Non-invasive PGT

Preimplantation genetic testing is implemented worldwide as an effective tool to avoid transmission of single gene disorders and/or chromosome abnormalities. This approach requires the obtention of representative samples from embryos in order to infer its genetic status. Nowadays, the embryo biopsy is the first-choice method for embryo sampling. Biopsy procedures are safe and widely performed in the clinical routine. However, this intervention is invasive and requires trained personnel and investment in specific equipment. Recently, new sampling methods have been suggested under the term of “non-invasive”. These approaches are based on the existence of cell-free DNA into the embryo or its environment. An increasing number of studies suggest the collection of fluid from embryos or spent culture medium to obtain cell-free DNA to assess the genetic condition of preimplantation embryos avoiding embryo biopsy. The reliability of this attractive idea needs to be confirmed and validated. In this sense, this work offers a deep review of data published to date. Several methods of DNA detection, quantification and amplification have been tested and different protocols and culture systems, with or without additional embryo manipulations, are being investigated. In general terms, an enormous variability among published results is noteworthy. Central aspects as DNA detection rates, contamination with extraembryonic DNA and concordance between results (cell-free DNA versus embryo samples) are centring proofs-of-concept and validation experiments. However, basic questions as the biological origin and representativeness of cell-free DNA are pending to be answered. Solved, unsolved and serious limitations of the new approaches are discussed. A final reflection respecting the state of the technique is offered.