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

STUDY QUESTION: 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)? SUMMARY ANSWER: 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. WHAT IS KNOWN ALREADY: 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. STUDY DESIGN, SIZE, DURATION: 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. PARTICIPANTS/MATERIALS, SETTING, METHODS: 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. MAIN RESULTS AND THE ROLE OF CHANCE: 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. LIMITATIONS, REASONS FOR CAUTION: 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. WIDER IMPLICATIONS OF THE FINDINGS: 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. STUDY FUNDING/COMPETING INTEREST(S): This project has received funding from the European Union's Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement no. 813707. The authors declare no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Perspectives of preimplantation genetic testing patients in Belgium on the ethics of polygenic embryo screening.

RESEARCH QUESTION: What are the perspectives of preimplantation genetic testing (PGT) patients in Belgium on the ethics of PGT for polygenic risk scoring (PGT-P)? DESIGN: In-depth interviews (18 in total, 10 couples, 8 women, n = 28) were performed with patients who had undergone treatment with PGT for monogenic/single-gene defects (PGT-M) or chromosomal structural rearrangements (PGT-SR) between 2017 and 2019 in Belgium. Participants were asked about their own experiences with PGT-M/SR and about their viewpoints on PGT-P, including their own interest and their ideas on its desirability, scope and consequences. Inductive content analysis was used to analyse the interviews. RESULTS: Participants stated that their experiences with PGT-M/SR had been physically, psychologically and practically difficult. Most participants stated that, partly because of these difficulties, they did not see the added value of knowing the risk scores of embryos via PGT-P. Many participants worried that PGT-P could lead to additional anxieties, responsibilities and complex choices in reproduction and parenthood. They argued that not everything should be controlled and felt that PGT-P, especially non-medical and broad screening, was going too far. With regards to the clinical implementation of PGT-P, participants in general preferred PGT-P to be limited to people with a serious polygenic family history and wanted embryo selection decisions to be made by healthcare professionals. CONCLUSIONS: This study shows that individuals with experience of PGT-M/SR saw PGT-P as different from PGT-M/SR. They had various ethical concerns with regards to PGT-P, especially regarding broadly offering PGT-P. These stakeholder viewpoints need to be considered regarding potential PGT-P implementation and guidelines.

Mapping ethical, legal, and social implications (ELSI) of preimplantation genetic testing (PGT).

PURPOSE: Preimplantation Genetic Testing (PGT) has attracted considerable ethical, legal, and social scrutiny, but academic debate often fails to reflect clinical realities. METHODS: Addressing this disconnect, a review of 506 articles from 1999 to 2019 across humanities and social sciences was conducted to synthesize the Ethical, Legal, and Social Implications (ELSI) of PGT. This review mined PubMed, WoS, and Scopus databases, using both MeSH terms and keywords to map out the research terrain. RESULTS: The findings reveal a tenfold increase in global research output on PGT's ELSI from 1999 to 2019, signifying rising interest and concern. Despite heightened theoretical discourse on selecting "optimal" offspring, such practices were scarcely reported in clinical environments. Conversely, critical issues like PGT funding and familial impacts remain underexplored. Notably, 86% of the ELSI literature originates from just 12 countries, pointing to a research concentration. CONCLUSION: This review underscores an urgent need for ELSI research to align more closely with clinical practice, promoting collaborations among ethicists, clinicians, policymakers, and economists. Such efforts are essential for grounding debates in practical relevance, ultimately steering PGT towards ethical integrity, societal acceptance, and equitable access, aiming to harmonize PGT research with real-world clinical concerns, enhancing the relevance and impact of future ethical discussions.

Polygenic embryo screening: quo vadis?

