Contraceptive Technology Reports
Gauging the Effectiveness of Mifepristone and Misoprostol
Authors: Eric Schaff, MD, Professor of Family Medicine, Pediatrics, and Obstetrics and Gynecology, Reproductive Health Program, Department of Family Medicine, University of Rochester School of Medicine, Rochester, NY; and Jacinda Mawson, MA, Research Assistant, Reproductive Health Program, Department of Family Medicine, University of Rochester School of Medicine, Rochester, NY.
Peer Reviewer: Mimi Zieman, MD, Assistant Professor of Obstetrics and Gynecology, Director of Family Planning, Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta.
Introduction
In September 2000, the Food and Drug Administration (FDA) approved the use of mifepristone and misoprostol (Cytotec, G.D. Searle and Co., Chicago) as an effective and safe alternative to surgical abortion for women up to seven weeks pregnant. Of the approximately 1.2 million abortions annually in the United States, almost half occur before eight weeks gestation, when medical abortion may be appropriate.1 In light of a recent survey demonstrating a serious shortage of abortion services in 86% of U.S. counties,2 mifepristone has the potential to expand the number of clinicians providing a medical abortion, thereby increasing access to this important health service.
Background
In addition to the United States, many other countries have approved the mifepristone-prostaglandin regimen for medical abortion. Mifepristone for women up to seven weeks pregnant was approved in France in 1988 and in use in China in 1992.3,4 Approval for women up to nine weeks pregnant occurred in the United Kingdom in 1991 and in Sweden in 1992.5 The regimen was approved for women up to seven weeks pregnant in Russia, Austria, Belgium, Denmark, Finland, Germany, Greece, Israel, the Netherlands, Spain, and Switzerland in 1999.6 Surveys performed in France and Sweden have shown a steady increase in the number of women choosing the medical abortion option. In France in 1998, 26% of women up to 49 days pregnant who requested an abortion used mifepristone,6 and in Sweden, the number of women was more than 40%.5
Mechanisms of Action
Mifepristone acts as a competitive blocker by binding to the receptors for progesterone and cortisol. Mifepristone causes maternal decidual necrosis and detachment of the early embryo. It also increases the decidua’s production of prostaglandins, as well as the myometrium’s receptivity to prostaglandins, thereby increasing uterine contractility. In addition, mifepristone dilates and softens the cervix, which allows for easier expulsion of the embryo.7 The serum level of mifepristone peaks in about 1½ hours, has a terminal half-life of 18 hours, and is undetectable in the serum by 11 days.
Misoprostol is the second required medication in the regimen. It is a synthetic prostaglandin E1 formulated for oral use. It is approved for the prevention and treatment of stomach ulcers in patients taking nonsteroidal anti-inflammatory drugs. It is relatively inexpensive ($1/pill) and can be stored at room temperature. When misoprostol is administered as part of the mifepristone-misoprostol regimen, strong uterine contractions result. After an oral dose of misoprostol, the serum level peaks after about 20 minutes and is metabolized rapidly during the subsequent 60 minutes.
In contrast, when the oral tablets have been placed into the vagina, misoprostol has a delayed peak level about two-thirds as high as oral misoprostol, but serum levels are sustained for several hours, leading to greater bioavailability8 and uterine contractility.
