Drawing Lines: How the Public Defines 'Serious' Genetic Conditions for Reproductive Testing

Drawing Lines: How the Public Defines 'Serious' Genetic Conditions for Reproductive Testing | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Drawing Lines: How the Public Defines 'Serious' Genetic Conditions for Reproductive Testing Shizuko Takahashi, Rie Iizuka, Serene Ong, Lan Tianxiang, Tsutomu Sawai This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8793263/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 11 You are reading this latest preprint version Abstract Prior normative and empirical research has identified a gap between how patients and the public conceptualise “serious” conditions eligible for preimplantation genetic testing for monogenic disorders (PGT-M) and how seriousness is defined. Japan represents a highly restrictive regulatory context shaped by its historical experience with eugenics. Although PGT-M has been available since 1998, its use has been tightly limited, with the first birth occurring six years later and approximately 36 conditions approved to date. This study examines how Japanese adults of reproductive age understand “seriousness” in genetic disease and how they view PGT-M in relation to concerns about eugenic selection ( inochi no senbetsu , “sorting of lives”). We conducted a cross-sectional online survey of 458 adults aged 18–42 years. Measures included perceived seriousness across four dimensions (penetrance, age of onset, survival impact, functional limitation), willingness to use PGT-M, perceived barriers to access, and attitudes toward eugenic selection. Awareness of PGT-M was low (12%), yet 44% of respondents would consider its use. Participants defined seriousness more broadly than current Japanese policy permits: most rated highly penetrant or childhood-lethal conditions as serious, and over half also included conditions associated with mild to moderate functional limitations. Respondents distinguished disease prevention from enhancement. Economic burden was the most frequently cited barrier (70%). Many respondents who expressed ethical discomfort with eugenic selection nonetheless reported willingness to consider PGT-M. These findings reveal a substantial gap between policy, public reasoning, and reproductive preferences, with implications for European debates on seriousness and proportionality in reproductive genetic testing. Scientific community and society/Social sciences/Ethics Scientific community and society/Social sciences/Psychology/Human behaviour preimplantation genetic testing disease seriousness reproductive autonomy disability rights Japan inochi no senbetsu Figures Figure 1 Figure 2 INTRODUCTION Reviews on global regulations for preimplantation genetic testing (PGT) show a fragmented regulatory landscape that ranging from strict, state-governed oversight in many European jurisdictions to more permissive, professionally led frameworks in the United States. Ethical debates center on the tension between reproductive autonomy and concerns about potential eugenic applications. Germany, Switzerland, and Austria—once identified as among the most prohibitive jurisdictions—have since enacted legislation permitting PGT under stringent conditions. 1 Central to regulatory debate in restrictive contexts is the question of what constitutes a “serious” genetic condition and whether seriousness should be determined through fixed lists, case-by-case review, or professional discretion. Recent conceptual work by Kleiderman et. al (2025) in this journal argues that seriousness is not a technical threshold but a normative and procedural judgment, shaped by context, institutional aims, and whose perspectives are included in deliberation. 2 Yet, despite growing recognition of the importance of patient and public involvement, these perspectives remain largely absent from policy-making. Historically, Japan has been criticized for its restrictive approach to preimplantation genetic testing (PGT) and undermining reproductive autonomy. 3 PGT is an umbrella term encompassing several applications; PGT for monogenic conditions (PGT-M) is central to the bioethical debate and is the focus of this paper. This restrictive stance was exemplified in 2018, when the Japan Society of Obstetrics and Gynecology (JSOG) ethics committee denied approval for PGT-M for retinoblastoma—a childhood eye cancer with 95% survival when treated but requiring enucleation, chemotherapy, and extensive follow-up care. 4 The committee ruled the condition as ‘not sufficiently serious’ because it was treatable and not fatal. 5 The mother faced a paradoxical dilemma: treatment success became grounds for denying prevention. This case exemplifies Japan's highly restrictive criteria, having approved only approximately 36 conditions to date. 6 Central to this restrictiveness is inochi no senbetsu , an ethically charged phrase meaning 'sorting life.' In Japanese discourse, senbetsu (選別) implies selection based on value criteria, carrying connotations of eugenic discrimination. 7 , 8 This linguistic framing has profound implications for bioethical debates, where PGT-M evokes concerns about value-based discrimination against people with disabilities. Subsequently, this case was appealed and approved under revised 2022 PGT-M approval policies. 9 This restrictiveness reflects Japan's unique historical context: while most countries abolished eugenic sterilization policies by the 1970s, Japan maintained its Eugenic Protection Law (優生保護法) until 1996. 10 , 5 The fresh memory of coercive eugenics means Japanese policymakers are highly sensitive around practices construed as selecting against disability while leaving unresolved whether conditions must significantly impair daily functioning, threaten survival before adulthood, or lack effective treatment to qualify for PGT-M. Japan's restrictive approach thus reflects ongoing tensions between preventing population-level eugenic practices and respecting individual reproductive autonomy. This ambiguity is not unique to Japan. Professional guidelines worldwide invoke seriousness as a criterion for PGT-M but rarely specify what constitutes serious conditions or who should decide. 8 Among genetic healthcare professionals, substantial discrepancy exists between clinical criteria and professional judgment. 11 Evidence from North America shows that approximately half of genetic healthcare professionals consider conditions serious that standard guidelines do not classify as such. 2 , 12 In Japan's framework, seriousness appears to center on mortality and severe early-onset disability, yet crucial questions remain underspecified, including the relevance of penetrance, age of onset, and degree of functional impairment. These unresolved questions have gained renewed attention with the expansion of PGT beyond monogenic conditions to polygenic conditions (PGT-P), which involve the assessment of probabilistic disease risk based on multiple genetic variants, where the boundaries of seriousness are even less clearly defined. Therefore, the question of which conditions should be considered ‘serious enough’ to justify PGT intensifies. This persistent divergence underscores that seriousness is not a purely clinical threshold but a contested normative judgment. Recent stakeholder data reveals growing discrepancy: 70% of genetic counselors, clinicians, researchers, and patients would consider PGT-M for conditions that current regulations decline. 13 This points to a widening policy-practice-preference gap warranting empirical investigation. Building on these unresolved questions about seriousness criteria, this study addresses: (1) What do Japanese adults of reproductive age consider sufficiently serious to warrant PGT-M? (2) How do attitudes toward inochi no senbetsu relate to views on PGT-M? (3) Is there a gap between public perceptions and current policy? METHODS Study Design and Participants We conducted a cross-sectional online survey of Japanese adults in September 2025. Eligible participants were Japanese nationals aged 18–42 years, corresponding to the age range covered for infertility treatment under Japan's national health insurance. Participants were recruited through Lancers ( www.lancers.jp ), a major Japanese crowdsourcing platform, and compensated 500 JPY for the 15-minute survey. The study was approved by the Research Ethics Review Board of the Graduate School of Humanities and Social Sciences, Hiroshima University (Approval No. HR-HUM-003154). All participants provided informed consent. Survey Development The survey instrument was developed by reviewing ethical, legal, and social implications (ELSI) literature on PGT-M and prenatal genetic testing, with particular attention to the framework made by Kleiderman et. al (2025), international debates on disease seriousness criteria, reproductive autonomy, and disability rights. 2 , 14 Drawing on this review—as well as our previous stakeholder research of healthcare providers (ID: HR-HUM-002563), genetic counselors, researchers, and patients and conceptual analysis of reproductive genetic ethics. All scientific and medical information presented in the survey was reviewed and validated by two genetics experts and three bioethics scholars. The survey comprised: (1) introduction to PGT-M and Japan’s regulations, (2)demographics, (3) awareness and willingness to use PGT-M, (4) acceptable indications and barriers, (5) views on inochi no senbetsu , (6) perceptions of disease seriousness using clinical parameters (penetrance, survival, functioning), and (7) factors influencing seriousness perceptions (Provided in the Supplementary Information, Supplementary 1). Statistical Analysis Descriptive statistics were calculated for all variables. For Likert scale items, we dichotomized responses into substantial influence (somewhat large, very large) versus minimal influence (none, slight, moderate). Logistic regression was used to examine factors associated with willingness to use PGT-M, with demographic variables entered in Model 1 and attitudinal variables added in Model 2. Analyses were conducted in R (version 4.1.0), with p < 0.05. RESULTS Participant Characteristics A total of 458 individuals completed the survey (Supplemental Information); 50.4% were female, mean age 34.5 years. Nearly half (45.4%) were unmarried, and 89.3% had no prior experience with fertility treatment. Demographics are as shown in Table 1 . Table 1 Participant Demographics and Characteristics (N = 458) Characteristic n % Age 18–25 years 25 5.5 26–30 years 69 15.2 31–35 years 119 26.2 36–42 years 239 52.5 Prefer not to answer 3 0.7 Gender Identity Male 212 46.4 Female 236 51.6 Non-binary/third gender 4 0.9 Prefer not to answer 3 0.7 Has Children Yes 166 36.5 No 279 61.3 Prefer not to answer 10 2.2 Marital Status Married 197 43.3 Never married 209 45.9 Cohabiting with partner 24 5.3 Divorced/separated 19 4.2 Widowed 1 0.2 Prefer not to answer 5 1.1 Relationship to Genetic Disease Patient or family member 46 10.1 No relationship 376 82.6 Other 12 2.6 Prefer not to answer 21 4.6 History of Infertility Treatment Yes 33 7.2 No 412 90.5 Prefer not to answer 10 2.2 Educational Attainment Primary school 2 0.4 Secondary school 45 9.9 Vocational/technical school 120 26.4 Some university 8 1.8 Bachelor's degree 234 51.4 Graduate/professional degree 34 7.5 Prefer not to answer 12 2.6 Employment Status Full-time 245 53.8 Part-time 77 16.9 Homemaker 33 7.2 Unemployed, seeking work 26 5.7 Student 8 1.8 Other 58 12.7 Prefer not to answer 8 1.8 Religious Affiliation None 290 63.7 Buddhism 114 25.1 Shinto 13 2.9 Christianity 11 2.4 Other 7 1.5 Prefer not to answer 20 4.4 Prior Knowledge of PGT-M Yes 57 12.4 No 407 87.6 Willingness to Use PGT-M Prior awareness of PGT-M was strikingly low (12.4%) despite steady increases in the use of in vitro fertilization (IVF) use in Japan. 