Whereas best practice of clinical prediction of human phenotypes by polygenic risk score (PRS) has yet to be fully implemented, commercial industries already offer pre-implantation genetic testing for PRS (PGT-P) to select embryos with 'desirable' potential. However, its efficacy is questionable due to the current technical challenges, which also raise ethical concerns. Our in-silico simulations utilizing biobank resources revealed that the embryo selected by PGT-P substantially differs depending on the choice of methods and the random fluctuation of the PRS construction. Here, we outline the technical challenges and also the ethical concerns that remain even if the technical challenges are solved, and hope to call on a society-wide discussion for this technology.

The authors have declared no competing interest.

S.N. was supported by Takeda Science Foundation. Y.O. was supported by JSPS KAKENHI (22H00476), AMED (JP21gm4010006, JP22km0405211, JP22ek0410075, JP22km0405217, JP22ek0109594, JP223fa627002, JP223fa627010, JP233fa627011, JP23zf0127008), JST Moonshot R&D (JPMJMS2021, JPMJMS2024), Takeda Science Foundation, Bioinformatics Initiative of Osaka University Graduate School of Medicine, Institute for Open and Transdisciplinary Research Initiatives and Center for Infectious Disease Education and Research (CiDER), and Center for Advanced Modality and DDS (CAMaD), Osaka University. N.O. was supported by AMED (JP22dk0307113).

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Osaka University Research Ethics Review Committee gave ethical approval for this work under the ID of 734-18

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

The genotype data of Biobank Japan are available at NBDC Human Database (https://humandbs.biosciencedbc.jp/en/) with the accession ID of JGAS000114 and JGAS000412. The GWAS summary statistics for height and the height PRS calculated with SBayesC are publicly available at https://portals.broadinstitute.org/collaboration/giant/index.php/GIANT_consortium_data_files.