Effectiveness
Effectiveness of a medical abortion is defined as having termination of a pregnancy without the need for surgical intervention for any reason. Failures may be due to a continuing pregnancy (defined as persistent embryonic cardiac activity by ultrasound at two weeks), a persistent nonviable pregnancy (defined as a retained gestational sac without embryonic cardiac activity by ultrasound at two weeks or longer), persistent or excessive bleeding requiring aspiration curettage for hemostatic control, other medical indications such as persistent nausea or pain, and nonmedical reasons requested by the woman. In a meta-analysis of mifepristone and oral misoprostol regimens, failure rates up to 49 days pregnant were due to incomplete abortion (excessive bleeding or a persistent nonviable pregnancy) in approximately 3% of cases and continuing pregnancy in about 1% of cases. For pregnancies of 50-56 days gestation, incomplete abortions occurred in 6% of women and continuing pregnancies comprised 3%. For gestational age from 57-63 days, the rate of incomplete abortion was 10%, and continuing pregnancy was 7%.9
Mifepristone used alone had an effectiveness rate for induced abortion ranging from 64-85%.7 When combined with a prostaglandin administered two days later, the effectiveness improved to 92-98% for pregnancies up to 49 days gestation.10-13 In pregnancies longer than 49 days gestation, the mifepristone plus oral misoprostol regimen has an efficacy rate of 77-88%.14 If vaginal misoprostol is used for pregnancies up to 63 days pregnant, the efficacy rate can reach 98%.11, 15-16 Under the FDA protocol, about 40% of women expel the products of conception within four hours after taking oral misoprostol, and about 60% will complete their abortions within 24 hours.17 When vaginal misoprostol is used, however, almost 90% of women complete their abortions within six hours.15
Acceptability
Medical abortion has been found to be highly acceptable to women, both in developed and developing countries.18-20 When women in a multicenter trial in the United States were surveyed about their experience with the mifepristone-misoprostol regimen, 91% of women said that if they needed another abortion, they would choose the medical option over the surgical option again.19 The most common reasons given by women for finding medical abortion acceptable include: it avoids surgery and some consider the medical abortion more natural; it involves less pain; and some find it easier emotionally.21 The most unacceptable parts of the experience are related to the time involved (i.e., a required observation period on day three after misoprostol and the multiple-visit regimen). Women have found home administration of misoprostol, which also decreases the number of required visits, to be highly acceptable.22 The FDA requires a return visit for misoprostol administration, but does not address any observation period.
The FDA Protocol
The FDA labeling requires three visits: an initial visit, a visit on day three (two days after using mifepristone) for administering misoprostol, and a follow-up visit on or before day 14 to confirm a complete medical abortion.
FDA Requirements. The administration of mifepristone must be under the supervision of qualified physicians who meet these requirements:
• familiar with the protocol and medications;
• able to date an early pregnancy accurately;
• able to identify an ectopic pregnancy;
• able to manage surgical completion of an incomplete abortion, or having established a referral source to manage the surgical completion;
• have access to emergency services, including blood transfusion and resuscitation if needed.
Surgical completion of an incomplete abortion is a basic skill of all obstetrician-gynecologists and many family physicians. This is necessary because women present with incomplete abortion from spontaneous miscarriages. Ideally, clinical training for these specialties should ensure that all graduates can perform this basic skill.
Clinicians must review the FDA-approved Medication Guide and Patient Agreement (for a copy of the Medication Guide, click here. For a copy of the Patient Agreement, click here.). Clinicians also should be familiar with any applicable state and local laws regarding the provision of abortion services. All serious adverse events such as hospitalizations, blood transfusions, ongoing pregnancies, and other major complications must be reported to Danco Laboratories in New York City. (See Resources at end of article.)
Day 1. Women must be screened by medical history, pregnancy dating, and laboratory tests to establish that they are candidates for medical abortion using the mifepristone/misoprostol regimen. They must have thorough counseling and give their informed consent.
Medical abortion is indicated for:
• women in good general health;
•women who are willing to have a surgical abortion if indicated;
• women who have a confirmed intrauterine pregnancy < 49 days;
• women willing and able to sign informed consent;
• women who have access to a telephone and emergency transportation;
• women who are willing to comply with the office visit schedule.
It is contraindicated for:
• women who live where surgical completion and emergency services are not available;
• women who have no access to transportation to reach emergency services;
• women with coagulopathy;
• women with intrauterine devices (IUDs). IUDs must be removed before treatment starts;
• women who are on chronic glucocorticoid therapy and have adrenal failure;
• women unwilling to undergo a surgical abortion if it were medically indicated;
• women with confirmed or suspected ectopic pregnancies;
• women with a history of allergy to mifepristone or misoprostol;
• women with chronic inflammatory bowel disorder. (Misoprostol could exacerbate the disorder).
