RU 486/Prostaglandin: Considerations for Appropriate Use in Low-Resource Settings

RU 486 use in developing countries (particularly Bangladesh) was recently discussed at The International Symposium on Antiprogestins, held in Dhaka, Bangladesh, October 7–8, 1991.

Glasier Anna , “Postcoital Contraception with Mifepristone, ”The Lancet 337(June 8, 1991):1414–1415.

SCRIP No. 1679/80 December 20/25 1991, p. 24.

Memorandum on Safety and Efficacy of French Abortifacient RU 486: Experience in International Markets Support Manufacturer's Claims of Effectiveness and Safety; Questions Remain Regarding Legal, Regulatory and Political Barriers to Drug's Use in the United States, November 27, 1991, 102nd Congress United States House of Representatives Committee on Small Business, Subcommittee on Regulation, Business Opportunities and Energy.

World Health Organization,“Pregnancy Termination with Mifepristone and Gemeprost: A Multicenter Comparison Between Repeated Doses and Single Dose of Mifepristone, ”Fertility and Sterility 56(1)(July 1991):32–40.

Altman Lawrence K. , “A Simpler Way to Employ RU486 is Reported, ”The New York Times, April 9, 1991.

Roussel-Uclaf also includes anemia and malnutrition as contraindications to the use of RU 486/prostaglandin, but research is demonstrating that these conditions may be overly cautious as absolute contraindications.

Goldsmith Marsha F. , “As Data on Antiprogesterone Compounds Grow, Societal and Scientific Aspects Are Scrutinized, ”Journal of the American Medical Association 265(13)(April 3, 1991):1628–1629.

Aubény E. , “RU486 Combined with PG Analogs in Voluntary Termination of Pregnancy, ”Advances in Contraception 7(1991): 339–343.

Editorial,“A Death Associated with Mifepristone/Sulprostone, ”The Lancet 337(April 20, 1991):969–970.

Kalra P.A. , “Cardiac Standstill Induced by Prostaglandin Pessaries, ”The Lancet (June 24, 1989): 1460–1461.

Id.

Heard Michael and Guillebaud John , “Medical Abortion: Safe, Effective and Legal in Britain, ”British Medical Journal 304 (January 25, 1992):195–196.

Id.

Collins P.W. , “Chemistry and Synthetic Development of Misoprostol, ”Digestive Diseases and Sciences, 30(11) (November 1985 Supplement):114S–117S.

Product Information, Cytotec, Physicians Desk Reference, Medical Economics Data, Oradell, NJ 1991: 2060–2062, at 2061.

Norman J.E. , “Uterine Contractility and Induction of Abortion in Early Pregnancy by Misoprostol and Mifepristone, ”The Lancet 338 (Nov. 16, 1991):1233–1236.

Id. p. 1235.

Élisabeth Aubény and Étienne-émile Baulieu , “Activite contragestive de l'association au RU 486 d'une prostaglandine active par voie orale, ”C.R. Acad. Sci. 312 (11) (Series III, 1991):539–545.

Personal Communication, Dr. Etienne-Emile Baulieu, February 3, 1992.

Product information, Cytotec, supra, note 16, p. 2060.

Kapp Marshall B. , “Prescribing Approved Drugs for Non- approved Uses: Physicians' Disclosure Obligations to Their Patients, ”9 Law, Med. and Health Care 21, 22 (1981). In 1972 the F.D.A. proposed a rule that would give it authority to restrict physicians to prescribe drugs only for the specific purposes for which they were approved, but intense physician lobbying kept the rule from becoming final. Although not subject to F.D.A. authority, physicians prescribing drugs for nonapproved uses are governed by medical malpractice law. Id. p. 21.

Schönhöfer Peter S. , “Brazil: Misuse of Misoprostol as an Abortifacient May Induce Malformations, ”The Lancet 337(June 22, 1991):1534–1535.

Id.

Id.

Fonseca Walter , “Misoprostol and Congenital Malformations, ”The Lancet 338 (July 6, 1991): 56. Other articles have addressed skull malformations and other anomalies following prostaglandin therapy in pregnant women and in newborns. See, for example: Collins Francis S. and Mahoney Maurice J. , “Hydrocephalus and Abnormal Digits after Failed First-Trimester Prostaglandin Abortion Attempt,”(involving 15-methyl F2a) J Pediatr 1983 102:620–623; Ringel Richard , “Periosteal Changes Secondary to Prostaglandin Administration,”(involving long-term PGE1 therapy in neonates) J Pediatr 1983 103:251–253 and Hedwig Hoevels-Guerich , “Widening of Cranial Sutures after Long-term Prostaglandin E2 Therapy in Two Newborn Infants,”(involving intravenous administration of PGE2 to newborns for 95 and 97 days) J Pediatr 1984 105:72–74.

