Journal of the College of Physicians and Surgeons Pakistan 2008, Vol.

18 (10): 625-629 625

INTRODUCTION
The role of prostaglandins in ripening of cervix, induction
of labour and control of Postpartum Haemorrhage
(PPH) is well-established.
Recently, investigators have shown the use of
alternative prostaglandin PGE
1
Misoprostol for cervical
ripening and induction of labour.
1,2
It is prostaglandin E
1
analogue, which was introduced as the treatment of
gastric ulcer, but later on FDA approved a new label for
the use of Misoprostol during pregnancy.
3
It has been
used for many years for the first and second trimesters
of pregnancy termination and induction of labour,
because it acts as uterotonic and softens the cervix by
increasing proteoglycon content and changing the
biophysical properties of collagen.
4
Misoprostol can be
administered orally, rectally or vaginally for the induction
of labour. Intravaginal Misoprostol is an efficacious,
economical and safe method of induction of labour in
patients with toxemia of pregnancy, even with modified
Bishops score of < 4 in eclampsia.
5,6
Induction of underprivileged grand multiparous women
with live fetus or fetal death can be performed safely and
cost-effectively by vaginal Misoprostol,
7
with minimum
required dose and careful monitoring. Over 45
randomized trials including more than 4500 women
found vaginal Misoprostol to be more effective than
oxytocin or (vaginal) PGE
2
.
8
The objective of this study was to compare the safety
and efficacy of oral versus vaginal administration of
50 g Misoprostol in terms of failure to achieve vaginal
delivery due to complications; induction to delivery
interval and requirement of dose in relation to Bishops
score, respectively.
METHODOLOGY
This quasi-experimental study was conducted at
Gynaecology and Obstetrics Department (Unit-IV) of
ABSTRACT
Objective: To compare the safety and efficacy of Misoprostol through oral and vaginal routes for induction of labour at
term.
Study Design: Quasi-experimental study.
Place and Duration of Study: Department of Gynaecology and Obstetrics (Unit-IV), Liaquat University Hospital,
Jamshoro, Pakistan, from January to December 2004.
Methodology: Eighty term patients who met the inclusion criteria were selected for induction of labour with (50 g)
Misoprostol, either by oral or vaginal route. The patients were allocated in two groupsA and B, using non-probability
convenient sampling technique. The dose was repeated at an interval of 6 hours upto maximum dose of 150 g.
Improvement in Bishops score, analgesic requirements, route of delivery, maternal complications, neonatal outcomes
were noted.
Results: The commonest indication in group-A was premature rupture of membranes in 16 patients (40%) and in 8 (20%)
patients of group-B. Mean improvement in Bishops score after 6 hours was greater in group-A (3.6 + 3.09) than group-B
(3.3 + 3.45, p=0.70). Induction to delivery interval was less in group-A (6.7 + 4.4 hours) than group-B (7.5 + 4.3 hours,
p=0.41). Oxytocin augmentation was required more in group-B as compared to group-A. Normal vaginal deliveries were
achieved in 95% of group-A and in 80% of group-B. The dose of 50 g was effective in 31(77.5%) patients of group-A as
compared to 24 (60.0%) patients of group-B, while 100 g was needed in 6 (15.0%) patients of group-A as compared to
13 (32.5%) patients in group-B. There was no significant difference between both the groups with regard to analgesic
requirement, instrumental delivery, maternal complications and neonatal outcome.
Conclusion: Safety and efficacy was comparable between low-dose vaginal and oral Misoprostol uses for induction of
labour. However, oral route was better with respect to treatment interval, number of doses required and route of delivery.
Both routes of administration can alternatively be used for induction of labour in developing countries where cost of drug
does matter.
Key words: Misoprostol. Pregnancy. Oral. Vagina. Efficacy. Complication. Outcome. Labour.
Department of Gynaecology and Obstetrics, Liaquat University
of Medical and Health Sciences, Jamshoro, Hyderabad.
Correspondence: Dr. Razia Mustafa Abbassi, 13-A, Sindhi
Muslim Housing Society, Hyderabad.
E-mail: dr-razia-abbasi@hotmail.com
Received June 18, 2007; accepted August 30, 2008.
Safety and Efficacy of Oral Versus Vaginal Misoprostol Use for
Induction of Labour at Term
Razia Mustafa Abbassi, Pushpa Sirichand and Sadaf Rizvi
ORIGINAL ARTICLE
Liaquat University Hospital, Jamshoro, Sindh, Pakistan
from January to December 2004. A total of 839 obstetric
patients were received for delivery during this period
including 606 women at term (37-42 weeks). Out of
those, 80 women who needed induction of labour were
selected for using 50 g Misoprostol tablet. The patients
were allocated in two groups using non-probability
convenient sampling technique, with 40 women each in
groups-A and B. Group-A received the agent orally,
while group-B received it intra-vaginally.