Recently, the use of polygenic risk scores in embryo screening (PGT-P) has been introduced on the premise of reducing polygenic disease risk through embryo selection. However, it has been met with extensive critique: considered "technology-driven" rather than "evidence-based", concerns exist about its validity, utility, ethics, and societal effects. Its scientific foundations and criticisms thus need to be carefully considered. However, seeing as PGT-P is already offered in some settings, further questions need to be addressed, in order to give due diligence to various aspects of PGT-P. By examining the complexities of clinical introduction of PGT-P, we discuss whether PGT-P could be responsibly implemented in the first place, what elements need to be addressed if PGT-P is clinically implemented, and subsequently how counselling and decision-making of its users could be envisaged. By dissecting these elements, we provide an overview of important practical questions of PGT-P and emphasize elements of PGT-P that we think have yet to be given sufficient attention. These questions and elements are for example related to the potential target group, scope, and decision-making possibilities of PGT-P. The aspects we raise are crucial to consider by the scientific community and policy makers for the development of guidelines and/or an ethical framework for PGT-P.

A critical view on using "life not worth living" in the bioethics of assisted reproduction.

This paper critically engages with how life not worth living (LNWL) and cognate concepts are used in the field of beginning-of-life bioethics as the basis of arguments for morally requiring the application of preimplantation genetic diagnosis (PGD) and/or germline genome editing (GGE). It is argued that an objective conceptualization of LNWL is largely too unreliable in beginning-of-life cases for deriving decisive normative reasons that would constitute a moral duty on the part of intending parents. Subjective frameworks are found to be more suitable to determine LNWL, but they are not accessible in beginning-of-life cases because there is no subject yet. Conceptual and sociopolitical problems are additionally pointed out regarding the common usage of clear case exemplars. The paper concludes that a moral requirement for the usage of PGD and GGE cannot be derived from the conceptual base of LNWL, as strong reasons that can be reliably determined are required to limit reproductive freedom on moral grounds. Educated predictions on prospective well-being might still be useful regarding the determination of moral permissibility of PGD and/or GGE. It is suggested that due to the high significance of subjective experience in the normativity of beginning-of-life bioethics, the discipline is called to more actively realize the inclusion of people with disabilities. This regards for instance research design, citation practices, and language choices to increase the accessibility of societal debates on the reproductive ethics of genetic technologies.

[Ethical Reflections on Preimplantation Genetic Diagnoses].

With fertility rates at an all-time low, children have become even more the 'treasures' of their families. Progress in genetic selection technology has made preimplantation genetic diagnosis an increasingly common practice in clinics. However, the practice of purposively selecting genes for future children remains controversial. In this article, the process of preimplantation genetic diagnosis is introduced and related philosophical and social perspectives are reviewed. Finally, the ethics related to this practice are discussed in the contexts of obligation theory, utility theory, and four ethical principles. The authors hope this article sheds light on the diverse perspectives used to consider and discuss the ethical issues surrounding gene selection and, importantly, helps nurses provide care grounded in ethics and humanity in ethically uncertain circumstances.

Heritable human genome editing: correction, selection and treatment.

Heritable human genome editing (HHGE) to correct a nuclear gene sequence that would result in a serious genetic condition in a future child is presented as 'treatment' in various ethics and policy materials, and as morally preferable to the 'selection' practice of preimplantation genetic testing (PGT), which is subject to the disability critique. However, whether HHGE is 'treatment' for a future child, or another form of 'selection', or whether HHGE instead 'treats' prospective parents, are now central questions in the debate regarding its possible legalisation. This article argues that the idea of 'treatment' for a future child is largely a proxy for 'seriousness of purpose', intended to distinguish HHGE to avoid serious genetic conditions from less obviously justifiable uses; that HHGE is best understood, and morally justified, as a form of 'treatment' for prospective parents who strongly desire an unaffected genetically related child and who have no, or poor, options to achieve this; that HHGE would be morally permissible if consistent with that child's welfare; that legalisation is supportable with reference to the right to respect for private and family life under Article 8 of the European Convention on Human Rights; and that HHGE is morally distinguishable from PGT.

Who's Afraid of the Big Bad (Germline Editing) Wolf?

