Doi:10.1016/j.ijgo.2007.09.006

International Journal of Gynecology and Obstetrics (2007) 99, S172–S177 a v a i l a b l e a t w w w . s c i e n c e d i r e c t . c o m w w w . e l s e v i e r. c o m / l o c a t e / i j g o Misoprostol for the termination of pregnancy up to 12completed weeks of pregnancy A. Faúndes a,⁎, C. Fiala b, O.S. Tang c, A. Velasco d a Department of Gynecology and Obstetrics, State University of Campinas (UNICAMP), Campinas, SP, Brazilb Gynmed Clinic, Vienna, Austriac Department of Obstetrics and Gynecology, University of Hong Kong, Hong Kong SAR, Chinad Department of Gynecology and Obstetrics. Hospital Eusebio Hernández (Maternidad Obrera), Havana, Cuba The aim was to review the current knowledge about the use of misoprostol alone for abortioninduction during the first 12 weeks of pregnancy. Publications reporting experiences withmisoprostol alone for pregnancy termination within the first 12 weeks of pregnancy were included in the analysis. Vaginal administration of 800 μg repeated up to three times at 6, 12 or 24 h intervals has an 85% to 90% effectiveness, defined as complete abortion, in most studies. Oral administration is less effective, but sublingual administration at 3-hour interval has the same effectiveness, with more frequent side effects. The oral and sublingual routes appear to be better accepted thanvaginal administration. Most studies are limited to the first 9 weeks of pregnancy. The experience onpregnancy termination between 10 and 12 weeks is not yet sufficient for a recommendation.
2007 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd.
All rights reserved.
The regimen of mifepristone followed by a suitableprostaglandin analogue (usually misoprostol) has become It is estimated that 46 million pregnancies are terminated increasingly available and is now the gold standard for voluntarily each year, 27 million carried out under safe conditions and 19 million falling into the category of “unsafeabortions” Until the second half of the twentieth century, Mifepristone is an antiprogestin that blocks most proges- dilatation and curettage (D & C) was the most common and terone receptors. When a prostaglandin is administered 24 to virtually only method used for safe termination of early 48 h after mifepristone, uterine contractions expel the pregnancy. Abortion by vacuum aspiration gained greater products of conception and the effectiveness of the acceptance in the 1960s and has become the standard of care.
combination is greatly enhanced. This medical abortion First trimester pregnancy can also be terminated safely regimen is highly effective and well accepted and pharmacologically (medical abortion).
women who wish to avoid invasive procedures regardmedical abortion as a more natural and preferable option. The combination of metrotrexate and misoprostol hasalso been used, but this combination has not proven ⁎ Corresponding author. Tel.: +55 19 3289 2856; fax: +55 19 3289 2440.
0020-7292/$ - see front matter 2007 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd.
All rights reserved.
Misoprostol for the termination of pregnancy up to 12 completed weeks of pregnancy Where mifepristone is not accessible, various misoprostol- Recently, the buccal route of administration has also only regimens are being used, and dozens of reports have been investigated, but not yet for this indication been published on the outcomes of various treatments. The Intervals between doses vary from 3 to 48 h .
comparison of the results of the published data on the use of According to pharmacokinetics and clinical experience, the misoprostol is not possible due to a lack of uniformity in many interval between vaginal doses may not need to be shorter variables: intervals between doses vary from 3 to 48 h, the than 5–6 h and probably no longer than 24 h.
time point for assessing this outcome varies from a few daysto several weeks (), and the gestational age of women There is experience on the use of these regimens up to differs between reports. These factors make it difficult to 63 days (9 weeks) pregnancy , but too few conclude what regimen might be the most effective.
