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Literature review current through: Oct 2016. | This topic last updated: Aug 29, 2016.
INTRODUCTION Medication abortion (also referred to as medical abortion) is the termination
of pregnancy with use of medications alone rather than surgery. Mifepristone, an antiprogestin,
is approved for use in the United States, in combination with misoprostol, for the termination of
pregnancies up to 70 days of gestation. First-trimester medication abortion beyond 70 days is
associated with a lower efficacy and requires in-hospital supervision.
The use of mifepristone in combination with misoprostol for medication termination of pregnancy
in the first trimester is reviewed here. Use of misoprostol alone for medication abortion and other
methods of pregnancy termination are discussed separately. (See "Misoprostol as a single agent
for medical termination of pregnancy" and "Overview of pregnancy termination".)
MEDICATION VERSUS SURGICAL TERMINATION Medication and surgical (uterine dilation
and suction aspiration) abortion are both safe and effective approaches for appropriately
selected patients [1]. The choice is based upon availability, gestational age (medication abortion
is less successful in the late first trimester), and patient preference. Women seeking abortion
care should be counseled about the advantages and disadvantages of both options.
Prior to 2000, Medication abortion in the first trimester was available only using a prostaglandin
with or without methotrexate. Since 2000, medication abortion with mifepristone and misoprostol
was approved for use by the US Food and Drug Administration (FDA) in the United States.
Surgical abortion is still performed in the majority of cases and also in cases in which
medication abortion is incomplete. The United States Centers for Disease Control and
Prevention (CDC) reported that, in 2009, 16.2 percent of abortions at 8 weeks of gestation and
0.9 percent at >8 weeks were performed with medication alone [2].
First-trimester surgical abortion is effective in terminating pregnancy in 98 to 99 percent of
procedures and has a complication rate of 0 to 3 percent [3]. The major complications of
surgical abortion are incomplete evacuation, uterine perforation, problems related to anesthesia,
and endometritis. (See "Surgical termination of pregnancy: First trimester", section on
'Complications'.)
The overall success rate of medication abortion with mifepristone and misoprostol is not quite as
high as its surgical counterpart; surgical aspiration to complete the termination is required in 2 to
8 percent of cases [4,5]. Incomplete evacuation is considered failure of the method rather than a
complication.
In terms of complications, data from Planned Parenthood affiliates in 2009 to 2010 that included
233,805 medication abortions showed significant adverse events or outcomes occurred in 0.65
percent of women [6]. The complication rate for medication abortion is similar to surgical
abortion, but the types and etiologies of the complications are different. Endometritis has a
similar incidence as in surgical abortion; life-threatening infections are rare, but have occurred
more often than with surgical abortion. Hemorrhage occurs at similar rates, but the cause is
typically uterine atony or retained products of conception rather than the causes in surgical
abortion, which are usually cervical laceration or uterine injury due to instrumentation. (See
'Side effects and complications' below.)
The teratogenic risk to an ongoing pregnancy is higher with medication abortion than with
surgical abortion, but ongoing pregnancy is rare. (See 'Teratogenicity' below.)
The main difference between surgical and medication abortion is the patients experience. The
surgical procedure is completed in one office visit and takes place in a healthcare facility.
Patients experience a gynecologic procedure in the lithotomy position and then leave the visit
knowing that the abortion is complete. Analgesics or anesthesia may be used, but there may be
some discomfort during the procedure and mild to moderate uterine cramping and bleeding for
several days afterward.
Medication abortion avoids a surgical procedure and anesthesia, but takes a longer time
(several days) and at least one more clinic visit than a surgical abortion. The patient usually
experiences more uncomfortable effects and over a longer period of time (bleeding, cramping,
nausea, vomiting). The patient has a greater awareness of the blood loss and may be able to
identify pregnancy tissue that passes. Some patients prefer the greater degree of control they
have over the process and having part of the process in a nonclinical setting [7]. In addition,
some patients will require a surgical abortion if the medication abortion is unsuccessful. If the
patient has an ongoing pregnancy, there is a risk of fetal abnormalities. (See 'Teratogenicity'
below.)
Acceptability is high for both medication and surgical abortion, but satisfaction appears to be
higher after surgical abortion. This was illustrated in two randomized trials that found that the
rate of patient satisfaction was significantly higher for surgical abortion (92 verus 82 percent in
one trial [8]; 94 versus 69 percent in another [7]). In contrast, in a prospective cohort study, a
higher proportion of women who underwent medication abortion would choose the same
method if a future abortion was required (81 versus 58 percent in the surgical abortion group)
[9].
