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7/26/2019 Review Lit Part 1
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Physiology of onset of labour and cervical
ripening.
Normal labour is a process defined as the onset of persistent regular
uterine contractions along with progressive cervical dilatation and
effacement in which the foetus is born between 37 to 42 completed
weeks of pregnancy by vertex. It is a physiological event involving a
seuential! integrated set of changes within the myometrium! decidua!
and uterine cervix that occur gradually over a period of days to weeks
leading to expulsion of products of conception per vaginum.
"rogesterone is found to be essential in establishing and maintaining
pregnancy and inhibiting myometrial contractility #$aralis et al!
%&&'(. In most mammals! at the onset of parturition! a fall in maternal
progesterone is seen along with a rise in oestrogen levels but in
humans fall in the level of maternal progesterone has not been
observed! rather its action is blocked by an endogenous antiprogestin
whose secretion from foetal kidney rises markedly at the end of
pregnancy. In women! concentration of progesterone plateaus while
oestrogen concentration increases prior to onset of labour and results
in increase in oestrogen)progesterone ratio causing a rise in the
prostaglandin production in the uterine tissue #*isra +enu! 2,%4(.
-here is also an increase in the expression of several receptors in the
uterus like oxytocin receptors! prostaglandin receptors! primary gap
unction proteins and prostaglandin endoperoxide / synthetase
#"0/12( which are essential for the initiation of labour. -hey cause
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an increase in the myometrial sensitivity to oxytocin and
prostaglandins #*isra +enu! 2,%4(. xytocin induces myometrial
contractions and via receptors in decidua stimulates prostaglandin
synthesis leading to onset of labour #/usslein "! %&4(. -he cervix is
mainly made up of collagen! a fibrous connective tissue that under
goes extensive remodelling and anatomic and physiologic alterations
throughout pregnancy. -he changes occurs in four stages 5 softening!
ripening! dilatation and postpartum repair #*yers! 2,,&(.
"rostaglandins along with uterine contractions play a role in ripening
of the cervix and leads to cervical dilatation and effacement. -here is
an increase in the local production of prostaglandins seen in the
cervical tissue during late pregnancy and labour which suggests its
effect on cervical ripening #6llwood! %&,(. iochemical connective
tissue changes in the uterine cervix appears to precede uterinecontractions and cervical dilatation #Norwit8! 2,%9( but sometimes
these changes does not occur and labour is not initiated at term or due
to some reason pregnancy needs to be terminated before term. :hen
the uterine contractions are initiated before its spontaneous onset then
it is known as induction of labour.
Induction of Labour
Induction of labour is a procedure where labour is induced artificially
to stimulate uterine contraction and ripening of cervix before its
spontaneous onset! with or without ruptured membranes
#;unningham et al! :illiams bstetrics! 2,%4( with an intention of
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achieving vaginal delivery when labour is not initiated at term or due
to some reason pregnancy needs to be terminated before term. It is
one of the most common procedures being performed in obstetrics. Its
rate in the <nited 1tates has more than doubled from &.9= in %&&% to
23.2= in 2,%% #*artin! 2,%3(. It is indicated when benefits of
delivery to either mother or foetus is more than the risk of continuing
pregnancy #1anche8+amos! 2,,9(. -he various indications of
induction of labour are postdated pregnancy! pregnancyinduced
hypertension! premature rupture of membranes! intrauterine growth
restriction! chorioamnionitis! +hisoimmunisation! oligohydramnios!
abruption placentae! malformed foetus and intrauterine foetal demise
#1anche8+amos! 2,,9(.
/istory of Induction of >abour
/istory of induction of labour goes back to the time of Hippocrates
who described mammary stimulation and mechanical dilation of
cervical canal as a means to induce labour #de +ibes ;! %&(.
?rtificial rupture of membrane was practiced as early as 2nd century
?.@ by Soranus for induction of labour. *anual dilatation of cervix
was first described by Moshion and Bourgeois used strong enemas
and mixtures of several folk medicines for induction and
augmentation of labour #0raham! %&9,(. *echanical methods were
commonly used from the 2nd through the %7th century. In the %th
century in a meeting in >ondon! physicians discussed the use of
artificial rupture of membranes to induce labour. In the beginning of
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%&th century amniotomy and other mechanical methods were the most
commonly used methods for the induction of labour #1anche8+amos
and $aunit8! 2,,&(.
