Disease characteristics and their impact on PGT-M acceptability in childhood-onset CPS

Between the first and second surveys, the number of respondents who considered PGT-M to be “unacceptable” decreased significantly for all conditions. In contrast, responses indicating “Neither” for NF1 and FAP, as well as “acceptable” for LFS, increased. More than half of the responses for LFS indicated “acceptable,” reflecting the highest level of acceptability among the three conditions. At the time of data collection, however, no formal approval for PGT-M involving LFS had been publicly reported in Japan. Subsequently, JSOG reported one approved case involving LFS in March 2026. This subsequent development is consistent with the relatively high professional acceptability observed in our survey and should be interpreted in light of Japan’s JSOG-led professional self-regulatory system.Under this framework, eligibility is not determined by pre-approved disease lists, but is instead assessed through case-by-case review of individual clinical applications. Publicly available ethics deliberation materials issued by JSOG prior to the 2022 guideline revision indicate that the working definition of disease severity emphasized conditions in which, before reaching adulthood, daily functioning is markedly impaired or survival may be threatened. During these deliberations, concerns were raised that removing the “before adulthood” qualifier could substantially broaden the scope of eligible conditions. As a result, the principle of childhood onset was retained, while limited flexibility was maintained through individualized review within the existing framework (Japan Society of Obstetrics and Gynecology 2022).

A 2009 French study on the acceptability of PGT-M for CPSs reported that acceptability was higher for diseases characterized by high penetrance, childhood onset, multifocality, and limited options for prevention or treatment. Conversely, PGT-M was less acceptable for adult-onset, localized diseases with available preventive or treatment options and better quality of life—even when such diseases exhibited high penetrance (Julian-Reynier et al. 2009). Consistent with these findings, in the present study, respondents more frequently selected “childhood onset” and “neither curable nor preventable” as justifications for considering PGT-M in LFS than in the other two conditions. These disease characteristics likely contributed to the high acceptability of PGT-M in LFS.

In contrast, FAP and NF1 were considered less acceptable for PGT-M. The primary reasons were the availability of prevention and treatment (for FAP), adult onset (also for FAP), and variable phenotype and severity (for NF1). As with LFS, disease characteristics can shape the perceived appropriateness of PGT-M. Selumetinib was approved in 2022 as a treatment for NF1 (Suenobu et al. 2023), and therapeutic advancements may potentially lower the perceived necessity for PGT-M in such conditions. Thus, ongoing surveys will be essential to inform evidence-based clinical and policy decisions within the broader community genetics context.

Ethical tensions around “Selection of Life” and their influence on PGT-M acceptance

The questionnaire included an item asking whether respondents considered PGT-M to constitute “selection of life” (inochi no sentaku), a phrase commonly used in debates on prenatal diagnosis, particularly in relation to decisions involving termination of pregnancy. Although the term is more frequently associated with prenatal testing, it has also appeared in discussions of PGT-M in Japan and in international bioethical literature (e.g., Knoppers et al. 2006). The item was included to examine whether this ethical framing extends to PGT-M. Agreement was interpreted as reflecting heightened ethical concern regarding embryo selection.

International research suggests that when embryos are perceived as complete human lives, decisions about discarding embryos become ethically unacceptable, resulting in lower support for PGT-M (Knoppers et al. 2006). In Japan, framing embryo selection as “selection of life” has been associated with concerns about eugenics and discrimination, lending the expression a morally cautionary tone. Consistent with this perspective, respondents who characterized PGT-M as “selection of life” were less likely to consider the procedure acceptable, suggesting that perceptions of the moral status of embryos are closely linked to professional evaluations of PGT-M. A similar framing was observed in our previous study on PGT for hereditary breast and ovarian cancer, suggesting that this ethical lens is not limited to childhood-onset conditions (Terui-Kohbata et al. 2022).

Between the first and second surveys, there was a notable shift in perceptions among genetic medical professionals. The proportion who viewed PGT-M as “selection of life” decreased, while the proportion who felt “neither” increased—approaching the response distribution previously observed among non-medical participants (Terui-Kohbata et al. 2022). This shift may have been driven by the revised definition of severity in the 2022 JSOG guidelines and the increased involvement of genetic healthcare professionals in PGT-M–related practice.

