How Can PGT Help My Patients?

To appreciate how PGT can be helpful to couples it is important to understand chromosomes. Chromosomes are the physical structures made of DNA that contain the genes necessary for development. Chromosomes are located in the center of the cell, in the area called the nucleus. A normal human cell should contain exactly 46 chromosomes. There are 23 pairs of chromosomes. The first 22 pairs are identified by number and organized by size. The 23rd pair, the sex chromosomes, determines gender. Females have two of the same sex chromosome, called the X chromosome, while men have two different sex chromosomes, known as the X and Y chromosomes. A normal set of chromosomes is 46, XX for a female and 46, XY for a male. In a normal conception, both the egg and sperm cells should contribute exactly 23 individual chromosomes, one of each of the 22 numbered pairs (called autosomes) and one of the sex chromosome pair. When an egg with 23 chromosomes fuses with a sperm with 23 chromosomes, the correct chromosome number of 46 (23 pairs) is again present, and the fertilized embryo has the best possible chance of developing appropriately. When an egg or sperm cell divides improperly as it is developing, the mature egg or sperm may contain more or less than 23 chromosomes. If this egg or sperm is used for fertilization, the resulting embryo will not contain exactly 46 chromosomes, but more or less than 46, known as aneuploidy.

PGT uses the most advanced technology currently available to provide the earliest possible information about the health of an embryo in order to minimize the chances for miscarriage or chromosomally abnormal pregnancies. PGT using next generation sequencing (NGS) technology is a relatively new and technically demanding procedure and thus there is a small chance for inaccuracy. The first step in NGS testing is the extraction of DNA from a single cell or a small number of cells. About 4% of the time the biopsied cells fail to get into the DNA extraction solution or the DNA is degraded to the point where it cannot be analyzed. In such cases, it is sometimes possible to take another biopsy and achieve a result. Very infrequently an embryo will have an extra whole set or sets of chromosomes and these may not always be detected by NGS. However, such polyploidy embryos are not compatible with live births. Sometimes there are errors in early division of an embryo creating cells that have different genetic content compare to other cells in the same embryo. This finding is called mosaicism. If an embryo is mosaic and multiple cells are tested from such an embryo, some normal and some cells containing a gain or loss of a chromosome(s), the NGS technology may show a chromosomal copy number value between 1 and 2 copies, or between 2 and 3 copies, with a value of 2 as normal for autosomes. Results displaying mosaicism are analyzed to determine levels of mosaicism as low, moderate, or high. In our lab, embryos displaying low mosaicism of 25% or less may be considered for transfer. Errors, therefore, may be due to technical limitations or mosaicism. These could result in a false positive (calling a normal embryo abnormal) or a false negative (calling an abnormal embryo normal). The technical accuracy of NGS in our lab is approximately 98%. 

Yes. Substantial data indicates that PGT does not increase birth defects over that of the general population. Removal of a few cells from the outer layer (trophectoderm) does not alter the ability of that embryo to develop a normal pregnancy; in fact, biopsy avoids disrupting the embryo’s inner most cells that will form the fetus. In embryos undergoing PGT testing, many fewer pregnancies will end in miscarriages due to chromosomal disorders since abnormalities are identified prior to embryo transfer.

The combination of normal genetic testing with normal embryo morphological (physical) appearance indicates the highest chance of an embryo transfer resulting in a healthy pregnancy. Sometimes embryos that have a normal genetic test will have a physical problem that prevents them from typical development. Alternatively, some embryos that have abnormal genetic tests will appear to be physically normal. Therefore, embryos that have both a normal genetic test result and proper morphology are desirable. Final decisions regarding number and selection of embryos to transfer into the uterus are made with the advice of your medical team at your local clinic. With the benefit of PGT, couples can consider single embryo transfer with higher confidence of a pregnancy without the consequence of twin or triplets pregnancies.