IN VITRO FERTILIZATION AND GENETIC SCREENING

The first birth following in vitro fertilization (IVF) took place in the United Kingdom in 1978, and the number of IVF births per year has increased steadily since then. More than 35,000 infants were born with the help of IVF in 2000 in the United States alone, and more than 1 million infants have been born worldwide following IVF. Although IVF has become an integral part of fertility medicine, ethical and policy issues continue to be debated as technologies change and IVF becomes more common. Among the topics debated are those relating to the moral status of embryos, disposition of frozen embryos, use of genetic testing of embryos to detect the presence of moderate rather than serious genetic disorders, and the adequacy of regulation.

Technologies

For an IVF cycle, physicians stimulate a female patient with hormones to induce the release of more than one egg. When tests show the eggs are ready to be released, physicians remove the eggs in an office procedure, fertilize them in vitro (in glass) with spermatozoa from the male partner or a donor, culture the fertilized eggs for two to three days to at least the stage of a four-cell embryo, and transfer the embryos to the woman's uterus for possible pregnancy.

Although IVF was primarily designed for women with blocked fallopian tubes who could benefit from the way IVF bypasses these tubes, advances over the years have extended the versatility of IVF as a method for circumventing infertility. For example women who do not ovulate can use donated eggs, and men with extremely low sperm counts can be aided by the manual injection of a single spermatozoan into an egg in a technique known as intracytoplasmic sperm injection (ICSI).

Another technique used in conjunction with IVF is pre-implantation genetic diagnosis (PGD), which is available for couples at risk for passing serious genetic diseases, such as Tay-Sachs disease and cystic fibrosis, to their offspring. In one form of PGD, the embryo biopsy, technicians remove a single cell from an embryo created through IVF and amplify the DNA to detect the presence of the disease-linked gene in question. Physicians then selectively transfer only those embryos without the anomaly to the woman's uterus. PGD is also used to detect chromosomal abnormalities that cause serious disorders in offspring or that interfere with conception. The first birth following IVF/PGD occurred in 1990. More than 1,000 infants had been born worldwide by 2002, with a pregnancy rate of about 24 percent (Robertson 2003).

Moral Status of Embryos

Perspectives about the moral status of embryos differ significantly among individuals. Some believe that early stage embryos are human beings with the moral status of persons that must be protected from injury or destruction. Others believe embryos are potential human beings warranting special respect but not the moral status of persons. Policy advisory groups in the United States have generally adopted the latter perspective (Ethics Advisory Board 1979). Due to a lack of consensus about the status of embryos, however, as of 2004 federal funds cannot under law be used to finance research in which human embryos are injured or destroyed. To the extent that investigators study human embryos, they do so with private research funds.

Disposition of Frozen Embryos

When couples undergo IVF or IVF/PGD, extra embryos are often created and frozen for later thaw and transfer. More than 100,000 embryos were frozen in the United States alone in 2002. Couples who no longer want or need their spare embryos can direct that the embryos be discarded, donated for research and eventual destruction, or donated to other couples. Difficulties can arise, however, if a couple divorces and has no prior written agreement about what should be done with the embryos or if one party seeks to nullify the agreement. The first appellate court to rule on this matter held that the person who wants to avoid parenthood (by not transferring the embryos) generally ought to prevail over the person who wants to achieve parenthood (by transferring the embryos) (Davis v. Davis 1992). Judges rely on case-by-case rule making in frozen embryo cases. In general they accept the principle established in Davis v. Davis, but differ on whether they will enforce prior agreements (Elster 2002).

Extending PGD

PGD is generally regarded as an ethically acceptable way of preventing human suffering when the disease in question is serious or fatal. Some have voiced reservations, however, about the potential for tests that can be used to detect less serious diseases such as deafness or predispositions to diseases such as Alzheimer's disease or breast cancer. The concern is that this will discourage tolerance for imperfections and devalue the inherent worth of individuals. Another concern is that negative selection (discarding affected embryos) will, when technologies allow it, set the stage for positive selection (seeking embryos with socially desirable traits), which would magnify differences between the rich and the less well-off; have eugenic overtones; and contribute to the mindset that people can be made to order, like commodities.

Those who do not share these concerns argue that IVF/PGD is so costly and intrusive that only a small number of people will use it. They point out that PGD is an alternative to prenatal testing for at-risk couples who know they will not terminate the pregnancy of a fetus with serious disorders and who welcome the opportunity to transfer only unaffected embryos for a potential pregnancy. In addition supporters of PGD question the wisdom of interfering with a technique that could prevent the birth of babies with serious disorders now on the basis of speculative concerns about possible future uses of PGD.

