Uterine Rupture in Second-Trimester
Misoprostol-Induced Abortion After
Cesarean Delivery
A Systematic Review
Vinita Goyal, MD
OBJECTIVE: To determine the risk of uterine rupture
when using misoprostol for second-trimester abortion in
women with a history of cesarean delivery.
DATA SOURCES: MEDLINE, EMBASE, CINAHL, LILACS,
and the Cochrane Library were searched systematically
for all articles published before September 2008.
METHODS OF STUDY SELECTION: Sixty-three articles
were found using the above data sources. I excluded case
reports, narrative reviews or commentaries, studies that
excluded women with a history of cesarean delivery,
studies with unrelated outcomes, studies not conducted
in humans, and studies that were not available in English.
The remaining 16 studies that described misoprostol use
for second-trimester abortion in women with a history of
cesarean delivery were examined.
TABULATION, INTEGRATION, AND RESULTS: The number
of participants with and without cesarean delivery, regi-
men of medical abortion used, and cases of uterine
rupture were reviewed. To estimate the risk of uterine
rupture in women with prior cesarean delivery undergo-
ing second-trimester abortion with misoprostol and
number needed to harm, I pooled the results of all 16
studies. The risk of uterine rupture in women with prior
cesarean delivery was 0.28% (95% confidence interval
[CI] 0.08 1.00%). The risk of uterine rupture in women
without prior cesarean delivery was 0.04% (95% CI
0.01 0.20%). Based on these risks, if 414 women with a
history of cesarean delivery were given misoprostol for
From the Department of Obstetrics and Gynecology, University of North
Carolina School of Medicine, Chapel Hill, North Carolina.
Corresponding author: Vinita Goyal, MD, Department of Obstetrics and
Gynecology, CB #7570, UNC School of Medicine, Chapel Hill, NC 27599-
7570; e-mail: vgoyal@email.unc.edu.
Financial Disclosure
The author did not report any potential conflicts of interest.
2009 by The American College of Obstetricians and Gynecologists. Published
by Lippincott Williams & Wilkins.
ISSN: 0029-7844/09
VOL. 113, NO. 5, MAY 2009
second-trimester abortion, one would experience uter-
ine rupture.
CONCLUSION: The risk of uterine rupture among
women with a prior cesarean delivery undergoing sec-
ond-trimester abortion using misoprostol is less than
0.3%. This may be acceptable to both patients and
providers.
(Obstet Gynecol 2009;113:111723)
T
he risk of uterine rupture is increased with the use
of prostaglandins for labor induction at term in
women with uterine scars compared with women
without this history.1 Misoprostol has been of special
concern in this setting.2,3 Hence, the American Col-
lege of Obstetricians and Gynecologists suggests, mi-
soprostol use in women with prior cesarean birth
should be avoided because of the possibility of uterine
rupture.4
In addition to labor induction at term, misopros-
tol also is used for labor-induction abortion in the
second trimester. Although fewer than 5% of second-
trimester abortions in the United States involve labor
induction, one quarter of second-trimester abortions
in England and nearly all second-trimester abortions
in Sweden and Finland are performed medically.5
Labor-induction abortion is appropriate for practitio-
ners who lack sufficient skill in performing dilation
and evacuation.6 The use of misoprostol is favored in
the developing world owing to its low cost and
stability at room temperature.
Use of misoprostol for second-trimester abortion
has increased, yet the risk of uterine rupture in
women with scarred uteri is unknown. The American
College of Obstetricians and Gynecologists also
warns, misoprostol use for second-trimester preg-
nancy termination also has been associated with
uterine rupture.4 No randomized trials have com-
OBSTETRICS & GYNECOLOGY 1117
pared rates of uterine rupture in women with and
without a history of cesarean delivery undergoing
second-trimester abortion with misoprostol. How-
ever, numerous observational studies have reported
uterine rupture in this situation. The aim of this
systematic review is to determine the likelihood of
uterine rupture when using misoprostol for second-
trimester abortion in women with a prior cesarean
delivery.
SOURCES
I conducted a literature search of all articles evaluating
misoprostol for second-trimester abortion in women
with a prior cesarean delivery that were published
before September 2008. MEDLINE (1966 2008), EM-
BASE (1974 2008), CINAHL (19812008), LILACS