16 Patient or family members with a genetic condition were more aware of PGT-M than all others (OR:2.48, 95%CI 1.18–5.22, p = 0.031). However, once informed about PGT-M, interest emerged: 44.3% expressed willingness to use it (7.4% ‘very much,’ 36.9% ‘somewhat’), 28.2% were neutral, 28.8% expressed negative views. This pattern-low awareness but notable openness once informed-suggests latent demand exceeding what restrictive policies assume. Notably, those with prior awareness were twice as willing to undergo testing (OR 2.26 CI 1.28-4.00 p = 0.00064). Details are available in Supplemental Table 1. Willingness to use PGT-M was associated with both demographic and attitudinal factors (Table 2 ). Among demographic variables, those without fertility treatment history were significantly less willing than those with such history (OR = 0.33, 95% CI 0.14–0.77, p = 0.010), suggesting that direct experience with reproductive medicine increases openness to genetic testing options. Table 2 Factors Associated with Willingness to Use PGT-M (N = 458) Variable Comparison OR (95% CI) p-value Sig. Demographic Factors Gender Female vs. Male (ref.) 0.67 (0.44–1.04) 0.070 NS Fertility treatment history No treatment vs. Had treatment (ref.) 0.33 (0.14–0.77) 0.010 * Employment status Student vs. Full-time (ref.) 9.66 (2.09–44.63) 0.004 ** Other demographics Age, children, marital status, education, religion - > 0.05 NS Attitudes toward Inochi no Senbetsu 'Unfair treatment of lives' Endorsed vs. Did not endorse (ref.) 0.57 (0.35–0.93) 0.023 * 'Ethically problematic' Endorsed vs. Did not endorse (ref.) 1.63 (1.14–2.32) 0.007 ** 'Inevitable due to science' Endorsed vs. Did not endorse (ref.) 1.72 (1.15–2.56) 0.007 ** Other attitudes 'Ranking lives,' 'Personal issue,' 'No impression' - > 0.05 NS Note: OR = odds ratio; CI = confidence interval; NS = not significant; ref. = reference group. *p < 0.05; **p < 0.01. Model includes both demographic and attitudinal variables. The most striking findings emerged from attitudinal variables. Participants who endorsed the view that inochi no senbetsu is 'ethically problematic' were significantly more likely to express willingness to use PGT-M (OR = 1.63, 95% CI 1.14–2.32, p = 0.007). Similarly, those who viewed embryo selection as 'inevitable due to scientific advancement' showed higher willingness (OR = 1.72, 95% CI 1.15–2.56, p = 0.007). In contrast, those who endorsed the view that embryo selection represents 'unfair treatment of lives' were less willing (OR = 0.57, 95% CI 0.35–0.93, p = 0.023). Defining Seriousness: A Broader Threshold Than Policy Permits (Fig. ) Disease Penetrance . When asked about the probability threshold at which a genetic condition becomes serious enough for PGT-M, the plurality of participants (57.4%) selected 50–74% penetrance—meaning the condition would develop in half to three-quarters of carriers. This represents moderate rather than high penetrance. An additional 25.8% selected even lower penetrance (25–49%), with only 12.7% requiring near-certain penetrance (75–100%) and 4.1% setting their threshold at minimal risk (0–24%). The modal response of 50–74% penetrance is notably lower than what current Japanese policy implicitly requires, which focuses predominantly on high-penetrance conditions. 15 Age of Survival . Regarding life-limiting conditions, the plurality of participants (47.6%) considered conditions restricting survival to school age through adolescence (6–20 years) as serious enough for PGT-M. Another 3.2% selected early childhood (1–5 years), and 9.4% selected infancy (0–1 year). Notably, 14.2% extended their threshold to early adulthood (21–40 years), indicating willingness to consider conditions that permit survival into adulthood but with limited lifespan. Only .7% selected thresholds of middle age or beyond. This distribution reveals that most participants do not require neonatal or infant lethality to consider a condition serious; survival through childhood or adolescence is sufficient for nearly half the sample. Daily Life Impact . For non-life-threatening conditions affecting daily functioning, 44.2% participants considered moderate impact (clear activity limitations with preserved independence) serious enough to justify PGT-M, while 42.7% selected severe impact (impaired independence requiring some assistance). Relatively few participants required either no impact (2.4%) or only mild impact (8.3%) as their threshold, and equally few required very severe impact (2.6%). The dominance of moderate and severe thresholds suggests that participants do not require complete loss of independence to consider a condition serious—significant quality of life impacts appear sufficient. These findings reveal that the public's conception of seriousness is considerably broader than current regulatory practice in Japan. 17 The plurality defines seriousness as moderate penetrance, survival limited to school age or adolescence, and moderate functional impairment—contrasting markedly with JSOG's emphasis on high-penetrance conditions with early onset and severe disability or lethality. How Social Context Shapes Perceptions of Seriousness Participants' ratings revealed that seriousness revealed is substantially shaped by social and structural context (Table 3 ). Among experiential factors rated as having substantial influence daily life impact ranked highest (84.0%), followed by economic burden (77.5%), physical burden (74.0%), appearance changes (72.5%), psychological burden (70.2%), and discrimination (62.6%). Table 3 Factors Influencing Disease Seriousness Perceptions (N = 458) Factor Minimal n (%) Substantial n (%) Experiential Factors Daily life impact (work, family, hobbies) 74 (16.2) 384 (84.0) Economic burden (treatment costs) 103 (22.5) 355 (77.5) Physical burden (pain, fatigue) 119 (26.0) 339 (74.0) Appearance changes 126 (27.5) 332 (72.5) Psychological burden 137 (29.9) 321 (70.2) Discrimination and stigma 172 (37.6) 286 (62.6) Support Factors (Influence when inadequate) Economic support (insurance, subsidies) 73 (15.9) 385 (84.1) Access to medical care 83 (18.1) 375 (81.8) Educational and employment support 109 (23.8) 349 (76.2) Psychological support 115 (25.1) 343 (74.8) Assistive technology 143 (31.2) 315 (68.8) Note: Minimal influence = none + slight + moderate; Substantial influence = somewhat large + very large. Critically, participants indicated that lack of adequate support systems substantially influences seriousness perceptions. Economic support showed the highest influence (84.1%), followed by access to medical care (81.8%), educational and employment support (76.2%), psychological support (74.8%), social connections (70.1%), and assistive technology (68.8%). These findings suggest that the same condition might be perceived as more or less serious depending on whether robust social infrastructure exists to support affected individuals. Attitudes with PGT-M: Purposes, Boundaries and Inochi no Senbetsu For personal use, preventing disease (65.5%), preventing disability (75.5%), and having healthy children (69.7%) were most commonly endorsed. Enhancement purposes received minimal support: high-ability children (6.6%), or children with similar characteristics to parents (4.8%). When considering acceptable uses by others, similar patterns emerged with slightly higher acceptance, suggesting a distinction between personal choice and permissibility for others. A slight majority (53.2%) believed that PGT-M availability would encourage people with genetic conditions and their families to pursue marriage, pregnancy, and childbirth more actively—challenging assumptions that PGT-M primarily represents eugenic selection. Regarding specific genetic predispositions acceptable to test, participants endorsed a wide range of serious conditions: early-onset mental/intellectual disability (76.9%), visual impairment (76.2%), physical disabilities (73.0%), hearing impairment (69.9%), cancer predisposition (66.6%), and developmental disorders (61.8%) all received majority support. However, support declined notably for later-onset conditions: dementia (38.6%), psychiatric conditions (34.5%), and metabolic disorders (29.5%). Intelligence enhancement received very low support (7.2%), with only 3.9% indicating they would not test for any predisposition. Most participants (72.3%) reported awareness of inochi no senbetsu . When asked about impressions, 58.5% associated it with prioritizing lives, 41.2% viewed it as ethically problematic, 27.5% considered it inevitable due to medical progress, and 25.7% believed it should be a private decision. Notably, 38.0% reported feeling guilt about selecting children through PGT-M-reflecting how this discourse has shaped emotional responses to reproductive genetic testing. Critically, participants were divided on whether PGT-M constitutes inochi no senbetsu . For selecting embryos without genetic abnormalities-the core function of PGT-M-only 36.9% agreed this represents inochi no senbetsu (sorting lives), while 47.2% disagreed. This proportion is comparable to attitudes toward morphology-based embryo selection (32.3% agreed), a widely practiced procedure in assisted reproduction. Participants appear to understand PGT-M as preventing suffering rather than devaluing existing lives, while maintaining clear boundaries against enhancement (Fig. 2 ). Barriers to Access: Economics Over Ethics Economic burden was the dominant barrier to PGT-M use (70.3%), followed by concern about differing values with partners (48.5%) and guilt about selecting children (38.0%). Ethical and social concerns, while present, were secondary to practical economic constraints. Other barriers included social pressure against use (18.8%), concerns about violating children's right not to know genetic information (17.9%), and social pressure to use PGT-M (8.7%). Only 2.8% indicated no particular barriers. For preferred funding, participants were divided equally between insurance coverage (33.6%) and government subsidies (33.6%), with only 22.7% supporting full private payment. Details are shown in Supplemental Table 2. DISCUSSION This study provides the first empirical evidence of how Japanese adults of reproductive age conceptualize disease seriousness for PGT-M. Five key findings emerge with implications for policy reform. Public Thresholds Exceed Regulatory Thresholds The public threshold for justifying PGT-M is lower than that in Japan's current regulatory framework. Three anchors illustrate this complexity. First, 57.4% of respondents define 'serious' as having a penetrance of 50–74%, indicating that a substantial-though not near-certain-risk is sufficient for PGT-M. Second, whereas JSOG-approved cases have historically focused almost exclusively on neonatal or early-childhood lethal conditions, about half of the respondents considered survival only to school age/adolescence to be serious. Third, 44.2% regard moderate functional limitation as serious (reduced capacity with maintained independence), indicating that quality-of-life concerns are not confined to catastrophic disability. These indicate a clear gap between regulatory practice and public judgments of seriousness, with important implications for the scope of conditions considered eligible for PGT-M. Together, the public thresholds would encompass categories largely excluded by the current JSOG list: hereditary cancer predispositions, adult-onset neurodegenerative conditions, and moderately impairing disabilities with near-normal lifespan. The retinoblastoma case exemplifies this misalignment: a childhood cancer requiring lifelong surveillance and extensive treatment is judged serious by the public but was initially denied by regulators. Our findings indicate that Japan's framework reflects neither public nor professional views. 13 The Social Construction of Seriousness Researchers in disability studies argue that disability is predominantly a social construct rather than a medical condition, framing it as a human rights issue. 18 How impairments are experienced depends heavily on material and social resources, a view that has informed efforts to identify structural factors contributing to the marginalization of people with disabilities. 2 Our findings align with this social model: 84.1% said economic support and 81.8% said access to medical care influence whether a condition counts as 'serious.' Japan's restrictive policy posits that limiting PGT-M safeguards against discrimination, yet our findings imply inadequate support systems intensify perceived seriousness and heighten demand for preventive measures. Supporting informed reproductive choices while enhancing support systems can be complementary goals. Deliberating Under Moral Ambivalence Without Rejecting PGT-M Our findings indicate that ethical discomfort with inochi no senbetsu —an abstract concern frequently invoked in Japanese bioethical discourse—does not translate straightforwardly into rejection of PGT-M. Participants who perceived PGT-M as ethically problematic were more willing to use the technology (OR = 1.63, p = 0.007). This paradox suggests that restrictive policy framing—which emphasizes the ethical gravity of embryo selection—does not suppress demand but rather induces guilt while leaving underlying reproductive motivations intact. Individuals appear capable of holding moral reservations while simultaneously recognizing personal circumstances where they might consider using the technology. The 38% who reported feeling guilty about PGT-M despite its therapeutic intent illustrates how this discourse shapes emotional experience without necessarily changing behavior. Furthermore, many individuals perceive PGT-M as expanding reproductive possibilities rather than as a mechanism of exclusion. A majority (53.2%) believed that PGT-M availability would encourage individuals with genetic conditions and their families to pursue marriage, pregnancy, and childbirth more actively. This perception challenges the prevailing tendency in Japan to associate PGT-M primarily with eugenic selection. Public Reasoning Beyond Inochi no Senbetsu Japan's reflection on its eugenic history has led to stringent regulations. In our study, awareness of inochi no senbetsu was high (72.3%) and 41.2% expressed ethical concerns, resulting in feelings of guilt among 38% of respondents, despite its therapeutic intent. However, our findings reveal that the public draws more nuanced distinctions than this discourse suggests. Although the abstract notion of inochi no senbetsu evokes negative connotations for many participants, most do not view genetic embryo selection as actually constituting inochi no senbetsu (sorting lives)— a view comparable to attitudes toward the widely-practiced morphology-based embryo selection (32.3% agreed). This suggests conceptual boundaries that distinguish PGT-M from practices more readily condemned under this framework, such as selective abortion following prenatal diagnosis. Participants appear to understand PGT-M as preventing suffering rather than devaluing existing lives, while maintaining clear boundaries against enhancement (Fig. 2 ). Participants demonstrated clear boundaries regarding acceptable purposes. Therapeutic uses—preventing disease or disability—were widely supported (71–80%), whereas enhancement received minimal endorsement (6–10%). Notably, participants expressed greater acceptance of others using PGT-M than of using it themselves, reflecting fundamental respect for reproductive autonomy. These findings suggest citizens advocate neither unrestricted selection nor outright prohibition, but rather a deliberative space where reproductive decisions can be made responsibly while preventing discriminatory effects through robust social support. The Economic Burden as a Matter of Reproductive Justice Our findings suggest the primary issue with Japan's current PGT-M system is economic rather than ethical. Economic barriers (70.3%) highlight how structural factors limit reproductive autonomy. Japan's classification of PGT-M as investigational results in costs exceeding 1,000,000 JPY (approximately 7,000–9,000 USD) per cycle not covered by national health insurance. 