Reproductive Genetic Technologies Research Articles

Ready for polygenic risk scores? An analysis of regulation of preimplantation genetic testing in European countries.

Would the different regulatory approaches for preimplantation genetic testing (PGT) in Europe permit the implementation of preimplantation genetic testing using polygenic risk scores (PGT-P)? While the regulatory approaches for PGT differ between countries, the space provided for potential implementation of PGT-P seems limited in all three regulatory models. PGT is a reproductive genetic technology that allows the testing for hereditary genetic disorders and chromosome abnormalities in embryos before implantation. Throughout its history, PGT has largely been regarded as an ethically sensitive technology. For example, ethical questions have been raised regarding the use of PGT for adult-onset conditions, non-medical sex selection, and human leukocyte antigen typing for the benefit of existing siblings. Countries in which PGT is offered each have their own approach of regulating the clinical application of PGT, and a clear overview of legal and practical regulation of PGT in Europe is lacking. An emerging development within the field of PGT, namely PGT-P, is currently bringing new ethical tensions to the forefront. It is unclear whether PGT-P may be applied within the current regulatory frameworks in Europe. Therefore, it is important to investigate current regulatory frameworks in Europe and determine whether PGT-P fits within these frameworks. The aim of this study was to provide an overview of the legal and practical regulation of the use of PGT in seven selected European countries (Belgium, France, Germany, Italy, the Netherlands, Spain, and the UK) and critically analyse the different approaches with regards to regulatory possibilities for PGT-P. Between July and September 2023, we performed a thorough and extensive search of websites of governments and governmental agencies, websites of scientific and professional organizations, and academic articles in which laws and regulations are described. We investigated the legal and regulatory aspects of PGT by analysing legal documents, regulatory frameworks, scientific articles, and guidelines from scientific organizations and regulatory bodies to gather relevant information about each included country. The main sources of information were national laws relating to PGT. We divided the PGT regulation approaches into three models. The regulation of PGT differs per country, with some countries requiring central approval of PGT for each new indication (the medical indication model: the UK, the Netherlands), other countries evaluating each individual PGT request at the local level (the individual requests model: France, Germany), and countries largely leaving decision-making about clinical application of PGT to healthcare professionals (the clinical assessment model: Belgium, Italy, Spain). In the countries surveyed that use the medical indication model and the individual requests model, current legal frameworks and PGT criteria seem to exclude PGT-P. In countries using the clinical assessment model, the fact that healthcare professionals and scientific organizations in Europe are generally negative about implementation of PGT-P due to scientific and socio-ethical concerns, implies that, even if it were legally possible, the chance that PGT-P would be offered in the near future might be low. The results are based on our interpretation of publicly available written information and documents, therefore not all potential discrepancies between law and practice might have been identified. In addition, our analysis focuses on seven-and not all-European countries. However, since these countries are relevant players within PGT in Europe and since they have distinct PGT regulations, the insights gathered give relevant insights into diverse ways of PGT regulation. To the best of our knowledge, this is the first paper that provides a thorough overview of the legal and practical regulation of PGT in Europe. Our analysis of how PGT-P fits within current regulation models provides guidance for healthcare professionals and policymakers in navigating the possible future implementation of PGT-P within Europe. This project has received funding from the European Union's Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement no. 813707. The authors declare no conflict of interest. N/A.