Inclusion criteria were women with singleton pregnancy,
vertex presentation, gestational age > 37-weeks, intact
membranes or pre-labour rupture of membranes,
Bishops score < 5 and reactive fetal cardiac activity.
Women with Intrauterine Death (IUD), fetal abnormality
such as hydrocephalus and anencephaly and with
hypertensive disorders of pregnancy and diabetes
mellitus were also included in the study. Women with
multiple gestation, malpresentation, previous scarred
uterus, fetal distress, marked uterine anomaly or with
any contraindication to prostaglandin were excluded.
Women who met the inclusion criteria were selected and
a well-informed written consent was obtained from every
participant. Demographic data of cases such as age,
parity, induction, induction to delivery interval, dose of
Misoprostol required, maternal and fetal side effects,
birth weight, Apgar score at first 5 minutes (in live
fetuses), mode of delivery and fetal outcomes were
recorded. Initially, 1/4
th
(50 g) of Misoprostol was given
orally or vaginally in women with spontaneous rupture of
fetal membranes or with intact fetal membranes and
with poor Bishops score. Further, doses were repeated
6-hourly, where upto maximum dose of 150 g. Patients
were monitored and documented for uterine contraction,
tachysystole, hyperstimulation syndrome, vaginal
bleeding, nausea, vomiting, diarrhoea, pyrexia, rigors
and other unwanted side effects. Maternal and fetal
monitoring was carried out. Partograph was also
maintained. CTG was done before and after the dose of
Misoprostol and then intermittently during labour.
Induction to delivery interval was recorded in hours.
Need for augmentation of labour with artificial rupture of
membrane and oxytocin in either group was assessed.
All the data were entered and analysed through
software programme SPSS version 10.0.
RESULTS
There was no significant difference between the two
groups in terms of maternal demographic features such
as age and mean parity (Table I). Premature Rupture of
Membranes (PROM) at term was the common reason
for oral Misoprostol group, given to 16 (40%) out of 40
women (Table I). In majority of women in both groups
Bishops score was < 5. Initial mean Bishops score in
group-A was 4.1 + 1.36 and it was 4.4 + 1.15 (p=0.37)
in group-A. Mean Bishops score improvement after 6
hours was more in group-A (3.6 + 3.09) than in group-B
(3.3 + 3.46) but it was not statistically significant
(p=0.70). The mean induction to delivery interval was
6.7 + 4.4 hours in group-A and it was 7.5 + 4.3 hours in
group-B (p= 0.41, Table II). More patients in group-B as
compared to group-A required augmentation of labour.
Amniotomy alone was needed only in 3 patients and in
2 patients in group-A and B respectively. Majority of
women 24 (60.0%) in group-A and 32 (80%) in group-B
required amniotomy along with oxytocin infusion. In few
patients oxytocin alone was given.
There was, however, no significant difference in
analgesic requirement. Fetal outcome and maternal
complications in both groups indicated that dose of
50 g was well-tolerated by both groups.
Majority of the patients in both groups delivered
vaginally, however, more women in group-A (n=38,
626 Journal of the College of Physicians and Surgeons Pakistan 2008, Vol. 18 (10): 625-629
Razia Mustafa Abbassi, Pushpa Sirichand and Sadaf Rizvi
Table I: Indications for the use of Misoprostol (n = 80).
Indications Group (n=80)
A: Oral B: Vaginal
n=40 (%) n=40 (%)
PROM 16 (40.0%) 8 (20.0%)
Intrauterine fetal death 3 (7.5%) 5 (12.5%)
Hypertensive disorders of pregnancy 3 (7.5%) 5 (12.5%)
Post-dated pregnancy 1 (2.5%) 2 (5.0%)
Maternal diabetes mellitus 1 (2.5%) 1 (2.5%)
Abruptio placenta 1 (2.5%) 1 (2.5%)
Oligohydramnios 0 1 (2.5%)
Table II: Efficacy of Misoprostol in both groups (n = 80) .
