A. Bredenoord - Academia.edu (original) (raw)

Papers by A. Bredenoord

PLoS Biology, 2012

The Perspective section provides experts with a forum to comment on topical or controversial issu... more The Perspective section provides experts with a forum to comment on topical or controversial issues of broad interest.

Public Health Ethics, 2013

The clinical introduction of medical devices often occurs with relatively little oversight, regul... more The clinical introduction of medical devices often occurs with relatively little oversight, regulation and (longterm) follow-up. Some recent controversies underscore the weaknesses of the current regime, such as the complications surrounding the metal-on-metal hip implants and the scandal surrounding the global breast implant scare of silicone implants made by France's Poly Implant Prothese (PIP) Company. The absence of national registries hampered the collection of reliable information on the risks and harms of the PIP breast implants. To warrant long-term safety, a case can be made for mandatory post-marketing surveillance by means of the establishment of compulsory registries. In this edition of Public Health Ethics, Schofield calls for debate on how such a registry system should be initiated and maintained and how it would relate to the ethical requirement of consent. Here we use breast implant registries as a case to discuss whether and when a socalled 'thick opt-out' would be an appropriate method to include people in medical device registries. We conclude that a thick opt-out procedure for medical device registries is only justifiable in cases where inclusion does not involve burdens (or very low), when it does not involve a sensitive subject and when the data are stored anonymously (or at least not directly linked to the medical record). Otherwise, inclusion should be sought by means of an opt-in.

Reproductive BioMedicine Online, 2011

Preclinical experiments are currently performed to examine the feasibility of several types of nu... more Preclinical experiments are currently performed to examine the feasibility of several types of nuclear transfer to prevent mitochondrial DNA (mtDNA) disorders. Whereas the two most promising types of nuclear transfer to prevent mtDNA disorders, spindle transfer and pronuclear transfer, do not amount to reproductive cloning, one theoretical variant, blastomere transfer does. This seems the most challenging both technically and ethically. It is prohibited by many jurisdictions and also the scientific community seems to avoid it. Nevertheless, this paper examines the moral acceptability of blastomere transfer as a method to prevent mtDNA disorders. The reason for doing so is that most objections against reproductive cloning refer to reproductive adult cloning, while blastomere transfer would amount to reproductive embryo cloning. After clarifying this conceptual difference, this paper examines whether the main non-safety objections brought forward against reproductive cloning also apply in the context of blastomere transfer. The conclusion is that if this variant were to become safe and effective, dismissing it because it would involve reproductive cloning is unjustified. Nevertheless, as it may lead to more complex ethical appraisals than the other variants, researchers should initially focus on the development of the other types of nuclear transfer to prevent mtDNA disorders. RBMOnline

Journal of Medical Ethics, 2011

Human Reproduction Update, 2007

This paper aims to address the ethical issues regarding prenatal diagnosis and preimplantation ge... more This paper aims to address the ethical issues regarding prenatal diagnosis and preimplantation genetic diagnosis (PGD) of mitochondrial disorders. Owing to the absence of effective treatment, the prevention of the transmission of mitochondrial disorders is considered to be of key importance. The characteristics of mtDNA, such as heteroplasmy and the genetic bottleneck, make it difficult to estimate recurrence risks correctly and to provide an accurate prognosis for many mtDNA mutations. A limited number of mtDNA mutations allow reliable predictions, though results in the 'grey zone' are problematic. Both prenatal diagnosis and PGD for mtDNA disorders are complicated by the interpretation of the test results. As a consequence, these applications confront both clinical practice and society at large with several ethical questions and issues for further debate, among which the acceptability of suboptimal genetic testing, the value and research use of embryos, the evaluation of late abortion, the ethics of PGD for disorders with an incomplete penetrance and variable expression, the possible transfer of embryos with residual health risks, the acceptability of risks and drawbacks of genetic reproductive technology in general, and the scope and limits of reproductive autonomy and professional responsibility.

