Reproductive Technologies: IX. In Vitro Fertilization and Embryo Transfer

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IX. IN VITRO FERTILIZATION AND EMBRYO TRANSFER

In in vitro fertilization (IVF), a woman's ovaries are stimulated with fertility drugs to produce multiple eggs. The physician monitors the woman's response by examining urine samples, blood samples, and ultrasound imaging. After giving her an injection to control the timing of the egg release, the physician retrieves the eggs in one of two ways. In a laparoscopy, done under general anesthesia, the surgeon aspirates the woman's eggs through a hollow needle inserted into the abdomen, guided by a narrow optical instrument called a laparoscope. In the more recently developed transvaginal aspiration, done with local anesthesia, the physician inserts the needle through the woman's vagina, guided by ultrasound.

After they are retrieved, the eggs are placed in separate glass dishes and combined with prepared spermatozoa from the woman's partner or a donor. The dishes are placed for twelve to eighteen hours in an incubator designed to mimic the temperature and conditions of the body. If a single spermatozoon penetrates an egg, IVF has occurred.

A fertilized egg subdivides into cells over a period of forty-eight to seventy-two hours. Microscopic in size, it is generally called a pre-embryo or an embryo after it has divided into two or more cells. When the embryos have divided into four to sixteen cells, they are placed in a hollow needle (catheter) that is inserted into the woman's vagina. The embryo or embryos are released into the woman's uterus in the procedure known as embryo transfer. Implantation in the uterine wall, if it takes place, will occur within days after transfer; a pregnancy is detectable about two weeks after the transfer.

In established IVF clinics, the odds that a continuing pregnancy and birth will occur after embryo transfer are 20 to 30 percent. Because problems can arise at all stages of IVF, such as the inability to retrieve eggs or secure fertilization, the odds are less if they are calculated from the time fertility drugs are first given. Data from several national registries indicate a delivery rate of 9 to 13 percent if calculated from the starting point of hormonal stimulation (Cohen, 1991). The birthrates tend to cluster among clinics, so that some clinics account for a large percentage of the total births while others have few or no deliveries (Medical Research International). Tens of thousands of embryo transfers are carried out each year internationally, and thousands of babies have been born. Clinicians reported over 12,000 deliveries following IVF in one five-year period (1985–1990), and in one country (the United States) alone (Medical Research International).

Present and Future Variations

The first birth following IVF occurred in England in 1978 (Steptoe and Edwards). The technique was originally designed to circumvent blocked or damaged fallopian tubes in women trying to become pregnant. During the late 1970s and early 1980s, physicians combined the male partner's sperm and the female partner's eggs and transferred the embryos shortly after fertilization. If the couple had a large number of embryos, physicians either transferred all at once, which created the risk of a multiple pregnancy, or disposed of extra embryos, which wasted the embryos and was morally problematic.

The start of embryo freezing in the early 1980s has given physicians greater control over the number of embryos transferred at once. Two to four embryos are transferred in the first IVF cycle and the remaining embryos, if any, are frozen for later thawing and transfer. Embryo freezing saves the woman from the hormonal stimulation of repeated startup IVF cycles, and it allows embryo transfer when the woman's body has returned to a more natural state. By enabling the transfer of a small number of embryos at once, it reduces the odds of a multiple pregnancy and the subsequent risk this poses to the woman and the fetuses. Controlled transfer of embryos is arguably less morally problematic than the selective abortion of fetuses in a large multiple pregnancy. The birth of the first infant to have been frozen as an embryo took place in Australia in 1984. Embryo freezing is now a routine option in IVF.

Another variation that has increased the flexibility of IVF is the use of donated sperm, eggs, and embryos to circumvent fertility problems such as low sperm count in the male partner, lack of ovulation in the female partner, or lack of fertilization with the couple's own eggs and sperm, or to help couples at high risk avoid passing on a serious genetic disorder to their children. Sperm and embryo donation are more straightforward than egg donation, which is complicated by the need to synchronize the menstrual cycles of the donor and recipient. Women are either paid for their services in donating eggs or they donate in the course of their own medical treatment. In addition, some women donate eggs for their sisters or other close relatives. Donation of eggs or sperm raises questions about, among other things, confidentiality of medical records, the child's sense of identity, and the psychological well-being of the donor.

The embryos in IVF can be transferred to a surrogate if the genetic mother does not have a uterus or cannot carry a child to term for other reasons. Although the surrogate is usually unrelated, there have been instances of embryo transfer to the sister or even the mother of a woman who cannot carry a fetus to term. In the latter case, the surrogate is the child's gestational mother and genetic grandmother.

Sperm microinjection is another technique used in connection with IVF. If the male partner has low sperm count or poor sperm quality, a healthy spermatozoon can be manually inserted into the egg with special microinstruments. This alternative to sperm donation allows the transfer of embryos genetically related to the couple. This and other microsurgical procedures remain experimental and infrequent.

