Preimplantation Genetic Testing

Preimplantation genetic testing overview

  • During an IVF cycle, preimplantation genetic testing can be performed in order to check embryos for genetic abnormalities, including single gene mutations or chromosomal defects.
  • Abnormalities in chromosomes are believed to be the most common cause of failed implantation and miscarriage and cause birth defects such as Down syndrome.
  • Preimplantation genetic testing can improve the chance of a healthy, live birth and reduce the risk of passing on a genetic disorder to a child.
  • Risks and considerations for genetic testing include the accuracy of testing and ethical considerations related to embryo selection.

What is preimplantation genetic testing?

Preimplantation genetic testing identifies genetic flaws in embryos prior to transfer to the uterus during an IVF cycle. The two main benefits offered by preimplantation genetic testing are:

  • Reduced risk of passing a genetic disease to a child
  • Increased chance of a successful pregnancy and birth from IVF treatment with a chromosomally normal embryo.

Depending on the mother’s age, approximately 25-85 percent of embryos will have genetic abnormalities. Embryos with genetic defects, either in a single gene or in the chromosomes, are more likely to cause implantation failure, miscarriage or a birth defect in the resulting child. Chromosome abnormalities account for most genetic pregnancy problems as opposed to single gene defects. Both types of genetic abnormalities can occur in embryos derived from natural conception and assisted reproduction and are a large reason why about 20 percent of all pregnancies end in miscarriage.

Two types of genetic tests are used to identify genetic flaws in embryos: preimplantation genetic screening (PGS) and preimplantation genetic diagnosis (PGD). PGS is used to identify chromosomal abnormalities, and PGD is used to detect single gene disorders, such as those that cause cystic fibrosis or sickle cell anemia. Doctors may recommend one or both tests, depending on a couple’s medical and family history.

After preimplantation genetic testing, only embryos without genetic defects are selected for embryo transfer. This embryo screening technique increases the success of pregnancy and live birth rates with IVF treatment.

When are PGS and PGD used and what’s the difference?

How preimplantation genetic testing is performed

There are two basic steps to preimplantation genetic screening. First, a biopsy is performed. Second, a laboratory that specializes in genetic analysis of small amounts of deoxyribonucleic acid (DNA) analyzes the biopsy.

At the Loma Linda University Center for Fertility and IVF, biopsies are only performed on day 5 or day 6 after egg retrieval, when embryos are at the blastocyst stage of development. Blastocyst biopsy has been shown to be safe with no effect on embryo development. The blastocyst contains two cell types, the inner cell mass (ICM) that eventually develops into fetal tissues, and the trophectoderm (TE) that gives rise to the developing placenta and other extra-embryonic tissues.

Blastocyst biopsy involves the gentle removal of 3-10 TE cells for genetic testing. The ICM is left undisturbed. The biopsied cells are put into a very small tube and sent for analysis. Immediately after biopsy, technicians freeze the embryos until they obtain results from the genetic analysis lab.The results generally are received within a few days of the biopsy. The physician will then prepare the patient for a frozen embryo transfer cycle once genetic testing results are evaluated and discussed.

Next generation sequencing method

LLU Center for Fertility uses what is known as the next generation sequencing (NGS) method in PGS and PGD embryo genetic analysis. NGS is an advanced DNA sequencing technology that evaluates the order of the four chemical bases that make up a DNA molecule.

DNA carries the genes, as well as the instructions for how they are assembled, that control growth and development in organisms, including human embryos. The NGS method of DNA sequencing is what reveals genetic flaws including chromosomal abnormalities and gene mutations.

Next generation sequencing replaces the previous Sanger method of sequencing. Sanger works very well evaluating a specific DNA sequence, but lacks the efficiency of, and is more expensive than, NGS. For example, NGS can sequence the entire human genome in a day, whereas it would take the Sanger method more than a decade.

NGS also provides more in-depth results than past genetic analysis methods. This lowers the chance of misdiagnosis and improves the accuracy of identifying genetic flaws that can cause miscarriages or genetic disorders.

Learn more about why we use next generation sequencing

Risks & ethical issues of preimplantation genetic testing

Risks

Health risks to children born after PGD or PGS testing are very rare and are the same as for those children born through normal IVF treatment.

An additional risk is that genetic testing results cannot be 100 percent accurate. Errors may include:

  • Misdiagnosis due to allele dropout (faulty amplification of genetic material)
  • Not detecting an abnormality that is present.

Ethical considerations

Along with the medical risks of preimplantation genetic testing, there are ethical concerns many patients struggle with. For example, a woman may find through PGD that she has BRCA mutations that predispose her and her potential female child to breast or ovarian cancer. This creates stress due to worry whether her child may get cancer or whether that affected embryo should be destroyed to prevent that prospect.

Many genetic mutations that are discovered through genetic testing might not be associated with a genetic disease. While genetics are the cause of single gene mutations, environment and development factors can further determine if the child will ever get the disease and to the extent they will be affected.

Another ethical issue that revolves around preimplantation genetic testing is reproduction to produce a child to serve as a donor for another child. If a couple has a child with leukemia, they can undergo IVF treatment with PGD to only transfer an embryo that has the same human leukocyte antigen as their sick child. The resulting baby would then be a perfect match to the couple’s sick child and could serve as a tissue donor for bone marrow transplants.

Genetic counseling is recommended for all couples considering preimplantation genetic testing of their embryos.