Public Attitudes, Interests, and Concerns Regarding Polygenic Embryo Screening.

Importance: Polygenic embryo screening (PES) is a novel technology that estimates the likelihood of developing future conditions (eg, diabetes or depression) and traits (eg, height or cognitive ability) in human embryos, with the goal of selecting which embryos to use. Given its commercial availability and concerns raised by researchers, clinicians, bioethicists, and professional organizations, it is essential to inform key stakeholders and relevant policymakers about the public's perspectives on this technology. Objective: To survey US adults to examine general attitudes, interests, and concerns regarding PES use. Design, Setting, and Participants: For this survey study, data were collected from 1 stratified sample and 1 nonprobability sample (samples 1 and 2, respectively) between March and July 2023. The surveys measured approval, interest, and concerns regarding various applications of PES. In the second sample, presentation of a list of potential concerns was randomized (presented at survey onset vs survey end). The survey was designed using Qualtrics and distributed to participants through Prolific, an online sampling firm. Sample 1 was nationally representative with respect to gender, age, and race and ethnicity; sample 2 was recruited without specific demographic criteria. Analyses were conducted between March 2023 and February 2024. Main Outcomes and Measures: Participants reported their approval, interest, and concerns regarding various applications of PES and outcomes screened (eg, traits and conditions). Statistical analysis was conducted using independent samples t tests and repeated-measures analyses of variance. Results: Of the 1435 respondents in sample 1, demographic data were available for 1427 (mean [SD] age, 45.8 [16.0] years; 724 women [50.7%]). Among these 1427 sample 1 respondents, 1027 (72.0%) expressed approval for PES and 1169 (81.9%) expressed some interest in using PES if already undergoing in vitro fertilization (IVF). Approval among these respondents for using PES for embryo selection was notably high for physical health conditions (1109 [77.7%]) and psychiatric health conditions (1028 [72.0%]). In contrast, there was minority approval for embryo selection based on PES for behavioral traits (514 [36.0%]) and physical traits (432 [30.3%]). Nevertheless, concerns about PES leading to false expectations and promoting eugenic practices were pronounced, with 787 of 1422 (55.3%) and 780 of 1423 (54.8%) respondents finding them very to extremely concerning, respectively. Sample 2 included 192 respondents (mean [SD] age 37.7 [12.2] years; 110 men [57.3%]). These respondents were presented concerns at survey onset (n = 95) vs survey end (n = 97), which was associated with less approval (28-percentage point decrease) and more uncertainty (24 percentage-point increase) but with only slightly higher disapproval (4 percentage-point increase). Conclusions and Relevance: These findings suggest that it is critical for health care professionals and medical societies to consider and understand the perspectives of diverse stakeholders (eg, patients undergoing IVF, clinicians, and the general public), given the absence of regulation and the recent commercial availability of PES.

Divergence Between Clinician and Patient Perspectives on Polygenic Embryo Screening: A Qualitative Study.

Objective: To explore and compare the perspectives of clinicians and patients on polygenic embryo screening. Design: Qualitative. Subjects: Fifty-three participants: 27 reproductive endocrinology and infertility specialists and 26 patients currently undergoing in vitro fertilization or had done so within the last five years. Main Outcome Measures: Qualitative thematic analysis of interview transcripts. Results: Both clinicians and patients often held favorable views of screening embryos for physical or psychiatric conditions, though clinicians tended to temper their positive attitudes with specific caveats. Clinicians also expressed negative views about screening embryos for traits more often than patients, who generally held more positive views. Most clinicians were either unwilling to discuss or offer polygenic embryo screening to patients or were willing to do so only under certain circumstances, while many patients expressed interest in polygenic embryo screening. Both sets of stakeholders envisioned multiple potential benefits or uses of polygenic embryo screening; the most common included selection and/or prioritization of embryos, receipt of more information about embryos, and preparation for the birth of a predisposed or "affected" child. Both sets of stakeholders also raised multiple potential, interrelated concerns about polygenic embryo screening. The most common concerns among both sets of stakeholders included the potential for different types of "biases" - most often in relation to selection of embryos with preferred genetic chances of traits -, the probabilistic nature of polygenic embryo screening that can complicate patient counseling and/or lead to excessive cycles of in vitro fertilization, and a lack of data from long-term prospective studies supporting the clinical use of polygenic embryo screening. Conclusion: Despite patients' interest in polygenic embryo screening, clinicians feel such screening is premature for clinical application. Though now embryos can be screened for their genetic chances of developing polygenic conditions and traits, many clinicians and patients maintain different attitudes depending on what is specifically screened, despite the blurry distinction between conditions and traits. Considerations raised by these stakeholders may help guide professional societies as they consider developing guidelines to navigate the uncertain terrain of polygenic embryo screening, which is already commercially available.