In the beginning of 2,th century! Dale observed that "itocin extracted
from infundibular lobe of pituitary gland causes myometrial
contractions. In %&,& Blair Bell used it as hormonal method for
labour induction. -his method for induction of labour had become
popular among obstetricians. It was used by intramuscular or
subcutaneous routes but due to numerous adverse effects reported like
uterine rupture and maternal deaths! its use declined as it was not
available in pure form. Kurzro and Lieb #%&3,( noted that human
sperm was able to cause uterine contractions. !lf von "uler #%&37(
first isolated a compound from the seminal fluid of monkey! sheep
and goat and he named it prostaglandin believing it to be a secretion
from male prostate gland. +esearch on prostaglandins remained
dormant until after :orld :ar II when work was reinitiated in this
area by scientists in $arolinska institute in 1weden #;ollins! %&&,(.
*eanwhile "age #%&43( suggested that pituitary extract oxytocin may
be given by intravenous route. In %&93! structural formula of oxytocinwas discovered and synthetic oxytocin has been used for induction of
labour since %&99 #1anche8+amos and $aunit8! 2,,&(. 1uccess of
induction depends upon the status of cervix which is measured by
ishop score! a standardi8ed scoring system developed in %&'4 for
assessing the status of cervix before induction. It included cervical
dilatation! effacement! consistency! position of the cervix within the
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pelvis and station of the head in relation to ischial spines. -he original
ishop score was modified by ;alder in %&74 which is known as the
*odified ishop score. In this effacement of the cervix was replaced
by its length in centimetres. -he maximum possible score is %2. -he
total cervical score indicates the probability of spontaneous onset of
labour. -he less the cervical score the lesser are the chances of vaginal
delivery. xytocin alone is not a good choice for inducing labour in
women with a poor ishop score! especially if the score is less than '.
In such cases! a cervical ripening agent is reuired which causes
softening and distensibility of cervix for successfully inducing labour.
#-enore! 2,,3(. In women with unfavourable cervix! prostaglandins
have been shown to be more successful for induction of labour.
-he two prostaglandins commonly used are dinoprostone and
misoprostol. @inoprostone #"062( is available in gel form! which can
be used either by intracervical route #,.9mg( or intravaginal route
#2mg(! and as a %,mg slow release vaginal insert. @inoprostone has
the disadvantage of being costly and reuires refrigeration.
*isoprostol #"06%( is the latest addition to the prostaglandins used in
obstetrics. It is useful in inducing abortion and labour and is also usedas a lifesaving drug in postpartum haemorrhage. -he :/ has
included it in its Alist of essential drugsB in *arch 2,,9. It is very
effective for cervical ripening and induction of labour although it has
not been labelled by the <1C@? for this indication #-enore! 2,,3(
but its offlabel use for induction of labour is endorsed by ?;0 as
well as +;0 #?;0 2,,3 website www.acog.org! +;0 2,,%
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website www.rcog.uk accessed on %')%)%'(. It has several advantages
over dinoprostone as it is cheap! has a longer shelflife and can be
stored at room temperature so it can be used in underdeveloped and
developing countries where supply of electricity is always a problem.
Structure of Prostaglandins
"rostaglandin belongs to bioactive autacoids known as eicosanoids#1erhan and levy! 2,,3(. "rostaglandin 62 was the first eicosanoid
elucidated. -he term prostaglandin was first coined by <lf von 6uler
in %&39 #Don 6uler! %&7(. ergstrom in %&97 elucidated the structure
of prostaglandin 6% and C%E. In the early %&',s! ergstrom et al and
Dan @orp et al independently identified arachidonic acid as a
precursor to prostaglandins by mass spectrophotometry #1erhan and
>evy! 2,,3(. In the late %&',s and early %&7,s ;orey synthesi8ed
prostaglandins for the first time #1erhan and >evy! 2,,3(. >ater
1amuelsson and colleagues #%&'4( discovered the chemical structure
of prostaglandins and its biosynthetic pathways.
