Preimplantation genetic testing screens for genetic events in embryos as a result of in vitro fertilization procedures (IVF). PGT-aneuploidy (PGT-A) is used to analyze the number of chromosomes, PGT-SR, the structure rearrangement of each chromosome, and PGT-monogenic (PGT-M), the presence of genetic mutations in single gene, potentially linked to a disorder. All PGT methods are used to determine the suitability of an embryo for implantation.
Chromosomes are sequences of DNA molecules packaged into thread-like structures. We have a total of 23 pairs of chromosomes which consists of 22 pairs of autosomes (non-sex chromosomes) and a pair of either XX or XY chromosomes (sex chromosomes).
Any chromosomal abnormalities, either in number or structure, in an embryo could cause miscarriage or a range of disorders such as Down syndrome (three copies of chromosome 21), or Turner syndrome (when a female has only one X chromosome).
Genetic test results from preimplantation genetic testing of aneuploidy or structural rearrangement classify an embryo into one of the three categories—euploidy, aneuploidy, and mosaic. An euploidy embryo means the chromosomes are normal, and a recommendation for implantation is made. An aneuploidy embryo means one or more chromosomal aberrations are detected, and it is not recommended for implantation. A mosaic embryo means some of the embryonic cells have normal chromosomes and some cells do not. The recommendation to implant a mosaic embryo depends on the chromosomal aberrations and if there are no other viable embryos available.
When predisposition to a specific single genetic variant (typically single nucleotide variant - SNV) is known within a family, embryos are analyzed for the presence of the known mutation. This allows for selection of only non-carrier embryos to be transferred to the host.
A preimplantation genetic test is performed by taking a biopsy of a single cell or multiple cells from a developing embryo before implantation.
First-generation preimplantation genetic tests are PCR-based for detection of mutations on a single gene or fluorescent in situ hybridization assays (FISH) for chromosomal numeric or structural aneuploidies. Both of these techniques have limitations such as resolution, accuracy, time to results, and coverage.
Array-CGH or aCGH, a more comprehensive screening method, is a microarray-based technology that can analyze the entire set of chromosomes for structural and numerical changes with higher resolution, coverage, and faster turn-around time than the first-generation tests.
Next-generation DNA sequencing, the current gold standard in PGT, is the most advanced, rapid, and comprehensive method for preimplantation screening. DNA is extracted from a single cell or multiple cells, amplified, and sequenced. In the same run, the DNA sequences are analyzed for single gene mutation and chromosomal structural and numerical changes to determine whether an embryo is carrying a mutation and/or is euploid, aneuploid, or mosaic.
Preimplantation genetic testing is used to screen in vitro fertilized embryos for chromosomal abnormalities and genetic mutations with the goal of reducing miscarriage occurrences, increasing the probability of a successful pregnancy, and delivering a healthy baby. PGT is a prioritization tool that can reduce the total number of IVF cycles, thus shortening time to pregnancy and lowering IVF-related costs.