Reproductive decision‐making in the context of mitochondrial DNA disorders: views and experiences of professionals

Abstract

Although a scientific and ethical debate about the possible reproductive options for carriers of mitochondrial DNA (mtDNA) mutations is developing, not much information regarding the views and experiences of professionals exists. This paper explores the attitudes and experiences of professionals involved on a daily basis with their patients' reproductive decision-making in the context of mtDNA disease. Qualitative international multicenter design using in-depth semi-structured interviews with 20 professionals has been utilized. We identified four main themes emerging from the interviews. Firstly, we illustrate the discussion among professionals as to what extent mitochondrial genetics differs from other areas in genetics, both technically and ethically. Secondly, we show the discomfort and doubts of professionals when an mtDNA mutation is involved, because of the uncertainty remaining after testing. Thirdly, we discuss how professionals struggle with the tension between, on the one hand, the ideal of reproductive autonomy and, on the other hand, the reality of their professional responsibility and complex clinical decision-making. Fourthly, we delineate the strategies used by professionals in order to make attempts to control uncertainty. This paper illustrates the impact on professionals of reproductive decision-making in the context of mtDNA disease. It shows their feelings of discomfort when interpreting and explaining uncertain or ambiguous data and may be perceived as an example of how professionals deal with the inherent limitations in genetic knowledge representing the state of the art. Insight into the experiences of professionals may contribute to a further improvement of reproductive genetic counseling in the context of mtDNA disorders.

Previous Estimates of Mitochondrial DNA Mutation Level Variance Did Not Account for Sampling Error: Comparing the mtDNA Genetic Bottleneck in Mice and Humans

“…5 This variability is important because the randomness in the inheritance of mtDNA mutations severely limits our ability to provide genetic counseling to affected families. 6,7 The processes responsible for this variability in mutation levels among family members and the exact timing of these processes during reproduction are currently a matter of some controversy. [8][9][10][11] To understand mtDNA mutation inheritance, we must therefore have a reliable means of measuring and comparing the variation generated during the transmission of a heteroplasmic mtDNA mutation, both in the clinical setting and also in several recently developed animal model systems.…”

The Concept of “Genetic Responsibility” and Its Meanings: A Systematic Review of Qualitative Medical Sociology Literature

“…In subgroup C1, professional GR was primarily construed as a form of rational/principleoriented responsibility. With respect to the management of the uncertainties implied in genetic test results, genetic counselors saw it as their responsibility to secure informed consent by providing as much relevant, balanced information as possible (ArribasAyllon et al, 2009;Bredenoord et al, 2010;Hines et al, 2010), to protect the autonomy of the patient (Hines et al, 2010), and (if relevant) to prevent harm to the patient's relatives by supporting or even intervening in disclosure to the family. As Bredenoord et al (2010) put it with regard to the specific uncertainties of GT for mitochondrial DNA disorders, the moral impetus of securing informed, autonomous decision making is central to professional GR: "In our view, it belongs to the responsibility of professionals working in this field to try to help affected couples to make a wellinformed decision, even if this cannot always consist in providing them with precise data about remaining risks" [Bredenoord et al (2010), p. 16].…”

“…The norms of responsible behavior included respect for the autonomy of the counselee (expressed in an appeal not to direct their decision), the obligation to secure informed consent, and a duty to prevent harm to the counselee's family members (sometimes against the will of the counselee). There were three subtypes in group C. Subgroup C1 comprised studies that investigated professional GR by directly drawing on the views of healthcare professionals about their daily work and practice in genetic counseling or GT (n = 5, code C1) (ArribasAyllon et al, 2009;Bredenoord et al, 2010;Hines et al, 2010;Townsend et al, 2012;Hens et al, 2013). These studies investigated the professionals' subjective assessments of the distribution of responsibility in clinical practice.…”

“…Studies mentioned that healthcare professionals involved in genetics/genomics were also aware of being responsible for providing psychosocial support to patients (Hines et al, 2010), controlling uncertainties in testing of complex diseases by referring patients to more experienced colleagues (Bredenoord et al, 2010) and actively supporting the patients' reproductive decision making in terms of helping them to figure out the relevant factors and values involved in the decision (Hines et al, 2010). In cases involving the GT of underaged children, genetic professionals were also reported to be responsible for actively balancing the parents' avoidance of responsibility not to cause harm to the children (Arribas-Ayllon et al, 2009).…”

Mitochondrial genetic diseases

“…Thus, pronuclear transfer between zygotes, as well as spindle replacement, may offer novel reproductive options to prevent maternally inherited mtDNA disease transmission. However, ethical and practical considerations remain, given the complexity of individual cases and the uncertainty surrounding future heteroplasmic loads and resulting disease burden in different tissues of offspring born following such procedures [5]. …”