(19822008), and the Cochrane Library (Issue 3, 2008)
were searched systematically. I used the following
search terms: abortion OR abortion, induced OR
abortion AND induced OR induced abortion AND
cesarean OR scarred uterus AND misoprostol
OR Cytotec AND second trimester OR pregnancy
trimester, second OR pregnancy AND trimester
AND second OR 2nd trimester.
STUDY SELECTION
All articles retrieved from the above search were
reviewed. Reasons for exclusion from this systematic
review included: case reports, narrative reviews or
commentaries, studies that excluded women with a
history of cesarean delivery, studies with unrelated
outcomes (eg, the primary outcome was limited to
side effects of misoprostol use, pain management,
subsequent pregnancy outcome), studies not con-
ducted in humans, and studies that were not available
in English. I examined all studies that described
misoprostol use for second-trimester abortion in
women with a history of cesarean delivery.
I reviewed the number of participants with and
without cesarean delivery, regimen of medical abor-
tion used, and cases of uterine rupture. The outcome
assessed was frequency of uterine rupture in women
with and without prior cesarean delivery. Uterine
rupture is defined as separation of all layers of the
uterus, resulting in hemorrhage or significant mater-
nal morbidity. This outcome is distinct from uterine
dehiscence, in which the uterine serosa is intact and
the potential for serious morbidity is absent.7
The Meta-analysis of Observational Studies in
Epidemiology guidelines were followed in reporting
the results of this systematic review.8
1118 Goyal Uterine Rupture in Second-Trimester Abortion
RESULTS
Using the above search strategy, I retrieved 25 articles
from MEDLINE, 29 from EMBASE, three from
CINAHL, four from the Cochrane Library, and two
from LILACS. Using the exclusion criteria detailed
above and excluding articles that were cited in mul-
tiple databases, 16 studies were reviewed (Fig. 1).
Eleven of the 16 studies included women with
and without history of cesarean delivery. The remain-
ing articles reported only on those patients with a
history of cesarean delivery. All studies were obser-
vational trials; no randomized trials were found.
To determine the risk of uterine rupture in
women with prior cesarean delivery undergoing sec-
ond-trimester abortion with misoprostol, I pooled the
results of all 16 studies. The 95% confidence interval
(CI) for the risk and number needed to harm (1/[risk
in women with prior cesarean delivery-risk in women
without cesarean delivery]) also were calculated.
The dose, route, and interval of misoprostol
administration varied widely (Table 1). Most regi-
mens included doses of 200 400 micrograms of
misoprostol for women with a history of cesarean
delivery. Two studies used up to 800 micrograms of
misoprostol in women with9 and without10 a history of
cesarean delivery. One study used 50 micrograms
of misoprostol.11 Routes of administration included vag-
inal, oral, and sublingual. Dosing intervals varied from
every 3 to up to every 12 hours. Seven studies used
misoprostol alone to induce abortion.9,1217 The remain-
ing studies used misoprostol in combination with other
medicinal agents to effect cervical dilation. Seven studies
described using oxytocin in addition to misopros-
tol.10,11,18 22 PGE2 was used in gel form in two studies19,23
and intravenously in one.23 One study used extraamni-
otic PGF2.20 One study included the use of a Foley
balloon for cervical dilation.11 Another used Dilapan
intracervical tents.10 Four study protocols included anti-
biotic administration for all patients.10,12,13,24 Two studies
described the use of mifepristone and misoprostol.10,23
Nearly half of the studies used surgical evacuation for
incomplete abortion,12,18 20 for failure to complete abor-
tion after a specified time interval,9,13 or for all patients
after expulsion of intrauterine contents.10 Feticide before
the use of misoprostol was described in two studies.23,24
Uterine rupture occurred in 3 of 3,556 (0.08%)
patients (Table 1). Among 722 women with a prior
cesarean delivery undergoing abortion in the second
trimester, two cases of uterine rupture were repo-
rted.10,23 The remaining uterine rupture occurred in 1
of 2,834 patients without this history.24 The risk of
uterine rupture in women with prior cesarean deliv-
OBSTETRICS & GYNECOLOGY
 Potentially relevant
studies of misoprostol
use for second-trimester
pregnancy termination in
women with prior
cesarean delivery
N=63

