Carboplatin-loaded ultradeformable vesicles for the management of endometrial cancer: in vitro and in vivo evaluation.

Aim: Present research work aimed to explore intravaginal route for the drug delivery for treatment of endometrial cancer (EC). Material & methods: Carboplatin (CBP)-loaded ultradeformable vesicle (CBP-UDV) was prepared and characterized for in vitro quality attributes and evaluated for its efficacy in rabbits using ultrasound imaging after intravaginal administration. Results & conclusion: The results showed that the formulation capable of carrying and localizing drug in uterus for prolonged period assisted by first uterine pass effect. Ultrasound imaging of the EC-induced rabbit model before and after treatment with CBP-UDV showed considerable regression in the EC tumor mass. The findings serve as the basis of successful utilization of the intravaginal route for management of EC by designing the formulation which can improve patient compliance.

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.

A pilot study to compare propranolol and misoprostol versus misoprostol and placebo for induction of labor in primigravidae; a randomized, single-blinded, placebo-controlled trial.

BACKGROUND: The Induction of labor is the most common obstetric procedure in daily practice. Introducing propranolol as a new drug to augment the action of prostaglandins will help in the induction process and decrease CS rates. Several researchers have used propranolol in the augmentation of labor. AIM: This pilot study compares propranolol and misoprostol versus misoprostol alone for labor induction in primigravids. METHODS: This is a Randomized clinical trial, single-blinded, placebo-controlled trial at Ain Shams University Maternity hospital. This study included 128 pregnant full-term primigravid women candidates for labor induction, randomized into two groups. All candidates underwent labor induction with 25 µg of vaginal misoprostol. Group I received 20 mg of oral propranolol tablets, while group II received sugary pills as a placebo. Candidates who responded successfully to induction were assessed for possible augmentation of labor by amniotomy or oxytocin infusion. The Primary outcome was induction to delivery interval, while the secondary outcomes were the duration of the latent phase, mode of delivery, and APGAR score of the neonate. RESULTS: The induction-delivery time was (11.8 ± 8.1 h. vs. 12.6 ± 8.9 h., P value = 0.027) and the duration of the latent phase of labor (7.9 ± 5.6 h. vs. 9.2 ± 6.03 h., P value = 0.017) were significantly shorter in the group of misoprostol and propranolol compared to the group of misoprostol and placebo. There was no statistically significant difference between both groups' mode of delivery, indications for cesarean section, misoprostol, and oxytocin doses, or neonatal outcome. (P value > 0.05). CONCLUSION: Propranolol, when used with misoprostol for induction of labor, results in augmentation of action of misoprostol and a significantly shorter induction-delivery interval. TRIAL REGISTRATION: We retrospectively registered this trial in clinicaltrial.gov on 01/09/2020 (NCT04533841). https://clinicaltrials.gov/ct2/show/NCT04533841.

In vitro and in silico computational methods for assessing vaginal permeability.

OBJECTIVE: Vaginal administration is an important alternative to the oral route for both topical and systemic use. Therefore, the development of reliable in silico methods for the study of drugs permeability is becoming popular in order to avoid time-consuming and costly experiments. METHODS: In the current study, Franz cells and appropriate HPLC or ESI-Q/MS analytical methods were used to experimentally measure the apparent permeability coefficient (Papp) of 108 compounds (drugs and non-drugs). Papp values were then correlate with 75 molecular descriptors (physicochemical, structural, and pharmacokinetic) by developing two Quantitative Structure Permeability Relationship (QSPR) models, a Partial Least Square (PLS) and a Support Vector Machine (SVM). Both were validated by internal, external and cross-validation. RESULTS: Based on the calculated statistical parameters (PLS model A: R2 = 0.673 and Q2 = 0.594, PLS model B: R2 = 0.902 and Q2 = 0.631, SVM: R2 = 0.708 and Q2 = 0.758). SVM presents higher predictability while PLS adequately interprets the theory of permeability. CONCLUSIONS: The most important parameters for vaginal permeability were found to be the relative PSA, logP, logD, water solubility and fraction unbound (FU). Respectively, the combination of both models could be a useful tool for understanding and predicting the vaginal permeability of drug candidates.