"rostaglandins are a 2,carbon fatty acid molecule derived from
dietary fatty acid. It consists of a cyclopentane ring with a fatty acid
moiety attached at 2 adacent carbons #Brien! %&&9(. "rostaglandins
are classified into & groups according to the structure or substitution
of the cyclopentane ring from ? to I.
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"rostaglandins of 6 series consist of a ketone group at ;& position
and hydroxyl group at ;%%. "rostaglandin 6% has a transdouble bond
between ;%3 and ;%4 while prostaglandin 62 has an additional cis
bond at ;9;' position #;ollins! %&9(. "rostaglandin C is a prosta9!
%3dien%oic acid substituted by hydroxy groups at position &! %% and
%9.
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"rostaglandins #"0s( act like hormones. -hey may be autocrine
#acting on same cell( or paracrine #affecting a neighbouring cell( in
action. -hey act by binding to membrane receptors of cells leading to
an increase in cyclic adenosine monophosphate #c?*"( #1usan et al!
2,%3(. -o exert a biological effect "0s must interact with receptors
specific to the type of prostaglandin as determined by its pentane ring!
termed as " receptors. -he "06sensitive receptors are termed as 6"
receptors and "0C2Esensitive receptors are designated C" receptors
#1enior! %&&3(. 6" receptors have been further sub divided into 6"%!
6"2 and 6"3 #1enior! %&&3(. *yometrial samples in term pregnancy
show maximum 6" and C" receptor concentrations at the fundus of
uterus with a decrease in concentration towards the cervix #1enior!
%&&3(. "0C2E has been shown to produce a purely contractile
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response of myometrium. "06 shows a biphasic effect with initial
excitation followed by a doserelated inhibition #1enior! %&&3(.
"rostaglandin 6 seems to play a greater role in the process of
parturition and has a more potent action on uterine activity than
"0C2E #$eirse and -urnbull! %&79( but it is chemically unstable
because of propensity for F/ ketone system in cyclopentane ring
which undergoes elimination of water to form E! Funsaturated ketone
system of "0? #;ollins! %&&,(. In early %&7,s! synthesis of analogues
of "06% was started to improve its pharmacological profile.
*isoprostol is a %9deoxy%'hydroxy%'methyl prostaglandin 6%
analogue and produces its biphasic effect by acting on 6"%6"3
receptors #1enior! %&&3(.
*I1"+1->
Naturally occurring "06% was found to inhibit gastric acid secretion
in %&'7 by Robert et al but it had several disadvantages. It underwent
rapid metabolism and therefore could not be given orally. :hen given
parenterally it had a short duration of action. It was chemically
unstable leading to a short shelflife besides having numerous side
effects like headache! abdominal cramps! diarrhoea! hyperthermia!
hypotension! shivering and uterotonic effects # Bergestrom et al !
%&'9(. Its duration of action was also found to be short. -o overcome
its shortcomings *isoprostol! a synthetic "06% analogue! was
synthesi8ed at 0. @. 1earle G company in %&73. It differs structurally
from natural "06 by a methyl ester at ;% which increases the
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antisecretory potency and duration of action! a methyl group at ;%'
and a hydroxyl group at ;%' #which was originally at ;%9( which
improves its safety profile and helps prolong the duration of action
#-ang and @anielsson! 2,,7(. -his structural change increased the
biological activity of the drug by 39 times by intravenous route and
had improved oral activity. *isoprostol is a viscous oil highly
susceptible to degradation to prostaglandin ? ust like natural "06%.
It was seen that a dispersion of misoprostol on hydroxyl propyl
methyl cellulose #/"*;( is more stable than its pure form.
;onventional tablets are prepared from the dispersion and have a
shelf life of several years at room temperature #;ollins! %&&,(.
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1tructure of misoprostol and naturally occurring prostaglandin 6.
*isoprostol has been found useful in the treatment of both gastric and
duodenal ulcers and its efficacy in preventing and treating
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nonsteroidal antiinflammatory drugs #N1?I@s( induced
gastrointestinal ulcer has been proven. It is the first drug found
effective in N1?I@induced gastropathy and is approved by the <1
C@? for this purpose. #;ollins! %&&,(. It has been marketed in <1?
since %& #1anche8+amos! 2,,9(. It was also found to have
uterotonic activity which could not be eliminated and was used for
first trimester abortion #/erting and Nissen! %&'(. *arianiNeto et al
#%&'( used this property for induction of labour in still birth #+ev.
paul. *ed! %&7( and *arguiles et al used it for induction of labour in
live fetus in %&&2. ?lthough it has not been approved by <1C@? but
now it is being used in obstetrics and gynaecology for induction of
labour! cervical ripening before hysteroscopy and in the management
of postpartum haemorrhage #?llen! 2,,&(.