MEDLINE articles EMBASE articles CINAHL articles Cochrane Library LILACS articles
excluded: n=11 excluded: n=27 excluded: n=3 articles excluded: excluded: n=2
Unrelated Guideline: 1 Duplicate n=4 Not available in
outcome: 1 Review article: 7 citation: 2 Duplicate English: 1
Review article: 1 Duplicate Case report: 1 citation: 2 Animal study: 1
Case report: 7 citation: 8 Unrelated
Excluded women Commentary: 2 outcome: 2
with cesarean: 1 Unrelated
Not available in outcome: 2
English: 1 Case report: 5
Not available in
English: 1
First trimester
only: 1

MEDLINE EMBASE CINAHL Cochrane LILACS

articles articles articles Library articles
included in included in included in articles included in
review review review included in review
n=14 n=2 n=0 review n=0
n=0

Articles included
in review
n=16

Fig. 1. Schema of literature search results.

Goyal. Uterine Rupture in Second-Trimester Abortion. Obstet Gynecol 2009.

ery was 0.28% (95% CI 0.08 1.00%). The risk of
uterine rupture in women without prior cesarean
delivery was 0.04% (95% CI 0.01 0.20%). Based on
these risks, if 414 women with a history of cesarean
delivery were given misoprostol for second-trimester
abortion, one would experience uterine rupture at-
tributable to the prior cesarean delivery (number
needed to harm).
Six studies specifically stated the inclusion of
women with only low transverse segment cesarean
deliveries.9,14 16,21,22 Among 179 women with a prior
low transverse cesarean delivery and 1,256 women
without a prior cesarean delivery, there were no
uterine ruptures. In the seven studies using misopros-
tol alone to induce abortion,9,1217 the risk of uterine
rupture was 0 (95% CI 0 1.48%) among the 256
women with prior cesarean delivery. In the remaining
nine studies10,11,18 24 using misoprostol plus another
method for labor induction, the risk of uterine rupture
was 0.43% (95% CI 0.121.55%) in the 466 women
with a history of cesarean delivery and 0.06% (95% CI
0.01 0.31%) in the 1,804 women without prior cesar-
ean delivery. The two women with history of cesarean
delivery who experienced uterine rupture were in-
duced with mifepristone and misoprostol in addition
to other medical agents.10,23
CONCLUSION
Among women with a prior cesarean delivery
undergoing second-trimester abortion using miso-
prostol, the risk of uterine rupture was less than
0.3%. Women with a history of low transverse
segment cesarean delivery and women induced
with misoprostol alone were not found to be at risk
for uterine rupture.
Both women with a prior cesarean delivery who
experienced uterine rupture were given mifepristone
in addition to misoprostol. Three other studies exam-
ined uterine rupture risk in women with prior cesar-
ean delivery who were given mifepristone for second-
trimester abortion.2527 Among the 294 women
included in these studies, two experienced uterine
rupture. Combining these three studies and the two
included in this review, the risk of uterine rupture
with the use of mifepristone for second-trimester
abortion in women with a history of cesarean delivery
is 1.15% (95% CI 0.452.92%). Given the small num-