Fetal heart rate patterns and the incidence of adverse events after oral misoprostol administration for cervical ripening among low-risk pregnancies.

OBJECTIVE: Though misoprostol is commonly used for inpatient cervical ripening, its use in outpatient settings has been limited by safety concerns. This study was conducted to assess the association between early fetal heart tracing (FHT) and maternal tocodynamometry patterns and the incidence of adverse fetal and pregnancy outcomes after the administration of oral misoprostol for cervical ripening. METHODS: We conducted a retrospective cohort study of 9908 low-risk patients at ≥37 weeks gestation who received oral misoprostol for cervical ripening prior to rupture of membranes between 01/01/2012 and 12/31/2017 at Kaiser Permanente Northern California hospitals as inpatients. We excluded patients who received a different agent for cervical ripening or had any need for additional inpatient monitoring, including hypertensive disorders of pregnancy, diabetes, or intrauterine growth restriction. Abnormal FHT, abnormal uterine activity, and adverse pregnancy or fetal-related events documented in the electronic health record in the four hours after administration of the first and second doses of misoprostol were assessed using descriptive statistics. RESULTS: We found that 0.9% of patients experienced tachysystole after the first dose of misoprostol (0.6% without decelerations; 0.3% with decelerations). The incidence of variable decelerations only and other FHT abnormalities (i.e. bradycardia, late or prolonged decelerations, or absent or minimal variability) in the first hour after misoprostol administration were 7.1% and 6.7% respectively, and diminished over time. The need for tocolytic use was 0.2% in the first hour and declined over time to 0.03% in the fourth hour after the first dose. Urgent cesarean delivery occurred in 0.1% of patients after receiving the first dose of misoprostol. Patients who did not experience variable, prolonged, or late decelerations in the first hour after the initial misoprostol dose were less likely to have such FHT abnormalities in the subsequent three hours compared to patients who had other FHT abnormalities (11.8% among patients with no FHT abnormalities vs. 43.7% among patients with other FHT abnormalities; p <.001). The overall trends in outcomes over time were similar after the second dose of misoprostol. CONCLUSION: The risk of short-term adverse outcomes associated with misoprostol is low among relatively low-risk patients. FHT abnormalities occurred in up to 32% of patients in the first four hours of monitoring post-misoprostol. Patients with no FHT abnormalities in the first hour after receiving misoprostol had a low risk of developing adverse outcomes and FHT abnormalities on continued monitoring, while patients with any type of deceleration in the first hour were at higher risk of adverse outcomes and FHT abnormalities. Our data may inform the development of protocols for cervical ripening that allow reduced monitoring for a subset of low-risk patients, however, more research is needed to validate findings and develop clinical protocols.

Mode of delivery after labor induction with vaginal dinoprostone versus oral misoprostol for women with unfavorable cervix at term.

OBJECTIVE: To compare the delivery mode after labor induction with 10 mg vaginal dinoprostone insert versus oral misoprostol 50 µg/4 h for women with an unfavorable cervix. MATERIAL AND METHODS: This is a retrospective observational study comparing the before/after introduction of oral misoprostol for labor induction, conducted at the Saint-Étienne University Hospital on a cohort of 396 women with a Bishop score <6. One hundred and twelve women (28.3%) were treated with a 10 mg vaginal dinoprostone insert versus 284 (71.7%) with oral misoprostol 50 µg/4 h. The primary outcome was the cesarean section rate. RESULTS: Labor induction with vaginal dinoprostone was independently associated with an increased rate of cesarean sections compared to oral misoprostol (aOR = 2.44; CI95% from 1.35 to 4.40; p = 0.003). The use of vaginal dinoprostone increased the induction rate during more than 48 h (18.8% versus 9.9%; p = 0.02), and the occurrence of fetal heart rate changes (34.8% versus 21.1%; p = 0.005). The maternofetal morbidity was similar. CONCLUSION: Labor induction with vaginal dinoprostone was independently associated with an increased rate of cesarean sections compared to oral misoprostol in women with an unfavorable cervix.

Evaluation of the clinical efficacy of vaginal treatment options for persistent high-risk human papillomavirus infection after excisional treatment of cervical high-grade squamous intraepithelial lesions: a systematic review and Bayesian network meta-analysis.