Given the available data, we suggest first-trimester medication abortion for eligible women who
place a high value on avoiding surgery or anesthesia and who are willing to accept more
discomfort and awareness of the procedure. For other women, particularly those who place a
high value on completing the procedure in one visit, we recommend surgical abortion.
INDICATIONS The US Food and Drug Administration has approved mifepristone for
termination of intrauterine pregnancy up to 70 days of gestation [10].
According to the manufacturer of mifepristone, pregnancy is dated from the first day of the last
menstrual period in a presumed 28-day cycle with ovulation occurring at mid-cycle [11]. The
duration of pregnancy may be determined from menstrual history and by clinical examination.
conditions that are poorly controlled and in which there is clinical concern for excessive blood
loss or a need for monitoring, surgical abortion under controlled conditions is generally
preferable.
Drug interactions with mifepristone should be investigated for patients who are on other
medications. Mifepristone is metabolized by cytochrome P450 3A4 (CYP3A4), and thus may
theoretically interact with agents that impact CYP3A4 function (table 2). However, specific drug
or food interactions with the single dose of mifepristone used for pregnancy termination have not
been reported. Even if interactions were shown to alter serum concentrations, those
concentrations are not correlated with efficacy and ingestion of a single dose in the range of 200
mg up to 800 mg produces approximately the same serum concentration [13-15].
Mifepristone itself acts as a moderate inhibitor of CYP3A4 metabolism and can thereby alter
concentrations of other drugs. Due to its prolonged half-life and irreversible CYP binding,
potential interactions of mifepristone should be checked particularly for medications that have a
narrow therapeutic index. Examples include: immunosuppressants (eg, cyclosporine, sirolimus,
tacrolimus); cardiovascular drugs (eg, calcium channel blockers, anti-arrhythmics, others);
analgesic/anesthetic agents (eg, fentanyl, ketamine, methadone, others). The effect of a single
dose of mifepristone on metabolism and effect of other drugs highly dependent upon CYP3A4
for their metabolism or activation may persist for up to two weeks. Interactions with these
medications should be checked prior to administration of mifepristone.
Some medications that inhibit CYP3A4 metabolism are associated with QT interval prolongation
(table 3) [16]. There are no reported cases of QT prolongation with use of mifepristone. The
manufacturer of mifepristone advises that use of the medication should be avoided with QT
interval-prolonging drugs or in patients with potassium channel variants resulting in a long QT
interval [17]. (See "Acquired long QT syndrome".)
CLINICIAN REQUIREMENTS The US Food and Drug Administration (FDA) requires that
mifepristone be prescribed only by physicians (not nurse practitioners, physician assistants, or
nurse midwives) who are able to [18]:
However, in 2016, the FDA revised the labeling with a protocol that is nearly identical to the
evidence-based regimen [10,19]. The FDA-approved regimen is:
Day one 200 mg of mifepristone taken by mouth
Twenty-four to 48 hours after taking mifepristone 800 mcg of misoprostol taken
buccally (in the cheek pouch); this is taken at a location appropriate for the patient (clinic,
home, or other location)
Seven to 14 days after taking mifepristone Follow-up with a clinician
Evidence for the regimen The evidence-based regimen resulted in fewer ongoing
pregnancies, a lower frequency of side effects, lower cost, greater convenience, and greater
efficacy at gestations between 50 and 63 days compared with the original FDA regimen.
Studies have evaluated the components of each regimen. This evidence is reviewed in the
sections that follow.
Mifepristone The oral mifepristone dose is 200 mg rather than 600 mg because it is as
effective. This was demonstrated in a meta-analysis of four randomized trials that found a
comparable complete abortion rate for 600 mg compared with 200 mg (risk ratio 1.07; 95% CI
0.87-1.32) [20]. Use of a lower dose has the benefit of decreasing the cost of the procedure.
Mifepristone is supplied in 200 mg tablets and use of doses lower than 200 mg do not offer a
benefit and may be less effective [21-23].
Mifepristone administered alone results in complete termination of pregnancy in 64 to 85 percent
of women at this gestational age [24-26]. Since these efficacy rates are inadequate for general
clinical use, a prostaglandin is administered after mifepristone.
