Introduction
In the last 20 years, labor induction rates have almost doubled in high-income countries,
with reported rates of 31.4% in the USA in 2020 [1], 34% in the United Kingdom in 2021 [2] and 21.8% in Germany 2020 [3]. There is an increasing tendency to only induce contractions after sufficient cervical
ripening [4].
Inducing labor when the cervix is still unripe does not accelerate the birth; instead,
it places additional stress on the fetoplacental unit due to contraction-related uterine
hypoperfusion, which may be harmful in pregnancies with reduced fetal reserve.
It is also associated with longer induction-to-delivery intervals compared to induction
when the cervix is already ripe, with increasing costs and low patient’s acceptance
due to painful contractions [5].
In this context, mechanical methods (balloon catheters, synthetic osmotic cervical
dilators) for pre-induction cervical ripening have gained growing interest [6].
While in a German-wide survey 2013 [7] only 1.8% of obstetric units used mechanical methods for cervical ripening/induction
of labor, this rate was 38% for synthetic osmotic dilators and 53% for balloon catheters,
respectively, in a recent German-wide survey from 2020 [8].
Compared to prostaglandin E2 (PGE2)/misoprostol the use of mechanical methods for pre-induction cervical ripening is
associated with a significantly lower rate of uterine hyperstimulation, lower monitoring
cost during the cervical ripening period, lower overall costs, the absence of serious
maternal and fetal side effects and higher patient’s satisfaction [5].
In the light of rising hospital costs and increasing burden on obstetric staff, particularly
during the COVID-19 pandemic, mechanical methods have shown a promising approach for
outpatient pre-induction in low-risk patients with an unripe cervix at term [5]. On the other hand, mechanical methods require the additional administration of
oxytocin to induce/augment labor more often when compared to PGE2/misoprostol [5] and they may be associated with an increased risk of infectious morbidity [9].
During the past several decades, the vast majority of studies on mechanical methods
for cervical ripening/induction of labor investigated the use of balloon catheters
[6], while data on the use of synthetic osmotic cervical dilators were somewhat limited.
Dilapan-S is a second generation synthetic osmotic dilator made from a patented anisotropic
xerogel AQUAACRYL. It is a synthetic gel rod, which increases in volume by absorbing
fluids from the surrounding tissues throughout the cervical canal and thus exerting
steady radial pressure on the cervical wall, which dilates the cervix. This pressure
also promotes the release of endogenous prostaglandins, which causes collagen degradation
and therefore further softens the cervix [10].
Experimental and clinical studies have shown that Dilapan-S is superior to laminaria
regarding the degree and speed of cervical dilatation associated with shorter induction-to-delivery
intervals [11]
[12]
[13]. The thin rod (4 mm) can expand up to 12 mm over a 12 hours period and 92% dilatation
was reached within 8 hours, as recently shown in vivo in the USE Dilapan Ultrasound
study [14].
In the nineties of the last millennium, numerous randomized studies have compared
Dilapan (the first generation) with intracervically applied PGE2 gel for cervical ripening in patients with an unripe cervix [15]
[16]
[17]
[18]
[19]. It has been shown that the use of Dilapan was as effective as PGE2 in pre-induction cervical ripening and associated with lower costs and better patient’s
convenience [15]. Outpatient cervical ripening with Dilapan seemed as effective and safe as in the
inpatient setting [20]. Surprisingly, however, there is a gap in publications on Dilapan after 1999. One
explanation may be that Dilapan-S (the second generation of the device) was awaiting
approval from the Food and Drug Administration (FDA), which was acquired in 2015.
The goal of this review is to evaluate clinical studies on the use of Dilapan-S for
cervical ripening/induction of labor published between 2015 and 2022 in order to develop
evidence-based recommendations for clinical practice.
