Methods for the induction of labor: efficacy and safety.

This review assessed the efficacy and safety of pharmacologic agents (prostaglandins, oxytocin, mifepristone, hyaluronidase, and nitric oxide donors) and mechanical methods (single- and double-balloon catheters, laminaria, membrane stripping, and amniotomy) and those generally considered under the rubric of complementary medicine (castor oil, nipple stimulation, sexual intercourse, herbal medicine, and acupuncture). A substantial body of published reports, including 2 large network meta-analyses, support the safety and efficacy of misoprostol (PGE1) when used for cervical ripening and labor induction. Misoprostol administered vaginally at doses of 50 µg has the highest probability of achieving vaginal delivery within 24 hours. Regardless of dosing, route, and schedule of administration, when used for cervical ripening and labor induction, prostaglandin E2 seems to have similar efficacy in decreasing cesarean delivery rates. Globally, although oxytocin represents the most widely used pharmacologic agent for labor induction, its effectiveness is highly dependent on parity and cervical status. Oxytocin is more effective than expectant management in inducing labor, and the efficacy of oxytocin is enhanced when combined with amniotomy. However, prostaglandins administered vaginally or intracervically are more effective in inducing labor than oxytocin. A single 200-mg oral tablet of mifepristone seems to represent the lowest effective dose for cervical ripening. The bulk of the literature assessing relaxin suggests this agent has limited benefit when used for this indication. Although intracervical injection of hyaluronidase may cause cervical ripening, the need for intracervical administration has limited the use of this agent. Concerning the vaginal administration of nitric oxide donors, including isosorbide mononitrate, isosorbide, nitroglycerin, and sodium nitroprusside, the higher incidence of side effects with these agents has limited their use. A synthetic hygroscopic cervical dilator has been found to be effective for preinduction cervical ripening. Although a pharmacologic agent may be administered after the use of the synthetic hygroscopic dilator, in an attempt to reduce the interval to vaginal delivery, concomitant use of mechanical and pharmacologic methods is being explored. Combining the use of a single-balloon catheter with dinoprostone, misoprostol, or oxytocin enhances the efficacy of these pharmacologic agents in cervical ripening and labor induction. The efficacy of single- and double-balloon catheters in cervical ripening and labor induction seems similar. To date, the combination of misoprostol with an intracervical catheter seems to be the best approach when balancing delivery times with safety. Although complementary methods are occasionally used by patients, given the lack of data documenting their efficacy and safety, these methods are rarely used in hospital settings.

Longitudinal Ultrasound Evaluation of Dilapan-S During Cervical Ripening.

OBJECTIVE: To assess the diameter change of hygroscopic rod dilation during 12 hours of cervical ripening. METHODS: This was an observational, prospective study of term women undergoing labor induction with a bishop score ≤ 6. Women were allocated into two groups (soaked gauze or no gauze) stratified by parity. Using transvaginal ultrasound, maximal rod diameters were obtained in a longitudinal plane. Measurements were taken at four pre-specified time points (3, 6, 8, and 12 hours). All rods were removed at 12 hours from insertion. Patient satisfaction scores between the groups were assessed. To evaluate if measures were significantly different among the four time points, a generalized linear model was used. Independent t-tests were used to compare mean rod diameter values and pain measures between the two groups. Fisher Exact tests were used to evaluate categorical satisfaction measures. RESULTS: Forty-four women were recruited with a total of 178 hygroscopic rods placed. Mean rod diameters (mm) were significantly different among the four time periods (3 hour: 7.9 mm [SD 0.9]; 6 hour: 9.4 mm [SD 0.9]; 8 hour: 10.0 mm [SD 0.9]; 12 hour: 10.9 mm [SD 0.8]; P-value <.001). After stratifying by the use of gauze, there was no difference in rod diameters at 3, 6, 8, and 12 hours respectively. There was no difference in patient satisfaction scores between the two groups. CONCLUSION: The majority of hygroscopic rod dilation occurs within the first 8 hours of cervical ripening. Placement of saturated gauze does not accelerate rod dilation.

A randomized controlled trial of Dilapan-S vs Foley balloon for preinduction cervical ripening (DILAFOL trial).

