Oxytocin versus prostaglandins for labour Induction of women with an unfavourable cervix after 24 hours of cervical ripening (OPIC): protocol for an open multicentre randomised non-inferiority trial.

INTRODUCTION: It remains uncertain whether the most appropriate management for women with an unfavourable cervix after 24 hours of cervical ripening is repeating the ripening procedure or proceeding directly to induction by oxytocin. No adequately powered trial has compared these strategies. We hypothesise that induction of labour with oxytocin among women who have just undergone an ineffective first ripening procedure is not associated with a higher risk of caesarean delivery than a repeated cervical ripening with prostaglandins. METHODS AND ANALYSIS: We will conduct a multicentre, non-inferiority, open-label, randomised controlled trial aimed at comparing labour induction by oxytocin with a second cervical ripening that uses prostaglandins (slow-release vaginal dinoprostone; oral misoprostol 25 µg; dinoprostone vaginal gel 2 mg). Women (n=1494) randomised in a 1:1 ratio in 10 French maternity units must be ≥18 years with a singleton fetus in vertex presentation, at a term from ≥37+0 weeks of gestation, and have just completed a 24-hour cervical ripening procedure by any method (pharmacological or mechanical) with a Bishop score ≤6. Exclusion criteria comprise being in labour, having more than 3 contractions per 10 min, or a prior caesarean delivery or a history of uterine surgery, or a fetus with antenatally suspected severe congenital abnormalities or a non-reassuring fetal heart rate. The primary endpoint will be the caesarean delivery rate, regardless of indication. Secondary outcomes concern delivery, perinatal morbidity, maternal satisfaction and health economic evaluations. The nature of the assessed procedures prevents masking the study investigators and patients to group assignment. ETHICS AND DISSEMINATION: All participants will provide written informed consent. The ethics committee 'Comité de Protection des Personnes Ile de France VII' approved this study on 2 April 2021 (No 2021-000989-15). Study findings will be submitted for publication and presented at relevant conferences. TRIAL REGISTRATION NUMBER: NCT04949633.

Implementation of glucose 5% supplementation protocol to reduce the duration of labor among women with cervical ripening by prostaglandins: The GLUCOSHORT before-and-after study.

INTRODUCTION: Previous publications have shown that glucose supplementation could reduce labor duration in women with induction of labor with a favorable cervix but none have shown it for women with an unfavorable cervix.  The purpose of our study was to assess the impact on labor duration of a protocol of glucose supplementation used for induction of labor in women with an unfavorable cervix. MATERIAL AND METHODS: The protocol implemented in November 2017 added glucose supplementation by 5% dextrose at 125 mL/h to Ringer lactate for women with an unfavorable cervix with labor induced with dinoprostone gel. The study included women who underwent this protocol with a singleton, term, cephalic fetus from June 2017 through April 2018. The primary outcome was the labor duration. The secondary outcomes were mode of delivery, postpartum hemorrhage rate, neonatal outcomes, and durations other stage of labor. These outcomes were compared between the pre-intervention (from June 1 to October 31, 2017) and post-intervention (from December 1, 2017 to April 30, 2018) periods. RESULTS: The pre-intervention period included 116 women, and the post-intervention period 123. The characteristics of women and the induction of labor were similar in the two periods. The median duration from induction to delivery was not significantly different between the two periods (13.2 h, IQR 9.1-18.6 versus 13.6 h IQR 9.3-18.3, P=.67). The secondary outcomes did not differ significantly between the two groups. DISCUSSION: Glucose supplementation administered to women with an unfavorable cervix undergoing induction does not appear to reduce the induction-delivery duration.

Neonatal outcomes for women at risk of preterm delivery given half dose versus full dose of antenatal betamethasone: a randomised, multicentre, double-blind, placebo-controlled, non-inferiority trial.