BACKGROUND: To evaluate the clinical efficacy of different vaginal administration on cervical persistent high-risk human papillomavirus (HR-HPV) infection after excisional treatment for high-grade squamous intraepithelial lesions (HSIL). METHODS: Six databases (PubMed, EmBase, Cochrane Central, China Knowledge Network database, China Biomedical Literature Service, and WanFang database) were searched to collect randomized controlled trials (RCTs) of various types of vaginal administration compared to no treatment on persistent HR-HPV infection after HSIL excisional treatment, and comprehensive analysis of the clearance of different drugs on HR-HPV was performed using Bayesian reticulation meta-analysis. RESULTS: The study analyzed the efficacy of eight interventions, including Interferon, Baofukang, Paiteling, Bletilla striata Sanhuang Powder, Lactobacilli vaginal capsules, Fuanning + Interferon, Interferon + Lactobacilli vaginal capsules, and Interferon + Baofukang, on the clearance of HR-HPV after excisional treatment through pooling and analyzing data from 52 RCTs. The results of the study demonstrated that Interferon + Lactobacilli vaginal capsules [OR 16.0 (95% CIs 8.1-32.0)], Interferon + Fuanning [OR 16.0 (95% CIs 1.1-52.0)], and Interferon + Baofukang [OR 14.0 (95% CIs 6.8-28.0)] were all found to significantly improve postoperative HR-HPV clearance rates when compared to no treatment. Furthermore, when studies with high-risk bias were excluded, Interferon + Lactobacilli vaginal capsules [OR 8.6 (95% CIs 4.7-19.0)] and Interferon + Baofukang [OR 22.0 (95% CIs 8.7-59.0)] were still found to be positively associated with increased postoperative HR-HPV clearance rate. Additionally, the study´s results also indicate that Interferon + Baofukang was effective in enhancing the postoperative HR-HPV clearance rates, mainly when the studies were restricted to a follow-up period of at least 12 months [OR 9.6 (95% CIs 2.9-34.0)]. However, it is important to note that the majority of the trials (29 out of 52, 51.6%) were rated as moderate to high risk of bias, and the certainty of the evidence was moderate to very low. CONCLUSION: The application of various forms of vaginal administration, except for individual use of Lactobacilli vaginal capsules, is more efficacious than no treatment in patients with cervical persistent HR-HPV infection after excisional treatment. However, all of the estimates of the effect size for change in the efficiency of HR-HPV clearance are uncertain. Our confidence in effect estimates and ranking of treatments is low, which needs larger, more rigorous, and longer follow-up RCTs to resolve.

Outpatient vs inpatient induction of labor with oral misoprostol: A retrospective study.

INTRODUCTION: Induction of labor is one of the most common obstetrical procedures today, with a successively rising rate. With a limited number of hospital beds, the option of starting induction at home has gained increasing attention. The primary aim of this study was to compare the proportion of women achieving vaginal delivery and the duration of hospital stay before delivery in induction of labor with oral misoprostol starting at home and induction with oral misoprostol at the hospital, in a low-risk population. MATERIAL AND METHODS: Women with home induction (n = 282) were individually matched to controls induced at the hospital during the same time period regarding parity, age, body mass index, labor unit and indication for induction. RESULTS: The rates of vaginal birth were similar in outpatients and inpatients (84.8% vs 86.2%; p = 0.5). Time from hospital admission to delivery in the outpatient group was significantly shorter than in the inpatient group (12.8 vs 20.6 h; p < 0.001), as was total hospital stay (2 vs 3 days; p < 0.001). There were no significant differences between the groups in neonatal or maternal outcomes. One patient undergoing outpatient induction had an unplanned home birth. CONCLUSIONS: Starting induction at home reduced the time spent in hospital without affecting the vaginal delivery rate. Although underpowered to assess safety, this study did not show any differences in adverse maternal and perinatal outcomes between inpatients and outpatients. Further research is needed to evaluate the safety of outpatient induction of labor with misoprostol.

Intravaginal Drug Delivery Systems to Treat the Genitourinary Syndrome of Menopause: Towards the Design of Safe and Efficacious Estrogen-loaded Prototypes.