Mifepristone is not effective in treating an ectopic pregnancy. Women with undiagnosed adnexal masses, abdominal pain, or, on ultrasound, either no intrauterine pregnancy or a possible pseudogestational sac (a collection of fluid in the uterus resembling an early gestational sac but with no yolk sac or embryo) should be excluded from a Mifeprex abortion until an ectopic pregnancy is ruled out.23 (Methotrexate may be considered; see information that follows.) In addition, ectopic pregnancy also must be considered in women with no vaginal bleeding in response to misoprostol when there was no initial ultrasound documenting an intrauterine pregnancy.
Exercise caution for:
• women with chronic illnesses who should be evaluated individually;
• women with severe anemia because of the possibility of excessive bleeding;
• women who are more than 35 years of age who also smoke 10 or more cigarettes per day.
There is no information regarding the effects of either medication on breast-feeding.
Clinical Screening. Medical abortion can be performed as soon as a pregnancy can be confirmed. The clinician must date the pregnancy by clinical or ultrasound criteria. There should be no symptoms nor signs of an ectopic pregnancy before administering mifepristone.
Women qualifying for medical abortion should be screened for Rh blood type, and if negative, a 50-mcg dose of Rh immune globulin should be administered on day 1 or prior to misoprostol administration. In addition, a hemoglobin or hematocrit may be indicated. Routine screening of quantitative human chorionic gonadotropin (hCG) is not necessary unless serial levels are being used to monitor the abortion.
Gestational Dating. Accurate pregnancy dating is related to the success of a medical abortion. Women must be no more than 49 days from the first day of the last menstrual period and not from the date of conception that is usually about two weeks later. Gestational age may be estimated from the last menstrual period, the timing of likely unprotected sexual intercourse, and a small uterus noted on bimanual examination. Unfortunately, there are times when those three parameters do not concur. For example, obesity, extreme uterine retroversion, and fibroids may make the uterine size difficult to assess, thereby warranting an ultrasound examination.
Ultrasonography provides the most accurate measure of gestational age and can be used to confirm a complete abortion. Unfortunately, ultrasonographic examinations may add significant costs to the procedure. Many U.S. sites that currently provide abortion services have office-based ultrasonography. While ultrasonography has been used extensively in medical abortion trials in the United States, it is not used routinely in Europe.24
Ruling Out an Ectopic Pregnancy. Ectopic pregnancy is a potentially life-threatening condition because of the eventual rupture of the ectopic pregnancy and internal hemorrhage. The incidence rate for ectopic pregnancies can be as high as 1% of pregnant women. With a high index of suspicion, ectopic pregnancies can be detected in an asymptomatic stage when treatment results in the least morbidity. Ectopic pregnancy can be detected with quantitative hCG levels and ultrasonography.
Risk factors for ectopic pregnancy include a history of surgery on the fallopian tubes, sexually transmitted diseases, prior ectopic pregnancy, vague crampy lower abdominal pain or abnormal vaginal bleeding in the first trimester, or the lack of bleeding response to this regimen. On examination, the uterus may be smaller than expected, and an adnexal mass may be present. On ultrasonography, either no intrauterine pregnancy is identified or a small collection of fluid representing a pseudogestational sac may be seen or an adnexal mass may be identified. The hCG discriminatory zone is the hCG value at which the presence of a gestational sac is expected with a normal intrauterine pregnancy (IUP). The absence of a gestational sac when the hCG is above the discriminatory zone, i.e., an hCG value above 2000 IU/L by vaginal probe or 3600 IU/L by abdominal probe, strongly suggests an ectopic pregnancy.23
Mifepristone is not known to be effective to treat an early ectopic pregnancy. Methotrexate 50 mg/m2 is most effective to treat an early ectopic pregnancy when an adnexal mass is less than 3.5 cm, there is no embryonic cardiac activity, and the beta-hCG level is less than 5,000 IU/L-10,000 IU/L. However, it is not 100% effective, and tubal rupture may still occur.25 The definitive treatment is surgical removal of the ectopic pregnancy.
