Abstract Recently, American colleagues called for a systematic collection of anonymized data on how many embryos and foetuses are deselected per institution per year, and for which conditions. These authors argued that if this information would be reported to a government agency or international body, the information would provide a baseline against which jurisdiction-specific trends in selection could be assessed. People who have disabilities, together with other key stakeholders, laypeople and experts, would then be in a position to assess the social impact of human selecting technologies and to make recommendations for action to mitigate negative effects as appropriate. However, such a systematic data collection does already exist in the Netherlands and has been in place for more than 30 years. It was first introduced to monitor the practise of prenatal diagnosis by the eight licence holders sending in all data to the Minister of Public Health, Welfare and Sports. Later, the same method was expanded to preimplantation genetic diagnosis. For 8 years, these data have been discussed in the parliament, which shows that the practice of embryo selection can indeed be kept under democratic control, albeit retrospectively. embryo selection, PGD, social impact Introduction On 2 November 2017, a letter to the editor of Nature was published in which it was stated that the rise in preimplantation genetic diagnosis (PGD) and prenatal diagnosis over the last three decades has been accompanied by selective elimination of foetuses and embryos. The authors argued that, as far as they were aware, governments or international bodies do not systematically collect society-wide reliable data regarding the reasons and the numbers of selective terminations of pregnancy and preimplantation embryos that were not used for transfer. Since more and more less-invasive testing methods are being introduced and the application in humans of reproductive genome editing is likely to accelerate prenatal selection, the authors reasoned that the need for good data is very strong. Furthermore, they argued that many people are concerned about the societal consequences of the application of these methods. Without evidence, people have two choices which are both less optimal: to ignore the possible effects of these screening methods at the level of the society, or to disturb the decision-making process between the doctor and the patient. They suggested a third way. They called for the systematic collection of anonymized data on the number of embryos and foetuses are deselected per institution per year, and the diagnosed conditions. If this would take place in the framework of a government agency or international body, the information would provide a baseline against which specific trends and developments regarding selection could be assessed. Every citizen, including those with disabilities and other key stakeholders, laypeople and experts, would then be able to evaluate the social impact of human selecting technologies and to make recommendations for action to mitigate negative effects as appropriate (Thompson, 2017). After reading this I submitted the following reaction: In the Netherlands, government licences require all prenatal diagnostic centres to report annually the results of all their prenatal diagnostic tests and the grounds for pregnancy terminations. This practice was established about 30 years ago. PGD Netherlands (a partnership between the only licensed Dutch PGD centre, located in Maastricht, and IVF centres in Utrecht, Groningen and Amsterdam) must also report its results to the government on a yearly basis. These reports, which include all indications and decisions on selection, are discussed in the Dutch parliament. This shows that the practice of embryo selection can be kept under democratic control, albeit retrospectively. The information can also be used for review of care and decision-making with respect to licence renewal. The prenatal diagnostic data are only accessible to medical professionals, but the PGD reports are available to all stakeholders, including referring doctors and those living with disabilities (Geraedts, 2017a). Invited by the Editor-in-Chief of Molecular Human Reproduction, I am happy to provide some background information on this data collection practise in this opinion article. Reproductive options for couples carrying inherited diseases Many couples who carry a genetic disease and who would like to eliminate the increased risk to obtain a child without the condition that runs in the family can now make use of either prenatal diagnosis and selective termination of pregnancy or PGD and selective transfer of embryos without the mutation for the condition at stake. Whatever their choice, these couples need genetic and reproductive counselling to inform them about the disease, its causes and its recurrence risk, and discuss the options for having healthy children. Thereafter, these couples need to take an autonomous decision to refrain from having children, to adopt, to opt for gamete donation or to use assisted reproductive technology (ART) with prenatal diagnosis or PGD. Soon after the birth of Louise Brown as the first IVF baby in 1978, scientists and clinicians began to develop methods for selecting embryos in vitro to avoid the need for selective abortion after prenatal diagnosis. Couples may also prefer PGD over prenatal diagnosis for religious or ethical beliefs on abortion or opt for PGD after one or more unsuccessful rounds of prenatal diagnosis. However, they may also choose PGD because they require assisted reproduction anyway because of an infertility treatment (Geraedts, 2017b). Ethical concerns of PGD Since its introduction (Handyside et al., 1990), PGD has become a very important tool for prevention of genetic disease in future generations. On the other hand, it has raised many concerns. Soon after its establishment in 1997, the ESHRE PGD Consortium conducted a survey among the centres offering PGD