Dealing with uncertainties: ethics of prenatal diagnosis and preimplantation genetic diagnosis to prevent mitochondrial disorders

Abstract

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.

Mitochondrial Genetics and Disease

“…It is for this reason that prenatal diagnosis of a mitochondrial DNA-based disorder, with but a few exceptions, is fraught with difficulties, both technical and ethical. 8 …”

A Logical Analysis of Slippery Slope Arguments

“…According to the imagery of a ''slippery slope'', we should not allow selling human organs on the ground that this would mean stepping on a slippery slope and sliding all the way to its bottom-that is, to the undesirable state of affairs that only the rich will be able to afford transplants. 4 An objection may be raised at this point: According to deontological theories (e.g., Kantian ethics), some actions are intrinsically bad (malum in se)-that is, they are forbidden because of their intrinsic nature and not because of the undesirable state of affairs they cause. In this essay, I do not deal with deontological reasoning and it may therefore be objected that it has no relevance to deontologists.…”

“…It is not clear whether their form is a conditional or a biconditional. 4 Other metaphors that have been used to refer to this type of reasoning are ''wedge argument'', ''thin edge of the wedge'', camel's nose'', and sometimes ''domino'' because an SSA resembles a row of falling dominoes, with each event causing the next one in line (see [16]). 5 I am grateful to an anonymous referee at this journal for alerting me to this problem.…”

“…Compare this example, reported by Bostrom[3], ''To forestall a slide down a slippery slope towards an ultimately debased 'posthuman' state, human enhancement technologies should be banned globally'' (see p. 202). 14 One argument in this context is that prenatal diagnosis may open the door for ''sexing for all disorders in which the mutation's penetrance and/or the expression is lower or milder in one sex'' (see[4]). …”

A selected pre-amplification strategy for genetic analysis using limited DNA targets

“…For pre-implantation genetic diagnosis, only single human blastomeres, or first polar body, can be offered for further analysis (4,5). In forensic medicine, the samples obtained are often damaged or degraded (6).…”