17 This creates significant disparities, rendering PGT-M accessible only to those with substantial financial resources. Participants recognized this and expressed support from medical insurance (33.6%) and government subsidy programs (33.6%). This economic barrier may paradoxically intensify guilt: those who might benefit most face both financial exclusion and moral burden from restrictive discourse. Comparative Context and Policy Implications Our findings align with existing research: a U.S. study showed growing endorsement for conditions with reduced penetrance based on patients' evaluations of utility for family planning. 19 The importance of incorporating patients' perceptions of disease seriousness is increasingly recognized among healthcare professionals. 11 , 20 Regulatory approaches vary across jurisdictions: no formal framework (United States), approved condition lists (United Kingdom), case-by-case ethical assessment (Western Australia, Germany), and restrictive systems like Japan. 1 Our data support a governance model based on case-by-case evaluation that centers individual circumstances rather than disease labels. However, such review mechanisms must operate in a timely manner—the six-year review of the retinoblastoma case illustrates how procedural delays can undermine reproductive rights. For nearly three decades, Japan's PGT-M policy remained largely unchanged, grounded in assumptions rather than empirical evidence. Once public views were systematically examined, a markedly different picture emerged. The governance of reproductive genetic technologies should remain responsive to empirical evidence and ongoing public deliberation. Strengths and Limitations Strengths include a sizable sample (N = 458), multi-dimensional measurement of seriousness, and engagement with culturally salient discourse. Limitations include potential crowdsourcing bias, as our sample was more educated than the national average, which may have inflated acceptance rates. The cross-sectional design captures attitudes at a single point rather than tracking how views evolve. Hypothetical scenarios, and social desirability effects may bias responses towards socially acceptable positions on sensitive topics like disability and enhancement. Future research should compare patients, family members, and public; conduct longitudinal studies as PGT-M familiarity grows; examine how genetic counselors operationalize 'seriousness' within institutional constraints. Given that cross-border reproductive care is increasingly common with restriction on care, 21 cross-national comparisons are also needed to inform internationally harmonized approaches to determine whether these patterns reflect uniquely Japanese dynamics or broader global trends. Conclusion The retinoblastoma mother sought to spare a future child a burden she knew well. Our data show many Japanese adults would consider such risks serious enough to justify PGT-M —while rejecting enhancement and resisting eugenic logic. Current policy, built on rigid thresholds centered on fatality, sidelines patients' lived deliberation and creates moral burden without reducing demand. A more ethical path requires: incorporating lived experience into criteria-setting through patient participation in review panels; ensuring timely case-by-case review rather than gatekeeping; addressing economic barriers as reproductive justice; and grounding policy in empirical evidence rather than ideology. When citizens are consulted, they seek neither prohibition nor laissez-faire—they ask for structured, informed choices anchored in disease prevention, non-enhancement, and robust social support. Policy that acknowledges moral complexity while respecting reproductive autonomy can honor both the legitimate concerns underlying inochi no senbetsu and the reproductive needs of families affected by genetic conditions. Declarations Disclosure of the use of generative AI : During the preparation of this manuscript, the authors used ChatGPT (version 5.2) and Sketchbook to help generate a visual abstract. As English is not the first language of some authors, the ChatGPT (version 5.2) was used solely for linguistic refinement. The authors reviewed and edited the content after use and take full responsibility for the accuracy, integrity, and originality of the work. ACKNOWLEDGMENTS We thank the study participants for sharing their perspectives. We thank the members of Hiroshima University, Center for Collaborative Sciences for their support in executing this survey in Japan. AUTHOR CONTRIBUTIONS: ST : Conceptualization, Methodology, Investigation, Formal analysis, Data curation, Software, Validation, Visualization, Project administration, Writing – original draft, Writing – review & editing. RI : Conceptualization, Methodology, Investigation, Validation, Visualization, Project administration, Writing – original draft, Writing – review & editing. SO : Methodology, Writing – review & editing. LT : Formal analysis, Writing – review & editing. TS : Conceptualization, Methodology, Investigation, Formal analysis, Data curation, Validation, Supervision, Funding acquisition, Writing – review & editing. FUNDING: TS (last author) received funding from the Japan Society for the Promotion of Science (JSPS) KAKENHI [Grant Number 24K00039, 24H00813], the JST Research Institute of Science and Technology for Society (RISTEX) [Grant Number JPMJRS22J4], and the Uehiro Foundation on Ethics and Education [Grant Number UEHIRO2023-0119]. This research was supported by Hiroshima University, Center for Collaborative Sciences. ST and SO work are supported by the Social Science Research Council (Singapore) through the Ministry of Education’s Social Sciences Research Thematic Grant (SS-RC2023-SSRTG-006), and the Singapore Ministry of Health’s National Medical Research Council under the Open Fund–Large Collaborative Grant (OFLCG22may-0010). DISCLOSURE The authors declare no conflicts of interest. DATA AVAILABILITY Data is available on reasonable request to the corresponding author, subject to ethical approval and data sharing agreements. References Ginoza MEC, Isasi R. Regulating Preimplantation Genetic Testing across the World: A Comparison of International Policy and Ethical Perspectives. Cold Spring Harb Perspect Med . 2020;10(5):a036681. doi:10.1101/cshperspect.a036681 Kleiderman E, Boardman F, Newson AJ, Laberge AM, Knoppers BM, Ravitsky V. Unpacking the notion of “serious” genetic conditions: towards implementation in reproductive decision-making? Eur J Hum Genet . 2025;33(2):158-166. doi:10.1038/s41431-024-01681-0 Munné S, Cohen J. The status of preimplantation genetic diagnosis in Japan: a criticism. Reprod Biomed Online . 2004;9(3):258-259. doi:10.1016/S1472-6483(10)62138-4 Berry J. Retinoblastoma: Treatment and outcome - UpToDate. UpToDate. August 29, 2025. Accessed October 9, 2025. https://www.uptodate.com/contents/retinoblastoma-treatment-and-outcome Tsuge A. Ethical and Social Debates and Underlying Thoughts about Preimplantation Genetic Testing for Monogenic disease (PGT-M). J Jpn Assoc Bioeth . 2024;34(35):4-12. Takahashi S, Nord‐Bronzyk AJ, Muyskens KL. Daoist Views on Disability and Genetic Intervention. Hastings Cent Rep . 2025;55(3):45-46. doi:10.1002/hast.5012 Ando T. Inochi e no toi to seimeirinri. Jpn Assoc Relig Stud Proc . 2014;31:1-8. Shimazono S. Inochi no senbetsu wa naze sakerubekina no ka? Shusseizen shindan o meguru Nihon no keiken kara. Shiseigaku Kenkyu . 2008;10:32-60. Japanese Society of Obstetrics and Gynecology. “Jutoku na idensei shikkan o taisho to shita chakushouzen idengakuteki kensa ni kansuru saisoku henkou no oshirase.”[Notice of amendment to the Detailed Rules on Preimplantation Genetic Testing for Serious Hereditary Diseases.]. Published online March 7, 2022. https://www.jsog.or.jp/news/pdf/20220307_rinri.pdf Sear R. Demography and the rise, apparent fall, and resurgence of eugenics. Popul Stud . 2021;75(sup1):201-220. doi:10.1080/00324728.2021.2009013 Siermann M, Claesen Z, Pasquier L, et al. A systematic review of the views of healthcare professionals on the scope of preimplantation genetic testing. J Community Genet . 2022;13(1):1-11. doi:10.1007/s12687-021-00573-w Wertz DC, Knoppers BM. Serious genetic disorders: Can or should they be defined?*. Am J Med Genet . 2002;108(1):29-35. doi:10.1002/ajmg.10212 Takahashi S, Iizuka R, Sawai T. Reevaluating ‘seriousness’ in genetic conditions: balancing clinical criteria and lived experiences. Eur J Hum Genet . Published online March 15, 2025. doi:10.1038/s41431-025-01829-6 Alon I, Bussod I, Ravitsky V. Mapping ethical, legal, and social implications (ELSI) of preimplantation genetic testing (PGT). J Assist Reprod Genet . 2024;41(5):1153-1171. doi:10.1007/s10815-024-03076-y Sasaki A. Comments on the HBOC Guideline for PGT-M in Japan. In: Ohta T, Iwata H, Suzuki N, eds. Practical Guide to Hereditary Breast and Ovarian Cancer III . Springer Nature Singapore; 2025:85-89. doi:10.1007/978-981-96-6779-6_7 Takahashi S. Better than sex? The rise of assisted reproductive technologies as a reproductive norm. Cult Health Sex . Published online May 2, 2025:1-16. doi:10.1080/13691058.2025.2495751 Nakasato K, Yamamoto BA, Kato K. Evaluating standards for ‘serious’ disease for preimplantation genetic testing: a multi-case study on regulatory frameworks in Japan, the UK, and Western Australia. Hum Genomics . 2022;16(1):16. doi:10.1186/s40246-022-00390-3 Mintz KT, Stramondo JA, Tabor HK. Nothing about Us without Us in Precision Medicine: A Call to Reframe Disability Difference in Genetics and Genomics. Hastings Cent Rep . 2024;54(S2). doi:10.1002/hast.4928 Winkelman WD, Missmer SA, Myers D, Ginsburg ES. Public perspectives on the use of preimplantation genetic diagnosis. J Assist Reprod Genet . 2015;32(5):665-675. doi:10.1007/s10815-015-0456-8 Porto A, Gaber Caffrey R, Crowley‐Matoka M, Spencer S, Li M, Propst L. Offering preimplantation genetic testing for monogenic disorders (PGT‐M) for conditions with reduced penetrance or variants of uncertain significance: Ethical insight from U.S. laboratory genetic counselors. J Genet Couns . 2022;31(1):261-268. doi:10.1002/jgc4.1482 Von Schondorf-Gleicher A, Mochizuki L, Orvieto R, Patrizio P, Caplan AS, Gleicher N. Revisiting selected ethical aspects of current clinical in vitro fertilization (IVF) practice. J Assist Reprod Genet . 2022;39(3):591-604. doi:10.1007/s10815-022-02439-7 Additional Declarations There is no duality of interest Supplementary Files Supplementary1SurveyInstrument.pdf.docx Supplementary 1. PGT-M Survey in English Complete English translation of the survey instrument administered to Japanese participants, including introduction to PGT-M, demographic questions, awareness and willingness measures, acceptable indications, barriers, and views on inochi no senbetsu (selection of life). Supplementary2.Table.docx Supplementary 2. PGT-M Awareness and Willingness to Use Supplementary table showing respondent awareness of preimplantation genetic testing for monogenic disorders (PGT-M) and their willingness to use it, stratified by demographic characteristics and prior knowledge (N=458). Supplementary3.Table.docx Supplementary 3. Barriers to PGT-M Use Supplementary table presenting the frequency and percentage of barriers to PGT-M use identified by respondents, including economic burden, partner value differences, guilt about selection, and social pressures (N=458). Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: revise 16 Mar, 2026 Review # 3 received at journal 12 Mar, 2026 Review # 2 received at journal 06 Mar, 2026 Reviewer # 3 agreed at journal 26 Feb, 2026 Reviewer # 2 agreed at journal 21 Feb, 2026 Reviewer # 1 agreed at journal 17 Feb, 2026 Reviewers invited by journal 17 Feb, 2026 Submission checks completed at journal 09 Feb, 2026 First submitted to journal 06 Feb, 2026 Unknown event 06 Feb, 2026 Editor assigned by journal 05 Feb, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8793263","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":592797226,"identity":"14a7166e-f579-4285-aed6-282c116e6ae4","order_by":0,"name":"Shizuko Takahashi","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA20lEQVRIie3OIQsCMRTA8XccmCbWJfcVnhj1w9wQXNFqnhyYBOtAgx/hmthOBloOrS8YTqyGA4tF8MRicl4T3D8MBu/HewA+3y/GAw2QQvP1q1Ug7Srk+aQg9ddEzOP4yrKuWnGVQzGyIGbLzwSPG91m1B+uzQADs7eAlDsIl7rHCjtMaABhfVISnjoOM1LbkigklYf3kgjjIEByHDOyEVKEYVASOGjHYSTjYJH1W0l2wc10rxiSY4kw6lxctl2BO3XKb6NOU8xch733nGXAowrkVaPKFp/P5/uHHsfDS1S1abbCAAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0002-8186-0664","institution":"National University of Singapore","correspondingAuthor":true,"prefix":"","firstName":"Shizuko","middleName":"","lastName":"Takahashi","suffix":""},{"id":592797227,"identity":"ac24c1db-2244-48f1-80d1-58541349decf","order_by":1,"name":"Rie Iizuka","email":"","orcid":"","institution":"Hiroshima University","correspondingAuthor":false,"prefix":"","firstName":"Rie","middleName":"","lastName":"Iizuka","suffix":""},{"id":592797228,"identity":"09fa18c3-2a0a-457d-8b0a-cb7038bd8c49","order_by":2,"name":"Serene Ong","email":"","orcid":"","institution":"National University of Singapore","correspondingAuthor":false,"prefix":"","firstName":"Serene","middleName":"","lastName":"Ong","suffix":""},{"id":592797229,"identity":"5cdfd5f4-6b99-4352-ab8b-3ac93109348a","order_by":3,"name":"Lan Tianxiang","email":"","orcid":"https://orcid.org/0000-0001-7661-8307","institution":"National University of Singapore","correspondingAuthor":false,"prefix":"","firstName":"Lan","middleName":"","lastName":"Tianxiang","suffix":""},{"id":592797230,"identity":"e79cd291-b8b4-445c-a989-150dcb2ac951","order_by":4,"name":"Tsutomu Sawai","email":"","orcid":"https://orcid.org/0000-0002-3806-0573","institution":"Hiroshima University","correspondingAuthor":false,"prefix":"","firstName":"Tsutomu","middleName":"","lastName":"Sawai","suffix":""}],"badges":[],"createdAt":"2026-02-05 07:00:25","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8793263/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8793263/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":103212080,"identity":"e31ca95a-ecbb-4091-a1be-302bfe9b7447","added_by":"auto","created_at":"2026-02-23 08:50:33","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":177418,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eThresholds for Disease Seriousness Perceptions (N=458)\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8793263/v1/478054b2baa0d94b5b284715.png"},{"id":103505264,"identity":"675af99d-f4d5-42cc-afb7-b881921b247f","added_by":"auto","created_at":"2026-02-26 13:29:09","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":150698,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eAcceptable Purposes for PGT-M Use (N=458)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eNote: \u003c/em\u003eMultiple selections permitted; percentages do not sum to 100%.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-8793263/v1/a941201b1d7aa366aef2f9fe.png"},{"id":107704520,"identity":"bca25c9a-dd0a-481c-9a17-81c8a8665d37","added_by":"auto","created_at":"2026-04-24 08:45:57","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":678047,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8793263/v1/c60c31da-0333-419a-8a7a-fe4d19c79585.pdf"},{"id":103212079,"identity":"20206f79-684c-4309-9e00-90f0cba8512c","added_by":"auto","created_at":"2026-02-23 08:50:33","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":947728,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSupplementary 1. PGT-M Survey in English\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eComplete English translation of the survey instrument administered to Japanese participants, including introduction to PGT-M, demographic questions, awareness and willingness measures, acceptable indications, barriers, and views on \u003cem\u003einochi no senbetsu\u003c/em\u003e (selection of life).\u003c/p\u003e","description":"","filename":"Supplementary1SurveyInstrument.pdf.docx","url":"https://assets-eu.researchsquare.com/files/rs-8793263/v1/9448387103627e4026d75b10.docx"},{"id":103212082,"identity":"f32fa81d-751a-4092-bec4-62d802800dda","added_by":"auto","created_at":"2026-02-23 08:50:33","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":15471,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSupplementary 2. PGT-M Awareness and Willingness to Use\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSupplementary table showing respondent awareness of preimplantation genetic testing for monogenic disorders (PGT-M) and their willingness to use it, stratified by demographic characteristics and prior knowledge (N=458).\u003c/p\u003e","description":"","filename":"Supplementary2.Table.docx","url":"https://assets-eu.researchsquare.com/files/rs-8793263/v1/c83e4fc2ca5d35321e1b4f80.docx"},{"id":103212081,"identity":"d272773f-4d4d-46e4-943f-ea9b5c0996ed","added_by":"auto","created_at":"2026-02-23 08:50:33","extension":"docx","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":15180,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSupplementary 3. Barriers to PGT-M Use\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSupplementary table presenting the frequency and percentage of barriers to PGT-M use identified by respondents, including economic burden, partner value differences, guilt about selection, and social pressures (N=458).\u003c/p\u003e","description":"","filename":"Supplementary3.Table.docx","url":"https://assets-eu.researchsquare.com/files/rs-8793263/v1/2da5da422c5ab6b6e6268a9b.docx"}],"financialInterests":"There is no duality of interest","formattedTitle":"Drawing Lines: How the Public Defines 'Serious' Genetic Conditions for Reproductive Testing","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eReviews on global regulations for preimplantation genetic testing (PGT) show a fragmented regulatory landscape that ranging from strict, state-governed oversight in many European jurisdictions to more permissive, professionally led frameworks in the United States. Ethical debates center on the tension between reproductive autonomy and concerns about potential eugenic applications. Germany, Switzerland, and Austria\u0026mdash;once identified as among the most prohibitive jurisdictions\u0026mdash;have since enacted legislation permitting PGT under stringent conditions.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e Central to regulatory debate in restrictive contexts is the question of what constitutes a \u0026ldquo;serious\u0026rdquo; genetic condition and whether seriousness should be determined through fixed lists, case-by-case review, or professional discretion. Recent conceptual work by Kleiderman et. al (2025) in this journal argues that seriousness is not a technical threshold but a normative and procedural judgment, shaped by context, institutional aims, and whose perspectives are included in deliberation.\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e Yet, despite growing recognition of the importance of patient and public involvement, these perspectives remain largely absent from policy-making.\u003c/p\u003e \u003cp\u003eHistorically, Japan has been criticized for its restrictive approach to preimplantation genetic testing (PGT) and undermining reproductive autonomy.\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e PGT is an umbrella term encompassing several applications; PGT for monogenic conditions (PGT-M) is central to the bioethical debate and is the focus of this paper.\u003c/p\u003e \u003cp\u003eThis restrictive stance was exemplified in 2018, when the Japan Society of Obstetrics and Gynecology (JSOG) ethics committee denied approval for PGT-M for retinoblastoma\u0026mdash;a childhood eye cancer with 95% survival when treated but requiring enucleation, chemotherapy, and extensive follow-up care.\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e The committee ruled the condition as \u0026lsquo;not sufficiently serious\u0026rsquo; because it was treatable and not fatal.\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e The mother faced a paradoxical dilemma: treatment success became grounds for denying prevention. This case exemplifies Japan's highly restrictive criteria, having approved only approximately 36 conditions to date.\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eCentral to this restrictiveness is \u003cem\u003einochi no senbetsu\u003c/em\u003e, an ethically charged phrase meaning 'sorting life.' In Japanese discourse, \u003cem\u003esenbetsu\u003c/em\u003e (選別) implies selection based on value criteria, carrying connotations of eugenic discrimination.\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e,\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e This linguistic framing has profound implications for bioethical debates, where PGT-M evokes concerns about value-based discrimination against people with disabilities.\u003c/p\u003e \u003cp\u003eSubsequently, this case was appealed and approved under revised 2022 PGT-M approval policies.\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e This restrictiveness reflects Japan's unique historical context: while most countries abolished eugenic sterilization policies by the 1970s, Japan maintained its Eugenic Protection Law (優生保護法) until 1996.\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e,\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e The fresh memory of coercive eugenics means Japanese policymakers are highly sensitive around practices construed as selecting against disability while leaving unresolved whether conditions must significantly impair daily functioning, threaten survival before adulthood, or lack effective treatment to qualify for PGT-M. Japan's restrictive approach thus reflects ongoing tensions between preventing population-level eugenic practices and respecting individual reproductive autonomy.\u003c/p\u003e \u003cp\u003eThis ambiguity is not unique to Japan. Professional guidelines worldwide invoke seriousness as a criterion for PGT-M but rarely specify what constitutes serious conditions or who should decide.\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e Among genetic healthcare professionals, substantial discrepancy exists between clinical criteria and professional judgment.\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e Evidence from North America shows that approximately half of genetic healthcare professionals consider conditions serious that standard guidelines do not classify as such.\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e,\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e In Japan's framework, seriousness appears to center on mortality and severe early-onset disability, yet crucial questions remain underspecified, including the relevance of penetrance, age of onset, and degree of functional impairment. These unresolved questions have gained renewed attention with the expansion of PGT beyond monogenic conditions to polygenic conditions (PGT-P), which involve the assessment of probabilistic disease risk based on multiple genetic variants, where the boundaries of seriousness are even less clearly defined. Therefore, the question of which conditions should be considered \u0026lsquo;serious enough\u0026rsquo; to justify PGT intensifies. This persistent divergence underscores that seriousness is not a purely clinical threshold but a contested normative judgment.\u003c/p\u003e \u003cp\u003eRecent stakeholder data reveals growing discrepancy: 70% of genetic counselors, clinicians, researchers, and patients would consider PGT-M for conditions that current regulations decline.\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e This points to a widening policy-practice-preference gap warranting empirical investigation. Building on these unresolved questions about seriousness criteria, this study addresses: (1) What do Japanese adults of reproductive age consider sufficiently serious to warrant PGT-M? (2) How do attitudes toward \u003cem\u003einochi no senbetsu\u003c/em\u003e relate to views on PGT-M? (3) Is there a gap between public perceptions and current policy?