Genetic testing can greatly improve the chance of achieving a successful pregnancy. Our fertility experts outline the advantages and disadvantages of pre-implantation genetic testing below.

 

What is the difference between genetic testing, preimplantation genetic screening (PGS), preimplantation diagnosis (PGD), and preimplantation genetic testing (PGT)?

Genetic testing can be confusing at first because of the various terminology changes over the past couple of years.

Preimplantation genetic screening (PGS), formerly called Comprehensive Chromosome Screening (CCS), counts all 46 chromosomes of an embryo to look for “aneuploidy.”

Aneuploidy just means that the embryo is “abnormal” and has either extra or missing chromosomes. Aneuploidy embryos result in children with chromosomal diseases and also are more likely to result in a miscarriage.

Euploid is the term used for a “normal” healthy embryo with the correct number of chromosomes.

Preimplantation genetic diagnosis (PGD) is another type of genetic screening which detects the presence of genes for specific diseases, such as, Huntington disease, Tay-Sach disease, cystic fibrosis, and approximately 2,000 other inherited single-gene disorders.

Preimplantation genetic testing for aneuploidy (PGT-A) is simply a new terminology for Preimplantation genetic screening (PGS). PGT-A is the terminology that you will most likely hear from fertility clinics.

The term “genetic testing” in general is an umbrella term to describe all of the above.

 

Does a Preimplantation Genetic Screening (PGS) Test Guarantee Success?

 

Who should get genetic testing?

All patients who are looking to conceive should be offered genetic testing.

A consultation with a genetic counselor can identify whether the couple is at an increased risk for having a baby with a genetic disease.

Individuals with strong family histories of inherited diseases or specific cancers should also seek a consultation with a genetic counselor to see if there is a genetic cause.

 

When is it safe for genetic testing (PGT) to be performed on an embryo?

Following fertilization, embryos progress through multiple stages of differentiation.

A day 3, or cleavage-stage embryo, consists of eight cells called blastomeres, each of which has the potential to develop into a placenta and or fetus.

Day 5 embryos, or blastocysts, are made of approximately 200 cells and have clearly differentiated which cells are destined to be the placenta (trophectoderm) and which will become the fetus (inner cell mass).

PGD involves the removal of cells from a single embryo to assess the genetic make-up of that embryo.

Biopsy of a day 3 embryo involves removal of 1 or 2 blastomeres from an eight-cell embryo whereas day 5 trophectoderm biopsy involves removal of a few cells from the placental portion of a 200 cell embryo.

Therefore, day 3 biopsies require the removal of a greater proportion of the total embryo mass.

Moreover, because each cell is less differentiated on day three, the cells that are removed from a day 3 embryo may have otherwise contributed to the formation of the fetus.

By contrast, day 5 trophectoderm biopsy removes a much smaller proportion of the overall embryo mass, and those cells are exclusively removed from the placental compartment

Research recently performed at RMA and published in a peer-reviewed journal (Fertility & Sterility) demonstrates that day 3 biopsy is harmful to embryos, resulting in a 39% reduction in the embryo’s chance to become a healthy baby.

Obtaining a small amount of genetic DNA from the trophectoderm at the blastocyst stage (day 5) did not impair the embryo’s ability to implant.

Furthermore, trophectoderm biopsy has been shown to be more accurate than cleavage-stage biopsy because there is more DNA for genetic analysis.

So in conclusion, doing genetic testing on embryos at day 5 is the safest and more accurate time to perform genetic testing of an embryo.

 

euploid aneuploid embryos

 

What conditions and or diseases can be tested?

As the field of genetic medicine has evolved, our understanding of the genetic basis of diseases has increased exponentially.

Over 100 genetic diseases can be tested from a single tube of blood.  Many of these are extremely rare, however, common diseases such as cystic fibrosis, Tay Sachs disease, fragile X syndrome, and others are important to identify in couples seeking to conceive.

BRCA, or the “breast cancer” gene is another important disease that can be tested for via genetic testing.

 

How can genetic testing help patients just by knowing that they’re carrying that gene?

If an individual is found to carry a gene that predisposes them to a certain disease, such as cancer, early intervention may help prevent severe forms of the disease.

For couples looking to conceive, many of these conditions are recessive, which means that they do not show symptoms of the disease but merely carry it.