Cervical ripening/induction of labor with Dilapan-S
An observational, non-interventional study from Germany 2015 [21] evaluated 83 patients near term with a Bishop Score (BS) < 4, who underwent cervical
ripening with Dilapan-S left in place for at least 12 hours (‘overnight’) in an outpatient
setting followed by intravenous oxytocin or PGE2 gel or misoprostol orally.
The primary outcome was the rate of vaginal delivery: 65% of all patients delivered
vaginally (82.6% of multiparous women). The average time from cervical ripening to
delivery was 36 hours. No adverse fetal or maternal outcomes were observed.
The main limitations of this study are its low level of evidence (LoE III), the lack
of a comparison group and missing data on the improvement of BS (gain in BS) after
the cervical ripening period, the mean number of rods used, and some perinatal outcome
parameters as well as the inadequate statistical power with regard to method-related
complications (e.g. rate of uterine hyperstimulation or infectious morbidity).
In a prospective multicenter international observational study including 444 pregnant
women with ≥ 37+0 to 42 weeks of gestation Dilapan-S (n = 276) and Dilasoft (n = 168)
were used for cervical ripening/induction of labor in patients with an unripe cervix
(BS 2.9 ± 1.2) [10]. Up to 5 rods were placed and they were removed after 12 or 24 hours. After cervical
ripening with Dilapan-S, labor induction was carried out mostly with PGE1- and PGE2- compounds (not specified) or oxytocin intravenously with or without artificial rupture
of membranes.
The primary outcome criteria were the duration of Dilapan-S insertion (hours), total
induction-delivery interval and the rate of vaginal delivery within 24 hours. The
results are shown in [Table 1].
Table 1
Dilapan-S for cervical ripening/induction of labor: studies 2015–2022.
|
Author/year
|
n
|
study
|
comparing group
|
primary outcomes
|
results
|
|
h = hours; NS = nonsignificant; RCT = randomized controlled trial; S = significant
|
|
Maier JT 2015 [21]
|
83
|
observational
|
–
|
rate of vaginal delivery
|
65% (parous: 82.6%)
|
|
Gupta JK 2018 [10]
|
444
|
multicenter observational
|
–
|
duration of Dilapan insertion
total insertion–delivery
rate of vaginal delivery/24 hours
|
25.4 ± 4.5 h
24.2 h < 12 h in place
39.1 h > 12 h in place
46% (total 69.8%)
|
|
Shindo R 2017 [22]
|
17363
|
retrospective observational
|
balloon < 40 ml
balloon ≥ 40 ml
|
rate of vaginal delivery
|
cervical dilators: 74.6%
balloon < 40 ml: 72.3% [NS]
balloon ≥ 40 ml: 73.8%
|
|
Saad AF 2019 [23]
|
419
|
RCT
|
Foley balloon
(60 ml, 12 h)
|
rate of vaginal delivery
|
Dilapan-S: 81.3%
Foley balloon: 76.1% [NS]
higher maternal satisfaction with Dilapan-S
|
|
Baev OR 2019 [24]
|
127
|
prospective
|
Dilapan +
pretreatment of 200 µg oral mifepristone
|
rate of vaginal delivery (total/24 h)
|
Dilapan-S: 60.3% (43.1%/24 h)
Mifepristone/Dilapan-S: 76.8%
(73.9%/24 h) [p < 0.045]
|
|
Pekarev OG 2020 [25]
|
200
|
prospective
|
Dilapan + mifepristone
Foley balloon (12 h)
intracervical PGE2
(0.5 mg)
|
improvement in BS (mean)
|
Dilapan-S + mifepristone: 11.4 [S]
Dilapan-S: 10.2
Foley balloon: 9.4
PGE2: 9.7
|
|
Crosby DA 2018 [26]
|
52
|
prospective observational
|
10 mg PGE2 vaginal pessary
|
maternal neonatal infections
uterine hyperstimulation
perinatal outcomes
|
15.4 vs. 15.4%
0 vs. 0%
no significant differences
|
|
Gupta JK 2022 [27]
|
674
|
RCT
|
10 mg PGE2 vaginal pessary
|
failure to achieve vaginal delivery
|
Dilapan-S: 37.4%
PGE2 vaginal pessary: 34.3%
|
|
Gavara R 2022 [28]
|
303
|
RCT
|
oral misoprostol
(25 µg every 2 h)
|
Rate of vaginal delivery within 36 hours
|
Dilapan-S: 61.6%
oral misoprostol: 59%
-
uterine tachysystole: 23.3 vs. 46.4% p = 0.01
-
better sleep, lower pain score with Dilapan-S (p < 0.05)
|
The mean vaginal delivery rate was significantly higher (76.6 vs. 64.8%; p = 0.0077),
when Dilapan-S was inserted for < 12 hours. Spontaneous labors (no induction agent
needed) after cervical ripening with Dilapan-S occurred in 10.1% of women.
