Methods of induction of labor in women with obesity: A secondary analysis of two multicenter randomized controlled trials.

INTRODUCTION: Obesity is an increasing public health concern worldwide and can lead to more complications in pregnancy and childbirth. Women with obesity more often require induction of labor for various indications. The aim of this study is to assess which method of induction of labor is safest and most effective in women with obesity. MATERIAL AND METHODS: This is a secondary analysis of two randomized controlled trials about induction of labor. Women with a term singleton pregnancy in cephalic presentation, an unfavorable cervix, intact membranes and without a previous cesarean section were randomly allocated to cervical priming with a Foley catheter or vaginal prostaglandin-E2-gel (PROBAAT-I) or a Foley catheter or oral misoprostol (PROBAAT-II). The inclusion and exclusion criteria for the studies were identical. Induction methods were compared in women with obesity (body mass index ≥30.0). Main outcomes were cesarean section and postpartum hemorrhage (blood loss >1000 mL). RESULTS: A total of 2664 women, were included in the trials, 517 of whom were obese: 254 women with obesity received a Foley catheter, 176 oral misoprostol and 87 prostaglandin E2 (PGE2). A cesarean section was performed in 29.1% of women allocated to Foley vs 22.2% in the misoprostol and 23.0% in the PGE2 groups. Comparisons between groups revealed no statistically significant differences: the relative risk [RR] was 1.31 (95% confidence interval [CI] 0.94-1.84) in the Foley vs misoprostol group and 1.27 (95% CI 0.83-1.95) in the Foley vs PGE2 group. The rates of postpartum hemorrhage were comparable (10.6%, 11.4% and 6.9%, respectively; P = 0.512). In women with obesity, more often a switch to another method occurred in the Foley group, (20.1% vs 6.3% in misoprostol vs 1.1% in the PGE2 group; P < 0.001). The risk of a failed Foley placement was higher in women with obesity than in women without obesity (8.3% vs 3.2%; adjusted odds ratio 3.12, 95% CI 1.65-5.90). CONCLUSIONS: In women with obesity we found a nonsignificant trend towards an increased rate of cesarean sections in the group induced with a Foley catheter compared to oral misoprostol; however, the study lacked power for this subgroup analysis. The finding of a higher risk of failed placement of a Foley catheter in women with obesity can be used in shared decision making.

Finding the sentinel lymph node in early cervical cancer: When is unusual not uncommon?

OBJECTIVE: To report our institutional experience with sentinel lymph node (SLN) detection using indocyanine green for cervical cancer, in terms of detection rates, detection of SLN at unusual locations, and factors associated with unusual SLN locations. In addition, we performed a systematic review of the literature to identify factors associated with unusual SLN localizations. METHODS: This is a retrospective cohort study of women with early-stage cervical cancer undergoing sentinel lymph node mapping between 2015 and 2019. Outcome measures were SLN detection rates, detection rates of unusual locations for SLN and risk factors for aberrant lymphatic drainage pathways. In addition, studies evaluating factors associated with unusual SLN locations in cervical cancer were assessed in a systematic review. RESULTS: A total of 100 patients were included. The unilateral SLN detection rate was 88%, whereas the bilateral detection rate was 75%. In 37% of all patients, SLN were found in unusual locations, and in 10% of patients SLN were solely found in unusual locations. Body mass index (BMI) was associated with finding SLN in unusual locations, with unusual nodes detected in 52% of patients with BMI <25 kg/m2 and in 28% of patients with BMI ≥25 kg/m2. The systematic review identified three studies, identifying lower BMI, nulliparity and tumor size of >20 mm as factors associated with finding SLN at unusual locations. CONCLUSION: Aberrant drainage sites represent a significant proportion of SLN detected in cervical cancer. Factors associated with increased rates of unusual nodal locations are a lower BMI, with a possible association with nulliparity and tumor size of >20 mm.

Mechanical methods for induction of labour.

