Mifepristone was developed during the early 1980s by a team of researchers working for the French pharmaceutical company Roussel Uclaf. While investigating glucocorticoid receptor antagonists, the team discovered compounds that blocked the similarly shaped progesterone receptor. Further refinement led to the production of RU-486, the medication that is now known as mifepristone.
Clinical testing of mifepristone as a means of inducing medical abortion began in France in 1982. Results from these trials showed that when used as a single agent, mifepristone induced a complete abortion in up to 80% of women up to 49 days' gestation.1 By adding small doses of a prostaglandin analogue a few days later to stimulate uterine contractions, investigators discovered that the paired medication regimen could effect a complete medical abortion in nearly 100 percent of women.2,3,4
In 1988, France and China became the first countries to license the combination of mifepristone and a prostaglandin analogue for abortion during early pregnancy. Since then, this medical abortion regimen has been approved in over thirty-five countries worldwide including Austria, Belgium, Denmark, Great Britain, Greece, India, Israel, Russia, South Africa, Sweden, Tunisia, Taiwan, the USA and Vietnam. Millions of women worldwide have used mifepristone and a prostaglandin analogue to terminate pregnancy with impressive safety and efficacy.
In the Guidelines for Termination of Pregnancy (TOP) Implementation issued by the Maternal, Child and Women's Health Directorate in April of 1997, among the Principles of Introduction was a statement anticipating the introduction of medical abortion to South Africa: "Once medical abortifacients become available in South Africa they should be introduced into the health services to farther decentralise services in a safe and effective manner."5 In 2001, the Medicines Control Council (MCC) of the Republic of South Africa approved mifepristone. The Department of Health and other key organizations working towards the enhancement of Sexual and Reproductive Health services in the RSA have continued to evaluate international and national safety, efficacy and acceptability data6,7 since that time, but a formal policy which would allow for provision of medical abortion as described by the 1997 Guidelines has yet to be finalized.
Mifepristone blocks the progesterone receptor, leading to profound changes in the endometrium. Mifepristone also softens the cervix to facilitate expulsion of the pregnancy.8,9 The prostaglandin analogue misoprostol accelerates the process of expulsion by stimulating uterine contractions as well as softening the cervix.10
The original regimen tested and approved for medical abortion included a single oral dose of 600 mg of mifepristone followed 48 hours later by a 400-µg oral dose of misoprostol. Using this regimen, the highest rates of complete abortion (about 95%) have been seen in women up to 49 days' gestation, with a small, progressive decrease in efficacy when extending the gestational age to 63 days. 3,11 More recent research has established that a 200 mg dose is equally as effective as a 600 mg dose of mifepristone.12 Different routes of administration and corresponding dosage variations of misoprostol have also been evaluated, and studies have demonstrated that misoprostol can be safely administered at home.13,14 Several evidence-based alternative regimens are widely accepted clinical practice, and are included in the practice protocols of many professional organizations.15,16
The MCC-approved regimen includes the 600 mg dose and a limit of 56 days' gestation (calculated from onset of the last menstrual period) for eligibility for mifepristone medical abortion. Contraindications to medical abortion with mifepristone and misoprostol include allergy to either of these medications, chronic systemic use of corticosteroids, chronic adrenal failure, hemorrhagic disorder or current therapy with anticoagulants, confirmed or suspected ectopic pregnancy, porphyrias, severe uncontrolled asthma, and the presence of an intrauterine device (removal of the IUD eliminates this contraindication).
Side effects are expected with medical abortion. Some side effects, such as pain and bleeding, result from the abortion process itself. Side effects of the medications include nausea, vomiting, diarrhea, fever, and chills. In most cases, side effects can be managed with appropriate counseling and symptomatic treatments, such as oral analgesics for pain. Complications of medical abortion are rare; vaginal bleeding requiring transfusion occurs in approximately 1 in 2000 cases.17 Uterine infection (endometritis) is also rare because medical abortion does not require insertion of an instrument into the uterus. Approximately 2%-5% of women undergoing medical abortion will require vacuum aspiration to complete the abortion or to control bleeding.17,18 Serious complications, including death, are extremely rare occurrences following either spontaneous, surgical, or medical abortion.
