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Literature review current through: Oct 2016. | This topic last updated: Jul 28, 2014.
INTRODUCTION Medical methods for induced abortion have emerged over the past two
decades as safe, effective, and feasible alternatives to surgery. Nonsurgical alternatives expand
a woman's treatment options and, in turn, the quality of care [1]. Moreover, in some settings,
surgical options are not available to women or are not medically feasible.
In first trimester abortion, combined treatment with misoprostol with mifepristone appears to be
more effective than misoprostol-alone regimens, and thus, are considered the gold standard for
medical induction [2,3]. However, misoprostol-alone regimens may be the treatment of choice in
settings in which mifepristone is not available or is too costly.
Misoprostol is commonly used as a single agent for second trimester induced abortion in the
United States and many other parts of the world [4,5].
This topic review will discuss use of misoprostol in pregnancy termination. Use of mifepristone
and other medical and surgical approaches to pregnancy termination and use of misoprostol for
fetal demise or labor induction are reviewed separately. (See "First-trimester medication abortion
(termination of pregnancy)" and "Overview of pregnancy termination" and "Spontaneous
abortion: Management" and "Fetal death and stillbirth: Incidence, etiology, and prevention" and
"Techniques for ripening the unfavorable cervix prior to induction".)
High risk of uterine rupture (ie, second or third trimester inductions in women with more
than one prior hysterotomy, a prior classical or T-shaped uterine incision, or extensive
transfundal uterine surgery)
Intrauterine device (IUD, must be removed before misoprostol is administered)
Allergy to prostaglandins
Contraindications to medical or surgical uterine evacuations (eg, hemodynamically
unstable, coagulopathy) (see "Overview of pregnancy termination")
Relative contraindications Misoprostol-alone regimens should be used with caution in
women who are at risk for complications of pregnancy termination (eg, coagulopathy).
Precautions specific to misoprostol are considered here. A full discussion of abortion
complications is presented separately. (See "Overview of pregnancy termination", section on
'Complications'.)
Risk factors for uterine rupture Uterine rupture is a risk of misoprostol use at any time
during pregnancy. While the risk is likely higher in women with a uterine scar, there are few
reports of this complication (table 1) [17]. In a systematic review of available studies, the risk of
rupture was 0.3 percent among women with a prior cesarean delivery who were undergoing
second trimester misoprostol-induced abortion [18]. Advanced gestational age, high gravidity
(3 pregnancies) or uterine anomalies may also increase risk of rupture.
Uterine rupture has only been reported once in women undergoing first trimester ruptures [19].
In the second trimester, uterine rupture is rare, but has been reported more frequently than in
the first trimester [20-28]. Case reports of uterine rupture in women undergoing second trimester
abortion with misoprostol include women with scarred [20-25] and unscarred uteri [25-28].
Scarred uterus There are no high quality data regarding the risk of uterine rupture
with use of misoprostol for first or second trimester pregnancy termination. Among five
published case series of women with a prior cesarean section who were undergoing
second trimester misoprostol abortion (n = 858), two cases of uterine rupture were
We counsel women that a uterine scar is not a contraindication for first trimester
misoprostol induction, but that the risk may increase with increasing gestational age,
particularly in the late second trimester. We counsel women about risk and monitor them
for signs of rupture.
Unscarred uterus In reports of uterine rupture in women without previous uterine
surgery, risk factors included grand multiparity [25,26], gestational age greater than 23
weeks [24], and use of oxytocin in addition to misoprostol [25]. However, oxytocin can
generally be used safely in combination with misoprostol [26]. For pregnancies at 23 or
more weeks, it is controversial whether it is necessary to decrease the misoprostol dose
or increase dosing interval, though it may be prudent to do so [32,33].
Breastfeeding Misoprostol is excreted transiently and at low levels in human breast milk [34].
It appears that the levels rise and decline within three to five hours of administration [6,34]. It is
reasonable to counsel women who receive misoprostol while breastfeeding to pump and discard
all milk produced within five hours after each dose.
PRETREATMENT EVALUATION AND PREPARATION All women should undergo an initial
evaluation, including a medical history and a physical examination confirming gestational age.
Ultrasound is necessary only if there is uncertainty about gestational age, pregnancy location or
the presence of gestational trophoblastic disease. If an ultrasound is not performed, the
pregnancy should be confirmed with a urine or serum human chorionic gonadotropin (hCG).
Blood type and antibody status are checked and Rh immune globulin given if indicated. If a
patient has an IUD, it must be removed.
One of the advantages of misoprostol induction is that it can be performed safely and effectively
without mechanical dilation (eg, rigid or osmotic dilators). Some providers augment the
procedure with pretreatment laminaria for inductions after 15 weeks. However, two randomized
trials in women undergoing second trimester termination reported that use of laminaria
compared with no mechanical dilation did not reduce (16 and 17 hours) [35] and may prolong
(14 versus 11 hours) [36] induction time; one trial found an increase in the use of morphine in
patients treated with laminaria [36]. A full discussion of cervical preparation for pregnancy
termination can be found separately. (See "Overview of pregnancy termination", section on
'Cervical preparation'.)
