Antiprogestin drugs: Medical and legal issues. (Comment).

The Webster decision of the U.S. Supreme Court,(1) one aspect of which upheld state conditions limiting delivery of late abortion services, underscores the need for safe and reliable means to perform abortion early in pregnancy.(2) The Missouri statute reviewed in Webster raised an additional issue in its preamble, which contained the words: "The life of each human being begins at conception."(3) The Court saw no need to address the implications of this language yet, and is prepared instead to await a judicial challenge to legislation specifically providing for state intervention on these grounds.(4) It is difficult to predict whether and to what extent the Court will find a legislative restriction on abortion early in pregnancy to be constitutional, but for many reasons, providing access to abortion at the earliest possible stage in pregnancy is advisable. Antiprogestin drugs permit a new, safe and effective means to achieve early abortion.

Antiprogestins are synthetic steroids that inhibit the activity of progesterone by blocking the cells' progesterone receptors.(5) Progesterone, a hormone necessary for pregnancy, rises in level after ovulation, and prepares the uterus for implantation of the fertilized ovum.(6) After implantation, it sustains the embryo until the placenta has formed. Antiprogestin drugs prevent implantation if fertilization has occurred. In this sense, they may be described as "last-chance" contraception. However, if implantation is complete, antiprogestins will prevent gestation of an early embryo, causing its abortion. They thus may also be described as "contragestational."(7)

Antiprogestins can act at different points along a developmental continuum before, during and after completion of implantation. The egg, which is fertilized in the fallopian tube, takes about six days to reach a place in the lining of the uterus where it begins the process of implantation,(8) which takes another 6-8 days to complete.(9) Thus, implantation is usually accomplished 12-16 days after fertilization, or about 28-32 days from the beginning of the last menstrual period.

According to its medical definition, pregnancy begins at the completion of implantation of the embryo in the woman's womb.(10) This definition has been adopted by the American College of Obstetricians and Gynecologists.(11) The Committee on Medical Aspects of Human Reproduction of the International Federation of Gynecology and Obstetrics unanimously agreed that "pregnancy is only established with the implantation of the fertilized ovum."(12) This medical definition of pregnancy coincides with medical practice regarding in vitro fertilization; in these programs, pregnancy is considered to begin at the completion of implantation of an egg fertilized outside the womb. In the United States, the loss of fertilized eggs in in vitro fertilization programs is accepted and is not considered abortion.(13) Comparable policies have been recommended in government and law reform reports in the United Kingdom;(14) Victoria, Australia;(15) Ontario, Canada;(16) and France.(17)

During the first 14 days of development, the products of the fertilized egg are variously termed the conceptus, the zygote, the blastocyst or the "preembryo."(18) After implantation, the embryo forms in the center of the conceptus, and the remaining 99 percent of the tissue gives rise to the placenta and other extraembryonic membranes.(19) The embryo develops into a fetus at about eight weeks after fertilization or 10 weeks after the last menstrual period.(20) Depending on the stage of gestation, 22-31 percent of conceptions end in spontaneous abortion, which can occur before or after implantation; such reproductive failures may range as high as 62 percent.(21)

Abortion can be artificially induced by antiprogestins before the development of the fetus.(22) When administered early in pregnancy, the antiprogestin drug RU 486 (known scientifically as mifepristone and generically as mifegyne) has been generally shown to be 85 percent effective as an abortifacient when used alone(23) and 95 percent effective when used in combination with a prostaglandin.(24) The drug, which was developed by the French-based company Roussel-UCLAF, has also been investigated in animals and humans for a variety of other health indications, including inhibition of ovulation,(25) luteal interception,(26) induced delivery following spontaneous fetal death(27) and treatment of gynecologic malignancy(28) and breast cancer.(29) It also may be used to treat Cushing's syndrome, because of its collateral antiglucocorticoid effect.(30)

In many countries (including France, where RU 486 with prostaglandin is now used widely for early first-trimester abortions), the laws controlling the availability of abortion exempt medical practitioners and women undergoing abortion from criminal liability.(31) In the United States, abortion is available on request as a matter of a woman's constitutional right to privacy,(32) but delivery and financing of services can be variously controlled by state laws.(33) In Canada, abortion (particularly in the early stage of pregnancy) is available as a matter of a woman's constitutional rights of liberty and security of the person,(34) health services, including abortion, are provided through provincial health insurance plans, with the federal government setting minimum standards of comprehensiveness and accessibility. (35) In all countries that legislatively or constitutionally permit abortion, approval of abortifacient drugs is a matter of administrative law and is not distinguishable in principle or approach fro m approval of therapeutic drugs. For regulatory approval in any country, all drugs are required to meet reasonable standards of safety and efficacy in intended use. (36)