Choices of incidental findings of individuals undergoing genome wide sequencing, a single center's experience.

Genome wide sequencing is an emerging clinical tool that may provide information on genetic variants that are not directly related to the patient's primary disorder. These incidental findings (IFs) may include information about conditions that can be treated and may also indicate conditions for which treatments are not currently available. Data is currently limited regarding what IFs an individual would want to disclose. This study reports on 305 individual choices for return of IFs that were completed at the Medical College of Wisconsin's clinical sequencing laboratory. Individuals were given access to five categories of IFs to select from: no incidental findings, untreatable childhood disorders, treatable adulthood disorders, untreatable adulthood disorders, and carrier of a disorder. Retrospective chart review was conducted and individual choices were recorded and analyzed. The majority of individuals (76.1%) selected every IF to be reported, 14.4% wanted a subset of the options, and 9.5% did not want any IFs reported. This study contributes to the limited data that demonstrates what an individual would actually choose when undergoing genetic sequencing. Furthermore, this data supports the opinion that individuals want and utilize the ability to choose the findings reported.

Views of primary care providers regarding the return of genome sequencing incidental findings.

Sequencing of the entire exome or genome is increasingly used in clinical practice. Debate continues, however, regarding which incidental findings (IFs) should be returned and who should be involved in those decisions. Previous empirical research regarding stakeholder attitudes to the return of IFs has primarily involved genetics professionals; non-genetics health professionals have not been widely surveyed. Given this, a survey regarding return of IFs was administered at the Best Practices in Pediatrics Conference following an educational presentation on genetics terminology and genetic condition examples. A total of 258 participants completed the survey. Of particular note, respondents who were positively disposed to sequencing did not always report wanting to learn about IFs, even if actionable. This is noteworthy given recent American College of Medical Genetics and Genomics guidelines recommending particular actionable IF be returned 'without reference to patient preference'. This study's findings are important because they provide insight regarding the attitudes to the return of genome sequencing results for an important professional group, primary care providers. Ultimately, as likely gatekeepers to referrals for this technology, their opinions about the test will be key to its successful deployment.

A prospective study assessing anxiety, depression and maternal-fetal attachment in women using PGD.

BACKGROUND: PGD has been described in previous cross-sectional and retrospective studies as a stressful experience. No prospective studies of the psychological impact of PGD are currently available. METHODS: Using a prospective study design, validated measures exploring anxiety and depression were used to assess women using PGD prior to treatment, following embryo transfer, following the pregnancy test result and at 24 weeks of pregnancy. Maternal-fetal attachment was also assessed during pregnancy. RESULTS: The prospective design revealed the cyclical pathway through PGD for many women, often comprising repeated cycles of ovarian stimulations and IVF and frozen embryo transfers. As predicted, there were significant fluctuations in women's anxiety scores, with increases observed following embryo transfer and pregnancy testing. Women's anxiety scores returned to baseline levels during pregnancy as assessed at 24 weeks gestation. Depression scores did not significantly fluctuate during PGD. Maternal-fetal attachment scores in this sample did not differ from the normative Australian data. CONCLUSIONS: For some women, the PGD pathway is convoluted and requires multiple IVF cycles and embryo transfers to achieve pregnancy. A subset of women experience significant emotional burden during PGD treatment, and it is these women who require closer attention and support. In this sample, emotional adjustment in pregnancy following PGD appears to be sound.

Psychological adjustment, knowledge and unmet information needs in women undergoing PGD.

BACKGROUND: Women often enter preimplantation genetic diagnosis (PGD) treatment following traumatic reproductive and genetic histories, the detrimental psychological effects of which are known to be long lasting in some cases. In addition, attempting IVF with PGD requires an in-depth understanding of the aspects of the technology. The level of information that is required and retained by women entering treatment is important for clinicians to understand. To date, neither of these issues has been explored empirically. To address this, we assessed mood and information-seeking behavior in a sample of women entering PGD. METHODS: Fifty women entering PGD treatment completed self-administered questionnaires that assessed anxiety, depression, knowledge of technical aspects of PGD, expectancy of establishing a pregnancy and unmet information needs. RESULTS: Anxiety and depression rates were similar to normal population data. State anxiety was associated with degree of financial worry [beta = 0.36, t = 2.60, P = 0.01, 95% confidence interval (CI): 0.03-0.23], and living in an inner metropolitan area (beta = 0.30, P = 0.03, 95% CI: 0.32-10.81). Unmet information needs were positively associated with women's education (beta = 0.97, P = 0.01, 95% CI: 0.22-1.73). Lastly, expectancy of establishing a pregnancy was above that of what clinicians provide as realistic PGD pregnancy chances and, unexpectedly, was also associated with degree of financial worry (beta = 0.36, P = 0.01, 95% CI: 0.07-0.56). CONCLUSIONS: Women entering PGD are emotionally well adjusted although the financial costs associated with PGD are associated with increases in anxiety. The study is limited by its small sample size and the fact that partners were not assessed.