There is no high quality evidence regarding the use of antibiotic prophylaxis for medical abortion
(ie, no invasive methods for cervical preparation or uterine evacuation). However, due to several
deaths due to clostridial sepsis in the United States in patients who received vaginal misoprostol
in combination with mifepristone, some organizations, such as Planned Parenthood (the largest
abortion provider in the United States), have introduced the use of prophylactic antibiotics
[37,38]. However, deaths due to clostridial infection have been reported among women
administering misoprostol both vaginally and buccally [39]. (See "First-trimester medication
abortion (termination of pregnancy)", section on 'Prophylactic antibiotics'.)
Pretreatment evaluation for pregnancy termination is discussed in detail separately. (See
"Overview of pregnancy termination", section on 'Preoperative considerations' and "Prevention
of Rh(D) alloimmunization in pregnancy".)
DATA ON DRUG ADMINISTRATION The optimal misoprostol regimen at any gestational age
is determined by achieving a balance among effectiveness, adverse effects, and acceptability to
patients. As an example, higher doses and shorter dosing intervals increase effectiveness, but
also may result in higher rates of adverse effects and complications [6].
For pregnancies between 9 and 12 weeks, there are no high quality data comparing
vaginal with oral administration. However, observational studies of vaginal misoprostol
use have reported consistently high rates of complete abortion (85 to 90 percent) [4958].
At 13 or more weeks, randomized trials comparing vaginal with oral dosing found that the
vaginal route was more effective (86 to 100 versus 45 to 89 percent) and had a shorter
induction-to-delivery interval (10 to 15 hours versus 12 to 35 hours) [5,42,43,59].
Adverse effects were similar between the two routes, with the possible exception of a
higher incidence of fever with vaginal dosing [42], and of nausea and diarrhea with oral
dosing [59]. Findings on adverse effects are not consistent and thus do not provide high
quality evidence for guiding route of administration.
At 24 to 28 weeks, one randomized trial of women with a fetal demise compared oral and
vaginal regimens and found a slightly longer time to expulsion in women receiving oral
misoprostol [60].
Sublingual versus vaginal dosing In pregnancies at 12 weeks of gestation or less,
data suggest that the sublingual route may be as effective as the vaginal route when
dosed appropriately [40,44,61]. In a randomized trial that compared two vaginal and two
sublingual regimens in 2000 women, vaginal misoprostol administered every 3 or 12
hours and sublingual misoprostol every three hours were similarly effective (83 to 85
percent), but sublingual misoprostol every 12 hours was less effective (78 percent) [61].
Women preferred sublingual to vaginal administration. Side effects tended to be more
common among women taking misoprostol at 3-hour compared to 12-hour intervals,
vaginal or sublingual; and this finding was significant for incidence of fever. Diarrhea and
chills were slightly more common in women taking misoprostol sublingually compared to
vaginally, but this difference was not statistically significant and, regardless, may not be
clinically relevant.
Similarly, the sublingual route may be as effective as the vaginal route for termination
after 12 weeks [46,59,62-66]. One meta-analysis demonstrated that efficacy at 24 hours
was similar (pooled RR 1.04, 95% CI 0.93-1.7), but that vaginal misoprostol may be
more successful at 48 hours (pooled RR 0.96; 95% CI 0.93-0.99) and may shorten the
induction-to-abortion interval (WMD -4.54, 95% CI -8.03 to -1.05) [65]. A second metaanalysis of 40 randomized trials examining medical methods of uterine evacuation for
women 12 to 28 weeks pregnant found that while misoprostol was more frequently
vaginally administered, sublingual administration was equally effective [66]. Rates of
adverse effects are similar between the two types of dosing; however, patients prefer the
sublingual route [46,62,63].
Buccal versus oral or vaginal dosing Buccal administration of misoprostol as a single
agent for medical termination of pregnancy in the first trimester appears promising
[67,68]. Randomized trial data for administration of misoprostol in combination with
mifepristone for pregnancy up to eight to nine weeks of gestation have found that the
efficacy of buccal dosing is similar to vaginal and better than oral dosing [69,70]. Buccal
administration was associated with a slight increase in nausea over either oral or vaginal
dosing. Patient satisfaction was high across all routes. Used as a single agent, buccal
misoprostol was found to have an efficacy of 76 percent among women less than 9
weeks pregnant (n = 147) [47].
Studies regarding buccal dosing in the second trimester have also yielded favorable
results, but there are no studies regarding use of buccal misoprostol as a single agent for
second trimester pregnancy termination [71,72]. In one randomized trial, the initial
misoprostol dose was administered vaginally, and subsequent doses were given either
buccally or vaginally [73]. The median time to abortion in the buccal group did not differ
significantly in the buccal compared with vaginal dosing groups (15 versus 12 hours); no
difference was found in patient preference for route of administration.