Estrogens locally delivered to the vagina by tablets, capsules, rings, pessaries, and creams are the most common and highly recommended platforms to treat the genitourinary syndrome of menopause (GSM). Estradiol, an essential estrogen, is routinely administered alone, or in combination with progestins, to effectively alleviate the symptoms associated with moderate to severe menopause when non-pharmacological interventions are not indicated. Since the risk and side effects of estradiol use depends on the administered amount and duration of use, the lowest effective dose of estradiol is recommended when long-term treatment is required. Although there is a wealth of data and literature comparing vaginally administered estrogen-containing products, there is a lack of information revealing the effect of the delivery system used and formulation constituent's attributes on the efficacy, safety, and patient acceptability of these dosage forms. This review therefore aims to classify and compare various designs of commercially available and non-commercial vaginal 17ß-estradiol formulations and analyze their performance in terms of systemic absorption, efficacy, safety, and patient satisfaction and acceptance. The vaginal estrogenic platforms included in this review are the currently marketed and investigational 17ß-estradiol tablets, softgel capsules, creams, and rings for the treatment of GSM, based on their different design specifications, estradiol loads, and materials used in their preparation. Additionally, the mechanisms of the effects of estradiol on GSM have been discussed, as well as their potential impact on treatment efficacy and patient compliance.

Development of children born to women with twin pregnancies treated with cervical pessary or vaginal progesterone: Follow-up of a randomized controlled trial.

INTRODUCTION: Preterm birth is the most common cause of neonatal morbidity and mortality. Women with twin pregnancies and a short cervical length are at high risk for preterm birth. Vaginal progesterone and cervical pessary have been proposed as potential strategies to reduce preterm birth in this high-risk population. Therefore, we aimed to compare the effectiveness of cervical pessary and vaginal progesterone in improving developmental outcomes of children born to women with twin pregnancies and mid-trimester short cervical length. MATERIAL AND METHODS: This was a follow-up study (NCT04295187) of all children at 24 months of age, born from women treated with cervical pessary or progesterone to prevent preterm birth in a randomized controlled trial (NCT02623881). We used a validated Vietnamese version of Ages & Stages Third Edition Questionnaires (ASQ-3) and a red flag questionnaire. In surviving children, we compared the mean ASQ-3 scores, abnormal ASQ-3 scores, the number of children with any abnormal ASQ-3 scores and red flag signs between the two groups. We reported the composite outcome of perinatal death or survival with any abnormal ASQ-3 score in offspring. These outcomes were also calculated in a subgroup of women with a cervical length ≤28 mm (<25th percentile). RESULTS: In the original randomized controlled trial, we randomized 300 women to pessary or progesterone. After counting the number of perinatal deaths and lost to follow-up, 82.8% parents in the pessary group and 82.5% parents in progesterone group returned the questionnaire. The mean ASQ-3 scores of the five skills and red flag signs did not differ significantly between the two groups. However, the percentage of children having abnormal ASQ-3 scores in fine motor skills was significantly lower in the progesterone group (6.1% vs 1.3%, P = 0.01). There were no significant differences in the composite outcome of perinatal death or survival with any abnormal ASQ-3 score in unselected women and in those with cervical length ≤28 mm. CONCLUSIONS: Cervical pessary and vaginal progesterone may have comparable effects on developmental outcomes in children at ≥24 months of age, born to women with twin pregnancies and short cervical length. However, this finding could be likely due to a lack of study power.

Effectiveness and acceptability of home use of misoprostol for medical abortion up to 10 weeks of pregnancy.