Another procedure for IVF is the examination of sperm, eggs, and embryos for chromosomal and genetic abnormalities. Preimplantation diagnosis has been conducted on an experimental basis in the United States, Britain, and other European countries. It is being developed for couples at high risk for passing to their children a genetic disorder such as cystic fibrosis or Tay-Sachs disease but who will not terminate a pregnancy and are therefore not candidates for prenatal screening.

Preimplantation diagnosis includes polar-body analysis (analyzing the DNA of the first polar body of the human egg), trophectoderm biopsy (examining extra-embryonic cells surrounding the inner cell mass), and embryo biopsy (removing a single cell from a four- or eight-cell embryo). It also includes chromosomal analysis to select only female embryos for transfer to couples who are at high risk for passing on a sex-linked disease, such as hemophilia, to male children. Pregnancies and births have been reported following embryo biopsy and sex preselection. Many variables remain to be worked out in preimplantation diagnosis, and physicians urge caution before expanding it in the IVF setting (Trounson). Correcting genetic flaws after they have been diagnosed is a distant, though foreseeable, possibility (Verlinksy et al.).

Ethical Issues in IVF

A recurring and unresolved issue in IVF involves the status of the embryo (McCormick). The Ethics Advisory Board, set up by the U.S. Department of Health, Education and Welfare, and later disbanded without its recommendations' being acted on, issued a report in 1979 stating that "The human embryo is entitled to profound respect, but this respect does not necessarily encompass the full legal and moral rights attributed to persons" (U.S. Department of Health, Education and Welfare, p. 107). The Warnock Commission issued a report in Britain in 1984 that also accorded the embryo a "special status," though not the same status "as a living child or adult" (Warnock).

The notion that the embryo is an entity with a special status deserving special respect is contested by those who regard the embryo as fully a human being from the moment of conception. An instruction issued by the Vatican concluded that the "human being must be respected—as a person—from the very first instant of his existence" (Catholic Church; Shannon and Cahill). The unique genetic makeup of the embryo, among other things, is given as evidence of its individuality.

Beliefs about the embryo's status are central to conclusions about what in IVF is permissible and what is not. Some observers who regard the embryo as a human being believe IVF is ethically acceptable provided all embryos are transferred and given a chance to survive. Others believe external fertilization is always immoral. If the embryo is regarded as a human being, it has "full human rights," including the right not to be experimented upon without its consent (Ramsey, 1972a, 1972b). Even if one regards IVF as no longer experimental, the conclusion of immorality still extends to IVF's variations, which begin as experimental procedures posing the risk of higher-than-normal embryo loss.

If, on the other hand, the embryo is regarded as only potentially a human, fewer ethical strictures on IVF techniques apply. The Ethics Advisory Board concluded that IVF was ethically acceptable for married couples and that research on human embryos was acceptable provided the research was designed to establish IVF safety, would yield "important scientific information," complied with federal laws protecting research subjects, and proceeded only with the consent of tissue donors. No research was to take place beyond the fourteenth day after fertilization. After fourteen days, the embryo begins to develop an embryonic disk or "primitive streak" and is no longer capable of spontaneous twinning, which means it is on the way to becoming a single individual.

IVF has been criticized as a fundamentally dehumanizing technique that takes place in a laboratory, involves the scientist as a third party, is geared to the production of human beings, and is aimed at conquering nature and producing a "quality" child (Kass). The language of IVF and its business and marketing overtones contribute to a situation in which tissues and children are treated as commodities to be produced and in which intimacy is devalued (Lauritzen). The Vatican instruction concluded that IVF is unnatural because the sperm are secured by masturbation and the union takes place outside the body. Tissue donation is especially illicit, as it is "contrary to the unity of marriage, [and] to the dignity of the spouses" (Catholic Church).

Some feminists have expanded on this theme by criticizing laboratory conception as an intervention that divides reproduction—once a continuous process taking place naturally within the woman's body—into discrete and impersonal parts subject to a male-dominated medical profession (Arditti et al.). They argue that in IVF, women are perennial research subjects in an unending set of techniques that have significant emotional costs (Williams); that IVF benefits men and compromises women; and that it curtails women's autonomy and magnifies gender-based power differences in society (Wikler). Other feminists support IVF if it is bounded by feminist ethics and if it builds women's control over reproduction rather than taking it away (Sherwin).

IVF's variations challenge notions of the family, the interests of the potential child, the distribution of societal resources, and the rights of prospective parents. Tissue donation from relatives creates new biological if not legal relationships—for example, when a sister donates an egg to a sister for IVF or a brother donates sperm for his brother's IVF attempt. Embryo freezing creates the prospect of some embryos being stored indefinitely or transferred in a later generation, possibly endangering the resulting child's sense of identity. It also sets the stage for custody disputes and conflicts over the disposition of unwanted embryos (Davis v. Davis, 1992).