Combined-route regimens for second trimester terminations Regimens that combine
an initial vaginal misoprostol dose followed by oral doses have been commonly used for
terminations after 12 weeks and appear to be as effective as vaginal-only regimens
[36,43,74-76]. The rationale is to maximize effectiveness and acceptability, while
minimizing induction-to-delivery interval, adverse effects and complications. In a
randomized trial of 43 women at 13 to 23 weeks of gestation, an initial 800 mcg vaginal
misoprostol dose was followed every eight hours by 400 mcg given either orally or
vaginally; effectiveness (82 and 87 percent) and induction-to-delivery interval (16 and 21
hours) were similar between the oral and vaginal groups [76]. A randomized trial
demonstrated that 200 mcg buccal doses repeated at six-hour intervals, following an
initial 400 mcg vaginal dose, result in a similar induction-to-delivery interval (15 versus
12 hours, respectively) [73].
Dose and dosing interval The optimal regimen is a dose and dosing interval balance which
generate sufficient and sustained uterine activity while minimizing adverse effects [77]. Longer
dosing intervals have the benefit of exposing a woman to a decreased risk of adverse effects.
Conversely, shorter dosing intervals (closer to three hours) may be necessary to generate
sufficient uterine activity, in particular if misoprostol is given via a route with a rapid rise and fall
in serum levels (ie, oral and sublingual) [8]. Uterine hyperstimulation is rare; however, the risk
may increase with shorter dosing intervals.
9 or less weeks Vaginal administration of misoprostol appears to be more effective at
800 mcg (generally 80 to 90 percent) than 200 or 400 mcg (23 to 46 percent), according
to observational data [51].
A vaginal dosing interval of 3 to 24 hours (800 mcg PV; total of three to five doses) is
typically used to terminate pregnancies up to nine weeks, with reported success rates of
85 to 93 percent in non-comparative studies [77].
There are no high quality data comparing different doses of sublingual misoprostol for
terminations at 12 weeks. In studies of sublingual-dosing alone and comparative trials
with vaginal dosing, 400 to 800 mcg SL is typically used [40,44,61]. As noted above, 3rather than 12-hour dosing interval was found to be significantly more effective in a
randomized trial (84 versus 78 percent) [61].
10 to 12 weeks Lower success rates for misoprostol-alone have been reported for
pregnancies at 10 to 12 weeks of gestation (84 to 87 percent) in a few descriptive
studies [51,56,57,78,79]. The most effective regimen appears to be 800 mcg PV every
12 to 24 hours for a maximum of three doses [56,57].
Data from a case series of 50 women suggest that sublingual administration is also
effective; the regimen used was 600 mcg SL every three hours up to five doses [44].
13 to 22 weeks Two misoprostol regimens, 400 mcg PV every three hours OR 600
PV mcg every 12 hours were safe, effective, and resulted in low induction-to-delivery
interval in randomized trials [80-82]. However, these two regimens have not been
compared to each other.
As noted above, uterine sensitivity to prostaglandins and risk of uterine rupture increase
with gestational age. Therefore, it may be prudent to use a decreased dose or increased
dosing interval in this gestational age range [89] (see 'Pharmacokinetics' above). Uterine
rupture is rare, however. There no uterine ruptures reported among the 700 cases
included in the SFP review [87].
A retrospective review of second trimester terminations among women with prior
cesarean section found that, among the 279 women undergoing termination, there were
3 cases of rupture [90]. All three cases of rupture were among women with two or more
prior cesarean sections. The type of prior incision, termination regimen used, and the
length of induction were not specified. In another study, no significant increased risk of
uterine rupture was found in women with a prior uterine scar compared to those with no
uterine scar (1/44 versus 2/457) in a population of 518 women undergoing second
trimester medical termination with a combination of methods, including misoprostol alone
[91].
Number of doses In pregnancies at 12 or less weeks, it appears that there is little increase
in effectiveness after the second dose of misoprostol [58,92], although most studies have
evaluated regimens of three to five doses [77]. As an example, in one study, effectiveness after
a second or third dose were similar (86 and 88 percent) [92].
Data on second trimester medical terminations with misoprostol show that multiple doses are
highly effective compared to single doses. As noted above, recommended doses are lower than
doses used for first trimester terminations since the uterine is more sensitive to misoprostol and
the risk of rupture appears greater [65,66,93]. As an example, 25 to 50 mcg doses are generally
used for labor induction in the third trimester. The need for repeat doses should be evaluated
prior to administration and based on lack of relevant clinical signs of progression (eg, insufficient
uterine activity or cervical dilation).
CLINICAL REGIMEN The regimens listed below are consistent with the regimens proposed
by a meeting convened by the World Health Organization (WHO) as a prelude to WHO
guidelines (table 2) [77,89,94]. All gestational ages refer to weeks of amenorrhea.