reports on the use of misoprostol between 9–13 weeks Most publications report vaginal administration of multiple to affirm that these regimens are equally effective doses of 800 μg of misoprostol (4 tablets of 200 μg) up to three doses. The available information suggests that effec-tiveness is dose related with doses up to 800 μg if administered The misoprostol-only regimen has been approved for the termination of early pregnancy in only one country (Brazil) at thetime of writing (February 2007). However, its widespread use in When misoprostol is used alone, the oral route is less countries with restricted abortion laws appears to be associated effective than vaginal . Vaginal administration with reduction in maternal morbidity and mortality .
should therefore be chosen unless there are reasons toavoid it. The sublingual route is a reasonable alternative Alternative routes may be sought as some acceptability • Suspected ectopic pregnancy or non-diagnosed adnexal mass.
studies, have shown that women prefer a non-vaginal route Moreover, when given vaginally, fragments of thetablets may remain visible for many hours.
The sublingual route is a reasonable alternative Although the sublingual route is significantly less effective thanthe vaginal route if misoprostol is administered every 12 h, the • If molar pregnancy is diagnosed, intrauterine aspiration effectiveness is similar if administered with a 3-h interval between doses . The main drawback of the sublingual route • If there is an intrauterine device (IUD) in place, this should is that it may cause more frequent gastrointestinal side-effects be removed before administering misoprostol.
(such as nausea, vomiting, shivering and hyperthermia) than • Coagulation disorders/currently taking anticoagulants.
vaginal administration . These side effects are dose • Women should be advised that the treatment can fail and dependent and last only for a short time.
they should be prepared to terminate the pregnancy by Summary of studies with vaginal administration of misoprostol alone for first trimester abortion surgical method, because there have been reports of con- genital malformations in newborn infants of mothers givenmisoprostol during the first trimester of pregnancy .
Despite the wide range of results from different studies and • Breastfeeding: Small amounts of misoprostol or its active different regimens, the success rate, defined as a complete metabolite may appear in breast milk . There is no in- abortion, is around 90% during the first trimester of pregnancy formation on the effects on nursing infants. It is recom- Success depends on the length of the time interval mended therefore that breast milk is not given to the infant between treatment and the assessment of the outcome.
for 4 h after oral administration or 6 h after vaginal miso-prostol administration.
Depending on the regimen used, pregnancy continues in • Anemia detected at the time of abortion should be treated 4% to 8% of women with gestational age of up to 63 days without delaying the procedure. The average blood loss when vaginal misoprostol is used alone ().
during medical abortions may be more than in surgicalabortions .
• Previous cesarean section: there is evidence from one study that the safety and efficacy of early abortion (up to seven In the majority of cases, expulsion of the products of weeks) is unaffected by previous cesarean section .
conception occurs hours after administration: close to 70% Although extremely rare, uterine rupture in early pregnancy within the first 12 h around 80% during the first 24 h, 95% within 48 h and further increases until at least 72 hafter the initial dose However there may be a large variability depending on route, dose and time intervalbetween misoprostol doses.
The first choice is 800 μg administered by the vaginal routeevery 6, 12 or 24 h for a maximum of three doses. Three doses Prolonged or serious side effects are rare.
of 800 μg at 3-hourly intervals can also be used sublinguallyMoistening the tablets appears to slightly increase plasma levels but no improvement in the clinical effects has beendemonstrated Doses higher than 800 μg are not Vaginal bleeding during abortion induced with misoprostol recommended due to increased side effects .
is generally more intense than regular menstrual bleedingand is usually no different from that which occurs with a spontaneous abortion Although there may be greatvariations, there is typically menstrual-like or heavier Several studies carried out in developed and developing coun- bleeding for the first week and then spotting for an tries have shown that home administration of misoprostol is ef- additional week. The mean pre- to post-abortion fall in fective and safe up to 9 weeks since the last menstrual period.
hemoglobin varies between 0.2 and 1.0 g/dL ( Most of those studies have been done using the combination of Prolonged and intensive bleeding affects between 1% and mifepristone and misoprostol and only a few with 10% of women and may necessitate emergency surgical uterine evacuation, preferably with manual vacuum as-piration. The need for transfusion has been rarely reported • Voluntary termination of the pregnancy and informed consent of the woman about her choices and the nature of • Backup arrangements for surgical abortion.
