MATERNAL- FETAL MEDI CI NE

Early amniotomy after vaginal misoprostol for induction of labor:

a randomized clinical trial
Mohamed H. Makarem

Kamal M. Zahran

Mohamad S. Abdellah

Mohamed A. Karen
Received: 5 November 2012 / Accepted: 28 January 2013 / Published online: 21 February 2013
Springer-Verlag Berlin Heidelberg 2013
Abstract
Objectives To test the effectiveness and safety of early
amniotomy after vaginal misoprostol for the induction of
labor.
Study design A randomized clinical trial that included
320 women with medical or obstetric indication for labor
induction. They were randomly assigned into two equal
groups, amniotomy group and control group. Each partic-
ipant received vaginal misoprostol 50 lg every 6 h for
induction of labor. In amniotomy group, amniotomy was
done in the early active phase of labor while in the control
group, the membranes were left to rupture spontaneously or
as judged by the senior resident in the duty.
Results More subjects in the amniotomy group achieved
vaginal delivery within 24 h than in the control group [117
(73.13 %) vs. 105 (65.63 %)]. Subjects in the amniotomy
group reported shorter induction to delivery interval
(09.72 4.61 h vs. 13.61 5.61, P = .002), and better
neonatal outcome compared to the control group. There
were no statistically signicant differences between both
group with regard to number of doses of misoprostol, need
for oxytocin, Cesarean Section indication and maternal side
effects.
Conclusion Early amniotomy after vaginal misoprostol
for labor induction is associated with higher successful
vaginal delivery rate, shorter labor duration and better
neonatal outcome.
Keywords Amniotomy Induction of labor Misoprostol
Introduction
Amniotomy (dened as articial rupture of fetal mem-
branes) has long been believed to reduce the duration of
labor [2, 10]. Many health care providers believed that
shortening the duration of labor is benecial and use
amniotomy to reduce the risk of maternal morbidity in
cases of complicated and prolonged labor [8]. Amniotomy
is also used when it is judged important to conduct internal
monitoring of the fetus or to obtain amniotic uid for visual
inspection [15]. The mechanism of action behind amniot-
omy is thought to be the release of prostaglandin E2
(PGE2) and rise in oxytocin level [7].
Opponents of amniotomy argue that the amniotic sac and
uid play an important role in protecting the fetus against
uterine contractions, helping with cervical modications
(ripening, effacement and dilatation) and pre-stretching the
perineum. It is believed that the pressure exerted by the
membranes on the uterus stimulates oxytocin surges [7].
Risks associated with amniotomy include umbilical cord
prolapse or compression, maternal or neonatal infection,
fetal heart rate (FHR) decelerations, bleeding from pla-
centa previa or low-lying placenta, and possible fetal injury
[1, 12].
Many trials have been conducted addressing the subject
of combined use of oxytocin and amniotomy [11, 22]. One
study reported that elective amniotomy shortens the active
phase of labor and decreases the need for oxytocin aug-
mentation [11]. Another study reported that early inter-
vention with amniotomy and oxytocin appears to be
associated with a modest reduction in the rate of Cesarean
section (CS) over standard care [22].
M. H. Makarem K. M. Zahran M. S. Abdellah (&)
M. A. Karen
Department of Obstetrics and Gynecology,
Faculty of medicine, Womens Health Centre,
Assiut University, P.O. 71116, Assiut, Egypt
e-mail: msayed21@yahoo.com
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Arch Gynecol Obstet (2013) 288:261265
DOI 10.1007/s00404-013-2747-6
The introduction of misoprostol as a ripening agent for
labor induction has resulted in an overall lower incidence
of CS, a higher incidence of vaginal delivery within 24 h of
application and a reduced need for oxytocin (Pitocin)
augmentation [24]. Vaginal administration of misoprostol
gives more rapid delivery with less hyperstimulation and
tachysystole as compared to oral administration [3, 23].
Although there has been work on the role of amniotomy
in spontaneous labor [19], surprisingly, there has been little
previous work on the role of early amniotomy in the con-
text of labor induction [16]. Furthermore to the best of our
knowledge, there is no randomized controlled study
addressed the subject of amniotomy after vaginal miso-
prostol for induction of labor. We hypothesized that when
early amniotomy is conducted after the cervix has been
ripened by vaginal misoprostol, the effect of amniotomy
could be much better than after oxytocin.