9 or less weeks Misoprostol may be administered either in a clinic or at home.
800 mcg SL every three hours for up to three doses [61] OR
800 mcg PV every 3 to 12 hours for up to three doses [40,61] OR
800 mcg buccally every two to three hours
has not had bleeding greater than a menstrual period, it is likely that she may have an
incomplete abortion or continuing pregnancy [95].
In-clinic treatment Examination of presumed products of conception or pelvic examination
are performed before each additional misoprostol dose is administered in order to determine
whether the fetus has been expelled. The frequency and strength of uterine contractions are
also monitored, and additional doses should be deferred if uterine contractions are strong
(strong to palpation or by patient report) and/or too frequent (>3 contractions/10 min) [89].
In pregnancies at 13 weeks or greater, if a woman does not abort after 24 hours, the option of a
second course of misoprostol treatment or surgical evacuation can be offered [80,82]. There are
insufficient data on the safety and effectiveness of augmentation with other uterotonics (eg,
prostaglandins or oxytocin) [89]. As with misoprostol, if additional uterotonics are used,
precautions should be taken to avoid uterine hyperstimulation, as it may lead to rupture.
Expulsion of the placenta should be confirmed. Expulsion usually occurs shortly after the fetus
is delivered. After expulsion, the placenta should be examined to see whether it is complete.
Advice regarding time interval to wait for placental expulsion varies from 30 minutes to four
hours; in a retrospective study, there was no morbidity associated with a waiting period of four
hours [96]. If two or more hours have passed and the placenta has not delivered, an infusion of
oxytocin 10 units in 500 mL of normal saline administered intravenously at a rate of 20 to 30
drops per minute may be given [89]. If the placenta has not delivered after infusion of oxytocin or
the woman starts bleeding excessively, manual or surgical removal of the placenta may be
required.
Before discharge from the clinic, clinicians should observe women for at least four hours to
monitor vital signs and observe for severe abdominal pain or excessive vaginal bleeding.
If 48 hours have passed and abortion is not complete, surgical evacuation is typically performed
[89].
hours, and antipyretics may be given as needed. If fever persists beyond 24 hours, a women
should be evaluated for infection.
Concern has emerged in North America following the reports of six cases of Clostridiaassociated fatal toxic shock syndrome following use of mifepristone and misoprostol for early
pregnancy termination (five cases associated with sordellii and one with perfringens) [107-110].
An additional case (of perfringens) was recently reported in a woman who used laminaria and
misoprostol for second trimester termination. Although several hypotheses on the mechanism of
infection have been put forth, no consensus has been reached [111-113]. (See "First-trimester
medication abortion (termination of pregnancy)", section on 'Fever and infection'.)
Prevention of adverse effects Pretreatment with antipyretic and antidiarrheal medications
may slightly reduce the severity of gastrointestinal adverse effects [114]. In a randomized trial of
women undergoing pregnancy termination at 7 weeks, pretreatment with loperamide 4 mg and
acetaminophen 500 mg prior to misoprostol 800 mcg pv compared to no pretreatment led to a
significant reduction in incidence of diarrhea (23 versus 44 percent), but no difference in
vomiting or fever/chills.
COMPLICATIONS Complications specific to misoprostol-only pregnancy termination are
discussed below. As with any uterine evacuation procedure, bleeding or infection may occur.
(See "Overview of pregnancy termination", section on 'Complications'.)
Incomplete abortion
First trimester For women undergoing first trimester inductions, management of ongoing
pregnancy (cardiac activity on ultrasound) or incomplete abortion (sac or other evidence of
products of conception, but no gestational growth and no cardiac activity on ultrasound) are
generally different. We assess women at the follow-up visit (one to two weeks) and advise
surgery for all ongoing pregnancies. For incomplete abortion, we advise expectant management
or a second dose of misoprostol. For women who receive a second dose, we schedule a second
follow-up assessment at one to two weeks.
We generally don't give more than one additional dose. This is because the cumulative benefit
of additional doses is not established and requiring multiple follow-up visits increases the
chance of loss-to-follow-up.
Second trimester For women in second trimester, management of retained products of
conception (POCs) depends on the point in the process at which they are suspected or
diagnosed.
After fetal expulsion and before discharge from the hospital or clinic, clinicians should confirm
that the fetus and placenta have been completely expelled.
Many clinicians manage retained products of conception (POCs) with surgical evacuation.
Clinicians can choose either dilatation and curettage or manual vacuum aspiration, depending
on the clinical situation. (See "Surgical termination of pregnancy: First trimester" and "Overview
of second-trimester pregnancy termination".)
However, some clinicians treat retained POCs after a second trimester induction with an
additional dose or two of misoprostol. The efficacy of this practice has not been established in
the literature, but avoiding surgical intervention is always recommended, and there are no
known dangers of giving additional misoprostol doses after fetal expulsion.
It is rare for retained POCs to be detected only after discharge from the clinic, and there is no
standard approach. Management (expectant management, additional misoprostol, or surgery)
should be tailored to the patient's preferences and the clinical situation.
