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Objective: To assess efficacy and safety of a single-dose vaginal clindamycin gel for bacterial vaginosis treatment.Methods: We conducted a double-blind, placebo-controlled, randomized study comparing clindamycin gel with placebo (2:1 ratio). Entry required clinical diagnosis of bacterial vaginosis, that is, all four Amsel's criteria, without other genital infections. Nugent scores of 7-10 were required for efficacy assessment, per updated 2019 U.S. Food and Drug Administration guidance. Patients were evaluated at screening, day 7-14, and day 21-30 (test of cure). Clinical cure was defined as resolution of three of four Amsel's criteria. Bacteriologic cure was defined as Nugent score lower than 4. Therapeutic cure was both clinical and bacteriologic cure. Primary outcome was clinical cure at the test-of-cure visit. Secondary endpoints were clinical cure at day 7-14, and bacteriologic and therapeutic cures at day 7-14 and test of cure. A sample size of 188 patients in the clindamycin group compared with 94 patients in the placebo group had 90% power to detect statistically significant difference (P=.05, 2-tailed).Results: Participants were seen between July 9, 2020, and November 12, 2020. Of 307 randomized women, 56.0% were Black and 88.3% reported one or more previous bacterial vaginosis episodes. In the modified intention-to-treat population, 70.5% of patients in the clindamycin group and 35.6% in the placebo group achieved clinical cure at test of cure (primary outcome) (difference of 34.9, 95% CI 19.0-50.8), as did 77.5% of patients in the clindamycin group and 42.6% of patients in the placebo group in the per-protocol population (difference of 34.9, 95% CI 17.0-52.7). Statistically significant differences between groups were seen for all secondary endpoints. Clinical cure rate in patients in the clindamycin group with more than three bacterial vaginosis episodes in the prior year was 70.0%. Approximately 15% (15.3%) of patients in the clindamycin group experienced one or more treatment-emergent adverse events related to study treatment, as did 9.7% of patients in the placebo group. The most frequent treatment-related, treatment-emergent adverse event was vulvovaginal candidiasis.Conclusion: A new, single-dose clindamycin vaginal gel was highly effective, with excellent safety, in women disproportionately affected by bacterial vaginosis, with Nugent scores of 7-10 at study entry.Funding Source: The study was funded by Daré Bioscience, Inc.Clinical Trials Registration: ClinicalTrials.gov, NCT04370548. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to compare intracervical (IC) and intravaginal (IV) application of prostaglandin E2 (PGE2) for labor induction in term pregnancies with unfavorable cervix.Study Design: This prospective randomized trial included 212 pregnant women with term pregnancy and unfavorable cervix randomly assigned for labor induction with either IC (0.5 mg) or IV (2 mg) PGE2 formulation. Main outcome measured was time interval from labor induction to delivery. Difference in mode of delivery and adverse perinatal outcomes between two studied groups was also investigated. Significance was set at p < 0.05.Results: Studied groups did not significantly differ regarding main characteristics such as age, parity, body mass index or Bishop score. Women in IV group compared to those in IC group had shorter induction to delivery time interval (p < 0.001) and induction to active phase time interval (p = 0.001), higher prevalence of vaginal delivery within 24 h of labor induction (63,3% vs 40,6%, p = 0.002) and higher prevalence of successful induction of labor (95,9% vs. 86,5%, p = 0.020). The analysis did not reveal significant difference in mode of delivery between groups (p = 0.453) or other adverse perinatal outcomes.Conclusion: IV application of PGE2 compared to IC application is more efficacious and comparably safe for labor induction in term pregnancies with unfavorable cervix and should be the method of choice for labor induction. [ABSTRACT FROM AUTHOR]

Background: Considering the importance of sexual function, high prevalence of sexual dysfunction (especially dyspareunia caused by atrophic vaginitis) in breastfeeding women, and lack of effective interventions, the present research aimed to determine the effect of oxytocin (OXT) vaginal gel on sexual function (primary outcome), sexual satisfaction, and depression (secondary outcomes) in the breastfeeding women.Methods: This randomized triple-blind controlled trial was conducted on 64 breastfeeding women who referred to health centers in the city of Tabriz, Iran, in 2020-21. Participants were equally assigned to intervention/control groups using block randomization. 200 IU of OXT vaginal gel was given to the participants in the intervention group daily for eight week and the same protocol was carried out for the control group with placebo. Standard questionnaires of Female Sexual Function Index (FSFI), Edinburgh Postpartum Depression Scale (EPDS) and Sexual satisfaction scale for women (SSSW) were completed at baseline and 8 weeks after intervention. ANCOVA test was used to compare post-intervention mean score of the groups, adjusted for the baseline values.Results: After intervention, there was no statistically significant difference between groups in terms of mean total score of FSFI (Adjusted Mean Difference (AMD): 1.14; 95% Confidence Interval (95% CI): -1.28 to 9.16; P= 0.349) and sexual satisfaction (AMD: 5.01; 95% CI: -0.53 to 10.56; P= 0.075). However, there was statistically significant difference between the groups in terms of mean scores of sexual contentment (AMD: 1.56; 95% CI: 0.29 to 2.83; P = 0.017) and depression (AMD: -1.90; 95% CI: -1.27 to -2.54; P < 0.001). One participant in the OXT group and one participant in the placebo group reported mild uterine contraction and one person in the placebo group reported vaginal burning sensations.Conclusions: No evidence was found for the effects of OXT gel in the improvement of FSFI, even though, OXT significantly improved sexual satisfaction in the domain of contentment, and improved the symptoms of depression in comparison to the placebo group. However, a definite conclusion requires more research in this regard.Trial Registration: the Iranian Registry of Clinical Trials (IRCT), code: IRCT20120718010324N55 , Date of registration: 27/05/2020, URL: https://en.irct.ir/user/trial/44986/view . [ABSTRACT FROM AUTHOR]

Objectives: We conducted a detailed pharmacokinetic assessment in macaques treated with vaginal gels formulated with HIV integrase strand transfer inhibitors (INSTIs) to better understand drug distribution and identify INSTI concentrations associated with previously demonstrated in vivo protection against vaginal simian HIV challenge.Methods: Six macaques received vaginal gel containing 1% raltegravir (30 mg) once-weekly over 6 weeks. Following a washout period, five macaques received once-weekly gel containing 0.23% L-870,812 (7 mg). Drug concentrations were measured in plasma, mucosal fluids and vaginal tissues at baseline and 2, 5 and 24 h post-dosing.Results: The median maximum concentration (Cmax) for raltegravir and L-870,812 in plasma was below the limit of quantification and 41.1 ng/mL, respectively. The Cmax in vaginal fluids (1441 and 1250 μg/mL) and tissues (266.7 and 368.4 μg/g) was achieved 2-5 h after dosing, respectively. A similar half-life was observed for raltegravir and L-870,812 in vaginal fluids (8-10 h) and remained 3-4 orders of magnitude above the protein-adjusted IC95 (0.016 and 0.106 μg/mL, respectively) at 24 h. Drug concentrations in vaginal fluids correlated well with those in vaginal tissues (Pearson r ≥ 0.788). Both drugs were consistently detected in rectal fluids 2 h after vaginal dosing, albeit at much lower levels (31-92-fold) than those in vaginal fluids.Conclusions: To the best of our knowledge, this study provides the first data on INSTI levels in vaginal tissues associated with in vivo protection and demonstrates rectal drug distribution of INSTIs after vaginal dosing. These findings may inform dose selection for topical products with INSTIs for HIV prevention. [ABSTRACT FROM AUTHOR]

Aim: We investigated the arcuate artery blood flow in the region of the abnormally localized placenta in women who had undergone insertion of an obstetric pessary and were receiving micronized progesterone.Materials and Methods: The study included 120 pregnant women with high perinatal risks and abnormal placental localization. The patients were randomized to receive the Arabin's pessary and vaginal micronized progesterone (Group A, n = 60) or vaginal micronized progesterone only (Group B, n = 60). Randomization was carried based on the order of hospital admission: odd patient numbers were allocated to Group A and even numbers to Group B. Patients underwent a series of ultrasound scans to evaluate the placental migration and presence of abnormal placental attachment. Depending on the results of the scan, study participants were divided into the following groups: (1) patients without placental migration: A1 (n = 23) and B1 (n = 42); and (2) patients with placental migration: A2 (n = 37) and B2 (n = 18). Women in subgroups A1 and B1 were further divided into the subgroups based on the presence of abnormal placental attachment: A1x (n = 5) and B1x (n = 12) with abnormal placental attachment; and A1O (n = 18) and B1O (n = 30) without the abnormal placental attachment.Conclusion: In patients with abnormal placental attachment, the resistance of blood flow in the arcuate arteries was significantly higher than in those with normal placental attachment. A significant increase in the blood flow resistance occurred between 24 and 28 weeks of gestation. The combined use of the obstetric pessary and vaginal micronized progesterone in women with abnormal placental localization helped maintain the resistivity index at low levels and reduce the rate of abnormal placental attachment by 1.3-fold (OR 0.694 (95% CI: 0.21-2.29)). [ABSTRACT FROM AUTHOR]

Objective: Vaginal progesterone and cervical pessary are both shown to be effective in preventing preterm. We conducted a meta-analysis to evaluate whether the combination of these two interventions has any additional benefit in preventing preterm birth and improving perinatal outcomes in asymptomatic women with a singleton gestation who had a midtrimester sonographic short cervix compared with vaginal progesterone alone.Methods: Five databases were searched from their inception to 21 February 2019. We estimated relative risk (RR) and 95% confidence intervals (CIs) for dichotomous outcomes. The primary outcome was preterm birth <34 weeks, and second outcomes included low birth weight (LBW) delivery, perinatal death, and neonatal intensive care unit (NICU) admission.Results: Three RCTs with a total of 820 participants were identified. Cervical pessary had no significant prevention effect of preterm birth when combined with vaginal progesterone compared to the control group with vaginal progesterone alone (RR = 0.91; 95% CI, 0.47-1.77). No significant difference has been revealed between groups in LBW delivery (RR = 1.13; 95% CI, 0.86-1.48), perinatal death (RR = 1.27; 95% CI, 0.58-2.78) and NICU admission (RR = 1.24; 95% CI, 0.84-1.85).Conclusions: Comparing with vaginal progesterone alone, cervical pessary plus vaginal progesterone did not reduce the rates of preterm birth at <34 weeks of gestation. There was no difference in LBW delivery, perinatal death, and NICU admission. We need more evidence to balance the benefit and side effects on the combination of vaginal progesterone and cervical pessary for preventing preterm birth. [ABSTRACT FROM AUTHOR]