Germline genome editing has garnered dire predictions about its societal effects, but experience with other reproductive technologies should caution us about making extravagant claims. Amniocentesis was predicted to result in increased stigmatization of people born with Down syndrome, but in fact people with these conditions have been increasingly integrated into schools and workplaces. Artificial insemination by donor was predicted to result in women choosing to "optimize" their children, but in fact most women eschewed the offerings of the so-called "genius sperm bank," and when choosing among donors, have tended to look for those who most resemble their husbands and partners. IVF was predicted to cause parents to view children as commodities, but no such change has been evidenced. Preimplantation genetic diagnosis was predicted to become widespread and used for an ever-increasing range of conditions, including those unrelated to serious disease or shortened life span, but this has not happened either. Critics of germline genome editing have argued that even if it were safe and effective, it would inevitably be abused by prospective parents who wish to improve upon what is already predicted to be a healthy outcome, and that this practice would become sufficiently widespread among those able to afford it that we would be creating a new genetic caste system. Before developing policy around such predictions, it is important to learn from the past.

Drugs, genes and screens: The ethics of preventing and treating spinal muscular atrophy.

Spinal muscular atrophy (SMA) is the most common genetic disease that causes infant mortality. Its treatment and prevention represent the paradigmatic example of the ethical dilemmas of 21st-century medicine. New therapies (nusinersen and AVXS-101) hold the promise of being able to treat, but not cure, the condition. Alternatively, genomic analysis could identify carriers, and carriers could be offered in vitro fertilization and preimplantation genetic diagnosis. In the future, gene editing could prevent the condition at the embryonic stage. How should these different options be evaluated and compared within a health system? In this paper, we discuss the ethical considerations that bear on the question of how to prioritize the different treatments and preventive options for SMA, at a policy level. We argue that despite the tremendous value of what we call 'ex-post' approaches to treating SMA (such as using pharmacological agents or gene therapy), there is a moral imperative to pursue 'ex-ante' interventions (such as carrier screening in combination with prenatal testing and preimplantation genetic diagnosis, or gene editing) to reduce the incidence of SMA. There are moral reasons relating to autonomy, beneficence and justice to prioritize ex-ante methods over ex-post methods.

When pregnancy is a research risk.

A published study reported by Munné using uterine lavage to retrieve in vivo blastocysts for preimplantation genetic testing has been the subject of several technical and ethical critiques. None of these critiques has been based on a review of the study's IRB-approved informed consent. This commentary seeks to do that, examining the Munné (and related Nadal) consent forms for their conformity to existing requirements for a full and informed consent.

Medical research and reproductive medicine in an ethical context: a critical commentary on the paper dealing with uterine lavage published by Munné et al.

A recent study published in Human Reproduction claimed that uterine lavage offers a non-surgical, minimally invasive strategy for the recovery of human embryos from fertile women who do not want or need IVF for medical reasons but who desire preimplantation genetic testing (PGT) for embryos. To prove this hypothesis, the researchers recruited dozens of young Mexican women. The prospective oocyte donors underwent ovarian stimulation to induce the production of multiple mature oocytes. Subsequently, these women were inseminated by donor semen. A few days later, the developing embryos were collected by uterine lavage (uterine flushing) and subjected to genetic testing for aneuploidies (PGT-A). Oocyte donors with persistently elevated hCG levels, indicating the implantation of one or more embryos after uterine lavage, had to undergo uterine curettage and/or treatment with methotrexate. A critical opinion paper discussing the aforementioned study was published by De Santis and colleagues and has raised critical issues that are largely technical in nature. However, this opinion paper neglects-from our point of view-critical issues of the Mexican study regarding ethical principles and moral standards in human research. These aspects are summarized below.

Is it ever morally permissible to select for deafness in one's 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.

Assessment of pre-implantation genetic testing for embryo aneuploidies: A SWOT analysis.

