Cervical ripening in prolonged pregnancies by silicone double balloon catheter versus vaginal dinoprostone slow release system: The MAGPOP randomised controlled trial.

BACKGROUND: Prolonged pregnancies are a frequent indication for induction of labour. When the cervix is unfavourable, cervical ripening before oxytocin administration is recommended to increase the likelihood of vaginal delivery, but no particular method is currently recommended for cervical ripening of prolonged pregnancies. This trial evaluates whether the use of mechanical cervical ripening with a silicone double balloon catheter for induction of labour in prolonged pregnancies reduces the cesarean section rate for nonreassuring fetal status compared with pharmacological cervical ripening by a vaginal pessary for the slow release of dinoprostone (prostaglandin E2). METHODS AND FINDINGS: This is a multicentre, superiority, open-label, parallel-group, randomised controlled trial conducted in 15 French maternity units. Women with singleton pregnancies, a vertex presentation, ≥41+0 and ≤42+0 weeks' gestation, a Bishop score <6, intact membranes, and no history of cesarean delivery for whom induction of labour was decided were randomised to either mechanical cervical ripening with a Cook Cervical Ripening Balloon or pharmacological cervical ripening by a Propess vaginal pessary serving as a prostaglandin E2 slow-release system. The primary outcome was the rate of cesarean for nonreassuring fetal status, with an independent endpoint adjudication committee determining whether the fetal heart rate was nonreassuring. Secondary outcomes included delivery (time from cervical ripening to delivery, number of patients requiring analgesics), maternal and neonatal outcomes. Between January 2017 and December 2018, 1,220 women were randomised in a 1:1 ratio, 610 allocated to a silicone double balloon catheter, and 610 to the Propess vaginal pessary for the slow release of dinoprostone. The mean age of women was 31 years old, and 80% of them were of white ethnicity. The cesarean rates for nonreassuring fetal status were 5.8% (35/607) in the mechanical ripening group and 5.3% (32/609) in the pharmacological ripening group (proportion difference: 0.5%; 95% confidence interval (CI) -2.1% to 3.1%, p = 0.70). Time from cervical ripening to delivery was shorter in the pharmacological ripening group (23 hours versus 32 hours, median difference 6.5 95% CI 5.0 to 7.9, p < 0.001), and fewer women required analgesics in the mechanical ripening group (27.5% versus 35.4%, difference in proportion -7.9%, 95% CI -13.2% to -2.7%, p = 0.003). There were no statistically significant differences between the 2 groups for other delivery, maternal, and neonatal outcomes. A limitation was a low observed rate of cesarean section. CONCLUSIONS: In this study, we observed no difference in the rates of cesarean deliveries for nonreassuring fetal status between mechanical ripening with a silicone double balloon catheter and pharmacological cervical ripening with a pessary for the slow release of dinoprostone. TRIAL REGISTRATION: ClinicalTrials.gov NCT02907060.

Low-dose vaginal misoprostol vs vaginal dinoprostone insert for induction of labor beyond 41st week: A randomized trial.

INTRODUCTION: The aim of this study was to compare the efficacy and safety of a low-dose protocol of vaginal misoprostol and vaginal dinoprostone insert for induction of labor in women with post-term pregnancies. MATERIAL AND METHODS: We designed a prospective, randomized, open-labeled trial with evaluators blinded to the end-point, including women of at least 41 weeks of gestational age with uncomplicated singleton pregnancies and a Bishop score <6. They were randomized into dinoprostone or misoprostol groups in a 1:1 ratio. Baseline maternal data and perinatal outcomes were recorded for statistical analysis. Successful vaginal delivery within 24 hours was the primary outcome variable. A P value <0.05 was considered statistically significant. This study was registered in ClinicalTrials.gov (number NTC03744364). RESULTS: We included 198 women for analysis (99 women in each group). Vaginal birth rate within 24 hours did not differ between groups (49.5% vs 42.4%; P = 0.412). When the Bishop score was <4, dinoprostone insert showed a higher probability of vaginal delivery within 12 hours (17.8% vs 4%; P = 0.012). In the dinoprostone group, removal of the insert was more likely to be due to an adverse event (5.1% vs 14.1%; P = 0.051) and an abnormal fetal heart rate pattern during active labor (44.4% vs 58.6%; P = 0.047). Both groups were similar in neonatal outcomes including Apgar score, umbilical cord pH and neonatal intensive care unit admission. CONCLUSIONS: Low-dose vaginal misoprostol and vaginal dinoprostone insert seem to be equally effective and safe for induction of labor in pregnant women with a gestational age beyond 41 weeks.

