Hormonal support in women with Asherman syndrome does not lead to better outcomes: A randomized trial

PURPOSE: The purpose of the study was to investigate if adjuvant hormones after successful adhesiolysis lead to a reduction in spontaneous recurrence of adhesions and influence reproductive outcomes. METHODS: A single-blind randomized controlled trial comparing administration of oral estrogen (the usual care group) with not giving estrogen (no estrogen) in women after successful adhesiolysis for Asherman syndrome. Women were included between September 2013 and February 2017, with a follow-up of 3 years to monitor recurrences and reproductive outcomes. Analyses were based on an intention to treat analyses. This study was registered under NL9655. RESULTS: A total of 114 women were included. At 1 year, virtually all patients (except 3) were either having a recurrence or were pregnant. Women who did not receive estrogen did not have more recurrences of adhesions in the first year prior to pregnancy (66.1% in the usual care group, 52.7% in the no-estrogen group, p  = 0.15). Of the women in usual care, 89.8% got pregnant within 3 years, and 67.8% got a living child; this was 83.6% and 60.0%, respectively, in the no-estrogen group ( p  = 0.33 and p  = 0.39, respectively). CONCLUSION: Usual care does not lead to better outcomes as compared with not giving exogenous estrogen but is associated with side effects

Atosiban versus fenoterol as a uterine relaxant for external cephalic version: randomised controlled trial

Objective To compare the effectiveness of the oxytocin receptor antagonist atosiban with the beta mimetic fenoterol as uterine relaxants in women undergoing external cephalic version (ECV) for breech presentation. Design Multicentre, open label, randomised controlled trial. Setting Eight hospitals in the Netherlands, August 2009 to May 2014. Participants 830 women with a singleton fetus in breech presentation and a gestational age of more than 34 weeks were randomly allocated in a 1:1 ratio to either 6.75 mg atosiban (n=416) or 40 μg fenoterol (n=414) intravenously for uterine relaxation before ECV. Main outcome measures The primary outcome measures were a fetus in cephalic position 30 minutes after the procedure and cephalic presentation at delivery. Secondary outcome measures were mode of delivery, incidence of fetal and maternal complications, and drug related adverse events. All analyses were done on an intention-to-treat basis. Results Cephalic position 30 minutes after ECV occurred significantly less in the atosiban group than in the fenoterol group (34% v 40%, relative risk 0.73, 95% confidence interval 0.55 to 0.93). Presentation at birth was cephalic in 35% (n=139) of the atosiban group and 40% (n=166) of the fenoterol group (0.86, 0.72 to 1.03), and caesarean delivery was performed in 60% (n=240) of women in the atosiban group and 55% (n=218) in the fenoterol group (1.09, 0.96 to 1.20). No significant differences were found in neonatal outcomes or drug related adverse events. Conclusions In women undergoing ECV for breech presentation, uterine relaxation with fenoterol increases the rate of cephalic presentation 30 minutes after the procedure. No statistically significant difference was found for cephalic presentation at delivery

Development and internal validation of a clinical prediction model for external cephalic version

Objective: To develop a prediction model for the chance of successful external cephalic version (ECV). Study design: This is a secondary analysis of a multicenter, open-label randomized controlled trial that assessed the effectiveness of atosiban compared to fenoterol as uterine relaxant during ECV in women with a singleton fetus in breech presentation with a gestational age of 36 weeks or more. Potential predictors included maternal, pregnancy, fetal, and treatment characteristics and were recorded in all participants. Multivariable logistic regression analysis with a stepwise backward selection procedure was used to construct a prediction model for the occurrence of successful ECV. Model performance was assessed using calibration and discrimination. Results: We included a total of 818 women with an overall ECV success rate of 37%. Ten predictive factors were identified with the stepwise selection procedure to be associated with a successful ECV: fenoterol as uterine relaxant, nulliparity, Caucasian ethnicity, gestational age at ECV, Amniotic Fluid Index, type of breech presentation, placental location, breech engagement, possibility to palpate the head and relaxation of the uterus. Our model showed good calibration and a good discriminative ability with a c-statistic of 0.78 (95% CI 0.75 to 0.81). Conclusion: Prediction of success of ECV seems feasible with a model showing good performance. This can be used in clinical practice after external validation