OBJECTIVE: The objective of the study was to test the hypothesis that Dilapan-S is not inferior to the Foley balloon for preinduction cervical ripening at term. STUDY DESIGN: Pregnant women ≥37 weeks scheduled for induction with unfavorable cervix (≤3 cm dilated and ≤60% effaced) were randomly assigned to 12 hours of either Foley balloon inflated with 60 mL saline or Dilapan-S for cervical ripening. If the cervix remained unfavorable, then 1 more round of the assigned dilator was used. Management following ripening was left up to the clinical providers. The primary outcome was vaginal delivery. A satisfaction survey was also obtained after the preinduction period. Sample size was based on a noninferiority margin of 10%, 90% power, and an estimated frequency of vaginal delivery of 71% in Foley balloon and 76% in Dilapan-S. RESULTS: From November 2016 through February 2018, 419 women were randomized (209 to Foley balloon; 210 to Dilapan-S). In the intent-to-treat analysis, vaginal delivery was more common in Dilapan-S vs Foley balloon (81.3% vs 76.1%), with an absolute difference with respect to the Foley balloon of 5.2% (95% confidence interval, -2.7% to 13.0%) indicating noninferiority for the prespecified margin. The difference was not large enough to show superiority. Noninferiority was confirmed in the per-protocol population (n = 204 in the Foley balloon, n = 188 in Dilapan-S), supporting the robustness of the results. Secondary outcomes were not different between groups, except for a longer time the device remained in place in Dilapan-S compared with the Foley balloon. Maternal and neonatal adverse events were not significantly different between groups. A priori interaction analyses showed no difference in the effect on vaginal delivery by cervical dilation at randomization, parity, or body mass index >30 kg/m2. Patients with Dilapan-S were more satisfied than patients with the Foley balloon as far as sleep (P = .01), relaxing time (P = .001), and performance of desired daily activities (P = .001). CONCLUSION: Dilapan-S is not inferior to the Foley balloon for preinduction cervical ripening at term. Advantages of Dilapan-S over Foley include Food and Drug Administration approval, safe profile, no protrusion from the introitus, no need to keep under tension, and better patient satisfaction.

Comparison of the Induction-to-Delivery Interval in Terminations of Pregnancy with or without Dilapan-S®.

OBJECTIVE: In France, terminations of pregnancy (TOP) for medical reasons beyond the second trimester use mifepristone and misoprostol. We sought to determine the effectiveness of Dilapan-S®, an osmotic cervical dilator, in shortening the induction-to-delivery interval (IDI). MATERIALS AND METHODS: This retrospective study of TOP in 2010-2012 compared the results from 2 hospitals with different TOP protocols starting at 16 weeks' gestation, one (164 women) with and one (106) without Dilapan-S®. The principal endpoint was the IDI. Results were analyzed according to 2 definitions of induction onset: definition 1, first dose of misoprostol in both centers, or definition 2, dilator placement if used, and otherwise first dose of misoprostol. RESULTS: With definition 1, the IDI was shorter with dilators (5 h 48 min vs. 10 h 18 min, p < 0.001); the rates of uterine evacuation within 12 and 24 h were higher (94.5 and 100 vs. 68.9 and 91.5%, p < 0.001), and the time between first misoprostol dose and amniotomy was shorter (0 h 47 min vs. 4 h 30 min, p < 0.001). Under definition 2, the IDI was longer with dilators (18 h 24 min vs. 10 h 18 min, p < 0.001), but the rate of evacuation within 24 h did not differ significantly. CONCLUSION: Dilapan-S® acts on cervical ripening and dilatation, thereby allowing early amniotomy. Assessing potential side effects and women's satisfaction requires prospective trials.

The use of adjunctive mechanical dilation at the time of induction termination and adverse health outcomes: a systematic review.

