What is PGT-A and eSET?

embryologist looking through a microscope

Beginning a fertility journey sometimes feels like moving to a new country where a totally different language is spoken, and this particular language is a bit like alphabet soup. It is hard to keep all of the letters and words straight. We are constantly encountering new acronyms relating to fertility, which are all so important to decipher if your goal is to be an educated patient and advocate for yourself regarding your treatment choices.

Some of these are fairly easy to understand. ICSI is intracytoplasmic sperm injection which is another way of fertilizing eggs. PUPO is probably my favorite and it means ‘pregnant until proven otherwise’ and usually refers to the time right after a transfer or insemination. PGT-A is pre-implantation genetic screening for aneuploidy. It is also referred to as NGS and CCS and, to be as complicated as possible, it used to be called PGS, or pre-implantation genetic screening.

PGT-A is a test done on embryos created during the IVF process. It is covered under the Progyny benefit for all members and its goal is to improve the chance of a healthy pregnancy. Because it is a bit complicated and because at Progyny we believe that all patients should be fully educated on their options, we spent a bit of time with Dr. Robin Fogle of Atlanta Center for Reproductive Medicine to understand what PGT-A is and why it’s typically recommended for patients undergoing IVF (in-vitro fertilization).

What is PGT-A?

PGT-A is a process whereby the chromosomal makeup of an embryo is determined prior to it being transferred into a patient’s uterus. The technology has evolved over the years such that incorporation of PGT-A in the treatment of the appropriate patient population has been shown to improve pregnancy and live birth rates after IVF.

A healthy child results from an embryo comprised of 46 chromosomes. 23 of these chromosomes come from the egg and the other 23 come from the sperm. As women age, the chromosomal makeup of their remaining eggs deteriorates dramatically such that at the age of 38, half of a woman’s eggs are thought to be chromosomally abnormal, or aneuploid. Unfortunately, the normal or euploid eggs are not preferentially released during attempts at conception nor during the IVF process. In an IVF setting, that means that some proportion of the resulting embryos will be aneuploid and, if used, will result in a failed transfer cycle, a miscarriage, or an ongoing pregnancy of a chromosomally abnormal fetus. It is impossible to determine which embryos are euploid just by examining them under a microscope, so PGT-A is used to accomplish this.

What is the benefit of PGT-A?

The benefits of PGT-A are dependent on the age of the female patient. Specifically, using PGT-A in women ages 35 and over can increase their live birth rates and decrease their miscarriage rates. This results in a shorter time to pregnancy. Additionally, because of the higher implantation rates of euploid embryos, a single embryo transfer (eSET) can be comfortably recommended to the majority of patients using PGT-A. This greatly reduces the occurrence, and related risks, of twin and triplet pregnancies.

Another subset of patients who can benefit greatly from PGT-A are women with recurrent pregnancy loss (RPL) due to repetitive creation of abnormal embryos. When employing PGT-A, these patients will likely experience a greatly reduced risk of miscarriage.

How does PGT-A work?

With PGT-A, an embryologist carefully removes 5-6 cells from the trophoblast (placental portion) of an embryo that has been cultured to day 5, 6 or 7. At this stage, the embryo is made up of over 100 cells and the fetal cells have clearly differentiated from the placental cells. The biopsy, when done correctly, does not damage the embryo. The DNA from these biopsied cells is then amplified and studied to determine the chromosomal makeup of the embryo, all while the embryo itself is safely cryopreserved in the lab. The results of the PGT-A testing allow the embryologist and physician to transfer the embryo with the highest chance of success and to avoid transfer of embryos that will result in a miscarriage or abnormal pregnancy.

What is Preconception Genetic Testing?

Before trying to conceive, many patients undergo genetic carrier screening. This is a blood test that is performed on the intended parents (or donors). It checks if you and your partner (or the egg and sperm source) are carriers for the same genetic mutation, which together can put the parent(s) at risk for an unhealthy child. Current expanded carrier screening panels test for hundreds of diseases. If found to be a “carrier couple,” patients can undergo IVF with preimplantation genetic testing for monogenic disorders (PGT-M) to help them identify the embryo most likely to result in a healthy child. PGT-A and genetic carrier screening are not necessarily related and both are typically recommended.

What is elective single embryo transfer or eSET?

Elective single embryo transfereSET, is when the patient(s) and doctoagree that transferring a single embryo is best, despite the fact that there are additional embryos that could be transferred simultaneously.  

Over the years, the success rates with IVF, due mostly to dramatic improvements in the lab, have increased greatly. Before this, it was routine practice to transfer multiple embryos at one time in order to achieve even a singleton pregnancy, knowing that the majority of embryos would fail to implant. However, in doing so, there were frequent situations where multiple embryos were transferred, and twins or triplets resulted. Now, given the high implantation rates of embryos cultured in top-rated IVF labs, there is a push towards transferring only one embryo at a time to decrease the risk of twins or triplets.

Why is eSET beneficial?

The primary reason eSET is so beneficial is because it reduces the likelihood of a twin gestation which is much riskier than many people realize. For example, twins are at higher risk for preterm delivery which then results in an increased likelihood of cerebral palsy, learning disabilities, and language delays in the offspring. Carrying twins is also dangerous for the mother or gestational carrier due to an increased risk of gestational diabetes, hypertension, and cesarean delivery. It is clear that carrying a singleton pregnancy is the best way of ensuring a healthy baby and healthy mother. The risk of transferring more than one embryo at a time is multiple gestation (twins, triplets or more) which then increases the risk of the overall pregnancy. The uterus is designed to carry a single fetus at a time. Though many twin pregnancies do fine, others have complications related to a premature delivery as the uterus becomes unable to contain and/or nourish the pregnancy. In extreme cases, delivery occurs before either fetus is viable and the entire pregnancy is lost.

What are the financial considerations for eSET?

Some patients ask to transfer more than one embryo at a time to reduce the financial burden of a second transfer if the first embryo doesn’t work. However, they fail to estimate the medical and therapeutic costs required to care for twins or triplets. These costs far outweigh the cost of one additional embryo transfer that might be needed to achieve success, and the doctors in the Progyny Provider Network often encourage eSET for patients.   

PGT-A is important to discuss with your doctor as women of all ages may benefit. Even egg donors, who are usually between the ages of 21 and 30 and are selected for their fertility, have as many as 20-30% egg aneuploidy rate. We also recommend that you discuss eSET with your physician. Some patients assume transferring two embryos will vastly improve your chances of pregnancy and save you money. In reality, transferring multiple embryos doesn’t dramatically increase your overall pregnancy rate, it greatly increases the odds of a pregnancy with complications. While Progyny covers PGT-A in its comprehensive fertility benefit plan, many other plans may not cover it so be sure to check with your clinic and insurance provider. 

For more information, contact your dedicated Progyny Patient Care Advocate.