"harmacokinetics of misoprostol
*isoprostol is currently being administered through various routes
orally! vaginally! sublingually! buccal and rectal. "harmacokinetic
profiles of the various routes of administration of misoprostol have
been studied taking the following parameters into consideration the
peak concentration of drug attained in plasma #;max(! the time taken
to reach the peak concentration #-max( and the area under the serum
concentration versus time curve #?<;(.
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CigH Mean plasma concentrations of misoprostol acid
over time by various routes.
*isoprostol! after its oral administration is rapidly absorbed and
converted by deesterification to *isoprostol ?cid which is its
primary active metabolite. -his metabolite possesses significant
properties of the original drug. #1choenhard! %&9(. It is further
metabolised over time by Foxidation of the Eside chain! oxidation
of the Fside chain and by reduction to prostaglandin C analogues
#1choenhard! %&9(. -he plasma protein binding of *isoprostol ?cid
#*"?( is approximately 9= and is independent of age! drug
concentration or any other drug commonly coadministered with it!
except for salicylic acid #;ollins! %&&,(.
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CigH *etabolism of *isoprostol
Collowing a meal #high fat diet( rate of absorption of the drug #;max(
was significantly reduced. -he plasma elimination halflife of *"? in
humans is about 2, minutes #$arim! %&7(. It was excreted twice the
amount in urine as compared to faeces #;ollins! %&&,(. -ang et al
#2,,2( found that after a single dose of 4,,Jg oral misoprostol! the
plasma peak concentration is attained in about 3, minutes. It rapidly
declines in %2, minutes and remains low thereafter #-ang and
0em8ell@anielsson! 2,,7(.
Daginal route was found more effective in studies as compared to oral
route. Kieman et al #%&&7( found that on vaginal administration!
plasma concentration of *"? increases gradually reaching its peak
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concentration after 7,, minutes before slowly declining. @etectable
drug levels are still present in plasma even after ' hours. 1ystemic
bioavailability of the drug was three times greater by vaginal route as
compared to oral route #Kieman et al! %&&7( but absorption of the drug
vaginally is inconsistent as seen by the greater coefficient of variation
of the area under curve #?<;(. ? direct effect on the uterus and
cervix may possibly explain the higher efficacy of this route
#@anielsson et al! %&&&(.
In the buccal route of drug administration the tablet is placed between
the teeth and the cheek. -he absorption curve for the buccal and
vaginal route are similar and the time taken to attain maximum
concentration is also similar but the peak plasma concentration levels
of the buccal route are lower #*eckstroth et al! 2,,'(.
?nother route by which misoprostol can be administered is the
sublingual route. -he tablet is placed under the tongue and it dissolves
within 2, minutes. -ang et al #2,,2( found that after administration of
4,, Jg misoprostol! sublingual route had the shortest time to peak
concentration #3, minutes(! the highest peak concentration and the
greatest bioavailability as compared to other routes. -he area under
curve of misoprostol is four times greater with the sublingual as
compared to the buccal route #1chaff et al! 2,,4(. -his is probably
due to the abundant blood supply under the tongue as well as
bypassing firstpass metabolism through the liver. -he greater ?<;
and the peak concentration attained in plasma may be the reason for
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the higher freuency of adverse effects reported with sublingual route
#1chaff et al! 2,,4(.
+ectal route of administration is mainly used in the management of
postpartum haemorrhage. -he time taken to achieve peak plasma
concentration is 2, minutes but the area under the curve is ust one
third of the vaginal route #-ang et al! 2,,7(.
6ffects of misoprostol on the uterus
-he initial effect of misoprostol on uterine contractility is an increase
in uterine tone irrespective of the dose and route of administration
#?ronsson et al! 2,,4(. -his effect was seen to start earlier and was
more pronounced when misoprostol was given orally #7.L3 minutes(
as compared to the vaginal route #2,.&L9.3( #@anielsson et al! %&&&(.
