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

Abstract

Preimplantation genetic testing for monogenic disorders (PGT‐M) was originally developed to identify embryos affected with serious childhood‐onset disorders, but its use has recently broadened. Guidance on the use of PGT‐M in the United States (U.S.) is currently limited, with no formal laws or guidelines established on its use. The goals of this study were to determine for which types of conditions U.S. laboratories currently do not offer PGT‐M, to explore ethical considerations U.S. laboratory genetic counselors (GCs) take into consideration when deciding to accept or reject a PGT‐M request, and to explore whether U.S. laboratory GCs believe PGT‐M should be offered for conditions with reduced penetrance or for variants of uncertain significance (VUS). Qualitative analysis of semi‐structured interviews with nine genetic counselors, from five different PGT‐M laboratories, was conducted. Participants were required to be GCs working at a PGT‐M laboratory in the U.S. and either actively counsel patients on PGT‐M or determine a patient's eligibility for PGT‐M. Two participants reported their separate laboratories have no limitations for allowable PGT‐M testing, while the other seven participants representing three other laboratories reported having limitations. The main ethical consideration GCs reported considering when deciding to accept or reject a PGT‐M request was patient autonomy, with a focus on the patient understanding risks of the testing. All participants reported believing PGT‐M should be allowable for conditions with reduced penetrance and VUS, with all participants stating their respective laboratories allow for this currently. However, all participants reported a lack of sufficient guidelines and that having guidelines from a professional organization would be beneficial to their practice. In conclusion, lack of current guidelines in the United States has created discrepancies between PGT‐M laboratories. PGT‐M laboratory GCs support the use of PGT‐M for conditions with reduced penetrance and VUS with informed consent. The need for guidelines is supported.

Preimplantation genetic testing: A remarkable history of pioneering, technical challenges, innovations, and ethical considerations

“…Balancing the desire for patient autonomy and minimizing risks of disease through PGT with the need to provide clear information, while addressing individual patient perspectives represents a challenge (35028914) (Siermann et al, 2022). Recent articles have indicated areas where appropriate guidelines and patient support may overcome some challenges (Hughes et al, 2021; Porto et al, 2022; Siermann et al, 2022).…”

Preimplantation Genetic Testing for Adult-Onset Neurodegenerative Disease

“…There are no specific guidelines for PGT-M in the United States, and different laboratories may have their own discretion for accepting PGT-M cases. 16 Our team has anecdotally witnessed more than 1 instance of a family learning their genetic diagnosis, only to then be unsuccessful in finding a laboratory capable of providing PGT-M due to the specific type of variant or other technical barriers. In addition, PGT-M technology cannot eliminate genetic risk in future generations.…”