Norman J.E. , supra, note 17, p. 1235.

Product information, Cytotec, supra, note 16, p. 2060.

Swahn M.L. , “Effect of Oral Prostaglandin E2 on Uterine Contractility and Outcome of Treatment in Women Receiving RU 486 (Mifepristone) for Termination of Early Pregnancy, ”Human Reproduction 4(1)(1989):21–28.

Swahn M.L. , “Oral Administration of RU 486 and 9-Methylene PGE2 for Termination of Early Pregnancy, ”Contraception 41(5)(1990):461–473.

Frydman R. , “Transplacental Passage of Mifepristone, ”The Lancet 2(1985):1252.

Lim B.H. , “Normal Development after Exposure to Mifepristone in Early Pregnancy, ”The Lancet 336(July 28, 1990):257–258; Pons Jean-Claude , “Development after Exposure to Mifepristone in Early Pregnancy, ”The Lancet 338 (Sept. 21, 199:0:763 and Ulmann André , “Development After in utero Exposure to Mifepristone, ”The Lancet 338 (Nov. 16, 1991):1270.

Henrion R. , “RU 486 Abortions, ”Nature 338(1989):110 and Pons J-C , “Development after Exposure to Mifepristone in Early Pregnancy, ”The Lancet 338(September 21, 1991):763.

Grimes David A. and Cates Willard Jr. , “Complications from Legally-Induced Abortion: A Review, ”Obstet and Gynecol Survey 34(3)(1979): 177–191, at 178.

Sharp curettage has a major complication rate 2.3 times higher than suction curettage. Id. p. 177.

Personal Communication, Dr. Hershel Lawson, Center for Disease Control, Atlanta, GA, February 24, 1992.

Grimes David A. and Cates Willard Jr. , supra, note 34, p. 186.

Personal Communication, Dr. Herbert Lawson, supra, note 36.

Grimes David A. and Cates Willard Jr. , supra, note 34, p. 180.

Birman Chantal , “The Experiences of Women Having an Abortion with RU 486, ”Women's Global Network for Reproductive Rights Newsletter 31(Oct./Dec., 1989):7–9.

Urquhart D.R. and Templeton A.A. , “Psychiatric Morbidity and Acceptability Following Medical and Surgical Methods of Induced Abortion, ”British Journal of Obstetrics and Gynaecology 98(April 1991):396–399.

Tang G.W. , “A Pilot Study of Acceptability of RU 486 and ONO 802 in a Chinese Population, ”Contraception 44(5)(November 1991):523–532.

Id. 530.

Id. pp. 526, 530.

Id. p. 529.

See Winikoff Beverly , “Studying the Acceptability and Feasibility of Medical Abortion,”Law, Medicine & Health Care 20:2 (this issue).

Coyaji Banoo , “Safe Motherhood and RU-486 in the Third World, ”People 17(3)(1990):13–15.

Royston Erica Armstrong Sue , eds., Preventing Maternal Deaths, (Geneva: World Health Organization 1989): Pp. 31, 35.

Id. p. 111.

The anti-choice movement opposing RU 486 is not limited to industrialized countries. The Pro-Life Society of Zambia has vowed to fight RU 486 should it come into use there. Michael Andindilile,“Pro-Life Society to Fight Abortion Drug, ”Times of Zambia, Saturday, July 11, 1990.

See Renata Klein , RU 486: Misconceptions, Myths and Morals, (Australia: Spinifex Press Pty Ltd. 1991) and Kabir Sandra and Germain Adrienne , “Is RU 486 Likely to be Appropriate for Women in Bangladesh?”(Paper prepared for the International Symposium on Antiprogestins, unpublished, 1991).

Riding Alan , “Abortion Politics Are Said to Hinder Use of French Pill, ”The New York Times, July 29, 1990: Pp. 1, 9.

The French National Advisory Committee on Ethics on the Life Sciences and Health concluded that RU 486/prostaglandin falls within the scope of legislation on abortion. Knoppers Bartha M. , “Abortion Law in Francophone Countries,”38 Am J of Comparative Law 889,901 (1990). The 1967 Abortion Act in the U.K. was amended in 1990 to permit the provision of nonsurgical abortions. Human Fertilisation and Embryology Act 1990, Sect. 37 (3). For a discussion of the legal developments regarding RU 486 in France and the United Kingdom, see Reed Boland,“RU 486 in France and England,”in this issue of Law, Medicine & Health Care.