The mean number of dilators used was 3.8 (± 1.2) and the mean gain in BS was 3.6 being
approximately 6.5 (± 2.8) after extraction of Dilapan. In total, 3.4% of women experienced
non-serious complications such as bleeding during device insertion/removal (2.7%),
cramping or pain (0.2%) and other not specified (0.4%); 2% had spontaneous dilator
expulsions. The rate of uterine hyperstimulation was 0.2%.
Maternal infections were observed in 3.2% of patients, which to the authors’ opinion
were not attributed to the effects of Dilapan-S.
This is the largest cohort study evaluating the efficacy of Dilapan-S/Dilasoft as
a ripening agent prior to induction of labor. The limitations of this study are the
moderate level of evidence (LoE IIb), the lack of a comparison group, the great variability
of labor induction methods following the use of Dilapan-S/Dilasoft possibly influencing
outcomes.
It is to be regretted that the study includes no analysis on patient’s satisfaction
with the use of Dilapan.
A secondary analysis of this international multicenter study was conducted [29] evaluating the determinants of vaginal delivery and safety in women undergoing cervical
ripening with Dilapan-S prior to induction of labor.
Most of the results presented in this paper have already been reported in the previous
publication of the same group [10]. It has been shown that vaginal delivery rates were significantly correlated with
Bishop Scores of pre Dilapan-S, post Dilapan-S and difference (Spearman’s coefficient,
0.82, 0.86 and 0.7 respectively; p < 0.05). In the multivariate analysis prior vaginal
delivery and post Dilapan-S Bishop Scores were identified as strong predictors of
vaginal delivery.
Comparison of cervical ripening with Dilapan-S versus balloon catheters
A retrospective, observational study from Japan [22] including a total of 17363 nulliparous women compared the efficacy and safety of
four mechanical methods (synthetic osmotic dilators n = 4350, balloon catheter with
a filling volume < 40 ml n = 4103, balloon catheter with a filling volume ≥ 40 ml
n = 6618, overlapping groups = combination of methods n = 1990) for cervical ripening/induction
of labor near term. The primary outcome was the rate of vaginal delivery. The results
of the study are shown in [Table 1]. The perinatal outcome (Apgar Score, umbilical artery pH) was significantly better
in the dilator group.
The study has several limitations: the low level of evidence (LoE III) and the lack
of data on the kind of devices used, their time left in place, the pre- and post-Bishop
scores, induction-to-delivery-intervals, the mode of labor induction (oxytocin?, PGs?),
the rates of uterine hyperstimulation or other complications associated with the use
of the devices and on infectious morbidity.
The objective of a single-center, randomized, open-label trial was to test the hypothesis
that Dilapan-S is not inferior to the Foley catheter for pre-induction cervical ripening
at term [23]; 419 women with an unfavorable cervix (BS < 6) were randomized; 209 to Foley balloon
(filling volume 60 ml, time left in place at least 12 hours), and 210 to Dilapan-S
(time left in place 12 hours but no longer than 24 hours). As many rods as possible
were inserted into the cervical canal.
In both groups, second round of dilators/balloon catheters were used, if the cervix
remained still unfavorable (BS < 6).