Prostaglandin-Endoperoxide Synthase 1 Mediates the Timing of Parturition in Mice Despite Unhindered Uterine Contractility.

Cyclooxygenase (COX)-derived prostaglandins stimulate uterine contractions and prepare the cervix for parturition. Prior reports suggest Cox-1 knockout (KO) mice exhibit delayed parturition due to impaired luteolysis, yet the mechanism for late-onset delivery remains unclear. Here, we examined key factors for normal onset of parturition to determine whether any could account for the delayed parturition phenotype. Pregnant Cox-1KO mice did not display altered timing of embryo implantation or postimplantation growth. Although messenger RNAs of contraction-associated proteins (CAPs) were differentially expressed between Cox-1KO and wild-type (WT) myometrium, there were no differences in CAP agonist-induced intracellular calcium release, spontaneous or oxytocin (OT)-induced ex vivo uterine contractility, or in vivo uterine contractile pressure. Delayed parturition in Cox-1KO mice persisted despite exogenous OT treatment. Progesterone (P4) withdrawal, by ovariectomy or administration of the P4-antagonist RU486, diminished the delayed parturition phenotype of Cox-1KO mice. Because antepartum P4 levels do not decline in Cox-1KO females, P4-treated WT mice were examined for the effect of this hormone on in vivo uterine contractility and ex vivo cervical dilation. P4-treated WT mice had delayed parturition but normal uterine contractility. Cervical distensibility was decreased in Cox-1KO mice on the day of expected delivery and reduced in WT mice with long-term P4 treatment. Collectively, these findings show that delayed parturition in Cox-1KO mice is the result of impaired luteolysis and cervical dilation, despite the presence of strong uterine contractions.

Castor oil for induction of labor in post-date pregnancies: A randomized controlled trial.

BACKGROUND: Castor oil is a substance used for labor induction in an inpatient setting. However, its efficacy as an agent for the induction of labor, for post-date pregnancies in an outpatient setup is unknown. OBJECTIVE: Efficacy of castor oil as an agent for the induction of labor, for post-date pregnancies in outpatient settings. METHODS: Eighty-one women with a low-risk post-date singleton pregnancy with a Bishop score≤7, without effective uterine contractions were randomized to the intervention, 60ml of castor oil, or the control, 60ml of sun-flower oil. The primary outcome was proportion of women entering the active phase of labor 24, 36, 48h after ingestion. Secondary outcomes included meconium stained amniotic fluid, abnormal fetal heart rate tracing, cesarean section rate, instrumental deliveries, birth weight, 5min Apgar score, chorioamnionitis, hypertensive complications, retained placenta, and post-partum hemorrhage. FINDINGS: Intervention and control groups included 38 and 43 women, respectively. No differences in baseline characteristics, except for age were noted. The observed interaction between castor oil and parity was significant (pinteraction=0.02). Multiparous women in the intervention group exhibited a significant beneficial effect on entering active labor within 24, 36 and 48h after castor oil consumption compared with the placebo (Hazard Ratio=2.93, p=0.048; Hazard Ratio=3.29, p=0.026; Hazard Ratio=2.78, p=0.042 respectively). This effect was not noted among primiparous women. No differences in rate of obstetric complications or adverse neonatal outcomes were noted. CONCLUSION: Castor oil is effective for labor induction, in post-date multiparous women in outpatient settings.

Earlier induction of labour in post term pregnancies--A historical cohort study.