Objective: To determine whether vaginal progesterone for programmed endometrial preparation is noninferior to intramuscular progesterone in terms of live birth rates from frozen embryo transfer (FET).Design: Three-armed, randomized, controlled noninferiority trial.Setting: Multicenter fertility clinic.Patient(s): A total of 1,346 volunteer subjects planning vitrified-warmed transfer of high-quality nonbiopsied blastocysts were screened, of whom 1,125 subjects were ultimately enrolled and randomly assigned to treatment.Intervention(s): The subjects were randomly assigned to receive, in preparation for FET, 50 mg daily of intramuscular progesterone (control group), 200 mg twice daily of vaginal micronized progesterone plus 50 mg of intramuscular progesterone every third day (combination treatment), or 200 mg twice daily of vaginal micronized progesterone.Main Outcome Measure(s): The primary outcome was live birth rate per vitrified-warmed embryo transfer. The secondary outcomes were a positive serum human chorionic gonadotropin test 2 weeks after FET, biochemical pregnancy loss, clinical pregnancy, clinical pregnancy loss, total pregnancy loss, serum luteal progesterone concentration 2 weeks after FET, and patient's experience and attitudes regarding the route of progesterone administration, on the basis of a survey administered to the subjects between FET and pregnancy test.Result(s): A total of 1,060 FETs were completed. The live birth rate was significantly lower in women receiving only vaginal progesterone (27%) than in women receiving intramuscular progesterone (44%) or combination treatment (46%). Fifty percent of pregnancies in women receiving only vaginal progesterone ended in miscarriage.Conclusion(s): The live birth rate after vaginal-only progesterone replacement was significantly reduced, due primarily to an increased rate of miscarriage. Vaginal progesterone supplemented with intramuscular progesterone every third day was noninferior to daily intramuscular progesterone, offering an effective alternative regimen with fewer injections.Clinical Trial Registration Number: NCT02254577. [ABSTRACT FROM AUTHOR]

Aim: This study was performed to evaluate the effects of vaginal versus intramuscular progesterone supplementations on the mood, quality of life, and metabolic changes in pregnant women with the history of previous preterm birth.Methods: This study was conducted as a prospective, randomized, open label, clinical trial evaluated 100 pregnant women who referred for prenatal visit, with 16-17 weeks of gestation from September 2014 through October 2015. The mothers were then randomly allocated into two groups: the vaginal progesterone group to receive 400 mg cyclogest vaginal suppositories (Actavis, UK limited, England) once daily, and the intramuscular progesterone group to receive weekly intramuscular injections of 250 mg of 17-hydroxyprogesterone caproate (17-HPC) (Bayer Schering Pharma, Germany), starting from the 16th to the 35th weeks of pregnancy. Demographics, medical and obstetrical history, sleeping disturbances, alteration in sexual desire, nausea/vomiting, serum levels of fasting blood sugar (FBS), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) were evaluated, first and 8 weeks later.Results: About 11 (11.2%) screened positive for psychosocial disorders; 25 (25.5%) had sleep disturbance, 11 (11.2%) had alteration in sexual desire, and 29 (29.6%) had nausea/vomiting upon enrollment. After 2 months of receiving daily vaginal progesterone, there was a significant increase in the GHQ-28 score (p < .001), and rates of positive screening for psychosocial disorders (p = .001) in this group. No statistically significant differences were observed in the HDL levels (p = .06), LDL levels (p = .15), rates of impaired FBS (p = .08), nausea/vomiting (p = .2), sexual desire alteration (p = .56), and sleep disturbance (p = 1) in the participants who were randomized to this group.Conclusion: Our results indicated that psychosocial disorders increased significantly at 24th week gestational age after 2 months of progesterone consumption in both groups which could show psychological impact of progesterone regardless of the route of consumption. This calls for higher psychological attention in these women. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Preterm birth is a global health priority. Using a progestogen during high-risk pregnancy could reduce preterm birth and adverse neonatal outcomes.Methods: We did a systematic review of randomised trials comparing vaginal progesterone, intramuscular 17-hydroxyprogesterone caproate (17-OHPC), or oral progesterone with control, or with each other, in asymptomatic women at risk of preterm birth. We identified published and unpublished trials that completed primary data collection before July 30, 2016, (12 months before data collection began), by searching MEDLINE, Embase, CINAHL, the Maternity and Infant Care Database, and relevant trial registers between inception and July 30, 2019. Trials of progestogen to prevent early miscarriage or immediately-threatened preterm birth were excluded. Individual participant data were requested from investigators of eligible trials. Outcomes included preterm birth, early preterm birth, and mid-trimester birth. Adverse neonatal sequelae associated with early births were assessed using a composite of serious neonatal complications, and individually. Adverse maternal outcomes were investigated as a composite and individually. Individual participant data were checked and risk of bias assessed independently by two researchers. Primary meta-analyses used one-stage generalised linear mixed models that incorporated random effects to allow for heterogeneity across trials. This meta-analysis is registered with PROSPERO, CRD42017068299.Findings: Initial searches identified 47 eligible trials. Individual participant data were available for 30 of these trials. An additional trial was later included in a targeted update. Data were therefore available from a total of 31 trials (11 644 women and 16185 offspring). Trials in singleton pregnancies included mostly women with previous spontaneous preterm birth or short cervix. Preterm birth before 34 weeks was reduced in such women who received vaginal progesterone (nine trials, 3769 women; relative risk [RR] 0·78, 95% CI 0·68-0·90), 17-OHPC (five trials, 3053 women; 0·83, 0·68-1·01), and oral progesterone (two trials, 181 women; 0·60, 0·40-0·90). Results for other birth and neonatal outcomes were consistently favourable, but less certain. A possible increase in maternal complications was suggested, but this was uncertain. We identified no consistent evidence of treatment interaction with any participant characteristics examined, although analyses within subpopulations questioned efficacy in women who did not have a short cervix. Trials in multifetal pregnancies mostly included women without additional risk factors. For twins, vaginal progesterone did not reduce preterm birth before 34 weeks (eight trials, 2046 women: RR 1·01, 95% CI 0·84-1·20) nor did 17-OHPC for twins or triplets (eight trials, 2253 women: 1·04, 0·92-1·18). Preterm premature rupture of membranes was increased with 17-OHPC exposure in multifetal gestations (rupture <34 weeks RR 1·59, 95% CI 1·15-2·22), but we found no consistent evidence of benefit or harm for other outcomes with either vaginal progesterone or 17-OHPC.Interpretation: Vaginal progesterone and 17-OHPC both reduced birth before 34 weeks' gestation in high-risk singleton pregnancies. Given increased underlying risk, absolute risk reduction is greater for women with a short cervix, hence treatment might be most useful for these women. Evidence for oral progesterone is insufficient to support its use. Shared decision making with woman with high-risk singleton pregnancies should discuss an individual's risk, potential benefits, harms and practicalities of intervention. Treatment of unselected multifetal pregnancies with a progestogen is not supported by the evidence.Funding: Patient-Centered Outcomes Research Institute. [ABSTRACT FROM AUTHOR]

Background: MB66 film is a multipurpose prevention technology (MPT) product with monoclonal antibodies (mAbs) against HIV-1 (VRC01-N) and HSV-1 and 2 (HSV8-N). The mAbs were produced by transient expression in Nicotiana benthamiana (N). We conducted a Phase I clinical trial to assess the safety, pharmacokinetics (PK), and ex vivo efficacy of single and repeated doses of MB66 when used intravaginally.Methods and Findings: The clinical trial enrolled healthy reproductive-aged, sexually abstinent women. In Segment A, 9 women received a single MB66 film which was inserted into the vaginal posterior fornix by a clinician. In Segment B, 29 women were randomly assigned to MB66 (Active) or Placebo film groups and were instructed to insert 1 film vaginally for 7 consecutive days. Visits and clinical sampling occurred predose and at various time points after single and repeated film doses. The primary endpoint was number of adverse events (AEs) Grade 2 or higher related to product use. Secondary endpoints included film dissolution rate, Nugent score (a Gram stain scoring system to diagnose bacterial vaginosis), vaginal pH, post-use survey results, cytokine concentrations in cervicovaginal lavage (CVL) specimens (assessed by Luminex assay), mAb concentrations in vaginal fluid collected from 4 sites (assessed by ELISA), and HIV and HSV neutralization activity of CVL samples ex vivo (assessed by TZM-bl and plaque reduction assay, respectively). The product was generally safe and well tolerated, with no serious AEs recorded in either segment. The AEs in this study were primarily genitourinary in nature with the most commonly reported AE being asymptomatic microscopic hematuria. There were no differences in vaginal pH or Nugent scores or significant increases in levels of proinflammatory cytokines for up to 7 days after film insertion in either segment or between Active and Placebo groups. Acceptability and willingness to use the product were judged to be high by post-use surveys. Concentrations of VRC01-N and HSV8-N in vaginal secretions were assessed over time to generate pharmacokinetic curves. Antibody levels peaked 1 hour postdosing with Active film (median: 35 μg/mL) and remained significantly elevated at 24 hours post first and seventh film (median: 1.8 μg/mL). Correcting for sample dilution (1:20), VRC01-N concentrations ranged from 36 to 700 μg/mL at the 24-hour time point, greater than 100-fold the IC50 for VRC01 (0.32 μg/mL); HSV8-N concentrations ranged from 80 to 601 μg/mL, well above the IC50 of 0.1 μg/m. CVL samples collected 24 hours after MB66 insertion significantly neutralized both HIV-1 and HSV-2 ex vivo. Study limitations include the small size of the study cohort, and the fact that no samples were collected between 24 hours and 7 days for pharmacokinetic evaluation.Conclusions: Single and repeated intravaginal applications of MB66 film were safe, well tolerated, and acceptable. Concentrations and ex vivo bioactivity of both mAbs in vaginal secretions were significantly elevated and thus could provide protection for at least 24 hours postdose. However, further research is needed to evaluate the efficacy of MB66 film in women at risk for HIV and HSV infection. Additional antibodies could be added to this platform to provide protection against other sexually transmitted infections (STIs) and contraception.Trial Registration: ClinicalTrials.gov NCT02579083. [ABSTRACT FROM AUTHOR]

Purpose: To compare between continuous and interrupted use of vaginal probiotic after vaginal clindamycin cream for treatment and prevention of recurrence of bacterial vaginosis.Methods: A double-blinded randomized controlled clinical trial, 273 women were randomly allocated to use clindamycin 2% vaginal cream 5 g at bedtime for 7 days followed after 1 week by continuous probiotics vaginal capsule once daily for 6 weeks (n = 129) or clindamycin 2% vaginal cream 5 g at bedtime for 7 days followed by one probiotic vaginal capsule twice a week for 6 weeks (n = 144). The initial evaluation was at 1 week after cessation of probiotics treatment to estimate the cure rates, the follow-up visits were at 1, 3, 6, and 9 months from the initial visit. The primary outcome of this study was cure rate; the secondary outcomes were the frequency of recurrence, the presence of vaginal discharge, pH > 4.5, positive whiff test and detection of clue cells.Results: At the initial visit there was no significant difference in cure rate between continuous probiotics group and interrupted probiotics group (87.4 versus 82.5%; p = .81). There was no significant difference between the two groups in the recurrence rate at one, three, six and 9 months follow up visits (p = .16, p = .42, p = .59, p = .66). There was no significant difference between both groups regarding vaginal discharge reduction, pH dropping, the presence of positive whiff test and detection of clue cells at one, three, six and 9 months follow up visits. Except at 9-month visits, the differences in vaginal discharge reduction and positive whiff test were statically significant.Conclusions: After initial treatment of bacterial vaginosis with vaginal clindamycin cream, the continuous use of vaginal probiotics is equally effective to short repetitive courses in terms of cure rates and prevention of relapse. [ABSTRACT FROM AUTHOR]