Misoprostol Misoprostol, a synthetic prostaglandin E1, is used sequentially with mifepristone
for first-trimester medication abortion. The drug is inexpensive, can be stored at room
temperature, and is widely available. Misoprostol is the sole prostaglandin approved by the FDA
for use for medication abortion, and the FDA requires misoprostol be used in conjunction with
mifepristone for medication abortion.
Other prostaglandins have been used in combination with mifepristone for termination of
pregnancy, but are inferior to misoprostol. Gemeprost is supplied as a vaginal pessary.
Gemeprost is expensive, needs to be refrigerated, and is not registered for use in the United
States. It has also been found in a randomized trial to be associated with more treatment
failures than misoprostol [27]. Another prostaglandin, sulprostone, was associated with
cardiovascular adverse effects [28].
Route of administration and dose Misoprostol is manufactured and approved by the FDA
for use as an oral tablet, but several routes of administration (oral, vaginal, buccal, sublingual)
have been used for mifepristone/misoprostol first-trimester medication abortion. The dose
ranges from 400 to 800 mcg and depends upon the route.
We recommend buccal administration of misoprostol rather than other routes. Oral
administration of misoprostol is a reasonable option for women at 49 days of gestation. We
recommend caution with the vaginal administration of misoprostol due to a possible association
with severe infection.
Buccal and vaginal dosing have greater bioavailability, a later peak serum concentration, and a
longer duration of bioactivity than oral administration [29-32]. These pharmacokinetics are likely
responsible for the decrease in side effects with vaginal dosing [1,20]. Vaginal and buccal
administration is more effective than oral, particularly for gestations of >49 days.
Vaginal administration was the original route used in the evidence-based regimen, but use of
this route was proposed as a contributing factor in rare cases of clostridial sepsis and death in
women undergoing medication abortion [33,34]. In addition, women have reported a preference
for oral rather than vaginal administration in some studies [35,36], but appear to find both oral
and buccal dosing acceptable [37]. In response, buccal dosing has become the preferred route.
Sublingual administration is under investigation and is not commonly used clinically. (See
'Clostridial sepsis' below.)
There are few high quality data comparing buccal and oral dosing. In the only randomized trial,
buccal dosing was more effective than oral, but a subgroup analysis found a significant
decrease in the rate of failure to achieve complete abortion only for >49 days (5 versus 13
percent; risk ratio 0.37, 95% CI 0.18-0.73) and insufficient statistical power to assess the
difference at 49 days (3 versus 4 percent; risk ratio 0.72, 95% CI 0.25-2.04) [37]. The rate of
gastrointestinal side effects and patient satisfaction were similar for the two routes of
administration.
Most trials have compared vaginal and oral dosing, since the vaginal route was the original route
of administration used for the evidence-based regimen. Randomized trial data have shown that
the vaginal route is more effective and is associated with fewer side effects than oral dosing,
which is used in the FDA/manufacturer regimen [38]. A meta-analysis of four randomized trials
found that oral compared with vaginal dosing resulted in a significantly higher rate of failure to
achieve complete abortion (11 versus 4 percent; risk ratio 3.05, 95% CI 2.24-4.14) and side
effects, including nausea and diarrhea [20].
Buccal and vaginal administration were found to have similar efficacy and incidence of side
effects in one randomized trial, but this provides only indirect support for comparing buccal with
oral dosing [39]. In addition, women reported a preference for oral rather than vaginal
administration in some studies [35,36].
The buccal misoprostol dose used in the evidence-based and revised FDA regimen is 800 mcg;
however, 400 mcg was found to be equally effective in a randomized trial [40]. For buccal
dosing, the patient places the tablets of misoprostol between the cheek and gum of the lower
jaw where the tablets remain for at least 30 minutes. Typically patients are instructed to swallow
any remaining pill fragments after 30 minutes.
Sublingual administration is under investigation, but the disadvantage of this route is that it has a
similar pharmacokinetic profile to oral dosing. One randomized trial found comparable efficacy
and side effects for sublingual and buccal administration [41].
The addition of a second dose of misoprostol after three to four hours has been proposed.
Studies show that this increases side effects, but may decrease the rate of ongoing pregnancy,
especially at later gestational ages [42-44]. Additional doses of misoprostol are not currently part
of either the FDA-approved regimen or the evidence-based alternative regimen.
Timing The interval from mifepristone to misoprostol is 24 to 48 hours in the
FDA/manufacturer regimen and 24 to 72 hours in the evidence-based regimen. Extending the
interval to 24 to 72 hours does not appear to impact efficacy.
