence that acidification of vaginal pH may increase the efficacy of vaginal prostaglandins in labor induction, with research being mainly focused on misoprostol. This study aims to evaluate the impact of this intervention on the progress of labor induction with dinoprostone (PGE2) vaginal tablet. METHODS: This double-blind, parallel-group, randomized study was conducted between October 2021 and December 2022 at Alexandra General Hospital, Athens, Greece. A total of 230 women with singleton, full term pregnancy that were scheduled for labor induction were randomly divided into two groups: Group A, who received acidic vaginal wash (5 % acetic acid) and Group B, who received a normal saline vaginal wash. Afterwards, participants received a vaginal tablet of 3 mg dinoprostone every 6 h (maximum two doses). RESULTS: There were no statistically significant differences in mode of delivery, duration of different labor stages, Bishop score changes and possible complications. Participants in the acidification group needed less often labor augmentation with oxytocin and epidural anesthesia (p=0.03). CONCLUSIONS: Vaginal acidification seems to have no effect on the efficacy of the dinoprostone vaginal tablet. Even though it may reduce the need for oxytocin augmentation, there is no apparent benefit on clinical outcomes, such as reduction in cesarean section rates or shorter labor duration. Future research is necessary in order to validate these findings.

Pharmabiotic/phytobiotic formulas approach and their intravaginal effect on different parameters.

Postpartum reproductive infections in cows generate significant economic losses. The use of lactic acid bacteria in animal health is an alternative tool to avoid antibiotic therapy in the prevention/treatment of bovine reproductive infections. In previous studies, 6 lactic bacteria from bovine mammary glands and vagina with beneficial, safe and technological characteristics were selected, and included in probiotic/phytobiotic formulas (combined with Malva and Lapacho extracts). In this work, probiotic and phytobiotic formulations were designed and their long-term viability determined. They were administered intravaginally to 30 females pregnant bovine pre and postpartum. The modification of the native microbiota and permanence/colonization of cultivable bacteria was evaluated, and also the safety of the designed products through the application of nutritional, clinical, hematological and biochemical parameters. The microorganisms maintained their viability up to 9 months at refrigeration temperature. The number of cultivable bacteria showed different pattern: total aerobic mesophylls increased slightly in all experimental groups, while Enterobacteriaceae increased after delivery, except in beneficial acid lactic bacteria + vegetable extract cows. Control and vegetable extract females showed the highest numbers of Enterobacteriaceae at the end of the trial (30 days postpartum). The number of lactic acid bacteria increased significantly in all the groups between 15 days pre and postpartum. The different parameters evaluated demonstrate the safety and harmlessness of the designed formulas, without producing local and systemic adverse effects in the cows.

Comparing cervical cerclage, pessary and vaginal progesterone for prevention of preterm birth in women with a short cervix (SuPPoRT): A multicentre randomised controlled trial.

BACKGROUND: Cervical cerclage, cervical pessary, and vaginal progesterone have each been shown to reduce preterm birth (PTB) in high-risk women, but to our knowledge, there has been no randomised comparison of the 3 interventions. The SuPPoRT "Stitch, Pessary, or Progesterone Randomised Trial" was designed to compare the rate of PTB <37 weeks between each intervention in women who develop a short cervix in pregnancy. METHODS AND FINDINGS: SuPPoRT was a multicentre, open label 3-arm randomised controlled trial designed to demonstrate equivalence (equivalence margin 20%) conducted from 1 July 2015 to 1 July 2021 in 19 obstetric units in the United Kingdom. Asymptomatic women with singleton pregnancies with transvaginal ultrasound cervical lengths measuring <25 mm between 14+0 and 23+6 weeks' gestation were eligible for randomisation (1:1:1) to receive either vaginal cervical cerclage (n = 128), cervical pessary (n = 126), or vaginal progesterone (n = 132). Minimisation variables were gestation at recruitment, body mass index (BMI), and risk factor for PTB. The primary outcome was PTB <37 weeks' gestation. Secondary outcomes included PTB <34 weeks', <30 weeks', and adverse perinatal outcome. Analysis was by intention to treat. A total of 386 pregnant women between 14+0 and 23+6 weeks' gestation with a cervical length <25 mm were randomised to one of the 3 interventions. Of these women, 67% were of white ethnicity, 18% black ethnicity, and 7.5% Asian ethnicity. Mean BMI was 25.6. Over 85% of women had prior risk factors for PTB; 39.1% had experienced a spontaneous PTB or midtrimester loss (>14 weeks gestation); and 45.8% had prior cervical surgery. Data from 381 women were available for outcome analysis. Using binary regression, randomised therapies (cerclage versus pessary versus vaginal progesterone) were found to have similar effects on the primary outcome PTB <37 weeks (39/127 versus 38/122 versus 32/132, p = 0.4, cerclage versus pessary risk difference (RD) -0.7% [-12.1 to 10.7], cerclage versus progesterone RD 6.2% [-5.0 to 17.0], and progesterone versus pessary RD -6.9% [-17.9 to 4.1]). Similarly, no difference was seen for PTB <34 and 30 weeks, nor adverse perinatal outcome. There were some differences in the mild side effect profile between interventions (vaginal discharge and bleeding) and women randomised to progesterone reported more severe abdominal pain. A small proportion of women did not receive the intervention as per protocol; however, per-protocol and as-treated analyses showed similar results. The main study limitation was that the trial was underpowered for neonatal outcomes and was stopped early due to the COVID-19 pandemic. CONCLUSIONS: In this study, we found that for women who develop a short cervix, cerclage, pessary, and vaginal progesterone were equally efficacious at preventing PTB, as judged with a 20% equivalence margin. Commencing with any of the therapies would be reasonable clinical management. These results can be used as a counselling tool for clinicians when managing women with a short cervix. TRIAL REGISTRATION: EU Clinical Trials register. EudraCT Number: 2015-000456-15, clinicaltrialsregister.eu., ISRCTN Registry: ISRCTN13364447, isrctn.com.

