Cervical ripening as an outpatient procedure in the pandemic - minimizing the inpatient days and lowering the socioeconomic costs.

OBJECTIVES: With an increasing incidence of labor induction the socioeconomic costs are increasing and the burden on hospital capacities is rising. In addition, the worldwide SARS-CoV-2 pandemic asks for improvements in patient care during pregnancy and delivery while decreasing the patient-staff contact. Here, we are retrospectively analyzing and comparing a mechanical ripening device that is utilized as an outpatient procedure to misoprostol and dinoprostone as inpatient induction methods in a low risk cohort. METHODS: This is a retrospective comparative analysis of obstetric data on patients who presented for cervical ripening and labor induction. Ninety-six patients received a mechanical ripening agent as an outpatient procedure. As a control group, we used 99 patients with oral misoprostol (PGE1) and 42 patients with vaginal dinoprostone (PGE2) for cervical ripening in an inpatient setting. Data from 2016 until 2020 were analysed. RESULTS: Baseline characteristics showed no significant differences. Delivery modes were similar in all groups. The time period from patient admission to onset of labor was significantly shorter in the outpatient group (p<0.001): 10.9 h/0.5 days (±13.6/0.6) for osmotic dilator vs. 17.9 h/0.7 days (±13.1/0.5) for oral misoprostol vs. 21.8 h/0.8 days (±15.9/0.7) for vaginal dinoprostone. With 20.4 h/0.8 days (±14.3/0.6) the osmotic dilator group displayed significantly the shortest inpatient stay from admission to delivery (p=0.027). The patient subgroup of misoprostol had 25.7 h/1.1 days (±14.9/0.6) of inpatient stay from admission to delivery and the patient group of dinoprostone 27.5 h/1.1 days (±16.0/0.7). There were fewer hospital days in the outpatient group: 84.9 h/3.5 days vs. 88.9 h/3.7 days vs. 93.6 h/3.9 days (outpatient osmotic dilator vs. inpatient misoprostol and dinoprostone, respectively). CONCLUSIONS: New approaches are required to decrease individual contacts between patients and staff while maintaining a high quality patient care in obstetrics. This analysis reveals that outpatient mechanical cervical ripening can be as safe and effective as inpatient cervical ripening with PGE1/PGE2, while lowering patient-staff contact and total hospital stays and therefore decreasing the socioeconomic costs.

Intravaginal misoprostol versus uterine curettage for missed abortion: A cost-effectiveness analysis.

PURPOSE: To evaluate the cost-effectiveness of a strategy based on direct-acting uterine curettage (UC) versus a pre-direct-acting misoprostol (1600 mg) in patients with missed abortion (MA), from the perspective of a National Health System. METHODS: An open prospective cohort study was carried out at Reina Sofía University Hospital (Córdoba, Spain) from January 1, 2019 to December 31, 2019 in 180 patients diagnosed with MA. The patients chose medical treatment with intravaginal misoprostol (800 µg/4 h) or UC after receiving complete and detailed information. The effectiveness, clinical characteristics of the patients, costs of treating and managing the disease, and satisfaction with the procedures were recorded. RESULTS: One hundred and forty-five patients (80.6%) chose misoprostol versus 35 patients (19.4%) who chose UC. The effectiveness of misoprostol has been 42% evaluated at 48 h; UC success rate has been 100%. The incidence of side effects is significantly higher in patients treated with misoprostol (p < 0.05); as well as the number of care received by the patient (p < 0.05). Satisfaction is higher in patients treated with UC (p < 0.05). However, the cost is almost 5-folds higher in patients treated with UC (p < 0.05). CONCLUSION: UC has a higher success rate, greater satisfaction, and a lower incidence of side effects, although significantly increases the cost compared to misoprostol in MA.

Cost-effectiveness analysis of vaginal misoprostol versus dinoprostone pessary: A non-inferiority large randomized controlled trial in France.