In cases of a favorable cervix, intravenous oxytocin was started up to a maximal dose
of 30 mU/min.
The primary outcome of the study was the rate of vaginal delivery, which was 81.3%
in the Dilapan- and 76.1% in the balloon catheter-group (p = 0.197) indicating noninferiority
for the pre-specified margin (10%).
Secondary outcomes (e.g. changes in BS, induction-to-delivery-interval, maternal and
neonatal adverse events, hospital stay) were not significantly different between groups
except for a longer time the device remained in place (Dilapan-S: 774 ± 295 min. vs.
Foley balloon 666 ± 319 min, p = 0.005). The second round of application was needed
in 13.1% with Dilapan-S and 9.8% in Foley balloon, respectively not statistically
significant (NS). There were also no significant differences between Dilapan-S and
Foley balloon in the frequency of vaginal bleeding (3.1 vs. 0.9%), cervical lacerations
(1 vs. 0.5%), uterine hyperstimulation (0 vs. 0%) and maternal infectious morbidity
(14.3 vs. 13.1%). Patients with Dilapan-S were significantly more satisfied than patients
with Foley balloon as far as sleep (p = 0.01), relaxing time (p = 0.001) and performance
of desired daily activities (p = 0.001).
This is still the largest RCT comparing the efficacy and safety of Dilapan-S versus
Foley balloon catheter for pre-induction cervical ripening at term (LoE Ib).
A potential selection bias cannot be excluded, however, given the nature of intervention,
randomization was not an option.
Minor limitations of this study are the lack of data on the number of patients requiring
oxytocin for labor induction/augmentation, the rate of dilator/balloon catheter expulsions,
the frequency of pain/discomfort at insertion/removal of the devices and costs associated
with both methods.
A prospective open-label study included 200 pregnant women at term with a BS between
0–6 points (mean 3.5) eligible for labor pre-induction [25]. Cervical ripening was performed with four different methods:
-
Dilapan-S combined with two doses of oral mifepristone (200 mg each) 24 h apart (n = 50)
-
Dilapan-S (4 rods) only for 12 hours (n = 50)
-
Foley catheter for 12 hours (n = 50) and
-
two doses of intracervical PGE2 gel (0.5 mg each) 6 h apart.
Cervical maturation was assessed using the BS and the ultrasound cervicometry with
the color mapping and calculation of strain ratio (SR) before the start of pre-induction
and 12 hours after.
The primary outcome of the study was the change in BS and sonoelastographic cervical
maturation after the intervention. The results are shown in [Table 1].
This corresponded to the sonoelastographic SR values, which were lowest among the
patients receiving the combination of Dilapan-S and mifepristone and highest among
the patients receiving intracervical gel.
Further details on cervical sonoelastographic findings are presented in the paper.
This is the first prospective study evaluating cervical ripening with different mechanical
and pharmacological methods by using the BS and ultrasound cervicometry with the color
mapping.
The authors concluded that cervical sonoelastography allows an objective assessment
of cervical maturation, specifically the degree of softening after pre-induction which
is a strong predictor of labor induction success. It should be noted that mifepristone
is contraindicated for induction of labor in the third trimester in women with a viable
fetus.
Comparison of cervical ripening with Dilapan-S and Prostaglandin E2/misoprostol
In a single-center prospective observational pilot study 52 low-risk nulliparous women
with an unfavorable cervix (BS ≤ 6) and post-date pregnancy (≥ 41 weeks gestation)
received either Dilapan-S (n = 26, 1–5 rods, left in place for up to 24 hours) or
the 10 mg PGE2 vaginal pessary (n = 26, left in place for up to 24 hours) [26].
If the cervix was still unfavorable after intervention, up to two intracervical applications
of PGE2 gel were used in both groups for further induction.
The primary outcome measures were compliance with study protocol, maternal infection,
rate of uterine hyperstimulation and perinatal/neonatal outcomes.