Uterine rupture Misoprostol, and other agents which stimulate uterine contractions (eg,
oxytocin, other prostaglandins), may increase risk of dehiscence of a prior uterine scar or uterine
rupture. (See 'Risk factors for uterine rupture' above.)
Preprocedure screening of patients for risk factors and close observation during treatment are
crucial to prevent or detect early signs of uterine rupture. In addition, the minimum cumulative
misoprostol dose should be used (ie, lowest dose, longest dosing interval, lowest number or
total doses).
associated with reduced narcotic analgesia (RR 0.64, 95% CI 0.49-0.84) and surgical
evacuation of the uterus (RR 0.71, 95% CI 0.53-0.95) [121].
Misoprostol versus mifepristone/misoprostol A combined regimen of mifepristone and
misoprostol is more effective than misoprostol-alone in a randomized trial [92]; the misoprostolonly regimen would be of use in those settings where mifepristone is not available.
In addition, compared with combined therapy, women who administer misoprostol-alone may
experience more fever and chills (probably due to higher and repeated doses), whereas women
administered the combined therapy may experience more nausea and vomiting [104].
Pretreatment with mifepristone may also reduce the pain associated with the procedure.
Misoprostol versus methotrexate/misoprostol Choice of misoprostol-alone and combined
methotrexate/misoprostol is controversial [3]. Data from randomized trials regarding the
comparative efficacy of the two regimens are variable. Data from a large retrospective series
reported that use of methotrexate with misoprostol was more effective than misoprostol-alone
[2]. However, methotrexate is not widely available and is more cumbersome to use than
mifepristone and misoprostol and misoprostol alone. Also, it can only be used safely through 7
weeks of gestation.
INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials,
The Basics and Beyond the Basics. The Basics patient education pieces are written in plain
language, at the 5th to 6th grade reading level, and they answer the four or five key questions a
patient might have about a given condition. These articles are best for patients who want a
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education pieces are longer, more sophisticated, and more detailed. These articles are written at
the 10th to 12th grade reading level and are best for patients who want in-depth information and
are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print
or e-mail these topics to your patients. (You can also locate patient education articles on a
variety of subjects by searching on patient info and the keyword(s) of interest.)
Beyond the Basics topics (see "Patient education: Abortion (pregnancy termination)
(Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
Pretreatment considerations
In women seeking pregnancy termination at nine or less weeks of gestation, we
recommend mifepristone with misoprostol versus misoprostol alone (Grade 1A).
However, in settings where other medications are not accessible, use of misoprostolalone for early pregnancy termination is an appropriate and effective choice. (See
'Misoprostol-alone compared to other regimens' above.)
Misoprostol is commonly used as a single agent for second trimester induced abortion
in the United States and many other parts of the world. (See 'Introduction' above.)
In women undergoing pregnancy termination at 14 or more weeks, we recommend
misoprostol over gemeprost (Grade 1A). (See 'Misoprostol versus other prostaglandins'
above.)
In women undergoing second trimester pregnancy termination who are at high risk of
uterine rupture (more than one hysterotomy, a prior classical or T-shaped uterine
incision, or extensive transfundal uterine surgery [eg, myomectomy]), we suggest against
using misoprostol (Grade 2B). Misoprostol induction for pregnancy termination appears
to be safe in women with one prior low transverse hysterotomy. Rupture is rarely
associated with misoprostol use in first trimester. (See 'Risk factors for uterine rupture'
above and "Choosing the route of delivery after cesarean birth", section on 'Inappropriate
candidates'.)
Clinical protocol
In women undergoing pregnancy termination with misoprostol-alone, we suggest
sublingual, rather than vaginal or oral, misoprostol dosing (Grade 2B). Buccal dosing
may be a reasonable alternative to sublingual. Sublingual and vaginal administration
REFERENCES
1.
Borgatta L, Mullally B, Vragovic O, et al. Misoprostol as the primary agent for medical
abortion in a low-income urban setting. Contraception 2004; 70:121.
2.
3.
Wiebe ER, Trouton KJ, Lima R. Misoprostol alone vs. methotrexate followed by
misoprostol for early abortion. Int J Gynaecol Obstet 2006; 95:286.
4.
5.
6.
7.
Zieman M, Fong SK, Benowitz NL, et al. Absorption kinetics of misoprostol with oral or
vaginal administration. Obstet Gynecol 1997; 90:88.
8.
9.
Danielsson KG, Marions L, Rodriguez A, et al. Comparison between oral and vaginal
administration of misoprostol on uterine contractility. Obstet Gynecol 1999; 93:275.
10.
11.
12.
13.
Creinin MD, Carbonell JL, Schwartz JL, et al. A randomized trial of the effect of
moistening misoprostol before vaginal administration when used with methotrexate for
abortion. Contraception 1999; 59:11.
14.