BACKGROUND: Mechanical methods were the first methods developed to ripen the cervix and induce labour. During recent decades they have been substituted by pharmacological methods. Potential advantages of mechanical methods, compared with pharmacological methods may include reduction in side effects that could improve neonatal outcomes. This is an update of a review first published in 2001, last updated in 2012. OBJECTIVES: To determine the effectiveness and safety of mechanical methods for third trimester (> 24 weeks' gestation) induction of labour in comparison with prostaglandin E2 (PGE2) (vaginal and intracervical), low-dose misoprostol (oral and vaginal), amniotomy or oxytocin. SEARCH METHODS: For this update, we searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP), and reference lists of retrieved studies (9 January 2018). We updated the search in March 2019 and added the search results to the awaiting classification section of the review. SELECTION CRITERIA: Clinical trials comparing mechanical methods used for third trimester cervical ripening or labour induction with pharmacological methods. Mechanical methods include: (1) the introduction of a catheter through the cervix into the extra-amniotic space with balloon insufflation; (2) introduction of laminaria tents, or their synthetic equivalent (Dilapan), into the cervical canal; (3) use of a catheter to inject fluid into the extra-amniotic space (EASI). This review includes the following comparisons: (1) specific mechanical methods (balloon catheter, laminaria tents or EASI) compared with prostaglandins (different types, different routes) or with oxytocin; (2) single balloon compared to a double balloon; (3) addition of prostaglandins or oxytocin to mechanical methods compared with prostaglandins or oxytocin alone. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and assessed risk of bias. Two review authors independently extracted data and assessed the quality of the evidence using the GRADE approach. MAIN RESULTS: This review includes a total of 112 trials, with 104 studies contributing data (22,055 women; 21 comparisons). Risk of bias of trials varied. Overall, the evidence was graded from very-low to moderate quality. All evidence was downgraded for lack of blinding and, for many comparisons, the effect estimates were too imprecise to make a valid judgement.   Balloon versus vaginal PGE2: there may be little or no difference in vaginal deliveries not achieved within 24 hours (risk ratio (RR) 1.01, 95% confidence interval (CI) 0.82 to 1.26; 7 studies; 1685 women; low-quality evidence) and there probably is little or no difference in caesarean sections (RR 1.00, 95% CI 0.92 to 1.09; 28 studies; 6619 women; moderate-quality evidence) between induction of labour with a balloon catheter and vaginal PGE2. A balloon catheter probably reduces the risk of uterine hyperstimulation with fetal heart rate (FHR) changes (RR 0.35, 95% CI 0.18 to 0.67; 6 studies; 1966 women; moderate-quality evidence), serious neonatal morbidity or perinatal death (RR 0.48, 95% CI 0.25 to 0.93; 8 studies; 2757 women; moderate-quality evidence) and may slightly reduce the risk of aneonatal intensive care unit (NICU) admission (RR 0.82, 95% CI 0.65 to 1.04; 3647 women; 12 studies; low-quality evidence). It is uncertain whether there is a difference in serious maternal morbidity or death (RR 0.20, 95% CI 0.01 to 4.12; 4 studies; 1481 women) or five-minute Apgar score < 7 (RR 0.74, 95% CI 0.49 to 1.14; 4271 women; 14 studies) because the quality of the evidence was found to be very low and low, respectively. Balloon versus low-dose vaginal misoprostol: it is uncertain whether there is a difference in vaginal deliveries not achieved within 24 hours between induction of labour with a balloon catheter and vaginal misoprostol (RR 1.09, 95% CI 0.85 to 1.39; 340 women; 2 studies; low-quality evidence). A balloon catheter probably reduces the risk of uterine hyperstimulation with FHR changes (RR 0.39, 95% CI 0.18 to 0.85; 1322 women; 8 studies; moderate-quality evidence) but may increase the risk of a caesarean section (RR 1.28, 95% CI 1.02 to 1.60; 1756 women; 12 studies; low-quality evidence). It is uncertain whether there is a difference in serious neonatal morbidity or perinatal death (RR 0.58, 95% CI 0.12 to 2.66; 381 women; 3 studies), serious maternal morbidity or death (no events; 4 studies, 464 women), both very low-quality evidence, and five-minute Apgar score < 7 (RR 1.00, 95% CI 0.50 to 1.97; 941 women; 7 studies) and NICU admissions (RR 1.00, 95% CI 0.61 to 1.63; 1302 women; 9 studies) both low-quality evidence. Balloon versus low-dose oral misoprostol: a balloon catheter probably increases the risk of a vaginal delivery not achieved within 24 hours (RR 1.28, 95% CI 1.13 to 1.46; 782 women, 2 studies, and probably slightly increases the risk of a caesarean section (RR 1.17, 95% CI 1.04 to 1.32; 3178 women; 7 studies; both moderate-quality evidence) when compared to oral misoprostol. It is uncertain whether there is a difference in uterine hyperstimulation with FHR changes (RR 0.81, 95% CI 0.48 to 1.38; 2033 women; 2 studies), serious neonatal morbidity or perinatal death (RR 1.11, 95% CI 0.60 to 2.06; 2627 women; 3 studies), both low-quality evidence, serious maternal morbidity or death (RR 0.50, 95% CI 0.05 to 5.52; 2627 women; 3 studies), very low-quality evidence, five-minute Apgar scores < 7 (RR 0.71, 95% CI 0.38 to 1.32; 2693 women; 4 studies) and NICU admissions (RR 0.82, 95% CI 0.58 to 1.17; 2873 women; 5 studies) both low-quality evidence. AUTHORS' CONCLUSIONS: Low- to moderate-quality evidence shows mechanical induction with a balloon is probably as effective as induction of labour with vaginal PGE2. However, a balloon seems to have a more favourable safety profile. More research on this comparison does not seem warranted. Moderate-quality evidence shows a balloon catheter may be slightly less effective as oral misoprostol, but it remains unclear if there is a difference in safety outcomes for the neonate. When compared to low-dose vaginal misoprostol, low-quality evidence shows a balloon may be less effective, but probably has a better safety profile. Future research could be focused more on safety aspects for the neonate and maternal satisfaction.

