Comparison of two misoprostol regimens for cervical priming before surgical pregnancy termination at 13 to 16 weeks gestations

doi:10.4236/ojog.2011.14036

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Open Journal of Obstetrics and Gynecology, 2011, 1, 187-190

doi:10.4236/ojog.2011.14036 Published Online December 2011 (http://www.SciRP.org/journal/ojog/ OJOG

Published Online December 2011 in SciRes. http://www.scirp.org/journal/OJOG

Comparison of two misoprostol regimens for cervical

priming before surgical pregnancy termination at

13 to 16 weeks gestations

Dennis G. Chambers, Robin J. Willcourt, Anthony R. Laver, Jane K. Baird, Wye Y. Herbert

The Queen Elizabeth Hospital Pregnancy Advisory Centre, Woodville Park, Adelaide, Australia.

Email: [email protected]

Received 14 October 2011; revised 19 November 2011; accepted 4 December 2011.

ABSTRACT

Background: The optimal regimen has still to be de-

termined for the use of misoprostol in the surgical

termination of pregnancy in the early second trimes-

ter. Objective: To compare the outcomes of two diffe-

rent regimens for cervical priming with misoprostol

before dilatation and evacuation (D & E) in 13 weeks

- 16 weeks gestation pregnancy terminations. Methods:

A retrospective analysis was performed of the medi-

cal records of two cohorts of 334 women each who

were treated with either 3 sublingual doses of 2 mi-

soprostol 200 µg tablets 30 minutes apart on admis-

sion or the same dosage preceded by 1 oral tablet of

misoprostol 200 µg at home 3 hours before admission.

Results: The addition of the home tablet of misopros-

tol increased the rate of one day completion of D & E

from 97.3% to 100% (P = 0.004), and the overall

mean theatre time for D&E was reduced by 12.3% in

parous women (P = 0.001) and 6.4% in nulliparous

women (P = 0.003) with the reduction being consis-

tent across all gestations. Conclusions: This retrospe-

ctive study showed that the addition of 1 oral tablet

of misoprostol 200 µg at home 3 hours before admis-

sion to a regimen of 3 sublingual doses of 2 misopro-

stol 200 µg tablets 30 minutes apart on admission sig-

nificantly increases the probability of all women at 13

weeks - 16 weeks gestation completing a termination

of pregnancy in one day with a single D & E proce-

dure and with a reduced theatre time.

Keywords: Early Second-Trimester Surgical Abortion;

D & E; Misoprostol; Cervical Priming

1. INTRODUCTION

The Pregnancy Advisory Centre (PAC) is a government

funded day-surgery clinic providing over 2500 surgical

and medical terminations of pregnancy (TOP) each year

in South Australia. Second trimester surgical termination

of pregnancies up to 22 weeks gestation have been per-

formed in this clinic using misoprostol and osmotic cer-

vical dilators where necessary since 1994. The incidence

of these terminations has remained constant over this pe-

riod with approximately 9% of all terminations occur-

ring at 13 weeks - 16 weeks gestation, an incidence in line

with published figures overseas [1]. Although most wo-

men in our clinic at 13 weeks - 16 weeks gestation have

been terminated in one day after cervical priming with 3

sublingual doses of 2 misoprostol 200 µg tablets 30 minu-

tes apart, with dilatation and evacuation (D & E) 3 hours

after the last dose, we have found that approximately 3%

of women could not be adequately cervically dilated in

one day with this regimen because they were very poor

responders to misoprostol. Therefore in December 2009

the clinic introduced the add ition to this reg imen of a sin-

gle oral tablet of misoprostol 200 µg taken at home 3

hours before admission. Oral administration was chosen

to avoid distressing cramping, bleeding and nausea that

occur more frequently following sublingual administra-

tion [2]. Because there is little published data on the out-

comes of different cervical priming regimens before D &

E at 13 weeks - 16 weeks we decided to research the out-

comes in our clinic of the two misoprostol regimens.