BACKGROUND: Antenatal betamethasone is recommended before preterm delivery to accelerate fetal lung maturation. However, reports of growth and neurodevelopmental dose-related side-effects suggest that the current dose (12 mg plus 12 mg, 24 h apart) might be too high. We therefore investigated whether a half dose would be non-inferior to the current full dose for preventing respiratory distress syndrome. METHODS: We designed a randomised, multicentre, double-blind, placebo-controlled, non-inferiority trial in 37 level 3 referral perinatal centres in France. Eligible participants were pregnant women aged 18 years or older with a singleton fetus at risk of preterm delivery and already treated with the first injection of antenatal betamethasone (11·4 mg) before 32 weeks' gestation. We used a computer-generated code producing permuted blocks of varying sizes to randomly assign (1:1) women to receive either a placebo (half-dose group) or a second 11·4 mg betamethasone injection (full-dose group) 24 h later. Randomisation was stratified by gestational age (before or after 28 weeks). Participants, clinicians, and study staff were masked to the treatment allocation. The primary outcome was the need for exogenous intratracheal surfactant within 48 h after birth. Non-inferiority would be shown if the higher limit of the 95% CI for the between-group difference between the half-dose and full-dose groups in the primary endpoint was less than 4 percentage points (corresponding to a maximum relative risk of 1·20). Four interim analyses monitoring the primary and the secondary safety outcomes were done during the study period, using a sequential data analysis method that provided futility and non-inferiority stopping rules and checked for type I and II errors. Interim analyses were done in the intention-to-treat population. This trial was registered with ClinicalTrials.gov, NCT02897076. FINDINGS: Between Jan 2, 2017, and Oct 9, 2019, 3244 women were randomly assigned to the half-dose (n=1620 [49·9%]) or the full-dose group (n=1624 [50·1%]); 48 women withdrew consent, 30 fetuses were stillborn, 16 neonates were lost to follow-up, and 9 neonates died before evaluation, so that 3141 neonates remained for analysis. In the intention-to-treat analysis, the primary outcome occurred in 313 (20·0%) of 1567 neonates in the half-dose group and 276 (17·5%) of 1574 neonates in the full-dose group (risk difference 2·4%, 95% CI -0·3 to 5·2); thus non-inferiority was not shown. The per-protocol analysis also did not show non-inferiority (risk difference 2·2%, 95% CI -0·6 to 5·1). No between-group differences appeared in the rates of neonatal death, grade 3-4 intraventricular haemorrhage, stage ≥2 necrotising enterocolitis, severe retinopathy of prematurity, or bronchopulmonary dysplasia. INTERPRETATION: Because non-inferiority of the half-dose compared with the full-dose regimen was not shown, our results do not support practice changes towards antenatal betamethasone dose reduction. FUNDING: French Ministry of Health.

Is duration of passive second stage associated with a risk of hysterotomy extension during cesarean?

OBJECTIVE: To assess obstetric factors associated with hysterotomy extension among women undergoing a second-stage cesarean. STUDY DESIGN: This 5-year retrospective cohort study (2013-2017) included all women with second-stage cesarean deliveries of live-born singleton fetuses in cephalic presentation at term. It took place at a tertiary center that practices delayed pushing. We performed univariable and multivariable logistic regression to assess the maternal, obstetric, and neonatal factors associated with hysterotomy extension mentioned in the surgical report. Operative time, postpartum hemorrhage, and maternal complications were also studied. RESULTS: Of the 3350 intrapartum cesareans, 2637 were performed at term for singleton fetuses in cephalic presentation: 747 (28.3%) during the second stage of labor, 83 (11.1%) of which were complicated by a hysterotomy extension. The median duration of the passive phase of the second stage did not differ between women with and without an extension (164 min versus 160 min, P = 0.85). No other second-stage obstetric characteristics, i.e., duration of the active phase, fetal head station, or fetal malposition, were associated with the risk of extension. Factors significantly associated with extension were the surgeon's experience and forceps use during the cesarean. Women with an extension, compared to women without one, had a longer median operative time (49 min versus 32 min, P<0.001) and higher rates of postpartum hemorrhage and blood transfusion (respectively, 30.1% versus 15.1%, p = 0.002 and 7.2% versus 2.4%, P = 0.03). CONCLUSION: The risk of a hysterotomy extension does not appear to be associated with second-stage obstetric characteristics, including the duration of the passive phase of this stage. In our center, which practices delayed pushing, prolonging this passive phase beyond 2 hours does not increase the risk of hysterotomy extension in second-stage cesareans.

Impact of history of myomectomy on preterm birth risk in women with a leiomyomatous uterus: a propensity score analysis.

