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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 second-trimester abortion, one would experience uter-
when using misoprostol for second-trimester abortion in ine rupture.
women with a history of cesarean delivery. CONCLUSION: The risk of uterine rupture among
DATA SOURCES: MEDLINE, EMBASE, CINAHL, LILACS, women with a prior cesarean delivery undergoing sec-
and the Cochrane Library were searched systematically ond-trimester abortion using misoprostol is less than
for all articles published before September 2008. 0.3%. This may be acceptable to both patients and
providers.
METHODS OF STUDY SELECTION: Sixty-three articles
(Obstet Gynecol 2009;113:111723)
were found using the above data sources. I excluded case
reports, narrative reviews or commentaries, studies that

T
excluded women with a history of cesarean delivery, he risk of uterine rupture is increased with the use
studies with unrelated outcomes, studies not conducted of prostaglandins for labor induction at term in
in humans, and studies that were not available in English. women with uterine scars compared with women
The remaining 16 studies that described misoprostol use without this history.1 Misoprostol has been of special
for second-trimester abortion in women with a history of
concern in this setting.2,3 Hence, the American Col-
cesarean delivery were examined.
lege of Obstetricians and Gynecologists suggests, mi-
TABULATION, INTEGRATION, AND RESULTS: The number soprostol use in women with prior cesarean birth
of participants with and without cesarean delivery, regi-
should be avoided because of the possibility of uterine
men of medical abortion used, and cases of uterine
rupture.4
rupture were reviewed. To estimate the risk of uterine
rupture in women with prior cesarean delivery undergo-
In addition to labor induction at term, misopros-
ing second-trimester abortion with misoprostol and tol also is used for labor-induction abortion in the
number needed to harm, I pooled the results of all 16 second trimester. Although fewer than 5% of second-
studies. The risk of uterine rupture in women with prior trimester abortions in the United States involve labor
cesarean delivery was 0.28% (95% confidence interval induction, one quarter of second-trimester abortions
[CI] 0.08 1.00%). The risk of uterine rupture in women in England and nearly all second-trimester abortions
without prior cesarean delivery was 0.04% (95% CI in Sweden and Finland are performed medically.5
0.01 0.20%). Based on these risks, if 414 women with a Labor-induction abortion is appropriate for practitio-
history of cesarean delivery were given misoprostol for ners who lack sufficient skill in performing dilation
and evacuation.6 The use of misoprostol is favored in
From the Department of Obstetrics and Gynecology, University of North the developing world owing to its low cost and
Carolina School of Medicine, Chapel Hill, North Carolina. stability at room temperature.
Corresponding author: Vinita Goyal, MD, Department of Obstetrics and Use of misoprostol for second-trimester abortion
Gynecology, CB #7570, UNC School of Medicine, Chapel Hill, NC 27599- has increased, yet the risk of uterine rupture in
7570; e-mail: vgoyal@email.unc.edu.
women with scarred uteri is unknown. The American
Financial Disclosure
The author did not report any potential conflicts of interest.
College of Obstetricians and Gynecologists also
warns, misoprostol use for second-trimester preg-
2009 by The American College of Obstetricians and Gynecologists. Published
by Lippincott Williams & Wilkins. nancy termination also has been associated with
ISSN: 0029-7844/09 uterine rupture.4 No randomized trials have com-

