Balancing ethics and clinical need: The Japanese experience with preimplantation genetic testing for monogenic disease regulation and implementation

Abstract

Preimplantation genetic testing (PGT) has emerged as an important extension of assisted reproductive technologies. Alongside these technological advances, PGT has also generated substantial ethical and social debate, particularly regarding the sanctity of human life. Ethical perspectives are deeply context-dependent and vary significantly across different backgrounds. The unique historical and social context of Japan necessitated careful ethical discussions as PGT was introduced. The Japan Society of Obstetrics and Gynecology (JSOG) provided official guidance under which PGT was implemented. With these technological advancements, reliable and highly accurate genetic analysis has become possible across a broad spectrum of pathogenic genotypes up to this stage. However, the most challenging issues have been the ethical debate surrounding indication criteria that prioritize severity. “Severity” is a highly nuanced and multifaceted concept, making the establishment of a clear, universally applicable standard inherently difficult. JSOG's first ethical approval for PGT in Duchenne muscular dystrophy cases led to the birth of the first child conceived via PGT at Keio University Hospital in 2004 in Japan, followed by over 13 years of research and ongoing discussion that addressed issues such as disease definition, severity criteria, scope of genetic analysis, disclosure policies, and safety and accuracy concerns. However, for certain genetic disorders, determining the appropriateness of PGT solely based on genotype or the clinical course observed in affected family members can be challenging, such as triplet repeat diseases or mitochondrial diseases. Ethical debate must be seen not as an obstacle to progress, but as an ongoing process of reflective engagement, offering context-dependent guidelines rather than absolute prohibitions. Within this delicate balance of complex debate, constructive engagement between ethics and scientific progress carries a profound responsibility to serve as a driving force in advancing the health and well-being of humanity.