After over 3 decades of research, an effective anti-HIV vaccine remains elusive. The recently halted HVTN702 clinical trial not only further stresses the challenge to develop an effective HIV vaccine but also emphasizes that unconventional and novel vaccine strategies are urgently needed. Here, we report that a vaccine focusing the immune response on the sequences surrounding the 12 viral protease cleavage sites (PCSs) provided greater than 80% protection to Mauritian cynomolgus macaques against repeated intravaginal SIVmac251 challenges. The PCS-specific T cell responses correlated with vaccine efficacy. The PCS vaccine did not induce immune activation or inflammation known to be associated with increased susceptibility to HIV infection. Machine learning analyses revealed that the immune microenvironment generated by the PCS vaccine was predictive of vaccine efficacy. Our study demonstrates, for the first time to our knowledge, that a vaccine which targets only viral maturation, but lacks full-length Env and Gag immunogens, can prevent intravaginal infection in a stringent macaque/SIV challenge model. Targeting HIV maturation thus offers a potentially novel approach to developing an effective HIV vaccine. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study was to explore the outcome of low-risk singleton pregnancies with very short cervical length (CL ≤15 mm) according to method of treatment and CL at diagnosis.Material and Methods: Retrospective study on singleton pregnancies devoid of risk factors for spontaneous preterm delivery identified in the course of universal screening programs by vaginal sonography at 20-24 weeks of gestation to have very short CL ≤ 15 mm.Results: The study group consisted of 233 pregnancies with CL ≤ 15 mm of which 88 had cervical cerclage inserted and the remaining 145 were treated with vaginal progesterone. Mean CL at diagnosis was significantly shorter in the cerclage group (5 mm) compared with the progesterone group (12 mm). Regardless of treatment there was no difference in the rate of spontaneous preterm delivery at <32 weeks of gestation in women with CL ≥ 9 mm at screening (11% and 12% in the cerclage and progesterone groups, respectively). In contrast, in the subgroup with CL ≤ 8 mm cervical cerclage resulted in significantly lower rates of spontaneous preterm delivery at <32 weeks of gestation compared with progesterone treatment (20% and 45%, respectively, P = .009) and the median gestational age at birth was significantly greater (37 weeks vs 36 weeks, respectively, P = .013).Conclusions: The majority of asymptomatic singleton pregnancies with short CL will remain undelivered until 32 weeks of gestation whether treated with progesterone or cerclage. Women with extreme cervical shortening appear to benefit more from cervical cerclage. [ABSTRACT FROM AUTHOR]

Objective: To compare the effect of misoprostol combined with a cervical single or double-balloon catheter versus misoprostol alone for labor induction of singleton pregnancies with an unfavorable cervix.Methods: Systematic review and meta-analysis of randomized controlled trials (RCTs) regarding the comparison of two schemes for labor induction of singleton cephalic pregnancies with a Bishop score ≤7 and no contraindication for vaginal delivery. Six research databases were searched for articles published in all languages up to 10 May 2018 comparing misoprostol (oral or vaginal) in combination with a cervical placed single or double balloon catheter versus misoprostol treatment alone. Random effects models and inverse variance were used for meta-analyses. Summary measures were mean differences (MDs) and risk ratios (RRs) with 95% confidence interval (CI). Risk of bias was evaluated with the Cochrane tool and publication bias was assessed with Begg's and Egger's tests.Results: Fifteen RCTs reported predefined outcomes. Pooled analyses showed that the combined treatment (misoprostol + catheter) was associated with a shorter induction to delivery time interval (MD = -1.99 hours; 95% CI: -3.42, -0.56); in addition to fewer uterine hyperstimulations (RR = 0.39; 95% CI: 0.23, 0.67) and Neonatal Intensive Care Unit (NICU) admissions (RR = 0.75; 95% CI: 0.58, 0.97) as compared to misoprostol alone. There were no significant differences in RRs for tachysystole, chorioamnionitis, cesarean delivery rate, birthweight, and Apgar score at 5 minutes.Conclusion: The combined use of misoprostol and a cervical balloon catheter reduces the intervention to delivery time interval and number of NICU admissions in women induced with an unfavorable cervix. [ABSTRACT FROM AUTHOR]

Purpose: To compare the effectiveness of the Cook vaginal cervical ripening balloon (CCRB) with prostaglandin E2 (PGE2) insert for induction of labor in late pregnancy in primipara.Methods: We evaluated the effectiveness and safety of induction of labor using the improved Bishop score after CCRB or PGE2 administration, total stage of labor, hours until delivery (hours from placement of CCRB or PGE2 insert to parturition and delivery), delivery rate within 24 h, spontaneous delivery rate, successful induction rate, overstimulation syndrome, urgent delivery rate, pain scores, cesarean section rate, and outcomes related to delivery and perinatal morbidity, such as puerperal infection rate, total cost, satisfaction survey, and so on.Results: The improved Bishop Score and delivery rate within 24 h in the CCRB group were significantly higher than in the PGE2 group. The total stage of labor and hours until delivery in the CCRB group were significantly shorter than that in the PGE2 group. Rate of overstimulation syndrome and pain scores in the CCRB group were significantly lower than in the PGE2 group. Compared with the PGE2 group, the mean duration of hospitalization in the CCRB group was shorter and the total cost was less. No difference in satisfaction between the PGE2 and CCRB groups was observed.Conclusions: Compared with PGE2, CCRB reduced the total stage of labor, hours until delivery, pain scores, mean length of hospitalization, and total cost. CCRB increased the rate of delivery within 24 h with similar safety and maternal satisfaction compared with PGE2. [ABSTRACT FROM AUTHOR]

Introduction: Recto-vaginal endometriosis surgical management needing partial colpectomy is a surgically challenging condition and has been associated with a notable risk of major postoperative complications. In the present study we sought to compare feasibility and safety of total laparoscopic (TL) and vaginal-assisted (VA) routes in women affected by symptomatic recto-vaginal endometriosis with vaginal mucosa infiltration scheduled for minimally invasive surgery.Material and Methods: Multi-centric, retrospective cohort study on medical records of consecutive reproductive age women submitted to complete macroscopic eradication of symptomatic recto-vaginal endometriosis with vaginal mucosa infiltration between March 2013 and November 2017. The two groups were compared in terms of preoperative data and surgical outcomes.Results: 84 women were included in the study (TL = 57 and VA = 27). The two groups were comparable in terms of preoperative, surgical and postoperative data. The major postoperative complications rate was 5.3% (3 of 57) in the TL group and 7.4% (2 of 27) in the VA group, without a significant difference. In the TL group we reported one case of bowel anastomosis dehiscence and two cases of pelvic abscess. In the VA group, one case of small bowel perforation after extensive adhesiolysis treated with ileal resection and one case of rectal sub-occlusion after segmental resection and mechanical anastomosis were noticed.Conclusions: In women affected by recto-vaginal endometriosis with vaginal mucosal infiltration, perioperative outcomes do not seem to be influenced by the surgical route adopted. [ABSTRACT FROM AUTHOR]

Objective: To compare cervical pessaries plus vaginal progesterone versus long-term tocolysis for preventing preterm birth for women with a short cervix.Methods: Retrospective evaluation of women with singleton pregnancy who received cervical pessaries plus vaginal progesterone (combined group) or ritodrine hydrochloride (tocolysis group) for short cervix (≤25 mm at 20-24 weeks, or ≤20 mm at 25-34 weeks) at a general hospital in Kagoshima, Japan, 2015-2019. The primary outcome was rate of preterm birth (<36 weeks); secondary outcomes were maternal hospital admittance and treatment complications.Results: Data were evaluated from 95 women (combined group, n=43; tocolysis group, n=52). There was no significant difference in cervical length or gestational age at intervention between the groups. Overall, 3/43 (7.0%) women delivered before 36 weeks in the combined group versus 16/52 (30.8%) in the tocolysis group (relative risk, 0.56; 95% confidence interval, 0.41-0.76; P=0.004). Median maternal admittance was shorter in the combined group (6.6 vs 41.0 days, P<0.001). Although 36/43 (83.7%) women in the combined group reported increased vaginal discharge, no major complications occurred.Conclusion: A combination of pessaries and vaginal progesterone reduced the rate of preterm birth (<36 weeks) for women with short cervix as compared with long-term tocolysis. [ABSTRACT FROM AUTHOR]

Prolonged pregnancies are associated with foetal and neonatal complications. This study was performed to evaluate the efficacy of intravaginal isosorbide mononitrate (IMN) for cervical ripening in prolonged pregnancies. 122 pregnant women were recruited. Women were assigned to 25 µg sublingual misoprostol plus 40 mg isosorbide mononitrate or placebo. Statistical analysis was done using SPSS software (version 23) and T-test, Mann-Whitney and Chi-square test. p ≤ .05 was considered significant. The mean time between beginning of cervical ripening to Bishop score >6 was significantly shorter in IMN plus misoprostol group when compared to misoprostol plus placebo group (p = .02). The mean time from beginning of cervical ripening to the beginning of active phase of Labour was comparable between two groups (p = .274). The misoprostol plus IMN group had significantly shorter interval from the beginning of cervical ripening to the time of delivery. Isosorbide mononitrate in combination with misoprostol has a promising effect on cervical ripening and progress in labour.IMPACT STATEMENTWhat is already known on this subject? Prolonged pregnancy is associated with foetal, neonatal, and maternal complications. Because of these complications, many obstetricians tend toward the induction of prolonged pregnancies to reduce perinatal morbidity and mortality. Isosorbide mononitrate is a nitric oxide donor agent which is used vaginally for cervical ripening in term pregnancies resulting in various outcomes.What do the results of this study add? Isosorbide mononitrate in combination with misoprostol had a greater effect on cervical ripening and progress in labour than misoprostol alone in prolonged pregnancies.What are the implications of these findings for clinical practice and/or further research? According to results of the current study; using isosorbide mononitrate in combination with misoprostol could enhance successful vaginal delivery in prolonged pregnancy. Evaluation of maternal satisfaction by using this protocol is recommended in future studies. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess Gonadotropin Releasing Hormone agonist (GnRHa) trigger results of fresh in vitro fertilisation (IVF), Intracytoplasmic Sperm Injection (ICSI) cycles in high-responder patients. Thirty-six high-responder patients, undergoing GnRH antagonist protocol combined with GnRHa trigger for final oocyte maturation, were included. All cycles were autologous fresh transfer cycles. Fifteen of 36 patients had previous IVF/ICSI cycles triggered with human chorionic gonadotropin (hCG) and both cycles of these patients were compared. The mean fertilisation rate, blastocyst development and clinical pregnancy rates were 67%, 44.4% and 44.4%, respectively. The hCG and GnRHa trigger cycles of the same patients were compared as two groups (n: 15). 2PN oocyte counts were significantly higher in agonist trigger cycles (p .048). There were no differences in terms of M2 oocyte count and fertilisation rate. The blastocyst formation and clinical pregnancy rates for hCG and GnRHa trigger cycles were 33.3-66.7% and 13.3-46.7%, respectively. These results were found to be 2-fold and 3.5-fold higher, but not statistically significant. GnRHa trigger in combination with LPS is a good option for final oocyte maturation due to its good pregnancy outcomes and virtually eliminating OHSS risks.IMPACT STATEMENTWhat is already known on this subject? Gonadotrophin releasing hormone agonist (GnRHa) trigger is effective in the induction of oocyte maturation and prevention of Ovarian Hyperstimulation Syndrome (OHSS) on IVF cycles using antagonist protocol.What do the results of this study add? The main strength of this study is the comparison of different triggers in different cycles of the same patients. GnRHa trigger in combination with Luteal Phase Support (LPS) is a good option for final oocyte maturation due to its good pregnancy outcomes and virtually eliminating OHSS risks.What are the implications of these findings for clinical practice and/or further research? We suppose that GnRHa trigger combined with modified LPS is clinically more successful than Human Chorionic Gonadotropin (hCG) in regard to OHSS prevention and reproductive outcomes on fresh IVF/ICSI cycles. More extensive studies are needed to draw firm conclusions. [ABSTRACT FROM AUTHOR]