Counseling and Informed Consent. A safe, effective, and acceptable medical abortion is dependent on the thoroughness of the counseling a woman receives. Women must be counseled on the alternatives, the benefits and risks, the costs, and their role in the process, i.e., when to return for follow-up, how to use misoprostol, what side effects to expect, possible warning signs of complications, and when and how to contact the on-call clinician. At the first visit, women must be given the manufacturer’s Medication Guide and sign the Patient Agreement (For areas to be covered in counseling, see Table 1.)
|
Table 1. Counseling and Informed Consent |
| The typical experience |
|
All women will experience vaginal bleeding and most will have uterine cramping. Pain and bleeding typically are most intense during the time when the products of conception are being expelled. The majority of women will abort within four hours of taking misoprostol, but some women will take longer. |
| Length of time involved in the abortion |
|
Two days are required between medications and several visits are needed. Light bleeding can last two to three weeks. |
| The medication regimen |
|
Mifepristone is administered as three 200 mg tablets (600 mg). Women return two days later to use misoprostol two 200 mcg tablets (400 mcg) orally. |
| Rh negative blood type |
|
Women who are Rh negative should receive Rh immunoglobulin prior to using misoprostol. |
| The expected side effects |
| Women should expect heavy bleeding and painful cramping. |
| What women will likely see |
|
There will be blood clots. The embryo is not detectable by the naked eye until about 8 ½ to nine weeks’ gestation. |
| What to do about bleeding and how to contact the on-call clinician |
|
Women should be encouraged to use maxi sanitary napkins to better monitor and report the amount of bleeding. If bleeding soaks more than four napkins in two hours, she should contact the on-call clinician for further evaluation. Women should have a phone number and name of the clinician who is available for emergencies. |
| What to do about cramping pain |
| Reassurance that the typical pain lasts only several hours may help. A heating pad or hot water bottle can help relieve some symptoms. Both non-narcotic and oral narcotic analgesics can be prescribed for pain control. |
| What happens when the medications fail |
| Women should know that there is a failure rate of about 5%, which is most commonly due to persistent bleeding. Discuss the need for surgical abortion if the pregnancy continues because of the possibility of birth defects in this pregnancy. |
| Post-abortion contraception |
|
There is a rapid return to fertility within the first month, so an effective contraception should be started after the medical abortion is confirmed if pregnancy is to be avoided. |
Administering Mifepristone and Prescribing a Pain Medication. After screening, counseling and informed consent, the woman must swallow three 200-mg tablets (600 mg) of mifepristone. The clinician should offer a prescription for pain relief that may include a nonsteroidal anti-inflammatory drug or an oral narcotic such as acetaminophen and codeine.
Day 3: Misoprostol Administration. Two days after using mifepristone, the woman returns to the office or clinic to take two 200-mcg tablets (400 mcg) of misoprostol orally. Although women commonly begin bleeding prior to this visit, women still will need to use misoprostol unless the abortion is documented to be complete, ideally by ultrasonography. When using misoprostol, women may remain under medical supervision at the clinic for three to six hours or she may elect to return home. The preferred location may be influenced by the woman’s preference, support system, distance from medical services, and the clinician’s experience. All women must be provided with contact information for the clinician on call.