OBJECTIVE: To assess the cost-effectiveness of vaginal misoprostol (PGE1; 25 µg) compared with a slow-release dinoprostone (PGE2) pessary (10 µg) for labor induction due to an unfavorable cervix at term. METHODS: We used data from an open-label multicenter, randomized non-inferiority trial that recruited women for whom labor was induced for medical reasons. The incremental cost-effectiveness ratio was assessed from the payer's perspective, with the focus on inpatient care costs and using the cesarean deliveries avoided (CDA) rate as the primary analysis and the rate of vaginal delivery within 24 h (VD24) as the secondary analysis. RESULTS: Analyses were based on 790 women in each group. Differences between treatment arms were the mean cost per patient of €4410 and €4399, a CDA rate of 80.1% and 77.9% and a VD24 rate of 46.1% and 59.4% for dinoprostone and misoprostol, respectively. Dinoprostone is not cost-effective according to the CDA rate and misoprostol was either a cost-effective or a dominant strategy according to the VD24. CONCLUSION: Misoprostol and dinoprostone have equal cost management with mixed efficacy according to the clinical outcome used. Finally, misoprostol may be an attractive option for hospitals as the price is lower and it is easier to use. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01765881. URL: https://clinicaltrials.gov/ct2/show/NCT01765881. ClinicalTrialRegistrer.eu: 2011-000933-35. URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2011-000933-35/FR.

Single-dose pharmacokinetics and pharmacodynamics assessment of oestriol and trimegestone containing vaginal rings in healthy women with childbearing potential.

PURPOSE: To evaluate the pharmacokinetics and pharmacodynamics of oestriol (E3) and trimegestone (TMG) in healthy women after application of three different vaginal rings over 21 days. The vaginal rings had a nominal delivery rate of 0.413/0.050 mg/day (Test 1), 0.311/0.090 mg/day (Test 2) and 0.209/0.137 mg/day (Test 3) E3/TMG. METHODS: Thirty-five healthy women were randomised to receive a single application of Test 1, 2 or 3 (Clinical Trial NCT03343912). The E3 and TMG plasma concentration was determined by LC-MS/MS. Oestradiol (E2) and progesterone (PG) serum concentrations, and bleeding patern were determined as pharmacodynamic parameters. Safety was assessed by evaluation of adverse events and local tolerability. RESULTS: The total and maximum exposure of E3 and TMG increased in a proportional ratio to dose. However, not in a magnitude which was expected from the dose differences for E3. During Test 2 and 3 treatment all E2 and PG values remained on a well suppressed level until end of treatment. E2 and PG serum levels increased distinctly earlier after ring removal with Test 1 compared to Test 2 and 3. Test 3 achieved 95.24% of "no bleeding" days under treatment followed by Test 1 (91.67%), and Test 2 (86.15%). CONCLUSIONS: The Test 3 formulation presented the best dose combination of E3/TMG for contraception. Moreover, all vaginal rings were well tolerated.

Preclinical safety assessment of a therapeutic human papillomavirus DNA vaccine combined with intravaginal interleukin-7 fused with hybrid Fc in female rats.