BACKGROUND: To evaluate if women with a history of myomectomy have a modified preterm birth risk compared to women with myomas during pregnancy. METHODS: Retrospective cohort study including all women with a history of myomectomy (operated group) or uterine myomas during pregnancy (unoperated group) who delivered in a tertiary center between January, 2011 and December, 2017. The operated group included women who had a myomectomy history with or without myomas during the ongoing pregnancy. The unoperated group included women with uterine myoma(s) seen on at least one ultrasound during pregnancy without history of myomectomy. The primary outcome was preterm birth < 37 weeks, and the secondary outcome spontaneous preterm birth < 37 weeks. To control for confounding factors, a propensity score approach was used. Two sensitivity analysis were performed, one repeating the analysis using the propensity score after excluding operated women with persistent myomas and one using a classical multivariable logistic regression model. RESULTS: The cohort included 576 women: 283 operated women and 293 unoperated women. The rate of preterm birth was similar in the two groups: 12.6% in the unoperated group and 12.0% in the operated group (p = 0.82). No difference in preterm birth risk was shown between unoperated and operated women in the cohort matched on the propensity score: OR 0.86; 95%CI [0.47-1.59]. These results were consistent for spontaneous preterm birth (OR 1.61; 95%CI [0.61-4.23]) and for the sensitivity analyses. CONCLUSION: In women with a leiomyomatous uterus, a history of myomectomy is not associated with a reduced preterm birth risk.

Leiomyomatous uterus and preterm birth: an exposed/unexposed monocentric cohort study.

BACKGROUND: The risk of preterm birth may increase in the presence of uterine leiomyomas during pregnancy. Whether myomectomy abrogates this risk has never been studied. OBJECTIVE: Our aim was to evaluate the association between the presence of uterine leiomyomas during pregnancy and preterm birth and, if an association exists, to evaluate its persistence in case of a history of myomectomy. STUDY DESIGN: This exposed/unexposed monocentric retrospective cohort study included all women with singleton pregnancies delivering >22 weeks in a tertiary university hospital maternity unit from January 2011 through September 2015. Women with a leiomyomatous uterus were compared to women with no myomas. Women in the leiomyomatous uterus group were women with uterine leiomyoma(s) during pregnancy (≥1 leiomyoma, measuring ≥20 mm or multiple leiomyomas whatever the size) seen on at least 1 obstetric ultrasound without history of myomectomy, or women with a history of myomectomy (removal of ≥1 leiomyoma, measuring ≥20 mm or multiple leiomyomas whatever the size) by hysteroscopy, laparoscopy, or laparotomy with or without persistent leiomyomas. The association between leiomyomatous uterus and preterm birth was assessed through univariate and multivariable logistic regression. RESULTS: Among the 19,866 women in the cohort, 301 (1.5%) had a leiomyomatous uterus (154 unoperated women and 147 operated women). The rate of premature delivery was 12.0% in the leiomyomatous uterus group and 8.4% in the nonleiomyomatous uterus group. After adjusting for the risk factors for preterm birth, leiomyomatous uterus was significantly associated with preterm birth (adjusted odds ratio, 2.5; 95% confidence interval, 1.7-3.7). This association was significant for unoperated women (adjusted odds ratio, 2.7; 95% confidence interval, 1.6-4.6) as well as operated women (adjusted odds ratio, 2.3; 95% confidence interval, 1.3-3.9) when compared to the nonleiomyomatous uterus group. CONCLUSION: Uterine leiomyomas are associated with preterm birth and this association persists after myomectomy.

Endometrial cancer in the elderly: does age influence surgical treatments, outcomes, and prognosis?