Background: Bacterial vaginosis (BV) increases HIV risk and adverse reproductive outcomes. Standard-of-care (SOC) for BV are antibiotics; however, cure rates are low. Probiotics for vaginal health may be useful in improving cure and recurrence although the regulatory framework governing probiotics and the conduct of randomized clinical trials to evaluate these has not been established in South Africa. We performed an exploratory single-blind trial evaluating a commercial oral-vaginal-combination probiotic as adjunct to SOC for BV treatment.Methods: Women with symptomatic vaginal discharge were screened for BV and common sexually transmitted infections (STIs). BV+ (Nugent 7-10) but STI- women were randomized to vaginal metronidazole alone (n = 12) or to metronidazole followed by a commercial oral/vaginal probiotic (n = 18). The primary qualitative outcome was to test the regulatory landscape for conducting randomized probiotic trials in South Africa; and acceptability of vaginal application by women. BV cure at 1 month (Nugent≤3) was the primary quantitative endpoint. Secondary quantitative endpoints were BV recurrence, symptoms, vaginal microbiota and genital cytokine changes over 5 months post-treatment.Results: The  South African Health Products Regulatory Authority (SAHPRA) reviewed and approved this trial. As probiotics continue to be regulated as health supplements in South Africa, SAHPRA required a notification application for this trial. Acceptability and adherence to the oral and vaginal application of the probiotic were high, although women reported a preference for oral capsules. 44.8% of women cleared BV one-month post-treatment, and no significant differences in BV cure (RR = 0.52, 95% CI = 0.24-1.16), recurrence, vaginal pH, symptoms, microbiota or vaginal IL-1α concentrations were found between SOC and intervention groups in this pilot study with an over-the-counter product.Conclusion: Navigation of the SAHPRA registration process for evaluating a commercial probiotic in a randomised trial laid the foundation for planned larger trials of improved probiotic products for vaginal health in South Africa. Although adherence to the vaginally delivered probiotic was high, women preferred oral application and we recommend that improvements in the content and method of application for future probiotics for vaginal health should be considered.Trial Registration: This trial was registered on 17 October 2017 with the South African National Clinical Trial Register ( http://www.sanctr.gov.za/ ; BV-trial1; DOH-27-1117-5579 ). [ABSTRACT FROM AUTHOR]

Background: Effective prevention of preterm birth as cause of serious risks for the infant as well as the mother pre- and postpartum is one of the still unsolved problems in modern medicine.Method: The government of the State of Thuringia in cooperation with the professional organization of obstetricians and gynecologists decided in 2016 to reestablish and promote a self-care screening program based on intravaginal (i.vag.) pH measurement to reduce the incidence of preterm birth by early diagnosis and therapy of genital infection.Results: Starting at zero in 2016, > 80% of pregnant women in the state had their vaginal pH monitored at the end of 2018 (n = 17.180). This was associated with a reduced incidence of early preterm birth measured by gestational week ≤ 32 (1.46 vs. 1.26%).Conclusion: The fourth millennium goal missed worldwide in 2015 as well as the newly declared third objective of the UN could come closer using the simple and cheap i.vag. pH-self-screening regime in prevention of preterm birth, an approach partly turning the woman from being object of medical care to being the subject in self-control of her pregnancy. This is also a well perceived change in paradigm from the perspective of females as well as physicians. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effect of adjunctive use of vaginal progesterone after McDonald cerclage on the rate of second-trimester abortion in singleton pregnancy.Methods: A randomized controlled trial at Woman's Health Hospital, Assiut University, Egypt, between April 2017 and March 2019 enrolled women eligible for McDonald cerclage. After cerclage, participants were randomly assigned to receive progesterone (400 mg pessary) once daily until 37 weeks or no progesterone. The primary outcome was rate of abortion before 28 weeks. Secondary outcomes included gestational age at delivery, preterm delivery, mean birthweight, Apgar score, and admission to the neonatal intensive care unit (NICU).Results: The rate of spontaneous abortion was higher in the no-progesterone group (P=0.016). Mean gestational age and mean birthweight was higher in the progesterone group (P<0.001 and P=0.002, respectively). The frequency of preterm neonates, neonates with Apgar score less than 7, and admission to NICU was higher in the progesterone group than in the no-progesterone group (P=0.005, P=0.008, and P=0.044, respectively).Conclusion: Adjunctive use of vaginal progesterone after McDonald cerclage was found to decrease the frequency of second-trimester abortion and to improve perinatal outcomes in singleton pregnancy. Clinicaltrials.gov: NCT02846909. [ABSTRACT FROM AUTHOR]

Objective: To evaluate opioid consumption among parturients with varying degrees of perineal lacerations.Methods: This was a retrospective analysis of women who delivered vaginally at our institution from 1 January 2014 to 12 April 2015. We collected information regarding the degree of perineal lacerations (no lacerations, first-/second-degree, third-/fourth-degree), analgesic consumption, and postpartum pain scores. The primary outcome was opioid use from 0-48 h postpartum. Univariate and multivariable regression analyses were performed to test for the association of laceration severity with opioid use.Results: We included 5598 women in the analysis; 1948 had no lacerations, 3434 had first-/second-degree lacerations, and 216 had third-/fourth-degree lacerations. In univariate analysis, parturients with third-/fourth-degree lacerations had significantly higher use of opioids within 48 h postpartum (53.2%) compared to women with no lacerations (30.03%) or first-/second-degree lacerations (28.6%) (p < .001). In the multivariable analysis, women with third-/fourth-degree lacerations had higher odds of opioid use than those without laceration [OR (95% CI) = 2.61 (1.75-3.85), p < .001]. In pairwise comparisons, those with third-/fourth-degree lacerations had higher odds of opioid use than those without lacerations [OR (95% CI) = 3.55 (2.20-5.74)], and those with first-/second-degree lacerations [OR (95% CI) = 2.15 (1.49-3.10)] (p < .001). Oxycodone equivalent consumption was significantly different among groups with a median (IQR) of 5.00 mg (0.00-27.50), 0.00 mg (0.00-5.00) and 0.00 mg (0.00-5.00) in women with third-/fourth-degree, first-/second-degree, and no lacerations, respectively, during the 0-48 h postpartum (p < .001).Conclusion: The use of opioids and opioid doses are higher in women with third-/fourth-degree perineal lacerations compared to those with first-/second-degree or no lacerations. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to evaluate the effects of combined management of placenta previa with the Arabin cervical pessary and progesterone.Study design: In this randomized controlled study, we followed up 217 patients with placenta previa and high risk of preterm birth. The main group (n = 81) underwent combined management with the Arabin cervical pessary and progesterone; the control group (n = 136) received progesterone only. Placental migration was monitored using Doppler scanning from 24 weeks of pregnancy onwards.Results: Patients receiving the combination of the Arabin cervical pessary and progesterone had a three-fold reduced rate of bleeding during pregnancy compared with patients in the control group (11.3% versus 33.1%; p = .006). Placental migration occurred 1.8 times more often in the pessary group (48.1% versus 26.4%; p = .037), and preterm labor <34 weeks occurred 2.7 times less often compared with the control group (p = .031). The use of the Arabin cervical pessary caused a change in the anterior cervico-uterine angle by 7.4 degrees, and reduction in the arcuate artery RI at 32-33 weeks of pregnancy compared with the control group.Conclusions: The use of the Arabin cervical pessary combined with progesterone in patients with placenta previa significantly reduced the rate of preterm delivery <34 weeks and bleeding during pregnancy. [ABSTRACT FROM AUTHOR]