This study was conducted to establish the toxicological profile of combination treatment with therapeutic HPV DNA vaccines (GX-188E) and the long-acting form of recombinant human interleukin-7 fused with hybrid Fc (IL-7hyFc). GX-188E was administered intramuscularly by electroporation with or without IL-7hyFc intravaginally once per 2 weeks for 8 weeks (five times) in female Sprague-Dawley rats. Because up-regulation of immune responses and migration of antigen-specific T cells in cervicoviginal tissue were predicted as therapeutic effects, we distinguished adverse effects from therapeutic effects based on the severity of the systemic immune response, reversibility of lymphoid tissue changes, target tissue damage, and off-target immune responses. We observed that the number of neutrophils was increased, and the number of lymphocytes was decreased in the blood. Further, myofiber degeneration, necrosis, fibroplasia, and cell infiltration were observed at the GX-188E administration site. These changes were fully or partially recovered over a 4-week period. Analysis of lymphocytes in spleen revealed that CD4+ T cells and total T cells decreased in rats treated with GX-188E in combination with a high dose of IL-7hyFc (1.25 mg/animal). However, these changes were not considered adverse because they were transient and may have been related to electroporation-mediated DNA delivery or the local migration of lymphocytes induced by IL-7. Therefore, the potential toxicity of the combination of GX-188E and IL-7hyFc treatment was comparable to that of GX-188E treatment alone, and the no observed adverse effect level for GX-188E with IL-7hyFc was considered as 320 µg/animal for GX-188E and 1.25 mg/animal for IL-7hyFc.

Timed artificial insemination in crossbred mares: Reproductive efficiency and costs.

Timed artificial insemination (TAI) has boosted the use of conventional artificial insemination (CAI) by employing hormonal protocols to synchronize oestrus and ovulation. This study aimed to evaluate the efficiency of a hormonal protocol for TAI in mares, based on a combination of progesterone releasing intravaginal device (PRID), prostaglandin (PGF2α ) and human chorionic gonadotropin (hCG); and compare financial costs between CAI and TAI. Twenty-one mares were divided into two groups: CAI group (CAIG; n = 6 mares; 17 oestrous cycles) and TAI group (TAIG; n = 15 mares; 15 oestrous cycles). The CAIG was subjected to CAI, involving follicular dynamics and uterine oedema monitoring with ultrasound examinations (US), and administration of hCG (1,600 IU) when the dominant follicle (DF) diameter's ≥35 mm + uterine oedema + cervix opening. The AI was performed with fresh semen (500 × 106 cells), and embryo was recovered on day 8 (D8) after ovulation. In TAI, mares received 1.9 g PRID on D0. On D10, PRID was removed and 6.71 mg dinoprost tromethamine was administered. Ovulation was induced on D14 (1,600 IU of hCG) regardless of the DF diameter's, and AI was performed with fresh semen (500 × 106 cells). On D30 after AI, pregnancy was confirmed by US. The pregnancy rate was 80.0% in TAIG and 82.3% in CAIG (p > .05). The TAI protocol resulted in 65% reduction in professional transport costs, and 40% reduction in material costs. The TAI was as efficient as CAI, provided reduction in costs and handlings, and is recommended in mares.

Oral versus intra-vaginal imidazole and triazole anti-fungal treatment of uncomplicated vulvovaginal candidiasis (thrush).