?lthough the initial rise in uterine tone was delayed after vaginal
administration of misoprostol! regular uterine contractions were
established after % to 2 hours which increased gradually and lasted
even up to 4 hours #@anielsson et al! %&&&(. *eckestroth et al #2,,'(
found that uterine activity was similar with both vaginal and buccal
routes of administration of misoprostol even though serum levels of
misoprostol were much higher with vaginal route. +ectal route was
seen to have the lowest uterine contractility as well as delayed onset
of action.
?ronsson et al #2,,4( compared its effect on uterine contractility
when administered sublingually with oral and vaginal routes. -hey
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observed that the sublingual route had the advantage of rapidly
increasing the uterine tone and with intensity comparable to oral
route. 1imilar to the vaginal route! regular uterine contractions were
established %2 hours after sublingual administration but it was seen
to last for 3 hours only as compared to 4 hours with vaginal route.
1o it can be concluded that regular uterine contractions are established
irrespective of the route of administration. If administered
sublingually! its action starts earlier than other routes but lasts only for
3 hours #-ang et al! 2,,7(.
6ffects of misoprostol on cervix
-he cervix is mainly made up of connective tissue. ;ervical ripening
reuires a decrease in total collagen content with an increase in
collagenolytic activity. -he extracellular ground substance of the
cervix is degraded by an influx of inflammatory cells in the stroma
which produce cytokines and prostaglandins and leads to degradation
of collagen and conseuent cervical softening #?ronsson et al! 2,,4(.
"l#efaey et al #%&&4( studied the effect of prostaglandin analogues!
misoprostol and gemeprost! on cervical priming before surgically
induced abortion and noted that both caused disintegration and
dissolution of collagen in the connective tissue stroma leading to
cervical dilatation before evacuation but misoprostol was preferred
due to less side effects. $gai et al #%&&9( found oral misoprostol
effective in cervical dilatation before vaccum aspiration in first
trimester abortions. -he mean cervical dilatation was significantly
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greater in the misoprostol group as compared to placebo treated group
in both nulliparous as well as multiparous females. Danielsson et al
#%&&&( noted that all the patients between %% weeks of pregnancy
enrolled in their study who had received misoprostol either orally or
vaginally had a dilated cervical canal. %ronsson et al #2,,4( noted
that irrespective of the route and dosage when misoprostol was
administered prior to vaccum aspiration in first trimester of pregnancy
all patients had a dilated cervical canal. ?ll these studies prove the
efficacy of misoprostol in cervical priming. Now misoprostol is being
widely used for its ripening effect on cervix before induction of
labour and vaccum aspiration in early pregnancy.
1ide 6ffects of *isoprostol
*isoprostol is a safe and well tolerated drug with a safety margin of
at least 9,,%,,, fold between lethal dose in animals and therapeutic
dose in human beings #$otsonis et al! %&9(. No clinically significant
adverse effect affecting any of the organ systems has been reported as
yet with the use of misoprostol #-ang and 0em8ell@anielsson! 2,,7(
*isoprostol has the following side effects at therapeutic dosageH
&astrointestinal side effects'
>umbiganon et al #2,,2( studied the side effects of ',,Jg of oral
misoprostol during first 24 hours when used in the management of
third stage of labour. -hey reported that in 9= of the women
diarrhoea started one hour after delivery and peaked between 2'
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hours. Its incidence declined thereafter to ,.%= between %&24 hours
following ingestion of the drug. -hey have also observed mild nausea
and vomiting after its use but have not mentioned the incidence.
1chaff et al #2,,4( found that 4,= users had mild nausea! 2,= had
diarrhea and 9,= experienced abdominal cramps following
sublingual administration of ,,Jg misoprostol.
*eckestroth et al #2,,'( observed that after administration of 4,,Jg
misoprostol irrespective of route! 3= of the participants experienced
abdominal pain and %2.9= women had nausea out of which 9=
vomited.
-ang G 0em8ell@anielsson #2,,7( in their review article on
misoprostol have stated diarrhoea as a consistent maor adverse
reaction which is usually mild and selflimiting.
