Preimplantation genetic testing (PGT) is used in reproductive medicine, in conjunction with in vitro fertilization (IVF). This process analyzes embryos for genetic characteristics before transfer to the uterus. PGT aims to improve the chances of a healthy pregnancy and birth for couples at risk of passing on genetic conditions. PGT-P, or Preimplantation Genetic Testing for Polygenic disorders, is a specialized form of PGT focusing on complex traits influenced by multiple genes.
Understanding PGT-P
PGT-P screens embryos for predisposition to polygenic disorders, conditions influenced by many genes and environmental factors. Unlike monogenic disorders, caused by a single gene mutation, polygenic disorders involve multiple genes, each contributing a small effect. This makes their inheritance pattern more complex and less predictable than single-gene disorders.
PGT-P differs from other forms of PGT, such as PGT-M (for monogenic/single gene defects like cystic fibrosis) and PGT-A (for aneuploidy, or chromosomal abnormalities like Down syndrome). While PGT-M and PGT-A typically provide a definitive “yes” or “no” answer regarding a specific genetic condition or chromosomal abnormality, PGT-P provides a risk assessment. The purpose of PGT-P is to estimate an embryo’s genetic susceptibility to complex conditions, rather than offering a diagnosis. This distinction is important because polygenic disorder development is not solely determined by genetics; environmental factors also play a significant role.
The PGT-P Process
The PGT-P process begins with in vitro fertilization (IVF), as embryos must be created in a laboratory for testing. After eggs are retrieved and fertilized, embryos develop for several days to the blastocyst stage (five to seven days post-fertilization). At this stage, the embryo differentiates into two main parts: the inner cell mass, which becomes the fetus, and the trophectoderm, which forms the placenta.
A small number of cells, typically 3-10, are removed from the trophectoderm layer of each embryo during a trophectoderm biopsy. This biopsy is performed by an embryologist and has low risk to the embryo. The biopsied cells contain the embryo’s genetic material, which is sent to a genetics laboratory for analysis.
In the laboratory, DNA from the biopsied cells is amplified for genetic analysis. Genetic analysis techniques, such as whole-genome sequencing or single nucleotide polymorphism (SNP) microarrays, examine hundreds of thousands of genetic variants across the embryo’s genome. This data is used to calculate a “polygenic risk score” (PRS) for each embryo, which estimates its genetic predisposition to specific polygenic conditions. The PRS is derived from large datasets that correlate genetic variations with disease outcomes in large populations. Disease risks for each embryo may be merged into a single number, sometimes called an Embryo Health Score (EHS), which helps rank embryos from lowest to highest risk.
Embryos are then cryopreserved (frozen) while awaiting test results, which typically take about 14 days. The results inform the selection of embryos for transfer to the uterus, aiming for those with a lower estimated risk for the screened conditions.
Conditions Addressed by PGT-P
PGT-P assesses genetic risk for common complex diseases influenced by multiple genes and environmental factors. These conditions are often prevalent in adults and tend to cluster in families, though their inheritance patterns are not as straightforward as single-gene disorders. Examples include heart disease (e.g., coronary artery disease, heart attack) and type 1 and type 2 diabetes.
PGT-P also assesses susceptibility to specific cancers, including breast cancer, prostate cancer, testicular cancer, basal cell carcinoma, and malignant melanoma. Neurodevelopmental conditions like schizophrenia can also be screened. PGT-P evaluates an embryo’s predisposition or susceptibility, indicating an increased likelihood of developing a condition, not a definitive diagnosis. The actual development of these conditions is also influenced by lifestyle, environmental exposures, and other non-genetic factors throughout an individual’s life.
Weighing the Use of PGT-P
Considering PGT-P involves evaluating its capabilities and limitations, alongside personal and ethical considerations. The predictive accuracy of polygenic risk scores is a significant limitation, as these scores are estimates of susceptibility rather than guarantees of disease presence or absence. The influence of environmental factors on polygenic conditions means that a low polygenic risk score does not eliminate the possibility of developing the condition, and a high score does not guarantee its development. Additionally, the predictive accuracy of polygenic risk scores can be lower in populations with different ancestries than those primarily represented in the research data used to develop the scores.
The decision to use PGT-P also carries emotional and financial implications. The process adds to the overall cost of IVF, and there is no guarantee that embryos with significantly lower risk scores will be identified, especially if only a limited number of embryos are available. Prospective parents might also face complex decisions about discarding embryos based on risk assessments, which raises ethical discussions about embryo selection and the moral status of embryos. Some professional societies advise against the routine clinical implementation of PGT-P, citing concerns about its utility and ethical implications.
Genetic counseling is recommended for individuals or couples considering PGT-P. A genetic counselor provides a comprehensive understanding of the test’s benefits, limitations, and result interpretation within family history and individual circumstances. This professional guidance helps ensure prospective parents make an informed decision aligned with their values and expectations for their future child’s health.