BACKGROUND: Anti-fungals are available for oral and intra-vaginal treatment of uncomplicated vulvovaginal candidiasis. OBJECTIVES: The primary objective of this review is to assess the relative effectiveness (clinical cure) of oral versus intra-vaginal anti-fungals for the treatment of uncomplicated vulvovaginal candidiasis. Secondary objectives include the assessment of the relative effectiveness in terms of mycological cure, in addition to safety, side effects, treatment preference, time to first relief of symptoms, and costs. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, and two trials registers on 29 August 2019 together with reference checking and citation searching. SELECTION CRITERIA: We included randomised controlled trials published in any language comparing at least one oral anti-fungal with one intra-vaginal anti-fungal in women (aged 16 years or over) with a mycological diagnosis (positive culture, microscopy for yeast, or both) of uncomplicated vulvovaginal candidiasis. We excluded trials if they solely involved participants who were HIV positive, immunocompromised, pregnant, breast feeding or diabetic. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures as recommended by Cochrane. MAIN RESULTS: This review includes 26 trials (5007 participants). Eight anti-fungals are represented. All but three trials included participants with acute vulvovaginal candidiasis. Trials were conducted in Europe: UK (3), Croatia (2). Finland (2), the Netherlands (2), Germany (1), Italy (1), Sweden (1) and one trial across multiple European countries, USA (7) Thailand (2), Iran (2), Japan (1) and Africa (Nigeria) (1). The duration of follow-up varied between trials. The overall risk of bias of the included trials was high. There was probably little or no difference shown between oral and intra-vaginal anti-fungal treatment for clinical cure at short-term follow-up (OR 1.14, 95% CI 0.91 to 1.43; 13 trials; 1859 participants; moderate-certainty evidence) and long-term follow-up (OR 1.07, 95% CI 0.77 to 1.50; 9 trials; 1042 participants; moderate-certainty evidence). The evidence suggests that if the rate of clinical cure at short-term follow-up with intra-vaginal treatment is 77%, the rate with oral treatment would be between 75% and 83%; if the rate of clinical cure at long term follow-up with intra-vaginal treatment is 84%, the rate with oral treatment would be between 80% and 89%. Oral treatment probably improves mycological cure over intra-vaginal treatment at short term (OR 1.24, 95% CI 1.03 to 1.50: 19 trials; 3057 participants; moderate-certainty evidence) and long-term follow-up (OR 1.29, 95% CI 1.05 to 1.60; 13 trials; 1661 participants; moderate-certainty evidence). The evidence suggests that if the rate of mycological cure at short-term follow-up with intra-vaginal treatment is 80%, the rate with oral treatment would be between 80% and 85%; if the rate of mycological cure at long-term follow-up with intra-vaginal treatment is 66%, the rate with oral treatment would be between 67% and 76%. In terms of patient safety, there is a low risk of participants withdrawing from the studies due to adverse drug effects for either treatment (23 trials; 4637 participants; high-certainty evidence). Due to the low certainty of evidence, it is undetermined whether oral treatments reduced the number of side effects compared with intra-vaginal treatments (OR 1.04, 95% CI 0.84 to 1.29; 16 trials; 3155 participants; low-certainty evidence). The evidence suggests that if the rate of side effects with intra-vaginal treatment is 12%, the rate with oral treatment would be between 10% and 15%. We noted that the type of side effects differed, with intra-vaginal treatments being more often associated with local reactions, and oral treatments being more often associated with systemic effects including gastro-intestinal symptoms and headaches. Oral treatment appeared to be the favoured treatment preference over intra-vaginal treatment or no preference (12 trials; 2206 participants), however the data were poorly reported and the certainty of the evidence was low. There was little or no difference in time to first relief of symptoms between oral and intra-vaginal treatments: four trials favoured the oral treatment, four favoured intra-vaginal, one study reported no difference and one was unclear. The measurements varied between the 10 trials (1910 participants) and the certainty of the evidence was low. Costs were not reported in any of the trials. AUTHORS' CONCLUSIONS: Oral anti-fungal treatment probably improves short- and long-term mycological cure over intra-vaginal treatment for uncomplicated vaginal candidiasis. Oral treatment was the favoured treatment preference by participants, though the certainty of this evidence is low. The decision to prescribe or recommend an anti-fungal for oral or intra-vaginal administration should take into consideration safety in terms of withdrawals and side effects, as well as cost and treatment preference. Unless there is a previous history of adverse reaction to one route of administration or contraindications, women who are purchasing their own treatment should be given full information about the characteristics and costs of treatment to make their own decision. If health services are paying the treatment cost, decision-makers should consider whether the higher cost of some oral anti-fungals is worth the gain in convenience, if this is the patient's preference.

A cost-effectiveness analysis of vaginal carbon dioxide laser therapy compared with standard medical therapies for genitourinary syndrome of menopause-associated dyspareunia.