See Glasier Anna , supra, note 2.

Henshaw Stanley K. , “Induced Abortion: A World Review, 1990, ”Family Planning Perspectives 22(2)(1990): 76–89.

Id.

In the past two decades, 65 jurisdictions have liberalized their abortion laws while four countries have limited the grounds for the procedure. Cook Rebecca J. , “Abortion Laws and Policies: Challenges and Opportunities, ”Int. J. Gynecol. Obstet. Suppl. 3 (1989): 61–87, at 61.

In the United States, the states of Utah and Louisiana and the territory of Guam have passed legislation making abortion a crime (with exceptions). Utah S.B. No. 23 (1991); LAS-R.S. 14:87 (1992) [held unconstitutional in Sojourner T. v. Roemer and Okpalobi v State, 772 F. Supp. 930 (E. D. La.), (Aug. 7, 1991)]; Guam Bill No. 848 [held unconstitutional in Guam Society of Obstetricians and Gynecologists v. Joseph F. Ada, 972 F. 2nd 1366 (April 14, 1992)].

Yen S.S.C. , “The Human Menstrual Cycle,”in Yen S.S.C. and Jaffe R. , eds., Reproductive Endocrinology, Physiology, Pathophysiology and Clinical Management, (Philadelphia: W.B. Saunders, 1986), second ed., p. 200.

See Cook Rebecca J. , “Anti-Progesterones and the Law, ”IPPF Medical Bulletin 20(5)(1986):2–3. Cook advocates that laws should accommodate the use of antiprogesterones as a last chance contraceptive for women with amenorrhea of up to 35 days from the first day of the last menstrual period. The law would reflect the biological reality that not all women have regular, 28-day menstrual cycles. Id. p. 3.

1978 (3 April) Penal Law, Sec. 16.3.

Cook Rebecca J. , supra, note 57.

In section 31.20, Guam's abortion law defines abortion as“the purposeful termination of a human pregnancy after implantation of a fertilized ovum….”Guam Bill No. 848 (1989)(emphasis added); the Utah law defines abortion as“the termination or attempted termination of human pregnancy after implantation of a fertilized ovum…”Utah S.B. No. 23, Section 76-7-301 (1) (1991).

Republic of Zambia, Termination of Pregnancy Act, Chapter 554 of the Laws of Zambia (1972).

Section 3209 of the Pennsylvania Abortion Control Act requires that, before a physician may perform an abortion on a married woman, the woman must sign a statement that she has notified her husband of her intended abortion (each form must bear a notice that false statements are punishable by law). 18 Pa. Cons. Stat. Ann. §§ 3201–3220 (1983 & Supp. 1991). This section was declared unconstitutional by the United States Court of Appeals, Third Circuit, in Planned Parenthood of Southeastern Pennsylvania v. Casey, 947 F2d. 682 (1991).

Knoppers Bartha M. , supra, note 53, p. 914, citing France: Code de la santé publique, art. 162–5, as amended by Loi de 1975; Belgium: Code pénal, art. 350(3); Luxembourg: Code pénal, art 353.

On average the mortality rate for abortion increases by 30 percent with each passing week of gestation. The mortality rate at nine to ten weeks of gestation is one-fourth the mortality rate at 13 to 15 weeks of gestation. Robert G. Castadot,“Pregnancy termination: techniques, risks, and complications and their management,”Fertility and Sterility 45(1) (1986):5–17, at 8.

Cook Rebecca J. , supra, note 57.

Paxman J.M. and Barberis M. , “Menstrual Regulation and the Law, ”Int. J. Gynecol. Obstet. 17(1980):493–503, at 16, 17.

Id.

Taylor Cathy M. and Pernoll Martin L. , “Normal Pregnancy & Prenatal Car,e”in Current Obstetric & Gynecologic Diagnosis & Treatment, Pernoll Martin L. and Benson Ralph C. , eds., Sixth Edition, (Norwalk, Connecticut: Appleton & Lange, 1987): 164.

Gestational trophoblastic tumors arise in fetal rather than maternal tissue. April G. O'Quinn and Barnard David E. , “Gestational Trophoblastic Disease,s”in Current Obstetric & Gynecologic Diagnosis & Treatment, Pernoll Martin L. and Benson Ralph C. , eds., Sixth Edition, (Norwalk, Connecticut: Appleton & Lange, 1987): 891–900, at 891.