The recently re-named pre-implantation genetic testing for determining embryo aneuploidies (PGT-A) is presently very popular although its acceptance by the scientific community is controversial. This approach still encounters drawbacks. This paper uses a SWOT (strengths, weaknesses, opportunities and threats) analysis to discuss salient points to be considered when examining the pre-implantation genetic testing (PGT-A) strategy to gather information from a range of perspectives. One of the strengths associated with the procedure is represented by an increase in implantation rate although data from the highest level of evidence do not support an increase in cumulative pregnancy rates. The current difficulty in the management of mosaicisms represents a weakness of PGT-A. The application of the strategy represents an opportunity to favor the single embryo transfer while other advantages, such as reduction of time to pregnancy and emotional distress are controversial. Potential important threats, at present still undefined, are represented by the biopsy-related damage to the blastocyst and the impact on neonatal and long-term outcomes.

Preimplantation genetic testing for more than one genetic condition: clinical and ethical considerations and dilemmas.

STUDY QUESTION: Which clinical and ethical aspects of preimplantation genetic testing for monogenic disorders or structural rearrangements (PGT-M, PGT-SR) should be considered when accepting requests and counselling couples for PGT when applied for more than one condition (combination-PGT; cPGT-M/SR)? SUMMARY ANSWER: cPGT is a feasible extension of the practice of PGT-M/SR that may require adapting the criteria many countries have in place with regard to indications-setting for PGT-M/SR, while leading to complex choices that require timely counselling and information. WHAT IS KNOWN ALREADY: Although PGT-M/SR is usually performed to prevent transmission of one disorder, requests for PGT-M/SR for more than one condition (cPGT-M/SR) are becoming less exceptional. However, knowledge about implications for a responsible application of such treatments is lacking. STUDY DESIGN, SIZE, DURATION: Retrospective review of all (40) PGT-M/SR applications concerning more than one genetic condition over the period 1995-2018 in the files of the Dutch national PGT centre. This comprises all relevant national data since the start of PGT in the Netherlands. PARTICIPANTS/MATERIALS, SETTING AND METHODS: Data regarding cPGT-M/SR cases were collected by means of reviewing medical files of couples applying for cPGT-M/SR. Ethical challenges arising with cPGT-M/SR were explored against the background of PGT-M/SR regulations in several European countries, as well as of relevant ESHRE-guidance regarding both indications-setting and transfer-decisions. MAIN RESULTS AND THE ROLE OF CHANCE: We report 40 couples applying for cPGT-M/SR of which 16 couples started their IVF treatment. Together they underwent 39 IVF cycles leading to the birth of five healthy children. Of the couples applying for cPGT, 45% differentiated between a primary and secondary condition in terms of perceived severity. In the light of an altered balance of benefits and drawbacks, we argue the 'high risk of a serious condition' standard that many countries uphold as governing indications-setting, should be lowered for secondary conditions in couples who already have an indication for PGT-M/SR. As a consequence of cPGT, professionals will more often be confronted with requests for transferring embryos known to be affected with a condition that they were tested for. In line with ESHRE guidance, such transfers may well be acceptable, on the condition of avoiding a high risk of a child with a seriously diminished quality of life. LIMITATIONS, REASONS FOR CAUTION: We are the first to give an overview of cPGT-M/SR treatments. Retrospective analysis was performed using national data, possibly not reflecting current trends worldwide. WIDER IMPLICATIONS OF THE FINDINGS: Our observations have led to recommendations for cPGT-M/SR that may add to centre policy making and to the formulation of professional guidelines. Given that the introduction of generic methods for genomic analysis in PGT will regularly yield incidental findings leading to transfer requests with these same challenges, the importance of our discussion exceeds the present discussion of cPGT. STUDY FUNDING/COMPETING INTEREST(S): The research for this publication was funded by the Dutch Organization for Health Research and Development (ZonMw), project number: 141111002 (Long term safety, quality and ethics of Preimplantation Genetic Diagnosis). None of the authors has any competing interests to declare.

Refining the ethics of preimplantation genetic diagnosis: A plea for contextualized proportionality.