BACKGROUND: Topical vaginal estrogen therapy is considered the gold standard treatment for genitourinary syndrome of menopause-associated dyspareunia, but early investigations of energy-based devices show promise for patients with contraindications or those who are refractory to vaginal estrogen cream therapy. Although evaluating safety, efficacy, and long-term outcomes for novel technologies is critically important when new technologies become available to treat unmet healthcare needs, evaluation of the costs of these new technologies compared with existing therapies is also critically important but often understudied. OBJECTIVE: We sought to perform a cost-effectiveness analysis of 3 therapies for genitourinary syndrome of menopause, including vaginal estrogen therapy, oral ospemifene therapy, and vaginal CO2 laser therapy and determine if vaginal laser therapy is a cost-effective treatment strategy for dyspareunia associated with genitourinary syndrome of menopause. STUDY DESIGN: An institutional review board-exempt cost-effectiveness analysis was performed by constructing a decision tree using decision analysis software (TreeAge Pro; TreeAge Software, Inc, Williamstown, MA) using integrated empirical data from the published literature. Tornado plots and 1-way and 2-way sensitivity analyses were performed to assess how changes in the model's input parameters altered the overall outcome of the cost-effectiveness analysis model. RESULTS: All 3 treatment methods were found to be cost-effective below the willingness-to-pay threshold of $50,000.00 per quality-adjusted life year for moderate dyspareunia. The incremental cost-effectiveness ratio for vaginal CO2 laser therapy was $16,372.01 and the incremental cost-effectiveness ratio for ospemifene therapy was $5711.14. Although all 3 treatment strategies were on the efficient frontier, vaginal CO2 laser therapy was the optimal treatment strategy with the highest effectiveness. In a 1-way sensitivity analysis of treatment adherence, vaginal CO2 laser therapy was no longer cost-effective when the adherence fell below 38.8%. Vaginal estrogen cream and ospemifene therapies remained cost-effective treatment strategies at all ranges of adherence. When varying the adherence to 100% for all strategies, oral ospemifene therapy was "dominated" by both vaginal CO2 laser therapy and vaginal estrogen cream therapy. In a 2-way sensitivity analysis of vaginal CO2 laser therapy adherence and vaginal CO2 laser therapy cost, vaginal CO2 laser therapy still remained the optimal treatment strategy at 200% of its current cost ($5554.00) when the adherence was >55%. When the cost fell to 20% of its current cost ($555.40), it was the optimal treatment strategy at all adherence values above 29%. CONCLUSION: This study showed that vaginal fractional CO2 laser therapy is a cost-effective treatment strategy for dyspareunia associated with GSM, as are both vaginal estrogen and oral ospemifene therapies. In our model, vaginal CO2 laser therapy is the optimal cost-effective treatment strategy, and insurance coverage should be considered for this treatment option if it is proven to be safe and effective in FDA trials.

Progesterone and preterm birth.

Progestogens (vaginal progesterone and intramuscular 17-hydroxyprogesterone acetate) are widely recommended for women at high risk of preterm birth. Typical regimens include 17-hydroxyprogesterone caproate (250 mg intramuscularly weekly), starting at 16-20 gestational weeks until 36 weeks or delivery for women with a singleton gestation and a history of spontaneous preterm birth, or vaginal progesterone (90-mg vaginal gel or 200-mg micronized vaginal soft capsules) for women with a short cervix (typically ≤25 mm). Although some randomized trials support this approach, neither of the largest trials (PROLONG for 17-hydroxyprogesterone acetate or OPPTIMUM for vaginal progesterone) demonstrated efficacy. There are almost no data on long-term effects, and none that shows benefit beyond the neonatal period. Although some analyses suggest the cost-effectiveness of the approach, a cervical length screening program followed by progesterone for those with a short cervix will reduce preterm birth rates by less than 0.5%. The present review assesses evidence on the efficacy, likely impact, and long-term effects of implementing the recommendations for progestogens in full. Clinicians and pregnant women can look forward to resolution of the conflicting views on efficacy once the Patient-Centered Outcomes Research Initiative (PCORI)-funded individual patient data meta-analysis is published.