INTRODUCTION: The administration of mifepristone, followed by misoprostol, is widely used for medical abortion. Many studies have demonstrated home abortion to be safe in pregnancies up to 63 days of gestation, and recent data support its safety when extended to more advanced pregnancies. We studied the efficacy and acceptability of home use of misoprostol up to 70 days of gestation in a Swedish setting and compared the outcomes between pregnancies with a gestational age of up to 63 days and pregnancies with gestational age 64-70 days. MATERIAL AND METHODS: This prospective cohort study was performed between November 2014 and November 2021 at Södersjukhuset and Karolinska University Hospital, Stockholm, and some patients were also recruited from Sahlgrenska University Hospital, Göteborg and Helsingborg Hospital. The primary outcome was the rate of complete abortions and was defined as complete abortion without any need for surgical or medical intervention and assessed by clinical assessment, pregnancy test and/or vaginal ultrasound. Secondary objectives were assessed by daily self-reporting in a diary and included pain, bleeding, side effects and women's satisfaction and perception of home use of misoprostol. A comparison of categorical variables was made with Fisher's exact test. The significance level was set to a p-value ≤0.05. The study was registered at Clinicaltrials.gov on July 14, 2014 (NCT02191774). RESULTS: During the study period we enrolled 273 women opting for medical abortion with home use of misoprostol. In the early group, up to 63 days of gestation, 112 women were included with a mean gestational length of 45 days and in the late group, 64-70 days of gestation, 161 women with a mean gestations length of 66.3 days were included. Complete abortion occurred in 95% (95% CI 89-98) of women in the early group and in 96% (95% CI 92-99) in the late group. No differences were found regarding side effects and acceptability was similarly high in both groups. CONCLUSIONS: Our results show high efficacy and acceptability of medical abortion when misoprostol is administered at home up to 70 days of gestation. This supports previous findings about maintained safety when misoprostol is administered at home even past a very early pregnancy.

Clinical significances of Bishop score and vaginal bleeding to controlled-release dinoprostone delivery system (PROPESS) efficacy for cervical ripening: A retrospective single-center study in Japan.

AIMS: To evaluate the effect of vaginal bleeding on the efficacy of controlled-release dinoprostone delivery system (PROPESS) for cervical ripening and the factors affecting the PROPESS efficacy in a Japanese clinical setting. METHODS: A total of 100 term pregnant women in whom PROPESS was used due to an unfavorable cervix (Bishop score ≤ 6) were enrolled. We retrospectively investigated which factors, including vaginal bleeding, were associated with the success of cervical ripening using logistic regression analysis. Moreover, the effect of vaginal bleeding on vaginal acidity was examined in 24 selected cases (control, 11; rupture of membrane, 4; and vaginal bleeding, 8). RESULTS: A 25 women successfully ripened the cervix (effective group), and 75 were unsuccessful (noneffective group). Bishop score at insertion (adjusted odds ratio: 1.87; 95% confidence interval: 1.23-2.86; p = 0.004), and vaginal bleeding at PROPESS insertion (adjusted odds ratio 6.63; 95% confidence interval 1.21-36.36; p = 0.029) affected cervical ripening success. The cases with vaginal bleeding showed a significantly higher vaginal pH than the control cases (median value: 6.75 and 5.0, respectively). We identified no obvious adverse outcomes, such as tachysystole, fetal heart rate abnormality, or low Apgar/pH, associated with vaginal bleeding at insertion. CONCLUSIONS: Our findings suggest that the PROPESS efficacy depends on Bishop score at insertion and that vaginal bleeding at PROPESS insertion might have a significantly positive effect on cervical ripening in term pregnant women.

Safety and effectiveness of a novel home-use therapeutic ultrasound device for the treatment of vaginal dryness in postmenopausal women: a pilot study.

To evaluate safety and effectiveness of therapeutic ultrasound for treatment of postmenopausal vaginal dryness. In a pilot study, postmenopausal women with self-reported vaginal dryness were randomized (1:1) to double-blind ultrasound treatment (n = 21) or sham (n = 21) for 12 weeks. Primary effectiveness endpoint was change from baseline to week 12 in Vaginal Assessment Scale symptoms (dryness, soreness, irritation, dyspareunia). Secondary effectiveness endpoint was scoring of clinician-reported Vaginal Health Index (elasticity, fluid, pH, mucosa, moisture). After 12 weeks, participants received open-label ultrasound treatment to 1 year. Safety endpoint was treatment-emergent adverse events. In the modified intent-to-treat population, women showed (mean ± standard error) reduction in Vaginal Assessment Scale with ultrasound treatment versus sham (n = 15, −0.5 ± 0.2 vs n = 15, −0.4 ± 0.3; P = 0.9) and improved Vaginal Health Index (n = 9, 2.7 ± 0.9 vs n = 9, 0.6 ± 1.4; P = 0.3). In the per-protocol analysis population, ultrasound treatment (n = 9) versus sham (n = 8) significantly reduced symptoms score (−0.6 ± 0.3 vs −0.0 ± 1.0; P = 0.4) and significantly improved Vaginal Health Index (2.7 ± 0.9 vs −0.4 ± 1.2; P = 0.03). Improvement in effectiveness endpoints were seen at 1 year compared with baseline. There were no differences in treatment-emergent adverse events between ultrasound treatment versus sham and no serious adverse events. Home-use ultrasound was safe and effective for treating vaginal dryness after 12 weeks. Effectiveness was maintained to 1 year. Therapeutic ultrasound could offer a new, nonhormonal treatment option for postmenopausal women with vulvovaginal atrophy.

