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.

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.

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. TRIAL REGISTRATION:  Dutch Trial Register, NTR 1877.

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 ECV.

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

OBJECTIVE: To compare the costs of induction of labor and expectant management in women with preterm prelabor rupture of membranes (PPROM). DESIGN: Economic analysis based on a randomized clinical trial. SETTING: Obstetric departments of eight academic and 52 non-academic hospitals in the Netherlands. POPULATION: Women with PPROM near term who were not in labor 24 h after PPROM. METHODS: A 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 MEASURES: Primary health outcome was the incidence of neonatal sepsis. Direct medical costs were estimated from start of randomization to hospital discharge of mother and child. RESULTS: Induction 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 €8094 for induction and €7340 for expectant management (difference €754; 95% confidence interval -335 to 1802). This difference predominantly originated in the postpartum period, where the mean costs were €5669 for induction vs. €4801 for expectant management. Delivery costs were higher in women allocated to induction than in women allocated to expectant management (€1777 vs. €1153 per woman). Antepartum costs in the expectant management group were higher because of longer antepartum maternal stays in hospital. CONCLUSIONS: In 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.

Induction of labor versus expectant management in women with preterm prelabor rupture of membranes between 34 and 37 weeks: a randomized controlled trial.

BACKGROUND: At present, there is insufficient evidence to guide appropriate management of women with preterm prelabor rupture of membranes (PPROM) near term. METHODS AND FINDINGS: We conducted an open-label randomized controlled trial in 60 hospitals in The Netherlands, which included non-laboring women with >24 h of PPROM between 34(+0) and 37(+0) wk of gestation. Participants were randomly allocated in a 1:1 ratio to induction of labor (IoL) or expectant management (EM) using block randomization. The main outcome was neonatal sepsis. Secondary outcomes included mode of delivery, respiratory distress syndrome (RDS), and chorioamnionitis. Patients and caregivers were not blinded to randomization status. We updated a prior meta-analysis on the effect of both interventions on neonatal sepsis, RDS, and cesarean section rate. From 1 January 2007 to 9 September 2009, 776 patients in 60 hospitals were eligible for the study, of which 536 patients were randomized. Four patients were excluded after randomization. We allocated 266 women (268 neonates) to IoL and 266 women (270 neonates) to EM. Neonatal sepsis occurred in seven (2.6%) newborns of women in the IoL group and in 11 (4.1%) neonates in the EM group (relative risk [RR] 0.64; 95% confidence interval [CI] 0.25 to 1.6). RDS was seen in 21 (7.8%, IoL) versus 17 neonates (6.3%, EM) (RR 1.3; 95% CI 0.67 to 2.3), and a cesarean section was performed in 36 (13%, IoL) versus 37 (14%, EM) women (RR 0.98; 95% CI 0.64 to 1.50). The risk for chorioamnionitis was reduced in the IoL group. No serious adverse events were reported. Updating an existing meta-analysis with our trial results (the only eligible trial for the update) indicated RRs of 1.06 (95% CI 0.64 to 1.76) for neonatal sepsis (eight trials, 1,230 neonates) and 1.27 (95% CI 0.98 to 1.65) for cesarean section (eight trials, 1,222 women) for IoL compared with EM. CONCLUSIONS: In women whose pregnancy is complicated by late PPROM, neither our trial nor the updated meta-analysis indicates that IoL substantially improves pregnancy outcomes compared with EM. TRIAL REGISTRATION: Current Controlled Trials ISRCTN29313500

Induction of labour versus expectant management in women with preterm prelabour rupture of membranes between 34 and 37 weeks (the PPROMEXIL-trial).

BACKGROUND: Preterm prelabour rupture of the membranes (PPROM) is an important clinical problem and a dilemma for the gynaecologist. On the one hand, awaiting spontaneous labour increases the probability of infectious disease for both mother and child, whereas on the other hand induction of labour leads to preterm birth with an increase in neonatal morbidity (e.g., respiratory distress syndrome (RDS)) and a possible rise in the number of instrumental deliveries. METHODS/DESIGN: We aim to determine the effectiveness and cost-effectiveness of immediate delivery after PPROM in near term gestation compared to expectant management. Pregnant women with preterm prelabour rupture of the membranes at a gestational age from 34+0 weeks until 37+0 weeks will be included in a multicentre prospective randomised controlled trial. We will compare early delivery with expectant monitoring. The primary outcome of this study is neonatal sepsis. Secondary outcome measures are maternal morbidity (chorioamnionitis, puerperal sepsis) and neonatal disease, instrumental delivery rate, maternal quality of life, maternal preferences and costs. We anticipate that a reduction of neonatal infection from 7.5% to 2.5% after induction will outweigh an increase in RDS and additional costs due to admission of the child due to prematurity. Under these assumptions, we aim to randomly allocate 520 women to two groups of 260 women each. Analysis will be by intention to treat. Additionally a cost-effectiveness analysis will be performed to evaluate if the cost related to early delivery will outweigh those of expectant management. Long term outcomes will be evaluated using modelling. DISCUSSION: This trial will provide evidence as to whether induction of labour after preterm prelabour rupture of membranes is an effective and cost-effective strategy to reduce the risk of neonatal sepsis. CONTROLLED CLINICAL TRIAL REGISTER: ISRCTN29313500.

Recent trends in breech delivery in the Netherlands.

The effect of publication of the results of the Term Breech Trial in October 2000 on the mode of delivery of babies in breech presentation in the Netherlands was subject of this study. The results showed an immediate amplifying impact on top of the already existing trend of rising caesarean section rates for term singleton breech presentations. The willingness of obstetricians in the Netherlands to adopt the conclusions of the Term Breech Trial so quickly originate from scientific, legal, psychological and emotional sources. The same amplifying impact applied for all non-term breeches and breeches from multiple gestations, but not for babies in other than breech presentation.