2. MATERIALS AND METHODS

The study design was a retrospective review of the clini-

cal records of two cohorts of consecutive cases of wo-

men undergoing surgical termination of pregnancy at 13

to 16 weeks gestation. This clinical audit study confor-

med to the standards required for Australian National

Health and Medical Research Council exclusion for eth-

ics approval. The first cohort of 334 women was treated

with 3 sublingual doses of 2 misoprostol 200 µg tablets

administered 30 minutes apart on admission. The second

cohort of 334 women was treated with the same dosage

after admission preceded by 1 oral tablet of misoprostol

D. G Chambers et al. / Open Journal of Obstetrics and Gynecology 1 (2011) 187-190

188

200 µg at home 3 hours before admission. The dosage

after admission of 6 misoprostol tablets to taling 1200 µg

is the dosage we h ave used for approximately the last 1 0

years. This is the optimal dosage that we have found

achieves adequate cervical priming pr ior to D & E with-

out adverse effects; it was determined by incremental in-

creases over several years of study [3].

In both cohorts three hours after the last dose of mi-

soprostol the woman was taken to theatre for D & E. All

D & E procedures at our clinic are performed under in-

travenous propofol anesthesia with the addition of an

intracervical block of lignocaine local anesthetic with

adrenaline. The cervix is dilated with rigid Hawkin-Am-

bler dilators to a dilatation equal to the number of gesta-

tional weeks in millimeters (mm). When the cervical di-

latation and softening th e miso pro sto l primi ng of th e cer-

vix has achieved is ad equate the range of rigid dilatation

required is 0 mm - 3 mm and force is never used. A pre-

vious study from this clinic has demonstrated a connec-

tion between forceful dilatation and perforation of the

uterus [4]. If the target dilatation of the weeks gestation

in mm cannot be achieved without force further cervical

priming with osmotic dilators and misoprostol is used.

Routine intra-operative ultrasound guidance is used al-

lowing the operator to see instruments in the uterus and

direct them to the fetal parts safely.

After the use of the additional home tablet of miso-

prostol in 334 early second trimester women we decided

to audit our results, and this number decided the size of

the cohorts. Medical records were examined and data

was collected relating to parity, gestation, the number of

procedures, the number of days of treatment, the theatre

time for each woman at D & E, and complications in

each cohort. The theatre times were used rather than o-

peration times as these was collected with more exact

precision, the time of en try into and exit from the opera-

ting theatre being collected and recorded separately by

both the anesthetist and theatre nurse with cross check-

ing; the time of entry was the time at which the woman

was wheeled into the operating theatre from the anes-

thetic room, and the exit time was the time she was

wheeled out of the theatre into the recovery room. Trans-

fer times onto and off the operating table were the same

for all women and as all instruments used were in pre-

packed and presterilized bundles there were no steriliza-

tion delays. We also surveyed the incidence of side ef-

fects experienced by the 334 women taking misoprostol

200 µg at home 3 hours before admission. On admission

these women completed a questionnaire in which they

self assessed the severity—mild, moderate, or severe—

of any side effects of cramps, bleeding, nausea or diar-

rhea. All the procedures analyzed were carried out by the

same operators who had many years experience. The

statistical analysis was performed using Fisher’s exact

test.

3. RESULTS

In the cohort without home misoprosto l there was 1 wo-

man at 13 weeks, 1 wo man at 14 weeks and 7 women at

16 weeks gestation who could not be completed in a sin-

gle stage procedure; inadequate cervical priming at this

procedure necessitated further cervical priming and D &

E the next day. In the cohort with a home dose of miso-

prostol added all women were completed in a one stage

D & E procedure. The addition of the home tablet of mi-

soprostol increased the rate of one day completion of D

& E from 97.3% to 100% (P = 0.004). The theatre times

in each cohort for nulliparous women, with a break down

by weeks gestation, are shown in Table 1, and the times

for parous women with a similar breakdown are shown

in Table 2. The overall mean theatre time for D & E was

reduced by 12.3% in parous women (P = 0.001) and

6.4% in nulliparous women (P = 0.003) with the reduc-

tion being consistent across all gestations and parities.