Since we have two copies of each gene, a good copy can protect an individual and prevent disease. When both members of a couple are carriers of a disease there is a 25% chance they will both contribute the bad copy to their child which will result in illness.

 

Where do I go for genetic testing?

Your fertility clinic can perform your genetic testing for you. Most fertility clinics use a reference laboratory that specializes in genetic testing that they send your bloodwork to. There are several commercial laboratories available around the U.S.

Pre-Implantation Genetic Testing for Aneuploidy (PGT-A) is s platform that can accurately determine if an embryo possesses the right number of chromosomes (euploidy) or too few or too many (aneuploidy) with more precision than the vast majority of other platforms.

This is important because published data suggests 50-70% of miscarriages are due to aneuploidy. Selecting the best embryo with PGT-A can substantially reduce these risks.

Pre-Implantation Genetic Testing for Aneuploidy (PGT-A) is performed by highly specialized laboratories that have expertise in extracting this information from the small amount of DNA that can be obtained from an embryo biopsy.

It is important to select an IVF clinic with extensive experience in this area as it is more complicated than typical genetic testing.

 

Is genetic testing covered by health insurance?

Most health insurances cover basic genetic testing for couples looking to conceive. Each insurance plan is different, so it is best to check with your insurance provider.

At RMA, your financial counselor will check with your provider for you so there is one less thing for you to worry about.

 

What criteria do experts use when referring patients for genetic testing?

At RMA, we offer every couple looking to conceive the opportunity to speak with a genetic counselor who is best qualified to discuss which diseases a couple might be at risk to carry and what tests they should consider.

 

What do genetics counselors do?

Genetic counselors are specially trained healthcare professionals with backgrounds in medical genetics and counseling.

These individuals can identify genetic causes of diseases in individuals presenting with a disease. They can also identify families that carry a genetic disease or couples at high risk to have a child with a genetic disease.

Genetic counselors will speak with a patient, asking them questions about their family history and ethnic background to identify what they may be at risk to carry.

 

What are the advantages and disadvantages of genetic testing?

The main advantage is that early detection may prevent more severe forms of a disease or prevent a couple from having a sick child.

The main disadvantage is that it may cause psychological stress to an individual if they were not previously aware of an increased risk of developing a disease that has no cure.

 

What if I get bad news back from my genetic test?

Part of ordering a test is knowing what do to with the results.

Early detection of a disease is a good thing. There may be steps that you can take to prevent the disease from progressing or at least help with its symptoms.

Genetic testing on an embryo can prevent the birth of a child with fatal genetic conditions.

If you are struggling with the news you received from your genetic test, we offer emotional support through our counseling support staff.

 

What is gene therapy?

Gene therapy refers to a series of experimental therapies aimed at using genetic manipulation of the DNA in our cells to treat disease.

In most cases, it would involve inserting new copies of a gene into cells to replace mutated or missing copies of a gene. In other cases, it might involve inserting new genes aimed at targeting a specific disease or turning off a gene that is functioning improperly.

At present, this is highly experimental, very risky, and has not been proven to be effective in any condition.

 

What are these new DNA sequencing tools?

The technology used in genetic testing has evolved dramatically in the past decade.

PCR (polymerase chain reaction) is a process where specific DNA sequences can be investigated and amplified – this requires knowing the DNA sequence you are looking for. The basis of most genetic testing involves this PCR method.

Sequencing allows us to actually look at the DNA sequence, essentially seeing the entire DNA code.

In the past, it has been a time-consuming and expensive process called Sanger Sequencing.

A new set of technologies called Next Generation DNA Sequencing uses semi-conductors to streamline the process by using “chips” which allow for simultaneous processing of many samples.

Computers are then used to interpret the massive amounts of data generated to allow for the interpretation of these results. It is a promising new technology that is still developing. Studies are still being performed to see if it is as accurate as traditional techniques like Sanger Sequencing and PCR.

 

What is whole-genome testing?

Whole-genome testing refers to the idea that the entire DNA sequence (all of our genes) might be scanned to look for genetic mutations.

At present, we are able to sequence a person’s entire genome – meaning we can obtain the specific DNA sequences. Unfortunately, interpreting this information is extremely difficult.

Only a small percentage of genes are understood well and the majority of our DNA is still a mystery to us. This field is expanding rapidly and new genetic tests and associations are becoming rapidly available.