VOL. 113, NO. 5, MAY 2009 OBSTETRICS & GYNECOLOGY 1117


pared rates of uterine rupture in women with and RESULTS
without a history of cesarean delivery undergoing Using the above search strategy, I retrieved 25 articles
second-trimester abortion with misoprostol. How- from MEDLINE, 29 from EMBASE, three from
ever, numerous observational studies have reported CINAHL, four from the Cochrane Library, and two
uterine rupture in this situation. The aim of this from LILACS. Using the exclusion criteria detailed
systematic review is to determine the likelihood of above and excluding articles that were cited in mul-
uterine rupture when using misoprostol for second- tiple databases, 16 studies were reviewed (Fig. 1).
trimester abortion in women with a prior cesarean Eleven of the 16 studies included women with
delivery. and without history of cesarean delivery. The remain-
ing articles reported only on those patients with a
SOURCES history of cesarean delivery. All studies were obser-
I conducted a literature search of all articles evaluating vational trials; no randomized trials were found.
misoprostol for second-trimester abortion in women To determine the risk of uterine rupture in
with a prior cesarean delivery that were published women with prior cesarean delivery undergoing sec-
before September 2008. MEDLINE (1966 2008), EM- ond-trimester abortion with misoprostol, I pooled the
BASE (1974 2008), CINAHL (19812008), LILACS results of all 16 studies. The 95% confidence interval
(19822008), and the Cochrane Library (Issue 3, 2008) (CI) for the risk and number needed to harm (1/[risk
were searched systematically. I used the following in women with prior cesarean delivery-risk in women
search terms: abortion OR abortion, induced OR without cesarean delivery]) also were calculated.
abortion AND induced OR induced abortion AND The dose, route, and interval of misoprostol
cesarean OR scarred uterus AND misoprostol administration varied widely (Table 1). Most regi-
OR Cytotec AND second trimester OR pregnancy mens included doses of 200 400 micrograms of
trimester, second OR pregnancy AND trimester misoprostol for women with a history of cesarean
AND second OR 2nd trimester. 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
STUDY SELECTION of misoprostol.11 Routes of administration included vag-
All articles retrieved from the above search were inal, oral, and sublingual. Dosing intervals varied from
reviewed. Reasons for exclusion from this systematic every 3 to up to every 12 hours. Seven studies used
review included: case reports, narrative reviews or misoprostol alone to induce abortion.9,1217 The remain-
commentaries, studies that excluded women with a ing studies used misoprostol in combination with other
history of cesarean delivery, studies with unrelated medicinal agents to effect cervical dilation. Seven studies
outcomes (eg, the primary outcome was limited to described using oxytocin in addition to misopros-
side effects of misoprostol use, pain management, tol.10,11,18 22 PGE2 was used in gel form in two studies19,23
subsequent pregnancy outcome), studies not con- and intravenously in one.23 One study used extraamni-
ducted in humans, and studies that were not available otic PGF2.20 One study included the use of a Foley
in English. I examined all studies that described balloon for cervical dilation.11 Another used Dilapan
misoprostol use for second-trimester abortion in intracervical tents.10 Four study protocols included anti-
women with a history of cesarean delivery. biotic administration for all patients.10,12,13,24 Two studies
I reviewed the number of participants with and described the use of mifepristone and misoprostol.10,23
without cesarean delivery, regimen of medical abor- Nearly half of the studies used surgical evacuation for
tion used, and cases of uterine rupture. The outcome incomplete abortion,12,18 20 for failure to complete abor-
assessed was frequency of uterine rupture in women tion after a specified time interval,9,13 or for all patients
with and without prior cesarean delivery. Uterine after expulsion of intrauterine contents.10 Feticide before
rupture is defined as separation of all layers of the the use of misoprostol was described in two studies.23,24
uterus, resulting in hemorrhage or significant mater- Uterine rupture occurred in 3 of 3,556 (0.08%)
nal morbidity. This outcome is distinct from uterine patients (Table 1). Among 722 women with a prior
dehiscence, in which the uterine serosa is intact and cesarean delivery undergoing abortion in the second
the potential for serious morbidity is absent.7 trimester, two cases of uterine rupture were repo-
The Meta-analysis of Observational Studies in rted.10,23 The remaining uterine rupture occurred in 1
Epidemiology guidelines were followed in reporting of 2,834 patients without this history.24 The risk of
the results of this systematic review.8 uterine rupture in women with prior cesarean deliv-

1118 Goyal Uterine Rupture in Second-Trimester Abortion 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 duced with mifepristone and misoprostol in addition
uterine rupture in women without prior cesarean to other medical agents.10,23
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 CONCLUSION
abortion, one would experience uterine rupture at- Among women with a prior cesarean delivery
tributable to the prior cesarean delivery (number undergoing second-trimester abortion using miso-
needed to harm). prostol, the risk of uterine rupture was less than
Six studies specifically stated the inclusion of 0.3%. Women with a history of low transverse
women with only low transverse segment cesarean segment cesarean delivery and women induced
deliveries.9,14 16,21,22 Among 179 women with a prior with misoprostol alone were not found to be at risk
low transverse cesarean delivery and 1,256 women for uterine rupture.
without a prior cesarean delivery, there were no Both women with a prior cesarean delivery who
uterine ruptures. In the seven studies using misopros- experienced uterine rupture were given mifepristone
tol alone to induce abortion,9,1217 the risk of uterine in addition to misoprostol. Three other studies exam-
rupture was 0 (95% CI 0 1.48%) among the 256 ined uterine rupture risk in women with prior cesar-
women with prior cesarean delivery. In the remaining ean delivery who were given mifepristone for second-
nine studies10,11,18 24 using misoprostol plus another trimester abortion.2527 Among the 294 women
method for labor induction, the risk of uterine rupture included in these studies, two experienced uterine
was 0.43% (95% CI 0.121.55%) in the 466 women rupture. Combining these three studies and the two
with a history of cesarean delivery and 0.06% (95% CI included in this review, the risk of uterine rupture
0.01 0.31%) in the 1,804 women without prior cesar- with the use of mifepristone for second-trimester
ean delivery. The two women with history of cesarean abortion in women with a history of cesarean delivery
delivery who experienced uterine rupture were in- 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
Uterine Rupture