Table 1. Nulliparous women D & E mean theatre times 13 weeks - 16 weeks gestations with and without home misoprostol priming;

n = number at each gestation.

MMean time 13 weeks gestation 14 weeks gestation15 weeks gestation16 weeks gestation Overall mean time

No home misoprostol 13.2 minute s n = 5 9 16.1 minutes n=65 16.7 minutes n = 4519.4 minutes n = 17 15.6 minute s n = 1 86

WWith home misoprostol 13.1 minutes n = 6 6 14.6 minutes n=57 16.3 minutes n = 2616.5 minutes n = 26 14.6 minutes n = 1 7 5

Table 2. Parous women D & E mean theatre times 13 weeks - 16 weeks gestations with and without home misoprostol priming; n =

number at each gestation.

Mean time 13 weeks gestation 14 weeks gestation15 weeks gestation16 weeks gestati on Overall mean time

No home misoprostol 14.9 minutes n=50 15.1 minutes n=56 16.5 minutes n=36 16.8 minutes n=6 15.5 minutes

n=148

With home msoprostol 12.4 minutes n=53 14.1 minutes n=51 14.5 minutes n=35 14.1 minutes n=20 13.6 minutes n=159

D. G Chambers et al. / Open Journal of Obstetrics and Gynecology 1 (2011) 187-190 189

Figure 1. Percentage of women with side effects from one oral

tablet of misoprostol 200 µg taken at home 3 hours before

admission.

The incidence of side effects in 1000 women taking

misoprostol 200µg at home is shown in Figure 1. The

only significant side effect was mild cramping in 52.2%

of women; mild nausea was reported in 28.3% of women,

but this was difficult to separate from pregnancy morn-

ing sickness. None of the side effects of the home dose

of oral misoprostol 200 µg were severe enough to re-

quire treatment.

There was one cervical laceration requiring suture at

16 weeks gestation in the cohort without home misopro-

stol; there was no other uterine trauma, hemorrhage, in-

fection or other serious complication occurring in either

cohort. This gave complication rates of 0.3% for the no

home misoprostol and 0.0% for the home misoprostol co-

horts. The demographic makeup of both cohorts was si-

milar including maternal age, parity, and gestational age.

4. DISCUSSION

Every year at the PAC clinic in Adelaide, Australia ap-

proximately 9% of the women seeking termination of

pregnancy are in th e 13 to 16 weeks g estation rang e; this

corresponds with published incidence data from overseas

[1]. This early second trimester group provides different

challenges to the late second trimester 17 weeks and o-

ver gestation group which in the main cannot be safely

terminated with misoprostol cervical priming alone, the

addition of osmotic cervical dilators usually being re-

quired to ensure safe D & E [5]. In a previous study

from this clinic inadequate cervical priming has been

determined as increasing the risk of uterine perforation

during second trimester D & E [4]. The misoprostol do-

sage recommended in the curren t literature is 400 µg va-

ginally or buccally for cervical priming at 12 to 16 weeks

gestation [6]. This is be low the dosage level that we have

found to be optimally effective and safe, namely 6 to 7

tablets of misoprostol 200 µg, a total of 1.200 to 1.400

µg. With this higher dosage we have never experienced

any serious adverse effects; in particular, despite 20% -

25% of our parous women having a Caesarean scar, we

have never seen a uterine rupture in 10 years of this usa-

ge. We attribute this to never exceeding a misoprostol

dose of 400 µg in an y 30 minute period , and never using

the vaginal route of administration for cervical priming.