Variable Group (n=80)
A: Oral B: Vaginal
n=40 (%) n= 40 (%) p-value
Dose requirement
Single (50 g) 31 (77.5%) 24 (60.0%) 0.17
Two (100 g) 6 (15.0%) 13 (32.5%)
Three (150 g) 3 (7.5%) 3 (7.5%)
Bishops score
< 5 39 (97.5%) 40 (100.0%) NS
> 5 1 (2.5%) 0
Change in Bishops score
Initial Bishops score 4.1 + 1.36 4.4 + 1.15 0.37
Bishops score after 6 hours 3.6 + 3.09 3.3 + 3.46 0.70
Difference between Bishops score 1.98 + 1.0 1.65 + 0.2 0.16
Induction to delivery interval (hours) 6.7 + 4.4 7.5 + 4.3 0.41
Need of augmentation
Oxytocin infusion 3 (7.5%) 6 (15.0%) 0.006*
Amniotomy alone 3 (7.5%) 2 (5.0%)
Oxytocin + amniotomy 24 (60.0%) 32 (80.0%)
Labour outcome
Successfully induced 39 (97.5%) 35 (87.5%) 0.20
Failed induction 1 (2.5%) 5 (12.5%)
Mode of delivery
Vaginal 38 (95.0%) 33 (82.5%) 0.14
Instrumental 1 (2.5%) 1 (2.5%)
Caesarean section 1 (2.5%) 6 (15.0%)
* P-value is statistically significant; Results are expressed as mean + standard deviation;
NS= Not significant.
95%) achieved vaginal delivery as compared to group-B
in which 33 (82.5%) patients delivered vaginally. Only
one patient in group-A and 6 in group-B underwent
caesarean section. For 5 patients, the reason for
caesarean section was non-progress of labour. One
case in each group had caesarean section due to fetal
distress. There was no major complication, such as
uterine rupture, observed in both groups. However, side
effects such as uterine hyperstimulation and pyrexia
were same in both groups. Women induced with oral
Misoprostol had higher frequency of chills. In both
groups, Misoprostol was repeated after 6 hours. The
initial dose of 50 g Misoprostol was effective in majority
of patients in both groups followed by artificial rupture of
membranes and intervenous oxytocin. In only 6
patients, 3 in each group, 150 g Misoprostol was
required. Fetal outcome was good in both groups. Thirty
one (88.5%) babies delivered with Apgar score > 5 were
included in group-A and 34 (91.89%) in group-B. Only
4 (11.4%) babies in group-A and 3 (8.1%) in group-B
had Apgar score < 5 at first 5 minutes (Table III). There
was no still birth or neonatal death in either group.
DISCUSSION
Misoprostol is being increasingly used for labour
induction since last few years because of its efficacy,
low-cost, and effectiveness due to its stability at room
temperature. There have been increasing number of
published reports of Misoprostol use, through different
routes (oral, vaginal and rectal) and in varying doses
(25 g to 200 g). Higher incidence of tachysystole is
reported with repeated doses.
2
In this study, intervention
was started with dose of 50 g of Misoprostol and
repeated at 6-hourly interval. The oral route was more
effective than vaginal route especially in terms of
induction to delivery interval and the number of doses
required. Most of the patients delivered with 50 g oral
versus vaginal use, which was comparable with the
study conducted by Windrim,
9
who reported 50 g oral
Misoprostol being as effective in inducing labour as
vaginal administration in the same dose. Several other
researchers have found that initial dose of 50 g oral
Misoprostol is less effective and associated with longer
induction to delivery interval presumably because of first
bypass effect.
10
Previous work done has shown that vaginal Misoprostol
was more efficacious than oral Misoprostol in equivalent
doses.
11
This is because of the 3 times greater
bioavailability of vaginal than oral Misoprostol, however,
this also led to greater uterine hyperstimulation leading
to non-reassuring fetal heart sound.
12
Gaskin reported
that despite its increased efficacy, high rates of
tachysystole and hyperstimulation associated with 50 g
vaginal Misoprostol, given are a cause for concern.
13
In
this study, only one woman in group-A and 2 in group-B
developed hyperstimulation, while none developed
tachysystole. Induction to delivery interval was slightly
shorter in group-A than group-B. This finding is similar to
the study of Paungmora et al., who found that in oral
group, induction to delivery time was shorter than
vaginal group but not significantly different.
14
In that
study, 153 pregnant women were given Misoprostol 100
g oral or 50 g vaginally at interval of 6 hours and the
induction to delivery was 14.3 hours in oral as compared
to vaginal group where it was 15.8 hours. However,
Shetty in 2001 reported different results in which mean
induction to delivery interval was significantly shorter in
vaginal versus oral Misoprostol group (17.8 vs. 27.9
hours) while both had received 50 g Misoprostol.
15
However, this difference may be associated with several
factors including their larger sample size as well as
advanced statistical analysis of the data. Oxytocin
requirement was more in group-B than in group-A in the
present study but results were not significantly different.