OBJECTIVE: This study aimed to assess if the use of mechanical dilation at the time of induction termination is associated with changes in the time from initiation of labor to expulsion of the fetus (induction-to-expulsion interval) and with the frequency of health complications when compared with medication management alone. DATA SOURCES: PubMed, CINAHAL, Scopus, and the Cochrane Central Register of Controlled Trials were queried from January 2000 to May 2023. STUDY ELIGIBILITY CRITERIA: We included randomized controlled trials of individuals who were assigned to undergo mechanical dilation (ie, laminaria, Dilapan-S, and intracervical Foley balloon catheter) in combination with the use of medication and compared it with the outcomes of medication use (eg, prostaglandins, antiprogestins, oxytocin) alone. METHODS: The primary outcome was the induction-to-expulsion interval. The secondary outcomes were the incidence of clinical chorioamnionitis, sepsis, hemorrhage, the need for blood transfusion and uterotonics, cervical laceration, the need for adjunctive procedures (eg, dilation and curettage), failed induction termination, uterine rupture, intensive care unit admission, or death. Assessment of bias was performed using the Cochrane Risk of Bias tool. A subgroup analysis was performed among studies deemed to be at low risk of bias. RESULTS: Of 864 abstracts identified, 11 met the inclusion criteria. Five studies demonstrated a shorter induction-to-expulsion interval among those randomized to mechanical dilation, whereas 6 studies demonstrated a similar or longer induction-to-expulsion interval. There were no significant differences reported in the frequency of any adverse outcomes between the trial arms. In addition, most studies (8/11) exhibited moderate to high levels of bias. In an analysis of the 3 studies deemed to have a low risk of bias, 1 (n=60) demonstrated a longer induction-to-expulsion interval with adjunctive laminaria, 1 (n=60) demonstrated a shorter induction-to-expulsion interval with adjunctive intracervical Foley balloon catheter use, and 1 demonstrated no difference in the induction-to-expulsion interval with adjunctive Dilapan-S use (n=180). CONCLUSION: Only a small number of studies, most of which were of low quality, assessed mechanical dilation for induction termination. The results of these studies were inconsistent in terms of the induction-to-expulsion interval of adjunctive mechanical methods in comparison with medication management alone. Studies did not reveal significant differences between the groups in adverse outcomes. Further research should investigate the use of mechanical dilation at the time of induction termination using high-quality methods.

Comparison of Efficacy of Vaginal Misoprostol versus a Synthetic Osmotic Dilator (Dilapan-S) for Cervical Preparation before Operative Hysteroscopy: A Randomized Controlled Study.

Objectives: To compare the need for mechanical cervical dilatation following vaginal misoprostol or synthetic osmotic dilator (Dilapan-S) usage for cervical preparation before operative hysteroscopy. Materials and Methods: Fifty-five premenopausal women scheduled for operative hysteroscopic procedures with a 26 Fr resectoscope were included in this randomized, controlled clinical trial. After randomization, either 400 µg of vaginal misoprostol or intracervical synthetic osmotic dilator (Dilapan-S) was inserted 12 h before operative hysteroscopy. The need for additional mechanical cervical dilatation before insertion of the resectoscope was compared between the two groups. Initial cervical diameter before mechanical dilatation, intraoperative complications (cervical tears, creation of a false passage), and ease of dilatation were also compared between the two groups. Results: In the misoprostol group, 92% of women required additional mechanical cervical dilatation, whereas only 36% of women in the Dilapan-S group required additional dilatation (P < 0.05). The median initial cervical diameter achieved with Dilapan was 9 mm (Q1: 7 mm; Q3: 10 mm), and with misoprostol, it was 6 mm (Q1: 4.5 mm; Q3: 8 mm) (P < 0.05). There was no significant difference in other outcome parameters between the two groups. Conclusion: Synthetic osmotic dilator (Dilapan-S) is more efficacious than vaginal misoprostol at ripening the cervix before operative hysteroscopy.

A randomised open-label trial to assess outpatient induction of labour (HOMEIND) and compare efficacy of Propess vs Dilapan-S® for induction of labour at 39 weeks' gestation in normal risk nulliparous women: study protocol for a randomised controlled trial.