This flexibility in dosing increases convenience for women, since they can schedule their
abortion accordingly when time permits and a support person is available. Studies have
consistently supported similar efficacy for buccal administration of misoprostol 24 to 48 hours
after mifepristone with success rates of 95 to 98 percent [39,45].
Most studies evaluating the effect of varying intervals on efficacy evaluated vaginal or buccal
dosing of the misoprostol. A meta-analysis of randomized trials included three trials for which
the summary data showed no significant difference in the rate of complete abortion when the
interval was decreased from 48 to 24 hours (risk ratio 1.24, 95% CI 0.95-1.63) [20]. One trial
showed no difference in efficacy for an interval of 72 compared with 48 hours (risk ratio 1.68,
95% CI 0.95-3.01), but this trial lacked sufficient statistical power to detect a difference [46]. In
the same trial, 72 compared with 24 hours resulted in a significant increase in the rate of
incomplete abortion (4 versus 2 percent; risk ratio 1.93, 95%CI 1.05-3.58). Most comparisons in
the meta-analysis showed no difference in side effects with a variation in interval from 24 to 72
hours.
Intervals from mifepristone to misoprostol of less than 24 hours appear to be less effective
[20,47]. There are no data on misoprostol administration more than 72 hours after mifepristone.
Clinician versus self-administration The revised FDA and the evidence-based regimen
includes self-administration of misoprostol at home rather than by a clinician in a clinic setting.
This approach appears to be as safe and effective as administration in a clinic setting, and offers
advantages in terms of cost and convenience. This was best illustrated in a systematic review of
9 prospective studies including 4522 women undergoing first-trimester medication abortion that
found that self-administration at home compared with administration by a clinician was
associated with no significant differences in the rate of complete abortion (86 to 97 percent
versus 80 to 99 percent; odds ratio 0.8, 95% CI 0.5-1.5) [48]. Self-administration was associated
with higher patient satisfaction. There was a slight increase in the duration of pain and vomiting
(0.3 days longer) with self-administration, but no increase in contact with health services.
CLINICAL PROTOCOL First-trimester medication abortion typically includes the following
steps:
Initial visit and mifepristone administration The patient is seen in an outpatient
setting. This visit includes confirmation of pregnancy, counseling about options and
informed consent, blood typing and administration of Rh immune globulin if needed. A
single dose of mifepristone is administered.
Misoprostol administration Misoprostol is self-administered by the patient in a
nonclinical setting 24 to 72 hours after mifepristone administration.
Follow-up visit A final visit is conducted within two weeks after treatment to ensure
that the pregnancy was completely expelled, to identify any complications requiring
treatment, and to provide contraception.
Initial clinic visit The first clinic visit is used to assess a woman's eligibility for medication
abortion and to dispense mifepristone.
Preprocedure evaluation and preparation
Pregnancy confirmation and gestational age Pregnancy should be confirmed by urinary
or serum human chorionic gonadotropin (hCG) measurement or pelvic ultrasound.
Gestational age must be assessed by clinical evaluation or ultrasound because the duration of
gestation is critical to deciding whether a woman is a candidate for medication termination of
pregnancy. (See 'Indications' above and "Overview of pregnancy termination", section on
'Determining gestational age'.)
Sonographic evaluation also allows exclusion of ectopic pregnancy. For women with symptoms
or high risk factors, ectopic pregnancy should be excluded before proceeding with mifepristone
Mifepristone The woman is given mifepristone if she meets eligibility criteria (table 4) and
after she consents to the procedure. Occasionally, patients will experience bleeding or cramping
after the mifepristone dose. Most women only have symptoms after the misoprostol, especially if
it is given within 24 to 36 hours of mifepristone. However, even if bleeding and cramping occurs,
unless expulsion of the gestation has been confirmed, patients should take the misoprostol as
instructed. Approximately 1 to 5 percent of patients will expel the conceptus after a single dose
of mifepristone only, without misoprostol [49].
Prophylactic antibiotics Use of prophylactic antibiotics for medication abortion is
controversial [50]. The rate of infection following medication abortion is low, approximately 0.3
percent in prospective studies [28,30,49,51-53]. However, some cases of serious infection do
occur. In particular, there have been rare cases of sepsis and death in women with clostridial
infections. A possible contributing factor to these infections was use of a vaginal route for
misoprostol. No further cases have been found since most clinicians and large clinical
organizations modified their practice to include one or more of the following interventions: use of
prophylactic antibiotics, use of a non-vaginal route of administration, or counseling about
seeking medical attention in case of signs of life-threatening infection. However, it is uncertain
whether these interventions, and which intervention, has prevented further cases of clostridial
sepsis. (See 'Fever and infection' below.)
