Perceptions of reproductive healthcare providers regarding their involvement in offering expanded carrier screening in fertility clinics: a qualitative study.

RESEARCH QUESTION: What are the main arguments of reproductive healthcare providers in favour or against their involvement in offering expanded carrier screening (ECS) for recessive disorders at fertility clinics in the Netherlands? DESIGN: Semi-structured interview study with 20 reproductive healthcare providers between May 2020 and January 2021. Participants included 11 gynaecologists, seven fertility doctors, one nurse practitioner and one clinical embryologist, recruited from academic medical centres (n = 13), peripheral facilities associated with academic centres (n = 4), and independent fertility treatment centres (n = 3) in the Netherlands. An interview guide was developed, and thematic content analysis was performed using ATLAS.ti software. RESULTS: Arguments of reproductive healthcare providers in favour of their potential involvement in offering ECS included: (i) opportunities offered by the setting; (ii) motivation to assist in reproduction and prevent suffering; and (iii) to counter unwanted commercialization offers. Arguments against involvement included: (i) lack of knowledge and familiarity with offering ECS; (ii) insufficient staff and resources, and potential high costs for clinics and/or couples; (iii) the emotional impact it may have on couples; (iv) perceived complexity of counselling and expected elongation of waiting lists; and (v) expected low impact on reducing the burden of diseases. Participants felt that more evidence and research on the costs-benefits, implications and demand are needed prior to their involvement. CONCLUSION: While agreeing that the field of medically assisted reproduction provides a unique opportunity to offer ECS, reproductive healthcare workers feel a lack of capability and limited motivation to offer ECS to all or a selection of couples at their fertility clinics.

Dynamics of reproductive genetic technologies: Perspectives of professional stakeholders.

Reproductive and genetic medicine are evolving rapidly, and new technologies are already impacting current practices. This includes technologies that can identify a couples' risk of having a child with a genetic disorder. Responsible implementation of new technologies requires evaluation of safety and ethics. Valuable insights for shaping governance processes are provided by various stakeholders involved, including healthcare professionals. Their willingness to adopt these technologies and guide the necessary systemic changes is required for the successful implementation of these technologies. In this study, twenty-one semi-structured interviews were conducted with professionals from different disciplines in the field of reproductive and genetic healthcare in the Netherlands. Three emerging technologies were discussed: expanded carrier screening (ECS), non-invasive prenatal diagnosis (NIPD) and germline genome editing (GGE). By probing stakeholders' views, we explored how culture, structure and practice in healthcare is being shaped by innovations and changing dynamics in genetic and reproductive medicine. The general consensus was that the implementation of reproductive genetic technologies nationwide is a slow process in Dutch healthcare. A "typical Dutch approach" emerged that is characterized by restrictive legislation, broad support for people living with disabilities, values of an egalitarian society and limited commercialisation. Different scenarios for embedding ECS in future practice were envisioned, while implementation of NIPD in clinical practice was considered obvious. Views on GGE varied among stakeholders. Previous implementation examples in the Netherlands suggest introduction of new technology involves an organized collective learning process, with pilot studies and stepwise implementation. In addition, introducing and scaling up new technologies is complex due to perceived barriers from the legislative framework and the complex relationship between the government and stakeholders in this area. This paper describes how the international trends and advances of technologies are expected to manifest itself in a national setting.

Couples' experiences with expanded carrier screening: evaluation of a university hospital screening offer.

Preconception carrier screening offers couples the possibility to receive information about the risk of having a child with a recessive disorder. Since 2016, an expanded carrier screening (ECS) test for 50 severe autosomal recessive disorders has been available at Amsterdam Medical Center, a Dutch university hospital. This mixed-methods study evaluated the experiences of couples that participated in the carrier screening offer, including high-risk participants, as well as participants with a general population risk. All participants received genetic counselling, and pre- (n = 132) and post-test (n = 86) questionnaires and semi-structured interviews (n = 16) were administered. The most important reason to have ECS was to spare a future child a life with a severe disorder (47%). The majority of survey respondents made an informed decision (86%), as assessed by the Multidimensional Measure of Informed Choice. Among the 86 respondents, 27 individual carriers and no new carrier couples were identified. Turn-around time of the test results was considered too long and costs were perceived as too high. Overall, mean levels of anxiety were not clinically elevated. High-risk respondents (n = 89) and pregnant respondents (n = 13) experienced higher levels of anxiety before testing, which decreased after receiving the test result. Although not clinically significant, distress was on average higher for carriers compared to non-carriers (p < 0.0001). All respondents would opt for the test again, and 80.2% would recommend it to others. The results suggest that ECS should ideally be offered before pregnancy, to minimise anxiety. This study could inform current and future implementation initiatives of preconception ECS.

Preconception expanded carrier screening: a focus group study with relatives of mucopolysaccharidosis type III patients and the general population.