Day 14: Post-treatment Evaluation. Approximately 14 days after the administration of mifepristone, the woman must return to her health care provider to confirm that a complete abortion has occurred. A history of vaginal bleeding alone is not sufficient. Medical abortion can be confirmed with a history of vaginal bleeding combined with a normal-sized uterus on bimanual examination, a significant decrease in quantitative hCG (at least 50%),26 or the absence of a gestational sac on ultrasonography. With ultrasonography, it is common to find a widened endometrial stripe with heterogeneous material (sometimes referred to as debris). In women for whom bleeding is resolving, no intervention is required for this common finding. Aspiration curettage should be performed for medical abortion failures including women with excessive or persistent bleeding and the rare continuing pregnancy. (See Table 2.)
|
Table 2. FDA Protocol and Alternative Regimens |
|||
|
FDA Protocol with |
Alternative Regimen with |
||
| Mifepristone |
600 mg |
200 mg |
|
| Misoprostol | |||
| Timing |
Day 3 |
Day 2, 3, or 4 |
|
| Place |
Office |
Office or home |
|
| Repeat dose |
— |
If needed |
|
| Gestational age |
Up to seven weeks |
Up to nine weeks |
|
| First follow-up |
About day 14 |
After misoprostol use |
|
The FDA has consistently adhered to a policy that permits clinicians to use approved medications off-label or "evidence-based." Studies have shown that dosages of mifepristone can be lowered without compromising efficacy27 and that doses of mifepristone from 100-800 mg result in similar serum levels.7 A randomized trial found no difference between mifepristone 200 mg vs. mifepristone 600 mg followed by misoprostol 400 mcg orally up to 7 weeks gestation.28 As noted earlier, mifepristone 200 mg followed by vaginal misoprostol 800 mcg has been effective up to 63 days gestation.11,15-16,29A recent report of mifepristone 200 mg and vaginal misoprostol 800 mcg demonstrated equal effectiveness when misoprostol was administered from 1-3 days after mifepristone.30
In addition, several studies demonstrate the safety and acceptability of home use of misoprostol for medical abortion after mifepristone.9, 22, 29-30 If follow-up occurs earlier than 14 days, women should be counseled that they still might need medical care during the next month if a delayed complication arises.
Managing Side Effects and Complications
There is an continuum from expected side effects that are managed expectantly to complications that require skilled intervention. (See Table 3.)
|
Table 3. Management of Side Effects |
||
| Side Effect | Management | Complication |
| Gastrointestinal | Usually symptoms are self-limited. Anti-nausea medications can be used. |
Rarely, IV fluids are needed for dehydration and aspiration curettage. |
| Uterine abdominal pain | Reassurance, hot water bottle, nonsteroidal anti-inflammatory drug, or oral narcotic such as acetaminophen with codeine. |
Rarely, a stronger narcotic medication or aspiration curettage is needed. |
| Vaginal bleeding | Reassurance, uterotonices (misoprostol 400 mcg orally, or methergine 0.2 mg orally), birth control pills. |
Occasionally, aspiration curettage is needed; rarely, IV fluids or transfusion is needed. |
| Persistent vague abdominal pain |
Consider pelvic infection and ectopic pregnancy. |
As indicated. |
Gastrointestinal Symptoms. Nausea, vomiting, and diarrhea are commonly reported by women experiencing a medical abortion. Despite this, the majority of women report that the side effects are acceptable. This finding is most likely explained by: 1) the realistic expectations women have from counseling; 2) the similarity of medical abortion symptoms to first-trimester pregnancy symptoms; and 3) the obscuring of gastrointestinal symptoms by the more displeasing crampy abdominal pain and vaginal bleeding.
Most gastrointestinal symptoms can be managed with reassurance. Occasionally, an anti-nausea medication and rarely IV fluids are needed for persistent vomiting to prevent dehydration.
Crampy Abdominal (Uterine) Pain. Most women will experience crampy abdominal (uterine) pain. Reassurance, a heating pad, a nonsteroidal anti-inflammatory drug, or a mild narcotic such as acetaminophen with codeine should be sufficient to ease the discomfort. Most intense pain resolves in a few hours after the pregnancy has been expelled.
Other Misoprostol-related Side Effects. Misoprostol is associated with other prostaglandin-like side effects such as headache, chills, and fever, which are usually self-limited and can be managed expectantly.