There are no randomized trials regarding use of prophylactic antibiotics for first-trimester
medication abortion. The largest study was an observational study conducted by Planned
Parenthood of over 227,000 women with gestational ages up to 63 days who underwent
mifepristone/misoprostol abortion [33]; the rate of serious infection decreased from 0.93 to 0.06
per 1000 women with use of prophylactic doxycycline (100 mg orally twice a day for 7 days,
starting on the day of mifepristone administration) compared with no antimicrobial prophylaxis.
Doxycycline provides coverage for chlamydia, most gonorrhea strains, and has in vitro efficacy
against clostridial species. Based on these data, the number needed to treat with a week of
doxycycline is more than 5000 women to prevent one serious infection requiring intravenous
antibiotics. Of note, during the time period of the study, the route of administration of misoprostol
was also changed from vaginal to buccal; therefore, it is possible that this is also partially
responsible for the decrease in infection rate.
The disadvantages of routine use of prophylactic antibiotics include: cost, increased complexity
of the regimen, and antibiotic resistance.
The Society of Family Planning (SFP) states that, although individual practitioners may decide to
use antibiotics with provision of medication abortion, the SFP does not believe universal
antibiotics is required for all women having a medication abortion [54]. They also make the
following recommendation based on limited or inconsistent scientific evidence: although the risk
of serious infection is low, recent data indicate that there may be significant reduction in the risk
of serious infection by providing treatment doses of doxycycline starting at the time the
medication abortion treatment is initiated.
Given the available evidence, we suggest universal use of antibiotic prophylaxis for firsttrimester medication abortion. This is a reasonable choice for those who value potential
prevention of rare cases of severe infection more than the disadvantages associated with
routine antibiotic use.
Since decisions regarding use of prophylactic antibiotics are made based upon weak evidence,
we advise that the women undergoing first-trimester medication abortion be counseled about
this controversy and be involved in making this decision on an individual basis.
Further instructions The patient should be given further instructions regarding returning to
clinic for a misoprostol dose or self-administration.
Written and verbal instructions should be given regarding symptoms and adverse effects and
what to do in the case of significant pain, bleeding, or other adverse reactions. For pain, a
nonsteroidal anti-inflammatory drug (NSAID) may be taken. If pain is unrelieved, the patient
should call her clinician and an oral narcotic analgesia may be prescribed. Analgesic,
antiemetic, and antidiarrheal medicines can be taken, as required. She should also be given a
telephone number to call with questions or in case of an emergency.
weeks posttreatment and a phone call at one month) with a routine postabortion clinic visit
(urine or serum hCG testing and/or ultrasound) [59]. Interestingly, among women who declined
to participate in the trial, a common reason was the desire to avoid follow-up visits, and trial
participants reported that they prefer self-assessment to a routine clinic visit. Similar to previous
studies, the self-assessment group and routine follow-up groups had similar rates of complete
abortion (94 and 95 percent), but the self-assessment group had three cases of ongoing
pregnancy that were not detected by the urine hCG test and all were discovered in the second
trimester, compared with no ongoing pregnancies in the routine follow-up group. Thus, to reliably
detect ongoing pregnancy, we recommend a follow-up clinic visit with clinical evaluation. If selfassessment is strongly desired or a clinic visit is not possible, clinicians should counsel on both
the risk and the symptoms of ongoing pregnancy, and follow a protocol that includes use of urine
pregnancy testing and a standardized telephone encounter.
Confirming complete abortion Confirming complete expulsion of the pregnancy involves
taking a history and performing a pelvic examination; ultrasound examination is also performed
by most clinicians. Women who do not expel the pregnancy after medication abortion require
surgical evacuation. (See "Surgical termination of pregnancy: First trimester".)
In most studies of medication termination of pregnancy, the number of women lost-to-follow-up
ranges from 0.6 to 5 percent [60], although it reached 11 percent in one study [61]. The need for
medical confirmation of pregnancy termination must be emphasized to users of this method, and
women must be informed of the possibility of congenital abnormalities in the event that
pregnancy continues. (See 'Teratogenicity' below.)