Many European countries uphold a 'high risk of a serious condition' requirement for limiting the scope of preimplantation genetic diagnosis (PGD). This 'front door' rule should be loosened to account for forms of PGD with a divergent proportionality. This applies to both 'added PGD' (aPGD), as an add-on to in vitro fertilization (IVF), and 'combination PGD' (cPGD), for a secondary disorder in addition to the one for which the applicants have an accepted PGD indication. Thus loosening up at the front has implications at the back of PGD treatment, where a further PGD rule says that 'affected embryos' (in the sense of embryos with the targeted mutation or abnormality) should not be transferred to the womb. This 'back door' rule should be loosened to allow for transferring 'last chance' affected embryos in aPGD and cPGD cases, provided this does not entail a high risk that the child will have a seriously diminished quality of life.

Is selecting better than modifying? An investigation of arguments against germline gene editing as compared to preimplantation genetic diagnosis.

BACKGROUND: Recent scientific advances in the field of gene editing have led to a renewed discussion on the moral acceptability of human germline modifications. Gene editing methods can be used on human embryos and gametes in order to change DNA sequences that are associated with diseases. Modifying the human germline, however, is currently illegal in many countries but has been suggested as a 'last resort' option in some reports. In contrast, preimplantation genetic (PGD) diagnosis is now a well-established practice within reproductive medicine. Both methods can be used to prevent children from being born with severe genetic diseases. MAIN TEXT: This paper focuses on four moral concerns raised in the debate about germline gene editing (GGE) and applies them to the practice of PGD for comparison: Violation of human dignity, disrespect of the autonomy and the physical integrity of the future child, discrimination of people living with a disability and the fear of slippery slope towards immoral usage of the technology, e.g. designing children for specific third party interests. Our analysis did not reveal any fundamental differences with regard to the four concerns. CONCLUSION: We argue that with regard to the four arguments analyzed in this paper germline gene editing should be considered morally (at least) as acceptable as the selection of genomes on the basis of PGD. However, we also argue that any application of GGE in reproductive medicine should be put on hold until thorough and comprehensive laws have been implemented to prevent the abuse of GGE for non-medical enhancement.

Reprogenetics, reproductive risks and cultural awareness: what may we learn from Israeli and Croatian medical students?

BACKGROUND: Past studies emphasized the possible cultural influence on attitudes regarding reprogenetics and reproductive risks among medical students who are taken to be "future physicians." These studies were crafted in order to enhance the knowledge and expand the boundaries of cultural competence. Yet such studies were focused on MS from relatively marginalized cultures, namely either from non-Western developing countries or minority groups in developed countries. The current study sheds light on possible cultural influences of the dominant culture on medical students in two developed countries, potentially with different dominant cultures regarding reprogenetics and reproductive risks: Israel and Croatia. METHODS: Quantitative-statistical analyses were employed, based on anonymous questionnaires completed by 150 first year medical students in Israel and Croatia. The questionnaires pertained to the knowledge and attitudes regarding genetics, reproduction and reproductive risks. These questionnaires were completed before the students were engaged in learning about these topics as part of the curriculum in their medical school. RESULTS: Substantial differences were revealed between the two groups of medical students. Israeli medical students were less tolerant regarding reproductive risks and more knowledgeable about genetics and reproductive risks than Croatian medical students. For example, while nearly all Israeli medical students (96%) disagreed with the idea that "Screening for reproductive risks in prospective parents is wrong," less than 40% of their Croatian counterparts shared a similar stance. Similarly, all (100%) Israeli medical students correctly observed that "A carrier of a recessive genetic disease actually has the disease" was wrong, as opposed to only 82% of Croatian students. CONCLUSIONS: By linking applicable theoretical literature to these findings, we suggest that they may reflect the hidden influence of the dominant culture in each country, disguised as part of the "culture of medicine." Acknowledging and learning about such influence of the dominant culture, may be an important addition to the training of medical students in cultural competence, and specifically their cultural awareness. Such an acknowledgement may also pave the road to drawing the attention of existing physicians regarding a less known yet an important aspect of their cultural competence, insofar as the cultural awareness component is concerned.

[Preimplantation genetic testing: legal and ethical aspects in clinical practice]. / Tests génétiques préimplantatoires†: enjeux légaux et éthiques dans la pratique clinique.