OBJECTIVE: to evaluate a change of guideline for earlier induction of labour in post term pregnancies and its possible impact on selected birth interventions and outcome of the newborn. DESIGN: a historical cohort study. SETTINGS: Department of Obstetrics at Aarhus University Hospital in Denmark. PARTICIPANTS: 18,247 women giving birth between 1 January 2009 and 12 December 2012. METHODS: to compare induction of labour in two consecutive time periods before and after implementation of a new guideline on induction of labour (42 weeks versus 41 weeks plus five days gestational age) in post term pregnancy. t-Test and χ(2) were used to calculate means of gestational age and relative risk (RR) of selected birth and newborn outcomes. Stratification by Mantel-Haenszel-analysis was used to adjust for possible confounders. Robson׳s classification system 'Ten Group Classification System' was used to create comparable groups within the performed analysis. FINDINGS: a difference in means of three gestational days after implementation of the new guideline on earlier induction of labour was found together with an overall unadjusted decrease in emergency caesarean section rate of 30% (RR 0.70, 95% CI; 0.54-0.91). Stratified analysis on parity showed a reduction in emergency caesarean section but only in nulliparous women (RR 0.78, 95% CI; 0.66-0.92), whereas the analysis in multiparous women showed a non-statistically significant increased risk of emergency caesarean section (RR 1.39, 95% CI; 0.89-2.18). No differences were found in assisted vaginal childbirths and outcome in newborns concerning Apgar score, pH and standard base excess in women induced in 42 weeks versus 41 weeks plus five days gestational age. CONCLUSION: the findings of this study suggest that earlier induction of labour due to post term pregnancy has a positive influence, but only in nulliparous women, by lowering the risk of emergency caesarean section evidently without increasing the risk on adverse outcome in newborns.

Comparison of 25 and 50 microgram of misoprostol for induction of labour in nulliparous women with postdate pregnancy in Port Harcourt.

BACKGROUND: Induction of labor for postdate pregnancy using misoprostol is one of the most common interventions in pregnancy. However, the optimal dose of misoprostol is yet to be determined with previous reports utilizing different dosages. OBJECTIVE: The main objective of this study was to compare the effectiveness and safety of 25 µg versus 50 µg of intravaginal misoprostol for induction of labor in nulliparous women with postdate pregnancy. METHODOLOGY: This was a prospective study in which 88 nulliparous women with postdate pregnancy were randomly selected to receive either 25 µg or 50 µg of misoprostol for induction of labor. Student's t-test and Chi-square test were used to compare proportions. RESULTS: There was no significant difference between the two groups with regard to the induction-vaginal delivery interval between the two doses. The proportion of women delivering vaginally with a single dose of misoprostol (11/40 vs. 23/43, P = 0.01) and vomiting were significantly greater in the 50 µg group. However, there was no significant difference between both groups in terms of the need for augmentation of labor, caesarean section, tachysystole and hyperstimulation syndrome. CONCLUSION: Intravaginal administration of 25 µg of misoprostol appears to be as effective, but safer than 50 µg for induction of labor in nulliparous women with postdate pregnancy.

[Factors predicting unsuccessful labor induction with dinoprostone in post-term pregnancy with unfavorable cervix]. / Facteurs prédictifs d'échec d'entrée en travail par dinoprostone en cas de grossesse prolongée et de conditions locales défavorables.

OBJECTIVE: To identify predictive factors for unsuccessful induction of labor within 24hours after dinoprostone insertion in post-term pregnancy with unfavorable cervix. MATERIAL AND METHODS: We retrospectively reviewed 325 singleton pregnancies with a diagnosis of post-term pregnancy and unfavorable cervix (Bishop score<6) during the period January 2012-Decembre 2012. Patients were classified into 2 groups: successful labor, defined as cervical ripening, within 24hours after dinoprostone insertion (Group R; n=248; 76.3 %) or failure group (Group E; n=77; 23.7 %). Antepartum and perpartum characteristics of women were compared. RESULTS: Nulliparity (74.0 versus 56.0 %; OR=2.23; 95 % CI: 1.27-4.00; P=0.005), gestational age ≤41 SA+4 (53.2 versus 33.9 %; OR=2.22; 95 % CI: 1.32-3.74; P=0.003) and history of dilatation and curettage (27.3 versus 10.5 %; OR=3.19; 95 % CI: 1.66-6.11; P=0.0005) were significantly associated with unsuccessful induction of labor. Bishop score was significantly higher in Group R (3.6 versus 1.9; P=0.001). Also, consistency (74.0 versus 44.4 %; OR=3.57; 95 % CI: 2.04-6.40; P<10(-5)) and absence of dilatation of the cervix (59.7 versus 23.0 %; OR=4.97; 95 % CI: 2.89-8.56; P<10(-6)) were identified as significant predictive factors for unsuccessful induction of labor. CONCLUSION: Nulliparity, gestational age ≤41 SA+4, history of dilatation and curettage and Bishop score, in particular consistency and dilatation, are correlated with failure of cervical ripening in post-term pregnancy with unfavorable cervix.