Researching the future: scenarios to explore the future of human genome editing.

BACKGROUND: Forward-looking, democratically oriented governance is needed to ensure that human genome editing serves rather than undercuts public values. Scientific, policy, and ethics communities have recognized this necessity but have demonstrated limited understanding of how to fulfill it. The field of bioethics has long attempted to grapple with the unintended consequences of emerging technologies, but too often such foresight has lacked adequate scientific grounding, overemphasized regulation to the exclusion of examining underlying values, and failed to adequately engage the public. METHODS: This research investigates the application of scenario planning, a tool developed in the high-stakes, uncertainty-ridden world of corporate strategy, for the equally high-stakes and uncertain world of the governance of emerging technologies. The scenario planning methodology is non-predictive, looking instead at a spread of plausible futures which diverge in their implications for different communities' needs, cares, and desires. RESULTS: In this article we share how the scenario development process can further understandings of the complex and dynamic systems which generate and shape new biomedical technologies and provide opportunities to re-examine and re-think questions of governance, ethics and values. We detail the results of a year-long scenario planning study that engaged experts from the biological sciences, bioethics, social sciences, law, policy, private industry, and civic organizations to articulate alternative futures of human genome editing. CONCLUSIONS: Through sharing and critiquing our methodological approach and results of this study, we advance understandings of anticipatory methods deployed in bioethics, demonstrating how this approach provides unique insights and helps to derive better research questions and policy strategies.

Physician-Investigator, Research Coordinator, and Patient Perspectives on Dual-Role Consent in Oncology: A Qualitative Study.

Importance: Classic statements of research ethics generally advise against dual-role consent in which physician-investigators seek consent for research participation from patients with whom they have preexisting treatment relationships. Yet dual-role consent is common in clinical oncology research, as studies are often conducted in close relationship with clinical care. Objective: To explore key stakeholders' perspectives on dual-role consent in clinical oncology trials. Design, Setting, and Participants: This qualitative study with 43 participants was conducted at a National Cancer Institute-designated comprehensive cancer center from 2018 to 2022. Semistructured qualitative interviews of physician-investigators, research coordinators, and patients were performed. Respondents were recruited from 3 populations: (1) physician-investigators engaged in clinical oncology research; (2) research coordinators engaged in clinical oncology research; and (3) patients, with and without prior clinical trial experience, who had received a new cancer diagnosis at least 2 months prior to enrollment in this study. Main Outcomes and Measures: Interviews were audio recorded and professionally transcribed. A thematic analysis approach was used to develop a codebook that included both theory-driven, a priori codes and emergent, inductive codes. Two authors double-coded all transcripts and met regularly to compare coding, discuss discrepancies, refine the codebook, and draft memos describing relevant themes and their frequency. Results: Among the 43 respondents, 28 (65.1%) were female; 9 (20.9%) were African American, 8 (18.6%) were Asian, 6 (14.0%) were Hispanic, and 21 (48.8%) were White; 15 were physician-investigators (6 [40.0%] with 6-10 years of experience, 4 [26.7%] with at least 20 years of experience), 13 were research coordinators (5 [38.5%] with 0-5 years of experience, 5 [38.5%] with 6-10 years of experience), and 15 were patients (9 [60.0%] aged 46-64 years). Four main themes were found: interviewees (1) perceived greater potential for role synergy than for role conflict; (2) reported dual-role consent as having mixed effects on the consent process, increasing prospective participants' understanding and likelihood of agreement while also challenging voluntariness; (3) preferred a team-based approach to the consent process in which physician-investigators and research coordinators share responsibility for communicating with prospective participants and safeguarding voluntariness; and (4) offered strategies for managing tensions in dual-role consent. Conclusions and Relevance: This qualitative study found that concerns about dual-role consent in clinical oncology, while valid, may be outweighed by corresponding advantages, particularly if appropriate mitigation strategies are in place. These findings support a team-based approach to informed consent, in which physician-investigators and research coordinators promote both the understanding and voluntariness of prospective participants.