Prior No
Cesarean Cesarean
Participants Intervention Delivery Delivery
18
Bhattacharjee All between 13 and 26 wk of Misoprostol 400 micrograms sublingually/ 0/80 0/80
gestation vaginally every 6 h for 24 h up to 20 wk
80 women with at least one Misoprostol 200 micrograms sublingually/
prior lower-segment vaginally every 6 h for 24 h beyond
cesarean delivery 20 wk
80 women with no history of After 24 h: additional misoprostol or
cesarean delivery concentrated oxytocin (only for
unscarred uteri)
Bhattacharjee19* All between 10 and 22 wk of Misoprostol 400 micrograms sublingually/ 0/80 0/80
gestation vaginally every 6 h for 24 h
80 women with prior cesarean After 24 h: additional doses of misoprostol
delivery or PGE2 gel or concentrated oxytocin
80 women with no history of
cesarean delivery
Daponte12 85 women with second- All patients received misoprostol 400 0/85
trimester gestation (up to 20 micrograms vaginally initially, then:
wk) with single prior Group A: 200 micrograms vaginally
cesarean delivery 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
Daponte13 12 women with second- All patients received misoprostol 400 0/12
trimester gestation (up to micrograms vaginally initially, then:
20 wk) with more than one Group A: 200 micrograms vaginally
prior cesarean delivery every 6 h up to maximum of 800
micrograms
Group B: 400 micrograms vaginally
every 6 h up to maximum of 800
micrograms
Daskalakis24 All between 17 and 24 wk of All patients received misoprostol 400 0/108 1/216
gestation micrograms orally and 400
108 women with previous micrograms vaginally initially, then
cesarean delivery misoprostol 400 micrograms vaginally
216 women without history of every 6 h for a maximum of five doses
cesarean delivery, matched Feticide before misoprostol if greater than
for maternal and gestational 20 wk of gestation
age
Dickinson20 All between 14 and 28 wk of Since 2001, standard regimen was 0/101 0/619
gestation misoprostol 400 micrograms vaginally
101 women with at least one every 6 h for a maximum of 48 h;
prior cesarean delivery however, six different regimens were
619 women without history of used throughout study period
cesarean delivery If not delivered after 48 h, given
extraamniotic PGF2 via transcervical
Foley catheter every 2 h or oxytocin 5
international units/h
Esteve10 All between 19 1/7 and 25 6/7 Mifepristone 200 mg orally 1/17 0/411
wk of gestation 36 to 48 h later: misoprostol vaginally (800
17 women with prior cesarean micrograms in women without
delivery cesarean delivery and 400 micrograms
411 women without history of in women with prior cesarean
cesarean delivery delivery) and insertion of two Dilapan
intracervical tents if deemed necessary
(continued)

1120 Goyal Uterine Rupture in Second-Trimester Abortion OBSTETRICS & GYNECOLOGY


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
10
Esteve (continued) 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
Herabutya9 All between 14 and 26 wk of Misoprostol 600 micrograms vaginally 0/56 0/528
gestation every 12 h at beginning of study
56 women with prior cesarean Dose later increased to misoprostol 800
delivery micrograms vaginally every 12 h
528 women without history of Misoprostol 600 micrograms vaginally
cesarean delivery every 6 h until abortion also used
Liaquat11 All between 14 and 26 wk of Misoprostol 50 micrograms vaginally 0/5 0/49
gestation every 4 h for a maximum of four
5 women with prior cesarean doses
delivery Oxytocin infusion used when products of
49 women without history of conception failed to expel despite
cesarean delivery open cervical os
After 48 h, Foley balloon technique used
for termination of pregnancy
Mazouni23 160 women between 15 and All women received mifepristone 600 mg 1/37 0/123
24 wk of gestation orally 36 h before prostaglandin
Group 1: 37 women with Group 1: misoprostol 200 micrograms
prior cesarean delivery vaginally every 3 h
Group 2: 123 women without Group 2: misoprostol 400 micrograms
known uterine scar 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
Pongsatha21 All with second-trimester Misoprostol 400 micrograms orally every 0/21 0/226
gestation 4 h in cases of intrauterine fetal
21 women with prior low demise
transverse cesarean delivery Misoprostol 400 micrograms vaginally
226 women without history of every 312 h with live fetus used
cesarean delivery most commonly; however, regimen
varied
Oxytocin IV infusion as needed for
augmentation of labor when
misoprostol discontinued
Pongsatha22 17 women with second- Misoprostol 400 micrograms vaginally 0/17
trimester gestation and prior every 6 h until adequate contractions
low transverse cesarean or dilated cervix
delivery Oxytocin IV infusion as needed for
augmentation of labor
(continued)

VOL. 113, NO. 5, MAY 2009 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 would be impractical. Hence, observational reports
cannot be determined with precision owing to statis- will provide the best available estimates of risk.
tical instability. The risk of uterine rupture in women with prior
This review has both strengths and weaknesses. cesarean delivery undergoing second-trimester abor-
One strength is the thorough, transparent search tion with misoprostol is similar to that with vaginal
strategy for relevant reports. Another is the ability to birth after cesarean delivery.29 This risk may be
pool data from studies to generate a larger sample acceptable to both patients and providers.
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, REFERENCES
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