Outpatient cervical ripening by nitric oxide donors for prolonged pregnancy: a randomized controlled trial.

OBJECTIVE: To assess whether outpatient cervical ripening at 41 0/7 weeks of gestation with the nitric oxide donor isosorbide mononitrate reduces cesarean delivery rates in nulliparous women with an unfavorable cervix. METHODS: We recruited nulliparous pregnant women with a Bishop score less than 6 in a randomized, multicenter, double-blind, placebo-controlled trial. Women received 40 mg vaginal isosorbide mononitrate or a placebo at 41 0/7, 41 2/7, and 41 4/7 weeks of gestation. They returned home between visits. At 41 5/7 weeks of gestation, for women who had not yet given birth, labor was induced with oxytocin or prostaglandins, depending on cervical status. We needed 685 women per group to detect a 25% reduction in the cesarean delivery rate, the primary outcome measure, from 25% in the placebo group to 18.75% in the isosorbide mononitrate group (1-ß=0.8, α=0.05, two-sided). RESULTS: The NOCETER (NO donors for reduction of CEsareans at TERm) trial was a negative study. The cesarean delivery rate was 27.3% (185/678) in the isosorbide mononitrate group and 27.2% (186/684) in the placebo group (relative risk 1.00, 95% confidence interval [CI] 0.84-1.19). None of the maternal secondary efficacy outcomes differed between groups. Side effects were more common among women receiving isosorbide mononitrate than in the placebo group (78.8% [534/678] compared with 27.9% [191/684], relative risk 2.82, 95% CI 2.49-3.20). Composite perinatal morbidity did not differ between groups. CONCLUSION: Outpatient cervical ripening with vaginal isosorbide mononitrate for prolonged pregnancy in nulliparous women does not reduce cesarean delivery rate. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00930618.

[Brain damage in a child after outpatient induction of labour]. / Hjerneskade hos et barn efter ambulant igangsættelse af fødsel.

A 32-year-old woman had labour induced (25 + 25 microgram misoprostol vaginally) at 291 days gestation for post-term pregnancy. A cardiotocography (CTG) showed normal conditions. The woman went home to await regular contractions in line with hospital policy. She awoke at 3.15 a.m. with abdominal pain and came to the labour ward at 3.45 a.m. with less pain but a desire to push. The cervix was dilated but the foetal head sat high in the pelvis. Internal CTG showed a pre-terminal pattern. A girl was born at 4.27 a.m. She had hypoxic-ischaemic encephalopathy (APGAR at 1, 5 and 10 min.: 1, 3, 3; umbilical cord arterial blood pH 6.71, base excess -19.9 mmol/l). At the age of three years she had severe cerebral palsy.

Induction of labour in postdates pregnant women.

OBJECTIVE: To differentiate the effect of gestation on the mode of delivery by analysing the difference in the mode of induction, length of labour and the difference in parity or Bishop score and their effect on the mode of delivery of postdates women. STUDY DESIGN: A cross-sectional observational study. PLACE AND DURATION OF STUDY: PAEC General Hospital, Islamabad, from July 2006 to July 2008. METHODOLOGY: Patients were induced at 41 weeks (Group B) and > 40 weeks (Group A) of gestation. Tab misoprostol and PGE2 tablets were administered according to amniotic fluid index (AFI) and parity. Study variables included duration of gestation, mode of induction, length of labour, difference in parity and Bishop score assessed before induction in each group. The outcome was assessed by applying Chi-square test by comparing mode of delivery with the study variables in both groups. RESULTS: A total of 78 patients were inducted in the study. They were divided in group B (n = 39) induced 41 weeks and group A (n = 39) induced at 40 weeks. Eighty four percent (n = 35) patients in group B delivered vaginally as compared to 71% (n = 28) in the 40 weeks group (p < 0.0001). The higher number of vaginal deliveries in 41 weeks group was independent of association between the induction agent, parity and mode of delivery. CONCLUSION: The mean length of gestation was the single most important factor among the studied variables in predicting a vaginal delivery.