A history of vaginal bleeding and cramping is not sufficient evidence that the pregnancy has
been terminated. A lack of bleeding, however, can be a sign of ongoing pregnancy. The patient
should be asked whether she passed what appeared to be tissue and whether this passage of
tissue coincided with several hours of severe cramps that decreased in severity after the tissue
was passed.
A pelvic examination finding of a uterus that is firm and of nongravid size may be used for
confirmation of complete abortion without the use of ultrasound [62]. Confirmation of expulsion
with pelvic ultrasound is required if incomplete abortion is suspected [63,64]. Signs and
symptoms of an incomplete abortion include: ongoing cramping or bleeding, dilated cervix,
uterus enlarged or unchanged from the initial examination.
On pelvic ultrasound, absence of a gestational sac is confirmation of a complete abortion.
Heterogeneous echoes in the uterus without a gestational sac are not evidence of incomplete
expulsion [64]. Measured endometrial thickness on transvaginal ultrasound is not a clinically
useful predictor for the subsequent need for surgical intervention [65-69].
Serum hCG testing is not typically used to confirm complete abortion. A single measurement of
hCG at the follow-up visit is not informative, because hCG concentration may remain elevated
for weeks after complete abortion.
Evaluating for complications The history and clinical examination are also useful to
evaluate for side effects and complications. The patient should be asked about continued pain,
fever, or excessive vaginal bleeding. (See 'Side effects and complications' below.)
Postabortion contraception Contraception should be addressed at the follow-up visit, if not
sooner. The patient should be counseled that ovulation usually occurs by three weeks after
medication abortion and another pregnancy can occur before resumption of normal menses
[70]. Post-termination contraception is discussed in detail separately. (See "Postabortion
contraception".)
SIDE EFFECTS AND COMPLICATIONS The side effects and complications with medication
abortion generally include those associated with the regimen as a whole (mifepristone and
misoprostol) [24]. Side effects primarily consist of gastrointestinal discomfort (nausea, vomiting,
diarrhea), pain, and excessive vaginal bleeding. Some women experience headache, dizziness,
or fatigue. On occasion, surgical intervention may be required to terminate the pregnancy if side
effects are poorly tolerated (eg, severe pain or vomiting) [49].
persists for a day or more after expulsion of the pregnancy, or a purulent vaginal discharge [9497]. Postabortal endometritis is treated in the same manner as other types of postpartum
endometritis. (See "Postpartum endometritis".)
Clostridial sepsis Clostridial sepsis has been responsible for seven deaths following firsttrimester medication abortion in the United States and Canada between 2000 and 2010 [94-97].
In the majority of cases, the microbial agent identified was Clostridium sordellii. C. perfringens
was identified in one case, and in an additional case, a patient with a fatal C. perfringens
infection received laminaria and vaginal misoprostol, but no mifepristone to terminate a 19-week
gestation. With one exception, all of the septic deaths involved the off-label dosing regimen
consisting of 200 mg of oral mifepristone followed by 800 mcg of vaginal misoprostol.
Reports are rare of fulminant lethal clostridial sepsis in women of childbearing age, but there is
generally an association with childbirth, spontaneous and induced abortion, or cervical or
uterine procedures [98,99]. Sepsis related to C. sordellii is difficult to diagnose because of its
subtle clinical manifestations and may rapidly progress to death (death within three days of
hospitalization) [100].
A causal relationship between sepsis and the use of mifepristone has not been established. The
US Food and Drug Administration (FDA) is working with the manufacturers of mifepristone and
misoprostol tablets to conduct special tests to ensure there is no contamination of either product
with C. sordellii. Because of the adverse events described above, the FDA required that a black
box warning be included as part of mifepristone drug information.
Physiologic explanations for the development of serious infection have been proposed. Both
misoprostol and mifepristone induce cervical dilation. Studies in rats show that cervical dilation
with mifepristone may allow for ascending infection of necrotic decidual tissue [101].
Endocrinologic and immune mechanisms may also interact to increase the risk of infection in
women undergoing mifepristone/misoprostol abortion. Mifepristone-induced glucocorticoid
receptor blockade may result in an inappropriate cytokine response of the immune system [100].
Toxins from C. sordellii may also repress glucocorticoid activity. Mifepristone and toxins
additively prevent glucocorticoid suppression of tumor necrosis factor alpha, therefore interfering
with the immune response [102]. Misoprostol may suppress the immune reaction to clostridial
infections [103,104].