“Are we not going too far?“: Socio-ethical considerations of preimplantation genetic testing using polygenic risk scores according to healthcare professionals

The recent introduction of polygenic risk scores within preimplantation genetic testing (PGT-P) has been met with many concerns. To get more insights into the perspectives of relevant stakeholders on the socio-ethical aspects of PGT-P, an interview study with 31 healthcare professionals involved in reproductive medicine and genetics in Europe and North-America was performed. Healthcare professionals in our study were concerned that PGT-P was going too far in terms of selection, with regards to both medical conditions and non-medical traits. Healthcare professionals were worried about the ethical ‘slippery slope’ of PGT-P, the increasing medicalization of reproductive health, the commercial context of PGT-P, and potential stigmatization and discrimination. There were also concerns that the availability and the ‘technological imperative’ of PGT-P could lead to pressure and a sense of responsibility for parents to use PGT-P. Additionally, it could cause new anxieties about the child's health before the child has even been born. Since PGT-P provides polygenic risk scores before birth, the autonomy of the child has to be considered. These socio-ethical concerns heighten existing debates regarding reproductive genetic technologies and show that the specifics of PGT-P make this screening option especially ethically controversial.

Patient Perceptions on the Advancement of Noninvasive Prenatal Testing for Sickle Cell Disease among Black Women in the United States

Background Noninvasive prenatal testing (NIPT) designed to screen for fetal genetic conditions, is increasingly being implemented as a part of routine prenatal care screening in the United States (US). However, these advances in reproductive genetic technology necessitate empirical research on the ethical and social implications of NIPT among populations underrepresented in genetic research, particularly Black women with sickle cell disease (SCD). Methods Forty (N = 40) semi-structured interviews were conducted virtually with Black women in the US (19 participants with SCD; 21 participants without SCD) from June 2021 to January 2022. We employed a qualitative approach to examine the study participants’ perceptions of the potential advancement of NIPT for screening SCD in the fetus. Data were analyzed using NVivo 12 qualitative software. Results The themes revealed the complexities involving the intersectional lived experiences of SCD, prenatal care, lack of synergy among health providers, and NIPT decision-making. The results further revealed that even when Black women have shared commonalities in their lived experiences while navigating SCD and motherhood, their perceptions of NIPT screening technologies are divergent. Conclusion Expanding the ethical discourse on the social implications of NIPT is critical to fully elucidate how Black women perceive NIPT’s utility, particularly as NIPT advances to screen for SCD in the fetus. Neglecting to include Black women with genetic conditions in empirical studies on NIPT may contribute to ongoing health inequities and limit and constrain reproductive choices among Black women with and without SCD.

Danish milk consumers are critical of advanced breeding methods in dairy production, but only 1 in 5 is unwilling to drink milk from dairy cows bred with semen derived from such methods

Assisted reproductive technologies and genetic technologies can accelerate progress in breeding programs in dairy farming, but it is unclear how consumers will react to the use of these technologies. Using representative questionnaire data on Danish citizens (n = 2,036) this cross-sectional study examined consumer attitudes to the application of advanced technologies in dairy cattle breeding. Attitudes were examined in 2 ways. First, we prompted about general attitudes to assisted reproductive technologies and genetic technologies in dairy cow breeding. Here we found that most of the participants were critical of cow impregnation involving hormone therapy and the insertion of cloned fetuses. Second, we used a vignette experiment to study whether acceptance of and willingness to drink milk varies with the type of technique that farmers use for their breeding work, as well as the traits being bred for. We included 5 breeding methods with differing degrees of technological complexity. Participants were randomly assigned to receive tailored information about 1 of the 5 breeding methods. The information specified that dairy farmers' own use of advanced technologies is limited to using semen in artificial insemination on the farm. The potentially concerning technologies are here not applied at farm level but are represented in the semen used in artificial insemination because they were used by breeders on earlier generations of cows and bulls to develop semen with higher genetic merit. There was much less concern about this indirect use of the technologies. Only 1 in 5 participants thought the most advanced method we prompted about (use of semen from breeding methods involving genetic engineering and cloning) was unacceptable. Unwillingness to drink milk from cows produced through such a breeding method was also modest (18%) and not much higher than the unwillingness to drink milk from a cow produced by natural fertilization (10%). A likely reason for the unexpectedly low level of unwillingness to drink milk is that people regard the genetic engineering as distant from the final product. We also found that high-frequency organic milk consumers were more critical of advanced breeding methods. Thus, 28% within this group were unwilling to drink milk from cows impregnated with semen derived from earlier generations of cows and bulls bred using gene editing and cloning. Further, this share rose if the high-frequency organic consumers were very averse to the manipulation of nature. The organic sector may need to cater to this subgroup (e.g., by ensuring the traceability of the semen that organic farmers use to artificially inseminate their cows).