Evaluation of isosorbide mononitrate for cervical ripening prior to induction of labor for postdated pregnancy in an outpatient setting.

OBJECTIVE: To determine the safety and effectiveness of self-administered treatment with isosorbide mononitrate (IMN) for cervical ripening in Indian women with postdated pregnancies. METHODS: A randomized, placebo-controlled study was conducted with 200 women with postdated pregnancies and unfavorable cervices who self-administered vaginally either 2 40-mg tablets of IMN or 2 40-mg tablets of pyridoxine as placebo prior to admission for induction of labor. The main outcome variables were change in Bishop score, time from admission to delivery, and presence or absence of fetal and maternal morbidity. RESULTS: The Bishop score was significantly improved 24 hours after initiation of the outpatient IMN treatment (P<0.001) and the needs for further cervical ripening and oxytocin infusion were less in the study than in the control group (P<0.001 and P=0.008). The time from admission to delivery was also less (P<0.001). Moreover, the IMN treatment had no major adverse maternal or fetal effects. The vast majority of women in both groups were either satisfied or very satisfied with the outpatient treatment. CONCLUSION: The self-administration, at home, of isosorbide mononitrate leads to a safe and effective cervical ripening prior to labor induction in women with postdated pregnancies. CTRI Registration No.:CTRI/2011/091/000121.

Poor spontaneous and oxytocin-stimulated contractility in human myometrium from postdates pregnancies.

Prolongation of pregnancy i.e. going more than 10 days over the estimated due date, complicates up to 10% of all pregnancies and is associated with increased risk to both mother and fetus. Despite the obvious need for contractions of the uterus to end pregnancy, there have been no studies directly examining the role of uterine smooth muscle, myometrium, in the aetiology of prolonged pregnancy. This study tested the hypothesis that the intrinsic contractile characteristics of myometrium taken from women with prolonged pregnancy (>41 weeks and 3 days) was reduced compared to those delivering at term (39-41 weeks). We recruited women undergoing Caesarean Section (CS) delivery either pre-labour (n = 27) or in labour (n = 66) at term or postdates. The contractile ability of the postdates myometrium, whether spontaneous or elicited by oxytocin or high-K solution, was significantly reduced compared to term myometrium. These differences remained when adjusted for parity and other maternal characteristics. The findings remained significant when expressed per cross sectional area. Histological examination revealed no differences between the two groups. The contractile differences were however related to intracellular Ca transients suggesting an effect of [Ca] on reduced force production in the postdates group. In summary, myometrium from prolonged pregnancies contracts poorly in vitro even when stimulated with oxytocin and in active labour. Responses to high K(+) and measurements of Ca suggest that alterations in excitation contraction coupling, rather than any histological changes of the myometrium, may underlie the differences between term and postdates myometrium. We show that postdates pregnancy is associated with poor myometrial activity and suggest that this may contribute to increased myometrial quiescence and hence, prolonged gestation.

Comparison of low-dose oxytocin and dinoprostone for labor induction in postterm pregnancies: a randomized controlled prospective study.

AIMS: The aim of this study was to compare the efficacy of oxytocin and dinoprostone in achieving successful labor induction and vaginal delivery in postterm women with an unfavorable cervix. METHODS: Postterm women with an uncomplicated pregnancy and a Bishop score of ≤6 were randomized to receive either dinoprostone vaginal pessary (Propess®) or low-dose oxytocin. The primary outcomes were the length of the induction-to-delivery period and the incidence of vaginal delivery. RESULTS: A total of 144 women were available for the analysis. The overall vaginal delivery rates were 75% (54/72) for the dinoprostone group and 80.6% (58/72; p = 0.35) for the oxytocin group; the mean induction-to-vaginal delivery interval was 13.3 and 10.3 h in the dinoprostone and the oxytocin group, respectively (p = 0.003). Uterine hyperstimulation was 7.4% compared with 6.8% (p = 0.8), and abnormal fetal heart rate was 26.4% compared with 18% (p = 0.2), respectively. CONCLUSION: Both oxytocin and dinoprostone seem to have similar obstetric outcomes in postterm pregnancies with an unfavorable cervix, except for a significant superiority of oxytocin for delivery in a shorter period.