Patient experience in prostaglandins-induced cervical ripening: A comparative study using a standardized questionnaire.

OBJECTIVE: Cervical ripening for induction of labor is often associated with negative patient experience. The debate over the most effective cervical ripening method persist, with a significant gap in research specifically addressing patient satisfaction. Our study aims to compare patient experience with two induction methods, slow-release intravaginal dinoprostone device and orally administered misoprostol. METHOD: We conducted a before-and-after comparative study at a university tertiary hospital, including all patients undergoing cervical ripening with a Bishop score of 3 or lower. Our study compared two separate two-month periods, where the methods for cervical ripening differed. The first period employed an intravaginal dinoprostone slow-release device, while the second period used oral misoprostol. The primary outcome was patient experience, assessed using the EXIT questionnaire, a standardized and validated self-reported measure. Secondary outcomes were efficacy and safety outcomes. RESULTS: A total of 165 patients were included, 81 induced with dinoprostone and 84 induced with misoprostol. The EXIT questionnaire completion rate was 67.9 % (n = 55) in the dinoprostone group and 76.1 % (n = 64) in the misoprostol group (p = 0.23). Patients induced with misoprostol reported higher levels of satisfaction compared to those induced with dinoprostone, which can be attributed to reduced discomfort associated with the induction process (mean satisfaction score 2.26 ± 0.98 versus 2.80 ± 0.85 on a 1 to 5 likert-scale, p-value < 0.01). Adverse effects were reported less frequently with misoprostol compared to dinoprostone (20.2 % vs 48.1 %, p-value < 0.01). Time between cervical ripening and delivery was shorter in the misoprostol group (27.0 ± 10.2 h vs 32.5 ± 10.0, p < 0.01). There were no difference in mode of delivery or other obstetrical and neonatal outcomes. CONCLUSION: For women undergoing cervical ripening, oral misoprostol appears to be a less invasive method for labor induction, associated with higher levels of satisfaction and reduced discomfort compared to the intravaginal dinoprostone slow-release device.

Recent advances in in vitro models simulating the female genital tract toward more effective intravaginal therapeutic delivery.

INTRODUCTION: Intravaginal drug delivery has emerged as a promising avenue for treating a spectrum of systemic and local female genital tract (FGT) conditions, using biomaterials as carriers or scaffolds for targeted and efficient administration. Much effort has been made to understand the natural barriers of this route and improve the delivery system to achieve an efficient therapeutic response. AREAS COVERED: In this review, we conducted a comprehensive literature search using multiple databases (PubMed Scopus Web of Science Google Scholar), to discuss the potential of intravaginal therapeutic delivery, as well as the obstacles unique to this route. The in vitro cell models of the FGT and how they can be applied to probing intravaginal drug delivery are then analyzed. We further explore the limitations of the existing models and the possibilities to make them more promising for delivery studies or biomaterial validation. Complementary information is provided by in vitro acellular techniques that may shed light on mucus-drug interaction. EXPERT OPINION: Advances in 3D models and cell cultures have enhanced our understanding of the FGT, but they still fail to replicate all variables. Future research should aim to use complementary methods, ensure stability, and develop consistent protocols to improve therapy evaluation and create better predictive in vitro models for women's health.