6lati G :eeks #2,,&( in their review article on use of misoprostol in
obstetrics G gynaecology for different indications like first and
second trimester termination of pregnancy! missed abortion!
intrauterine foetal death! induction of labour! management of
postpartum haemorrhage! before any transcervical procedures! with
dosage ranging from 2,',,Jg have stated that nausea! vomiting and
diarrhoea are common adverse reaction of misoprostol intake
affecting about 39= of women. -he gastrointestinal side effects are
more common after oral or sublingual administration. @iarrhoea is the
commonest side effect but usually mild and selflimiting within a day.
Domiting usually resolves within ' hours of delivery. ?bdominal
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cramps may start within ten minutes of administration of misoprostol
and continue for a few hours. N1?I@1 can be given for pain relief.
(ever and shivering are commonly associated with the use of
misoprostol but are transient and can be controlled with the use of
antipyretics and physical cooling. >umbiganon et al #%&&&( studied
the doserelated side effect of misoprostol versus oxytocin in the
management of third stage of labour. oth shivering and pyrexia
#-emperatureM 3( were found more commonly in ',,Jg
misoprostol group as compared to 4,,Jg misoprostol and oxytocin
group #2= and 7.9=! respectively(.
>umbiganon et al #2,,2( studied the effects of ',,Jg oral
misoprostol in the management of third stage of labour and observed
that incidence of shivering peaked within one hour of delivery which
was %3.'= as compared to 2.%= in the oxytocin group. It then
gradually subsided within 2' hours. "yrexia peaked at 2' hours after
delivery with an incidence of %%.3= in the misoprostol group as
compared to %.= in the oxytocin group.
-ang and 0em8ell@anielsson #2,,7( in their review article of
different studies conducted by others #/o et al! 2,,9O :alraven et al!
2,,9O @erman et al! 2,,'( on the use of oral or sublingual misoprostol
for the management of third stage of labour or for postpartum
haemorrhage have reported chills in 3297= women! hyperpyrexia
#-emperatureM4,;( with the use of ',,Jg misoprostol and
hyperpyrexia with delirium when ,,Jg misoprostol was used.
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6lati G :eeks #2,,&( in their review article stated that transient chills
and fever are common side effects of misoprostol. /yperpyrexia
#-emperatureM4,( are usually seen to be associated with higher dose
#,,Jg(! freuent intervals and oral or sublingual route of
administration of misoprostol.
!terine Hypersti)ulation
<terine hyperstimulation syndrome is diagnosed when tachysystole #'
or more uterine contractions in %, minutes( or hypertonus #single
contraction lasting over a 2 minute period( occurs along with foetal
heart rate changes. :eeks et al #2,,7( in their review article of
misoprostol for induction of labour with a live foetus have found that
incidence of uterine hypercontractility is high with misoprostol as
compared with oxytocin but serious sideeffects are primarily seen
with too high doses or where wrong dosage freuency has been used.
:hen misoprostol is used in low doses! 29Jg vaginal misoprostol 4
hourly! 9,Jg oral misoprostol 4 hourly or 2,Jg oral misoprostol
solution 2 hourly it is as safe and effective! with no excessive uterine
stimulation! as vaginal dinoprostone.
6lati G :eeks #2,,&( in their review article on use of misoprostol in
obstetrics and gynaecology too have stated that hyperstimulation may
occur from the use of excessive or repeated doses of misoprostol and
incidence of hyperstimulation is similar to dinoprostone gel when
used in lower doses like 29Jg vaginal or 2,Jg oral misoprostol
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solution. *etaanalysis of oral misoprostol shows higher rates of
hyperstimulation with high doses. /yperstimulation is not seen with
lower doses. 9,Jg misoprostol or less by oral route have same
efficacy and rate of hyperstimulation as vaginal dinoprostone.
!terine #upture
-he risk of uterine rupture in vaginal birth after previous caesarean
delivery is reported between '%2= #:ing et al! %&&( #"laut et al!
%&&&(. <terine rupture has been reported after induction of labour
with misoprostol especially in women with a previous uterine scar
#-ang G 0em8ell@anielsson! 2,,7(. -herefore! it is not
recommended to administer it in cases with a previous uterine scar
#6lati G :eeks! 2,,&(.