Compliance to study protocol was 25/26 (96%); it was possible to insert Dilapan-S
in all but one woman.
There were no significant differences between the groups regarding primary outcomes
([Table 1]). The mean change in BS was comparable (3.3 vs 3.7) as well as the rate of vaginal
delivery/24 h (19.2 vs 15.4%, NS). Dilapan was left in place longer than the PGE2 vaginal pessary (22.8 vs. 17.3 h, p = 0.005). The mean number of rods used was 2.6
(range 1–4), and the mean pain score out of ten at Dilapan-S insertion was 2.2 (range
0–7).
The limitations of this otherwise well-designed pilot study are the low level of evidence
(LoE III), the lack of randomization and the insufficient number of pregnant women
included in the study, which resulted in an inadequate statistical power for some
primary outcome criteria (e.g. rate of uterine hyperstimulation, maternal and neonatal
infection).
The aim of an open-label randomized trial including 674 women ≥ 37+0 weeks’ gestation,
was to compare the efficacy, maternal and neonatal safety, and maternal satisfaction
of Dilapan-S (n = 337) to 10 mg PGE2 vaginal insert (n = 337) for induction of labor [27]. The proportion of nulliparous women was rather high (79.7 % in Dilapan-S group
and 80.7 % in PGE2 group).
Up to five rods were inserted into the cervical canal and left in place for a minimum
of 12 hours and up to a maximum of 24 hours. If the cervix remained unfavorable after
first round (BS < 6), a second (then third) round of dilators were planned for an
additional 12 to 24 hours. The PGE2 vaginal insert remained in place for up to 24–32 hours.
If spontaneous labor had not started, amniotomy was conducted after the BS was > 6,
followed by intravenous oxytocin according to the hospital protocols.
The most common indications for induction of labor were post-term pregnancy, fetal
growth restriction (FGR) and reduced fetal movements.
The primary outcome was failure to achieve vaginal delivery within 36 hours after
randomization (i.e. cesarean delivery being performed), which occurred in 37.4% of
patients allocated to Dilapan-S and 34.3% of patients allocated to the PGE2 vaginal pessary (adjusted risk difference: 0.02; 95% CI 0.05 to 0.10). Analgesia
during cervical ripening was significantly more often required in women receiving
PGE2 compared to women with Dilapan-S (66.3 vs. 51.2%, p < 0.0001), and the rate of complications
was higher with vaginal PGE2 (22.6%) than with Dilapan-S (7.6%); e.g. uterine tachysystole: 5.0 vs. 0.4%, uterine
hyperstimulation with non-reassuring/abnormal fetal heart rate (FHR): 4.3% vs. 0.
There was also a higher need for reinsertion of vaginal PGE2 by approximately 10%.
Amniotomy undertaken for induction of labor was significantly more frequently needed
in the Dilapan-S group (70.2 vs. 42.6%, p < 0.0001) as well as oxytocin required for
induction of labor compared to the PGE2 group (62.7 vs. 39.3%; p < 0.0001). There was no evidence of any difference in neonatal
outcomes between the groups. Using a questionnaire consisting of 23 questions maternal
satisfaction during the cervical ripening process was better with the use of Dilapan-S
compared to the PGE2 vaginal pessary.
This is the only randomized trial comparing Dilapan-S to vaginally applied PGE2 [LoE 1b].
To achieve adequate statistical power regarding the primary outcome a total of 410
participants per group was needed; however, final recruitment had to be interrupted
because of the impact of the COVID-19 pandemic (unavailability of research midwives).
Although from the investigator’s point of view the original primary outcome of failure
to deliver vaginally within 36 hours after randomization appears reasonable, it may
be somewhat arbitrary, since Cochrane Collaboration Reviews and the National Institute
for Health and Care Excellence (NICE) propose the vaginal birth rate within 24 hours
of the start of induction of labor as the clinically most relevant measure. The abandonment
of assessing a pre-induction BS may be debatable since an unripe cervix (BS < 6) is
a common inclusion criterion in most such comparative studies.