Evaluation of treatment, prognostic factors, and survival in 198 vulvar melanoma patients: Implications for clinical practice.

OBJECTIVE: To identify clinicopathological characteristics, treatment patterns, clinical outcomes and prognostic factors in patients with vulvar melanoma (VM). MATERIALS & METHODS: This retrospective multicentre cohort study included 198 women with VM treated in eight cancer centres in the Netherlands and UK between 1990 and 2017. Clinicopathological features, treatment, recurrence, and survival data were collected. Overall and recurrence-free survival was estimated with the Kaplan-Meier method. Prognostic parameters were identified with multivariable Cox regression analysis. RESULTS: The majority of patients (75.8%) had localized disease at diagnosis. VM was significantly associated with high-risk clinicopathological features, including age, tumour thickness, ulceration, positive resection margins and involved lymph nodes. Overall survival was 48% (95% CI 40-56%) and 31% (95% CI 23-39%) after 2 and 5 years respectively and did not improve in patients diagnosed after 2010 compared to patients diagnosed between 1990 and 2009. Recurrence occurred in 66.7% of patients, of which two-third was non-local. In multivariable analysis, age and tumour size were independent prognostic factors for worse survival. Prognostic factors for recurrence were tumour size and tumour type. Only the minority of patients were treated with immuno- or targeted therapy. CONCLUSION: Our results show that even clinically early-stage VM is an aggressive disease associated with poor clinical outcome due to distant metastases. Further investigation into the genomic landscape and the immune microenvironment in VM may pave the way to novel therapies to improve clinical outcomes in these aggressive tumours. Clinical trials with immunotherapy or targeted therapy in patients with high-risk, advanced or metastatic disease are highly needed.

Mechanical methods for induction of labour.