VOL. 113, NO. 5, MAY 2009 Goyal Uterine Rupture in Second-Trimester Abortion 1119
Table 1. Participant Characteristics, Intervention, and Risk of Uterine Rupture for Studies Included in
Systematic Review
Participants
18
Bhattacharjee All between 13 and 26 wk of
gestation
80 women with at least one
prior lower-segment
cesarean delivery
80 women with no history of
cesarean delivery
Bhattacharjee19* All between 10 and 22 wk of
gestation
80 women with prior cesarean
delivery
80 women with no history of
cesarean delivery
Daponte12 85 women with second-
trimester gestation (up to 20
wk) with single prior
cesarean delivery
Daponte13 12 women with second-
trimester gestation (up to
20 wk) with more than one
prior cesarean delivery
Daskalakis24 All between 17 and 24 wk of
gestation
108 women with previous
cesarean delivery
216 women without history of
cesarean delivery, matched
for maternal and gestational
age
Dickinson20 All between 14 and 28 wk of
gestation
101 women with at least one
prior cesarean delivery
619 women without history of
cesarean delivery
Esteve10 All between 19 1/7 and 25 6/7
wk of gestation
17 women with prior cesarean
delivery
411 women without history of
cesarean delivery
1120 Goyal Uterine Rupture in Second-Trimester Abortion
Uterine Rupture
Prior No
Cesarean Cesarean
Intervention Delivery Delivery
Misoprostol 400 micrograms sublingually/ 0/80 0/80
vaginally every 6 h for 24 h up to 20 wk
Misoprostol 200 micrograms sublingually/
vaginally every 6 h for 24 h beyond
20 wk
After 24 h: additional misoprostol or
concentrated oxytocin (only for
unscarred uteri)
Misoprostol 400 micrograms sublingually/ 0/80 0/80
vaginally every 6 h for 24 h
After 24 h: additional doses of misoprostol
or PGE2 gel or concentrated oxytocin
All patients received misoprostol 400 0/85
micrograms vaginally initially, then:
Group A: 200 micrograms vaginally
every 6 h up to maximum of 1,600
micrograms
Group B: 400 micrograms vaginally
every 6 h up to maximum of 1,600
micrograms
All patients received misoprostol 400 0/12
micrograms vaginally initially, then:
Group A: 200 micrograms vaginally
every 6 h up to maximum of 800
micrograms
Group B: 400 micrograms vaginally
every 6 h up to maximum of 800
micrograms
All patients received misoprostol 400 0/108 1/216
micrograms orally and 400
micrograms vaginally initially, then
misoprostol 400 micrograms vaginally
every 6 h for a maximum of five doses
Feticide before misoprostol if greater than
20 wk of gestation
Since 2001, standard regimen was 0/101 0/619
misoprostol 400 micrograms vaginally
every 6 h for a maximum of 48 h;
however, six different regimens were
used throughout study period
If not delivered after 48 h, given
extraamniotic PGF2 via transcervical
Foley catheter every 2 h or oxytocin 5
international units/h
Mifepristone 200 mg orally 1/17 0/411
36 to 48 h later: misoprostol vaginally (800
micrograms in women without
cesarean delivery and 400 micrograms
in women with prior cesarean
delivery) and insertion of two Dilapan
intracervical tents if deemed necessary
(continued)
OBSTETRICS & GYNECOLOGY
Table 1. Participant Characteristics, Intervention, and Risk of Uterine Rupture for Studies Included in
Systematic Review (continued)
Participants
10
Esteve (continued)
Herabutya9 All between 14 and 26 wk of
gestation
56 women with prior cesarean
delivery
528 women without history of
cesarean delivery
Liaquat11 All between 14 and 26 wk of
gestation
5 women with prior cesarean
delivery
49 women without history of
cesarean delivery
Mazouni23 160 women between 15 and
24 wk of gestation
Group 1: 37 women with
prior cesarean delivery
Group 2: 123 women without
known uterine scar
Pongsatha21 All with second-trimester
gestation
21 women with prior low
transverse cesarean delivery
226 women without history of
cesarean delivery
Pongsatha22 17 women with second-
trimester gestation and prior
low transverse cesarean
delivery
VOL. 113, NO. 5, MAY 2009
Uterine Rupture
Prior No
Cesarean Cesarean
Intervention Delivery Delivery
4 h after misoprostol placement:
amniorrhexis and intravenous
oxytocin infusion
If amniorrhexis not possible, Dilapan tents
removed if loose in cervical canal
and misoprostol vaginally (600
micrograms in women without
cesarean delivery and 400
micrograms in women with prior
cesarean delivery) inserted; 3 h later
amniorrhexis performed and oxytocin
infusion begun
Misoprostol 600 micrograms vaginally 0/56 0/528
every 12 h at beginning of study
Dose later increased to misoprostol 800
micrograms vaginally every 12 h
Misoprostol 600 micrograms vaginally
every 6 h until abortion also used
Misoprostol 50 micrograms vaginally 0/5 0/49
every 4 h for a maximum of four
doses
Oxytocin infusion used when products of
conception failed to expel despite
open cervical os
After 48 h, Foley balloon technique used
for termination of pregnancy
All women received mifepristone 600 mg 1/37 0/123
orally 36 h before prostaglandin
Group 1: misoprostol 200 micrograms
vaginally every 3 h
Group 2: misoprostol 400 micrograms
vaginally every 3 h
If no onset of labor or contractions after
three doses, procedure stopped and
repeated 24 h later
If second treatment failed, IV sulprostone
9 mL/h increased by 9 mL/h every
90 s until fetus expelled
Misoprostol 400 micrograms orally every 0/21 0/226
4 h in cases of intrauterine fetal
demise
Misoprostol 400 micrograms vaginally
every 312 h with live fetus used
most commonly; however, regimen
varied
Oxytocin IV infusion as needed for
augmentation of labor when
misoprostol discontinued
Misoprostol 400 micrograms vaginally 0/17
every 6 h until adequate contractions
or dilated cervix
Oxytocin IV infusion as needed for
augmentation of labor
(continued)
Goyal Uterine Rupture in Second-Trimester Abortion 1121
Table 1. Participant Characteristics, Intervention, and Risk of Uterine Rupture for Studies Included in
Systematic Review (continued)
Uterine Rupture