BACKGROUND: Induction of labour (IOL) at 39 weeks has been shown to decrease maternal and neonatal adverse outcomes. Given the growing demand for 39-week IOL, it is imperative that effective methods be assessed for induction in the outpatient setting. The aim of this study is to answer the clinical question as to whether Dilapan-S® vs Propess® as a method of cervical ripening is non-inferior in the outpatient setting at 39 weeks and to ascertain whether Dilapan-S® 12 h is non-inferior to Dilapan-S® 24 h. METHODS: This study is an open-label parallel group single-centre randomised trial. Participants are normal risk nulliparous women who have no pregnancy-related or medical contraindication to IOL. Women will be randomised to one of three induction groups-Dilapan-S® (12-h insertion or 24-h insertion) or Propess. Induction will be initiated between 39+0 and 39+4 weeks' gestation and participants will return home for either 12 or 24 h. They will be readmitted 12/24 h later in order to continue with induction of labour. Patient recruitment will take place over 30 months within a single centre. The study will recruit a maximum 109 women for each study arm. Total duration of participants' involvement in the trial will be 8 weeks to allow for postpartum follow-up. DISCUSSION: This study will definitively answer whether Dilapan-S is non-inferior to Propess® as a method of induction of labour in the outpatient setting and whether cervical ripening with Dilapan-S over a 12-h timeframe is non-inferior to cervical ripening with Dilapan-S over a 24-h timeframe. TRIAL REGISTRATION: EudraCT Number 2019-004697-25 Registered 14 September 2020.

Synthetic Osmotic Dilators for Pre-Induction Cervical Ripening - an Evidence-Based Review.

Mechanical methods have gained growing interest for pre-induction cervical ripening in women with an unripe cervix, since they have a better safety profile compared to prostaglandins. Balloon catheters have been the gold standard method for decades, while there was a lack of data on synthetic osmotic cervical dilators. Not until 2015, when Dilapan-S was approved by the Food and Drug Administration (FDA) for induction of labor, numerous studies have been published on the use of Dilapan-S in this field. The rate of vaginal deliveries associated with the use of Dilapan-S ranges from 61.6 to 81.7%, and no serious complications needing further interventions have been reported to this date. Dilapan-S was shown to be as effective as the Foley balloon catheter as well as the 10 mg PGE 2 vaginal insert and orally applied misoprostol (25 µg every 2 hours) in achieving vaginal delivery, but patient's satisfaction during the cervical ripening process was significantly higher compared to the other methods and the rate of uterine hyperstimulation was significantly lower compared to prostaglandins (PGs). Minor complications (e.g. vaginal bleeding) associated with the use of Dilapan-S were < 2%, and maternal infectious morbidity was not higher compared to Foley balloon and vaginal PGE 2 or misoprostol. Due to these beneficial properties Dilapan-S might be an ideal option for outpatient cervical ripening, as shown in a recent randomized clinical trial comparing inpatient to outpatient cervical ripening. Furthermore, according to the manufacturers' product information, Dilapan-S is the only cervical ripening method that is not contraindicated for induction of labor in women with a previous cesarean section. Upcoming guidelines should consider synthetic osmotic cervical dilators as an effective and safe method for cervical ripening/induction of labor acknowledging that more evidence-based data are mandatory, particularly in patients with a previous cesarean section.

Sonoelastography for the comparative assessment of cervical maturation after different approaches to cervical preparation ahead of labor induction.

AIM: To compare the efficacy of different approaches to cervical preparation to labor induction using the ultrasound cervical elastography. MATERIALS AND METHODS: This prospective open-label study included 200 pregnant women aged between 23 and 38 years eligible for labor pre-induction. Patients were divided into four groups (n = 50 per group). In Group I, four osmotic Dilapan-S cervical dilators combined with two doses of oral mifepristone (200 mg each) 24 h apart were used. The dilators were inserted for up to 12 h. In Group II, only the Dipalan-S dilators were used. In Group III, a Foley catheter was positioned intracervically for 12 h. In Group IV, we used two doses of intracervical prostaglandin E2 gel (0.5 mg each) 6 h apart. Cervical maturation was assessed using the Bishop scoring system and the ultrasound cervicometry with the color mapping and calculation of SR ratio. At baseline, all participants were also divided into three subgroups depending on the Bishop score before the pre-induction. Subgroup А (n = 66) included patients with the Bishop score between 0‒2 points, subgroup B (n = 69) between 3-4 points, and subgroup С (n = 65) between 4-6 points. RESULTS: Our study showed that the efficacy of Dilapan-S combined with mifepristone for cervical preparation to labor induction was higher than Dilapan-S, Foley catheter and intracervical prostaglandin E2 gel. In this group, the Bishop score after the pre-induction was the highest (11.4 (0.21) points versus 10.2 (0.2), 9.4 (0.3) и 9.67 (0.25) in Groups II, III and IV respectively (p < .05 for all). The lowest SR values were also observed among the patients receiving the combination of Dilapan-S and mifepristone: 1.23 (0.04) versus 1.63 (0.07), 1.7 (0.08) and 1.83 (0.1) in Groups II, III and IV respectively (p < .05 for all). The sonoelastographic SR values in subgroups B and C were statistically lower compared with subgroup A across all groups studied. Ultrasound elastography of the cervix allowed to perform a more objective assessment of cervical maturation compared with the Bishop scoring. CONCLUSION: Dilapan-S combined with mifepristone had higher efficacy for cervical preparation to labor induction compared with other approaches investigated.