In this survey, half of the respondents had direct experience with genetic counseling for PGT-M. According to the “2023 Case Review Results Report of Preimplantation Genetic Testing for Serious Genetic Diseases” published by JSOG, the number of PGT-M cases reviewed increased significantly (Japan Society of Obstetrics and Gynecology 2025), from 29 in 2015 (Japan Society of Obstetrics and Gynecology Ethics Committee 2017) to 72 in 2023. As the revised guidelines increase the likelihood that the range of indications for PGT-M will expand, the number of PGT-M cases is likely to increase, further expanding professional involvement in its implementation. These findings indicate that attitudes toward the ethical implications of PGT-M—particularly regarding “selection of life”—are dynamic and may continue to evolve in response to societal and institutional developments.

Institutional and professional factors shaping PGT-M implementation in Japan

Regarding the acceptability of PGT-M, factors such as whether genetic healthcare providers had prior counseling experience with CPS or PGT-M did not appear to influence their views. However, respondents involved in pediatric genetic counseling were less likely to regard PGT-M as acceptable. In addition, a significant difference was observed in the approach to providing information to clients based on the acceptability of PGT-M, suggesting that professional practice in genetic counseling may vary depending on the provider’s background.

The predominantly passive approach to providing information about prenatal testing and PGT-M may be shaped by the Japanese regulatory context. Because access requires centralized case-by-case approval by JSOG and eligibility is narrowly interpreted, professionals may hesitate to introduce PGT-M proactively when approval is uncertain. In addition, discussing PGT-M may involve sensitive value judgments in a sociocultural setting where “selection of life” carries strong ethical connotations. Japanese guidelines do not require routine proactive counseling about PGT-M, and thus information provision is left to professional discretion. Although the number of approved PGT-M cases has gradually increased in recent years according to JSOG reports, overall utilization remains limited compared with less centrally regulated systems. This centrally regulated, committee-based framework may partly explain the cautious attitudes observed among respondents, whose professional responsibilities are embedded within a restrictive institutional structure.

With the 2022 revision of the severity definition by JSOG, the review framework for PGT-M applications was also significantly restructured. Publicly available deliberation records from JSOG indicate that, even prior to the 2022 revision, PGT-M in Japan had been implemented through a multi-layered review process in which eligibility was assessed at the society level, while institutional ethics committees determined whether the procedure could be provided at individual medical facilities. Under this framework, clinical geneticists and certified genetic counselors play a key gatekeeping role by initiating consultations, interpreting disease severity, and guiding couples through the application process. Consequently, professionals’ ethical perspectives and interpretations of disease characteristics may directly influence whether and how couples gain access to PGT-M within the Japanese system. The revised PGT-M reviews involve not only the JSOG Ethics Councils but also disease-specific and medical genetics societies, increasing review steps but enabling broader, multidisciplinary input. This revised framework aims to ensure more comprehensive and ethically grounded assessments of eligibility for PGT-M. With this restructuring and new criteria for “serious” conditions, cases once ineligible may now qualify. These changes may be shifting professionals’ views closer to those of the public, especially on sensitive issues like “selection of life”. However, initial contact with clients typically occurs through clinical geneticists or genetic counselors at the applying institutions. Genetic professionals’ interpretation of disease characteristics, their individual values, and their perspectives on the “selection of life” may influence decisions about eligibility, potentially resulting in inconsistencies and client disadvantages.

To address such inconsistencies, some countries, including the United Kingdom, maintain a public list of eligible conditions for PGT-M to clarify the appropriateness of its application (Ginoza and Isasi 2020). While such standardization can mitigate variability in interpretation, Australia’s Ethical Guidelines for Assisted Reproductive Medicine warn that listing conditions may inadvertently stigmatize affected individuals by labeling diseases as inherently severe (National Health and Medical Research Council 2017). Furthermore, the regulatory approach itself may shape public attitudes toward PGT-M (Nakasato et al. 2022).

Within the current Japanese framework, genetic professionals occupy a pivotal position at the interface between institutional regulation and individual reproductive decision-making. The present findings suggest that variability in perceived acceptability of PGT-M may translate into differences in communication practices. Given that proactive information provision is not mandated by national guidelines, counseling practices may depend substantially on individual professional judgment. Ensuring that couples receive balanced, accurate, and non-directive information—regardless of providers’ personal views on the ethical status of PGT-M—remains essential to equitable access within a centrally regulated system. Continued monitoring of professional attitudes and counseling practices will therefore be important as indications and review structures evolve.