Objective: To determine the effectiveness of 3 mg vaginal dinoprostone administered six hours prior to copper intrauterine device (IUD) insertion compared to placebo in increasing ease of insertion and reducing insertion pain among nulliparous women.Study Design: This was a single-center double-blinded randomized controlled trial (RCT). We randomly divided the two hundred nulliparous women requesting a copper T380A IUD to receive 3 mg vaginal dinoprostone or placebo six hours before IUD insertion. The primary outcome was provider ease of insertion. Patients reported their perceived insertion pain using a 10 cm visual analog scale (VAS). We also reported number of failed IUD insertions.Results: Baseline characteristics were similar between groups. Ease of insertion score was lower in dinoprostone group than placebo group (3.6 ± 2.5 vs. 5.4 ± 2.8; p < 0.01) denoting easier insertion for clinicians in dinoprostone group. Mean pain score during copper IUD insertion was lower in dinoprostone group (3.7 ± 2.3 vs. 5.0 ± 2.8; p < 0.01). Failed IUD insertion occurred in two cases of dinoprostone group (2%) versus four cases in control group (4%) (p-value; 0.68).Conclusions: Although vaginal dinoprostone administration six hours prior to copper IUD insertion in nulliparous women leads to an easy IUD insertion, we do not routinely advise it as the reduction in IUD insertion pain scores with vaginal dinoprostone lacked clinical significance.Implications: In settings where it is feasible to provide dinoprostone vaginally six hours before copper IUD insertion, clinicians will find insertion easier, and nulliparous women may experience somewhat less pain during the procedure. Where waiting six hours is practical, this may prove to be useful. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Study Question: Are progesterone vaginal pessaries 400 mg twice a day (bid) non-inferior to progesterone vaginal gel (90 mg) once a day (od) in the primary endpoint of clinical pregnancy rate after 38 days of luteal phase support in women undergoing in vitro fertilisation (IVF)?Summary Answer: Non-inferiority of progesterone vaginal pessaries 400 mg bid to progesterone 8% vaginal gel (90 mg od) was shown for clinical pregnancy rate after 38 days of luteal phase support.What Is Known Already: To maximise successful embryo transfer after IVF, additionally administered progesterone is used for proper endometrium transformation in the luteal phase. Vaginally administered progesterone results in adequate secretory transformation of the endometrium.Study Design, Size, Duration: This multicentre, multinational, open, randomised, two-parallel group, non-inferiority Phase 3 clinical trial was carried out at 17 study sites in five European countries (Belgium, Bulgaria, Czech Republic, Hungary and Serbia) between October 2013 and August 2014. An interactive web response system (IWRS) was implemented for treatment allocation at the sites. Power analysis, based on the assumptions of a non-inferiority margin of -9%, a significance level of α 2.5% (one-sided), power 90%, at a reference pregnancy rate for the progesterone vaginal gel group of 30%, as well as applying a dropout rate of 10%, yielded a total number of 766 patients to be randomised.Participants/materials, Setting, Methods: Women aged between 18 and 40 years with a clinical indication for IVF/intracytoplasmic sperm injection (ICSI) and embryo transfer were eligible to participate. The clinical pregnancy rate was assessed by fetal heart movement measured by transvaginal ultrasound at day 38 (D38) (primary endpoint) and D70. Also assessed were biochemical pregnancy rate (assessed by serum β-hCG ≥25 IU/L), clinical implantation rates at D38, patient evaluation of vaginal bleeding and discharge (assessed by diary) and adverse event (AE) incidence, severity and relationship to study medication.Main Results and the Role Of Chance: A total of 769 female patients were randomised to progesterone 400 mg vaginal pessaries bid (n = 385, 50.1%) or progesterone 90 mg vaginal gel od (n = 384, 49.9%). Patients receiving progesterone vaginal pessaries and progesterone vaginal gel were comparable in demographics, baseline characteristics and number of retrieved oocytes. In the full analysis set (FAS; n = 369 progesterone vaginal pessaries and n = 368 progesterone vaginal gel), clinical pregnancy rates on D38 were 38.3% for progesterone vaginal pessaries and 39.9% for progesterone vaginal gel. In the per protocol analysis set (PP; n = 357 progesterone vaginal pessaries and n = 356 progesterone vaginal gel), clinical pregnancy rates on D38 were 38.1% for progesterone vaginal pessaries and 40.4% for progesterone vaginal gel. For the differences in pregnancy rates between the progesterone vaginal pessaries group and the progesterone vaginal gel, the lower limit of the 97.5% CI was -8.6 and -9.5% for the FAS and PP datasets, respectively. The original prespecified non-inferiority margin of -9% was thus met in the FAS dataset but was marginally below this in the PP dataset. However, the pregnancy rate of the comparator was higher than the anticipated rate of 30%, and a predetermined logistic regression model including treatment group, country and age group effects without interaction terms showed non-inferiority of progesterone vaginal pessaries to progesterone vaginal gel for both the FAS and PP populations, in that the lower limits of the 95% CIs were above 0.7 for both analyses. As a result of this, the relevant authorities accepted to widen the acceptable non-inferiority margin to -10%, and as such both the FAS and PP populations succeeded in showing non-inferiority. Biochemical pregnancy and clinical implantation rates were comparable for both treatments. Both treatment groups showed similar high compliance throughout the study, and the safety profiles were also comparable between the groups. Drug-related AEs occurred with frequencies of 15.1% with progesterone vaginal pessaries and 14.4% with progesterone vaginal gel.Limitations, Reasons For Caution: Clinical pregnancy rate is a surrogate for the outcome of live birth rate.Wider Implications Of the Findings: Progesterone 400 mg pessaries bid for luteal phase support is an effective, safe and tolerable treatment option for women undergoing IVF during ART.Study Funding/competing Interest(s): This work was funded by Actavis Group PTC ehf., Iceland, part of Teva Pharmaceuticals, and by L.D. Collins & Co. Ltd. Gedeon Richter plc has recently entered into a license and distribution agreement to commercialise the vaginal pessaries in the European Union (except Ireland/UK). The progesterone vaginal pessaries studied are now marketed as Cyclogest®, Amelgen®, Cyclovita®, Luteum and Cygest® throughout the EU, Asia and Middle East & North Africa. The competing interests are as follows. H.S.: employee of Gedeon Richter plc/PregLem S.A. C.K.: consultant to L.D. Collins & Co. Ltd and received consulting fees for work performed. T.D.H.: at the initiation and completion of this study, full professor at KU Leuven and Head of Leuven University Fertility Center at the University Hospital Gasthuisberg, Leuven, Belgium. In October 2015, T.D.H. became vice president of Global Medical Affairs Fertility at the pharmaceutical company Merck-marketing authorisation holder of the Progesterone vaginal gel (Crinone®)-and has remained a part-time professor at KU Leuven (Belgium) and adjunct professor at Yale University (New Haven, CT, USA). T.B.M.: at the initiation and completion of this study, employee of Actavis Group PTC ehf. I.K.: consultant to Actavis, later TEVA and received consulting fees for work performed. S.H.: at the initiation and completion of this study, employee of Actavis Group PTC ehf.Trial Registration Number: EudraCT number 2013-001105-81.Trial Registration Date: 2 July 2013.Date Of First Patient’s Enrolment: 9 October 2013. [ABSTRACT FROM AUTHOR]

Objective: Astodrimer is a dendrimer formulated in a vaginal gel to treat bacterial vaginosis (BV) and prevent recurrence. The objective of these studies was to confirm the efficacy and safety of Astodrimer 1 % Gel for treatment of BV.Study Design: Women with bacterial vaginosis were randomized 1:1 to Astodrimer 1 % Gel (Study 1 conducted in the United States, N = 127; Study 2 conducted in the United States, Germany and Belgium, N = 128) or placebo gel (Study 1, N = 123; Study 2, N = 123) at a dose of 5 g vaginally once daily for 7 days. The primary endpoint was clinical cure, defined as i) absence of bacterial vaginosis vaginal discharge; ii) <20 % clue cells; and iii) negative whiff test at day 9-12. Secondary efficacy analyses included clinical cure at day 21-30. Other endpoints at days 9-12 and 21-30 included Nugent cure (Nugent score ≤3), absence of symptoms, and adverse events. The primary analysis in the modified intent-to-treat population used the Cochran Mantel Haenszel test stratified by analysis center with a two-sided significance level of α = .05.Results: Astodrimer 1 % Gel was superior to placebo for the primary and selected secondary efficacy measures. Clinical cure rates at day 9-12 were 50.4 % (59/117) vs 16.5 % (19/115, P < .001) (Study 1) and 56.7 % (68/120) vs 21.4 % (25/117, P < .001) (Study 2) for astodrimer vs placebo. At day 21-30, clinical cure results showed a similar trend but the difference to placebo was not statistically significant. Nugent cure rates at day 9-12 were 12.8 % (15/117) vs 2.6 % (3/115, P = .004) (Study 1) and 13.3 % (16/120) vs 5.1 % (6/117, P = .030) (Study 2) for astodrimer vs placebo. A greater proportion of women receiving astodrimer reported absence of vaginal discharge and absence of vaginal odor at day 9-12 and day 21-30 compared with placebo. Adverse events were generally mild and self-limiting. For the combined studies, adverse events potentially related to treatment occurred in 14.7 % (37/252) of astodrimer patients vs 9.4 % (23/244) for placebo, including vulvovaginal candidiasis reported for 2.4 % (6/252) of astodrimer patients.Conclusion: These results support a role for Astodrimer 1 % Gel as an effective, safe and well-tolerated treatment for women with bacterial vaginosis. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to assess the role of repeat misoprostol administration in those with thickened endometrium in the management of early pregnancy failure (EPF).Methods: A retrospective cohort study in two university hospitals among women receiving misoprostol treatment for EPF. Those with thickened endometrium at the first follow-up visit, who received a repeat 800 µg dose of vaginal misoprostol in institution B and no treatment in institution A, constituted the study group. The primary outcome was treatment success, defined as complete uterine evacuation without the need for any operative intervention RESULTS: Overall, 608 women with thickened endometrium as assessed by transvaginal ultrasonography 2 days following initial misoprostol administration for EPF were included. Of them, 427 did not receive repeat misoprostol dose, and 181 received repeat misoprostol dose. The rate of surgical intervention did not differ between those who received a repeat misoprostol dose (6.1%) and those who did not (4.3%) (P = 0.32). The median endometrial thickness was similar in those that did and did not require subsequent surgical intervention (P = 0.65), and was a poor predictor of treatment outcome.Conclusions: Repeat misoprostol administration among women with thickened endometrium following initial misoprostol administration for EPF was not associated with improved treatment success rates. [ABSTRACT FROM AUTHOR]

Background: There is no consensus about the ideal cervical ripening method to use for induction of labour.Objective: To compare in current practice the effectiveness and safety of four cervical ripening methods.Methods: We performed a matched comparative study using data from the MEDIP prospective population-based cohort conducted during one month in 2015 in all maternity units of seven French perinatal networks (3042 consecutive women with a live fetus and induction of labour). We analysed 1671 women with singleton cephalic fetus, unscarred uterus, and bishop score <7. Dinoprostone vaginal pessary (reference) was compared to dinoprostone vaginal gel, misoprostol vaginal tablet, and balloon catheter. Effectiveness outcomes were the need for more than one induction agent, oxytocin use, failure to achieve vaginal delivery within 24 hours (VD < 24 hours), and caesarean delivery. Safety outcomes were meconium-stained amniotic fluid, uterine hyperstimulation, NICU admission, and post-partum haemorrhage. Coarsened exact matching was used to balance confounders among the groups. Outcomes were compared using multivariable logistic regression models.Results: Compared to the dinoprostone pessary (N = 1142, 68.3%), dinoprostone gel (N = 335, 20.1%) was associated with less failure to achieve VD < 24 hours (adjusted OR 0.66, 95% CI 0.47, 0.91). Misoprostol (N = 103, 6.2%) was associated with less need of more than one induction agent (aOR 0.56, 95% CI 0.34, 0.92) and less oxytocin use (aOR 0.60, 95% CI 0.37, 0.99). The balloon catheter (N = 91, 5.4%) was associated with more failure to achieve VD < 24 hours (aOR 2.62, 95% CI 1.37, 5.01), more caesarean delivery (aOR 1.84, 95% CI 1.09, 3.08), and less meconium-stained amniotic fluid (aOR 0.12, 95% CI 0.02, 0.70). Uterine hyperstimulation rates seemed lower with the balloon catheter (1.2% vs 4.2% for the pessary).Conclusions: In current practice, no cervical ripening method appears clearly superior to the others considering all effectiveness and safety outcomes. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to evaluate improvement of dyspareunia and associated vaginal dryness with a 17β-estradiol softgel vaginal insert (TX-004HR; TherapeuticsMD, Boca Raton, FL, USA) in women with postmenopausal vulvar and vaginal atrophy (VVA). Methods: Postmenopausal women with VVA and moderate to severe dyspareunia received TX-004HR (4, 10, or 25 μg) or placebo in the 12-week, randomized, double-blind, placebo-controlled, phase 3 REJOICE trial. Post hoc analyses examined improvement levels in dyspareunia and concurrent vaginal dryness with TX-004HR and assessed the effects of patient characteristics on vaginal dryness treatment. Results: Significantly more women treated with TX-004HR (all doses) than placebo had complete resolution or substantial improvement in dyspareunia or vaginal dryness (concurrent with dyspareunia) by 12 weeks, observed as early as week 2 with most doses. TX-004HR significantly improved both dyspareunia and vaginal dryness at least one level versus placebo by week 12 in women with both symptoms. Subgroup analyses showed TX-004HR improved vaginal dryness associated with dyspareunia regardless of age, body mass index, uterine status, prior pregnancy, and vaginal birth number. Conclusion: TX-004HR provided clinically meaningful improvements in dyspareunia and vaginal dryness associated with dyspareunia in postmenopausal women with VVA. Clinicians may be able to use this information when discussing patients' expectations regarding symptom improvement with the estradiol vaginal insert. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study is to compare the uterine activity response between women administered dinoprostone (prostaglandin E2) and misoprostol (prostaglandin E1) for induction of labour (IOL) by analysing not only the traditional obstetric data but also the parameters extracted from uterine electrohysterogram (EHG).Methods: Two cohorts were defined: misoprostol (25-µg vaginal tablets; 251 women) and dinoprostone cohort (10 mg vaginal inserts; 249 women). All the mothers were induced by a medical indication of a Bishop Score < = 6.Results: The misoprostol cohort was associated with a shorter time to achieve active labour (p = .017) and vaginal delivery (p = .009) and with a higher percentage of vaginal delivery in less than 24 h in mothers with a very unfavourable cervix score (risk ratio (RR): 1.41, IC95% 1.17-1.69, p = .002). Successful inductions with misoprostol showed EHG parameter values significantly higher than basal state for amplitude and pseudo Montevideo units (PMU) 60' after drug administration, while spectral parameters significantly increased after 150'. This response was not observed in failed inductions. In the successful dinoprostone group, the duration and number of contractions increased significantly after 120', PMU did so after 180', and no significant differences were found for spectral parameters, possibly due to the slower pharmacokinetics of this drug.Conclusion: Successful inductions of labour by misoprostol are associated with earlier effective contractions than in labours induced by dinoprostone. [ABSTRACT FROM AUTHOR]