Mifepristone/prostaglandin abortion had been used widely in Europe before its introduction in
the United States. However, there have not been similar cases of clostridial sepsis. Two deaths
have been reported, neither related to infection. One hypothesis for absence of similar cases of
C. sordellii infection in Europe is that vaginal dosing was uncommon in Europe [34] and
prophylactic antibiotic treatment often given [31,34].
In response to the fatal infections reported, and without an identified etiology, some clinicians,
including Planned Parenthood (the largest abortion provider in the United States) have started
giving all patients prophylactic antibiotics. (See 'Prophylactic antibiotics' above.)
Clinicians should be aware of the presenting symptoms of clostridial sepsis. Patients with C.
sordellii sepsis following abortion generally presented without fever, bacteremia, rash, or
significant findings on pelvic examination, but did have dramatic leukocytosis with a marked left
shift, hemoconcentration, tachycardia, hypotension crampy abdominal pain, pleural/peritoneal
effusion, and general malaise (weakness, nausea, vomiting, diarrhea). Gas gangrene was not
noted. There should be a high index of suspicion of sepsis if these findings are present, and the
patient should be evaluated and treated immediately. Optimal therapy is unproven, but probably
includes surgical debridement, removal of infected organs (eg, hysterectomy), and antibiotics
with good anaerobic activity [98]. Diagnosis may be challenging, since the organism can be
difficult to identify because of fastidious anaerobic growth, variable staining characteristics, and
complex biochemical profiles. C. sordellii appears to a rare transient organism in the vagina
[105]. (See "Toxic shock syndrome due to Clostridium sordellii", section on 'Treatment'.)
Mortality There have been few cases of death (approximately 10 cases) associated with
first-trimester medication abortion. In North America, the deaths have been due mainly to
clostridial sepsis and ectopic pregnancy. (See 'Fever and infection' above and 'Ectopic
pregnancy' above.)
Despite these reports of adverse events, the total experience in the industrialized world
indicates that the fatality rate for medication abortion does not appear to be significantly higher
than that of surgical abortion (case fatality rate 0.6/100,000 legal induced abortions) [106,107]
and is much lower than that of pregnancy (12 maternal deaths/100,000 live births). (See
"Overview of maternal mortality and morbidity", section on 'Maternal mortality ratio'.)
OUTCOME First-trimester mifepristone/misoprostol abortion is successful in 92 to 98 percent
of procedures [28-30,42,49,79-82].
The efficacy varies with several factors:
Gestational duration
Route of administration and dose of misoprostol
Parity The rate of successful abortion is lower with increasing parity and in women
who have had a previous abortion [49]. It is theorized that pregnancy is more
successfully established at an earlier gestational stage in parous women than in
nulliparous women [43,108,109].
Up to 49 days of gestation The successful completion of medication abortion in
pregnancies up to 49 days of gestation ranges from 91 to 98 percent [28,42,49,79]. In one early
large multicenter United States trial, the lower success rate of 92 percent may be related to the
lack of experience with medication abortion, as well as stringent criteria for success (figure 2)
[49].
Complete expulsion before prostaglandin administration occurred in 1 to 5 percent of women in
the United States trial; the frequency was higher at earlier gestations (figure 2) [49]. Similar
results were noted in the French trials [28]. Another 44 to 78 percent of women aborted in the
four-hour observation period after oral misoprostol (figure 3) [49]. The percentage was higher
after vaginal, as opposed to oral, misoprostol [29]. (See 'Route of administration and dose'
above.)
After 49 days of gestation Mifepristone was not initially approved by the US Food and Drug
Administration (FDA) in the United States for pregnancies over 49 days because initial research
reported a lower success rate beyond this gestational age [49,80,110]; oral misoprostol was
used with mifepristone in these studies (figure 2). By comparison, success remained high (94 to
97 percent) until 63 days of gestation when buccal or vaginal misoprostol (800 mcg) was given
after mifepristone (200 mg) [29,37,60,81,82,111]. Given the comparable success rate and
excellent safety profile, the evidence-based alternative regimen supported medication abortion
through 63 days of gestation.
Medication abortion has also been investigated at later gestational ages [112-116]:
64 to 70 days A randomized trial (n = 629) found similar efficacy using mifepristone
200 mg/misoprostol buccal 800 mcg in gestations of 64 to 70 days compared with 57 to
63 days (success rate for both was 93 percent) [116]. Thus the FDA revised the labeling
to include administration for pregnancies through 70 days of gestation.