Prediction models for successful external cephalic version: a systematic review

To provide an overview of existing prediction models for successful ECV, and to assess their quality, development and performance. We searched MEDLINE, EMBASE and the Cochrane Library to identify all articles reporting on prediction models for successful ECV published from inception to January 2015. We extracted information on study design, sample size, model-building strategies and validation. We evaluated the phases of model development and summarized their performance in terms of discrimination, calibration and clinical usefulness. We collected different predictor variables together with their defined significance, in order to identify important predictor variables for successful ECV. We identified eight articles reporting on seven prediction models. All models were subjected to internal validation. Only one model was also validated in an external cohort. Two prediction models had a low overall risk of bias, of which only one showed promising predictive performance at internal validation. This model also completed the phase of external validation. For none of the models their impact on clinical practice was evaluated. The most important predictor variables for successful ECV described in the selected articles were parity, placental location, breech engagement and the fetal head being palpable. One model was assessed using discrimination and calibration using internal (AUC 0.71) and external validation (AUC 0.64), while two other models were assessed with discrimination and calibration, respectively. We found one prediction model for breech presentation that was validated in an external cohort and had acceptable predictive performance. This model should be used to council women considering EC

Atosiban versus fenoterol as a uterine relaxant for external cephalic version: randomised controlled trial

To compare the effectiveness of the oxytocin receptor antagonist atosiban with the beta mimetic fenoterol as uterine relaxants in women undergoing external cephalic version (ECV) for breech presentation. Multicentre, open label, randomised controlled trial. Eight hospitals in the Netherlands, August 2009 to May 2014. 830 women with a singleton fetus in breech presentation and a gestational age of more than 34 weeks were randomly allocated in a 1:1 ratio to either 6.75 mg atosiban (n=416) or 40 μg fenoterol (n=414) intravenously for uterine relaxation before ECV. The primary outcome measures were a fetus in cephalic position 30 minutes after the procedure and cephalic presentation at delivery. Secondary outcome measures were mode of delivery, incidence of fetal and maternal complications, and drug related adverse events. All analyses were done on an intention-to-treat basis. Cephalic position 30 minutes after ECV occurred significantly less in the atosiban group than in the fenoterol group (34% v 40%, relative risk 0.73, 95% confidence interval 0.55 to 0.93). Presentation at birth was cephalic in 35% (n=139) of the atosiban group and 40% (n=166) of the fenoterol group (0.86, 0.72 to 1.03), and caesarean delivery was performed in 60% (n=240) of women in the atosiban group and 55% (n=218) in the fenoterol group (1.09, 0.96 to 1.20). No significant differences were found in neonatal outcomes or drug related adverse events. In women undergoing ECV for breech presentation, uterine relaxation with fenoterol increases the rate of cephalic presentation 30 minutes after the procedure. No statistically significant difference was found for cephalic presentation at delivery. Dutch Trial Register, NTR 187

Economic analysis comparing induction of labor and expectant management in women with preterm prelabor rupture of membranes between 34 and 37 weeks (PPROMEXIL trial)

ObjectiveTo compare the costs of induction of labor and expectant management in women with preterm prelabor rupture of membranes (PPROM). DesignEconomic analysis based on a randomized clinical trial. SettingObstetric departments of eight academic and 52 non-academic hospitals in the Netherlands. PopulationWomen with PPROM near term who were not in labor 24h after PPROM. MethodsA cost-minimization analysis was done from a health care provider perspective, using a bottom-up approach to estimate resource utilization, valued with unit-costs reflecting actual costs. Main outcome measuresPrimary health outcome was the incidence of neonatal sepsis. Direct medical costs were estimated from start of randomization to hospital discharge of mother and child. ResultsInduction of labor did not significantly reduce the probability of neonatal sepsis [2.6% vs. 4.1%, relative risk 0.64 (95% confidence interval 0.25-1.6)]. Mean costs per woman were Euro8094 for induction and Euro7340 for expectant management (difference Euro754; 95% confidence interval -335 to 1802). This difference predominantly originated in the postpartum period, where the mean costs were Euro5669 for induction vs. Euro4801 for expectant management. Delivery costs were higher in women allocated to induction than in women allocated to expectant management (Euro1777 vs. Euro1153 per woman). Antepartum costs in the expectant management group were higher because of longer antepartum maternal stays in hospital. ConclusionsIn women with pregnancies complicated by PPROM near term, induction of labor does not reduce neonatal sepsis, whereas costs associated with this strategy are probably higher

Trial profile.

<p>Trial profile.</p

Maternal outcomes.

<p>Data are presented as number (percent).</p>a<p>Percents, RRs, 95% CIs, and <i>p</i>-values given are related to available data per characteristic and may differ from the total number of patients.</p>b<p>Outcome characteristic with more than 5% missing data. Histological chorioamnionitis data available for 396 women (74%); histological funisitis data available for 388 women (73%).</p

Neonatal treatments.

a<p>Percentages given according to available data.</p>b<p>Mean treatment length calculated for neonates receiving each antibiotic.</p>c<p>Mean difference with 95% CI.</p>d<p>Mean treatment length calculated from neonates receiving each treatment.</p><p>NA, not applicable; SD, standard deviation.</p

Meta-analysis.

<p>Risk ratio according to Mantel-Haenszel (M–H) with fixed effects and 95% CIs for neonatal sepsis, culture-proven neonatal sepsis, RDS, and cesarean section rates.</p