Only pregnancy tests that are radioimmunoassay for the bT- subunit of the hCG are sensitive and specific for early pregnancy. In immunologic pregnancy tests, cross-reaction can occur with luteinizing hormone (LH). Thus, any condition that stimulates release of LH from the anterior pituitary may cause a false-positive reaction on the test. Antipsychotic agents and tranquilizers may cause release of LH. Test results are also altered by proteinuria and immunologic disease. Taylor Cathy M. and Pernoll Martin L. , supra, note 71, pp. 166–167.

Irani Kathy R. , “Menstrual Induction: Its Place in Clinical Practice, ”Obstetrics and Gynecology 46(5) (November 1975):596–598, at 598.

World Health Organization,“Menstrual Regulation by Intramuscular Injections of 16-Phenoxy-Tetranor PGEz Methyl Sulfonylamide or Vacuum Aspiration. A Randomized Multicentre Study, ”British Journal of Obstetrics and Gynaecology, 94 (October 1987): 949–956.

Penal Code Act XLV, Chapter XVI—Of Offences affecting the Human Body (1860).

Government of the People's Republic of Bangladesh, Population Control and Family Planning Division, Memorandum: Guidelines for Menstrual Regulation (MR), Memo No. 5-14/MCH- FP/Trg./80/358/1(96). Dated 25 January 1980. The memorandum cites an Extract from Report on Legal Aspects of Population Planning in Bangladesh, Chapter II – Abortion, p. 31:“…many Family Planning Clinics are carrying out the post-contraceptive method of 'Menstrual Regulation' as a means of birth control which does not come under Section 312 of the Penal Code. Under [the] statutory scheme, pregnancy is an essential element of the crime of abortion, but the use of menstrual regulation makes it virtually impossible for the prosecutor to meet the required proof…”Id.

In France, the 1939 amendment to the 1810 Napoleonic Penal Code made it a crime to perform abortion on a pregnant woman“or a woman who is presumed to be pregnant.” Knoppers Bartha M. , supra, note 53, p. 894; Under Section 58 of the Offences Against the Person Act (1861) and Section 1 of the 1929 Infant Life (Preservation) Act, abortion was defined as“unlawfully using any instrument or other means with the intent to procure a miscarriage of any woman.” Paxman J. and Barberis M. , supra, note 69, p. 496.

Id.

Henshaw Stanley K. , “Induced abortion: A world review: 1990,”Family Planning Perspectives 22(2)(March/April 1990):76–89.

Henshaw Stanley K. , “Hurdles Increase for Many Women Seeking Abortions,”The New York Times, Sunday, March 15, 1992: 1 and 11, at 11. From 1977–1988, 110 cases of arson, firebombing or bombing were reported against pro-choice facilities and organizations in the United States. Grimes David A. , “An Epidemic of Antiabortion Violence in the United States, ”Am J Obstet Gynecol 165 (1991):1263–1268, at 1264.

Center for Disease Control,“Abortion Surveillance: Preliminary Analysis—United States, 1989, ”MMWR 40(47)(November 29, 1991):817–818.

Chen A.J. , “Legalized Abortion: The Singapore experience, ”Studies in Family Planning 16(3)(May/June 1985):170–178.

Id.

Baird David T. , “Prostaglandin and Antigestigens for the Interruption of Early Pregnancy, ”Journal of Reproductive Fertility, Suppl. 36(1988):173–179.

Rodger Mary W. and Baird David T. , “Blood Loss Following Induction of Early Abortion Using Mifepristone (RU 486) and a Prostaglandin Analogue (Gemeprost), ”Contraception 40(4)(October 1989):439–447.

Moore Pamela J. , “Maternal Physiology During Pregnancy,”in Current Obstetric & Gynecologic Diagnosis & Treatment, Pernoll Martin L. and Benson Ralph C. , eds., Sixth Edition, (Norwalk, Connecticut: Appleton & Lange, 1987): 129.

Id.

Rodger Mary W. and Baird David T. , supra, note 86.

Coyagi Banoo , supra, note 47, p. 15.

Kabir Sandra and Germain Adrienne , supra, note 51, p. 8.

World Health Organization,“A Cross-Cultural Study of Menstruation: Implications for Contraceptive Development and Use, ”Studies in Family Planning 1981 12(1):3–16.

SCRIP No. 1382, February 1, 1989, p. 23.

“Decline in NHSC Physicians Threatens Patient Care, ”AJPH 1990 80(11):1395.