BACKGROUND: Mechanical methods were the first methods developed to ripen the cervix and induce labour. During recent decades they have been substituted by pharmacological methods. Potential advantages of mechanical methods, compared with pharmacological methods may include reduction in side effects that could improve neonatal outcomes. This is an update of a review first published in 2001, last updated in 2012. OBJECTIVES: To determine the effectiveness and safety of mechanical methods for third trimester (> 24 weeks' gestation) induction of labour in comparison with prostaglandin E2 (PGE2) (vaginal and intracervical), low-dose misoprostol (oral and vaginal), amniotomy or oxytocin. SEARCH METHODS: For this update, we searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP), and reference lists of retrieved studies (9 January 2018). We updated the search in March 2019 and added the search results to the awaiting classification section of the review. SELECTION CRITERIA: Clinical trials comparing mechanical methods used for third trimester cervical ripening or labour induction with pharmacological methods.Mechanical methods include: (1) the introduction of a catheter through the cervix into the extra-amniotic space with balloon insufflation; (2) introduction of laminaria tents, or their synthetic equivalent (Dilapan), into the cervical canal; (3) use of a catheter to inject fluid into the extra-amniotic space (EASI).This review includes the following comparisons: (1) specific mechanical methods (balloon catheter, laminaria tents or EASI) compared with prostaglandins (different types, different routes) or with oxytocin; (2) single balloon compared to a double balloon; (3) addition of prostaglandins or oxytocin to mechanical methods compared with prostaglandins or oxytocin alone. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and assessed risk of bias. Two review authors independently extracted data and assessed the quality of the evidence using the GRADE approach. MAIN RESULTS: This review update includes a total of 113 trials (22,373 women) contributing data to 21 comparisons. Risk of bias of trials varied. Overall, the evidence was graded from very-low to moderate quality. All evidence was downgraded for lack of blinding and, for many comparisons, the effect estimates were too imprecise to make a valid judgement.Balloon versus vaginal PGE2: there may be little or no difference in vaginal deliveries not achieved within 24 hours (average risk ratio (RR) 1.01, 95% confidence interval (CI) 0.82 to 1.26; 7 studies; 1685 women; I² = 79%; low-quality evidence) and there probably is little or no difference in caesarean sections (RR 1.00, 95% CI 0.92 to 1.09; 28 studies; 6619 women; moderate-quality evidence) between induction of labour with a balloon catheter and vaginal PGE2. A balloon catheter probably reduces the risk of uterine hyperstimulation with fetal heart rate (FHR) changes (RR 0.35, 95% CI 0.18 to 0.67; 6 studies; 1966 women; moderate-quality evidence), serious neonatal morbidity or perinatal death (RR 0.48, 95% CI 0.25 to 0.93; 8 studies; 2757 women; moderate-quality evidence) and may slightly reduce the risk of aneonatal intensive care unit (NICU) admission (RR 0.82, 95% CI 0.65 to 1.04; 3647 women; 12 studies; low-quality evidence). It is uncertain whether there is a difference in serious maternal morbidity or death (RR 0.20, 95% CI 0.01 to 4.12; 4 studies; 1481 women) or five-minute Apgar score < 7 (RR 0.74, 95% CI 0.49 to 1.14; 4271 women; 14 studies) because the quality of the evidence was found to be very low and low, respectively.Balloon versus low-dose vaginal misoprostol: it is uncertain whether there is a difference in vaginal deliveries not achieved within 24 hours between induction of labour with a balloon catheter and vaginal misoprostol (RR 1.09, 95% CI 0.85 to 1.39; 340 women; 2 studies; low-quality evidence). A balloon catheter probably reduces the risk of uterine hyperstimulation with FHR changes (RR 0.39, 95% CI 0.18 to 0.85; 1322 women; 8 studies; moderate-quality evidence) but may increase the risk of a caesarean section (average RR 1.28, 95% CI 1.02 to 1.60; 1756 women; 12 studies; I² = 45%; low-quality evidence). It is uncertain whether there is a difference in serious neonatal morbidity or perinatal death (RR 0.58, 95% CI 0.12 to 2.66; 381 women; 3 studies), serious maternal morbidity or death (no events; 4 studies, 464 women), both very low-quality evidence, and five-minute Apgar score < 7 (RR 1.00, 95% CI 0.50 to 1.97; 941 women; 7 studies) and NICU admissions (RR 1.00, 95% CI 0.61 to 1.63; 1302 women; 9 studies) both low-quality evidence.Balloon versus low-dose oral misoprostol: a balloon catheter probably increases the risk of a vaginal delivery not achieved within 24 hours (RR 1.28, 95% CI 1.13 to 1.46; 782 women, 2 studies, and probably slightly increases the risk of a caesarean section (RR 1.17, 95% CI 1.04 to 1.32; 3178 women; 7 studies; both moderate-quality evidence) when compared to oral misoprostol. It is uncertain whether there is a difference in uterine hyperstimulation with FHR changes (RR 0.81, 95% CI 0.48 to 1.38; 2033 women; 2 studies), serious neonatal morbidity or perinatal death (RR 1.11, 95% CI 0.60 to 2.06; 2627 women; 3 studies), both low-quality evidence, serious maternal morbidity or death (RR 0.50, 95% CI 0.05 to 5.52; 2627 women; 3 studies), very low-quality evidence, five-minute Apgar scores < 7 (RR 0.71, 95% CI 0.38 to 1.32; 2693 women; 4 studies) and NICU admissions (RR 0.82, 95% CI 0.58 to 1.17; 2873 women; 5 studies) both low-quality evidence. AUTHORS' CONCLUSIONS: Low- to moderate-quality evidence shows mechanical induction with a balloon is probably as effective as induction of labour with vaginal PGE2. However, a balloon seems to have a more favourable safety profile. More research on this comparison does not seem warranted.Moderate-quality evidence shows a balloon catheter may be slightly less effective as oral misoprostol, but it remains unclear if there is a difference in safety outcomes for the neonate. When compared to low-dose vaginal misoprostol, low-quality evidence shows a balloon may be less effective, but probably has a better safety profile.Future research could be focused more on safety aspects for the neonate and maternal satisfaction.

Balloon catheter for induction of labor in women with one previous cesarean and an unfavorable cervix.