In contrast, another study conducted by Shetty et al.
reported more oxytocin requirement with oral use
(68.6% out of 50 women as compared to 44% out of 51
in vaginal group). They studied 101 women using 100
g in the oral group as compared to 25 g in the vaginal
group.
16
Side effects of Misoprostol particularly gastrointestinal
tract symptoms, fever and chills were less in this study.
Only one patient in each group developed fever and 5 in
group-A developed chills. There were no gastrointestinal
symptoms in either group. The results are similar to the
observations made by Nopdonrattakoon in which only
one patient out of 101 developed diarrhoea and 2
developed low-grade fever indicating that 50 g dose by
either route is well-tolerated.
17
However, induction to
delivery interval and number of doses required was
better with vaginal route than oral Misoprostol use.
17
In
this study, uterine hyperstimulation was observed in one
(2.5%) patient in group-A and 2 (5%) patients in
group-B. In contrast, Carlan reported that out of 503
women with oral (200 g) and 501 with vaginal (50 g),
efficacy of Misoprostol was same in both groups but
frequency of uterine contractility and intervention was
more with oral versus vaginal Misoprostol (18.6% vs.
13.7%).
18
Another study which compared the efficacy of
100 g of oral Misoprostol with 25 g vaginal
Journal of the College of Physicians and Surgeons Pakistan 2008, Vol. 18 (10): 625-629 627
Misoprostol use for induction of labour
Table III: Side effects of Misoprostol and Apgar score at 1
st
five
minutes (n = 80).
Variable Group (n=80)
A: Oral B: Vaginal p-value
n=40 (%) n=40 (%)
Uterine activity
Uterine hyperstimulation 1 (2.5%) 2 (5.0%) NS
Tachysystole 0 0
Fetal heart rate changes
with hyperstimulation
1st stage 1 (2.5%) 2 (5.0%) NS
2nd stage 0 0
NS= Not significant
628 Journal of the College of Physicians and Surgeons Pakistan 2008, Vol. 18 (10): 625-629
Razia Mustafa Abbassi, Pushpa Sirichand and Sadaf Rizvi
Misoprostol for cervical ripening and labour induction
found that uterine hyperstimulation was more frequent
(6.9%) in women treated with 100 g doses of oral
Misoprostol and none in vaginal group developed
hyperstimulation.
19
The rate of caesarean section was
lower in group-A as compared to group-B in this study.
It was in contrast with the study of How and colleagues,
in which caesarean section rate was lower in vaginal as
compared to oral group (17% vs. 32% of 110 women
each).
20
In this study, PROM was the commonest reason for oral
Misoprostol and poor Bishops score was the reason for
vaginal Misoprostol in most of the women. Good results
in oral group were obtained in terms of induction to
delivery interval and outcome. Same observations were
reported in another study in which PROM was actively
managed in 30 out of 61 women with oral Misoprostol
(50 g) and 93.3% women delivered within 24-hours
with no increase in maternal or neonatal complication.
21
Crane compared 50 g oral Misoprostol in PROM with
intravenous oxytocin and found longer induction to
delivery interval but increased maternal satisfaction with
oral Misoprostol as compared to oxytocin.
22
Another
study showed similar results of oral Misoprostol group
with oxytocin.
23
Jahan Ara used oral Misoprostol 50 g
at 6 hours interval in patients with PROM at term and
found shorter induction to delivery interval and good
fetal outcome among 104 women (74% multigravida
within 12 hours as compared to 14.3% primigravida).
24
Parity was not the studied issue in the present study.
Apgar score at 5 minutes was less than 5 in 8.9% and
greater in 71.1% babies in the same study. Peter, et al.
used 50 g and 100 g of oral misoprostol in two groups
each having 30 and 31 women respectively, 4 hourly for
induction of labour following PROM and observed that
50 g was as effective as 100 g in accelerating the
progression to vaginal delivery following PROM. The
delivery interval in their study was 14.5 + 6.2 hours in
women who received 50 g versus 13 + 6.1 hours in
women who received 100 g.
25
Kallue assessed the role of vaginal Misoprostol (25 g)
in cervical ripening at term pregnancy and reported it as
a safest and most effective labour inducing agent
causing cervical ripening in 99% out of 307 women.
26
In this study, effectiveness in terms of failed induction
and safety were comparable between oral Misoprostol
and vaginal Misoprostol, but oral route was better in
respect to treatment interval and number of doses
required.
This study had some limitations including smaller
sample size and non-randomization of subjects.
CONCLUSION
The use of 50 g oral Misoprostol was a better option for
cervical ripening and induction of labour in women with
intact fetal membranes as well as with PROM. Efficacy
of vaginal Misoprostol was comparable with oral
Misoprostol in an optimal dose of 50 g.
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