A comparison between labor induction with only Dilapan-S and a combination of mifepristone and Dilapan-S in nulliparous women: a prospective pilot study.

OBJECTIVE: The aim of our study was to determine whether the combination of mifepristone and the osmotic dilator Dilapan-S improves the labor induction outcomes as compared to Dilapan-S alone. METHODS: This prospective comparative study included 127 eligible women, of whom 58 underwent cervical ripening with Dilapan-S (12-h exposure, the control group) and 69 with Dilapan-S, with a concurrent pretreatment of 200 mg oral mifepristone (the study group), 8 h before Dilapan-S insertion. RESULTS: The vaginal delivery rate in the control group and the study group was 60.3 and 76.8% (p = .045), respectively; the induction to delivery interval was 22.74 ± 3.01 h and 19,890 ± 2.42 h (p < .001), respectively; and the number of births within 24 h was 43.1 and 73.9% (p < .001), respectively. There was no difference in the rate of failed labor induction (6.9 versus 8.7%, p = .939). The Bishop's score improved significantly after the combined treatment as compared to with Dilapan alone (3.10 ± 0.58 versus 4.03 ± 1.35, p < .001). Moreover, in the study group, labor started earlier and proceeded faster with a lower additional oxytocin usage for labor induction or augmentation. There were no differences in the operative delivery rate and the perinatal outcomes. There were no adverse side effects of both mifepristone and Dilapan-S. CONCLUSION: Our study is the first one to show that in comparison to labor induction using only osmotic dilators Dilapan-S, the combination of mifepristone and Dilapan-S is more efficient in terms of improving cervical ripening and vaginal delivery rate and reducing labor duration and frequency of oxytocin augmentation. The results revealed that this combined method is safe and has no immediate adverse effects on newborns. More studies are needed to evaluate what clinical cases are the most appropriate for the application of this combined method, considering the parity, degree of cervical ripening, and indication for labor induction.

Synthetic osmotic dilators in the induction of labour-An international multicentre observational study.

INTRODUCTION: To evaluate the effects of synthetic osmotic dilators (Dilapan-S/ Dilasoft) in women who required induction of labour in a large prospective multicentre international observational study. MATERIALS AND METHODS: Primary outcomes were duration of Dilapan-S/Dilasoft insertion (hours), total induction - delivery interval (hours) and the rate of vaginal deliveries within 24 h (%). Secondary outcomes were the number of dilators inserted, Bishop score increase after extraction of Dilapan-S/Dilasoft, complications during induction (uterine contractions, uterine tachysystole and hyperstimulation, effect on the fetus) and post induction (infections and neonatal outcomes), agents / procedures used for subsequent induction of labour, immediate rate of spontaneous labours following cervical ripening period, rate of spontaneous vaginal deliveries, rate of instrumental vaginal deliveries and caesarean sections. RESULTS: Total of 543 women were recruited across 11 study sites, of which, 444 women were eligible for analysis. With Dilapan-S/Dilasoft use of <12 h (n = 188) the overall vaginal delivery rate was 76.6% with 45.7% of these births occurring within 24 h, 66% within 36 h and 75.5% within 48 h from insertion of Dilapan-S/Dilasoft. The mean insertion-delivery interval for this group was 24.3(±10.4) hours. With Dilapan-S/Dilasoft use of >12 h (n = 256), the overall vaginal delivery rate was 64.8%, with 16% of these births occurring within 24 h, 48.4% within 36 h and 54.7% within 48 h from insertion of Dilapan-S/Dilasoft. The mean insertion-delivery interval for this group was 39.1(±29.2) hours. The mean gain in the Bishops score was +3.6(±2.3). The mean number of Dilapan-S/Dilasoft dilators used was 3.8 (±1.1). The overall rate of caesarean section was 30.1%. The overall complication rate was low including infection risk. No adverse neonatal outcome was attributable to the use of Dilapan-S/Dilasoft. CONCLUSION: Dilapan-S/Dilasoft are safe and effective methods for cervical ripening. Their use is associated with low maternal and neonatal complication rates. Future research should aim at level I clinical trials comparing Dilapan-S to other mechanical or pharmacological cervical ripening agents. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT02318173.