Expressivist objections to prenatal screening and testing: Perceptions of people living with disability.

The 'expressivist objection' (EO) refers to the notion that using reproductive (genetic) technologies to prevent the birth of future would-be disabled people contain, and express, a negative valuation of life with disability. Whilst the EO has received increased attention in recent years in line with rapid technological and genomic developments, there remains scant research on how EO concerns are experienced and expressedby disabled people and their families, especially within and between impairment groups. Bringing together two studies-one with adults and family members living with genetic conditions (n=62) and one with parents of children with Down's syndrome (n=22)-we argue that disabled people and their families variously embrace, reject or rework the EO across contexts, and yetalso frequently situate it within broad support for reproductive technologies. We present three key factors that mediate responses to the EO: (1) the nature of impairment and its integration within identity; (2) social and cultural contexts relating to disability and (3) the (individual and collective) imagined futures of disabled people. In so doing, we blend the conceptual architecture of medical sociology and disability studies, arguing that this allows us to accurately illuminate the nuanced responses of disabled people and their families.

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.

Walking a Fine Germline: Synthesizing Public Opinion and Legal Precedent to Develop Policy Recommendations for Heritable Gene-Editing.

Gene-editing technologies, such as CRISPR/Cas9, are internationally ethically fraught. In the United States, policy surrounding gene-editing has yet to be implemented, while the science continues to speed ahead. However, it is not enough that policy be implemented: in order for policy to establish limits for the technology such that benefits are possible while threats are kept at bay, such policy must be ethical. In turn, the ethics of gene-editing is a culturally determined field of inquiry. This piece presents a proposal for a study whose goal is to arrive at ethical policy recommendations for policymakers. To achieve this goal, this study proposes, what needs to be done is, first, to understand the full history and foundation of gene-editing by conducting a thorough legal, bioethical, and policy review for precedent assisted reproductive technologies and genetic reproductive technologies. Following this effort, an empirical study must be conducted involving careful surveys of key stakeholder groups on their knowledge and opinions of gene-editing. Such stakeholder groups must include bioethicists, medical geneticists, and lay persons, including those in the disability community.

Revolutionising the Reproductive World (Vol. 26, No. 03n04, Full Issue)

For the months of March and April 2022, APBN looks at how we can improve and support women's reproductive health. In Features, we have Dr Samuel Prien and Dr Linsay Penrose from Texas Tech University Health Sciences on how we may select the best embryos that will provide the best chances for pregnancy; Dr Alok Javali and Dr Nicolas Rivron from IMBA-Institute of Molecular Biology in Vienna, Austria on how blastoids can be used as a drug discovery tool to improve IVF procedures; and Michelle Tan Min Shuen on reproductive genetic technology. In Columns, Sumir Bhatia, President, Asia Pacific, Lenovo Infrastructure Solutions Group talks about the future of genome sequencing and Justin Loh, Country Director for Singapore, Veritas Technologies tells us how we may protect patient data from data breaches. In Spotlights, we recap the highlights from the Future of Healthcare Week, discussing the path forward in a post-COVID world.

Why Science and Faith Need Each Other: Eight Shared Values That Move Us beyond Fear

Why Science and Faith Need Each Other: Eight Shared Values That Move Us beyond Fear

Fertilizing morality: How religiosity and orientations toward science shape the morality, immorality, and amorality of reproductive technologies.