Induction of labor by using vaginal PGE2 in women with FGR (below which centile not specified) or with reduced fetal movements
(based on patient’s information? or verified by CTG?) may raise concern, particularly,
if there is no information on fetal Doppler sonographic findings presented.
It should be considered that a significant proportion of small fetuses close or at
term is affected by placental insufficiency thus being at higher risk of decompensation
during labor especially once exposed to uterine hyperstimulation [30].
A limitation of this study is that more women in the Dilapan-S groups did not receive
the allocated intervention (25–50%) compared with the PGE2 group (11%) because of the initial lack of available trained staff to fit in Dilapan-S
rods.
The authors stated that despite of this difference in adherence levels between the
groups, sensitivity analyses suggest that conclusions remain robust when excluding
women not adherent to the intervention.
In an open-label, noninferiority randomized trial including 303 pregnant women ≥ 37+0
weeks of gestation with Bishop score < 6 mechanical cervical dilatation by using Dilapan-S
was compared to 25 µg misoprostol orally every 2 hours (up to six doses) for induction
of labor [28].
After 12 hours of cervical ripening, oxytocin was initiated with a maximum dose limited
to 40 mU/min and amniotomy was performed as soon as clinically feasible.
The most common indication for induction of labor was post-term pregnancy, followed
by elective induction.
The primary outcome was the rate of vaginal delivery within 36 hours of the study
intervention: 61.6% of patients achieved vaginal delivery within 36 hours of initiation
of study intervention in the Dilapan-S group versus 59.2% in the misoprostol group,
with an absolute difference of 2.4% (95% CI; 9% to 13%), indicating noninferiority
for the prespecified margin of 10%. There were no significant differences between
groups in secondary outcomes such as median change in BS (2 vs. 3), vaginal delivery
rate (72.8 vs. 72.3%), duration from initiation of cervical ripening to vaginal delivery
(24.9 ± 8.98 vs. 25.8 ± 16.19 hours), intrapartum maternal fever (8.9 vs. 11.2%) and
neonatal outcomes.
Uterine tachysystole during clinical ripening occurred in 53.6% of patients receiving
oral misoprostol, which was significantly more frequent than the 25.7% in the Dilapan-S
group (p < 0.01). Failure to place Dilapan-S was found in 2.6% of women. Patients
who received Dilapan-S reported lower pain scores (p = 0.02), had less abdominal discomfort
(p = 0.04) and were able to sleep more (p = 0.03) during cervical ripening compared
to patients receiving misoprostol.
This is so far the only randomized trial comparing the use of Dilapan-S with orally
applied misoprostol for induction of labor near term (LoE Ib).
One limitation of the study was the inability to blind the participants and investigators
owing to the nature of the intervention, however, the likelihood of selection bias
is low because the outcomes were prespecified and not affected by subjective interpretation.
Another limitation is that the study had inadequate statistical power to detect the
differences in secondary outcomes and rare events. The primary outcome criterion may
be worthy of discussion similar to the primary outcome in the SOLVE trial [27], as discussed above.
In addition, there is a lack of data on the BS before the intervention, the number
of cervical dilators required for cervical ripening, the rate of complications associated
with the insertion/removal of Dilapan-S (e.g. cervical injury, bleeding), and the
number of patients requiring oxytocin in each group and on costs. The authors themselves
acknowledged that unique differences in each intervention’s labor-management protocols
could have affected the outcomes.
Discussion
Mechanical methods have shown to be an attractive alternative to prostaglandins for
cervical ripening/induction of labor at term.
According to a recent Cochrane Review mechanical induction using balloon catheters
is as effective as induction of labor using vaginally applied PGE2 but is associated with a more favorable safety profile [31], however, there was not enough research on other mechanical methods such as osmotic
dilators to reach a robust conclusion [31]
[32].