Vaginal Progesterone for Pregnancy Prolongation After Arrested Preterm Labor: A Randomized Clinical Trial.

Importance: Women with arrested preterm labor (APTL) are at very high risk for spontaneous preterm delivery (SPTD), the leading cause of neonatal mortality and morbidity. To date, no maintenance therapy has been found to be effective for pregnancy prolongation. A few clinical trials with considerable methodological limitations have demonstrated some efficacy for 400 mg vaginal micronized progesterone (VMP) in women with APTL. Objective: To investigate the effectiveness of daily 400 mg VMP for the prolongation of pregnancy after APTL. Design, Setting, and Participants: This randomized clinical trial was conducted between December 19, 2018, and February 27, 2023, in 3 university-affiliated medical centers in Israel. Participants included women with singleton and twin pregnancies after APTL following tocolysis at 24 weeks 0 days to 34 weeks 0 days' gestation. Women with a history of preterm delivery or asymptomatic cervical shortening in the current pregnancy were excluded. Interventions: Participants were randomly allocated to receive VMP 200 mg twice a day or no treatment until 36 weeks 6 days' gestation. Main Outcomes and Measures: The primary end points were mean number of days from study enrollment to delivery and the rate of SPTD prior to 37 weeks' gestation. Results: A total of 129 participants were enrolled (65 in the VMP group and 64 in the no-treatment group). Mean (SD) age was 27.6 (5.1) years. Between the VMP and no-treatment groups, there was no difference in pregnancy prolongation (mean [SD], 40.0 [17.8] vs 37.4 [20.3] days; P = .44) and the rate of SPTD (16 [25%] vs 19 [30%]; relative risk, 0.8; 95% CI, 0.5-1.5; P = .52). In twin pregnancies, including 12 and 15 pairs in the VMP and no-treatment groups, respectively, VMP prolonged pregnancy (mean [SD], 43.7 [18.1] vs 26.1 [15.2] days; P = .02), postponed the delivery week (36.5 [1.4] vs 34.7 [2.2] weeks; P = .01), shortened the length of stay in the neonatal intensive care unit (4.9 [10.6] vs 13.2 [18.5] days; P = .03) and overall hospital stay (8.3 [9.6] vs 15.1 [17.2] days; P = .03), and was associated with a higher birth weight (2444 [528] vs 2018 [430] g; P = .01). Conclusions and Relevance: These findings show that VMP given in a dosage of 200 mg twice a day following APTL is not an effective treatment to prolong pregnancy or prevent SPTD. However, VMP demonstrated beneficial effects in twin pregnancies, warranting further investigation. Trial Registration: ClinicalTrials.gov Identifier: NCT02430233.

A randomized, pilot trial comparing vaginal hyaluronic acid to vaginal estrogen for the treatment of genitourinary syndrome of menopause.

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.

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.

Effectiveness of vaginal probiotics Lactobacillus crispatus chen-01 in women with high-risk HPV infection: a prospective controlled pilot study.

Female genital tract infection with high-risk human papilloma virus (HR-HPV) has the risk of developing into cervical cancer, and there is still a lack of effective therapeutic strategies. Probiotic intervention is considered as a potential intervention for HR-HPV, while exploration into living probiotic preparations for specific diseases remains limited and insufficient. This prospective controlled pilot study was conducted to observe the effect of intravaginal transplantation of a vaginal isolated natural probiotic strain, Lactobacillus crispatus chen-01, on the clearance of high-risk HPV infection. 100 women with high-risk HPV infection were enrolled and randomly divided into placebo group and probiotic treatment group, which received intravaginal transplantation of L. crispatus chen-01. Cervical exfoliated cells were collected 6 months later for detecting DNA load, typing of HPV, and cytological analysis. Our results showed that vaginal transplantation with L. crispatus chen-01 significantly reduced viral load of HPV, ameliorated HPV clearance rate, and improved vaginal inflammation state without causing obvious adverse reactions. Analysis of 16S rRNA sequencing revealed that L. crispatus chen-01 could effectively reconstitute the vaginal microbiota in women with high-risk HPV, which might be one of the underlying mechanisms of the beneficial effect of L. crispatus chen-01 transplantation. Our results suggested that vaginal transplantation of L. crispatus chen-01 might be a promising treatment for patients with high-risk HPV infection.

Short stature and vaginal dinoprostone as independent predictors of composite maternal-newborn adverse outcomes in induction of labor after one previous cesarean: a retrospective cohort study.