Sanchez-Ramos L, Danner CJ, Delke I, Kaunitz AM. The effect of tablet moistening on
labor induction with intravaginal misoprostol: a randomized trial. Obstet Gynecol 2002;
99:1080.
15.
16.
17.
Goldberg AB, Greenberg MB, Darney PD. Misoprostol and pregnancy. N Engl J Med
2001; 344:38.
18.
19.
Kim JO, Han JY, Choi JS, et al. Oral misoprostol and uterine rupture in the first trimester
of pregnancy: a case report. Reprod Toxicol 2005; 20:575.
20.
Daskalakis GJ, Mesogitis SA, Papantoniou NE, et al. Misoprostol for second trimester
pregnancy termination in women with prior caesarean section. BJOG 2005; 112:97.
21.
22.
23.
24.
Nayki U, Taner CE, Mizrak T, et al. Uterine rupture during second trimester abortion with
misoprostol. Fetal Diagn Ther 2005; 20:469.
25.
Mazzone ME, Woolever J. Uterine rupture in a patient with an unscarred uterus: a case
study. WMJ 2006; 105:64.
26.
27.
Syed S, Noreen H, Kahloon LE, Chaudhri R. Uterine rupture associated with the use of
intra-vaginal misoprostol during second-trimester pregnancy termination. J Pak Med Assoc
2011; 61:399.
28.
Cuellar Torriente M. Silent uterine rupture with the use of misoprostol for second
trimester termination of pregnancy : a case report. Obstet Gynecol Int 2011; 2011:584652.
29.
Berghella V, Airoldi J, O'Neill AM, et al. Misoprostol for second trimester pregnancy
termination in women with prior caesarean: a systematic review. BJOG 2009; 116:1151.
30.
Naguib AH, Morsi HM, Borg TF, et al. Vaginal misoprostol for second-trimester
pregnancy termination after one previous cesarean delivery. Int J Gynaecol Obstet 2010;
108:48.
31.
Fawzy M, Abdel-Hady el-S. Midtrimester abortion using vaginal misoprostol for women
with three or more prior cesarean deliveries. Int J Gynaecol Obstet 2010; 110:50.
32.
33.
Ngai SW, Tang OS, Ho PC. Prostaglandins for induction of second-trimester termination
and intrauterine death. Best Pract Res Clin Obstet Gynaecol 2003; 17:765.
34.
35.
Jain JK, Mishell DR Jr. A comparison of misoprostol with and without laminaria tents for
induction of second-trimester abortion. Am J Obstet Gynecol 1996; 175:173.
36.
Borgatta L, Chen AY, Vragovic O, et al. A randomized clinical trial of the addition of
laminaria to misoprostol and hypertonic saline for second-trimester induction abortion.
Contraception 2005; 72:358.
37.
38.
Fjerstad M, Trussell J, Sivin I, et al. Rates of serious infection after changes in regimens
for medical abortion. N Engl J Med 2009; 361:145.
39.
40.
41.
42.
Bebbington MW, Kent N, Lim K, et al. A randomized controlled trial comparing two
protocols for the use of misoprostol in midtrimester pregnancy termination. Am J Obstet
Gynecol 2002; 187:853.
43.
Dickinson JE, Evans SF. A comparison of oral misoprostol with vaginal misoprostol
administration in second-trimester pregnancy termination for fetal abnormality. Obstet
Gynecol 2003; 101:1294.
44.
Tang OS, Miao BY, Lee SW, Ho PC. Pilot study on the use of repeated doses of
sublingual misoprostol in termination of pregnancy up to 12 weeks gestation: efficacy and
acceptability. Hum Reprod 2002; 17:654.
45.
Cheung W, Tang OS, Lee SW, Ho PC. Pilot study on the use of sublingual misoprostol in
termination of pregnancy up to 7 weeks gestation. Contraception 2003; 68:97.
46.
47.
Ngoc NT, Blum J, Raghavan S, et al. Comparing two early medical abortion regimens:
mifepristone+misoprostol vs. misoprostol alone. Contraception 2011; 83:410.
48.
Ngoc NT, Shochet T, Raghavan S, et al. Mifepristone and misoprostol compared with
misoprostol alone for second-trimester abortion: a randomized controlled trial. Obstet Gynecol
2011; 118:601.
49.
50.
Carbonell JL, Rodrguez J, Velazco A, et al. Oral and vaginal misoprostol 800 microg
every 8 h for early abortion. Contraception 2003; 67:457.
51.
Carbonell JL, Velazco A, Varela L, et al. Misoprostol for abortion at 9-12 weeks'
gestation in adolescents. Eur J Contracept Reprod Health Care 2001; 6:39.
52.
Carbonell JL, Rodriguez J, Aragn S, et al. Vaginal misoprostol 1000 microg for early
abortion. Contraception 2001; 63:131.
53.
54.
Ngai SW, Tang OS, Chan YM, Ho PC. Vaginal misoprostol alone for medical abortion up
to 9 weeks of gestation: efficacy and acceptability. Hum Reprod 2000; 15:1159.