Oncofertility Decision Making: Findings from Israeli Adolescents and Parents.

PURPOSE: To date, few studies qualitatively investigate adolescent oncofertility decision making. This qualitative study seeks to understand the experiences of adolescents and parents in making oncofertility decisions within the pronatalist context of Israeli society. METHODS: Semi-structured interviews were conducted in Israel with adolescents between the ages of 12 and 19 years who were in remission for at least 2 months and had been offered fertility preservation (FP) of sperm, ova, or ovary cryopreservation, and their parents, separately. Transcripts were thematically analyzed. RESULTS: Thirty-five interviews were conducted-16 with adolescents and 19 with parents-representing 20 cases of FP decision making. Adolescents and parents do not necessarily view decision making in the same way. Both parties mention a variety of factors in and justifications for FP decisions. Although most participants imagine the adolescent will use cryopreserved biological materials only if s/he experiences reproductive difficulties, nearly all participants do not recall having discussed what to do with these materials in the case of death. Many adolescents and parents feel comfortable waiting to take further action regarding adolescent fertility until the topic has greater relevance to the adolescent's life. Satisfaction with FP decision making is nearly unanimous, regardless of whether FP was pursued. CONCLUSION: As in other cultural contexts, Israeli adolescents and parents demonstrate multifaceted decision making with respect to oncofertility. A significant finding from this study suggests that health professionals shy from discussing posthumous planning of cryopreserved materials with adolescent cancer patients and their parents. Further investigation is warranted to determine whether this is a uniquely Israeli phenomenon, the cause for it, and how to overcome it.

Adolescent oncofertility discussions: Recommendations from a systematic literature review.

BACKGROUND: Increasing cancer incidence and survivorship rates have made late-term effects, such as effects on fertility, a salient issue for adolescent cancer patients. While various barriers make it difficult for health care professionals to discuss oncofertility with adolescents and their parents, there are numerous reasons to hold such discussions, based on professional obligations and the ethical principles of respect for autonomy and beneficence. This systematic literature review presents and critically examines recommendations for adolescent oncofertility discussions. METHODS: Conducted according to PRISMA guidelines, this systematic literature review includes English, French, and German articles published up until December 31, 2014. Articles were sought via a combination of search terms in four databases. RESULTS: Eighty of 96 articles included in this review address recommendations for improving adolescent oncofertility discussions. These recommendations deal with how, when, what, and with whom professionals ought to have these discussions, as well as various systemic barriers and ways to address them. CONCLUSIONS: Based upon the principles of beneficence, respect for autonomy, and justice, we endorse several recommendations for oncofertility discussions with adolescents and their parents, including having a specific professional on the health care team initiate these discussions with all newly diagnosed patients; regularly doing so before, during, and after treatment; allowing adolescents to decide for themselves whom they wish to include in such discussions; employing various forms of communication; obtaining both adolescent assent and parental consent for fertility preservation (FP) procedures, especially at each stage (e.g., procurement and use); properly educating and training professionals to discuss oncofertility; promoting interdisciplinary collaboration; creating and implementing guidelines and policies; and ensuring equity of access to FP.

Attitudes, Beliefs, and Trends Regarding Adolescent Oncofertility Discussions: A Systematic Literature Review.