Scientific innovations continue to advance the possibilities of human reproduction, raising important empirical and ethical questions. In vitro fertilization, disease reproductive genetic technologies, and enhancement reproductive genetic technologies are three reproductive technologies with varying moral support. Instead of assuming moral poles, we use original, nationally representative survey data of US adults (N = 8107) and multinomial logistic regression to examine how religiosity and orientations toward science shape the moral acceptability, amorality, and the moral rejection of in vitro fertilization, disease reproductive genetic technologies, and enhancement reproductive genetic technologies. We find that increased confidence and trust in science lowered the odds of holding moral concerns, while greater religiosity was associated with higher odds of viewing these technologies as morally wrong. Moral attitudes further varied across religious tradition as certain religious groups had significantly higher odds of viewing these technologies as amoral. Findings have implications for advancing understandings of morality around the faith-science interface beyond conceptions of a moral binary.

Affecting future individuals: Why and when germline genome editing entails a greater moral obligation towards progeny.

Assisted reproductive technologies have greatly increased our control over reproductive choices, leading some bioethicists to argue that we face unprecedented moral obligations towards progeny. Several models attempting to balance the principle of procreative autonomy with these obligations have been proposed. The least demanding is the minimal threshold model (MTM), according to which every reproductive choice is permissible, except creating children whose lives will not be worth living. Hence, as long as the future child is likely to have a life worth living, prospective parents may be allowed to use preimplantation genetic diagnosis (PGD) to select embryos with genetic diseases or disabilities. Assuming a consequentialist person‐affecting view of morality, this paper investigates whether the MTM is an appropriate tool to guide procreative decisions given the continuous development of reproductive genetic technologies. In particular, I consider germline genome editing (GGE) and I argue that its application in human reproduction, unlike PGD, should be conceived as person‐affecting towards future progeny. I claim that even if we assume the plausibility of the MTM within PGD, we are committed to accepting that a greater moral obligation towards progeny should guide procreative decisions if GGE were available. In this case, the MTM should no longer be considered an appropriate instrument to guide procreative choices. Finally, I investigate when we face this greater moral obligation, concluding that it applies only when prospective parents have already engaged in the in vitro fertilization process.

Can reproductive genetic manipulation save lives?

It has recently been argued that reproductive genetic manipulation technologies like mitochondrial replacement and germline CRISPR modifications cannot be said to save anyone's life because, counterfactually, no one would suffer more or die sooner absent the intervention. The present article argues that, on the contrary, reproductive genetic manipulations may be life-saving (and, from this, have therapeutic value) under an appropriate population health perspective. As such, popular reports of reproductive genetic manipulations potentially saving lives or preventing disease are not necessarily mistaken, though such terminology still requires further empirical validation.

Is it ever morally permissible to select for deafness in one\u2019s child?

As reproductive genetic technologies advance, families have more options to choose what sort of child they want to have. Using preimplantation genetic diagnosis (PGD), for example, allows parents to evaluate several existing embryos before selecting which to implant via in vitro fertilization (IVF). One of the traits PGD can identify is genetic deafness, and hearing embryos are now preferentially selected around the globe using this method. Importantly, some Deaf families desire a deaf child, and PGD–IVF is also an option for them. Selection for genetic deafness, however, encounters widespread disapproval in the hearing community, including mainstream philosophy and bioethics. In this paper I apply Elizabeth Barnes’ value-neutral model of disability as mere-difference to the case of selecting for deafness. I draw on evidence from Deaf Studies and Disability Studies to build an understanding of deafness, the Deaf community, and the circumstances relevant to reproductive choices that may obtain for some Deaf families. Selection for deafness, with deafness understood as mere-difference and valued for its cultural identity, need not necessitate impermissible moral harms. I thus advocate that it is sometimes morally permissible to select for deafness in one’s child.

Balancing Needs and Autonomy: The Involvement of Pregnant Women's Partners in Decisions About cfDNA.