55.
Esteve JL, Varela L, Velazco A, et al. Early abortion with 800 micrograms of misoprostol
by the vaginal route. Contraception 1999; 59:219.
56.
Carbonell Esteve JL, Varela L, Velazco A, et al. Vaginal misoprostol for late first trimester
abortion. Contraception 1998; 57:329.
57.
Carbonell JL, Varela L, Velazco A, et al. Vaginal misoprostol for abortion at 10-13 weeks'
gestation. Eur J Contracept Reprod Health Care 1999; 4:35.
58.
Carbonell JL, Varela L, Velazco A, Fernndez C. The use of misoprostol for termination
of early pregnancy. Contraception 1997; 55:165.
59.
60.
61.
von Hertzen H, Piaggio G, Huong NT, et al. Efficacy of two intervals and two routes of
administration of misoprostol for termination of early pregnancy: a randomised controlled
equivalence trial. Lancet 2007; 369:1938.
62.
Tang OS, Lau WN, Chan CC, Ho PC. A prospective randomised comparison of
sublingual and vaginal misoprostol in second trimester termination of pregnancy. BJOG 2004;
111:1001.
63.
64.
Ganguly RP, Saha SP, Mukhopadhyay S, et al. A comparative study on sublingual versus
oral and vaginal administration of misoprostol for late first and early second trimester abortion.
J Indian Med Assoc 2010; 108:283.
65.
66.
Wildschut H, Both MI, Medema S, et al. Medical methods for mid-trimester termination of
pregnancy. Cochrane Database Syst Rev 2011; :CD005216.
67.
68.
Sayette H, Redwine D, Sivin I, et al.. Buccal use of misoprostol alone for early abortion:
The experience in four Latin American countries (abstract). Contraception 2011; 84:302.
69.
Winikoff B, Dzuba IG, Creinin MD, et al. Two distinct oral routes of misoprostol in
mifepristone medical abortion: a randomized controlled trial. Obstet Gynecol 2008; 112:1303.
70.
Middleton T, Schaff E, Fielding SL, et al. Randomized trial of mifepristone and buccal or
vaginal misoprostol for abortion through 56 days of last menstrual period. Contraception
2005; 72:328.
71.
72.
Patel A, Talmont E, Morfesis J, et al. Adequacy and safety of buccal misoprostol for
cervical preparation prior to termination of second-trimester pregnancy. Contraception 2006;
73:420.
73.
Ellis SC, Kapp N, Vragpvoc O, Borgata L. Randomized trial of buccal versus vaginal
misoprostol for induction of second trimester abortion. Contraception 2010; 81:441.
74.
75.
Makhlouf AM, Al-Hussaini TK, Habib DM, Makarem MH. Second-trimester pregnancy
termination: comparison of three different methods. J Obstet Gynaecol 2003; 23:407.
76.
Feldman DM, Borgida AF, Rodis JF, et al. A randomized comparison of two regimens of
misoprostol for second-trimester pregnancy termination. Am J Obstet Gynecol 2003; 189:710.
77.
Fandes A, Fiala C, Tang OS, Velasco A. Misoprostol for the termination of pregnancy
up to 12 completed weeks of pregnancy. Int J Gynaecol Obstet 2007; 99 Suppl 2:S172.
78.
Guix C, Palacio M, Figueras F, et al. Efficacy of two regimens of misoprostol for early
second-trimester pregnancy termination. Fetal Diagn Ther 2005; 20:544.
79.
80.
Wong KS, Ngai CS, Yeo EL, et al. A comparison of two regimens of intravaginal
misoprostol for termination of second trimester pregnancy: a randomized comparative trial.
Hum Reprod 2000; 15:709.
81.
82.
Dickinson JE, Evans SF. The optimization of intravaginal misoprostol dosing schedules
in second-trimester pregnancy termination. Am J Obstet Gynecol 2002; 186:470.
83.
84.
Dodd J, O'Brien L, Coffey J. Misoprostol for second and third trimester termination of
pregnancy: a review of practice at the Women's and Children's Hospital, Adelaide, Australia.
Aust N Z J Obstet Gynaecol 2005; 45:25.
85.
Langer BR, Peter C, Firtion C, et al. Second and third medical termination of pregnancy
with misoprostol without mifepristone. Fetal Diagn Ther 2004; 19:266.
86.
Prachasilpchai N, Russameecharoen K, Borriboonhirunsarn D. Success rate of secondtrimester termination of pregnancy using misoprostol. J Med Assoc Thai 2006; 89:1115.
87.
Perritt JB, Burke A, Edelman AB. Interruption of nonviable pregnancies of 24-28 weeks'
gestation using medical methods: release date June 2013 SFP guideline #20133.
Contraception 2013; 88:341.
88.