OBJECTIVE: To compare clinicopathological characteristics, surgical outcomes, and survival rates for nonelderly (<75 years old) and elderly (≥75 years old) women with endometrial cancer (EC). METHODS: This retrospective study included consecutive patients who underwent surgery for EC at the gynecologic-oncologic surgery department of Hôpital Européen Georges-Pompidou (Paris, France) from January, 2002 to December, 2015. Independent-group t tests and chi-square tests were used to compare elderly and nonelderly women. Survival rates were compared using log-rank (Mantel-Cox) tests. RESULTS: In the nonelderly and elderly groups, the mean age at EC diagnosis was 63 (range 33-74) and 81 (range 75-95) years, respectively. Compared with nonelderly patients, elderly patients (n = 104) presented with more advanced disease and more aggressive histological findings. However, surgical approaches did not differ between the two groups, and 76% of all patients underwent minimally invasive surgery. Pelvic lymphadenectomy was performed in 65% and 44% of nonelderly and elderly patients, respectively (P = 0.01), whereas para-aortic lymphadenectomy was performed in 26% and 9% of nonelderly and elderly patients, respectively (P < 0.0001). The incidence of perioperative complications was almost the same in the elderly and nonelderly groups. The 5-year disease-free survival rate was higher in the nonelderly group (P = 0.023), and the 5-year cancer-specific mortality rate was higher in the elderly group (P = 0.042). CONCLUSIONS: Although elderly patients present with cancers that are more aggressive, the management of EC in this population is not optimal. Further clinical studies need to be conducted for elderly women with EC, and specific treatment guidelines should be developed to improve their prognosis.

Maternal and perinatal outcomes of pregnancies in women with cystic fibrosis--A single centre case-control study.

BACKGROUND: Due to increased survival, more women with cystic fibrosis become pregnant. However, studies on the specificities of pregnancy in CF versus healthy women are lacking. METHODS: In this retrospective case-control study, we compared the maternal and perinatal outcomes of 33 pregnancies in CF women who delivered in our maternity ward from December 2000 to December 2013 and were matched to 66 controls. RESULTS: The median term of delivery was similar in cases and controls (38.1 ± 1.6 vs 38.4 ± 1.1 weeks gestation). Assisted reproductive technology pregnancies were more frequent in CF women (51% vs 3%, p < 0.001). In CF women, the initial BMI was lower (mean BMI 19.5 ± 2.4 vs 22.4 ± 4.9 kg/m(2); p = 0.001) and pre-existing diabetes was more frequent (30% vs 3%; p < 0.001). Those differences persisted during pregnancy for weight gain (9.1 ± 7.1 kg vs 13.3 ± 6.4 kg; p = 0.001) and diabetes (48% vs 8%; p < 0.001). Spontaneous labor and vaginal deliveries were less frequent in CF than in controls (respectively 45% vs 70%, p = 0.002; 51% vs 70%, p = 0.11). There was an equal number of caesarean sections (24% vs 21%; p = 0.80). Neonatal outcomes were similar in both groups, including birth weight (3042 ± 91 g vs 3119 ± 92 g). CONCLUSIONS: Multidisciplinary care of pregnancy in women with CF resulted in maternal and perinatal outcomes similar to those found in women in the general population.

Impact of maternal brain tumours on perinatal and maternal management and outcome: a single referral centre retrospective study.

OBJECTIVE: To evaluate the impact of maternal brain tumours on perinatal and maternal management and outcome. STUDY DESIGN: We performed a retrospective cohort study in a single referral centre with departments of obstetrics, neurology, and neurosurgery from January 2003 to July 2011. Cases were retrieved from our hospital databases, excluding pituitary adenomas, metastasis, and vascular tumours. Postnatal follow-up was of at least 6 months. Studied parameters were tumour type, gestational age at diagnosis if applicable, neurological events, obstetrical complications, pregnancy outcome, mode of delivery, peripartum analgesia, need for specific treatments, and maternal morbidity and mortality. RESULTS: 20 women (23 pregnancies) diagnosed with a brain tumour. Overall, there were 4 terminations of pregnancy, 4 elective premature caesarean deliveries, 15 live births ≥37 WG (9 caesarean and 6 vaginal deliveries), and 4 maternal deaths within 6 months postpartum. The brain tumour was diagnosed during pregnancy in 7 cases (group A), before pregnancy with preconception counselling in 10 (group B), and before pregnancy without preconception counselling in 6 (group C). In group A, there were 1 termination of pregnancy (TOP), 3 preterm elective caesarean deliveries, 3 live births ≥37 WG with one vaginal delivery, and 2 maternal deaths. In group B, there were 1 elective premature caesarean delivery and 7 live births ≥37 WG with 4 vaginal deliveries. In group C, there were 3 TOP, 3 live births ≥37 WG with one vaginal delivery, and 2 maternal deaths. CONCLUSIONS: Poor perinatal outcome and maternal death were associated with unplanned pregnancies and tumours diagnosed during pregnancy. Vaginal birth with epidural analgesia was nevertheless observed in all groups.