INTRODUCTION: When women with a previous cesarean section and an unfavorable cervix have an indication for delivery, the choice is to induce labor or to perform a cesarean section. This study aims to assess the effectiveness and safety of a balloon catheter as a method of induction of labor in women with one previous cesarean section and an unfavorable cervix compared with an elective repeat cesarean section. MATERIAL AND METHODS: We performed a prospective cohort study in 51 hospitals in the Netherlands on term women with one previous cesarean section, a live singleton fetus in cephalic position, an unfavorable cervix and an indication for delivery. We recorded obstetric, maternal and neonatal characteristics. We compared the outcome of women who were induced with a balloon catheter with the outcome of women who delivered by elective repeat cesarean section. Main outcomes were maternal and neonatal morbidity. Mode of delivery was a secondary outcome for women who were induced. Adjusted odds ratios (aOR) were calculated using logistic regression, adjusted for potential confounders. RESULTS: Analysis was performed on 993 women who were induced and 321 women who had a repeat cesarean section (August 2011 until September 2012). Among the women who were induced, 560 (56.4%) delivered vaginally and 11 (1.1%) sustained a uterine rupture. Composite adverse maternal outcome (uterine rupture, severe postpartum hemorrhage or postpartum infection) occurred in 73 (7.4%) in the balloon and 14 (4.5%) women in the repeat cesarean section group (aOR 1.58, 95% confidence interval [CI] 0.85-2.96). Composite adverse neonatal outcome (Apgar score <7 at 5 minutes or umbilical pH <7.10) occurred in 57 (5.7%) and 10 (3.2%) neonates, respectively (aOR 1.40, 95% CI 0.87-3.48). Women who were induced had a shorter postpartum admission time (2.0 vs 3.0 days (P < 0.0001)). CONCLUSIONS: In women with a previous cesarean section and a need for delivery, induction of labor with a balloon catheter does not result in a significant increase in adverse maternal and neonatal outcomes as compared with planned cesarean section.

Induction of labour at term with oral misoprostol versus a Foley catheter (PROBAAT-II): a multicentre randomised controlled non-inferiority trial.

BACKGROUND: Labour is induced in 20-30% of all pregnancies. In women with an unfavourable cervix, both oral misoprostol and Foley catheter are equally effective compared with dinoprostone in establishing vaginal birth, but each has a better safety profile. We did a trial to directly compare oral misoprostol with Foley catheter alone. METHODS: We did an open-label randomised non-inferiority trial in 29 hospitals in the Netherlands. Women with a term singleton pregnancy in cephalic presentation, an unfavourable cervix, intact membranes, and without a previous caesarean section who were scheduled for induction of labour were randomly allocated to cervical ripening with 50 µg oral misoprostol once every 4 h or to a 30 mL transcervical Foley catheter. The primary outcome was a composite of asphyxia (pH ≤7·05 or 5-min Apgar score <7) or post-partum haemorrhage (≥1000 mL). The non-inferiority margin was 5%. The trial is registered with the Netherlands Trial Register, NTR3466. FINDINGS: Between July, 2012, and October, 2013, we randomly assigned 932 women to oral misoprostol and 927 women to Foley catheter. The composite primary outcome occurred in 113 (12·2%) of 924 participants in the misoprostol group versus 106 (11·5%) of 921 in the Foley catheter group (adjusted relative risk 1·06, 90% CI 0·86-1·31). Caesarean section occurred in 155 (16·8%) women versus 185 (20·1%; relative risk 0·84, 95% CI 0·69-1·02, p=0·067). 27 adverse events were reported in the misoprostol group versus 25 in the Foley catheter group. None were directly related to the study procedure. INTERPRETATION: In women with an unfavourable cervix at term, induction of labour with oral misoprostol and Foley catheter has similar safety and effectiveness. FUNDING: FondsNutsOhra.

Women's Experiences with and Preference for Induction of Labor with Oral Misoprostol or Foley Catheter at Term.

Objective We assessed experience and preferences among term women undergoing induction of labor with oral misoprostol or Foley catheter. Study Design In 18 of the 29 participating hospitals in the PROBAAT-II trial, women were asked to complete a questionnaire within 24 hours after delivery. We adapted a validated questionnaire about expectancy and experience of labor and asked women whether they would prefer the same method again in a future pregnancy. Results The questionnaire was completed by 502 (72%) of 695 eligible women; 273 (54%) had been randomly allocated to oral misoprostol and 229 (46%) to Foley catheter. Experience of the duration of labor, pain during labor, general satisfaction with labor, and feelings of control and fear related to their expectation were comparable between both the groups. In the oral misoprostol group, 6% of the women would prefer the other method if induction is necessary in future pregnancy, versus 12% in the Foley catheter group (risk ratio: 0.70; 95% confidence interval: 0.55-0.90; p = 0.02). Conclusion Women's experiences of labor after induction with oral misoprostol or Foley catheter are comparable. However, women in the Foley catheter group prefer more often to choose a different method for future inductions.