services at that time (Viville and Pergament, 1998). It revealed common concerns regarding diagnostic accuracy, pregnancy rates, the possibility of genetic engineering of embryos, the use of IVF for the treatment of fertile couples, the safety of embryonic biopsy and the high costs. However, the eugenic potential of PGD represented the major argument against its development. During the last 20 years, the ability of selection of embryos with a wide range of defects has certainly increased. Furthermore, the development of more comprehensive selection methods will certainly further increase the possibilities of embryo selection in the future. Does this create an argument to limit the further development of PGD? In my opinion it does not. Autonomous decisions should be respected in both ways. At the same time, the protection of people with disabilities should strongly be supported. This can best be done by the clinical genetics professionals who are confronted with disabled persons daily. It should be made clear to the public at large that the purpose of embryo selection is to help to overcome the problems and worries of future parents and that there is no eugenic objective, which means that there is no discrimination in the interest of society. However, regarding embryo selection opinions strongly differ both within and among countries. This has been reflected in very wide variations of lawgiving between countries across Europe and the rest of the world. At the time of the ESHRE survey, four distinct legal situations regarding the performance of PGD were found (Viville and Pergament, 1998): – Countries with legislation concerning human embryos, including PGD; – Countries with legislation that specifically addressed PGD; – Countries with no legislation regarding PGD. In this case two situations could be distinguished: countries which had guidelines and/or were in the process of implementing legislation and countries that did not have any constraints at all; – Countries that banned all embryo manipulation including PGD. Over the years, the legal constructs affecting the performance of PGD have remained similar. However, there seem to be more countries with legislation regulating research on human embryos, including PGD, or countries with legislation or guidelines that specifically address PGD, and there are fewer countries that ban all embryo manipulation, including PGD. Indications for PGD With or without legislation, most European countries have set some limits for PGD indications. Social sexing—selecting the sex of the child for social reasons—is not allowed in almost all European countries. HLA typing without PGD for a genetic disease is not allowed in several countries; saviour sibling is only allowed if PGD is needed anyway. Regarding the indications, some countries allow PGD and prenatal diagnosis for all conditions, while others have again set limits. Fatal childhood diseases are almost always accepted indications. Since its introduction, the list of indications of PGD is expanding from early-onset lethal diseases to late-onset diseases. The major differences comprise serious chronic diseases and adult-onset diseases (Geraedts, 2017b). Most controversial is PGD for the latter genetic defects and especially if they show incomplete penetrance or variable expression. Furthermore, the acceptability of PGD decreases if there are preventive and/or therapeutic options available. Often the slippery slope argument is used: PGD will ultimately lead to would be parents who prefer to design their ‘perfect child’, which means that they want to select characteristics such as height, intelligence, sexual preference or any other property they want to select for their child. However, the technical possibilities are not that far, which is a problem and a blessing at the same time. The characteristics in question are multifactorial or complex, which makes it highly unlikely that the ‘designer baby’ will be realistic in the near future. Furthermore, even if it will ever be possible to select for these complex characteristics, that would be a reason for a social debate on setting boundaries, but not a convincing reason for a total ban on PGD (Geraedts and De Wert, 2009). Irrespective of the arguments used, regulatory differences exist and these, together with the availability of tests and financial reasons, have driven many patients to seek treatment abroad. However, there are certain disadvantages to such cross-border movements. It all depends on whether they are properly referred, whether they must search for the clinics themselves and whether they can find proper medical advice, counselling and support in a very vulnerable and emotionally challenging situation. Furthermore, if patients have received treatment abroad, the legal situation of PGD in their home country may complicate monitoring and follow-up after treatment. Clinics could also be reluctant to get involved in follow-up care of children born because of a prohibited treatment. Third, if PGD is prohibited, only a category of patients can afford expensive treatment abroad (Geraedts, 2017b). The development of PGD in the Netherlands In 1995, PGD was introduced on an experimental basis in Maastricht. Since 2003, it has been incorporated in the licencing system of the Ministry of Public Health, Welfare and Sport. At the start, PGD was only carried out for couples whose potential offspring were at risk of severe Mendelian disorders, structural chromosomal abnormalities or mitochondrial disorders. PGS (aneuploidy screening to improve medically assisted reproduction) has never been part of the programme. In January 2003, the Ministry of Public Health, Welfare and Sport adopted a new licencing system that allows genetic centres to perform prenatal and postnatal diagnosis under the Dutch Special Medical Procedures Act (Wet op de Bijzondere Medische Verrichtingen). On top of the existing licences for the eight Dutch Clinical Genetic Centres, the Maastricht centre was granted a special