A wealth of international research and experience, and a growing body of national data on medical abortion supports the safety, effectiveness and acceptability of this alternative to early surgical abortion for the women of South Africa.
- Grimes DA, Mishell DR Jr, Shoupe D, Lacarra M. Early abortion with a singler dose of the antiprogestin RU-486. Am J Obstet Gynecol 1988;158:1307-12.
- Ulmann A, Silvestre L, Chemama L, et al. Medical termination of early pregnancy with mifepristone (RU 486) followed by a prostaglandin analogue: study in 16, 369 women. Acta Obstet Gynecol Scand 1992;71:278-83.
- Spitz IM, Bardin CW, Benton L et al. Early pregnancy termination with mifepristone and misoprostol in the United States. N Engl J Med 1998; 338:1241-47.
- Peyron R, Aubény E, Targosz V, et al. Early termination of pregnancy with mifepristone (RU 486) and the orally active prostaglandin misoprostol. N Engl J Med 1993;328:1509-1513.
- Guidelines for Termination of Pregnancy for Health Workers - April 1997. Maternal, Child and Women's Health Directorate, Department of Health, Republic of South Africa; April 1997.
- Cooper D, Dickson K, Blanchard K, Cullingworth L, Brown H, Mavimbela N, von Mollendorf C, van Bogaert LJ and Winikoff B. Medical abortion eligibility and its acceptability in South Africa. Reproductive Health Matters 2005; 13(26):75-83.
- Cullingworth L, de Pinho H. A cost analysis of service provision of medical abortions in the public health sector at primary and secondary level. Women's Health Research Unit, Department of Public Health, University of Cape Town. 2002
- Spitz IM, Bardin CW. Mifepristone (RU 486) - A modulator of progestin and glucocorticoid action. N Engl J Med 1993; 329:404-12.
- Schindler AM, Zanon P, Obradovic D, Wyss R, Graff P, Herrmann WL. Early ultrastructural changes in RU-486-exposed decidua. Gynecol Obstet Invest 1985;20:62-67.
- Koopersmith TB, Mishell DR Jr. The use of misoprostol for termination of early pregnancy. Contraception 1996;53:238-242.
- Aubény 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.
- World Health Organization Task Force on Post-Ovulatory Methods of Fertility Regulation. Comparison of two doses of mifepristone in combination with misoprostol for early medical abortion: a randomised trial. Br J Obstet Gynaecol 2000;107:524-530.
- von Hertzen H, Honkanen H, Piaggio G, et al. WHO multinational study of three misoprostol regimens after mifepristone for early medical abortion. I: Efficacy. Br J Obstet Gynaecol 2003; 110; 808-818.
- Schaff EA, Eisinger SH, Stadalius LS et al. Low-dose mifepristone 200 mg and vaginal misoprostol for abortion. Contraception 1999;59:1-6.
- ACOG Practice Bulletin. Clinical Management Guidelines for Obstetrician-Gynecologists Number 67, October 2005. Medical Management of Abortion. Obstet Gynecol 2005; 106(4): 871-882.
- National Abortion Federation. Clinical Policy Guidelines 2005. Early Medical Abortion 2005; 7-9.
- Henderson JT, Hwang AC, Harper CC, et al. Safety of mifepristone abortions in clinical use. Contraception 2005; 72(3):175-178.
- Kruse B, Poppema S, Creinin MD, Paul M. Management of side effects and complications in medical abortion. Am J Obstet Gynecol 2000; 183: S65-S75.
Prepared by NAF, Ibis, WHRU, Gynuity Health Projects, and Ipas-South Africa
6 February 2006