Genetic Testing

With PGT, the embryos can be tested for genetic mutation before they are transferred to the uterus. For this reason, PGT increases the chance of IVF success and increases the probability of having a healthy baby.

Patients with many inherited familial diseases can have their embryos tested to determine their genetic make-up. If parents have known gene mutations for a particular genetic disease, preimplantation genetic testing, PGT, can be considered. (patients with a history of single-gene disorders (such as cystic fibrosis, sickle cell anaemia, SMA) and patients with a history of sex-linked disorders (such as Duchenne muscular dystrophy and Fragile X syndrome)).

PGT makes it possible for couples or individuals who have or who carry serious inherited disorders to decrease the risk of passing the disorder on to their child.

Furthermore, it is recommended to apply genetic test for the couples above 35 years old who have higher risk to have genetic disorders.

• Preimplantation genetic screening for abnormal chromosome number (PGT-A)
• Preimplantation genetic testing for monogenic disorders or single gene defects (PGT-M)
• Preimplantation genetic testing chromosomal structural rearrangement (PGT-SR) for known chromosomal mis-arrangements such as inversion and translocation.

PGS checks for extra or missing chromosomes that are called aneuploidy, thus; it has been renamed as Preimplantation Genetic Testing for Aneuploidies (PGT-A).

PGT-A is designed to assess whether embryos have the correct amount of genetic material. Genetic material is housed within structures called chromosomes, and when chromosomes are missing or extra, it can lead to improper development and functioning. Embryos with the incorrect amount of genetic material, known as aneuploid embryos, typically fail to transfer, which result in a miscarriage or lead to the birth of a child with a genetic disorder. Therefore, the biggest advantage of PGT-A is to identify embryos with a higher likelihood of resulting in a successful and healthy pregnancy.

PGT-A test can detect conditions like Down syndrome—an extra chromosome number 21.

By the time a woman is 35 years old, about half her embryos are expected to be aneuploid. By age 40, this increases to about 80%.

(Source: www.reproductivefacts.org)

PGT-M analyses for specific gene mutations that one (or both) of the parents is known to carry. A family background of genetic disorders in one or both parents can increase the possibility for a child to be born with a genetic mutation.

PGT-M checks for common disorders including Huntington’s disease and early-onset Alzheimer’s disease; sickle cell anaemia, cystic fibrosis, Tay-Sachs disease, for cancer predisposition genes, such as BRCA mutations; and for nonfatal but potentially serious conditions that are apparent at birth, such as focal dermal hypoplasia. These common disorders may vary as per regions.

PGT- SR is used to detect unbalanced chromosome rearrangements. Patients who have a known structural rearrangement are more at risk for producing embryos that do not have the correct amount of chromosomal material. The affected embryos are less likely to result in a live birth. Patients with these problems often have repeated miscarriages.

PGD is for someone who has or is a carrier of a known genetic disorder. PGD is also used for gender determination when there is risk for inherited disorders that can be carried to specific gender and for family balancing with desired gender.

PGS may be recommended for someone with recurrent miscarriage, someone who is older than 35  or whose ovaries do not work as well as expected, or someone with multiple failed fertility treatments. Some couples also can choose to do PGS for other reasons as explained above.

How is genetic testing performed with different techniques?

One or more cells are taken from an embryo and sent for genetic testing while the embryo is growing in the IVF laboratory.

The testing can be done at different stages using different techniques. Techniques include fluorescence in-situ hybridization (FISH), next generation sequencing (NGS), comparative genomic hybridization (CGH).

Fluorescence in situ hybridization (FISH) is a laboratory technique for detecting and locating a specific DNA sequence on a chromosome.

FISH technology can be used for discovering common abnormalities on such chromosomes 13, 15, 16, 17, 18, 21, 22, X, Y out of 23 chromosomes.

FISH technique is also one of the methods used in gender determination.

Next Generation Sequencing (NGS) is a newer technology that has been increasingly utilized for testing IVF embryos since about 2015. NGS appears to be better at detecting smaller segmental changes compared to aCGH. It is also better at detecting partial aneuploidy and small unbalanced translocations. Mosaicism is probably more likely to be discovered using Next-Generation Sequencing.

Comparative Genomic Hybridization (often referred to as CGH, or aCGH) is a microarray technology that allows comprehensive gen screening before the embryo transfer.

With microarray CGH, the actual DNA in the embryo is compared to a known normal DNA specimen utilizing thousands of specific genetic markers.

It is possible to screen the entire genome with a series of CGH (aCGH) methods to determine chromosomal diseases and imbalances.

aCGH ensures that all chromosomes (23 chromosomes) are examined and the healthiest embryo is selected for embryo transfer.