BACKGROUND: The rates of labor induction and cesarean delivery is rising worldwide. With the confluence of these trends, the labor induction rate in trials of labor after cesarean can be as high as 27-32.7%. Induction of labor after one previous cesarean (IOLAC) is a high-risk procedure mainly due to the higher risk of uterine rupture. Nevertheless, the American College of Obstetricians and Gynecologists considers IOLAC as an option in motivated and informed women in the appropriate care setting. We sought to identify predictors of a composite of maternal and newborn adverse outcomes following IOLAC. METHODS: The electronic medical records of women who delivered between January 2018 to September 2022 in a Malaysian university hospital were screened to identify cases of IOLAC. A case is classified as a composite adverse outcome if at least one of these 11 adverse outcomes of delivery blood loss ≥ 1000 ml, uterine scar complications, cord prolapse or presentation, placenta abruption, maternal fever (≥ 38 0C), chorioamnionitis, intensive care unit (ICU) admission, Apgar score < 7 at 5 min, umbilical artery cord artery blood pH < 7.1 or base excess ≤-12 mmol/l, and neonatal ICU admission was present. An unplanned cesarean delivery was not considered an adverse outcome as the practical management alternative for a clinically indicated IOLAC was a planned cesarean. Bivariate analysis of participants' characteristics was performed to identify predictors of their association with composite adverse outcome. Characteristics with crude p < 0.10 on bivariate analysis were incorporated into a multivariable binary logistic regression analysis model. RESULTS: Electronic medical records of 19,064 women were screened. 819 IOLAC cases and 98 cases with composite adverse outcomes were identified. Maternal height, ethnicity, previous vaginal delivery, indication of previous cesarean, indication for IOLAC, and method of IOLAC had p < 0.10 on bivariate analysis and were incorporated into a multivariable binary logistic regression analysis. After adjustment, only maternal height and IOLAC by vaginal dinoprostone compared to Foley balloon remained significant at p < 0.05. Post hoc adjusted analysis that included all unplanned cesarean as an added qualifier for composite adverse outcome showed higher body mass index, short stature (< 157 cm), not of Chinese ethnicity, no prior vaginal delivery, prior cesarean indicated by labor dystocia, and less favorable Bishop score (< 6) were independent predictors of the expanded composite adverse outcome. CONCLUSION: Shorter women and IOLAC by vaginal dinoprostone compared to Foley balloon were independently predictive of composite of adverse outcome.

Shorter stature and dinoprostone labor induction are independent predictors of a composite maternal-newborn adverse outcome excluding unplanned cesarean delivery.

Cervical ripening with vaginal Misoprostol plus Hyoscine-N-Butylbromide versus vaginal Misoprostol alone among pregnant women: a double-blind randomised controlled trial.

Objective: To compare cervical ripening time with the use of vaginal Misoprostol plus Hyoscine-N-Butylbromide, with vaginal Misoprostol alone. Design: A double-blind randomized controlled trial with Pan-African Clinical Trials Registry (PACTR) approval number PACTR202112821475292. Setting: Federal Medical Centre, Asaba, Nigeria. Participants: A total of 126 eligible antenatal patients for cervical ripening were enrolled. Interventions: Participants in Group A had 25µg of vaginal misoprostol with 1ml of intramuscular placebo, and those in Group B had 25µg of vaginal misoprostol with 20mg of Intramuscular Hyoscine (1 ml). Oxytocin infusion was used when indicated, and the labour was supervised as per departmental protocol. Main outcome measure: Cervical ripening time. Results: The mean cervical ripening time was statistically significantly shorter in the hyoscine group (8.48±4.36 hours) than in the placebo group (11.40±7.33 hours); p-value 0.02, 95% CI 0.80-5.05. There was no statistically significant difference in the mean induction-delivery interval in Group A (7.38±5.28 hours) compared to Group B (7.75±5.04 hours), with a value of 0.54. The mode of delivery was comparable. However, women in Group B (53, 84.1%) achieved more vaginal deliveries than women in Group A (50, 79.4%); p-value 0.49. Thirteen women in Group A (20.6%) had a caesarean section, while ten women (15.9%) in Group B had a caesarean section (p-value 0.49, RR 0.94, CI 0.80-1.11). Adverse maternal and neonatal outcomes were not statistically significant between the two groups. Conclusion: Intramuscular hyoscine was effective in reducing cervical ripening time when used as an adjunct to vaginal Misoprostol, with no significant adverse maternal or neonatal outcome. Funding: None declared.