Conception for Donation

Preimplantation genetic diagnosis (PGD) of embryos created by in vitro fertilization (IVF) has become an increasingly available option for couples seeking to avoid the birth of a child with a genetic disorder. While opposed by some, PGD is less contentious and emotionally less stressful than prenatal diagnosis and abortion after pregnancy has begun and has resulted in the births of approximately 1000 children over the past decade.¹

Sometimes couples seek PGD to accomplish 2 goals simultaneously: to facilitate creation of a child who will not only be healthy but also can become a source of hematologic stem cells, generally obtained from cord blood, which can be used to treat a sibling with a life-threatening hematologic disorder, such as Fanconi anemia or leukemia. In their report in this issue of THE JOURNAL, Verlinsky and colleagues² report PGD with HLA testing in 9 families wanting a child who could provide cord blood for siblings with hematologic disorders with no known genetic cause; ie, the children created were at no known risk for these hematologic diseases. Five apparently healthy HLA-matched children were born. No transplants have been attempted, as the siblings were all in remission at the time of the report.

Using genetic, reproductive, and transplantation technology in this way has clear benefits. It offers the opportunity to save the life of an existing child with an otherwise untreatable disorder and allows couples to avoid confronting the difficulties of prenatal diagnosis for HLA typing in mid pregnancy, with selective abortion of fetuses who are poorly matched with the living affected child. This approach, while apparently rare, has been reported.^{3 - 4}

What are the concerns about this evolving and expanding application of genetic and reproductive technology? As with all new technologies, biologic safety should be ensured. Thus far there are no known medical risks to the resulting offspring, but the numbers of children conceived for this purpose are limited. There also may be psychological risks to these children, although parents seeking these services are typically unusually caring and attentive. Conception in the "old-fashioned" way (ie, without techniques such as IVF or PGD) for the purpose of donation to another sibling has been common for many years without apparent ill effects on the offspring, but no systematic studies of this have been published.

Wolf et al⁴ argue that this combination of IVF and PGD to create a stem cell donor should be treated as research, not only for the advantages of institutional review and collection of data about adverse effects, but so that federal standards for minimizing risks to children can be applied. It is a peculiarity of the present US regulatory system that the special protections of the research regulations⁵ apply only to some new technologies; namely, those that are supported by federal funds or that involve drugs or devices under the jurisdiction of the US Food and Drug Administration. Other technologies of uncertain benefit and potential risk, such as new surgical procedures, genetic testing programs, and new reproductive technologies, often fall outside of the regulatory system.

Some oppose these reproductive technologies because they believe it is wrong to select the traits of offspring or to create embryos knowing that most will likely be destroyed.⁶ For the foreseeable future, the number of embryos created for PGD will be a small fraction of the total number created by IVF, so concern about destruction of embryos would more properly be focused on the much larger number that are discarded by couples who have completed their procreative plans and have residual frozen embryos. One of the remarkable effects of the debate over stem cell research is that some leading figures with long-standing objections to abortion have reconsidered their positions about the moral status of the embryo when confronted with the possibility of helping others with dread diseases. As Senator Orrin Hatch put it, "A critical part of being pro-life is to support measures that help the living."⁷

Slippery slope concerns are always important when new technologies generate new possibilities for intervention. As genetic testing and possibly gene therapy become more refined, PGD will expand the possibilities for selection or modification of trivial traits, such as eye color, or traits that are arguably more important but not clearly associated with disease, such as short stature or below-average intelligence. As is usually the case with slippery slope arguments, if the possibility of unwelcome future events were a sufficient reason to prohibit new technology, then there would be little innovation, since new technology almost always has undesirable consequences. Allowing acceptable use of technology is not incompatible with prohibiting unacceptable use.

Some are critical of parents who create a child for a clearly utilitarian purpose. In its worst form, this criticism imagines that the parent will use a child solely as a means, and then discard the child—eg, place the child for adoption—when he or she is no longer useful. There is little evidence for this, nor is it self-evident that even that outcome would argue against allowing the process. A life might be saved, and the adopted child, if placed in a loving home, is more likely than not to have a happy life, one that he or she would not have had if the procedure had been prohibited.

Another possible issue is whether parents who undergo PGD of embryos and conception for purposes of donation would want another child if it were not for the need for donation to their affected child. However, the rationale for this potential concern is not clear, as parents who create a child to save a life would seem to be on higher moral ground than those who procreate for the more common reasons; namely, unanticipated consequences of sexual pleasure, or selfish purposes such as enriching one's personal life, or the desire for heirs.

More important, making policy that restricts procreative privacy requires something more compelling than the possibility that a child may have psychological problems. If it is appropriate for physicians or regulators to deny reproductive services to parents who may produce unhappy children, there are more fruitful places to start, such as with couples who procreate despite a known 25% risk of producing a child with a severe autosomal recessive condition, or those whose children are at high risk for child abuse, neglect, or the consequences of parental drug abuse. The hazard associated with physicians making unsupported judgments about which children will turn out well is illustrated by the practice of some infertility clinics in refusing services to single women or lesbian couples.

Like much of new reproductive technology, PGD for HLA testing is largely unregulated in the United States. Great Britain⁸ and Australia⁹ have policies and review specific applications for PGD. Both countries support PGD with HLA typing but only if the embryo is at risk for disease. The authorities in both countries oppose conception for solid organ donation, although the reasons are unclear as kidney donation by minors has occurred for more than 30 years¹⁰ and has been generally supported by the US courts as long as independent consultants confirm that there is likely to be a psychologic benefit for the donor. The ethics committee of the American Society of Reproductive Medicine supports PGD for preventing the birth of a child with severe disease but has no position on PGD solely for HLA typing.¹¹

Robertson has criticized the UK and Australian positions on a number of grounds.^{12 - 13} He starts with the principle of procreative privacy as a fundamental value, so there should be compelling reasons to interfere with a couple's legitimate desires. He points out that cord blood donation from minors has minimal risk and has been ethically and legally accepted for many years; that PGD does not appear to present added risk for the donor child; that children created in this manner are not likely to be used merely as a means but are highly likely to be cared for by their biological parents; and that creating a child to save a life should be an occasion for praise, not criticism; and that slippery slope concerns are overstated or manageable.

In 1991 the Ayala family triggered a firestorm of adverse publicity when they revealed that they had conceived a child to be a bone marrow donor for their dying teenage daughter.¹⁴ Today both girls are alive, well, and apparently happy.¹⁵ Conception for donation of cord blood has become relatively common over the past 2 decades. New reproductive technologies, such as IVF, artificial insemination, and surrogate motherhood aroused passion and opposition when first introduced, and then were accepted as part of the landscape as they became more common and were shown to be safe. As with other reproductive and genetic technologies, whether PGD for HLA will have a similar outcome may hinge less on debate about ethical principles than on the evolving evidence of safety and efficacy.