Prior No
Cesarean Cesarean
Participants Intervention Delivery Delivery
Rouzi 14
10 women with second- Misoprostol 200 micrograms vaginally 0/10
trimester gestation and prior every 6 h, three doses maximum
cesarean delivery
Shammas15 All between 15 and 28 wk of Misoprostol 400 micrograms vaginally 0/63 0/457
gestation initially then misoprostol 200
63 women with at least one micrograms vaginally every 6 h
prior low transverse
cesarean delivery
457 women without history of
cesarean delivery
Tarim16 All with second-trimester Misoprostol 200 micrograms orally every h, 0/12 0/45
gestation six doses/d maximum
Group 1: 29 women with
previous vaginal delivery
Group 2: 16 nulliparous
women
Group 3: 12 women with one
prior low transverse
cesarean delivery
van Bogaert17 18 women with second- Misoprostol 400 micrograms sublingually 0/18
trimester gestation and prior and 800 micrograms orally
cesarean delivery
* Unable to separate first trimester from second trimester from data given; median gestational age in cases 14.5 weeks, in controls 15 weeks.

In addition to the uterine rupture reported, another patient also experienced uterine dehiscence.

ber of cases, the risk associated with mifepristone use
cannot be determined with precision owing to statis-
tical instability.
This review has both strengths and weaknesses.
One strength is the thorough, transparent search
strategy for relevant reports. Another is the ability to
pool data from studies to generate a larger sample
size. The studies included in this analysis were con-
ducted in 11 different countries, which may aid in the
extrapolation of results. Despite the data aggregation,
the limited number of women at risk and the even
smaller number of uterine ruptures preclude a precise
estimate.28
Another limitation is the lack of uniform gesta-
tional age, approach to labor induction, and manage-
ment of failed medical abortion. Different doses,
routes, and intervals of misoprostol were used in each
study. Fewer than half of the studies in this review
used misoprostol alone for induction of abortion.
Additionally, in the study in which both uterine
rupture and dehiscence were reported,23 no clinical
distinction was specified. These variations limit com-
parison of these reports. Because of the rarity of
uterine rupture in this setting, a randomized trial
would be impractical. Hence, observational reports
will provide the best available estimates of risk.
The risk of uterine rupture in women with prior
cesarean delivery undergoing second-trimester abor-
tion with misoprostol is similar to that with vaginal
birth after cesarean delivery.29 This risk may be
acceptable to both patients and providers.
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