Meconiu) staining of li*uor
/ofmeyr et al #%&&&( have concluded in their review article on the use
of misoprostol for induction of labour! in which 3% trials of vaginal
misoprostol and 9 trials of oral misoprostol were analysed! that
incidence of meconium stained liuor was increased when
misoprostol was used for induction of labour in third trimester as
compared to dinoprostone gel #++ %.3! &9= ;I %.,'%.7&(. -hey
also reported that incidence of meconium stained liuor was same
when 29Jg misoprostol was given 3 hourly or ' hourly. -he ;ochrane
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review #2,,3( have reported increased incidence of meconium stained
liuor at doses more than 29Jg of misoprostol. :eeks et al #2,,7( in
their review article have also stated that incidence of meconium
stained liuor is significantly more with the use of misoprostol as
compared to other prostaglandins. *econium passage may occur in
response to uterine hyperstimulation or as a direct effect of absorbed
misoprostol metabolites on the foetal gastrointestinal system.
Maternal and perinatal outco)es
"rostaglandins are now being extensively used for induction of labour
at term and they have the advantage of causing both cervical ripening
and uterine contractions as opposed to oxytocin which is effective in
women with a favourable bishop score. xytocin has been found to
be safe for this purpose and several trials are being conducted to
prove the efficacy and safety of prostaglandins on the perinatal
outcomes #*acer et al! %&4(
1anche8+amos et al #%&&3( conducted a randomised trial to compare
the safety and efficacy of 9,Jg intravaginal misoprostol with
intravenous oxytocin for induction of labour at term. "rior cervical
ripening was done with prostaglandin 62 gel in the women #49=(
given oxytocin! if reuired. <terine tachysystole was seen to occur
more commonly in the misoprostol group than in the oxytocin group
#34.4=! p ,.,9( but no other significant differences were observed in˂
the perinatal outcomes including uterine hyperstimulation syndromes!
rate of caesarean section or maternal and neonatal adverse effects.
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Induction to delivery interval was significantly shorter in the
misoprostol group #pP,.,,4(. It was therefore concluded that
intravaginal misoprostol is a safe and effective alternative for
induction of labour at term while minimi8ing the expenses associated
with intravenous oxytocin use.
/ofmeyer et al #%&&&( in their review article studied the effectiveness
and safety of misoprostol for cervical ripening and labour induction at
term. -hey analysed several clinical trials on misoprostol
administered orally and vaginally in various dosages and in
comparison with oxytocin and dinoprostone. In the trials comparing
misoprostol with oxytocin infusion! no differences in the maternal and
neonatal outcomes were observed. -he rate of caesarean section was
inconsistent varying from significant reduction in rates in misoprostol
group to no significant difference. In another trial comparing vaginal
misoprostol with dinoprostone gel! it was observed that although the
rate of vaginal deliveries was more and oxytocin augmentation
reuirement was less in the misoprostol group! uterine
hyperstimulation with and without foetal heart rate changes and
meconium staining of liuor was more freuently observed withmisoprostol. ;aesarean rate was overall similar and there were no
significant differences in the perinatal or maternal outcomes. In a trial
comparing lower dosage regimen of 29Jg misoprostol given 3 hourly
versus ' hourly! there were no differences in mode of delivery!
meconium stained liuor or maternal or perinatal effects.
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Keba *un8ar #2,%9( conducted a randomised controlled trial to
compare the safety and efficacy of oral misoprostol #%,,Jg given 4
hourly( with prostaglandin 62 vaginal tablet #3mg(. *ore than one
fourth #2=( women in the misoprostol group ended up with
caesarean section out of which = were done for foetal distress.
*econium staining of liuor was seen in %,= women and 4= had
uterine hyperstimulation but these were not statistically significant.
Neonatal outcomes were also similar in both the groups. It was
therefore concluded that misoprostol is as efficacious as prostaglandin
62 with similar maternal and neonatal outcomes and is a much
cheaper alternative to prostaglandin 62.
?8ubuike et al #2,%9( compared the safety and effectiveness of 29Jg
misoprostol versus 9,Jg misoprostol both given vaginally for
induction of labour at term. -hey concluded that there were no
significant differences between the two groups as far as
hyperstimulation syndromes and other maternal and neonatal
outcomes were observed.