Genetic Testing: PGS and PGD

Preimplantation genetic screening (PGS) and preimplantation genetic diagnosis (PGD) at a glance

  • Preimplantation genetic screening (PGS) examines embryos during in vitro fertilization (IVF) and before possible transfer to a woman’s uterus for a range of genetic problems caused by chromosomal aneuploidy, which means that there is a missing or an extra chromosome in the embryo.
  • Preimplantation genetic diagnosis (PGD) analyzes embryos created with IVF for a specific genetic disorder(s) one or both of the parents may carry.
  • Chromosomal abnormalities often result in failed IVF attempts because they are a major cause of unsuccessful embryo implantation and miscarriage.
  • Embryologists use genetic testing to analyze embryos to find defects, and those embryos will not be transferred to the woman’s uterus to achieve a pregnancy.
  • PGD can detect single gene defect disorders that can result in such diseases as muscular dystrophy, sickle cell anemia, cystic fibrosis and Tay-Sachs.
  • PGS can detect genetic conditions such as Trisomy 21, or Down syndrome, and Trisomy 18, known as Edwards syndrome.

What is preimplantation genetic testing?

Preimplantation genetic testing refers to the two types of tests that may be performed on embryos during IVF, preimplantation genetic screening (PGS) and preimplantation genetic diagnosis (PGD). Fertility specialists conduct these tests to determine if embryos have genetic abnormalities that often cause failed implantation and miscarriage, resulting in unsuccessful IVF. Embryos found to have such defects are excluded from being transferred to the mother’s womb for a pregnancy.

During IVF, couples may elect to have PGS or PGD testing to identify genetic or chromosomal abnormalities in the embryos. Embryos free of genetic defects are selected for transfer to the mother’s womb.

This testing increases the likelihood of becoming pregnant and also improves live birth rates using IVF. Research has shown that genetic defects in embryos are a major cause of failed pregnancy and live birth.

Preimplantation genetic testing has two important benefits:

  • Lower risk of parents passing on a genetic disorder to their child.
  • Higher possibility of a healthy pregnancy and successful birth through IVF with embryos free of genetic defects.

A fertility specialist can consult with couples interested in PGS or PGD to discuss available procedures.

How are the two types of genetic testing different?

Preimplantation genetic screening is an analysis of embryo cells to determine if there is the normal amount of chromosomes, called euploidy. An unequal division of either sperm or egg cells can result in an embryo having too few or too many chromosomes.

Most people have 46 chromosomes because they inherit 23 chromosomes from each parent. If an embryo or a cell is missing a chromosome or has an extra one, it is called aneuploidy. Monosomy is a missing chromosome and trisomy is an extra chromosome.

Trisomy of chromosome pairs 13, 18 and 21 can result in live birth, involving the genetic defects Down syndrome (Trisomy 21), Turner syndrome (Trisomy 18) and Patau syndrome (Trisomy 13). Down syndrome affects 1 in 700 babies, according to the Centers for Disease Control and Prevention.

Aneuploidy is one of the greatest causes of failed implantation for pregnancy and miscarriage, as well as a major cause of birth defects in children. Prospective parents may select PGS to prevent implantation of embryos with aneuploidy.

Candidates for genetic testing

Women and couples undergoing IVF should consider PGS if they are at risk of passing along aneuploidy to their child. Other candidates for PGS include:

  • Couples who have had a previous pregnancy with aneuploidy.
  • Women who have had two or more miscarriages.
  • Women who have experienced previous failed embryo implantation.
  • Women diagnosed with unexplained infertility.
  • Women older than age 35.
  • Women who have undergone numerous unsuccessful fertility treatments.

Preimplantation genetic diagnosis analyzes for specific gene mutations that one (or both) of the parents is known to carry or is suspected of carrying. 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.

The ultimate goal of PGD analysis is to select only chromosomally “normal” embryos for transfer, which improves the chance of having a baby and of having a baby without resulting health problems.

A disorder involving a single specific gene is due to a mutation in the DNA sequence. This results in diseases such as cystic fibrosis and sickle cell anemia. It can also cause an inherited genetic mutation such as the BRCA1 and BRCA2 mutations that greatly increase a woman’s risk of breast cancer and ovarian cancer.

During PGD, the fertility specialist will test the embryos for specific inherited and non-inherited genetic disorders before the embryo is transferred to the woman’s uterus. This is helpful for couples with known chromosomal or genetic abnormalities, women with recurrent IVF failure and couples with a history of recurrent pregnancy loss with or without a genetic basis.

PGD examines common disorders including:

  • Huntington’s disease.
  • Sickle cell anemia.
  • Muscular dystrophy.
  • Cystic fibrosis.
  • BRCA1 & BRCA2 mutations.
  • Fragile-X syndrome.
  • Tay-Sachs disease.

Parents may pass single-gene disorders to a child through genetic traits. Preimplantation genetic diagnosis can find the gene mutation that causes these disorders, allowing a couple to decide if they want to implant specific embryos.

How are PGS and PGD performed?

The two main steps to both PGD and PGS are the same. The first step is an embryo biopsy. The second step is analysis of the biopsy by a laboratory to conduct genetic testing on DNA.

In both forms of testing, the biopsy is at the blastocyst (day 5 of embryo culture) stage of development. The blastocyst consists of two cell types, trophectoderm (TE) that allows the placenta to develop and the inner cell mass (ICM) that later develops into the baby.

The biopsy removes 3-10 cells from the trophectoderm (pre-placenta) for laboratory testing for genetic disorders. The cells that are destined to make the baby are not disturbed. Results are usually available within 7-10 days following the biopsy. The blastocyst is frozen right after it is biopsied to wait for the results of the testing and then is thawed and transferred to the woman in a subsequent cycle.

Genetic testing risks

There are no documented health risks for children born after PGS or PGD testing beyond the normal health risks to mother and child through IVF. Risks of PGS and PGD include damage to embryos and inaccuracy in test findings, as the testing is not 100 percent accurate. For this reason, it is recommended that the patient undergo typical prenatal testing when she is pregnant.