Foley catheter versus vaginal misoprostol: randomized controlled trial (PROBAAT-M study) and systematic review and meta-analysis of literature.

OBJECTIVES: To assess effectiveness and safety of Foley catheter versus vaginal misoprostol for term induction of labor. STUDY DESIGN: This trial randomly allocated women with singleton term pregnancy to 30-mL Foley catheter or 25-µg vaginal misoprostol tablets. Primary outcome was cesarean delivery rate. Secondary outcomes were maternal and neonatal morbidity and time to birth. Additionally, a systematic review was conducted. RESULTS: Fifty-six women were allocated to Foley catheter, 64 to vaginal misoprostol tablets. Cesarean delivery rates did not differ significantly (25% Foley versus 17% misoprostol; relative risk [RR] 1.46, 95% confidence interval [CI] 0.72 to 2.94), with more cesarean deliveries due to failure to progress in the Foley group (14% versus 3%; RR 4.57, 95% CI 1.01 to 20.64). Maternal and neonatal outcomes were comparable. Time from induction to birth was longer in the Foley catheter group (36 hours versus 25 hours; p < 0.001). Meta-analysis showed no difference in cesarean delivery rate and reduced vaginal instrumental deliveries and hyperstimulation in the Foley catheter group. Other outcomes were not different. CONCLUSION: Our trial and meta-analysis showed no difference in cesarean delivery rates and less hyperstimulation with fetal heart rate changes and vaginal instrumental deliveries when using Foley catheter, thereby supporting potential advantages of the Foley catheter over misoprostol as ripening agent.

Induction of labour with a Foley catheter or oral misoprostol at term: the PROBAAT-II study, a multicentre randomised controlled trial.

BACKGROUND: Induction of labour is a common obstetric procedure. At present, different methods are used for induction of labour in women with an unfavourable cervix. Recently, we showed that in term women with an unfavorable cervix the use of a Foley catheter in comparison with vaginal Prostaglandin E2 gel, results in a comparable vaginal delivery rate. A meta-analysis on the subject indicated lower rates of hyperstimulation, and probably as a sequel fewer cases of postpartum haemorrhage. Misoprostol (PgE1) is another type of prostaglandin frequently used for labour induction, recommended by the international federation of gynaecology and obstetrics (FIGO). Misoprostol can be administered by vaginal, rectal and oral route. There is evidence that oral administration results in less asphyxia and hyperstimulation than vaginal administration. At present, valid comparisons between oral misoprostol and Foley catheter are lacking. Therefore, we propose a randomised controlled trial comparing Foley catheter to oral misoprostol in order to assess safety and cost-effectiveness. METHODS/DESIGN: We plan a multicentre, randomised, controlled, open-label clinical trial among term pregnant women with a vital singleton in cephalic presentation, unfavorable cervix, intact membranes and an indication for induction of labour. After informed consent, women will be randomly allocated by a webbased randomisation system to transcervical Foley catheter or oral misoprostol (50 mcg every 4 hours). The primary outcome will be a composite of complications of uterine hyperstimulation, i.e. post partum haemorrhage and asphyxia. Secondary outcomes are mode of delivery, maternal and neonatal morbidity, costs and women's preference. Serious adverse events such as severe maternal or neonatal morbitity or mortality will be monitored and reported to an independent data safety monitory board. With a sample size of 1860 women we will be able to demonstrate a 5% non-inferiority of the Foley catheter as compared to misoprostol for the composite outcome. DISCUSSION: Worldwide, various methods are being used for labour induction. Results of the proposed trial will contribute to the answer which method of induction of labour is most safe, cost-effective, and patient friendly and will help to construct evidence based guidelines. TRIAL REGISTRATION: The Netherlands Trial Register NTR3466.

The influence of various induction methods on adverse outcomes in small for gestational age neonates: A secondary analysis of the PROBAAT 1 and 2 trials.

