Preimplantation genetic testing (PGT) is an advanced laboratory technique used within the process of in vitro fertilization (IVF). PGT assesses the genetic makeup of an embryo before it is transferred to the uterus. The goal of this testing is to identify genetically healthy embryos, which helps increase the chance of a successful pregnancy and the birth of a healthy child. Understanding PGT involves knowing its purpose, how it is performed, and what the different results mean for family planning.
Defining Preimplantation Genetic Testing
PGT examines embryos created through IVF for genetic or chromosomal abnormalities before implantation occurs. This procedure provides fertility specialists with information about the embryo’s genetic composition, helping them select those most likely to result in a successful, ongoing pregnancy.
The current term, PGT, was introduced around 2017 to replace older terminology like Preimplantation Genetic Screening (PGS) or Preimplantation Genetic Diagnosis (PGD). Reproductive health organizations standardized the system, adding a specific letter to denote the type of condition being tested.
PGT is performed after the embryo is created in the lab but before it is placed inside the patient’s uterus. It is a screening tool, not a treatment that corrects genetic issues.
PGT is recommended for patients with a history of recurrent pregnancy loss, advanced maternal age, or those with a known genetic disorder in the family. Its use allows for the selection of embryos less likely to cause implantation failure or miscarriage, aiming to improve overall IVF outcomes.
The Specific Categories of PGT
PGT is divided into three distinct categories, each targeting a different type of genetic issue.
PGT-A (Aneuploidy)
PGT-A screens for aneuploidy, which is an incorrect number of chromosomes, such as having an extra copy (trisomy) or a missing copy (monosomy). This test ensures the embryo has the correct total of 46 chromosomes, arranged in 23 pairs. PGT-A is often recommended when advanced maternal age increases the risk of chromosomal errors. Identifying these numerical abnormalities helps prioritize the transfer of chromosomally normal, or euploid, embryos.
PGT-M (Monogenic Disorders)
PGT-M tests for monogenic disorders, which are caused by a mutation in a single gene. This test is used when parents are known to carry a specific genetic mutation, such as those causing Cystic Fibrosis or Tay-Sachs disease. The goal is to prevent the transmission of a known familial disease.
PGT-SR (Structural Rearrangements)
PGT-SR is designed for couples where one or both partners carry a structural chromosomal abnormality, such as a translocation or inversion. Although the carrier parent may be healthy, they are at a higher risk of producing embryos with an unbalanced arrangement. Unbalanced structural rearrangements can lead to recurrent miscarriages or developmental issues. PGT-SR analyzes the embryo to ensure the genetic material is present and properly arranged, requiring a unique workup to detect the specific rearrangement.
The PGT Procedure
The PGT procedure begins after embryos are created in the IVF laboratory and have grown for several days. Testing is performed when the embryo reaches the blastocyst stage, usually on day five or six of development. A blastocyst has two main cell groups: the inner cell mass (which forms the fetus) and the trophectoderm (which forms the placenta).
At this stage, an embryo biopsy is performed under a high-powered microscope. The embryologist carefully removes a small cluster of cells, typically five to ten cells, from the trophectoderm layer. This sampling uses specialized micropipettes and often a laser to separate the cells from the embryo.
The goal is to obtain enough genetic material for accurate analysis without compromising the embryo’s viability. Immediately following the biopsy, the embryo is frozen using vitrification, a fast-freezing method. Freezing is necessary because the genetic analysis of the biopsied cells takes several days to complete.
The biopsied cells are sent to a specialized genetics laboratory for analysis. The DNA is amplified and analyzed using advanced molecular techniques, such as Next-Generation Sequencing (NGS). This technology allows technicians to count or sequence the chromosomes to look for abnormalities associated with PGT-A, PGT-M, or PGT-SR.
Understanding PGT Results
PGT results are classified into three main categories.
Euploid
An embryo is considered euploid if testing shows the correct number of chromosomes, indicating a genetically normal result. These embryos are prioritized for transfer due to their higher potential for implantation and a healthy birth.
Aneuploid
An embryo is labeled aneuploid if it is found to have an incorrect number of chromosomes. Aneuploid embryos are not recommended for transfer, as they are a leading cause of implantation failure and miscarriage. For PGT-M and PGT-SR, results indicate whether the specific disorder or structural rearrangement was detected.
Mosaic
A third classification is the mosaic embryo, which contains a mixture of both euploid (normal) and aneuploid (abnormal) cells. The result is based on the proportion of abnormal cells found in the trophectoderm sample, categorized as low-level or high-level mosaicism. Decisions regarding the transfer of mosaic embryos are complex and require careful consultation, as outcomes can vary.
PGT is a screening tool, not a diagnostic test for the fetus itself, and misdiagnosis is rare with modern techniques. Even with a euploid PGT result, standard prenatal testing is recommended for all pregnancies.