The present study was carried out to investigate the
effectiveness and safety of early amniotomy after vaginal
misoprostol for induction of labor at term.
Materials and methods
This randomized clinical trial took place at the Womens
Health Center, Assiut University, from September 2008
through December 2010. Patients with medical or obstetric
indication for labor induction were recruited.
Inclusion criteria included: pregnant women at
36 weeks gestation or more, singleton living fetus, cephalic
presentation, amniotic uid index more than 5 cm, reactive
non-stress test and negative contraction stress test. Women
were excluded from the study if they had macrosomic
babies [estimated fetal weight (EFW) more than 4,000 g],
fetal anomalies, intrauterine growth restriction (IUGR),
previous uterine scars, prelabor premature rupture of fetal
membranes (PPROM), polyhydramnios, failed induction of
labor despite full dose of misoprostol, high head and head
not applied on the cervix at the time of early amniotomy, or
any other contraindication to vaginal delivery.
Gestational age was determined on the basis of the last
menstrual period, conrmed by ultrasound evaluation and
calculated in menstrual weeks.
Clinical work up included full history taking, clinical
examination, obstetric ultrasound evaluation, non-stress
test, contraction stress test and biophysical prole. A total
of 320 pregnant women attending the antenatal care clinic
and meeting the Inclusion criteria were assigned randomly
to have either early or late amniotomy. Subjects were
assigned to either group by means of a computer-generated
randomization tables and their allocation was kept in
consecutively numbered, sealed, opaque envelopes till the
time of intervention.
Misoprostol as 50 lg (1/4 of Misotac

200 lg tablet,
SIGMA pharmaceutical Company) was administrated
vaginally by the senior resident in the duty.
The administration of misoprostol was repeated every
6 h until three or more uterine contractions of 40 s duration
occur over 10 min, or when the maximum of four doses
(i.e. 200 lg) is reached.
In the absence of active labor 6 h after administration of
the last dose of misoprostol, failed induction was docu-
mented and Cesarean section was done.
Early amniotomy was done in the early active phase of
labor for group A (amniotomy group) when the cervix was
dilated 3 cm using the amniotomy hook, provided the head
is well applied to the cervix. Amniotomy was not done for
group B (control group) until the membranes ruptured
spontaneously or as judged by the senior resident in the
duty. Continuous fetal monitoring was done for every
participant after the start of uterine contractions.
The primary outcome measure was the frequency of
successful induction, dened as vaginal delivery within
24 h from the beginning of induction.
Secondary outcomes included: induction-delivery
interval, duration of labor, amniotomy-delivery interval,
number of misoprostol doses administered, the need for
augmentation of labor by oxytocin, occurrence of chorio-
amnionitis or postpartum fever. Perinatal outcomes inclu-
ded: cord prolapse, abnormal FHR changes during labor,
intrapartum meconium passage, Apgar scores less than 7 at
1 and 5 min, neonatal infections and newborn admission in
the neonatal intensive care unit (NICU).
For sample size calculation, we relied upon our previous
study that showed a 66.7 % vaginal delivery rate with vag-
inal misoprostol [24]. Using an alpha error of 5 and 95 %
power, aiming at detecting a 20 % difference between the
subgroups, a total of 96 women were needed in each arm.
Statistical analysis was performed using the SPSS
computer package (SPSS, Inc., Chicago, IL) version 17.0.
The v
2
-test or, if necessary, Fishers exact test was used to
compare continuous data. A signicance level of 5 % was
adopted. Risk ratio (RR) and 95 % condence interval (CI
95 %) were calculated to assess the magnitude of the
association between outcomes and using vaginal miso-
prostol as the reference category.
Results
Subjects were similar in mean age, parity, gestational age,
pre-induction Bishop Score and indications for induction
(Table 1). The main indications for induction of labor were
post-term followed by hypertensive disease of pregnancy.
More subjects in the amniotomy group achieved vaginal
delivery within 24 h than in the control group
262 Arch Gynecol Obstet (2013) 288:261265
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[117 (73.13 %) vs. 105 (65.63 %), P = 0.15]. Women in
the amniotomy group reported shorter labor duration of
about 4 h than those of control group (9.72 4.61 h vs.