OBJECTIVE: To evaluate the safety aspects of different induction methods in pregnancies with small-for-gestational-age neonates. STUDY DESIGN: This was a secondary analysis of two previously reported multicenter, randomized controlled trials conducted in the Netherlands. In the original trials, women were randomized to either a 30 cc Foley catheter, vaginal prostaglandin E2 (PROBAAT-1) or oral misoprostol (PROBAAT-2). A total of 425 patients with a term, singleton pregnancy in cephalic presentation with an indication for labor induction and a small-for-gestational-age neonate were included in this secondary analysis. Our primary outcome was a composed adverse neonatal outcome of Apgar score < 7 after 5 min and/or a pH in the umbilical artery < 7.05 and/or NICU admission. Secondary outcomes were mode of birth, operative birth for fetal distress and pH < 7.10 in the umbilical artery. For these outcome measures, multivariate as well as bivariate analyses were performed. RESULTS: An adverse neonatal outcome occurred in 4.7 % (10/214) induction with a Foley catheter, versus 12.8 % (19/149) after misoprostol (RR 0.36; 95 % CI 0.17-0.76) and 4.7 % (3/64) after Prostaglandin E2 (RR 0.98; 95 %CI 0.28-3.51). For individual components of the composed outcome of adverse events, a difference was found between a Foley catheter and misoprostol for Apgar score < 7 at 5 min (0.5 % versus 3.4; RR 0.14; 95 %CI 0.02-1.16) and NICU admission (1.9 % versus 6.1 %; RR 0.31; 0.10-0.97). No differences were found for mode of birth. CONCLUSIONS: For women who gave birth to a small-for-gestational-age neonate, a Foley catheter is probably a safer induction method compared to oral misoprostol.

Does the New FIGO 2018 Staging System Allow Better Prognostic Differentiation in Early Stage Cervical Cancer? A Dutch Nationwide Cohort Study.

The FIGO 2018 staging system was introduced to allow better prognostic differentiation in cervical cancer, causing considerable stage migration and affecting treatment options. We evaluated the accuracy of the FIGO 2018 staging in predicting recurrence free (RFS) and overall survival (OS) compared to FIGO 2009 staging in clinically early stage cervical cancer. We conducted a nationwide retrospective cohort study, including 2264 patients with preoperative FIGO (2009) IA1, IA2 and IB1 cervical cancer between 2007-2017. Kaplan-Meier analyses were used to assess survival outcomes. Logistic regression was used to assess risk factors for lymph node metastasis and parametrial invasion. Stage migration occurred in 48% (22% down-staged, 26% up-staged). Survival data of patients down-staged from IB to IA1/2 disease were comparable with FIGO 2009 IA1/2 and better than patients remaining stage IB1. LVSI, invasion depth and parametrial invasion were risk factors for lymph node metastases. LVSI, grade and age were associated with parametrial invasion. In conclusion, the FIGO 2018 staging system accurately reflects prognosis in early stage cervical cancer and is therefore more suitable than the FIGO 2009 staging. However subdivision in IA1 or IA2 based on presence or absence of LVSI instead of depth of invasion would have improved accuracy. For patients down-staged to IA1/2, less radical surgery seems appropriate, although LVSI and histology should be considered when determining the treatment plan.

Uterine rupture in pregnancy after an intervention complicated by uterine perforation: Case report and systematic review of literature.

OBJECTIVES: The present study is a descriptive study of characteristics of women who had a uterine rupture during pregnancy with a history of uterine perforation and no previous caesarean section. STUDY DESIGN: We present a case report of a woman with a uterine rupture in pregnancy subsequent to a perforation made by uterine sounding and we performed a systematic review including all case-reports of uterine ruptures after perforation during dilatation and curettage or due to uterine sounding. RESULTS: 14 case-reports were included in this review. 12 out of 14 women presented with abdominal pain prior to the uterine rupture. In eight out of 14 cases an abdominal ultrasound was performed and in five ultrasounds a uterine wall defect was detected, in two other cases free fluid was visible and in one case fetal bradycardia was seen. Neonatal outcome was uneventful in six cases, there where two immature fetuses born and in two cases there was fetal demise. CONCLUSION: Uterine rupture in a (supposed) unscarred uterus is a relatively unknown complication. We recommend clinicians to be aware of uterine rupture in pregnant women with abdominal pain and a history of uterine manipulation. When a uterine rupture is suspected and mother and fetus are in suspected good condition, an ultrasound examination could be an easy and fast next step.

Vulvar malignant melanoma: Pathogenesis, clinical behaviour and management: Review of the literature.

Vulvar malignant melanoma (VMM) is a rare disease, accounting for 5% of all vulvar malignancies and is characterized by low survival and high recurrence rates. It is considered as a distinct entity of mucosal melanoma. Prognostic factors are higher age, advanced Breslow thickness, and lymph node involvement whilst central localization and ulceration status are still under debate. Surgery is the cornerstone for the treatment of primary VMM, however, it can be mutilating due to the anatomical location of the disease. Elective lymph node dissection is not part of standard care. The value of sentinel lymph node biopsy in VMM is still being studied. Radiation therapy and chemotherapy as adjuvant treatment do not benefit survival. Immunotherapy in cutaneous melanoma has shown promising results but clinical studies in VMM are scarce. In metastatic VMM, checkpoint inhibitors and in case of BRAF or KIT mutated metastatic VMM targeted therapy have shown clinical efficacy. In this review, we present an overview of clinical aspects, clinicopathological characteristics and its prognostic value and the latest view on (adjuvant) therapy and follow-up.