Bleeding. Vaginal bleeding is necessary for a complete medical abortion. Although the amount of blood loss from surgical and medical terminations are fairly comparable, women undergoing a medical procedure observe the bleeding. Bleeding under the medical regimen is heaviest when products of conception are passed within the immediate three hours after using misoprostol. Women should be instructed to contact their health care provider on call if they saturate four or more maxi-sanitary napkins over two consecutive hours. For most women, light bleeding persists for 9-21 days, and about 8% of women continue bleeding for as much as one month.17 Oral contraceptives have been used after medical abortion in an attempt to minimize the duration of bleeding after the procedure, but they do not appear to have a significant effect.31
The most serious complication of the regimen is excessive bleeding, and all providers should be skilled to perform an aspiration curettage for an incomplete abortion or have a formal arrangement for this service. Excessive bleeding requiring surgical intervention ranges from 0.4%15 to 2.6%.17 Treatment may include oral fluids; slow position changes, i.e., rising from a lying position slowly; the administration of uterotonic agents (methergine 0.2 mg po/IM, or misoprostol 200-400 mcg orally or 400-800 mcg vaginally); fluid replacement with isotonic solutions; aspiration curettage; and, rarely, transfusion.
Health care providers are required to have a plan for surgical completion, which may be indicated for any of the following: persistent or excessive bleeding, other serious medical conditions, patient request, persistent nonviable pregnancy after more than two weeks, inability to return for further evaluation or lack of access to emergency services, and, lastly, ongoing pregnancy. Women who have excessive bleeding from a medical abortion present similarly to women with an incomplete spontaneous abortion (i.e., the cervix is typically soft and dilated and the pregnancy has partially detached or been expelled). Because the cervix is already dilated, mechanical cervical dilatation is rarely needed and, therefore, the paracervical block may not be required.
The following is an example of the steps needed to perform an aspiration curettage for an incomplete medical abortion. First, a bimanual examination is performed to locate the size and position of the uterus. A specular examination identifies the cervix and any blood in the vagina is removed. The cervix is cleaned with an antiseptic solution and then grasped with a nontraumatic or single-toothed tenaculum. A 6-mm (or 7-mm) flexible cannula is gently introduced approximately 6 cm into the cervix through the internal os and until the fundus is touched. The cannula is connected to either a manual vacuum 60 cc Ipas syringe or electrical suction.32, 33 The cannula is rotated and gentle curetting movements are performed. Aspiration should continue until there is no return of blood in the cannula and the intrauterine cavity is "felt" through the cannula and there is a gritty sensation. Routine examination of the products removed by floating them in water and using a bright light is helpful to confirm that the uterus was evacuated completely. Trophoblastic tissue will appear white and has a "cotton-ball" appearance.
Infection. Pelvic infections are rare because no instruments are introduced into the uterus for medical abortion. In studies involving more than 500 participants, infection rates varied from 0.09% to 0.5%.34
Teratogenicity. There is one report of a women who used mifepristone but not misoprostol with an ongoing pregnancy that was aborted at 11 weeks gestation with hyranencephally diagnosed by ultrasonography.35 Misoprostol has been associated with congenital abnormalities including scalp or skull defects, cranial-nerve palsies, and limb defects.36-39
Medical abortion is an early, safe, effective, and acceptable alternative to surgical abortion. The promise of mifepristone is that more clinicians will be willing to prescribe this regimen, thereby countering the current shortage of abortion providers in the United States.
References
1. Centers for Disease Control and Prevention. Abortion surveillance — United States, 1997. MMWR 2000; 48:1171-1191.
2. Henshaw SK. Abortion incidence and services in the United States, 1995-1996. Fam Plann Perspect 1998; 30:263-270, 287.
3. Ulmann A. The development of mifepristone: A pharmaceutical drama in three acts. JAMWA 2000; 55:117-120.
4. Shangchun W. Medical abortion in China. JAMWA 2000; 55:197-199.
5. Bygdeman M, Danielsson KG, Marions L. Medical termination of early pregnancy: The Swedish experience. JAMWA 2000; 55:195-196.