In Switzerland, since modifications of the law regulating reproductive medicine introduced the 1rst of September 2017, preimplantation genetic testing (PGT) has been legalised. Infertile couples undergoing in vitro fertilization (IVF) can benefit from this technology by detecting which embryos are aneuploid (ie abnormal number of chromosomes, PGT-A). This is performed in order to transfer euploid embryos (normal number of chromosomes) and to optimise success, though data are limited. Couples at risk of transmitting a severe monogenic disease or unbalanced translocation can undergo PGT for monogenic disease or chromosomal structural rearrangements (PGT-M/SR). These tests are subject to strict legal criteria. Their clinical application needs to be approved through a multidisciplinary approach taking into account legal and ethical issues while respecting the autonomy of the couples.

Depuis le 1er septembre 2017, les tests génétiques préimplantatoires (PGT) sont autorisés en Suisse suite aux modifications de la loi sur la procréation médicalement assistée (LPMA). Les couples infertiles qui effectuent une fécondation in vitro (FIV) peuvent bénéficier d'un PGT des aneuploïdies (PGT-A) dans le but de transférer des embryons euploïdes (nombre normal de chromosomes) et ainsi optimiser leurs chances de succès, sous réserve de données encore limitées. Les couples à risque de transmettre une maladie monogénique grave ou une translocation déséquilibrée peuvent avoir recours au PGT d'une anomalie d'un gène unique ou d'une anomalie de structure de chromosome (PGT-M/SR), dans les limites d'un cadre légal strict. Leur mise en pratique doit être décidée de manière pluridisciplinaire en tenant compte des enjeux légaux et éthiques dans le respect de l'autonomie des couples.

Review of patient decision-making factors and attitudes regarding preimplantation genetic diagnosis.

The increasing technical complexity and evolving options for repro-genetic testing have direct implications for information processing and decision making, yet the research among patients considering preimplantation genetic diagnosis (PGD) is narrowly focused. This review synthesizes the literature regarding patient PGD decision-making factors, and illuminates gaps for future research and clinical translation. Twenty-five articles met the inclusion criteria for evaluating experiences and attitudes of patients directly involved in PGD as an intervention or considering using PGD. Thirteen reports were focused exclusively on a specific disease or condition. Five themes emerged: (1) patients motivated by prospects of a healthy, genetic-variant-free child, (2) PGD requires a commitment of time, money, energy and emotions, (3) patients concerned about logistics and ethics of discarding embryos, (4) some patients feel sense of responsibility to use available technologies, and (5) PGD decisions are complex for individuals and couples. Patient research on PGD decision-making processes has very infrequently used validated instruments, and the data collected through both quantitative and qualitative designs have been inconsistent. Future research for improving clinical counseling is needed to fill many gaps remaining in the literature regarding this decision-making process, and suggestions are offered.

Challenges, Dilemmas and Factors Involved in PGD Decision-Making: Providers' and Patients' Views, Experiences and Decisions.

Providers and patients are considering and pursuing PGD for ever-more conditions, but questions arise concerning how they make, view and experience these decisions, and what challenges they may face. Thirty-seven in-depth semi-structured interviews were conducted (with 27 IVF providers and 10 patients). Patients and providers struggled with challenges and dilemmas about whether to pursue PGD in specific cases, and how to decide. Respondents varied in how they viewed, experienced and made these choices, and for which conditions to pursue PGD (from lethal, childhood-onset conditions to milder, treatable, or adult-onset disorders). Several factors were involved, including differences in gene penetrance, predictability, and phenotypic expression, and disease severity, age of onset, treatability, stigma and degree of disability. Providers and patients face questions regarding possibilities of screening for more than one condition in one set of embryos, and limitations of PGD (e.g., inaccurate results). Characteristics of providers (e.g., amount of PGD experience, understandings of genetics, and use of genetic counselors), and of patients (e.g., related to broader moral and social attitudes) can also affect these decisions. These data, the first to examine several key questions concerning PGD, suggest that providers and patients confront several dilemmas. These findings have critical implications for future practice, guidelines, education and research.