Induction of Labor Using a Foley Catheter or Misoprostol: A Systematic Review and Meta-analysis.

IMPORTANCE: Induction of labor is a widely used obstetric intervention, occurring in one in four pregnancies. When the cervix is unfavorable, still many different induction methods are used. OBJECTIVE: We compared Foley catheter alone to different misoprostol dosages and administration routes, and the combination of Foley catheter with misoprostol. EVIDENCE ACQUISITION: We reviewed the literature on the best induction method regarding their safety and effectiveness, using the outcome measures hyperstimulation, fetal distress, neonatal morbidity and mortality as well as cesarean delivery, vaginal instrumental delivery, and maternal morbidity. We searched Pubmed, Cochrane, and Web of Science from January 1, 1980 to February 12, 2016. Twenty-two randomized controlled trials (RCTs) were included, comparing Foley catheter with or without misoprostol to misoprostol alone (both vaginal and oral) for induction of labor (5,015 women). RESULTS: Most included studies were underpowered to detect differences in safety outcomes, as the majority are powered for time to delivery or cesarean delivery. Meta-analysis of these studies does not allow assessment of the safety profile of Foley catheter compared to misoprostol (any dose, any administration route) with sufficient power. For the safety outcomes of the total group of Foley catheter versus misoprostol (any dose, any administration route) (17 studies, 4,234 women) we found that Foley catheter results in less hyperstimulation compared to misoprostol (2% versus 4%; risk ratio [RR], 0.54; 95% confidence interval [CI], 0.37-0.79) and fewer cesarean deliveries for nonreassuring fetal heart rate, 5% vs 7%; RR, 0.72; 95% CI, 0.55-0.95; while there were no statistically significant differences in neonatal outcomes. The total number of cesarean deliveries was 26% versus 22% (RR, 1.16; 95% CI, 1.00-1.34). There were fewer vaginal instrumental deliveries with a Foley catheter compared to misoprostol (10% vs 14%; RR, 0.74; 95% CI, 0.60-0.91). Foley catheter with misoprostol compared to misoprostol alone (any dose, any administration route) (7 studies, 1,073 women) resulted in less hyperstimulation than misoprostol alone (17% vs 23%; RR, 0.71; 95% CI, 0.52-0.97). Cesarean deliveries for nonreassuring fetal heart rate were comparable (7% vs 9%; RR, 0.79; 95% CI, 0.51-1.22). Neonatal outcomes were infrequently reported. The total number of cesarean deliveries was 34% versus 34% (RR, 1.01; 95% CI, 0.86-1.19). CONCLUSION: In women with an unripe cervix at term, Foley catheter seems to have a better safety profile than misoprostol (any dose, any administration route) for induction of labor. Larger studies are needed to investigate the safety profile of a Foley catheter compared to separate dosing and administration regimens of misoprostol.

Foley catheter or prostaglandin E2 inserts for induction of labour at term: an open-label randomized controlled trial (PROBAAT-P trial) and systematic review of literature.

OBJECTIVE: To assess the safety and effectiveness of a transcervical Foley catheter compared to vaginal prostaglandin E2 inserts for term induction of labour. STUDY DESIGN: We conducted an open-label randomized controlled trial in five hospitals in the Netherlands. Women with a singleton term pregnancy in cephalic presentation, intact membranes, unfavourable cervix, and no prior caesarean section were enrolled. Participants were randomly allocated by a web-based randomization system to induction of labour with a 30 ml Foley catheter or 10mg slow-release vaginal prostaglandin E2 inserts in a 1:1 ratio. Due to the nature of the intervention this study was not blinded. The primary outcome was the caesarean section rate. Secondary outcomes were maternal and neonatal morbidity and time from intervention to birth. Additionally, we carried out a systematic review and meta-analysis of similar studies. RESULTS: We analyzed 226 women: 107 received a Foley catheter and 119 inserts. Caesarean section rates were comparable (20% versus 22%, RR 0.90, 95% CI 0.54-1.50). Secondary outcomes showed no differences. We observed no serious maternal or neonatal morbidity. Meta-analysis showed comparable caesarean section rates, but significantly fewer cases of hyperstimulation during the ripening phase when a Foley catheter was used. CONCLUSIONS: We found, in this relatively small study, no differences in effectiveness and safety of induction of labour with a Foley catheter and 10mg slow release vaginal prostaglandin E2 inserts. Meta-analysis confirmed a comparable caesarean section rate, and showed fewer cases of hyperstimulation when a Foley catheter was used.