Ethical and legal issues
Considerations on ethical and legal issues are evolving, along with the evolution of the technology for the control of genetic diseases, and have become one of the key subjects in discussing the acceptability of preconception and preimplantation testing for genetic disorders. Ethical and legal issues determine, to a considerable extent, whether these new approaches are promoted to become an integral part of preventive genetics services or are waived on ethical grounds.8 PGT could be regarded as an ethically acceptable procedure in the context of a general objective of genetic service, which, according to the WHO, is to help genetically disadvantaged people live and reproduce as normally and as responsibly as possible.9 Because PGT is heavily based on IVF, it also is relevant that IVF is considered to be ethically acceptable in many countries.170–174 However, complex ethical and legal issues are confronted differently in various countries (see Chapter 36).175 For example, in Germany, the future of PGT depends on an Embryo Protection Law, which has been in effect since 1991.172, 176 This law is very strict and prohibitive of embryo research. However, it prohibits only destructive research that impairs the chances of the embryo becoming a human being up to the eight‐cell stage. In fact, blastocyst biopsy may be possible without any conflict with the law because, together with chorionic villus sampling (CVS), such embryo biopsies are considered beneficial, allowing decisions to be made before replacement. Therefore, there is no conflict about the provision of PGT in Germany before the pronucleate stage, which is currently under way. However, this must be done for diagnostic purposes only, not for research. Even in the case of tripronucleate embryos, only observation is permitted, not experimentation.
This approach may also resolve the ethical issues impeding PGT in Austria, Switzerland, Malta, and other predominantly Catholic countries.177 The same holds for other countries where no preventive measures have been allowed on religious grounds. For example, the law has evolved recently in Switzerland, citizens voting to introduce PGT into clinical practice. In contrast, in France, there seems to be no law at all concerning either PGT or embryo research. However, the attitude of the National Ethical Committee toward PGT is influenced by the fact that the diagnosis is based on genetic analysis of only one or a few cells and that all male embryos are discarded after gender determination, while half of them are completely normal. However, the testing is presently based on specific diagnosis, rather than gender determination. Another concern is that PGT increases the need for IVF, which is provided free of charge in France. Finally, prenatal diagnosis, also provided free of charge, was enough to avoid genetic disorder, so the provision of PGT was considered to be an additional prenatal test, without taking into account the suffering caused by selective abortions after prenatal diagnosis. Nevertheless, there are presently a few well‐established centers in France providing a full range of PGT services.
In Italy, PGT and many aspects of IVF were forbidden by Act of Parliament for almost 7 years. Only three oocytes were allowed to be aspirated for fertilization in vitro, clearly reflecting the opinions of the hierarchy of the Roman Catholic Church.178 Prior to the law, Italy had been among the most active centers involved in the development and application of PGT for genetic and chromosomal disorders. After the laws were enacted, it was difficult to perform PGT, which nevertheless is presently performed without restriction.
In some countries, such as Belgium, the decision on embryo research and PGT rests completely with institutional review boards, so there is no problem with the development of the technique and its implementation into clinical practice. In other countries, such as the Netherlands, PGT is governed by the law on medical experiments, which contains a section on embryo research. It prohibits “cloning,” but probably will not ban PGT research because it provides an alternative to prenatal diagnosis and abortion of genetically affected fetuses. In the United Kingdom, PGT, as well as the practice of IVF and research involving human embryos, is regulated through a statutory body, the Human Fertilisation and Embryology Authority, and the Fertilisation and Embryology Act (1990), allowing research on human embryos up to 14 days of development under an appropriate license. In Spain, although a 1988 law regulating human embryo research forbade the fertilization of human oocytes for any purpose other than human procreation, it permitted research on embryos within 14 days of preimplantation development under the supervision of the national health and scientific authorities.179 Therefore, this law did not conflict with the development of research in preimplantation genetics and its application to assisted reproduction practices. In fact, according to a survey on PGT availability in Europe, the number of PGT centers presently available in the country is more than in most of the other European countries.
In the United States and Australia, the legal status of PGT and community attitudes differ in different states. For example, in the six states of Australia, only three have laws governing IVF and embryo research. In Victoria, embryo research is prohibited, except for approved experiments, although this law does not actually affect PGT because IVF is allowed for infertile couples, and PGT also can be justified as the procedure for avoiding the risk of transmitting genetic disease to affected children. In Western Australia, PGT cannot be done because of the Experimentation Law, whereas in South Australia it is possible unless destructive to an implantable human embryo.
In the United States, the issue of embryo research is closely associated with the debates on abortion and cloning, and there has been no government system for regulating reproductive research projects. Because there is no ethical advisory board (EAB) that is legally given responsibility for reviewing such research proposals, federal funding for human embryo research has not been available. In addition, a wide variation of policy positions exists among different states, mainly being compromised over consideration of the question of when human life begins. However, despite existing differences in current legal restrictions in this field, selection of pre‐embryos on genetic grounds may be ethically acceptable based on the premise that the goal of avoiding the birth of offspring with severe genetic handicaps is part of the constitutional rights of procreative liberty.180, 181 Although the National Institutes of Health Revitalization Act of 1993 lifted the requirement (45 CFR 46.204.d) for a federal‐level EAB review for IVF research, leaving consideration for clinical research relating to IVF to individual institutional review boards, none of the federal funds may be used for research in which a human embryo or embryos are destroyed, discarded, or knowingly subjected to risk of injury or death greater than allowed for research on fetuses in utero.
In Canada, recent legislation to regulate assisted human reproduction technologies has been introduced, entitled an “Act Respecting Assisted Human Reproduction,” which allows PGT for medical reasons but excludes identifying the sex of an embryo for social purposes.182, 183 The Society of Obstetricians and Gynaecologists of Canada have provided valuable guidelines that optimize obstetrical management and counseling for prospective parents undergoing IVF, integral to PGT. Emphasis is given to the increasing evidence that both infertility and subfertility remain as independent risk factors for subsequent complications and adverse perinatal outcomes, even without IVF. Their report also draws attention to the very low but actual risk of imprinting disorders, such as Beckwith–Wiedemann syndrome or Angelman syndrome, estimated to occur in fewer than one in 5,000 patients.
Important ethical issues have recently been raised with increasing use of PGT for gender determination for social reasons,184, 185 late‐onset disorders with genetic predisposition,6, 7, 186, 187 and PGT‐HLA to produce an HLA‐compatible donor to treat a family member with fatal bone marrow disease or cancer requiring a stem cell transplantation.5, 188, 189 Although there is no actual difference in the application of PGT for the latter conditions, the controversy can be explained by the fact that in traditional prenatal diagnosis, if the fetus was found to carry the gene predisposing to a late‐onset disorder or to be HLA unmatched, a couple would have to make an extremely