Objectives: To compare Misoprostol Vaginal Insert (MVI), a vaginal insert containing 200 μg of misoprostol) versus Dinoprostone Vaginal Insert (DVI), a vaginal insert containing 10 mg of dinoprostone), in the induction of labour.Study Design: We performed a retrospective analysis of the data between February 2016 and September 2017 of women induced with MVI (n = 100) and DVI in UK (n = 100) at NHS Fife. MVI was used for the same indications as DVI, but specifically indicated in women with a Modified Bishops score ≤ 4. Outcome measures included: the incidence of tachysystole and hyperstimulation; further use of prostaglandins; use of pre-delivery oxytocin; mode of delivery; median insertion-to-delivery-interval; and admission to the neonatal unit. Statistical data analysis was performed. A logistic regression analysis was also performed, adjusting for potential confounders such as body mass index (BMI), gestational age, parity and baseline Modified Bishops score.Results: Demographics such as parity, BMI, baseline Modified Bishops score and gestational age were assessed. A significantly higher rate of tachysystole and hyperstimulation was noted in the MVI group as compared to the DVI group. Only 8% of women in the MVI group as compared to a third (33%) of women in the DVI group required further prostaglandins. There was no difference in the modes of birth in either group and this result was statistically significant. The median induction to delivery interval was 15 h in the MVI group compared to 33 h in the DVI group. There was no difference in neonatal outcomes in either group. There was no significant difference in the use of pre-delivery oxytocin for subsequent augmentation of labour in either group. All the results, when adjusted to potential confounders using logistic regression, were in keeping with the unadjusted statistical analysis.Conclusion: The results of this study suggest that MVI significantly reduces the induction to delivery interval, has a similar caesarean section rate and neonatal outcomes, when compared with DVI. [ABSTRACT FROM AUTHOR]

Study Question: Which progesterone vaginal pessary dose regimen induces adequate secretory transformation of the endometrium, in comparison with progesterone vaginal gel and placebo?Summary Answer: The best secretory transformation of the endometrium was observed during treatment with 400 mg progesterone vaginal pessaries, administered twice daily.What Is Known Already: Vaginally administered progesterone is widely used for luteal phase support (LPS) in assisted reproductive techniques (ART). Although several vaginal formulations using various doses are available, little is known on the impact of formulation and doses at the endometrial level.Study Design, Size, Duration: The study had a randomised, observer-blind design and comprised two parts. The participants used study medication during two or three treatment periods, separated by washout periods. Subjects in Part 1 (n = 61 treated) received 200 mg progesterone vaginal pessaries twice daily (bid), 400 mg pessaries bid and the comparator 90 mg progesterone vaginal gel once daily (od) in a 3-way crossover design. Subjects in Part 2 (n = 64 treated) received 100 mg pessaries bid in one period and 400 mg pessaries od in the other period in a 2-way crossover design. A subgroup of these subjects (n = 22 treated) received placebo vaginal pessaries bid in a third period in a non-randomised manner. The study was performed from May 2012 until April 2013.Participants/materials, Setting, Methods: The study was performed at a clinical research centre in healthy female volunteers of reproductive age. The subjects used 2 mg estradiol bid for 24 days in each treatment cycle. Progesterone or placebo was administered vaginally from Day 15 onwards during 10 days. In each treatment period, an endometrial biopsy for histological evaluation was performed on Day 23 and pharmacokinetic parameters were determined after the first progesterone dose on Day 15 and after the last dose on Day 24.Main Results and the Role Of Chance: Frequencies of (early and late) secretory transformation of the endometrium, i.e. adequate responses, during treatment with 200 mg and 400 mg vaginal pessaries bid were comparable with those during 90 mg vaginal gel treatment (90-94%), whereas lower secretory transformation rates were observed during treatment with 100 mg bid and 400 mg od (64-75%). At the time of the endometrial biopsy in the cycle the late secretory state of the endometrium, which is characteristic of adequate luteal support, was observed more often with 400 mg pessaries bid (90%) than with vaginal gel (82%) and with lower pessary doses (64-78%). Pharmacokinetic parameters after repeated dosing of vaginal pessaries showed a dose-dependent, but not dose-proportional, increase of plasma progesterone levels. The lowest incidence of bleeding and spotting was reported during treatment with 400 mg pessaries bid.Limitations Reasons For Caution: The primary outcome parameter, rate of secretory transformation of the endometrium, is a surrogate for endometrial receptivity and for the actual clinical efficacy.Wider Implications Of the Findings: Delivery of progestesterone through 400 mg pessaries bid is an effective alternative method for luteal support in ART.Study Funding/competing Interest(s): The study was funded by Actavis Group PTC ehf., Iceland, part of Teva Pharmaceuticals, and L.D. Collins. I.D. and C.K. are directors of Dinox, a contract research organisation. I.K. is Managing Director of Pharmaplex and M.W. is Managing Director of M.A.R.C.O., service organisations involved in organisation/supervision and evaluation/reporting of clinical trials. All received funding for the conduct of the study from Actavis. S.H. and Th.M. are employees of Actavis.Trial Registration Number: EudraCT number 2012-001726-95. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study is to compare the efficacy of labor induction by Foley catheter balloon (FCB) insertion to intravaginal dinoprostone tablet placement in women with an unfavorable cervix.Materials and Methods: A prospective randomized controlled trial was conducted. Women were assigned to insertion of a FCB or placement of a vaginal dinoprostone tablets and their outcome were compared.Results: The study comprised 300 women. The time to active labor was significantly shorter in the FCB compared with the dinoprostone group, but required more oxytocin administration. A lower rate of cesarean section was found only in nulliparous women in the FCB group. The neonatal outcome was favorable and similar in both groups.Conclusion: Both methods had similar results regarding achieving vaginal delivery within 24 h and cesarean section rate. For nulliparous women, the FCB induction method had the advantage of a shorter time to active labor and a lower rate of cesarean section. [ABSTRACT FROM AUTHOR]

Aims: To assess the effectiveness of vaginal misoprostol in minimizing the pain perceived by patients with no risk factors for cervical stenosis (i.e., parous women of reproductive age who have no history of cesarean section or cervical surgery) during diagnostic office hysteroscopy.Methods: A total of 100 patients with no risk factors for cervical stenosis were randomized to the misoprostol group (n = 50) or the placebo group (n = 50). In the misoprostol group, 2 misoprostol tablets (400 µg) were administered vaginally 12 h before office hysteroscopy. In the placebo group, 2 placebo tablets were administered. The patients rated the intensity of pain perceived during the procedure and at 30 min after the procedure with the use of a 100 mm visual analog scale (VAS). The hysteroscopists also scored the difficulty of hysteroscope insertion into the uterine cavity with the use of a 100 mm VAS.Results: There were no significant differences between both groups in the VAS pain scores during or at 30 min after the procedure (28.3 ± 13.58 vs. 30.42 ± 15.13 and 11.1 ± 10.23 vs. 13.32 ± 11.12, respectively). The difficulty of hysteroscope insertion into the uterine cavity was comparable between both groups.Conclusion: Misoprostol administration prior to diagnostic office hysteroscopy appears to have no beneficial role in the subgroup of patients with no risk factors for cervical stenosis. [ABSTRACT FROM AUTHOR]

Objective: To assess the effectiveness of vaginal diazepam in addition to transcutaneous electrical nerve stimulation (TENS) in the treatment of vestibulodynia (VBD).Study Design: This study was a randomized, double-blind, placebo-controlled trial. Forty-two patients with VBD were randomized, 21 underwent diazepam and TENS (diazepam group) and 21 received placebo and TENS (placebo group). Vulvar pain was assessed on a on a 10-cm visual analogue scale (VAS) and dyspareunia according to the Marinoff dyspareunia scale. Vaginal surface electromyography (EMG) and vestibular current perception threshold (CPT) testing were performed at baseline and 60 days after treatment. The primary endpoints included the change in pain and dyspareunia from baseline to 60 days of pain and dyspareunia. The secondary endpoints was the variation in objectivity of pelvic floor muscle (PFM) function and vestibular nerve fiber current perception threshold (CPT).Results: The VAS scores for pain from basal values of 7.5 and 7.2 for the diazepam and placebo, respectively, showed significant (p 0.01) decreases from 4.7 to 4.3, but this difference was not statistically significant. The Marinoff dyspareunia scores in the diazepam group showed a significant difference (p 0.05) from values measured in the placebo group. The ability to relax the PFM after contraction (difference between maximal contraction and rest tone) was significantly greater for the diazepam group versus the placebo group (3.8 μv and 2.4 μv, respectively, p 0.01). The CPT values for all of the nerve fibers increased after the treatment, but this increase was significant in the diazepam group only for the values at a 5-Hz stimulation (C fibers) with a change of 47.8% vs 26.9% (p < 0.05). Only two patients reported a mild drowsiness in the diazepam group.Conclusions: The present study provided indications that vaginal diazepam plus TENS is useful to improve pain and PFM instability in women with VBD. [ABSTRACT FROM AUTHOR]