The application of nanomaterial science in the formulation a novel antibiotic: Assessment of the antifungal properties of mucoadhesive clotrimazole loaded nanofiber versus vaginal films.

Candidiasis is the origin of several chronic diseases and causes a wide range of symptoms from mucosal to systemic and deadly infections. Vaginal patches are one of the best drug delivery systems for the treatment of fungal infections in the vaginal environment, so a mucoadhesive film containing drugs such as clotrimazole and metronidazole is commercially available for patients. In the present study, a physicochemical comparison is made between clotrimazole loaded film and nanofiber fabricated with the new hybrid mucoadhesive formulation of dextran and alginate. Toxicity testing was performed using the MTT assay. Bioadhesion and antifungal effects were investigated for fibers and films. The release behavior of clotrimazole from two systems was evaluated by Franz cell in each case. The most important difference between nanofibrous and film mats were obtained in antifungal, mucoadhesive, Young's modulus and morphology. The nanofiber has a higher antifungal effect and two-fold adhesive to the mouse tissue, than film. The inherent flexibility of nanofiber obviated the need for a plasticizer, which may have cytotoxic side effects. The Clotrimazole loaded nanofibrous of Alginate/Dextran mats were successfully electrospun. They exhibited more bioadhesive with higher and faster antifungal properties versus similar formulation film. Further in vivo investigation is required for their application in vaginal candidiasis.

Outpatient balloon catheter vs inpatient prostaglandin for induction of labour (OBLIGE): a randomised controlled trial.

BACKGROUND: Approximately one in four pregnant women undergo an induction of labour. The purpose of this study is to investigate the clinical effectiveness, safety, and cost-effectiveness for mothers and babies of two methods of cervical ripening - inpatient care for women starting induction with vaginal prostaglandin E2 hormones, or allowing women to go home for 18 to 24 h after starting induction with a single-balloon catheter. METHODS/DESIGN: This is a multi-centre randomised controlled trial in New Zealand. Eligible pregnant women, with a live singleton baby in a cephalic presentation who undergo a planned induction of labour at term, will be randomised to outpatient balloon-catheter induction or in-hospital prostaglandin induction. The primary outcome is caesarean section rate. To detect a 24% relative risk reduction in caesarean rate from a baseline of 24.8%, with 80% power and 5% type 1 error, will require 1552 participants in a one to one ratio. DISCUSSION: If outpatient balloon-catheter induction reduces caesarean section rates, has additional clinical benefits, and is safe, cost-effective, and acceptable to women and clinicians, we anticipate change in induction of labour practice around the world. We think that home-based balloon-catheter induction will be welcomed as part of a patient-centred labour-induction care package for pregnant women. TRIAL REGISTRATION: Australia New Zealand Clinical Trials Registry (ANZCTR), ACTRN: 12616000739415. Registered on 6 June 2016.

Cervical pessary vs vaginal progesterone for prevention of preterm birth in women with twin pregnancy and short cervix: economic analysis following randomized controlled trial.

