"Hypertension in Pregnancy Intervention Trial At Term" and "Disproportionate Intrauterine Growth Intervention Trial At Term" Studies.

In 2003, in the context of a national research funding program in which obstetric research was prioritized, several perinatal centers took the initiative to jointly submit a number of applications to the subsidy programs of Effectiveness Research and Prevention of ZonMw. This has led to the funding of the Obstetric Consortium with several projects, including the "Hypertension in Pregnancy Intervention Trial At Term" and the "Disproportionate Intrauterine Growth Intervention Trial At Term" studies. The studies showed that induction of labor for hypertension and growth restriction at term was the appropriate management. Subsequent implementation improved maternal and perinatal outcomes.

Pessary or Progesterone to Prevent Preterm delivery in women with short cervical length: the Quadruple P randomised controlled trial.

BACKGROUND: Preterm birth is in quantity and in severity the most important topic in obstetric care in the developed world. Progestogens and cervical pessaries have been studied as potential preventive treatments with conflicting results. So far, no study has compared both treatments. METHODS/DESIGN: The Quadruple P study aims to compare the efficacy of vaginal progesterone and cervical pessary in the prevention of adverse perinatal outcome associated with preterm birth in asymptomatic women with a short cervix, in singleton and multiple pregnancies separately. It is a nationwide open-label multicentre randomized clinical trial (RCT) with a superiority design and will be accompanied by an economic analysis. Pregnant women undergoing the routine anomaly scan will be offered cervical length measurement between 18 and 22 weeks in a singleton and at 16-22 weeks in a multiple pregnancy. Women with a short cervix, defined as less than, or equal to 35 mm in a singleton and less than 38 mm in a multiple pregnancy, will be invited to participate in the study. Eligible women will be randomly allocated to receive either progesterone or a cervical pessary. Following randomization, the silicone cervical pessary will be placed during vaginal examination or 200 mg progesterone capsules will be daily self-administered vaginally. Both interventions will be continued until 36 weeks gestation or until delivery, whichever comes first. Primary outcome will be composite adverse perinatal outcome of perinatal mortality and perinatal morbidity including bronchopulmonary dysplasia, intraventricular haemorrhage grade III and IV, periventricular leukomalacia higher than grade I, necrotizing enterocolitis higher than stage I, Retinopathy of prematurity (ROP) or culture proven sepsis. These outcomes will be measured up until 10 weeks after the expected due date. Secondary outcomes will be, among others, time to delivery, preterm birth rate before 28, 32, 34 and 37 weeks, admission to neonatal intensive care unit, maternal morbidity, maternal admission days for threatened preterm labour and costs. DISCUSSION: This trial will provide evidence on whether vaginal progesterone or a cervical pessary is more effective in decreasing adverse perinatal outcome in both singletons and multiples. TRIAL REGISTRATION: Trial registration number: NTR 4414 . Date of registration January 29th 2014.

Cervical pessaries to prevent preterm birth in women with a multiple pregnancy: a per-protocol analysis of a randomized clinical trial.

INTRODUCTION: We recently showed that a cervical pessary prevents preterm birth and reduces poor neonatal outcomes in women with a twin pregnancy and a short cervix (<38 mm). The objective of this study was to evaluate the full potential treatment effect of the pessary in the whole group and in women with a short cervix. MATERIAL AND METHODS: We performed a per-protocol analysis of a multicenter randomized controlled trial (ProTWIN trial, NTR1858) where we excluded women who were allocated to the pessary but never had it placed. Women who had the pessary removed before 36 gestational weeks and did not deliver within 7 days after removal, were excluded. Analyses were performed on all women and in those with a cervical length <38 mm. RESULTS: In 23 (6%) women the pessary was not placed. In women with a cervical length <38 mm (25th percentile) the pessary reduced poor perinatal outcome (relative risk 0.32, 95% confidence interval 0.13-0.78) and birth at <32 weeks (relative risk 0.41, 95% confidence interval 0.20-0.87). After excluding 47 (12%) women, the time to delivery was longer in the pessary group than in the control group (whole group: hazard ratio 0.68, 95% confidence interval 0.55-0.82, cervical length <38 mm: hazard ratio 0.35, 95% confidence interval 0.22-0.57). CONCLUSIONS: The analysis confirms the principal findings of the intention-to-treat analysis. Time to delivery was longer in the pessary group than in the control group when censored data were used. This implies the pessary should not be removed until labor is evident.

Levonorgestrel releasing intrauterine system (Mirena) versus endometrial ablation (Novasure) in women with heavy menstrual bleeding: a multicentre randomised controlled trial.

BACKGROUND: Heavy menstrual bleeding is an important health problem. Two frequently used therapies are the levonorgestrel intra-uterine system (LNG-IUS) and endometrial ablation. The LNG-IUS can be applied easily by the general practitioner, which saves costs, but has considerable failure rates. As an alternative, endometrial ablation is also very effective, but this treatment has to be performed by a gynaecologist. Due to lack of direct comparison of LNG-IUS with endometrial ablation, there is no evidence based preferred advice for the use of one of these treatment possibilities. METHOD/DESIGN: A multicenter randomised controlled trial, organised in a network infrastructure in the Netherlands in which general practitioners and gynaecologists collaborate. DISCUSSON: This study, considering both effectiveness and cost effectiveness of LNG-IUS versus endometrial ablation may well improve care for women with heavy menstrual bleeding. TRIAL REGISTRATION: Dutch trial register, number NTR2984.

MisoREST: Surgical versus expectant management in women with an incomplete evacuation of the uterus after misoprostol treatment for miscarriage: A cohort study.

OBJECTIVE: To assess the effectiveness of curettage versus expectant management in women with an incomplete evacuation of the uterus after misoprostol treatment for first trimester miscarriage. STUDY DESIGN: We conducted a multicenter cohort study alongside a randomized clinical trial (RCT) between June 2012 until July 2014. 27 Dutch hospitals participated. Women with an incomplete evacuation after misoprostol treatment for first trimester miscarriage who declined to participate in the RCT, received treatment of their preference; curettage (n=65) or expectant management (n=132). A successful outcome was defined as an empty uterus on sonography at six weeks or uneventful clinical follow-up. We furthermore assessed complication rate and (re)intervention rate RESULTS: Of the 197 women who declined to participate in the RCT, 65 preferred curettage and 132 expectant management. A successful outcome was observed in 62/65 women (95%) in the surgical group versus 112/132 women (85%) in the expectant group (RR 1.1, 95% CI 1.03-1.2), with complication rates of 6.2% versus 2.3%, respectively (RR 2.7, 95% CI 0.6-12). CONCLUSION: In women with an incomplete evacuation of the uterus after misoprostol treatment, expectant management is an effective and safe option. This finding could restrain the use of curettage in women that have used misoprostol in the treatment of first trimester miscarriage.