For prevention of a recurrent preterm birth (PTB), intramuscular 17-α-hydroxy progesterone caproate (IM 17 OHPC) weekly is recommended. Vaginal progesterone is preferred for women at risk for PTB due to a short cervical length, but may be useful in women with a prior PTB. However, there is no consensus about the optimal vaginal formulation or its efficacy as compared to 17 OHPC to prevent recurrent PTB. We randomised 100 women with a singleton pregnancy between 16 and 24 weeks of gestation and ≥ one prior spontaneous PTB, of a singleton (>16 to <37 weeks of gestation) to receive the 200 mg vaginal progesterone effervescent tablet daily (Group A) or IM 17-OHPC, 250 mg weekly (Group B) till 37 weeks of gestation or delivery. The spontaneous PTB rate of <37 weeks was similar (20% in Group A and 20.8% in Group B, p =  .918). The PTB rate of <34 weeks or <28 weeks were also comparable. The mean birth weight and other neonatal outcomes were similar in the two groups. Two neonates in Group A and four neonates in Group B required NICU admission, one of whom (Group B) died due to prematurity. Twenty percent of women in Group A and 29.2% in Group B reported adverse effects from their respective study medications (p =  .408, NS). Thus, there did not appear to be a difference between vaginal progesterone and 17-OHPC when used for the prevention of a recurrent PTB. Impact statement What is already known on this subject? Progesterone administration is useful for prevention of a recurrent preterm birth (PTB) and these women are prescribed the intramuscular 17-α-hydroxy progesterone caproate (IM 17 OHPC), 250 mg, weekly. Some studies found that vaginal progesterone (once daily) is also beneficial in these women, but there is no consensus regarding its efficacy when compared to 17 OHPC, or its optimal formulation and dose. What do the results of this study add? In the present study, 100 women with a singleton pregnancy between 16 and 24 weeks of gestation and ≥ one prior spontaneous singleton PTB or mid-trimester abortion were randomised to receive 200 mg of vaginal progesterone effervescent tablet daily (Group A) or 250 mg IM 17-OHPC weekly (Group B) till 37 weeks of gestation or delivery. The spontaneous PTB rate <37 weeks was similar in the two groups (20% in Group A and 20.8% in Group B, p = .918). The PTB rate <34 weeks or <28 weeks were also comparable. The mean birth weight and other neonatal outcomes were similar. Twenty percent of women in Group A and 29.2% of women in Group B reported adverse effects from their respective study medications (p = .408, NS). Thus, there did not appear to be a difference between the vaginal progesterone effervescent tablet and 17-OHPC when used for the prevention of a recurrent PTB. What are the implications of these findings for clinical practice and/or further research? The vaginal progesterone effervescent tablet may be a suitable alternative to IM 17 OHPC to prevent recurrent PTB. Future studies should identify the most appropriate route (IM or vaginal) and vaginal progesterone formulation for PTB prevention in women at risk for a recurrent PTB and in women with a short cervical length. [ABSTRACT FROM AUTHOR]

Objective: To compare the efficacy of dydrogesterone, 17-OH progesterone (17OHP) and oral or vaginal micronized progesterone with cerclage for the prevention of preterm birth in women with a short cervix.Methods: The study included 95 women with singleton gestation and cervical length (CL) ≤ 25 mm. Among these, 35 women were asymptomatic at 15-24 weeks and 60 had symptoms of threatened late miscarriage (LM) or preterm delivery (PD) at 15-32 weeks. Patients were randomized to receive dydrogesterone, 17OHP or oral/vaginal micronized progesterone; after one week of therapy 15 women underwent cerclage.Results: Efficacy of vaginal progesterone (VP) for the prevention of preterm birth reached 94.1%. In asymptomatic women pregnancy outcomes were comparable to cerclage. In women with threatened LM/PD, combination therapy with VP, indomethacin and treatment of bacterial vaginosis (BV) with the subsequent use VP until 36 weeks together with CL monitoring significantly decreased the rate of preterm birth (RR 0.01; 0.0001-0.24) and low birth weight (LBW) (RR 0.04; 0.01-0.96). CL increase during the first week of treatment with a subsequent plateau phase indicated treatment efficacy. Dydrogesterone, 17OHP, and micronized oral progesterone (OP) were associated with PD in 91.7% of women.Conclusions: Combination management strategy including VP significantly benefits pregnancy outcomes in women with a short cervix compared with cerclage. Dydrogesterone, 17OHP, and OP were not found to be efficacious. [ABSTRACT FROM AUTHOR]

Background: Medical management of early pregnancy loss is an alternative to uterine aspiration, but standard medical treatment with misoprostol commonly results in treatment failure. We compared the efficacy and safety of pretreatment with mifepristone followed by treatment with misoprostol with the efficacy and safety of misoprostol use alone for the management of early pregnancy loss.Methods: We randomly assigned 300 women who had an anembryonic gestation or in whom embryonic or fetal death was confirmed to receive pretreatment with 200 mg of mifepristone, administered orally, followed by 800 μg of misoprostol, administered vaginally (mifepristone-pretreatment group), or 800 μg of misoprostol alone, administered vaginally (misoprostol-alone group). Participants returned 1 to 4 days after misoprostol use for evaluation, including ultrasound examination, by an investigator who was unaware of the treatment-group assignments. Women in whom the gestational sac was not expelled were offered expectant management, a second dose of misoprostol, or uterine aspiration. We followed all participants for 30 days after randomization. Our primary outcome was gestational sac expulsion with one dose of misoprostol by the first follow-up visit and no additional intervention within 30 days after treatment.Results: Complete expulsion after one dose of misoprostol occurred in 124 of 148 women (83.8%; 95% confidence interval [CI], 76.8 to 89.3) in the mifepristone-pretreatment group and in 100 of 149 women (67.1%; 95% CI, 59.0 to 74.6) in the misoprostol-alone group (relative risk, 1.25; 95% CI, 1.09 to 1.43). Uterine aspiration was performed less frequently in the mifepristone-pretreatment group than in the misoprostol-alone group (8.8% vs. 23.5%; relative risk, 0.37; 95% CI, 0.21 to 0.68). Bleeding that resulted in blood transfusion occurred in 2.0% of the women in the mifepristone-pretreatment group and in 0.7% of the women in the misoprostol-alone group (P=0.31); pelvic infection was diagnosed in 1.3% of the women in each group.Conclusions: Pretreatment with mifepristone followed by treatment with misoprostol resulted in a higher likelihood of successful management of first-trimester pregnancy loss than treatment with misoprostol alone. (Funded by the National Institute of Child Health and Human Development; PreFaiR ClinicalTrials.gov number, NCT02012491 .). [ABSTRACT FROM AUTHOR]

Background: Dehydroepiandrosterone (DHEA) is helpful for treating vaginal symptoms. This secondary analysis evaluated the impact of vaginal DHEA on hormone concentrations, bone turnover, and vaginal cytology in women with a cancer history.Methods: Postmenopausal women, diagnosed with breast or gynecologic cancer, were eligible if they reported at least moderate vaginal symptoms. Participants could be on tamoxifen or aromatase inhibitors (AIs). Women were randomized to 3.25 versus 6.5 mg/day of DHEA versus a plain moisturizer (PM) control. Sex steroid hormone levels, biomarkers of bone formation, vaginal pH, and maturation index were collected at baseline and 12 weeks. Analysis included independent t tests and Wilcoxon rank tests, comparing each DHEA arm with the control.Results: Three hundred forty-five women contributed evaluable blood and 46 contributed evaluable cytology and pH values. Circulating DHEA-S and testosterone levels were significantly increased in those on vaginal DHEA in a dose-dependent manner compared to PM. Estradiol was significantly increased in those on 6.5 mg/day DHEA but not in those on 3.25 mg/day DHEA (p < 0.05 and p = 0.05, respectively), and not in those on AIs. Biomarkers of bone formation were unchanged in all arms. Maturation of vaginal cells was 100% (3.25 mg/day), 86% (6.5 mg/day), and 64% (PM); pH decreased more in DHEA arms.Conclusion: DHEA resulted in increased hormone concentrations, though still in the lowest half or quartile of the postmenopausal range, and provided more favorable effects on vaginal cytology, compared to PM. Estrogen concentrations in women on AIs were not changed. Further research on the benefit of vaginal DHEA is warranted in hormone-dependent cancers. [ABSTRACT FROM AUTHOR]

Objective and Design: Prospective randomized controlled trial to test the effectiveness of topical oxytocin gel to improve vaginal atrophy in postmenopausal women.Patients and Methods: A total of 140 postmenopausal women presenting with vaginal atrophy and who satisfied the inclusion and exclusion criteria were randomized into two groups each of 70 patients; they received intravaginal oxytocin gel or placebo gel for 30 days. Serum estrogen level, visual, colposcopic and histological vaginal examination were performed before and after treatment.Results: Forty-seven out of 70 women in the oxytocin gel group improved after treatment and none in the placebo group (p = 0.001). Forty-five participants in the oxytocin group and seven in the placebo group reported relief of dyspareunia (p = 0.001). Thirty-four participants in the oxytocin group and seven in the placebo group reported relief of soreness (p = 0.001). There was no significant difference between the circulating levels of estradiol in both groups before and after treatment (p = 0.4 and 0.6 for the oxytocin group and the placebo group, respectively).Conclusion: Oxytocin gel is useful in the restoration of the vaginal epithelium in cases of postmenopausal atrophic vaginitis. Further studies with a longer follow-up period are required to test the long-term effects of oxytocin as a treatment for vaginal atrophy. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate how physicians in the United States (US) screen for, define, and treat a short cervix to prevent preterm birth.Methods: This was a cross-sectional, web-based survey of 500 physicians treating pregnant patients with a short cervix in the US. Respondents' geographic region was monitored to ensure balance across the nine US Census divisions.Results: Respondents were predominantly obstetrician/gynecologists (86%, 429/500; mean age 49 years). Physicians reported that a median of 90% of their pregnant patients undergo cervical length screening; 81% (407/500) use transvaginal ultrasound. Physicians consult multiple evidence sources to inform their patient care, most commonly clinical guidelines (83%; 413/500) and published research (70%; 349/500). Most physicians (98%; 490/500) reported treating pregnant patients with a short cervix; 95% (474/500) use synthetic and/or natural progestogen, alone or in combination with other treatment modalities. If reimbursement was not a concern, 47% of physicians (230/500) would choose vaginal progesterone as their preferred treatment to prevent preterm birth in all patients with a short cervix, and 45% (218/500) would choose a synthetic progestogen.Conclusion: US guidelines recommend transvaginal ultrasound for cervical length screening; 81% of physicians in this study reported using this method. Most physicians surveyed use progestogens to treat a short cervix, with approximately half choosing a synthetic progestin (45%) and half choosing natural progesterone (47%) as their preferred treatment, despite national guidelines recommending only vaginal natural progesterone for this indication. Additional physician education is required to implement current and best practices. [ABSTRACT FROM AUTHOR]