OBJECTIVE: To compare the cost-effectiveness of cervical pessary vs vaginal progesterone to prevent preterm birth and neonatal morbidity in women with twin pregnancy and a short cervix. METHODS: Between 4 March 2016 and 3 June 2017, we performed this economic analysis following a randomized controlled trial (RCT), performed at My Duc Hospital, Ho Chi Minh City, Vietnam, that compared cervical pessary to vaginal progesterone in women with twin pregnancy and cervical length < 38 mm between 16 and 22 weeks of gestation. We used morbidity-free neonatal survival as a measure of effectiveness. Data on pregnancy outcome, maternal morbidity and neonatal complications were collected prospectively from medical files; additional information was obtained via telephone interviews with the patients. The incremental cost-effectiveness ratio was calculated as the incremental cost required to achieve one extra surviving morbidity-free neonate in the pessary group compared with in the progesterone group. Probabilistic and one-way sensitivity analyses were also performed. RESULTS: During the study period, we screened 1113 women with twin pregnancy, of whom 300 fulfilled the inclusion criteria of the RCT and gave informed consent to participate. These women were assigned randomly to receive cervical pessary (n = 150) or vaginal progesterone (n = 150), with two women and one woman, respectively, being lost to follow-up. The rate of morbidity-free neonatal survival was significantly higher in the pessary group compared with the progesterone group (n = 241/296 (81.4%) vs 219/298 (73.5%); relative risk, 1.11 (95% CI, 1.02-1.21), P = 0.02). The mean total cost per woman was 3146 € in the pessary group vs 3570 € in the progesterone group (absolute difference, -424 € (95% CI, -842 to -3 €), P = 0.048). The cost per morbidity-free neonate was significantly lower in the pessary group compared with that in the progesterone group (2492 vs 2639 €; absolute difference, -147 € (95% CI, -284 to 10 €), P = 0.035). CONCLUSION: In women with twin pregnancy and a short cervix, cervical pessary improves significantly the rate of morbidity-free neonatal survival while reducing costs, as compared with vaginal progesterone. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Metronidazole versus lactic acid for treating bacterial vaginosis (VITA): protocol for a randomised controlled trial to assess the clinical and cost effectiveness of topical lactic acid gel for treating second and subsequent episodes of bacterial vaginosis.

BACKGROUND: Bacterial vaginosis (BV) affects 30-50% of women at some time in their lives and is an embarrassing and distressing condition which can be associated with potentially serious comorbidities. Current antibiotic treatments such as metronidazole are effective but can result in side effects, and recurrence is common. This trial aims to investigate whether lactic acid gel is clinically effective and cost effective in the treatment of recurrent BV compared with metronidazole. METHODS: VITA is an open-label, multicentre, parallel group randomised controlled trial for women with a clinical diagnosis of BV and at least one previous BV episode in the past 2 years. Participants will be randomised 1:1 to intravaginal lactic acid gel 5 ml once daily for 7 days or oral metronidazole tablets 400 mg twice daily for 7 days. All participants will be followed up for 6 months to assess health status and healthcare costs. A subgroup will be interviewed to further explore adherence, tolerability and acceptability of treatment. The estimated sample size is 1900 participants to detect a 6% absolute increase in response rate to 86% in those receiving lactic acid gel. The primary outcome is participant-reported resolution of BV at Week 2. DISCUSSION: Results from this trial will help inform UK treatment guidelines for BV and may provide an alternative effective treatment for recurrent episodes of this condition which avoids repeated exposure to antibiotics. TRIAL REGISTRATION: ISRCTN, ISRCTN14161293. Registered on 8 September 2017.

Ospemifene versus local estrogen: adherence and costs in postmenopausal dyspareunia.

Aim: Objective was to compare adherence and persistence, as well as direct healthcare costs and utilization, of ospemifene to available local estrogen therapies (LETs). Patients & methods: This retrospective database study used integrated medical and pharmacy claims data from the IQVIA Real-World Data Adjudicated Claims - US Database. Results: Ospemifene patients had significantly greater adherence and persistence compared with the other nonring LETs. Ospemifene had the lowest mean outpatient costs of any of the LET cohorts, including the estradiol vaginal ring. Total all-cause healthcare costs were also significantly less for ospemifene patients compared with all other LETs.

A Randomized Trial of Progesterone in Women with Bleeding in Early Pregnancy.