\u003c/p\u003e"},{"header":"METHODS","content":" \u003ch2\u003eStudy Design and Participants\u003c/h2\u003e \u003cp\u003eWe conducted a cross-sectional online survey of Japanese adults in September 2025. Eligible participants were Japanese nationals aged 18\u0026ndash;42 years, corresponding to the age range covered for infertility treatment under Japan's national health insurance. Participants were recruited through Lancers (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ewww.lancers.jp\u003c/span\u003e\u003cspan address=\"http://www.lancers.jp\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e), a major Japanese crowdsourcing platform, and compensated 500 JPY for the 15-minute survey. The study was approved by the Research Ethics Review Board of the Graduate School of Humanities and Social Sciences, Hiroshima University (Approval No. HR-HUM-003154). All participants provided informed consent.\u003c/p\u003e \n\u003ch3\u003eSurvey Development\u003c/h3\u003e\n\u003cp\u003eThe survey instrument was developed by reviewing ethical, legal, and social implications (ELSI) literature on PGT-M and prenatal genetic testing, with particular attention to the framework made by Kleiderman et. al (2025), international debates on disease seriousness criteria, reproductive autonomy, and disability rights.\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e,\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e Drawing on this review\u0026mdash;as well as our previous stakeholder research of healthcare providers (ID: HR-HUM-002563), genetic counselors, researchers, and patients and conceptual analysis of reproductive genetic ethics. All scientific and medical information presented in the survey was reviewed and validated by two genetics experts and three bioethics scholars.\u003c/p\u003e \u003cp\u003eThe survey comprised: (1) introduction to PGT-M and Japan\u0026rsquo;s regulations, (2)demographics, (3) awareness and willingness to use PGT-M, (4) acceptable indications and barriers, (5) views on \u003cem\u003einochi no senbetsu\u003c/em\u003e, (6) perceptions of disease seriousness using clinical parameters (penetrance, survival, functioning), and (7) factors influencing seriousness perceptions (Provided in the Supplementary Information, Supplementary 1).\u003c/p\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eDescriptive statistics were calculated for all variables. For Likert scale items, we dichotomized responses into substantial influence (somewhat large, very large) versus minimal influence (none, slight, moderate). Logistic regression was used to examine factors associated with willingness to use PGT-M, with demographic variables entered in Model 1 and attitudinal variables added in Model 2. Analyses were conducted in R (version 4.1.0), with p\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e "},{"header":"RESULTS","content":"\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\n \u003ch2\u003eParticipant Characteristics\u003c/h2\u003e\n \u003cp\u003eA total of 458 individuals completed the survey (Supplemental Information); 50.4% were female, mean age 34.5 years. Nearly half (45.4%) were unmarried, and 89.3% had no prior experience with fertility treatment. Demographics are as shown in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eParticipant Demographics and Characteristics (N\u0026thinsp;=\u0026thinsp;458)\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"3\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCharacteristic\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003en\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e%\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eAge\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18\u0026ndash;25 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e26\u0026ndash;30 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e69\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e15.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e31\u0026ndash;35 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e119\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e26.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e36\u0026ndash;42 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e239\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e52.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePrefer not to answer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eGender Identity\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e212\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e46.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e236\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e51.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNon-binary/third gender\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePrefer not to answer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eHas Children\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e166\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e36.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e279\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e61.3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePrefer not to answer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eMarital Status\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMarried\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e197\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e43.3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNever married\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e209\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e45.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCohabiting with partner\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5.3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDivorced/separated\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWidowed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePrefer not to answer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eRelationship to Genetic Disease\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePatient or family member\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e10.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo relationship\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e376\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e82.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOther\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePrefer not to answer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eHistory of Infertility Treatment\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e7.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e412\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e90.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePrefer not to answer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eEducational Attainment\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePrimary school\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSecondary school\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e9.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eVocational/technical school\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e120\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e26.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSome university\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBachelor\u0026apos;s degree\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e234\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e51.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGraduate/professional degree\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e7.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePrefer not to answer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eEmployment Status\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFull-time\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e245\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e53.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePart-time\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e77\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e16.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHomemaker\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e7.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUnemployed, seeking work\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eStudent\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOther\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e12.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePrefer not to answer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eReligious Affiliation\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e290\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e63.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBuddhism\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e114\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e25.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eShinto\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eChristianity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOther\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePrefer not to answer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003ePrior Knowledge of PGT-M\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e12.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e407\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e87.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\n \u003ch2\u003eWillingness to Use PGT-M\u003c/h2\u003e\n \u003cp\u003ePrior awareness of PGT-M was strikingly low (12.4%) despite steady increases in the use of \u003cem\u003ein vitro\u003c/em\u003e fertilization (IVF) use in Japan.\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e Patient or family members with a genetic condition were more aware of PGT-M than all others (OR:2.48, 95%CI 1.18\u0026ndash;5.22, p\u0026thinsp;=\u0026thinsp;0.031). However, once informed about PGT-M, interest emerged: 44.3% expressed willingness to use it (7.4% \u0026lsquo;very much,\u0026rsquo; 36.9% \u0026lsquo;somewhat\u0026rsquo;), 28.2% were neutral, 28.8% expressed negative views. This pattern-low awareness but notable openness once informed-suggests latent demand exceeding what restrictive policies assume. Notably, those with prior awareness were twice as willing to undergo testing (OR 2.26 CI 1.28-4.00 p\u0026thinsp;=\u0026thinsp;0.00064). Details are available in Supplemental Table 1.\u003c/p\u003e\n \u003cp\u003eWillingness to use PGT-M was associated with both demographic and attitudinal factors (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e). Among demographic variables, those without fertility treatment history were significantly less willing than those with such history (OR\u0026thinsp;=\u0026thinsp;0.33, 95% CI 0.14\u0026ndash;0.77, p\u0026thinsp;=\u0026thinsp;0.010), suggesting that direct experience with reproductive medicine increases openness to genetic testing options.\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u003ctable id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eFactors Associated with Willingness to Use PGT-M (N\u0026thinsp;=\u0026thinsp;458)\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"5\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eVariable\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eComparison\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eOR (95% CI)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ep-value\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eSig.\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" colspan=\"5\"\u003e\n \u003cp\u003eDemographic Factors\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eGender\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFemale vs. Male (ref.)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.67 (0.44\u0026ndash;1.04)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.070\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eFertility treatment history\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo treatment vs. Had treatment (ref.)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.33 (0.14\u0026ndash;0.77)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.010\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eEmployment status\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eStudent vs. Full-time (ref.)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9.66 (2.09\u0026ndash;44.63)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.004\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eOther demographics\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAge, children, marital status, education, religion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026gt;\u0026thinsp;0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"5\"\u003e\n \u003cp\u003e\u003cstrong\u003eAttitudes toward\u003c/strong\u003e \u003cstrong\u003eInochi no Senbetsu\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026apos;Unfair treatment of lives\u0026apos;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEndorsed vs. Did not endorse (ref.)