Psychological impact of preimplantation genetic diagnosis: a review of the literature.

Preimplantation genetic diagnosis (PGD) was first reported as successful in humans in the early 1990s and nearly two decades later the psychological impact of PGD has not yet been clearly defined. As PGD requires the use of IVF, this paper provides a brief summary of literature related to the various psychological aspects of IVF followed by a review of the literature related to the psychological and broader psychosocial impact of PGD. The current literature includes attitudinal studies of couples for whom PGD may be beneficial and results suggest that those with traumatic reproductive and genetic histories are more likely to find PGD an acceptable treatment option. A small number of studies have used samples of women and couples who have used PGD. Due to a general lack of homogeneity in scope, method and results, these studies have not provided a uniform understanding of the PGD experience. Promisingly, however, two studies on parents of children born after PGD that explored parental stress show no differences between PGD, IVF and natural conception couples. The paper concludes that the missing link in the literature is a prospective study of PGD using validated psychological scales. Suggestions for future research are provided.

Women's experience of pre-implantation genetic diagnosis: a qualitative study.

OBJECTIVE: To provide an in-depth account of the experience of pre-implantation genetic diagnosis (PGD). METHOD: Exploratory qualitative interview study. Participants were recruited from one major in vitro fertilization (IVF) clinic in Sydney, Australia. Data were collected through 14 in-depth interviews with women at different stages of PGD, utilized a thematic approach and facilitated by NVivo software. RESULTS: Women reported using PGD as empowering and led them to feel in control of their reproductive futures. Health professionals who did not tell women about PGD were seen as a barrier to accessing treatment. The ability to select embryos free from the genetic condition (for which it was at risk) alleviated stress. Despite this, stress experienced with PGD was significant for women, and often related to past experiences of reproductive trauma and grief. The outcome of embryos was also the cause of stress for women. CONCLUSION: Women undergoing PGD have a diverse range of reproductive and genetic histories, psychosocial circumstances and world views that all interact and impact their experience of PGD. Successful support and care of these women should address all of these factors and tailor the support provided for women using this physically and emotionally complex form of reproductive technology.

The strengths and limitations of empirical bioethics.

The past two decades have been witness to an "empirical turn" in bioethics. Whereas once this field of study concerned itself purely with theoretical analysis of ethical issues emerging in the design and delivery of health care, increasingly bioethics has embraced a range of empirical research methods from the social sciences and humanities. The emergence of "empirical bioethics" has, however, been the subject of enormous debate, both in regard to its methods and its purpose. For the most part these criticisms fail to appreciate the assumptions that underpin empirical bioethics or misrepresent the claims that are made about its moral utility. This article provides a brief account of the assumptions, strengths and limitations of empirical bioethics.

Narrative Symposium: Patient and Research Participant experiences with Genetic Testing.

Twelve personal narratives address the challenges, benefits, and pitfalls of genetic testing. Three commentary articles explore these stories and suggest lessons that can be learned from them. The commentators come from backgrounds that include bioethics, public health, psychology, and philosophy.

Establishing the role of pre-implantation genetic diagnosis with human leucocyte antigen typing: what place do "saviour siblings" have in paediatric transplantation?

BACKGROUND: Not all children in need of a haematopoietic stem cell transplant have a suitable relative or unrelated donor available. Recently, in vitro fertilisation (IVF) with pre-implantation genetic diagnosis (PGD) for human leucocyte antigen (HLA) tissue typing has been used to selectively transfer an IVF embryo in order to produce a child who may provide umbilical cord blood for transplantation to an ill sibling. Such children are sometimes called "saviour siblings". OBJECTIVE: To examine the published clinical and epidemiological evidence relevant to the use of this technology, with the aim of clarifying those situations where IVF and PGD for HLA typing should be discussed with parents of an ill child. DESIGN: A critical analysis of published literature on comparative studies of umbilical cord blood versus other sources of stem cells for transplantation; comparative studies of matched unrelated donor versus matched related donor transplantation; and the likelihood of finding an unrelated stem cell donor. CONCLUSION: IVF and PGD for HLA typing is only applicable when transplantation is non-urgent and parents are of reproductive age. Discussions regarding this technology may be appropriate where no suitable related or unrelated donor is available for a child requiring a transplant, or where no suitable related donor is available and transplantation is only likely to be entertained with a matched sibling donor. Discussion may also be considered in the management of any child lacking a matched related donor who requires a non-urgent transplant or may require a transplant in the future.