Embryo diagnosis for genetic defects raises safety questions for the embryo and potential child. Conceivably, it will lead to screening for many genetic problems and not just the life-threatening disorders envisioned now. On the one hand, discarding embryos after tests reveal a genetic abnormality might be less morally contentious than aborting pregnancies, at least for those who believe the embryo has a lesser status than a fetus. On the other hand, discarding "defective" embryos may blunt societal sensibilities and invite fertile couples into the costly and uncertain IVF procedure. The ability to preselect embryos according to sex raises concerns that the technique will be used for nonmedical reasons to give couples a child of their preferred gender, which may be male (Wertz and Fletcher).

IVF is highly selective in the people it can help. An expensive procedure covered by few insurance companies, it is available primarily to affluent couples. Critics question the wisdom of directing scarce resources to an elective and costly procedure with low odds of success (Callahan). Others advise paying more attention to preventing infertility in the first place (Blank). Aggressive marketing of IVF, including marketing that distorts success rates to make them seem greater than they actually are, arguably creates needs by making couples feel they ought to try IVF because it is there to try and by interfering with alternatives such as adoption or stopping efforts to conceive.

Concerns about the support of IVF and embryo research have been integrated into formal policy in a number of countries (Knoppers and LeBris). For example, the British Human Embryology and Fertilisation Act of 1990 created a licensing authority to conduct on-site visits to clinics in which human embryos are manipulated, review research proposals, and ensure that quality control is maintained in the laboratories (Morgan and Lee). A restrictive law in Germany, by contrast, makes criminal a range of techniques not therapeutic for the embryo, including sex preselection for nonmedical reasons ("German Embryo Protection Act"). Among the international documents relating to embryo manipulations are a recommendation from the Parliamentary Assembly of the Council of Europe that the Council of Ministers provide a "framework of principles" governing embryo and fetal research ("Parliamentary Assembly"), and a set of principles relating to IVF and its variations ("Council of Europe").

Fifteen states in the United States mention embryos in their statutes, but legislators passed most laws with abortion and fetuses in mind rather than IVF and embryos. Some of these laws would presumably make embryo research illegal, but their constitutionality has not been tested (Robertson). In 1989 the U.S. Supreme Court reviewed Missouri's abortion statute but declined to address the constitutionality of the statute's preamble that "the life of each human being begins at conception" (Webster v. Reproductive Health Services). This definition of personhood appears to contradict the Court's abortion rulings, but by leaving it untouched, the Court left the embryo's legal status unclear.

Several states have passed laws mandating insurance coverage for IVF under certain conditions (U.S. Congress, Office of Technology Assessment). The federal government does not fund proposals involving human embryos; by law, research must be reviewed by an ethics board ("Protection of Human Subjects"), but no board has replaced the Ethics Advisory Board, which was disbanded in 1979. This has led to a de facto funding moratorium.

Conclusion

Prior to and in the years following the first successful use of IVF, critics argued that it challenged the sanctity of marriage and family, posed the threat of psychological and physical harm to unborn children, involved the immoral destruction of human embryos, made women experimental pawns in research in which men asserted control over reproduction, and introduced the senseless creation of people in an era of overpopulation. It was also said to admit no clear stopping point, use scarce medical resources, and amount to an elective technique that did not cure infertility.

Supporters argued that IVF would spare couples the psychological trauma of infertility, meet the needs of tens of thousands of women with blocked fallopian tubes, lead to knowledge that would help ensure healthy children, and preserve the family by bringing children to couples who truly want them. They responded to criticism by saying IVF was no more unnatural than cesarean births, should not be diminished merely because it did not cure infertility, posed no apparent risks to children, and was not immoral, in that embryos were only potential human beings.

Today, basic IVF has shifted from experimental to standard medical practice. It is widely available, is regarded as safe, and is the only viable way women with blocked fallopian tubes can conceive a baby genetically related to them. New technical additions ensure, however, that external fertilization will remain at center stage in the ongoing bioethics debate over reproductive technologies.

The lasting unanswered questions relate to the high value placed on genetic parenthood, equitable access to techniques across race and class, the impact of laboratory conception on women's control over reproduction, and whether priority ought to be placed on conception in a time when discussions are directed to ways of reducing the gap in medical services available to richer and poorer citizens.

Perhaps most significant, however, is the matter of the limits to be placed on reproductive technologies. It appears that the scope of refinements is nearly endless. Should substantive and procedural limits be placed by government on any of IVF's variations? If so, which, and why? understanding the reasons for placing limits is as important as understanding the reasons laboratory conception is pursued with such intensity in the first place.

andrea l. bonnicksen (1995)

bibliography revised

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Encyclopedia of Bioethics