Cell-free fetal DNA (cfDNA) screening is used to identify the presence of fetal genetic variants early in pregnancy. Patients' informed decision-making is central to the success of this new screen in clinical practice. Although research has focused on pregnant women's decision-making, little is known about partners' role and preferences as a member of the decision-making dyad. Using a grounded theory approach, this study analyzed 23 in-depth interviews to examine partners' perspectives about cfDNA screening and preferences with respect to their role in the decision-making process. Participants wished to be actively involved in testing decisions. They articulated a distinct set of needs and preferences in the decision-making process. Such involvement was hindered by several biological and logistical barriers. This study demonstrates the need to develop mechanisms that foster informed decision-making for cfDNA screening and related new reproductive genetic technologies that focus on not just the pregnant woman but also the decision-making dyad that includes her partner as well.

Moral Schemas in Articulation and Intuition: How Religious People Evaluate Human Reproductive Genetic Technologies

As new and more effective human reproductive genetic technologies (RGTs) rapidly develop, religious voices remain an important part of public discussion about the moral standing of such technologies. Here, we compare how individuals from different religious traditions evaluate disease RGTs (detecting genetic diseases in vitro) when compared to enhancement RGTs, allowing parents to select features of a child. Findings are gleaned from analysis of 270 interviews with individuals from 23 Christian, Muslim, and Jewish religious organizations, with supporting data from a national survey of more than 10,000 Americans. We find that respondents engage in clearly defined discursive moral reasoning to evaluate the propriety of disease RGTs while moral intuitions manifest themselves in responses to enhancement RGTs. We argue that schemas provide resources for moral discourses while also shaping moral intuitions expressed through emotions. Our results have implications for how religious people respond to new technologies when their institutional and denominational structures do not have readily discernable moral frameworks to guide responses.

An Ethical Analysis of Assisted Reproduction Providers' Websites in Pakistan.

Assisted reproductive technologies (ARTs) and reproductive genetic technologies (RGTs) are intertwined and coevolving. These technologies are increasingly used to fulfill socially and culturally framed requests, for example, "family balancing," or to enable postmenopausal women or homosexual couples to have genetically linked children. The areas of ART and RGT are replete with ethical issues, because different social practices and legal regulations, as well as economic inequalities within and among countries, create vulnerable groups and, therefore, the potential for exploitation. This article provides an overview of the ART and RGT landscape in Pakistan and analyzes the available online content addressing Pakistani citizens and international clients. We explored the topic in view of socioeconomic challenges in Pakistan, particularly deeply rooted poverty, lack of education, gender discrimination, and absence of regulation. As online information given by ART and RGT providers is readily available and could easily raise false hopes, make use of discriminatory statements with regard to women, and promote gender selection to meet sociocultural expectations, it should be subjected to quality control.

CRISPR, a Crossroads in Genetic Intervention: Pitting the Right to Health against the Right to Disability.

Reproductive genetic technologies (RGTs), including gene-editing technology, are being discovered and refined at an exponential pace. One gene-editing innovation that demands our swift attention is CRISPR/Cas9, a system of clustered regularly interspaced short palindromic repeats and a protein called Cas9. As CRISPR and other RGTs continue being developed, we must remain vigilant concerning the potential implications of genetic-engineering technology on our interpersonal and legal relationships. In the face of increasingly numerous and refined RGTs, we must maintain the rights of everyone: potential parents, prospective children, and individuals (both living and prospective) with disabilities. For those who wish to become parents, how should procreation be regulated in light of developing RGTs, especially gene-editing technology? What duties do parents owe their children, and when does such a duty attach? What role should RGTs play in parents’ fulfillment of their duties to their children? This article will contextualize the right to health and what I will term the “right to disability” in the CRISPR/Cas9 landscape. The article will then explore these rights in reference to the “subjunctive-threshold” interpretation of harm. Finally, I will argue that RGTs must be thoughtfully regulated, with such regulations taking into account the opinions of geneticists, bioethicists, and lay people concerning both the right to health and the right to disability.

