Preimplantation Genetic Testing for Monogenic Conditions: Is Cell-Free DNA Testing the Next Step?

Genetic assessment of an embryo via preimplantation genetic testing (PGT) represents an important reproductive option for couples wanting to try and improve success rates from in vitro fertilisation (IVF) cycles, as well as reduce their risk of having a child born with a genetic condition. Currently, biopsy of the developing embryo prior to transfer allows genetic assessment of an embryo for either chromosome copy number (aneuploidy [PGT-A] or segmental rearrangement [PGT-SR]) or to avoid the transmission of a single gene condition (monogenic conditions [PGT-M]). However, this technology is invasive and commands considerable resources. Non-invasive PGT (niPGT) offers a potential alternate mode of embryonic analysis. Whilst the utility of niPGT-A has been recently explored, there has been limited consideration of niPGT-M as an option for couples at risk of passing on a single gene or chromosomal condition. This review examines the historical and current clinical context of preimplantation embryonic analysis for monogenic conditions, in addition to important considerations surrounding the origin and analysis of cell-free deoxyribose nucleic acid (cfDNA), whether it is sourced via blastocentesis or spent embryonic culture medium (SCM). Future capabilities of this testing modality will almost certainly be enhanced by integration of whole genome sequencing into everyday practice. In addition, the increased utilisation of reproductive carrier screening as part of standard reproductive healthcare will likely result in the identification of a larger high-risk population. As a result, stratification of limited and highly specialised reproductive genetic resources will be required. Prospective parents should continue to be made aware of the limitations of this technology, with prenatal confirmatory testing remaining an essential part of antenatal care in these patients. However, niPGT-M poses an important alternate testing modality for high-risk couples, particularly in the setting of embryos that cannot be biopsied for traditional PGT-M and as demand for this treatment continues to grow.

Automated summary

Preimplantation genetic testing offers an important reproductive option for couples seeking to improve IVF success rates and reduce genetic disease risks. Non-invasive PGT may provide an alternate mode of embryonic analysis, with potential for high-risk couples in situations where traditional testing is not possible.