Induction of labor in prolonged pregnancy with unfavorable cervix: comparison of sequential intracervical Foley catheter-intravaginal misoprostol and intravaginal misoprostol alone.

PURPOSE: To compare the outcome of induced labor at term using sequential intracervical Foley catheter with intravaginal misoprostol versus intravaginal misoprostol alone. METHODS: A prospective matched case control study among parturient with prolonged pregnancy and unfavorable cervix at a tertiary hospital in Nigeria. RESULTS: The study population was 100 with a mean age of 29.46 ± 3.88 years. Parturient with prior cervical priming using intracervical Foley catheter had significantly lower oxytocin augmentation of uterine contractions in labor (44 vs. 64%, P = 0.045), shorter mean insertion to active phase labor duration (233 ± 98 vs. 354 ± 154 min, P = 0.0001), shorter insertion to delivery interval (514 ± 175 vs. 627 ± 268, P = 0.014), more vaginal delivery <12 h (92.5 vs. 60%, P = 0.001) and less delivery by caesarean section (20 vs. 40%, P = 0.029). CONCLUSIONS: The sequential combination of intracervical Foley catheter and intravaginal misoprostol for cervical ripening and induction of labor appears to be a safe and more effective method compared to intravaginal misoprostol in parturient at term with unfavorable cervices.

Outpatient oral misoprostol for prolonged pregnancies: a pilot investigation.

UNLABELLED: We evaluated the effectiveness of oral misoprostol for outpatient cervical ripening and labor induction in prolonged pregnancies. We performed a randomized, double-blind, placebo-controlled study of women at 40 to 42 weeks' gestation with well-dated pregnancies, singleton gestations, Bishop scores less than 6, vertex presentations, and intact membranes. Subjects received either oral misoprostol 100 microg or placebo daily for 3 days unless the subject developed significant cervical change or began labor spontaneously. Study drug was repeated every 24 hours for a maximum of three doses if subjects did not develop significant cervical change or enter labor. Induction of labor was not allowed while the subject was enrolled in the study. Forty-three subjects were randomized to receive misoprostol and 44 randomized to receive placebo. A significant difference was noted in reduction of time from study entry to both active phase (p < 0.001) and delivery (p < 0.001) in the misoprostol group. Fewer women remained undelivered after the 72-hour study period in the misoprostol group. There were no differences in route of delivery or neonatal outcomes between groups. CONCLUSION: Daily administration of oral misoprostol over 3 days to women with prolonged pregnancies shortened time intervals from dosing to entry into active labor and delivery compared with placebo.

[Ambulatory treatment of prolonged pregnancy with prostaglandin E2 gel]. / Embarazo de 41 semanas o mayor. Manejo ambulatorio con gel de prostaglandina E2.

BACKGROUND: the rutinary labor induction with prostaglandin E2 (PGE2) in pregnancy at 41 weeks has showed a fetal benefit without an increase in maternal morbidity or cesarean delivery. OBJECTIVE: to show that the ambulatory management of prolonged pregnancy with PGE2 gel decreases the cesarean delivery and prenatal morbidity rates. METHODS: quasiexperimetal study of patients with an accurate dated pregnancy of 41 weeks and beyond were analyzed. The women were divided in two groups of 196 each one. In the treated group, the endocervical application of PGE2 was followed by cardiotocographic control. If there was no reason to interrupt the pregnancy they were evaluated twice a week. Perinatal outcomes, mode of delivery and indications for cesarean section were assessed in both groups. RESULTS: there was a decrease in rate of cesarean delivery in treated group, 43 % versus 54 % in control group (p < 0.05). Apgar score at 1 and 5 minute showed no difference, but there were two intrauterine deaths in control group. The indications for cesarean surgery were the same in both groups and there was a case of tachysystole in each one. CONCLUSION: we concluded that decrease in the rate of cesarean deliveries without increments of fetal and maternal morbidity in this study, point to a secure management choice with PGE2 in ambulatory patients.