Bracken H, Ngoc NT, Banks E, et al. Buccal misoprostol for treatment of fetal death at
14-28 weeks of pregnancy: a double-blind randomized controlled trial. Contraception 2014;
89:187.
89.
90.
Kkgz Gle U, Urunsak IF, Eser E, et al. Misoprostol for midtrimester termination of
pregnancy in women with 1 or more prior cesarean deliveries. Int J Gynaecol Obstet 2013;
120:85.
91.
92.
93.
94.
95.
Safe abortion: Technical and policy guidelines for health systems. World Health
Organization, Geneva, 2003.
96.
Green J, Borgatta L, Sia M, et al. Intervention rates for placental removal following
induction abortion with misoprostol. Contraception 2007; 76:310.
97.
98.
Harwood B, Meckstroth KR, Mishell DR, Jain JK. Serum beta-human chorionic
gonadotropin levels and endometrial thickness after medical abortion. Contraception 2001;
63:255.
99.
100.
Creinin MD, Harwood B, Guido RS, et al. Endometrial thickness after misoprostol use for
early pregnancy failure. Int J Gynaecol Obstet 2004; 86:22.
101.
Reynolds A, Ayres-de-Campos D, Costa MA, Montenegro N. How should success be
defined when attempting medical resolution of first-trimester missed abortion? Eur J Obstet
Gynecol Reprod Biol 2005; 118:71.
102.
Reeves MF, Fox MC, Lohr PA, Creinin MD. Endometrial thickness following medical
abortion is not predictive of subsequent surgical intervention. Ultrasound Obstet Gynecol
2009; 34:104.
103.
Honkanen H, Piaggio G, Hertzen H, et al. WHO multinational study of three misoprostol
regimens after mifepristone for early medical abortion. BJOG 2004; 111:715.
104.
Ngai SW, Tang OS, Ho PC. Randomized comparison of vaginal (200 microg every 3 h)
and oral (400 microg every 3 h) misoprostol when combined with mifepristone in termination
of second trimester pregnancy. Hum Reprod 2000; 15:2205.
105.
Baird DT. Medical abortion in the first trimester. Best Pract Res Clin Obstet Gynaecol
2002; 16:221.
106.
Durocher J, Bynum J, Len W, et al. High fever following postpartum administration of
sublingual misoprostol. BJOG 2010; 117:845.
107.
Philip NM, Winikoff B, Moore K, Blumenthal P. A consensus regimen for early abortion
with misoprostol. Int J Gynaecol Obstet 2004; 87:281.
108.
Shannon C, Brothers LP, Philip NM, Winikoff B. Infection after medical abortion: a review
of the literature. Contraception 2004; 70:183.
109.
Fischer M, Bhatnagar J, Guarner J, et al. Fatal toxic shock syndrome associated with
Clostridium sordellii after medical abortion. N Engl J Med 2005; 353:2352.
110.
Sinave C, Le Templier G, Blouin D, et al. Toxic shock syndrome due to Clostridium
sordellii: a dramatic postpartum and postabortion disease. Clin Infect Dis 2002; 35:1441.
111.
Couzin J. infectious disease. RU-486-linked deaths open debate about risky bacteria.
Science 2006; 312:986.
112.
Winikoff B. Clostridium sordellii infection in medical abortion. Clin Infect Dis 2006;
43:1447.
113.
Aronoff DM, Hao Y, Chung J, et al. Misoprostol impairs female reproductive tract innate
immunity against Clostridium sordellii. J Immunol 2008; 180:8222.
114.
Jain JK, Harwood B, Meckstroth KR, Mishell DR. Early pregnancy termination with
vaginal misoprostol combined with loperamide and acetaminophen prophylaxis.
Contraception 2001; 63:217.
115.
Daskalakis G, Papantoniou N, Mesogitis S, et al. Sonographic findings and surgical
management of a uterine rupture associated with the use of misoprostol during secondtrimester abortion. J Ultrasound Med 2005; 24:1565.
116.
Misoprostol and teratology: Reviewing the evidence, Philip, N, Shannon, C, Winikoff, B
(Eds), Population Council, New York 2002.
117.
Orioli IM, Castilla EE. Epidemiological assessment of misoprostol teratogenicity. BJOG
2000; 107:519.
118.
Castilla EE, Orioli IM. Teratogenicity of misoprostol: data from the Latin-American
Collaborative Study of Congenital Malformations (ECLAMC). Am J Med Genet 1994; 51:161.
119.
Addar MH. Methotrexate embryopathy in a surviving intrauterine fetus after presumed
diagnosis of ectopic pregnancy: case report. J Obstet Gynaecol Can 2004; 26:1001.
120.
Csapo AI. The prospects of PGs in postconceptional therapy. Prostaglandins 1973;
3:245.
121.
Dodd JM, Crowther CA. Misoprostol versus cervagem for the induction of labour to
terminate pregnancy in the second and third trimester: a systematic review. Eur J Obstet
Gynecol Reprod Biol 2006; 125:3.
Topic 5434 Version 13.0