permit to perform PGD. The indications did not change until 2008, when the Deputy Minister of Public Health, Welfare and Sport tried to expand the use of PGD by explicitly allowing the diagnosis of breast cancer type 1 (BRCA1) and BRCA2 mutations. However, the proposal was blocked by the smallest coalition party (the Christian Union) and a governmental crisis ensued. The controversy centred around the incomplete penetrance, variable expression and the therapeutic options available for hereditary breast and ovary cancer. After 1 month of discussions and negotiations, an overwhelming majority of Dutch MPs voted in favour of a compromise proposal on testing embryos for hereditary diseases. The government allowed the Maastricht University Medical Centre, the only molecular genetics facility in the Netherlands where PGD is used for embryo selection, to test for a wider range of diseases. As part of the compromise, the government also decided to create a National Indications Commission to determine for which new category of diseases embryo testing can be carried out, provided that several criteria are considered: the most important of these being severity and type of the disease and options for prevention and treatment. The focus of the discussion was hereditary tumours and hereditary breast and ovarian cancer, caused by mutations in BRCA1 and 2, in particular. Although the application of PGD for this type of adult-onset disease has not been supported in many countries, in the Netherlands there was strong support, because the life-time risk of breast cancer for a female carrier may be as high as 85% in seriously affected families and her risk of ovarian cancer as high as 60%. Furthermore, this is considering that periodic medical examinations aimed at early detection are not (entirely) reliable and the preventive removal of the ovaries and amputation of both breasts is rather invasive and has adverse effects for quality of life. Since 2009, the PGD licence holder is obliged to send a yearly report to the Dutch Minister of Public Health, Welfare and Sports. This report system was introduced to be fully transparent about all decisions and activities resulting in embryo selection and to take away any suspicion. It clearly is an extension of the yearly reporting system of all prenatal diagnostic activities in the country. This was introduced more than 30 years ago, when it was decided to leave the autonomy in the decision making to the professionals and the patients. However, in this respect there is a difference between prenatal diagnosis and PGD. The different parties involved might have conflicting interests: the principle of reproductive autonomy of the prospective parents on the one hand and the principle of professional responsibility of the professional for the welfare of the child on the other can best be realized after PGD, since it is possible to decide on the start of a treatment. In prenatal diagnosis, the future parents have taken that decision themselves, which means that it is not always possible for the professionals to serve the interests of the future child in an optimal way. The data collection and reporting of preimplantation embryo selection is carried out by PGD Netherlands, which is a collaborative effort of the genetic testing facility, located at the Medical University Centre at Maastricht and the IVF laboratories of the medical university centres at Amsterdam, Groningen, Maastricht and Utrecht. Because of this collaboration, patients from across the Netherlands will have relatively easy access to IVF and thereby to PGD. The Minister will send the yearly report to the parliament. This means that all data are under democratic control. For example, it has become clear that during the last 22 years, the number of treatment cycles has increased from less than 30 to more than 500 per year, that there are far more referrals and treatments for autosomal dominant diseases than for autosomal recessives, that the success of treatment is ~20% per started cycle and about 25% per embryo transfer, and that the number of treatments per couple is almost exactly 2.0. Furthermore, it can be seen for which diseases PGD has been carried out and which indications have been refused. Conclusion The publication of yearly reports with transparent information regarding all aspects of all PGD treatments in the country shows that democratic control of embryo selection can be achieved, albeit retrospectively. Funding For writing this opinion article, the author did not receive a grant from any source. Conflict of interest The author certifies that he has no affiliations with or involvement in any organization or entity with any financial interest, since he retired about 5 years ago. References Geraedts J. Clinical records: thirty years of Dutch embryo selection. Nature 2017a; 551: 565. Google Scholar PubMed Geraedts J. Healthy children without fear: reproductive options for patients or couples carrying inherited diseases. EMBO Rep 2017b; 18: 666– 669. Google Scholar CrossRef Search ADS PubMed Geraedts JP, De Wert GM. Preimplantation genetic diagnosis. Clin Genet 2009; 76: 315– 325. Google Scholar CrossRef Search ADS PubMed Handyside AH, Kontogianni EH, Hardy K, Winston RM. Pregnancies from biopsied human preimplantation embryos sexed by Y-specific DNA amplification. Nature 1990; 344: 768– 770. Google Scholar CrossRef Search ADS PubMed Thompson C. Human embryos: collect reliable data on embryo selection. Nature 2017; 551: 33. Google Scholar CrossRef Search ADS PubMed Viville S, Pergament D. Results of a survey of the legal status and attitudes towards preimplantation genetic diagnosis conducted in 13 different countries. Prenat Diagn 1998; 18: 1374– 1380. Google Scholar CrossRef Search ADS PubMed © The Author(s) 2018. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: firstname.lastname@example.org
Molecular Human Reproduction – Oxford University Press
Published: Mar 1, 2018
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