Truly, among mechanical methods for cervical ripening Foley balloon has been the gold
standard method for decades. In recent years, a paradigm shift has become obvious
from the perspective of labor induction. While so far most studies and Cochrane Reviews
used the criterion of delivery within 24 hours to assess the effectiveness of labor
induction, this view is being challenged as it has been increasingly recognized that
achieving a safe vaginal birth is more important than timescale alone [10].
This point of view has led to a renaissance of mechanical methods including balloon
catheters and synthetic osmotic cervical dilators for labor induction.
Efficacy and safety
In 2015 Dilapan-S was approved by the FDA for cervical ripening in the third trimester.
Since then, numerous clinical trials and RCTs have confirmed that Dilapan-S is a safe,
efficient and cost-effective method for cervical ripening/induction of labor associated
with high maternal satisfaction [23]
[27]
[28]. Depending on the definition of outcome criteria the rate of vaginal delivery ranges
from 61.6 to 81.3% [27]
[28].
In the largest RCT there were no significant differences in the rate of vaginal delivery
between Dilapan-S (81.3%) versus Foley catheter (76.1%), however, patients with Dilapan-S
were more satisfied than patients with the Foley balloon [23].
The advantages of Dilapan-S over Foley balloon catheter are the approval by national
authorities (e.g. FDA), no protrusion from the introitus, no need to keep under tension,
higher patient’s satisfaction and the less invasiveness of method, since Dilapan-S
is strictly placed into the cervical canal, while the Foley balloon has to be applied
extraamniotically.
A further advantage of Dilapan-S compared to Foley balloon is, that it is only contraindicated
in patients with the presence of clinically apparent genital tract infection, while
the commercially available and approved double-balloon catheter has several contraindications
(e.g. patients receiving or planning to undergo exogenous PG administration, prior
hysterotomy, ruptured membranes, maternal heart disease). In contrast to the double-balloon
catheter, Dilapan-S is not contraindicated in patients with a previous cesarean section
when considering the manufacturer’s product information.
The beneficial cervical softening effect with the use of Dilapan-S has also to be
experimentally verified by cervical sonoelastographic findings [25].
Two open-label randomized trials compared the efficacy and safety of Dilapan-S with
those of a 10 mg PGE2 vaginal insert [27] and the oral administration of 25 µg misoprostol every 2 hours [28].
Both RCTs came to the conclusion that Dilapan-S is as effective as vaginal PGE2 and oral misoprostol, respectively, in achieving vaginal delivery, however, the rate
of complications, in particular, uterine hyperstimulations with and without non-reassuring
FHR, was significantly higher using PGE2 and misoprostol.
An increasingly important issue associated with labor induction is maternal satisfaction,
which has shown to be significantly better when using Dilapan-S compared to PGE2/misoprostol [27]
[28].
Other studies have found that Dilapan-S was as effective as extraamniotic saline infusion
and oral misoprostol in nulliparous women with an unripe cervix at term [33], and that the combination of Dilapan-S and mifepristone led to a significancy higher
rate of vaginal deliveries compared to the use of Dilapan-S alone (76.8 vs. 60.3,
p = 0.045) [24]. However, mifepristone is contraindicated in women with induction of labor in the
third trimester and a viable fetus.
As highlighted by Gupta et al. [27] Dilapan-S would be a benefit in women with intrauterine growth restriction and reduced
fetal reserve, as it is associated with a low risk of uterine hyperstimulation.
According to a recent meta-analysis there is limited evidence on the optimal type
of labor induction in pregnancies with small fetuses, but it was pointed out that
mechanical methods seem to be associated with a lower occurrence of adverse intrapartum
outcomes [30].
In pregnancies complicated by a small fetus, the choice of the optimal method to induction
labor should be guided by the need to reduce the risk of adverse events related to
hypoxemia, rather than of achieving delivery in the shortest period of time [27]. Hence, Dilapan-S may be an appropriate option for labor induction in these patients.