Effect of topical oxytocin gel on vaginal mucosa in postmenopausal Egyptian women: a clinical randomized trial.

BACKGROUND: Vaginal atrophy is common after menopause and is often linked to sexual dysfunction, particularly dyspareunia. AIM: The study aimed to investigate the effect of intravaginally applied oxytocin on expressions of vaginal atrophy. METHODS: Fifty postmenopausal women aged 47 to 66 years with vaginal atrophy participated in this double-blinded placebo-controlled study. The women were randomized to intravaginal treatment with either gel with 600 IU/mL of oxytocin (oxytocin group) or gel alone (control group) once daily for 2 weeks. The gel consisted of hypromellose, pH 3.8 (Vagovital). OUTCOMES: The color of the vaginal mucosa, the vaginal pH, and the cytology of vaginal epithelial cells were investigated before and after treatment. RESULTS: The color of the vaginal mucosa shifted from pale to red in all 25 patients treated with oxytocin but only in 4 patients in the control group (P < .001). There was a significant decrease in intravaginal pH in the oxytocin group and the control group, with the delta value being significantly greater in the oxytocin group than in the control group (P < .001). The vaginal maturation index increased significantly (P < .001) in the oxytocin group but not in the control group. CLINICAL IMPLICATIONS: Topical oxytocin gel offers an effective solution to the sexual dysfunction that is related to vaginal atrophy after menopause. STRENGTHS AND LIMITATIONS: Strengths include studying different outcomes of applying the oxytocin gel for vaginal atrophy. Limitations include the small-scale population with a relatively short duration of treatment (2 weeks). CONCLUSION: Intravaginal treatment with a gel containing 600 IU/mL of oxytocin effectively counteracts physical expressions of vaginal atrophy. TRIAL REGISTRATION: ClinicalTrials.gov (NCT05275270; https://clinicaltrials.gov/ct2/show/NCT05275270).

Management of genitourinary symptoms in patients with breast cancer: an updated systematic review of available evidence from randomized trials.

PURPOSE: The purpose of this systematic review update is to synthesize available data on management of genitourinary symptoms (GUS) in breast cancer patients, a common and challenging clinical scenario. METHODS: EMBASE, Ovid Medline, and the Cochrane Library were searched from September 2014 to December 2021 for randomized controlled trials which examined various interventions for GUS in breast cancer patients. Outcomes of interest included improvements in vaginal symptoms (e.g., dryness, pain, dyspareunia, itching), vaginal hormone response measured by validated scales (e.g., Vaginal Health Index, and Vaginal Maturation Index), and Female Sexual Function Index (FSFI). A team of reviewers participated in the processes of study selection, data collection, and risk of bias appraisal. A descriptive approach to synthesis was used. RESULTS: Of 842 unique citations identified (412 from this update, 430 from previous review), eight studies (n = 539) met inclusion criteria. Interventions included 0.005% estriol gel (EG; n = 50), intravaginal testosterone (IVT; n = 21), intravaginal prebiotic (n = 13), hyaluronic acid (HA; n = 12), polyacrylic acid (PA; n = 25), pH-balanced gel (n = 118), Replens® (n = 24), and Lidocaine (n = 22). These were compared to placebo/saline/lubricants/usual care (n = 228). FSFI total score was significantly improved by all interventions except IVT and lidocaine, and not measured for Replens®. Significant improvements in vaginal hormone responses were reported for EG and pH-balanced gel; however, no significant effects were found for IVT, HA, or prebiotics. Vaginal symptoms were significantly improved by EG, IVT, PA, and PH-balanced gel. CONCLUSION: Treatment of GUS remains a challenging issue. It is evident that more prospective trials are needed.