Lewin Tamar , supra, note 81, p. 11.

Henshaw Stanley K. , “The Accessibility of Abortion Services in the United States, ”Family Planning Perspectives 1991 23(6):246–252.

Id. p. 248.

Lewin Tamar , supra, note 81, p. 11.

In 1988, regulations promulgated by the U.S. Department of Health and Human Services directed that family planning clinics, as a condition of receiving federal subsidies under Title X of the Family Planning Services and Population Act, may not discuss abortion with a client, even if a client initiates the discussion. 42 CFR $59.1-$59.10 (1989). The regulations have not been enforced because of legal challenges and because of the failure of the Health and Human Services Department to issue detailed enforcement guidelines. In 1989 the U.S. Supreme Court upheld the Title X regulations in Rust v. Sullivan, 111 S. Ct. 1759 (1991); Jeremy Sugarman and Madison Powers,“How the Doctor Got Gagged,”Journal of the American Medical Association 266 (23) (December 18, 1991):3323–3327. On March 20, 1992, a guidance memorandum was issued to the ten Department of Health and Human Services regional health administrators to clarify implementation of the regulations. The guidance memorandum has caused considerable confusion on how Title X regulations are to be implemented. Philip J. Hilts,“White House Allows Some Advice At Public Clinics About Abortion,”The New York Times, Saturday, March 21, 1992, pp. 1 and 5; Washington Memo,“Bush Administration Issues Plan for Implementation of Abortion 'Gag Rule,'”April 1, 1992, pp. 1–4.

For an excellent review of this issue, see Sereen Thaddeus and Deborah Maine, Too Far to Walk: Maternal Mortality in Context, Prevention of Maternal Mortality Program, Center of Population and Family Health, Columbia University, 1990.

Cook Rebecca J. and Maine Deborah , “Spousal Veto over Family Planning Services, Am. J. Pub. Health (1987) 77:339–340.

These are actual statistics presented in an evaluation of menstrual regulation services in rural clinics in Bangladesh. See Kay Bonnie J. and Kabir Sandra M. , “A Study of Costs and Behavioral Outcomes of Menstrual Regulation Services in Bangladesh, ”Soc. Sci. Med. 26(6)(1988): 597–604.

Maine Deborah , Safe Motherhood Programs: Options and Issues, Center for Population and Family Health, School of Public Health, Faculty of Medicine, Columbia University, New York, 1991, p. 42.

Id.

McLaurin Katie , “Health Systems' Role in Abortion Care: The Need for a Pro-Active Approach, ”Issues in Abortion Care 1, (Carrboro, North Carolina: IPAS, 1991).

Drug Facts and Comparisons, The Facts and Comparisons Divisions, (St. Louis:J.B. Lippincott Company, 1988):328C.

For a discussion of the relative risks of introducing RU 486/prostaglandin into developing countries, see Woodroffe Caroline , “Medical abortion and the availability of RU486—are women's rights being ignored in developing countries?” Health Policy and Planning 7(1) (1992):77–81.

Kolata Gina , “Patients Turning to Illegal Pharmacies, ”The New York Times, Monday, November 4, 1991, pp. A-1 and A-10.

Lee P. , “Drug Promotion and Labeling in Developing Countries: An Update, ”J Clin Epidemiol 44(suppl II)(1991):49S–55S.

Wolffers Ivan , Marketing Fertility: Women, Menstruation and the Pharmaceutical Industry (Amsterdam: WEMOS, May 1989); Coelho H. , “Selling Abortifacients Over the Counter in Pharmacies in Fortaleza, Brazil,”The Lancet 338(July 27, 1991):147; de Oddone Nelly Krayacich , “Paraguayan Pharmacies and the Sale of Pseudo-Abortifacients, ”J. Biosoc. Sci. 1991 2.3:201–209.

See Charo Alta , “A Political History of RU-486,”In Hanna K.E. , ed., Bio-Medical Politics (Washington, D.C.: National Academy Press, 1991):43–91.

“RU 486 Goes into Widespread Use in UK,”IPPF Open File, January 1992, p.9.

Id.

102nd Congress, United States House of Representatives, supra, note 4, p. 19.

“Drugs for the Treatment of Peptic Ulcers, ”The Medical Letter, vol. 33 (issue 858), November 29, 1991. The wholesale price for 800 mUgs. per day for 30 days is listed as $71.59. This gives a wholesale price of $1.19 for 400 mUgs.

Woodroffe Caroline , supra, note 107, p. 80.