PGT-M & PGT-A Fertility Testing

Preimplantation genetic diagnosis (PGT-M) & preimplantation genetic screening (PGT-A) overview

PGT-M and PGT-A are the two types of genetic tests that evaluate the genetic composition of an embryo created through in vitro fertilization (IVF) before it is transferred to a woman’s uterus.

Genetic flaws can prevent embryos from implanting in the uterus and are a leading cause of miscarriage. In cases where implantation is successful and live birth occurs, genetic flaws can result in genetic disorders and birth defects.

Preimplantation genetic diagnosis (PGT-M) analyzes embryos to determine if a specific genetic disorder associated with illness, such as cystic fibrosis or muscular dystrophy, is present.

Preimplantation genetic screening (PGT-A) evaluates embryos for abnormalities in the chromosomes that result in pregnancy failure as well as birth defects such as Down syndrome.

Parents’ family history of such genetic issues, as well as other factors noted by a fertility specialist, are leading indicators that either PGT-M or PGT-A may be advised.

Preimplantation genetic diagnosis

PGT-M analyzes embryos for a specific genetic mutation (error) associated with illness.

Preimplantation genetic diagnosis identifies single gene mutations and abnormalities in an embryo’s DNA sequence that cause a specific disease, such as cystic fibrosis or sickle cell anemia. If PGT-M testing detects a gene mutation related to a specific genetic disorder, a couple can choose not to transfer that embryo after IVF.

PGT-M technology can detect many, but not all, gene abnormalities in embryos, including single gene mutations such as BRCA1 and 2 mutations that predispose a woman and her offspring to breast and ovarian cancer.

Candidates for PGT-M

Preimplantation genetic diagnosis is advisable for couples who have, or are at risk for having, a specific genetic disorder they could pass on to their child. For example, even if a couple does not have cystic fibrosis they can still have a child with that disease if they are both carriers of the gene mutation.

Single gene disorders can be passed from parent to child through autosomal dominant, autosomal recessive, X-linked dominant or X-linked recessive gene traits. This means that in some cases, a couple may be at risk for having a child with a genetic disorder if only one parent is a carrier of a mutated gene. If a disorder is X-linked, or linked to the sex chromosome, children of one gender often have a higher risk for inheriting a specific disorder.

Most genetic mutations are rare, affecting about 1 percent of pregnancies with genetic disease or defects. Family history, including medical history and ethnic backgrounds, can indicate which mutation a couple may be at risk of carrying. For instance, people of Ashkenazi Jewish heritage are more likely to be carriers of Tay-Sachs disease.

A person can undergo carrier testing for specific genetic diseases if there is any likelihood that he or she may have inherited a genetic disorder. Since PGT-M can only evaluate embryos for a single disorder at a time, it’s essential to know which genes may be abnormal before an embryo is biopsied.

Common conditions PGT-M evaluates for include:

• Cystic fibrosis
• BRCA1 and BRCA2 mutations (breast and ovarian cancer)
• Hemophilia
• Sickle cell anemia
• Down syndrome
• Muscular dystrophy
• Huntington’s disease
• Tay-Sachs disease
• Fragile-X syndrome.

Preimplantation genetic screening

PGT-A evaluates embryos for a normal number of chromosomes (known as euploidy), and thus screens for a wide range of genetic defects.

Aneuploidy is the term used to describe a cell or an embryo which is either missing or has an extra copy of a chromosome. Typically, human cells have 46 chromosomes, matched in pairs. Twenty-three chromosomes are inherited from each parent during the process of fertilization.

A euploid embryo contains 46 chromosomes, or the normal amount. An aneuploid embryo carries an abnormal number of chromosomes, either too many or too few. Down syndrome, Edwards syndrome and Turner syndrome are three birth defects caused by aneuploidy.

Unequal division of the egg or sperm cells during fertilization can result in an embryo with too many or too few chromosomes. These disorders do not typically run in families but occur spontaneously and are very common in developing eggs and embryos. Up to 60 percent of early miscarriages are due to aneuploidy, and the risk for aneuploidy increases with a woman’s age.

Because PGT-A identifies genetically normal embryos before transfer to the uterus, it is used to improve the likelihood of implantation after IVF and reduce the risk of miscarriage. Other genetic tests, namely amniocentesis and chorionic villus sampling, can be used to test for genetic abnormalities after a woman is already pregnant.

Candidates for PGT-A

• Couples who have experienced two or more miscarriages
• Couples who have had previously unsuccessful IVF treatments
• Individuals with unexplained infertility
• Women of advanced maternal age
• Couples with a history of chromosomally abnormal children or pregnancies
• Those with chromosome translocations
• People with a family history of structural chromosome defects