Stocking the Genetic Supermarket: Reproductive Genetic Technologies and Collective Action Problems

Reproductive genetic technologies (RGTs) allow parents to decide whether their future children will have or lack certain genetic predispositions. A popular model that has been proposed for regulating access to RGTs is the ‘genetic supermarket’. In the genetic supermarket, parents are free to make decisions about which genes to select for their children with little state interference. One possible consequence of the genetic supermarket is that collective action problems will arise: if rational individuals use the genetic supermarket in isolation from one another, this may have a negative effect on society as a whole, including future generations. In this article we argue that RGTs targeting height, innate immunity, and certain cognitive traits could lead to collective action problems. We then discuss whether this risk could in principle justify state intervention in the genetic supermarket. We argue that there is a plausible prima facie case for the view that such state intervention would be justified and respond to a number of arguments that might be adduced against that view.

The expressivist objection to prenatal testing: The experiences of families living with genetic disease

The expressivist objection to prenatal testing is acknowledged as a significant critique of prenatal testing practices most commonly advanced by disability rights supporters. Such writers argue that prenatal testing and selective termination practices are objectionable as they express disvalue not only of the foetus being tested, but also of disabled people as a whole, by focusing exclusively on the disabling trait. While the objection has been widely critiqued on the basis of its theoretical incoherence, this paper highlights the way in which it, nevertheless, is a significant mediator in decisions around the use of reproductive genetic technologies. By drawing on 41 in-depth qualitative interviews (drawn from a sample of 61) conducted in the UK between 2007 and 2009 with families and individuals living with a genetic disease, Spinal Muscular Atrophy (SMA), this paper highlights the ways in which expressivist objections feature prominently in the reproductive decisions of families living with SMA and the significant emotional burden they represent. While the literature on the expressivist objection has focused on the reproductive decisions of those undergoing prenatal testing for a condition of which they have little (or no) prior knowledge, the context of intimate familial relationships and extensive experience with the tested-for condition fundamentally alters the nature and impact of expressivist objections within families living with an inheritable condition. By focussing on the reproductive decisions of families living with SMA and their strategic management of the expressivist objection, this paper will address the call, made primarily by disability rights supporters, for ‘experientially based’ (as opposed to medical) information about the tested-for disability to be made available to would-be parents considering selective termination. It will be argued that parents' experiential knowledge of the tested-for disability can, in fact, amplify expressivist objections to prenatal testing, and thus paradoxically constrain, rather than facilitate, reproductive decisions.

Experiential knowledge of disability, impairment and illness: The reproductive decisions of families genetically at risk

As the capacities of Reproductive Genetic Technologies expand, would-be parents face an increasing number of reproductive decisions regarding testing and screening for different conditions. Several studies have acknowledged the role that 'experiential knowledge of disability' plays in arriving at decisions around the use of these technologies; however, there is a lack of clarity within this literature as to what constitutes 'experiential knowledge of disability' and an over-reliance on medical diagnoses as a shorthand to describe different types of experience. Drawing on both social model of disability theory and the literature on chronic illness, this article presents an analysis of data from an in-depth qualitative interview study with 64 people with an inheritable condition in their family, Spinal Muscular Atrophy, and reports their views around reproduction and Reproductive Genetic Technologies. An experiential typology is presented which demonstrates the way in which experiences of 'disability', 'embodied experiences of impairment' or 'embodied experiences of illness, death and bereavement' are strategically privileged in accounts of reproductive decisions, in order to validate reproductive decisions taken, and, specifically, justify use (or non-use) of Reproductive Genetic Technologies. By highlighting the experiential categories within which participants embedded their reproductive decisions, this article draws attention to the porous and collapsible nature of diagnostic categories in the context of reproductive decision-making and genetic risk, and suggests new ways of researching 'experiential knowledge of disability' within these contexts which are able to account for the various contours of the embodied lived reality of life with 'disability'.