Policy Issues

IVF and other reproductive technologies are governed in a decentralized manner in the United States. Debates continue about whether more oversight is needed and, if so, what forms it should take. One point of view is that the system of oversight, which is based on state laws, medical licensing requirements, tort law, self-regulation by professional associations, administrative rule making, and the power of the marketplace, is thorough and effective (Adamson 2002). One federal law directs the government, in conjunction with professional associations, to collect and publicize data from fertility clinics to educate patients and the public about clinic performance. Those who believe that the oversight system is sufficient point to statistics on healthy children and improved birth rates for IVF as indicators of effective regulation and professional caution. They argue that concerns, such as those questioning the sizeable number of twin, triplet, and higher order births following IVF, can be addressed by professional self-management and improved technologies.

From another point of view, the government should take a more active role in monitoring IVF/PGD practice by developing a centralized oversight system and taking other steps to protect the health of patients and offspring. According to this view, the government should develop a centralized data gathering system or, at least, a national level forum for debating issues relating to infertility treatment. It should also enact laws to address specific concerns; for example, to limit the number of multiple births, and regulate by law the number of embryos that can be transferred per IVF cycle (International Society for Law and Technology [ISLAT] Working Group 1998).

The ability of the federal government to regulate IVF is limited by constitutional protections of reproductive liberty. In addition political controversies over the status of embryos make legislation difficult to enact. The likelihood of enacting in the United States a central oversight board for assisted reproductive technologies, as exists in the United Kingdom, is slim. In the meantime researchers are engaged in data gathering to assess the long-term safety of IVF, state legislatures are considering various forms of regulation, and practitioners are continuing to produce practice guidelines as part of self-regulatory policies.

Conclusion

IVF has led to the birth of more than 1 million children who may not otherwise have been born to couples experiencing various infertility problems. Issues about the status of embryos, disposition of frozen embryos, proper reach of PGD, and optimal forms of oversight have recurred in the years since l978. New ethical issues arise as the technologies and applications change. For example what payment is appropriate for egg donors? Should practitioners accept single persons as patients? What should be done with embryos abandoned by couples? What issues are raised when egg or sperm donors are related to the recipients? Should PGD be used to determine predisposition to disease? Should children conceived with donor eggs, sperm, or embryos be told how they were conceived?

Although no central forum exists for debating these issues in the United States, the public fascination with IVF ensures that the issues are aired and discussed. While it is tempting to call for governmental controls, the issues raised by rapidly changing technologies are not easily amenable to preemptive legislation, which can be rigid and easily dated. Moreover government policy precludes funding research in which embryos are injured or destroyed, which removes the power of the purse as a vehicle for oversight. Consequently, robust discussion, public education, regulations of medical facilities in general, and self-regulation by professional associations all contribute to oversight. Though complex and decentralized, this system allows monitoring while also respecting the reproductive liberty of couples seeking the services of fertility clinics.

ANDREA L. BONNICKSEN

SEE ALSO Assisted Reproduction Technology;Embryonic Stem Cells;Eugenics;Fetal Research;Genethics;Genetic Counseling;Playing God.

BIBLIOGRAPHY

Adamson, David. (2002). "Regulation of Assisted Reproductive Technologies in the United States." Fertility and Sterility 78: 932–940. An overview of numerous professional guidelines and government laws and policies that make up the regulatory framework for assisted reproductive technologies in the United States.

Davis v. Davis, 842 S.W.2d 588 (Tenn. 1992). First court case involving a dispute between male and female partners over the disposition of their frozen and stored embroyos.

Elster, Nanette R. (2002). "ARTistic Licence: Should Assisted Reproductive Technologies Be Regulated?" In Assisted Reproductive Technology: Accomplishments and New Horizons, eds. Susan M. Avery and Peter R. Brinsden. New York: Cambridge University Press. Review of court decisions, state and federal laws, and self-regulation of assisted reproductive technologies, including what Elster considers to be regulatory gaps.

Ethics Advisory Board. U.S. Department of Health, Education, and Welfare. (1979). Report and Conclusions: HEW Support of Research Involving Human In Vitro Fertilization and Embryo Transfer. Washington, DC: Government Printing Office. First report by a governmental advisory body on the ethics of in vitro fertilization; report concluded that research into IVF was ethically acceptable, with limits.

International Society for Law and Technology (ISLAT) Working Group. (1998). "ART into Science: Regulation of Fertility Techniques." Science 281: 65–66. Brief review of regulation of assisted reproductive technologies with recommendations for increased governmetnal oversight.

Robertson, John A. (2003). "Extending Preimplantation Genetic Diagnosis: The Ethical Debate." Human Reproduction 18: 1–7. Review of situations in which pre-implantation genetic diagnosis can be used; discussion of ethical and legal issues relating to these uses.

Society for Assisted Reproductive Technology and the American Society for Reproductive Medicine. (2002). "Assisted Reproductive Technology in the United States: 1999 Results Generated from the American Society for Reproductive Medicine/Society for Assisted Reproductive Technology Registry." Fertility and Sterility 78: 918–931.