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.57 (0.35\u0026ndash;0.93)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.023\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026apos;Ethically problematic\u0026apos;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEndorsed vs. Did not endorse (ref.)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.63 (1.14\u0026ndash;2.32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.007\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026apos;Inevitable due to science\u0026apos;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEndorsed vs. Did not endorse (ref.)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.72 (1.15\u0026ndash;2.56)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.007\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eOther attitudes\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026apos;Ranking lives,\u0026apos; \u0026apos;Personal issue,\u0026apos; \u0026apos;No impression\u0026apos;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026gt;\u0026thinsp;0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cp\u003e\u003cem\u003eNote:\u0026nbsp;\u003c/em\u003eOR = odds ratio; CI = confidence interval; NS = not significant; ref. = reference group. *p \u0026lt; 0.05; **p \u0026lt; 0.01. Model includes both demographic and attitudinal variables.\u003c/p\u003e\n \u003cp\u003eThe most striking findings emerged from attitudinal variables. Participants who endorsed the view that \u003cem\u003einochi no senbetsu\u003c/em\u003e is \u0026apos;ethically problematic\u0026apos; were significantly \u003cem\u003emore\u003c/em\u003e likely to express willingness to use PGT-M (OR\u0026thinsp;=\u0026thinsp;1.63, 95% CI 1.14\u0026ndash;2.32, p\u0026thinsp;=\u0026thinsp;0.007). Similarly, those who viewed embryo selection as \u0026apos;inevitable due to scientific advancement\u0026apos; showed higher willingness (OR\u0026thinsp;=\u0026thinsp;1.72, 95% CI 1.15\u0026ndash;2.56, p\u0026thinsp;=\u0026thinsp;0.007). In contrast, those who endorsed the view that embryo selection represents \u0026apos;unfair treatment of lives\u0026apos; were less willing (OR\u0026thinsp;=\u0026thinsp;0.57, 95% CI 0.35\u0026ndash;0.93, p\u0026thinsp;=\u0026thinsp;0.023).\u003c/p\u003e\n\u003c/div\u003e\n\u003ch3\u003eDefining Seriousness: A Broader Threshold Than Policy Permits (Fig. )\u003c/h3\u003e\n\u003cp\u003e\u003cem\u003eDisease Penetrance\u003c/em\u003e. When asked about the probability threshold at which a genetic condition becomes serious enough for PGT-M, the plurality of participants (57.4%) selected 50\u0026ndash;74% penetrance\u0026mdash;meaning the condition would develop in half to three-quarters of carriers. This represents moderate rather than high penetrance. An additional 25.8% selected even lower penetrance (25\u0026ndash;49%), with only 12.7% requiring near-certain penetrance (75\u0026ndash;100%) and 4.1% setting their threshold at minimal risk (0\u0026ndash;24%). The modal response of 50\u0026ndash;74% penetrance is notably lower than what current Japanese policy implicitly requires, which focuses predominantly on high-penetrance conditions.\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAge of Survival\u003c/em\u003e. Regarding life-limiting conditions, the plurality of participants (47.6%) considered conditions restricting survival to school age through adolescence (6\u0026ndash;20 years) as serious enough for PGT-M. Another 3.2% selected early childhood (1\u0026ndash;5 years), and 9.4% selected infancy (0\u0026ndash;1 year). Notably, 14.2% extended their threshold to early adulthood (21\u0026ndash;40 years), indicating willingness to consider conditions that permit survival into adulthood but with limited lifespan. Only .7% selected thresholds of middle age or beyond. This distribution reveals that most participants do not require neonatal or infant lethality to consider a condition serious; survival through childhood or adolescence is sufficient for nearly half the sample.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eDaily Life Impact\u003c/em\u003e. For non-life-threatening conditions affecting daily functioning, 44.2% participants considered moderate impact (clear activity limitations with preserved independence) serious enough to justify PGT-M, while 42.7% selected severe impact (impaired independence requiring some assistance). Relatively few participants required either no impact (2.4%) or only mild impact (8.3%) as their threshold, and equally few required very severe impact (2.6%). The dominance of moderate and severe thresholds suggests that participants do not require complete loss of independence to consider a condition serious\u0026mdash;significant quality of life impacts appear sufficient.\u003c/p\u003e\n\u003cp\u003eThese findings reveal that the public\u0026apos;s conception of seriousness is considerably broader than current regulatory practice in Japan.\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e The plurality defines seriousness as moderate penetrance, survival limited to school age or adolescence, and moderate functional impairment\u0026mdash;contrasting markedly with JSOG\u0026apos;s emphasis on high-penetrance conditions with early onset and severe disability or lethality.\u003c/p\u003e\n\u003ch3\u003eHow Social Context Shapes Perceptions of Seriousness\u003c/h3\u003e\n\u003cp\u003eParticipants\u0026apos; ratings revealed that seriousness revealed is substantially shaped by social and structural context (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e). Among experiential factors rated as having substantial influence daily life impact ranked highest (84.0%), followed by economic burden (77.5%), physical burden (74.0%), appearance changes (72.5%), psychological burden (70.2%), and discrimination (62.6%).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u003ctable id=\"Tab3\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eFactors Influencing Disease Seriousness Perceptions (N\u0026thinsp;=\u0026thinsp;458)\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"3\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eFactor\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eMinimal n (%)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eSubstantial n (%)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003eExperiential Factors\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDaily life impact (work, family, hobbies)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e74 (16.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e384 (84.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEconomic burden (treatment costs)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e103 (22.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e355 (77.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePhysical burden (pain, fatigue)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e119 (26.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e339 (74.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAppearance changes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e126 (27.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e332 (72.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePsychological burden\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e137 (29.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e321 (70.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDiscrimination and stigma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e172 (37.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e286 (62.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003e\u003cstrong\u003eSupport Factors (Influence when inadequate)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEconomic support (insurance, subsidies)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e73 (15.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e385 (84.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAccess to medical care\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e83 (18.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e375 (81.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEducational and employment support\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e109 (23.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e349 (76.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePsychological support\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e115 (25.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e343 (74.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAssistive technology\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e143 (31.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e315 (68.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cem\u003eNote:\u0026nbsp;\u003c/em\u003eMinimal influence = none + slight + moderate; Substantial influence = somewhat large + very large.\u003c/p\u003e\n\u003cp\u003eCritically, participants indicated that lack of adequate support systems substantially influences seriousness perceptions. Economic support showed the highest influence (84.1%), followed by access to medical care (81.8%), educational and employment support (76.2%), psychological support (74.8%), social connections (70.1%), and assistive technology (68.8%). These findings suggest that the same condition might be perceived as more or less serious depending on whether robust social infrastructure exists to support affected individuals.\u003c/p\u003e\n\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\n \u003ch2\u003eAttitudes with PGT-M: Purposes, Boundaries and Inochi no Senbetsu\u003c/h2\u003e\n \u003cp\u003eFor personal use, preventing disease (65.5%), preventing disability (75.5%), and having healthy children (69.7%) were most commonly endorsed. Enhancement purposes received minimal support: high-ability children (6.6%), or children with similar characteristics to parents (4.8%). When considering acceptable uses by others, similar patterns emerged with slightly higher acceptance, suggesting a distinction between personal choice and permissibility for others. A slight majority (53.2%) believed that PGT-M availability would encourage people with genetic conditions and their families to pursue marriage, pregnancy, and childbirth more actively\u0026mdash;challenging assumptions that PGT-M primarily represents eugenic selection.\u003c/p\u003e\n \u003cp\u003eRegarding specific genetic predispositions acceptable to test, participants endorsed a wide range of serious conditions: early-onset mental/intellectual disability (76.9%), visual impairment (76.2%), physical disabilities (73.0%), hearing impairment (69.9%), cancer predisposition (66.6%), and developmental disorders (61.8%) all received majority support. However, support declined notably for later-onset conditions: dementia (38.6%), psychiatric conditions (34.5%), and metabolic disorders (29.5%). Intelligence enhancement received very low support (7.2%), with only 3.9% indicating they would not test for any predisposition.\u003c/p\u003e\n \u003cp\u003eMost participants (72.3%) reported awareness of \u003cem\u003einochi no senbetsu\u003c/em\u003e. When asked about impressions, 58.5% associated it with prioritizing lives, 41.2% viewed it as ethically problematic, 27.5% considered it inevitable due to medical progress, and 25.7% believed it should be a private decision. Notably, 38.0% reported feeling guilt about selecting children through PGT-M-reflecting how this discourse has shaped emotional responses to reproductive genetic testing.\u003c/p\u003e\n \u003cp\u003eCritically, participants were divided on whether PGT-M constitutes \u003cem\u003einochi no senbetsu\u003c/em\u003e. For selecting embryos without genetic abnormalities-the core function of PGT-M-only 36.9% agreed this represents \u003cem\u003einochi no senbetsu\u003c/em\u003e (sorting lives), while 47.2% disagreed. This proportion is comparable to attitudes toward morphology-based embryo selection (32.3% agreed), a widely practiced procedure in assisted reproduction. Participants appear to understand PGT-M as preventing suffering rather than devaluing existing lives, while maintaining clear boundaries against enhancement (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\n \u003ch2\u003eBarriers to Access: Economics Over Ethics\u003c/h2\u003e\n \u003cp\u003eEconomic burden was the dominant barrier to PGT-M use (70.3%), followed by concern about differing values with partners (48.5%) and guilt about selecting children (38.0%). Ethical and social concerns, while present, were secondary to practical economic constraints. Other barriers included social pressure against use (18.8%), concerns about violating children\u0026apos;s right not to know genetic information (17.9%), and social pressure to use PGT-M (8.7%). Only 2.8% indicated no particular barriers. For preferred funding, participants were divided equally between insurance coverage (33.6%) and government subsidies (33.6%), with only 22.7% supporting full private payment. Details are shown in Supplemental Table\u0026nbsp;2.