BACKGROUND: Bleeding in early pregnancy is strongly associated with pregnancy loss. Progesterone is essential for the maintenance of pregnancy. Several small trials have suggested that progesterone therapy may improve pregnancy outcomes in women who have bleeding in early pregnancy. METHODS: We conducted a multicenter, randomized, double-blind, placebo-controlled trial to evaluate progesterone, as compared with placebo, in women with vaginal bleeding in early pregnancy. Women were randomly assigned to receive vaginal suppositories containing either 400 mg of progesterone or matching placebo twice daily, from the time at which they presented with bleeding through 16 weeks of gestation. The primary outcome was the birth of a live-born baby after at least 34 weeks of gestation. The primary analysis was performed in all participants for whom data on the primary outcome were available. A sensitivity analysis of the primary outcome that included all the participants was performed with the use of multiple imputation to account for missing data. RESULTS: A total of 4153 women, recruited at 48 hospitals in the United Kingdom, were randomly assigned to receive progesterone (2079 women) or placebo (2074 women). The percentage of women with available data for the primary outcome was 97% (4038 of 4153 women). The incidence of live births after at least 34 weeks of gestation was 75% (1513 of 2025 women) in the progesterone group and 72% (1459 of 2013 women) in the placebo group (relative rate, 1.03; 95% confidence interval [CI], 1.00 to 1.07; P = 0.08). The sensitivity analysis, in which missing primary outcome data were imputed, resulted in a similar finding (relative rate, 1.03; 95% CI, 1.00 to 1.07; P = 0.08). The incidence of adverse events did not differ significantly between the groups. CONCLUSIONS: Among women with bleeding in early pregnancy, progesterone therapy administered during the first trimester did not result in a significantly higher incidence of live births than placebo. (Funded by the United Kingdom National Institute for Health Research Health Technology Assessment program; PRISM Current Controlled Trials number, ISRCTN14163439.).

Vaginal pH: a simple assessment highly correlated with vaginal morphology and symptoms in postmenopausal women.

OBJECTIVE: The aim of the study was to determine the utility of vaginal pH as a marker of menopause and vulvar and vaginal atrophy (VVA) before and after local estrogen treatment. METHODS: Vaginal pH was determined using standard pH paper strips in two clinical trials involving postmenopausal women with signs and symptoms of VVA evaluated before and after intervention with vaginal estradiol in softgel capsules. The utility of vaginal pH was evaluated as a screening method for VVA due to menopause and correlations were analyzed between vaginal pH and VVA symptoms, physical changes, and maturation of the vaginal epithelium. RESULTS: Changes in vaginal pH were significantly correlated with changes in superficial and parabasal cell counts; vaginal epithelial changes of color, integrity, thickness, and secretion; and the VVA symptoms of vaginal dryness and dyspareunia (vaginal pain with intercourse). CONCLUSIONS: Vaginal pH consistently correlated with parabasal and superficial cells and the visual vaginal epithelial changes and symptoms of dryness and dyspareunia, and is thus a simple outpatient procedure that reflects the hormonal milieu and its effects on the vaginal epithelium.

Trends in oral and vaginally administered estrogen use among US women 50 years of age or older with commercial health insurance.

OBJECTIVE: We aimed to provide information through 2015 about use in the United States of estrogen products, including orally and vaginally administered products, in postmenopausal women. METHODS: We used prescription claims for US commercial health insurance to calculate, in women 50 years of age or older (n = 12,007,364), the age-standardized and age-specific annual prevalence of estrogen use, by formulation and route of administration, for the period 2006 through 2015. RESULTS: The age-standardized annual prevalence of a prescription claim for oral estrogens declined over time, from 83 per 1,000 women in 2007 to 42 per 1,000 women in 2015. The age-standardized annual prevalence of a prescription claim for vaginal estrogens peaked in 2011, at 42 per 1,000 women, before declining to 35 per 1,000 women in 2015. The age-standardized annual prevalence of a prescription claim for transdermal estrogen fluctuated between 15 and 17 per 1,000 women. In age groups under 65 years of age, annual prevalence rates for vaginal rings and inserts declined over the latter half of the study period. CONCLUSIONS: Analyses of US prescription claims data between 2006 and 2015 for women 50 years of age or older showed declining use of oral estrogen generally and vaginally administered estrogen products specifically in age groups less than 65 years of age.