Effects of injectable and intravaginal progesterone on ewes' reproductive performance at breeding season beginning.

Progesterone (P4) is a steroid hormone that has a regulatory role in the female reproductive system. Studies on the effects of injectable progesterone on ewes are scarce, mainly related to their reproductive responses in the breeding season. This study aimed to compare reproductive performance and serum P4 concentration using injectable or intravaginal P4 in ewes. Two hundred and forty and eight Santa Inês x Dorper ewes (BW; 52.67 ± 11.76 kg; mean ± SE), body condition score (BCS; 2.5 ± 0.8; scale of 1-5), were distributed in four treatments: (i) Control: without administration of P4; (ii) CIDR: intravaginal implantation of 330 mg of P4 for 7 days; (iii) 1P4: 15 mg of P4 intramuscular (IM); and (iv) 2P4I: 30 mg of P4 IM. The first 18 days of breeding season were considered the synchronization period. Except for ewes in the control group, all other ewes received 263 µg IM of cloprostenol sodium for lysis of eventual CL at 24 h before the P4 treatment. After the synchronization period, all ewes were kept together with males for extra 28 days in the breeding season. At the beginning of breeding season, 90% of the ewes had serum P4 concentration less than 1 ng/mL. The estrus rate was greater (P < 0.01) in ewes on the CIDR treatment, with similar estrus rate among the other treatments. The P4 implant was able to keep blood P4 concentration greater than 1 ng/mL in ewes that received an implant of P4 during the 7 days. After implant removal, there was a great increase in the estrus manifestation on ewes in the CIDR treatment, leading to an increase in pregnancy rate at the beginning of breeding season. The current study demonstrated that ewes that received an intramuscular injection of 15 or 30 mg of P4 had similar reproductive performance than ewes that did not receive any P4 intramuscular injection. However, when ewes were implanted with P4 (CIDR), these animals had an increase in estrus manifestation, leading to greater pregnancy earlier during the breeding season.

Comparison of the effect of oral and vaginal misoprostol on labor induction: updating a systematic review and meta-analysis of interventional studies.

OBJECTIVES: This study is aimed to compare the effect of oral misoprostol with vaginal misoprostol to induce labor as a systematic review and meta-analysis. METHODS: Electronic databases including PubMed [Medline], Scopus, Web of science, Embase, Ovid, Cochrane library, and ClinicalTrials.gov were searched using the relevant keywords. All RCTs comparing the effect of oral vs vaginal misoprostol on labor induction were considered. The Cochrane Risk of Bias checklist was used for assessing quality of included RCTs. All statistical analyses were completed using STATA (Version 16) and Revman (Version 5). RESULTS: Thirty-three RCTs with 5162 patients (1560 in oral and 2602 in vaginal groups) were included in this meta-analysis. Labor induction length did differ significantly between the two routes of misoprostol administration [Standardized Mean Difference: 0.40 h, 95% confidence interval (CI) 0.34, 0.46; I2: 66.35%; P = 0.04]. In addition, the risk of neonatal death, tachysystole, uterine hyperstimulation, preeclampsia, non-FHR and abortion was lower in the oral misoprostol group and the risk of hypertonus, PROM, oxytocin need and cesarean fever was higher in this group than the vaginal misoprostol group. CONCLUSIONS: Based on results of this meta-analysis, it can be inferred that currently, clinical specialists can decide to use this drug orally or vaginally on a case-by-case basis, depending on the condition of the pregnant mother and the baby.

Foley catheter plus misoprostol versus misoprostol alone for labor induction.

OBJECTIVE: This study aimed to analyze the effects of Foley catheter combined with misoprostol in the labor induction process. METHODS: This is a nonblinded, block randomized, controlled trial that compared the association between transcervical Foley catheter/vaginal misoprostol 25 µg combination and vaginal misoprostol 25 µg alone in normal-risk and healthy pregnant women undergoing labor induction in the south of Brazil. RESULTS: A total of 230 patients with indications for labor induction were evaluated and classified into the "combined" group (Foley catheter plus misoprostol), consisting of 107 patients, and the "misoprostol" group (misoprostol only), consisting of 123 patients. The "combined" group was observed to have a shorter labor induction time (p=0.008). In addition, there was a lower need for misoprostol use for overall cervical ripening (p<0.001) and a lower relative risk of needing a second, third, or fourth misoprostol tablet in the "combined" group (risk ratio [RR] 0.80, 95% confidence interval [CI] 0.71-0.91; RR 0.41; 95%CI 0.31-0.56; and RR 0.29, 95%CI 0.17-0.52, respectively) (p<0.001). No statistically significant difference was found in induction failure rate, cesarean section rate, or perinatal outcomes. CONCLUSION: A combination of methods leads to shorter labor induction, lower need for misoprostol doses, and lower risk of cesarean section, with no increase in the rate of perinatal complications. REBEC number is RBR-7xcjz3z.