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eThis study provides the first empirical evidence of how Japanese adults of reproductive age conceptualize disease seriousness for PGT-M. Five key findings emerge with implications for policy reform.\u003c/p\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003ePublic Thresholds Exceed Regulatory Thresholds\u003c/h2\u003e \u003cp\u003eThe public threshold for justifying PGT-M is lower than that in Japan's current regulatory framework. Three anchors illustrate this complexity. First, 57.4% of respondents define 'serious' as having a penetrance of 50\u0026ndash;74%, indicating that a substantial-though not near-certain-risk is sufficient for PGT-M. Second, whereas JSOG-approved cases have historically focused almost exclusively on neonatal or early-childhood lethal conditions, about half of the respondents considered survival only to school age/adolescence to be serious. Third, 44.2% regard moderate functional limitation as serious (reduced capacity with maintained independence), indicating that quality-of-life concerns are not confined to catastrophic disability. These indicate a clear gap between regulatory practice and public judgments of seriousness, with important implications for the scope of conditions considered eligible for PGT-M.\u003c/p\u003e \u003cp\u003eTogether, the public thresholds would encompass categories largely excluded by the current JSOG list: hereditary cancer predispositions, adult-onset neurodegenerative conditions, and moderately impairing disabilities with near-normal lifespan. The retinoblastoma case exemplifies this misalignment: a childhood cancer requiring lifelong surveillance and extensive treatment is judged serious by the public but was initially denied by regulators. Our findings indicate that Japan's framework reflects neither public nor professional views.\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eThe Social Construction of Seriousness\u003c/h2\u003e \u003cp\u003eResearchers in disability studies argue that disability is predominantly a social construct rather than a medical condition, framing it as a human rights issue.\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e How impairments are experienced depends heavily on material and social resources, a view that has informed efforts to identify structural factors contributing to the marginalization of people with disabilities.\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e Our findings align with this social model: 84.1% said economic support and 81.8% said access to medical care influence whether a condition counts as 'serious.' Japan's restrictive policy posits that limiting PGT-M safeguards against discrimination, yet our findings imply inadequate support systems intensify perceived seriousness and heighten demand for preventive measures. Supporting informed reproductive choices while enhancing support systems can be complementary goals.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003eDeliberating Under Moral Ambivalence Without Rejecting PGT-M\u003c/h2\u003e \u003cp\u003eOur findings indicate that ethical discomfort with \u003cem\u003einochi no senbetsu\u003c/em\u003e\u0026mdash;an abstract concern frequently invoked in Japanese bioethical discourse\u0026mdash;does not translate straightforwardly into rejection of PGT-M. Participants who perceived PGT-M as ethically problematic were \u003cem\u003emore\u003c/em\u003e willing to use the technology (OR\u0026thinsp;=\u0026thinsp;1.63, p\u0026thinsp;=\u0026thinsp;0.007). This paradox suggests that restrictive policy framing\u0026mdash;which emphasizes the ethical gravity of embryo selection\u0026mdash;does not suppress demand but rather induces guilt while leaving underlying reproductive motivations intact. Individuals appear capable of holding moral reservations while simultaneously recognizing personal circumstances where they might consider using the technology. The 38% who reported feeling guilty about PGT-M despite its therapeutic intent illustrates how this discourse shapes emotional experience without necessarily changing behavior.\u003c/p\u003e \u003cp\u003eFurthermore, many individuals perceive PGT-M as expanding reproductive possibilities rather than as a mechanism of exclusion. A majority (53.2%) believed that PGT-M availability would encourage individuals with genetic conditions and their families to pursue marriage, pregnancy, and childbirth more actively. This perception challenges the prevailing tendency in Japan to associate PGT-M primarily with eugenic selection.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec17\" class=\"Section2\"\u003e \u003ch2\u003ePublic Reasoning Beyond Inochi no Senbetsu\u003c/h2\u003e \u003cp\u003eJapan's reflection on its eugenic history has led to stringent regulations. In our study, awareness of \u003cem\u003einochi no senbetsu\u003c/em\u003e was high (72.3%) and 41.2% expressed ethical concerns, resulting in feelings of guilt among 38% of respondents, despite its therapeutic intent.\u003c/p\u003e \u003cp\u003eHowever, our findings reveal that the public draws more nuanced distinctions than this discourse suggests. Although the abstract notion of \u003cem\u003einochi no senbetsu\u003c/em\u003e evokes negative connotations for many participants, most do not view genetic embryo selection as actually constituting \u003cem\u003einochi no senbetsu\u003c/em\u003e (sorting lives)\u0026mdash; a view comparable to attitudes toward the widely-practiced morphology-based embryo selection (32.3% agreed). This suggests conceptual boundaries that distinguish PGT-M from practices more readily condemned under this framework, such as selective abortion following prenatal diagnosis. Participants appear to understand PGT-M as preventing suffering rather than devaluing existing lives, while maintaining clear boundaries against enhancement (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eParticipants demonstrated clear boundaries regarding acceptable purposes. Therapeutic uses\u0026mdash;preventing disease or disability\u0026mdash;were widely supported (71\u0026ndash;80%), whereas enhancement received minimal endorsement (6\u0026ndash;10%). Notably, participants expressed greater acceptance of others using PGT-M than of using it themselves, reflecting fundamental respect for reproductive autonomy. These findings suggest citizens advocate neither unrestricted selection nor outright prohibition, but rather a deliberative space where reproductive decisions can be made responsibly while preventing discriminatory effects through robust social support.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec18\" class=\"Section2\"\u003e \u003ch2\u003eThe Economic Burden as a Matter of Reproductive Justice\u003c/h2\u003e \u003cp\u003eOur findings suggest the primary issue with Japan's current PGT-M system is economic rather than ethical. Economic barriers (70.3%) highlight how structural factors limit reproductive autonomy. Japan's classification of PGT-M as investigational results in costs exceeding 1,000,000 JPY (approximately 7,000\u0026ndash;9,000 USD) per cycle not covered by national health insurance.\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e This creates significant disparities, rendering PGT-M accessible only to those with substantial financial resources. Participants recognized this and expressed support from medical insurance (33.6%) and government subsidy programs (33.6%). This economic barrier may paradoxically intensify guilt: those who might benefit most face both financial exclusion and moral burden from restrictive discourse.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec19\" class=\"Section2\"\u003e \u003ch2\u003eComparative Context and Policy Implications\u003c/h2\u003e \u003cp\u003eOur findings align with existing research: a U.S. study showed growing endorsement for conditions with reduced penetrance based on patients' evaluations of utility for family planning.\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e The importance of incorporating patients' perceptions of disease seriousness is increasingly recognized among healthcare professionals.\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e,\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eRegulatory approaches vary across jurisdictions: no formal framework (United States), approved condition lists (United Kingdom), case-by-case ethical assessment (Western Australia, Germany), and restrictive systems like Japan.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e Our data support a governance model based on case-by-case evaluation that centers individual circumstances rather than disease labels. However, such review mechanisms must operate in a timely manner\u0026mdash;the six-year review of the retinoblastoma case illustrates how procedural delays can undermine reproductive rights.\u003c/p\u003e \u003cp\u003eFor nearly three decades, Japan's PGT-M policy remained largely unchanged, grounded in assumptions rather than empirical evidence. Once public views were systematically examined, a markedly different picture emerged. The governance of reproductive genetic technologies should remain responsive to empirical evidence and ongoing public deliberation.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec20\" class=\"Section2\"\u003e \u003ch2\u003eStrengths and Limitations\u003c/h2\u003e \u003cp\u003eStrengths include a sizable sample (N\u0026thinsp;=\u0026thinsp;458), multi-dimensional measurement of seriousness, and engagement with culturally salient discourse. Limitations include potential crowdsourcing bias, as our sample was more educated than the national average, which may have inflated acceptance rates. The cross-sectional design captures attitudes at a single point rather than tracking how views evolve. Hypothetical scenarios, and social desirability effects may bias responses towards socially acceptable positions on sensitive topics like disability and enhancement. Future research should compare patients, family members, and public; conduct longitudinal studies as PGT-M familiarity grows; examine how genetic counselors operationalize 'seriousness' within institutional constraints. Given that cross-border reproductive care is increasingly common with restriction on care,\u003csup\u003e21\u003c/sup\u003e cross-national comparisons are also needed to inform internationally harmonized approaches to determine whether these patterns reflect uniquely Japanese dynamics or broader global trends.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe retinoblastoma mother sought to spare a future child a burden she knew well. Our data show many Japanese adults would consider such risks serious enough to justify PGT-M \u0026mdash;while rejecting enhancement and resisting eugenic logic. Current policy, built on rigid thresholds centered on fatality, sidelines patients' lived deliberation and creates moral burden without reducing demand.\u003c/p\u003e \u003cp\u003eA more ethical path requires: incorporating lived experience into criteria-setting through patient participation in review panels; ensuring timely case-by-case review rather than gatekeeping; addressing economic barriers as reproductive justice; and grounding policy in empirical evidence rather than ideology. When citizens are consulted, they seek neither prohibition nor laissez-faire\u0026mdash;they ask for structured, informed choices anchored in disease prevention, non-enhancement, and robust social support. Policy that acknowledges moral complexity while respecting reproductive autonomy can honor both the legitimate concerns underlying \u003cem\u003einochi no senbetsu\u003c/em\u003e and the reproductive needs of families affected by genetic conditions.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eDisclosure of the use of generative AI\u003c/strong\u003e\u003cstrong\u003e:\u003c/strong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003eDuring the preparation of this manuscript, the authors used ChatGPT (version 5.2) and Sketchbook to help generate a visual abstract. As English is not the first language of some authors, the ChatGPT (version 5.2) was used solely for linguistic refinement. The authors reviewed and edited the content after use and take full responsibility for the accuracy, integrity, and originality of the work.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eACKNOWLEDGMENTS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe thank the study participants for sharing their perspectives. We thank the members of Hiroshima University, Center for Collaborative Sciences for their support in executing this survey in Japan.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAUTHOR CONTRIBUTIONS:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eST\u003c/strong\u003e\u003cstrong\u003e:\u0026nbsp;\u003c/strong\u003eConceptualization, Methodology, Investigation, Formal analysis, Data curation, Software, Validation, Visualization, Project administration, Writing \u0026ndash; original draft, Writing \u0026ndash; review \u0026amp; editing.