13.61 5.61, P = 0.002), this difference was statistically
signicant. The mean duration from rupture of fetal
membrane to delivery was 2.22 0.80 in the control
group and 3.28 1.73 in the amniotomy group (P =
0.04). There were no statistically signicant differences
between both group with regard to number of doses of
misoprostol, need for oxytocin and Cesarean section indi-
cation, the main indications for CS in both groups were
failure to progress and fatal distress (Table 2).
Maternal adverse effects such as nausea, vomiting,
diarrhea, and hyperthermia were similar in the two groups
(Table 3). There were no reported cases of chorioamnio-
nitis or cord prolapse.
There was no statistically signicant difference between
both groups with regard to occurrence of tachysystole,
uterine hypertonus and uterine hyperstimulation.
Patients in the amniotomy group had better neonatal
outcome than the control group, they demonstrated lower
rate of meconium stained amniotic uid, lower rate of
Apgar score \7 at 1 and 5 min, less need for resuscitation
and lower NICU admission rate compared to the control
group, yet, the difference was statistically non-signicant
(Table 3).
Discussion
Induction of labor is a common obstetric intervention. The
rate of labor induction varies from 9.5 to 33.7 % of all
pregnancies annually [20]. Favorable cervical scoring
encourages the use of oxytocin. The problem of an unripe
cervix at termmakes a successful vaginal birth less likely and
the use of a ripening agent is highly recommended. Obser-
vational data derived from studies conducted in the 1960s
suggest that about one-third of women, in whominduction of
labor is attempted with oxytocin administration without
concurrent amniotomy, will remain undelivered 23 days
after the beginning of the induction attempt [14]. Not sur-
prisingly, in the light of these observations, amniotomy has
come to be used routinely at the time that oxytocin is started
to induce labor [14].
Pharmacological agents for induction of labor include
prostaglandins, misoprostol, mifepristone, and relaxin.
Misoprostol is an effective agent for cervical ripening. The
introduction of misoprostol as a ripening agent for labor
induction has resulted in an overall lower incidence of CS,
a higher incidence of vaginal delivery within 24 h of
application and a reduced need for oxytocin (Pitocin)
augmentation [24]. The goal of our study was to assess the
efcacy and safety of early amniotomy in women who
undergo labor induction by misoprostol. It has been well-
documented that the length of labor is correlated directly
with maternal chorioamnionitis, postpartum fever, and
neonatal infection [13, 18, 21].
When amniotomy is followed by oxytocin infusion, the
overall delivery time is reduced [17]. Nochum et al. [17]
study found that Labor augmentation by combined amni-
otomy and oxytocin among women with a prolonged latent
phase at term seems superior compared to either of them
alone.
To shorten the interval between amniotomy and deliv-
ery, oxytocic drugs are usually used either at the time that
the membranes are ruptured or after an interval of a few
hours if labor has not started. Evidence from controlled
trials shows that women who receive oxytocics from the
time of amniotomy are more likely to be delivered within
12 and 24 h, and less likely to give birth by cesarean
section or forceps than those who have had amniotomy
alone [5]. Amniotomy and immediate oxytocin infusion is
associated with the establishment of active labor at 4 h, a
shorter amniotomy delivery interval and greater maternal
satisfaction [6].
Women who receive early oxytocin require less anal-
gesia compared to those receiving oxytocin later [5]. This
does not necessarily mean that early oxytocin results in a
less painful labor; it may simply reect the shorter interval
between amniotomy and birth. Several trials suggest a
Table 1 Demographic characteristics of patients in both groups
Item Amniotomy (n = 160) Control (n = 160) P value
Age in years 23.97 4.26 24.33 4.29 NS
Parity 1.21 1.44 1.58 2.59 NS
Gestational age (weeks) 40.00 4.10 40.75 4.98 NS
Bishop score 8.68 .98 7.85 1.32 NS
Indication for induction
Post-term 126 (78.75 %) 132 (82.50 %) NS
Hypertension 34 (21.25 %) 28 (17.50 %) NS
NS statistically non-signicant
Arch Gynecol Obstet (2013) 288:261265 263
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lower incidence of postpartum hemorrhage when amniot-
omy is combined with early oxytocin administration
[5, 16]. Macones et al. and Fraser et al. [9, 16] found that
routine early amniotomy is associated with a reduction in
labor duration.
All these data are in agreement with our results where
we found that more subjects in the amniotomy group
achieved vaginal delivery within 24 h compared to the
control group [117 (73.13 %) vs. 105 (65.63 %)]; this
difference was statistically not signicant and women in
the amniotomy group reported shorter labor duration about
4 h less than those of control group [(09.72 4.61) h vs.