Objective: To assess the noninferiority of vaginal P (Endometrin) compared with daily intramuscular P for replacement in programmed vitrified-warmed blastocyst transfer cycles and to assess the noninferiority of vaginal P in combination with intramuscular progesterone every third day compared with daily intramuscular P.Design: Three-arm randomized controlled noninferiority study. To enable early recognition of inferiority if present, an a priori interim analysis was planned and completed once ongoing pregnancy data were available for 50% of the total enrollment goal. The results of this interim analysis are presented here.Setting: Assisted reproduction technology practice.Patient(s): Women undergoing transfer of nonbiopsied high quality vitrified-warmed blastocyst(s) in a programmed cycle.Intervention(s): Vitrified-warmed blastocyst transfer with mode of P replacement determined by randomization to either: (1) 50 mg daily intramuscular P only; (2) 200 mg twice daily vaginal Endometrin; or (3) 200 mg twice daily Endometrin plus 50 mg intramuscular P every 3rd day.Main Outcome Measure(s): Live birth. The primary outcome of this interim analysis was ongoing pregnancy.Result(s): A total of 645 cycles were randomly assigned to one of the three treatment arms, received at least one dose of P replacement therapy according to this assignment and underwent vitrified-warmed blastocyst transfer. These cycles were included in the intention-to-treat analysis. The study team, including the statistician, were blinded to the identity of the treatment arms, which were randomly labeled "A," "B," and "C" in the dataset. Ongoing pregnancy occurred in 50%, 47%, and 31% of cycles in arms A, B, and C respectively. Although arm C had an rate of positive hCG equivalent to the other two arms, the rate of pregnancy loss for arm C was significantly higher than for either of the two arms, resulting in a more than one-third lower rate of ongoing pregnancy. There were no statistically significant differences for any outcome tested between arms A and B. Results of a per-protocol analysis were nearly identical to those of the intention-to-treat analysis. On completion of these analyses, arm C was revealed to be the vaginal P only arm.Conclusion(s): Relative to regimens inclusive of intramuscular P, vaginal-only P replacement for vitrified-warmed blastocyst transfer results in decreased ongoing pregnancy, due to increased miscarriage, and should be avoided. Randomization to the vaginal-only arm was terminated with these findings. This trial is ongoing to assess the noninferiority of the vaginal plus every 3rd day intramuscular P arm compared with daily intramuscular P in terms of live birth.Clinical Trial Registration Number: NLM identifier NCT02254577. [ABSTRACT FROM AUTHOR]

Background: The efficacy of vaginal progesterone for preventing preterm birth and adverse perinatal outcomes in singleton gestations with a short cervix has been questioned after publication of the OPPTIMUM study.Objective: To determine whether vaginal progesterone prevents preterm birth and improves perinatal outcomes in asymptomatic women with a singleton gestation and a midtrimester sonographic short cervix.Study Design: We searched MEDLINE, EMBASE, LILACS, and CINAHL (from their inception to September 2017); Cochrane databases; bibliographies; and conference proceedings for randomized controlled trials comparing vaginal progesterone vs placebo/no treatment in women with a singleton gestation and a midtrimester sonographic cervical length ≤25 mm. This was a systematic review and meta-analysis of individual patient data. The primary outcome was preterm birth <33 weeks of gestation. Secondary outcomes included adverse perinatal outcomes and neurodevelopmental and health outcomes at 2 years of age. Individual patient data were analyzed using a 2-stage approach. Pooled relative risks with 95% confidence intervals were calculated. Quality of evidence was assessed using the GRADE methodology.Results: Data were available from 974 women (498 allocated to vaginal progesterone, 476 allocated to placebo) with a cervical length ≤25 mm participating in 5 high-quality trials. Vaginal progesterone was associated with a significant reduction in the risk of preterm birth <33 weeks of gestation (relative risk, 0.62; 95% confidence interval, 0.47-0.81; P = .0006; high-quality evidence). Moreover, vaginal progesterone significantly decreased the risk of preterm birth <36, <35, <34, <32, <30, and <28 weeks of gestation; spontaneous preterm birth <33 and <34 weeks of gestation; respiratory distress syndrome; composite neonatal morbidity and mortality; birthweight <1500 and <2500 g; and admission to the neonatal intensive care unit (relative risks from 0.47-0.82; high-quality evidence for all). There were 7 (1.4%) neonatal deaths in the vaginal progesterone group and 15 (3.2%) in the placebo group (relative risk, 0.44; 95% confidence interval, 0.18-1.07; P = .07; low-quality evidence). Maternal adverse events, congenital anomalies, and adverse neurodevelopmental and health outcomes at 2 years of age did not differ between groups.Conclusion: Vaginal progesterone decreases the risk of preterm birth and improves perinatal outcomes in singleton gestations with a midtrimester sonographic short cervix, without any demonstrable deleterious effects on childhood neurodevelopment. [ABSTRACT FROM AUTHOR]

Purpose: Bacterial vaginosis is a change in the normal vaginal bacterial flora that leads to loss of hydrogen peroxide producing lactobacilli and overgrowth of predominantly anaerobic bacteria. The present study was conducted to compare the effects of prebiotic vaginal gel with oral metronidazole tablet and metronidazole tablet alone on treatment and recurrence of bacterial vaginosis.Methods: The present triple-blind randomized clinical trial was conducted in Sadatmandi Hospital in Robat-Karim town, where 100 patients were randomly divided into intervention (receiving a 5 mg prebiotic vaginal gel applicator plus three 250 mg metronidazole tablets per day for 7 days) and control (receiving a 5 mg placebo vaginal gel applicator and three 250 mg metronidazole tablets per day for 7 days) groups. Then, patients were assessed for bacterial vaginosis on 90 ± 3 day after treatment. Data collected were analyzed in SPSS-21 using Chi square, repeated measures, and student's t tests at a significance level of P < 0.05.Results: The results obtained showed no significant difference between the two groups in terms of personal and social characteristics, clinical complaints, or laboratory markers. On the 10th day, healing rate based on Amsel and Nugent criteria was 76% in the intervention group and 30% in the control group [odds ratio (OR) 4.3; 95% confidence interval (CI) 2.7-9.4]. On the 90th day, healing rate was 84% in the intervention group and 62% in the control group (OR 3.7; 95% CI 1.3-8.9).Conclusions: Adjuvant treatment with prebiotic vaginal gel improves the efficacy of bacterial vaginosis treatment. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to investigate the effectiveness and safety of a method combining double-balloon catheter for cervical ripening and intravenous drip of oxytocin on the induction of term labor, providing the reference for clinical safety.Methods: A total of 120 pregnant women with a gestation between 37+0 and  41+6 weeks, indications of labor induction, singleton pregnancy with cephalic presentation were enrolled. The patients were divided into the research group receiving cervical dilation balloon combined with intravenous drip of oxytocin and the control group receiving an intravenous drip of oxytocin at a concentration of 0.5% for labor induction (n = 60 for each). The effectiveness and safety of labor induction were evaluated by the rates of successful cervical ripening promotion and labor induction, as well as the vaginal delivery rate, induced labor time, total duration of labor, the total amount of postpartum hemorrhage within 24 h after giving birth, the incidences of postpartum hemorrhage, cervical laceration, puerperal infection and neonatal outcomes.Results: There was no statistical difference in the basal demographic and clinical characteristics, including ages, gestational weeks, delivery times and Bishop scores at admission between two groups. The rate of successful cervical ripening promotion (research vs. control = 90.00% vs. 55.00%), the rate of successful induction (95.00% vs. 40.00%), the vaginal delivery rate (93.33% vs. 63.33%), the induced labor time (15.03 ± 5.40 vs. 30.68 ± 10.82 h), and the total duration of labor (8.12 ± 2.65 vs. 15.01 ± 6.06 h) were significantly different between two groups (all P < 0.05). There was no significant difference in the total amount of postpartum hemorrhage, incidences of postpartum hemorrhage, cervical laceration, puerperal infection as well as the neonatal outcomes, including neonatal weight, neonatal asphyxia and incidence of meconium aspiration syndrome between two groups.Conclusions: Compared to labor induction of oxytocin, the method combining double-balloon catheter for cervical ripening and intravenous drip of oxytocin for the induction of term labor has a higher vaginal delivery rate, shorter total duration of labor, and does not increase the incidences of postpartum hemorrhage and neonatal infection, which is a more effective and safer method for induction of term labor. [ABSTRACT FROM AUTHOR]

Importance: Spontaneous preterm birth is a major cause of perinatal morbidity and mortality. It is unclear if a cervical pessary can reduce the risk of spontaneous preterm delivery.Objective: To test whether in asymptomatic women with singleton pregnancies and no prior spontaneous preterm birth but with short cervical length on transvaginal ultrasound, use of a cervical pessary would reduce the rate of spontaneous preterm birth at less than 34 weeks of gestation.Design, Setting, and Participants: Parallel-group, nonblinded, randomized clinical trial conducted from March 1, 2016, to May 25, 2017, at a single center in Italy. Asymptomatic women with singleton gestations, no previous spontaneous preterm births, and cervical lengths of 25 mm or less at 18 weeks 0 days to 23 weeks 6 days of gestation were eligible.Interventions: Patients were randomized 1:1 to receive either cervical pessary (n = 150) or no pessary (n = 150). The pessary was removed between 37 weeks 0 days and 37 weeks 6 days of gestation or earlier if clinically indicated. The control group received standard care. For cervical length of 20 mm or shorter, women in both groups were prescribed vaginal progesterone, 200 mg/d, until 36 weeks 6 days of gestation. No bed rest or activity restriction was recommended.Main Outcomes and Measures: The primary end point was spontaneous preterm birth at less than 34 weeks of gestation. Secondary outcomes were adverse events.Results: Among 300 women who were randomized (mean age, 29 [SD, 6.3] years; mean gestational age, 22 [SD, 1.3] weeks), 100% completed the trial. The primary end point occurred in 11 women (7.3%) in the pessary group and 23 women (15.3%) in the control group (between-group difference, -8.0% [95% CI, -15.7% to -0.4]; relative risk, 0.48 [95% CI, 0.24-0.95]). During follow-up, the pessary group had a higher rate of increased or new vaginal discharge (86.7% vs 46.0%; between-group difference, +40.7% [95% CI, +30.1%-+50.3%]; relative risk, 1.88 [95% CI, 1.57-2.27]).Conclusions and Relevance: Among women without prior spontaneous preterm birth who had asymptomatic singleton pregnancies and short transvaginal cervical length, use of a cervical pessary, compared with no pessary use, resulted in a lower rate of spontaneous preterm birth at less than 34 weeks of gestation. The results of this single-center, nonblinded study among selected pregnant women require confirmation in multicenter clinical trials.Trial Registration: clinicaltrials.gov Identifier: NCT02716909. [ABSTRACT FROM AUTHOR]

Objectives:The primary objective of our study was to ascertain whether moistening the Brazilian formulation of vaginal misoprostol tablets increases cervical dilation before manual vacuum aspiration (MVA), compared with use of dry misoprostol, in first-trimester miscarriage. The secondary objective was to ascertain whether there was any correlation between vaginal pH and the degree of cervical dilation using a moistened or dry misoprostol tablet. Methods:In a single-centre, double-blind, randomised trial, 46 patients with first-trimester miscarriage were randomly allocated to treatment with dry or moistened (with 200 µl distilled water) 2 × 200 μg misoprostol tablets. Results:The median (range) cervical dilation in the wet and dry groups was 8 mm (6–12 mm) and 7 mm (5–10 mm), respectively (p = .06). The median time between misoprostol insertion and carrying out the procedure did not differ between the dry (406 min, range 180–550 min) and wet (448 min, range 180–526 min) groups (p = .1). No correlation was found between vaginal pH and cervical dilation using continuous data (p = .57;r= 0.08; 95% confidence interval −0.02, 0.3) or dichotomous data (pH ≤5/>5; cervical dilation ≥8 mm or <8 mm;p = .8). Conclusion:No difference was observed in cervical dilation between moistened and non-moistened misoprostol use prior to MVA. [ABSTRACT FROM PUBLISHER]