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eRI\u003c/strong\u003e\u003cstrong\u003e:\u0026nbsp;\u003c/strong\u003eConceptualization, Methodology, Investigation, Validation, Visualization, Project administration, Writing \u0026ndash; original draft, Writing \u0026ndash; review \u0026amp; editing.\u0026nbsp;\u003cstrong\u003eSO\u003c/strong\u003e:\u0026nbsp;Methodology, Writing \u0026ndash; review \u0026amp; editing.\u0026nbsp;\u003cstrong\u003eLT\u003c/strong\u003e\u003cstrong\u003e:\u003c/strong\u003e Formal analysis, Writing \u0026ndash; review \u0026amp; editing.\u0026nbsp;\u003cstrong\u003eTS\u003c/strong\u003e\u003cstrong\u003e:\u0026nbsp;\u003c/strong\u003eConceptualization, Methodology, Investigation, Formal analysis, Data curation, Validation, Supervision, Funding acquisition, Writing \u0026ndash; review \u0026amp; editing.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFUNDING:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTS (last author) received funding from the Japan Society for the Promotion of Science (JSPS) KAKENHI [Grant Number 24K00039, 24H00813], the JST Research Institute of Science and Technology for Society (RISTEX) [Grant Number JPMJRS22J4], and the Uehiro Foundation on Ethics and Education [Grant Number UEHIRO2023-0119]. This research was supported by Hiroshima University, Center for Collaborative Sciences. ST and SO work are supported by the Social Science Research Council (Singapore) through the Ministry of Education\u0026rsquo;s Social Sciences\u0026nbsp;Research Thematic Grant (SS-RC2023-SSRTG-006), and the Singapore Ministry of Health\u0026rsquo;s National Medical Research Council under the Open Fund\u0026ndash;Large Collaborative Grant\u0026nbsp;(OFLCG22may-0010).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDISCLOSURE\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no conflicts of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDATA AVAILABILITY\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData is available on reasonable request to the corresponding author, subject to ethical approval and data sharing agreements.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eGinoza MEC, Isasi R. Regulating Preimplantation Genetic Testing across the World: A Comparison of International Policy and Ethical Perspectives. \u003cem\u003eCold Spring Harb Perspect Med\u003c/em\u003e. 2020;10(5):a036681. doi:10.1101/cshperspect.a036681\u003c/li\u003e\n\u003cli\u003eKleiderman E, Boardman F, Newson AJ, Laberge AM, Knoppers BM, Ravitsky V. Unpacking the notion of \u0026ldquo;serious\u0026rdquo; genetic conditions: towards implementation in reproductive decision-making? \u003cem\u003eEur J Hum Genet\u003c/em\u003e. 2025;33(2):158-166. doi:10.1038/s41431-024-01681-0\u003c/li\u003e\n\u003cli\u003eMunn\u0026eacute; S, Cohen J. The status of preimplantation genetic diagnosis in Japan: a criticism. \u003cem\u003eReprod Biomed Online\u003c/em\u003e. 2004;9(3):258-259. doi:10.1016/S1472-6483(10)62138-4\u003c/li\u003e\n\u003cli\u003eBerry J. Retinoblastoma: Treatment and outcome - UpToDate. UpToDate. August 29, 2025. Accessed October 9, 2025. https://www.uptodate.com/contents/retinoblastoma-treatment-and-outcome\u003c/li\u003e\n\u003cli\u003eTsuge A. Ethical and Social Debates and Underlying Thoughts about Preimplantation Genetic Testing for Monogenic disease (PGT-M). \u003cem\u003eJ Jpn Assoc Bioeth\u003c/em\u003e. 2024;34(35):4-12.\u003c/li\u003e\n\u003cli\u003eTakahashi S, Nord‐Bronzyk AJ, Muyskens KL. Daoist Views on Disability and Genetic Intervention. \u003cem\u003eHastings Cent Rep\u003c/em\u003e. 2025;55(3):45-46. doi:10.1002/hast.5012\u003c/li\u003e\n\u003cli\u003eAndo T. Inochi e no toi to seimeirinri. \u003cem\u003eJpn Assoc Relig Stud Proc\u003c/em\u003e. 2014;31:1-8.\u003c/li\u003e\n\u003cli\u003eShimazono S. Inochi no senbetsu wa naze sakerubekina no ka? Shusseizen shindan o meguru Nihon no keiken kara. \u003cem\u003eShiseigaku Kenkyu\u003c/em\u003e. 2008;10:32-60.\u003c/li\u003e\n\u003cli\u003eJapanese Society of Obstetrics and Gynecology. \u0026ldquo;Jutoku na idensei shikkan o taisho to shita chakushouzen idengakuteki kensa ni kansuru saisoku henkou no oshirase.\u0026rdquo;[Notice of amendment to the Detailed Rules on Preimplantation Genetic Testing for Serious Hereditary Diseases.]. Published online March 7, 2022. https://www.jsog.or.jp/news/pdf/20220307_rinri.pdf\u003c/li\u003e\n\u003cli\u003eSear R. Demography and the rise, apparent fall, and resurgence of eugenics. \u003cem\u003ePopul Stud\u003c/em\u003e. 2021;75(sup1):201-220. doi:10.1080/00324728.2021.2009013\u003c/li\u003e\n\u003cli\u003eSiermann M, Claesen Z, Pasquier L, et al. A systematic review of the views of healthcare professionals on the scope of preimplantation genetic testing. \u003cem\u003eJ Community Genet\u003c/em\u003e. 2022;13(1):1-11. doi:10.1007/s12687-021-00573-w\u003c/li\u003e\n\u003cli\u003eWertz DC, Knoppers BM. Serious genetic disorders: Can or should they be defined?*. \u003cem\u003eAm J Med Genet\u003c/em\u003e. 2002;108(1):29-35. doi:10.1002/ajmg.10212\u003c/li\u003e\n\u003cli\u003eTakahashi S, Iizuka R, Sawai T. Reevaluating \u0026lsquo;seriousness\u0026rsquo; in genetic conditions: balancing clinical criteria and lived experiences. \u003cem\u003eEur J Hum Genet\u003c/em\u003e. Published online March 15, 2025. doi:10.1038/s41431-025-01829-6\u003c/li\u003e\n\u003cli\u003eAlon I, Bussod I, Ravitsky V. Mapping ethical, legal, and social implications (ELSI) of preimplantation genetic testing (PGT). \u003cem\u003eJ Assist Reprod Genet\u003c/em\u003e. 2024;41(5):1153-1171. doi:10.1007/s10815-024-03076-y\u003c/li\u003e\n\u003cli\u003eSasaki A. Comments on the HBOC Guideline for PGT-M in Japan. In: Ohta T, Iwata H, Suzuki N, eds. \u003cem\u003ePractical Guide to Hereditary Breast and Ovarian Cancer III\u003c/em\u003e. Springer Nature Singapore; 2025:85-89. doi:10.1007/978-981-96-6779-6_7\u003c/li\u003e\n\u003cli\u003eTakahashi S. Better than sex? The rise of assisted reproductive technologies as a reproductive norm. \u003cem\u003eCult Health Sex\u003c/em\u003e. Published online May 2, 2025:1-16. doi:10.1080/13691058.2025.2495751\u003c/li\u003e\n\u003cli\u003eNakasato K, Yamamoto BA, Kato K. Evaluating standards for \u0026lsquo;serious\u0026rsquo; disease for preimplantation genetic testing: a multi-case study on regulatory frameworks in Japan, the UK, and Western Australia. \u003cem\u003eHum Genomics\u003c/em\u003e. 2022;16(1):16. doi:10.1186/s40246-022-00390-3\u003c/li\u003e\n\u003cli\u003eMintz KT, Stramondo JA, Tabor HK. Nothing about Us without Us in Precision Medicine: A Call to Reframe Disability Difference in Genetics and Genomics. \u003cem\u003eHastings Cent Rep\u003c/em\u003e. 2024;54(S2). doi:10.1002/hast.4928\u003c/li\u003e\n\u003cli\u003eWinkelman WD, Missmer SA, Myers D, Ginsburg ES. Public perspectives on the use of preimplantation genetic diagnosis. \u003cem\u003eJ Assist Reprod Genet\u003c/em\u003e. 2015;32(5):665-675. doi:10.1007/s10815-015-0456-8\u003c/li\u003e\n\u003cli\u003ePorto A, Gaber Caffrey R, Crowley‐Matoka M, Spencer S, Li M, Propst L. Offering preimplantation genetic testing for monogenic disorders (PGT‐M) for conditions with reduced penetrance or variants of uncertain significance: Ethical insight from U.S. laboratory genetic counselors. \u003cem\u003eJ Genet Couns\u003c/em\u003e. 2022;31(1):261-268. doi:10.1002/jgc4.1482\u003c/li\u003e\n\u003cli\u003eVon Schondorf-Gleicher A, Mochizuki L, Orvieto R, Patrizio P, Caplan AS, Gleicher N. Revisiting selected ethical aspects of current clinical in vitro fertilization (IVF) practice. \u003cem\u003eJ Assist Reprod Genet\u003c/em\u003e. 2022;39(3):591-604. doi:10.1007/s10815-022-02439-7\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"european-journal-of-human-genetics","isNatureJournal":false,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"ejhg","sideBox":"Learn more about [European Journal of Human Genetics](http://www.nature.com/ejhg/)","snPcode":"41431","submissionUrl":"https://mts-ejhg.nature.com/cgi-bin/main.plex","title":"European Journal of Human Genetics","twitterHandle":"@ejhg_journal","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"preimplantation genetic testing, disease seriousness, reproductive autonomy, disability rights, Japan, inochi no senbetsu","lastPublishedDoi":"10.21203/rs.3.rs-8793263/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8793263/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003ePrior normative and empirical research has identified a gap between how patients and the public conceptualise “serious” conditions eligible for preimplantation genetic testing for monogenic disorders (PGT-M) and how seriousness is defined. Japan represents a highly restrictive regulatory context shaped by its historical experience with eugenics. Although PGT-M has been available since 1998, its use has been tightly limited, with the first birth occurring six years later and approximately 36 conditions approved to date.\u003c/p\u003e\n\u003cp\u003eThis study examines how Japanese adults of reproductive age understand “seriousness” in genetic disease and how they view PGT-M in relation to concerns about eugenic selection (\u003cem\u003einochi no senbetsu\u003c/em\u003e, “sorting of lives”).\u003c/p\u003e\n\u003cp\u003eWe conducted a cross-sectional online survey of 458 adults aged 18–42 years. Measures included perceived seriousness across four dimensions (penetrance, age of onset, survival impact, functional limitation), willingness to use PGT-M, perceived barriers to access, and attitudes toward eugenic selection.\u003c/p\u003e\n\u003cp\u003eAwareness of PGT-M was low (12%), yet 44% of respondents would consider its use. Participants defined seriousness more broadly than current Japanese policy permits: most rated highly penetrant or childhood-lethal conditions as serious, and over half also included conditions associated with mild to moderate functional limitations. Respondents distinguished disease prevention from enhancement. Economic burden was the most frequently cited barrier (70%). Many respondents who expressed ethical discomfort with eugenic selection nonetheless reported willingness to consider PGT-M.\u003c/p\u003e\n\u003cp\u003eThese findings reveal a substantial gap between policy, public reasoning, and reproductive preferences, with implications for European debates on seriousness and proportionality in reproductive genetic testing.\u003c/p\u003e","manuscriptTitle":"Drawing Lines: How the Public Defines 'Serious' Genetic Conditions for Reproductive Testing","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-23 08:50:28","doi":"10.21203/rs.3.rs-8793263/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"revise","date":"2026-03-16T15:46:38+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"This content is not available.","date":"2026-03-12T09:52:44+00:00","index":3,"fulltext":"This content is not available."},{"type":"editorInvitedReview","content":"This content is not available.","date":"2026-03-06T20:47:45+00:00","index":2,"fulltext":"This content is not available."},{"type":"reviewerAgreed","content":"This content is not available.","date":"2026-02-26T13:20:52+00:00","index":3,"fulltext":"This content is not available."},{"type":"reviewerAgreed","content":"This content is not available.","date":"2026-02-21T15:05:34+00:00","index":2,"fulltext":"This content is not available."},{"type":"reviewerAgreed","content":"This content is not available.","date":"2026-02-17T14:21:30+00:00","index":1,"fulltext":"This content is not available."},{"type":"reviewersInvited","content":"","date":"2026-02-17T14:20:38+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-02-09T10:14:00+00:00","index":"","fulltext":""},{"type":"submitted","content":"European Journal of Human Genetics","date":"2026-02-06T22:19:52+00:00","index":"","fulltext":""},{"type":"checksFailed","content":"","date":"2026-02-06T20:18:09+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-02-05T06:58:44+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"european-journal-of-human-genetics","isNatureJournal":false,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"ejhg","sideBox":"Learn more about [European Journal of Human Genetics](http://www.nature.com/ejhg/)","snPcode":"41431","submissionUrl":"https://mts-ejhg.nature.com/cgi-bin/main.plex","title":"European Journal of Human Genetics","twitterHandle":"@ejhg_journal","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"138ef2ea-7e11-4dcd-8d93-0f1dfa9f496a","owner":[],"postedDate":"February 23rd, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":63076624,"name":"Scientific community and society/Social sciences/Ethics"},{"id":63076625,"name":"Scientific community and society/Social sciences/Psychology/Human behaviour"}],"tags":[],"updatedAt":"2026-04-06T10:30:40+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-23 08:50:28","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8793263","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8793263","identity":"rs-8793263","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}