Preconception expanded carrier screening (ECS) enables prospective parents to assess their risk of having a child with an autosomal recessive disorder. Knowledge on motivations, feelings, and considerations people have towards the offer and use of ECS is limited. To enrich the public and professional discussion on ECS implementation, this study explored the perspectives towards various aspects of ECS in seven focus groups compromising first- and second-degree relatives of MPS III patients (N=9, N=4, N=5, N=5) and members of the general Dutch population (N=6, N=7, N=5). The focus groups were audio recorded and the transcripts were qualitatively analyzed to identify themes. Both relatives of MPS III patients and participants from the general population supported offering ECS, in particular for severe, childhood-onset disorders. Important barriers identified for ECS were a lack of genetic knowledge and a perceived lack of personal relevance and awareness, as well as out-of-pocket costs of testing. The majority of participants would prefer full disclosure of individual test results instead of couple-based test results. Moreover, offering people a choice for the way of reporting was proposed. All participants agreed that more efforts, for example by governmental campaigns, should be made to increase awareness on the availability, potentials, and limitations of ECS. Educating prospective parents about ECS is essential for increasing awareness and informed decision making. This study provides valuable insights that can be used by governments and public health authorities when considering implementation of preconception ECS.

How will new genetic technologies, such as gene editing, change reproductive decision-making? Views of high-risk couples.

Couples at increased risk of having offspring with a specific genetic disorder who want to avoid having an affected child have several reproductive options including prenatal diagnosis (PND) and preimplantation genetic testing (PGT). In the future, non-invasive prenatal diagnosis (NIPD), germline gene editing (GGE) and somatic gene editing (SGE) might become available. This study explores if, and how, availability of new genetic technologies, including NIPD, GGE, SGE, would change reproductive decision-making of high-risk couples. In 2018, semi-structured interviews were conducted with 25 genetically at-risk couples. Couples previously had received genetic counselling for PND and PGT, and in most cases opted for (one of) these techniques, at one Dutch Clinical Genetics Center between 2013 and 2017. Considerations participants mentioned regarding the hypothetical use of NIPD, GGE and SGE, seem similar to considerations regarding PND and PGT and are reflected in underlying concepts. These include safety and burden for mother and child, and moral considerations. Couples generally favoured NIPD over PND as this would be safe and enables earlier diagnosis. Increased opportunities of having a 'healthy' embryo and less embryo disposal were considerations in favour of GGE. Some regarded GGE as unsafe and feared slippery slope scenarios. Couples were least favourable towards SGE compared to choosing for a genetic reproductive technology, because of the perceived burden for the affected offspring. With the possibly growing number of technological options, understanding high risk couples' perspectives can assist in navigating the reproductive decision-making process. Counsellors should be prepared to counsel on more and complex reproductive options.

The ethics of clinical applications of germline genome modification: a systematic review of reasons.

STUDY QUESTION: What are the reasons for or against the future clinical application of germline genome modification (GGM)? SUMMARY ANSWER: A total of 169 reasons were identified, including 90 reasons for and 79 reasons against future clinical application of GGM. WHAT IS KNOWN ALREADY: GGM is still unsafe and insufficiently effective for clinical purposes. However, the progress made using Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)- CRISPR-associated system (Cas) has led scientists to expect to overcome the technical hurdles in the foreseeable future. This has invited a debate on the socio-ethical and legal implications and acceptability of clinical applications of GGM. However, an overview of the reasons presented in this debate is missing. STUDY DESIGN, SIZE, DURATION: MEDLINE was systematically searched for articles published between January 2011 and June 2016. Articles covering reasons for or against clinical application of intentional modification of the nuclear DNA of the germline were included. PARTICIPANTS/MATERIALS, SETTING, METHODS: Two researchers independently extracted the reported reasons from the articles and grouped them into categories through content analysis. MAIN RESULTS AND THE ROLE OF CHANCE: The systematic search yielded 1179 articles and 180 articles were included. Most papers were written by professionals in ethics, (science) journalism and biomedical sciences. Overall, 169 reasons were identified, including 90 reasons for, and 79 reasons against future clinical application of GGM. None of the included articles mentioned more than 60/169 reasons. The reasons could be categorized into: (i) quality of life of affected individuals; (ii) safety; (iii) effectiveness; (iv) existence of a clinical need or alternative; (v) costs; (vi) homo sapiens as a species (i.e. relating to effects on our species); (vii) social justice; (viii) potential for misuse; (ix) special interests exercising influence; (x) parental rights and duties; (xi) comparability to acceptable processes; (xii) rights of the unborn child; and (xiii) human life and dignity. Considerations relating to the implementation processes and regulation were reported. LIMITATIONS, REASONS FOR CAUTION: We cannot ensure completeness as reasons may have been omitted in the reviewed literature and our search was limited to MEDLINE and a 5-year time period. WIDER IMPLICATIONS OF THE FINDINGS: Besides needing (pre)clinical studies on safety and effectiveness, authors call for a sound pre-implementation process. This overview of reasons may assist a thorough evaluation of the responsible introduction of GGM. STUDY FUNDING/COMPETING INTEREST(S): University of Amsterdam, Alliance Grant of the Amsterdam Reproduction and Development Research Institute (I.D.), and Clinical Center, Department of Bioethics, National Institutes of Health Intramural Research Program (S.H.). There are no competing interests.