Single dose letrozole and misoprostol for termination of pregnancy through 63 days' gestation: A pilot study.

OBJECTIVES: We conducted a pilot study to evaluate a single dose of letrozole 30 mg prior to misoprostol 800 mcg buccally for medication abortion STUDY DESIGN: We enrolled 40 participants seeking medication abortion up to 63 days' gestation at a site in Salt Lake City, UT. Participants received a single dose of letrozole 30 mg in-clinic followed 2 days later by misoprostol 800 mcg buccally at home. They took a second dose of misoprostol if they had no bleeding within 24 hours of the first. Participants returned 7 to 10 days later for assessment of abortion outcome and side effects RESULTS: Thirty-seven participants (93%) returned for follow-up and 2 (5%) went to another facility from which research staff obtained outcome data. Three-fourths (29/39, 74%, 95% CI: 60%-89%) had a complete abortion; 4 (10%, 95% CI: 0.3%-20%) had an incomplete abortion and opted for aspiration, and 6 (15%, 95% CI: 4%-27%) had an ongoing pregnancy. All subjects with follow-up reported taking the first dose of misoprostol. Ten (27%) took the second dose as well; only three did so due to no bleeding. Nineteen participants (51%) reported side effects after letrozole prior to misoprostol and two people (5%) rated these effects as severe. Side effects following misoprostol occurred in 33 participants (89%) and were as expected based on previous literature. No serious adverse events were reported CONCLUSION: A single dose of letrozole 30 mg followed by misoprostol had lower than desirable efficacy and does not warrant further study. IMPLICATIONS: A single dose of letrozole does not appear to be an effective adjunct to misoprostol for medication abortion.

Intracervical Foley catheter plus intravaginal misoprostol compared to intravaginal misoprostol-only for cervical ripening: A systematic review and meta-analysis.

To compare the combination of intracervical Foley catheter and intravaginal misoprostol administration versus intravaginal misoprostol administration-only for cervical ripening. The Medline, EMBASE, ClinicalTrials.gov, PROSPERO, Scopus, and Cochrane Collaboration databases were searched systematically. Randomized controlled trials that included patients with a singleton viable fetus who underwent induction of labor that required cervical ripening with an unfavorable cervix (Bishop ≤ 6) were eligible for inclusion. Primary outcomes was time to delivery and rate of cesarean delivery. Thirteen trials with 2978 subjects met the inclusion criteria. There was no difference in the incidence of cesarean delivery between the two groups (RR, 0.90; 95 % CI, 0.72-1.14; I2 = 69 %). The combination group resulted in comparable time to delivery (MD -2.50 h; 95 % CI 0.38, -5.38; I2 = 97 %), shorter time to vaginal delivery (MD -3.49 h; 95 % CI -4.89, -2.09; I2 = 81 %), lower risk of neonatal intensive care unit (NICU) admission (RR 0.72, 95 % CI 0.58-0.90, I2 = 0 %), meconium-stained fluid (RR 0.48, 95 % CI 0.31-0.73, I2 = 28 %), and tachysystole with fetal heart trace changes (RR 0.49, 95 % CI 0.27-0.86, I2 = 43 %), compared with intravaginal misoprostol-only group. There was no statistical difference in rates of terbutaline use, endometritis or chorioamnionitis between the two groups. The combination of intravaginal misoprostol with intracervical Foley catheter for cervical ripening is not associated with shorter time to delivery. However, the combination group shows significant difference in shorter time to vaginal delivery, NICU admission, meconium-stained fluid, and tachysystole with fetal heart trace changes.