(13.61 5.61), P = 0.002], this difference was statisti-
cally signicant.
Meta-analysis provides no support for the hypothesis
that routine early amniotomy reduces the risk of Cesarean
delivery [5]. An association between early amniotomy and
Cesarean delivery for fetal distress is noted in one large
trial [9]. This suggests that amniotomy should be reserved
for women with abnormal labor progress [9]. The results of
our study did not match with the above-mentioned studies,
where the Cesarean section rate was less in the amniotomy
group [43 (26.88 %) vs. 55 (34.37 %)] in the control group,
this could be due to the fact that we used misoprostol 50 lg
which was associated with less hyperstimulation syndrome
and Hypertonus uterus compared to oxytocin.
The results of our study also match with Weis et al. [22]
study which showed that, in prevention trials, early
Table 2 Clinical outcomes of induction in both groups
Item Amniotomy (n = 160) Control (n = 160) P value
Number of doses of misoprostol
One dose 91 (56.87 %) 86 (53.75 %) NS
Two doses 37 (23.13 %) 38 (23.75 %) NS
Three doses 25 (15.62 %) 28 (17.50 %) NS
Four doses 7 (4.37 %) 8 (5 %) NS
Need for oxytocin 141 (88.13 %) 147 (91.88 %) NS
Induction delivery interval (hours) M SD 09.72 4.61 13.61 5.61 0.002
*
Range 03.0022.50 05.0026.50
ROM-delivery interval (hours) M SD 3.28 01.73 02.22 0.80 0.04
*
Range 00.5005.00 00.5004.00
Mode of delivery
Vaginal 117 (73.13 %) 105 (65.63 %) NS
CS 43 (26.88 %) 55 (34.37 %)
Indication of CS
Fetal distress 16 (10 %) 21 (13.13 %) NS
Failure to progress 18 (11.25 %) 22 (13.75 %) NS
Uterine over activity 9 (5.62 %) 12 (7.50 %) NS
M means, SD standard deviation, CS cesarean section, NS statistically non-signicant
*
Statistically signicant
Table 3 Maternal and fetal complications in both group
Item Amniotomy (n = 160) Control (n = 160) P value
Fever 11 (6.88 %) 10 (6.25 %) NS
Nausea and/or vomiting 35 (21.87 %) 29 (18.13 %) NS
Tachysystole 6 (3.75 %) 4 (2.50 %) NS
Hypertonus 5 (3.12 %) 4 (2.50 %) NS
Hyperstimulation syndrome 13 (8.13 %) 8 (5.00 %) NS
Meconium stained amniotic uid 13 (8.13 %) 19 (11.88 %) NS
Apgar score \7 at 1 min 16 (10 %) 19 (11.88 %) NS
Apgar score \7 at 5 min 8 (5 %) 15 (9.38 %) NS
Need for resuscitation 13 (8.13 %) 19 (11.88 %) NS
NICU admissions 8 (5 %) 13 (8.13 %) NS
NS statistically non-signicant, NICU neonatal intensive care unit
264 Arch Gynecol Obstet (2013) 288:261265
1 3
intervention with amniotomy and oxytocin appears to be
associated with a modest reduction in the rate of Cesarean
section over standard care. Our study also matches with a
recent study that found no difference between early
amniotomy and standard therapy regarding the CS rate
during induction of labor [16].
In 1993, Garite et al. [11] study supported our study in
that elective amniotomy shortens the active phase of labor
and decreases the need for oxytocin augmentation.
Controlled trials showed that routine early amniotomy is
associated with reduction in abnormal 5-min Apgar scores
and need for NICU admissions [4, 5, 9, 16].
This is in agreement with our study, where early
amniotomy was associated with better neonatal outcome
which was reected by less meconium-stained amniotic
uid, less Apgar score \7 at 1 and 5 min, lower need for
resuscitation and lower NICU admissions this might be due
to the associated shorter induction-delivery interval in the
amniotomy compared to the control group.
Our conclusion is that in well-selected cases, early
intervention with amniotomy after vaginal misoprostol for
labor induction appears to be associated with higher suc-
cessful vaginal delivery rate, shorter induction-delivery
interval and better neonatal outcome over standard care.
Conict of interest The authors have no conicts of interest con-
cerning the work reported in this paper.
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