Cramping usually starts within the first few hours and may • Dating of gestational age and ruling out ectopic pregnancy begin as early as 30 min after misoprostol administration. The pain may be stronger than that experienced during a regular • If required by national guidelines, blood group and Rhesus period and can be present in 80%–90% of women Non- factor should be determined and in cases where women are steroidal anti-inflammatory drugs (NSAIDs) or other analgesia Rhesus negative, a dose of anti-D serum should be admin- can be used for pain relief without affecting the success of the istered prior to treatment. However, there is currently little evidence to support that Rhesus factor isoimmunizationoccurs for pregnancies up to 63 days gestation Where resources are available, and depending on the Chills are a common side effect of misoprostol but are clinical situation, the following tests may be useful: transient. Hyperthermia can be very severe and morecommon with higher doses when the interval between • Hemoglobin, hematocrit and screening for STDs may also doses is shorter or with oral or sublingual administration be provided depending on local prevalence and guidelines.
. Fever does not necessarily indicate infection.
In addition, serological tests to diagnose for syphilis, HIV An antipyretic can be used for relief of fever, if needed. If and hepatitis B and C surface antigen may also be used.
fever or chills persist beyond 24 h after taking misoprostol, Misoprostol for the termination of pregnancy up to 12 completed weeks of pregnancy Indicators of bleeding in clinical studies of misoprostol alone for first trimester abortion the woman may have an infection and should seek medical include excessive bleeding, fever of more than 1 day and abdominal pain. Antibiotic treatment should be begunimmediately if there is any suspicion of infection, although it is less frequent after medical than after surgical methodof abortion .
Women should return for follow-up one or two weeks after About 20% of women report pregnancy-related nausea and the initial administration of the drug or earlier if they feel the vomiting before treatment. These symptoms may need. A good clinical history and bi-manual exam should increase after misoprostol administration. An anti-emetic enable the provider to determine the absence of symptoms can be used if needed, but symptoms will usually resolve and that the uterus is firm and well involuted. In case of uncertainty a pregnancy test and ultrasound examination may be needed to confirm a complete expulsion. The usualurinary pregnancy tests may be positive for up to 4 weeksfollowing the abortion as the pregnancy hormone hCG is Diarrhea may also occur following administration of misoprostol Those women who have not aborted within 72 h after the last dose should be given the option of a second course of misoprostol treatment or surgical abortion; they should beinformed that their chances of success of the second course The risk of fetal abnormalities after misoprostol used early in is around one in three If there is an urgent need to pregnancy is probably very low but women who do evacuate the uterus or if the woman is not prepared to not abort after misoprostol, should have access to surgical accept a new attempt of treatment with misoprostol, she abortion, if that is the woman's informed choice. Vacuum should be offered the alternative surgical abortion. There is aspiration is the recommended option.
clear evidence that vacuum aspiration is the preferredtechnique: both electric or manual vacuum aspirations are Women with incomplete abortion should be offered the Women should be given simple instructions on how to choice of aspiration evacuation or misoprostol treatment with recognize any complications that might require medical 600 μg of oral misoprostol if eligible .
Once administration of misoprostol has begun, women must have easy access to a health professional capable of answeringtheir questions and providing them with assistance or hospital Women should be informed about immediate return to care. During the early first trimester, the possibility of ectopic fertility, contraceptive methods, their characteristics, effec- tiveness and side effects, including their capacity to protect Women must be informed that they will have bleeding against sexually transmitted infections (STIs). After selection and cramping as described above, and that they can use of the most appropriate method, that method should be NSAIDs as required. The symptoms calling for clinical care tion with vaginal misoprostol before and after 42 days gesta-tion. Hum Reprod 2002;17(12):3079–83.
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