PURPOSE: Due to improved survival rates of adolescent cancers, increasing attention is paid to addressing patients' future quality of life after treatment. A salient quality of life issue for adolescent survivors is reproductive capacity. Discussing oncofertility, that is, cancer treatment's possible effects on fertility and fertility preservation (FP) options, is a means to address this concern by informing patients and parents regarding options available to them to prevent future struggles with infertility. This systematic literature review aggregates and summarizes the attitudes, beliefs, and patterns of behavior of all stakeholders (i.e., patients, parents, and healthcare providers) in oncofertility discussions when the patient is an adolescent (12-17 years old). METHODS: English, French, and German literature was systematically identified according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, via four databases, using several combinations of search terms. Book chapters, dissertations, and peer-reviewed qualitative and quantitative studies are included in this review. RESULTS: Adolescents and parents have similar informational and counseling needs. Both seek to be fully informed about cancer treatment's effects on fertility and FP options. Adolescents have varying experiences of oncofertility discussions and decision making due to sex and/or age differences. Parents and healthcare professionals alike sometimes underestimate the importance of fertility for adolescent cancer patients. Healthcare professionals hold various beliefs and practices with respect to adolescent oncofertility discussions. Many are cognizant of the various barriers that impede successful discussion and strive to overcome them. CONCLUSION: In order to overcome discussion barriers and meet adolescent patients and their parents' informational needs, it is essential to create and implement practice guidelines, as well as properly educate and train healthcare professionals about oncofertility issues.

Disclosing Genetic Information to Family Members About Inherited Cardiac Arrhythmias: An Obligation or a Choice?

Inherited cardiac arrhythmias such as long QT syndrome and Brugada syndrome, present clinical as well as ethical, legal, and social challenges. Many individuals who carry a deleterious mutation are largely asymptomatic and therefore may not be diagnosed until after the occurrence of a personal or family member's cardiac event. The familial nature of inherited genetic information raises numerous ethical, legal, and social issues regarding the sharing of genetic information, particularly when an individual found to carry a deleterious mutation refuses to disclose his or her results to at-risk family members who could benefit from life-saving treatments. This qualitative study sought to understand the experiences with genetic testing for individuals (n = 50) with a personal or family history of cardiac events or sudden death. Unstructured in-person focus groups or interviews were conducted for each participant in the study. The recordings of these interviews were transcribed verbatim and subsequently analyzed and coded. Participants' comments regarding sharing of genetic information centered around four main themes: (1) motivation to disclose; (2) extent of disclosure; (3) effect of disclosure on family dynamics; and (4) reasons for not sharing genetic information. The majority of individuals believed that affected individuals are obligated to disclose genetic information to family members. In the era of personalized medicine, the disclosure of genetic information provides individuals the opportunities to learn about the genetics, disease characteristics, and treatment options in order to reduce morbidity and mortality in themselves and their family members. Further research is necessary to identify and explore the barriers to sharing genetic information with at-risk family members.

Reproductive Decision Making and Genetic Predisposition to Sudden Cardiac Death.

BACKGROUND: With current genetic technology, it is possible to detect mutations associated with long QT syndrome (LQTS), a hereditary cardiac arrhythmia syndrome. As a result, prospective parents diagnosed with LQTS will have to decide whether or not to prevent its transmission to future generations, either by not procreating or through the use of assisted reproductive technologies or prenatal testing. This paper explores how a hereditary predisposition to sudden cardiac death can influence reproductive decision making. METHODS: This study draws from interviews and focus groups with individuals who have personal or family histories of cardiac arrhythmia or sudden death. A keyword search was conducted on interview transcripts to identify quotes for analysis. RESULTS: Participants expressed complex, often ambivalent attitudes about the prospect of having a child with a predisposition to sudden cardiac death. Their comments reveal conflicting understandings of genetic responsibility and reflect the variable effects of personal experience on reproductive decision making. This paper compares attitudes towards LQTS and other genetic conditions in analyzing the themes that emerged in interviews and focus groups. CONCLUSIONS: The "disability critique" of prenatal testing should be applied carefully to a context of genetic predisposition to sudden cardiac death in order to understand reproductive decision making. Firsthand experience with the condition, among other factors, can weigh heavily in those decisions.