The adequate use of Dilapan-S requires passing a ‘learning curve’ on how to insert
the rods into the cervical canal the proper way. According to the IFU and published
studies [10]
[23]
[27] as many rods as possible (usually 4–5) should be placed in the cervical canal and
it should be ensured that the tip of the rod slightly passes the internal os.
Failed insertion might be a problem: only two studies reported on failed insertion
in 2.6% and 3.8% of cases, respectively [26]
[28].
Expulsion of rods might be another concern; in the multi-center study by Gupta et
al. [10] spontaneous dilator expulsion occurred in 2% of cases, while others did not report
on this problem. Retention of whole or fragmented products or fragmentation of rods
were complications with an earlier version of Dilapan [9], but not recorded with Dilapan-S when considering studies since 2015.
There are no reliable data on maternal infectious mortality associated with the use
of Dilapan-S, however, recent studies have shown that maternal infection rates are
not higher when compared to the use of Foley catheter [23], the PGE2 vaginal insert [27] or oral misoprostol [28].
Cost-effectiveness
Outpatient cervical ripening with a balloon catheter or synthetic osmotic cervical
dilators has become increasingly important, particularly in the context of COVID-19
pandemic.
A recent randomized clinical trial comparing outpatient with inpatient pre-induction
cervical ripening using a synthetic osmotic dilator has shown that outpatient cervical
ripening decreased hospital stay and time from administration to active labor without
significant adverse outcomes [34].
According to a US cost consequence analysis outpatient cervical ripening with a synthetic
osmotic cervical dilator has the potential to reduce hospital costs, hospital stay,
and the cesarean section rate when compared to inpatients using the vaginal PGE2 insert or the single balloon catheter [35]. A further UK cost-consequence model by the same group [36] comparing Dilapan-S with vaginal PGE2 inserts (Propess) for inpatient induction of labor indicated that adoption of Dilapan-S
is likely to be cost-neutral and reduces staff workload in comparison to Propess.
A retrospective analysis comparing cervical ripening with Dilapan-S in an outpatient
procedure with the use of oral misoprostol or vaginal PGE2 gel in an inpatient setting has shown that cervical ripening with Dilapan-S resulted
in a significant reduction of time period from patient admission to the onset of labor,
shorter inpatient stay from admission to delivery and fewer hospital days in the outpatient
group thus decreasing socioeconomic costs [37].
Guidelines
The use of synthetic osmotic cervical dilators is inadequately represented in current
guideline recommendations, which is probably due to the amount of available evidence-based
data.
Only the most recent NICE guideline 2021 [38] states that for women with a BS of 6 or less mechanical methods to induce labor
(balloon catheter or osmotic cervical dilators) should be considered if pharmacological
methods are not suitable (e.g. in women with a higher risk of, or from hyperstimulation
or those who have had a previous cesarean section) acknowledging that mechanical methods
are less likely to cause hyperstimulation than pharmacological methods.
The German AWMF Guideline 015/088 [39] states that synthetic osmotic cervical dilators are a safe method for induction
of labor in patients with an unripe cervix and are also safe in patients with a previous
cesarean section.
The recent ACOG Practice Bulletin No. 205 ‘Vaginal Birth after Cesarean Delivery’
2019 [40] mentioned only the Foley catheter as an option for labor induction after a previous
cesarean section, but did not report on synthetic osmotic cervical dilators.
This may be due to the fact that there exist only two prospective observational studies
comparing Dilapan-S with vaginal PGE2 for cervical ripening/induction of labor in women with a previous cesarean section
[41]
[42].
Both studies are from the same working group and it is not yet possible to make evidence-based
recommendations based solely on these studies.
Overall, available evidence seems promising, but more well-designed, prospective,
and preferably randomized studies are needed such as comparing the use of balloon
catheters vs. synthetic osmotic cervical dilators for pre-induction cervical ripening
in outpatient settings and in women with previous cesarean section, as well as investigating
the efficacy and safety of Dilapan-S in patients with late fetal growth restriction
affected by placental insufficiency.