70 to 83 days A prospective study (n = 253) using mifepristone 200 mg/misoprostol
vaginal 800 mcg reported successful termination of pregnancy in 97 percent of
pregnancies at gestational ages 70 to 76 days and 90 percent of those at 77 to 83 days
[112]. In addition to the lower efficacy and use of vaginal misoprostol, this regimen was
administered in hospital.
64 to 91 days In a retrospective study (n = 483) using mifepristone 200 mg followed
by up to five doses of misoprostol (vaginal 800 mcg initially and then 400 mcg either
vaginal or oral every three hours) at 64 to 91 days of gestation reported successful
termination in 95 percent of pregnancies [113]. Efficacy declined with advancing
gestational age. Surgical evacuation was required in 1 woman (1/106) at 9 to 10 weeks,
but 9 (9/114) of those at 12 to 13 weeks. There were no major complications.
Use of medication abortion at gestational ages greater than 70 days has a lower efficacy and
requires in-hospital administration. Given the limited data to support this regimen, women
choosing this beyond 70 days should be counseled regarding the lower efficacy, the increased
likelihood of seeing the pregnancy tissue, and the recommendation for inpatient care.
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.)
Basics topics (see "Patient education: Abortion (The Basics)")
Beyond the Basics topics (see "Patient education: Abortion (pregnancy termination)
(Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
Medication abortion is the termination of pregnancy with use of medications alone
rather than surgery. Mifepristone, a progesterone antagonist, is approved for use in the
United States, in combination with misoprostol, for the termination of pregnancies up to
70 days of gestation. (See 'Introduction' above.)
The choice between medication abortion and surgical abortion in the first trimester is
based upon availability, gestational age (medication abortion is less successful in the
late first trimester), and patient preference. Given the available data, we suggest
medication abortion for women who place a high value on avoiding surgery or
anesthesia and who are willing to accept more discomfort and awareness of the
procedure (Grade 2C). For other women, particularly those who place a high value on
completing the procedure in one visit, we recommend surgical abortion (Grade 1B).
(See 'Medication versus surgical termination' above.)
Contraindications for first-trimester medication abortion include: ectopic pregnancy,
intrauterine device in place, chronic adrenal failure, long-term corticosteroid therapy,
bleeding diathesis, inherited porphyrias, and lack of the ability to comply with the
regimen or access to emergent care in the case of a complication (table 1). (See
'Contraindications' above.)
The regimen approved by the US Food and Drug Administration (FDA) and
recommended by the manufacturer consists of mifepristone (200 mg orally) followed 24
to 48 hours later by misoprostol (800 mcg buccally). An alternative evidence-based
regimen extends the window for misoprostol administration to 72 hours. (See 'Medication
regimen' above.)
For women undergoing first-trimester mifepristone/misoprostol medication abortion:
We recommend an oral mifepristone dose of 200 mg (Grade 1A). (See
'Mifepristone' above.)
We recommend buccal administration of misoprostol rather than other routes
(Grade 1B). Oral administration of misoprostol is a reasonable option for women at
49 days of gestation. We do not prefer vaginal administration of misoprostol due to
an association with a rare but life-threatening infection. (See 'Route of
administration and dose' above and 'Clostridial sepsis' above.)
Mifepristone followed in 24 to 72 hours by misoprostol as well as selfadministration of misoprostol has been found to be effective. (See 'Timing' above
and 'Clinician versus self-administration' above.)
First-trimester medication is successful in 92 to 98 percent of procedures. Failed
medication abortion is treated with surgical uterine evacuation. (See 'Outcome' above.)
We suggest universal use of antibiotic prophylaxis for first-trimester medication abortion
(Grade 2C). This is a reasonable choice for those who value potential prevention of rare
cases of severe infection more than the disadvantages associated with routine antibiotic
use. (See 'Prophylactic antibiotics' above.)
Side effects following administration of mifepristone and misoprostol primarily consist of
abdominal pain, excessive bleeding, and gastrointestinal discomfort. Complications
include hemorrhage, infection, incomplete abortion, and unrecognized ectopic
pregnancy. Rare cases of fatal sepsis have occurred. (See 'Side effects and
complications' above.)
Following first-trimester medication abortion, we recommend a follow-up clinic visit with
clinical evaluation rather than self-assessment with no clinic visit (Grade 1B). If selfassessment is strongly desired or a clinic visit is not possible, clinicians should counsel
on both the risk and the symptoms of ongoing pregnancy, and follow a protocol that
includes use of urine pregnancy testing and a standardized telephone encounter. (See
'Follow-up' above.)
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