Human Reproduction Update, 2008

BACKGROUND: Mitochondrial DNA (mtDNA) disorders are an important cause of human diseases. In view... more BACKGROUND: Mitochondrial DNA (mtDNA) disorders are an important cause of human diseases. In view of the limitations of prenatal diagnosis and preimplantation genetic diagnoses, alternatives such as ooplasmic transfer (OT) and nuclear transfer (NT) have been proposed to prevent the transmission of mtDNA mutations. Both OT and NT are radical in the sense that they do not entail genetic selection, but genetic intervention to correct the genetic cause of the disease. METHODS: After interviews with experts in the field, the relevant literature was searched and analyzed. Bioethical issues were divided into conceptual and normative points. RESULTS: OT is the transfer of normal mitochondria to a carrier's oocyte containing mutant mtDNA. In case of NT, a donated oocyte is enucleated and replaced with the nuclear DNA from a woman carrying a mtDNA mutation. NT can be performed both before and after in vitro fertilization, respectively, with the nucleus of an unfertilized oocyte, with the pronuclei of the zygote, or with the nucleus of a blastomere of an embryo. Conceptual questions regard whether these techniques amount to germ-line modification and human cloning. Normative questions concern, among others, the significance of intervening in the mtDNA, the implications of having 'three genetic parents', the ethics of oocyte donation and the health and safety risks for children conceived as a result of one of these techniques. CONCLUSIONS: Further interdisciplinary debate and research is needed to determine whether a clinical application of OT and NT can be morally justified, and if so, under which conditions.

Human Reproduction, 2010

In this article, we discuss sex selection not intended to help a couple avoid having a child with... more In this article, we discuss sex selection not intended to help a couple avoid having a child with a severe genetic disorder, but to avoid possible health risks further along the line of generations. Sex selection may be put to this use in the context of preventing mitochondrial DNA disorders by means of preimplantation genetic diagnosis (PGD) and possibly in the future also through nuclear transfer (NT; also known as mitochondrial gene replacement). A relevant analogy can be found in the context of PGD for X-linked diseases, where sex selection against healthy female carrier embryos would have the same 2-fold purpose of (i) avoiding difficult reproductive decisions for the future child and (ii) avoiding transmission of the mutation to a possible third generation. Because sex selection would still be done for reasons of health, this application should not give rise to the moral concerns associated with sex selection for non-medical reasons. However, the proportionality of adding the relevant procedures to PGD or NT is a relevant concern. We discuss post-and preconceptional sex selection strategies. We conclude that if PGD is already part of the procedure, either as the central technology or as a back-up test after NT, preferentially transferring male embryos could in principle be a morally acceptable way of reducing possible burdens and risks. To start an IVF/ PGD-cycle especially for this purpose would be disproportional. The alternative approach of preconceptional sex selection may be morally justified as a means to increase the chances of obtaining male embryos.

Human Reproduction, 2008

This paper discusses the pros and cons of introducing PGD for mitochondrial DNA (mtDNA) disorders... more This paper discusses the pros and cons of introducing PGD for mitochondrial DNA (mtDNA) disorders such as NARP (Neurogenic muscle weakness, Ataxia, Retinis Pigmentosa)/Leigh, MELAS (Mitochondrial myopathy, Encephalopathy, Lactic acidosis, and Stroke-like episodes), private mtDNA mutations and LHON (Leber Hereditary Optic Neuropathy). Although there is little experience with PGD for mtDNA disorders, it is reasonable to assume that in many cases, the best one can achieve is the selection of the 'least' affected embryos for transfer. So instead of 'promising' parents a healthy child, PGD in these cases can only aim at reducing reproductive risk. From an ethical point of view, this raises challenging questions about parental and medical responsibilities. The main argument in favour of PGD is that it offers couples at risk the opportunity of reducing their chances of having a severely affected child. Potential objections are manifold, but we conclude that none of them supplies convincing moral arguments to regard risk-reducing PGD as unacceptable. Nevertheless, introducing this new application of PGD in clinical practice will raise further complex issues of determining conditions for its responsible use.

European Journal of Human Genetics, 2009

Although morally acceptable in theory, preimplantation genetic diagnosis (PGD) for mitochondrial ... more Although morally acceptable in theory, preimplantation genetic diagnosis (PGD) for mitochondrial DNA (mtDNA) disorders raises several ethical questions in clinical practice. This paper discusses the major conditions for good clinical practice. Our starting point is that PGD for mtDNA mutations should as far as possible be embedded in a scientific research protocol. For every clinical application of PGD for mtDNA disorders, it is not only important to avoid a 'high risk of serious harm' to the future child, but also to consider to what extent it would be possible, desirable and proportional to try to reduce the health risks and minimize harm. The first issue we discuss is oocyte sampling, which may point out whether PGD is feasible for a specific couple. The second issue is whether one blastomere represents the genetic composition of the embryo as a whole -and how this could (or should) be investigated. The third issue regards the cutoff points below which embryos are considered to be eligible for transfer. We scrutinize how to determine these cutoff points and how to use these cutoff points in clinical practice -for example, when parents ask to take more or less risks. The fourth issue regards the number of cycles that can (or should) justifiably be carried out to find the best possible embryo. Fifth, we discuss whether follow-up studies should be conducted, particularly the genetic testing of children born after IVF/PGD. Finally, we offer the main information that is required to obtain a truly informed consent.

European Journal of Human Genetics, 2014