6. Christin-Maitre S, Bouchard P, Spitz IM. Drug therapy: Medical termination of pregnancy. N Engl J Med 2000; 342:946-956.
7. Spitz IM, Bardin CW. Clinical pharmacology of RU 486 — an antiprogestin and antiglucocorticoid. Contraception 1993; 48:403-444.
8. Zieman M, Fong SD, Benowitz NL, et al. Absorption kinetics of misoprostol with oral or vaginal administration. Obstet Gynecol 1997; 90:88-92.
9. Kahn JG, Becker BJ, MacIsaac L, et al. The efficacy of medical abortion: A meta-analysis. Contraception 2000; 61:29-40.
10. Norman JE, Thong KJ, Rodger MW, et al. Medical abortion in women of less than or equal to 56 days amenorrhea: A comparison between gemeprost (a PGE1 analogue) alone and mifepristone and gemeprost. Br J Obstet Gynaecol 1992; 99:601-606.
11. El-Refaey H, Rajasekar D, Abdalla M, et al. Induction of abortion with mifepristone (RU 486) and oral or vaginal misoprostol. N Engl J Med 1995; 332:983-987.
12. World Health Organization. Pregnancy termination with mifepristone and gemeprost: A multicenter comparison between repeated doses and a single dose of mifepristone. Fertil Steril 1991; 56:32-40.
13. Schaff EA, Stadalius LS, Eisinger SH, et al. Vaginal misoprostol administered at home after mifepristone (RU486) for abortion. J Fam Pract 1997; 44:353-360.
14. Aubeny E, Peyron R, Turpin CL, et al. Termination of early pregnancy (up to 63 days of amenorrhea) with mifepristone and increasing doses of misoprostol. Int J Fertil Menopausal Stud 1995; 40:Suppl 2:85-91.
15. Ashok PW, Penney GC, Flett GM, et al. An effective regimen for early medical abortion: A report of 2000 consecutive cases. Hum Reprod 1998; 13:2,962-2,965.
16. Urquhart DR, Templeton AA, Shinewi F, et al. The efficacy and tolerance of mifepristone and prostaglandin in termination of pregnancy of less than 63 days gestation: UK Multicenter Study — final results. Contraception 1997; 55:1-5.
17. Spitz IM, Bardin CS, Benton L, et al. Early pregnancy termination with mifepristone and misoprostol in the United States. N Eng J Med 1998; 338:1,241-1,247.
18. Winikoff B, Sivin I, Coyaji KJ, et al. Safety, efficacy, and acceptability of medical abortion in China, Cuba, and India: A comparative trial of mifepristone-misoprostol vs. surgical abortion. Am J Obstet Gynecol 1997; 176:431-437.
19. Winikoff B, Ellertson C, Elul B, et al. Acceptability and feasibility of early pregnancy termination by mifepristone-misoprostol: Results of a large multicenter trial in the United States. Arch Fam Med 1998; 7:360-366.
20. Henshaw RC, Naji SA, Russell IT, et al. A comparison of medical abortion (using mifepristone and gemeprost) with surgical vacuum aspiration: Efficacy and early medical sequelae. Hum Reprod 1994; 9:2,167-2,172.
21. Clark S, Ellertson C, Winikoff B. Is medical abortion acceptable to all American women: The impact of sociodemographic characteristics on the acceptability of mifepristone-misoprostol abortion. JAMA 2000; 55:177-182.
22. Schaff EA, Eisinger SH, Stadalius LS, et al. Low-dose mifepristone 200 mg and vaginal misoprostol for abortion. Contraception 1999; 59:1-6.
23. Creinin MD, Aubény E. Medical abortion in early pregnancy. In: Paul M, Lichtenberg E, Borgatta L, et al, eds. A Clinician’s Guide to Medical and Surgical Abortion. New York: Churchill Livingstone, 1999.