Our retrospective study co mpared two misoprostol do-

sages in two cohorts of women undergoing D & E termi-

nation of preg nanc y at 13 to 16 weeks, an d demonstr ated

that the larger dosage, when commenced at home 3 hours

before admission, enabled all cases to be completed in

one day with no serious complications, the success rate

rising from 97.3% to 100% (P = 0.004). The addition of

the home dose also reduced the overall average theatre

time for D&E by 12.3% in parous women (P = 0.001)

and 6.4% in nulliparou s women (P = 0.003), with the re-

duction being consistent across all gestations and p arities.

This reduction in theatre and operation times reflects th e

consistent greater ease in performing the D & E proce-

dures due to better cervical priming with the home dose

of misoprostol. The improved cervical priming also led

to a decreased need for the use of rigid cervical dilators

and abolished the need to ever use force with rigid dila-

tors, thus reducing the risk of cervical trauma.

A Cochrane review in 2008 concluded that cervical

preparation with osmotic dilators and/or misoprostol be-

fore second-trimester D & E is safe and effective [7].

Cervical preparation with osmotic dilators is an alterna-

tive to misoprostol but has the disad vantage of requiring

another procedural stage, and there is often a delay over-

night before the cervix is sufficiently primed to ensure

that the D & E can be performed safely. A third alterna-

tive for cervical priming is the administration of mi-

fepristone 200 mg, but this has the disadvantage of high-

er cost as well as more clinic visits by the patient; also

another effect of mifepristone is the possibility of expul-

sion of the fetus before D & E, with the consequent risk

to the woman’s health, as this expulsion may occur at

any time and place [8]. A Cochrane Review in 2010 con-

cluded that mifepristone is associated with high rates of

pre-procedural expulsions and does not appear to be a

useful method of cervical preparation before second-tri-

mester dilation and evacuation [9].

There were no serious complications in either of the

two cohorts we have surveyed undergoing D & E at 13

weeks - 16 weeks; there were 9 women in the cohort that

did not receive a misoprostol dose at home who needed

an additional 24 hours of cervical priming with osmotic

dilators to adequately prep are the cervix for safe D & E.

D. G Chambers et al. / Open Journal of Obstetrics and Gynecology 1 (2011) 187-190

190

All women receiving a home dose of misoprostol 3 hours

before admission had their D & E completed in one day

in a single stage procedure without any complications.

Nucatola et al. have reviewed complication rates for

misoprostol primed D & E at 12 weeks - 16 weeks, and

for their series they recorded a perforation rate of

0.045% which they determined was in line with rates

previously repo rted in the literature [10].

The same doctors performed all the operations in both

cohorts and all operators were very experienced at the

beginning of the study period and unlikely to have gain-

ed any relevant increase in experience by its end.

A limitation of the study was the use of theatre times

rather than operation times. Reliable operation times we-

re not available as, this being a retrospective study, ope-

ration times had not been recorded with the same accu-

racy as would occur in a prospective study; accurate

theatre times were available as our clinic has a protocol

in place for precision in the recording of theatre times.

We believe the consistency of difference of the theatre

times between the two cohorts indicates that they do re-

liably reflect operation times. It is our opinion that it

would have been unethical to conduct a prospective dou-

ble blind study as we already had firm evidence from our

first trimester study of home misoprostol dosage of the

significant benefits of this regime [3].

This retrospective study demonstrates that the addition

of one oral tablet of misoprostol 200 µg at home 3 hours

before admission to a regimen of 2 tablets 1/2 hourly for

three doses on admission enables 100% of women at 13

weeks - 16 weeks gestation to complete a termination of

pregnancy 3 hours after the last dose of misoprostol, in one

day, with a single D & E procedure, in a shorter time, and

with minimal complications. This certainty of outcome is

of help in the planning and scheduling of operation lists

5. ACKNOWLEDGEMENTS

We are grateful to Dr John Field, Statistician, Faculty of Health Sci-

ences, University of Adelaide for statistical analysis. No author has any

conflict of interest.

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