Limoges Regional University Hospital, Department of Gynecology and Obstetrics, Mother and Children's Hospital, Limoges, France (Coste-Mazeau); University of Limoges, Inserm, CHU Limoges, RESINFIT, Limoges, France (Coste-Mazeau).
Obstetric Department, University Hospital of Clermont-Ferrand, Clermont-Ferrand, France (Gallot).
Am J Obstet Gynecol MFM. 2024 Nov;6(11):101510. doi: 10.1016/j.ajogmf.2024.101510. Epub 2024 Sep 27.
Labor is induced in over 25% of women in France. Prostaglandins, especially intravaginal dinoprostone (Propess®), are widely used to initiate cervical ripening. If labor does not start within 24 hours, there is uncertainty about whether to administer a second dinoprostone pessary or to use oxytocin to induce labor in order to achieve a vaginal delivery.
Our principal objective was to determine whether placement of a second Propess®, followed by oxytocin (Syntocinon®) if necessary, in pregnant women for whom the first Propess® failed to induce cervical ripening increases the vaginal delivery rate compared to direct oxytocin injection. The vaginal delivery rate was therefore the primary outcome. The secondary outcomes were the cervical ripening failure rate and maternal and fetal morbidity and mortality.
RE-DINO is a prospective, open-label, multicenter, randomized superiority trial with 2 parallel arms running in 7 French hospitals. Patients at > 37 weeks of gestation who had unfavorable cervical conditions (Bishop score < 6) 24 hours after placement of the first Propess® (vaginal patch featuring progressive continuous diffusion of 10 mg dinoprostone), with fetuses in cephalic presentation, were included.
160 pregnant women were randomized, 80 patients in each group, from December 2016 through April 2022. Baseline characteristics such as age, BMI, maternal age at induction and Bishop score at induction were similar between both groups. Vaginal delivery occurred in 76.3% of cases in the 2nd Propess® group and 73.8% of cases in the Syntocinon® group (RR=1.03 [0.86; 1.24], p=.715). Although the cesarean section rate was similar in each group, there were significantly more cesarean sections for arrest of dilatation (52.6% vs 19%; p=.0262) in the Propess® group and a larger, borderline-significant difference in patients having operative vaginal delivery (24.6% vs 11.9%; p=.07) for abnormal fetal heart rate (80% vs 29%; p=.05). There was significantly more failure of cervical ripening in the Propess® group (57.1% vs 19%; RR=2.59 ; 95% CI [1.64; 4.11]; p<.0001) and the interval between study treatment and delivery was also significantly longer (28.1h vs 9,7h; p<.0001). There was a higher incidence of postpartum hemorrhage in the Propess® group, although this was not significant (11.3% vs 5% ; p=,15), but also more newborns with acidosis (39.3% vs 27.9% ; p=.18) or severe acidosis (8,6% vs 3.4% ; p=.27), more meconium fluid (11.3% vs 6.3% ; p=.26) and transferred to intensive care (5% vs 2.5% ; p=.68).
Our data showed no superiority of a second dinoprostone pessary over oxytocin in patients not responding to initial prostaglandins E2 maturation for labor induction. Repeated use of Propess® is not useful for induction of labor.
在法国，超过 25%的女性需要引产。前列腺素，特别是阴道内dinoprostone（Propess®），被广泛用于启动宫颈成熟。如果 24 小时内没有开始分娩，则不确定是再次给予 dinoprostone 阴道栓剂还是使用缩宫素引产以实现阴道分娩。
我们的主要目的是确定对于首次 Propess®未能诱导宫颈成熟的孕妇，放置第二个 Propess®，必要时给予催产素（Syntocinon®），是否会增加阴道分娩率，而不是直接给予催产素注射。因此，阴道分娩率是主要结局。次要结局为宫颈成熟失败率以及母婴发病率和死亡率。
RE-DINO 是一项前瞻性、开放标签、多中心、随机优效性试验，设有 2 个平行组，在法国 7 家医院进行。纳入的患者为妊娠超过 37 周、首次放置 Propess®（阴道贴剂，具有渐进持续扩散 10mg 地诺前列酮）后 24 小时宫颈条件不理想（Bishop 评分<6）、胎儿呈头位的孕妇。
2016 年 12 月至 2022 年 4 月期间，共随机分配了 160 名孕妇，每组 80 名。两组间的基线特征如年龄、BMI、引产时的产妇年龄和诱导时的 Bishop 评分相似。第二组 Proppess®组阴道分娩率为 76.3%，Syntocinon®组为 73.8%（RR=1.03[0.86；1.24]，p=0.715）。虽然两组剖宫产率相似，但 Proppess®组因扩张阻滞而行剖宫产的比例明显更高（52.6%比 19%；p=0.0262），因胎心异常行阴道助产的比例也有较大的边缘显著差异（24.6%比 11.9%；p=0.07）。宫颈成熟失败的比例在 Proppess®组明显更高（57.1%比 19%；RR=2.59；95%CI[1.64；4.11]；p<0.0001），研究治疗与分娩之间的间隔时间也明显更长（28.1h 比 9.7h；p<0.0001）。Proppess®组产后出血发生率较高，但无统计学意义（11.3%比 5%；p=0.15），但新生儿酸中毒（39.3%比 27.9%；p=0.18）或严重酸中毒（8.6%比 3.4%；p=0.27）、胎粪羊水污染（11.3%比 6.3%；p=0.26）和转入重症监护病房的比例也更高（5%比 2.5%；p=0.68）。
我们的数据显示，对于对初始前列腺素 E2 成熟反应不佳的患者，再次使用二诺前列酮阴道栓剂引产并不优于催产素。重复使用 Propess®对引产无益。