Synthetic osmotic dilators for cervical preparation prior to abortion-An international multicentre observational study.

OBJECTIVES: To evaluate the outcomes with the use of Dilapan-S for cervical preparation prior to medical or surgical abortion. STUDY DESIGN: International, multicentre, prospective observational study in women between 6 + 0-24 + 0 weeks' gestation. The study was conducted across 7 study sites in 4 countries, between 1/5/2015 to 31/12/2016. The primary outcomes studied were the number of dilators used and the duration required for cervical preparation prior to abortion. Secondary outcomes were complications of dilator use and infection. Participants were followed-up for 4 weeks post procedure to capture any delayed complications. RESULTS: A total of 483 women were enrolled with 439 women eligible for analysis. Medical abortion was performed in 38% (n = 165) women and surgical abortion in 62% (n = 274). For medical abortions and surgical abortions, an average of 3 osmotic dilators for time interval of 4-7 hours provided effective cervical preparation. Medical abortions were performed as day-case procedures (<12 h) in 81% of women. There was no difference in using either adjunctive misoprostol or Dilapan-S followed by misoprostol for cervical ripening effect to achieve complete medical abortion. Dilapan-S permitted surgical abortions to be performed as same-day procedures (<12 h), in 85% of women regardless of gestational age and without the need to use adjunctive or additional misoprostol. There were no serious adverse events reported with the use of Dilapan-S, including in women with a previous caesarean section. The overall infectious morbidity was 0.9% of cases with no causal relationship with the use of synthetic osmotic dilator use (for a length <24 h). In addition, Dilapan-S was reported as easy to insert and remove in over 90% of women. CONCLUSION: Dilapan-S is a safe and effective method for cervical preparation for medical and surgical abortions up to 24 weeks' gestation. It allows medical and surgical abortions to be performed as day case procedures and is associated with a low complication rate. Future research should aim at directly comparing Dilapan-S and preferred pharmacological agents in a randomised controlled trial.

Comparison of Dilapan-S and laminaria for cervical priming before surgical pregnancy termination at 17-22 weeks' gestation.

METHODS: A retrospective analysis of medical records of three consecutive cohorts of women. All cohorts received a digoxin feticide injection on Day 1. Two cohorts were treated with laminaria, cohort A of 151 women over 1-2 days and cohort B of 52 women over 1-3 days, and cohort C of 151 women was treated with Dilapan-S over 1-3 days. RESULTS: Adequate cervical priming for dilatation and evacuation (D&E) on Day 2 was achieved in 98% of the Dilapan-S cohort and 56% of cohort A and 40% of the cohort B laminaria cohorts. Return to theater for D&E 3-4 hours after dilator insertion on Day 2 occurred in 62.3% of Dilapan-S cohort C and 9.3% of cohort A and 4% of cohort B laminaria cohorts (P = 0.001). A mean D&E theater time of 19 minutes for laminaria cohort A was reduced by 10.1% in the Dilapan-S cohort C (P = 0.02). The incidence of unscheduled overnight delivery outside the clinic was 0% for Dilapan-S and 1.3% for cohort A and 3.8% for cohort B laminaria cohorts (P = 0.14). CONCLUSION: Dilapan-S osmotic dilators are superior to laminaria in producing more cervical priming and dilatation in a shorter time. This enables 17-22 week D&E procedures to be carried out in fewer days and in shorter theater times. They also eliminate the risk of an unscheduled overnight delivery outside the clinic.