24. Ellertson C, Elul B, Winikoff B. Can women use medical abortion without medical supervision? Reprod Health Matters 1997; 9:149-161.
25. Lipscomb GH, Bran D, McCord ML, et al. Analysis of 315 ectopic pregnancies treated with single-dose methotrexate. Am J Obstet Gynecol 1998;178:1,354-1,358.
26. Creinin MD. Change in beta-human chorionic gonadotropin after abortion with methotrexate and misoprostol. Am J Obstet Gynecol 1996; 174:776-778.
27. World Health Organization Task Force on Post-ovulatory Methods of Fertility Regulation. Termination of pregnancy with reduced doses of mifepristone. BMJ 1993; 307:532-537.
28. WHO Task Force on Post-ovulatory Methods of Fertility Regulation. Comparison of two doses of mifepristone in combination with misoprostol for early medical abortion: A randomized trial. Br J Obstet Gynaecol 2000; 107:524-530.
29. Schaff EA, Fielding, SL, Eisinger SH, et al. Low-dose mifepristone followed by vaginal misoprostol at 48 hours for abortion up to 63 days. Contraception 2000; 61:41-46.
30. Schaff EA, Fielding SL, Westhoff C, et al. Vaginal misoprostol administered one, two, or three days after mifepristone for early medical abortion (< 56 days gestation): A randomized trial. JAMA 2000; 284:1,948-1,953.
31. Tang OS, Gao PP, Cheng L, et al. A randomized double-blind placebo controlled study to assess the effect of oral contraceptive pills on the outcome of medical abortion with mifepristone and misoprostol. Hum Reprod 1999; 14:722-725.
32. Edwards J, Creinin MD. Surgical abortion for gestations of less than six weeks. Curr Probl Obstet Gynecol Fertil 1997; 20:11-19.
33. Westfall JM, Sophocles A, Burggraf H, et al. Manual vacuum aspiration for first-trimester abortion. Arch Fam Med 1998; 7:559-562.
34. Kruse B, Poppema S, Creinin MD, et al. Management of side effects and complications in medical abortion. Am J Obstet Gynecol 2000; 183:S65-S75.
35. Schaff EA. Personal communication of adverse report to the FDA. Rochester, NY; October 2000.
36. Fonseca W, Alencar AJ, Mota FS, et al. Misoprostol and congenital malformations. Lancet 1991; 338:56.
37. Gonzalez CH, Vargas FR, Perez AB, et al. Limb deficiency with or without Mobius sequence in seven Brazilian children associated with misoprostol use in the first trimester of pregnancy. Am J Med Genet 1993; 47:59-64.
38. Gonzalez CH, Marques-Dias MJ, Kim CA, et al. Congenital abnormalities in Brazilian children associated with misoprostol misuse in first trimester of pregnancy. Lancet 1998; 351:1624-1627.
39. Pastuszak AL, Schuler L, Speck-Martins CE, et al. Use of misoprostol during pregnancy and Mobius’ syndrome in infants. N Engl J Med 1998; 338:1,881-1,885.
Resources
The pharmaceutical company, Danco Laboratories, can be reached at (877) 4-Early Option or (877) 432-7596, and the Web site is www.earlyoptionpill.com. A brief clinical and administrative synopsis of any adverse events should be mailed to:
• Medical Director, Danco Laboratories, P.O. Box 4816, New York, NY 10185.
The National Abortion Federation (NAF) has produced educational materials for health care providers. Materials include a Medical Abortion Start-up Packet that includes a sample consent and charting forms, sample patient information sheets, a supply list, a comparison of mifepristone and methotrexate, and the NAF protocol for mifepristone. At press time, the start-up packet was being distributed at no cost. NAF can be reached at (800) 772-9100 or through its Web site at www.earlyoptions.org.
Recommended Reading
Supplement on medical abortion. Am J Obstet Gynecol 2000; 183(2 Suppl).
Crist T, Carhart L, Harrison W. Medical abortion. J Am Med Womens Assoc 2000; 55(3):243-4.
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