During this event, Vladimiro Silva, Founder & IVF Lab Director at Ferticentro, Coimbra, Portugal, discussed the relationship between PGT-A (Preimplantation Genetic Testing for Aneuploidies) and IVF success, breaking down the outcomes and the total cost involved.
When we’re talking about IVF and genetics, it’s important to emphasize that humans and mankind, cannot interfere with genetics. We can determine whether an embryo is viable or not, but we cannot change the genetic content of an embryo. Therefore, we need to counsel our patients very well; that’s the main point of PGT-A.
When we talk about genetics, unfortunately, genetics is primarily about information. We can understand what’s happening, but we cannot change it. We can do everything we can to create great embryos, using the best technologies, culture media, medications, and so on. We can maximize the odds by obtaining as many embryos as possible and ensuring their quality. Then, we can test those embryos to determine their genetic content.
PGT-A in IVF and genetics is used to prevent the transmission of genetic diseases. This summarizes situations where genetics play a crucial role in IVF. We can use genetics and IVF to prevent the transmission of genetic diseases if someone is a carrier of a genetic disease that can be passed to the offspring. We can use genetics to minimize that risk. We can screen for potential genetic problems, especially age-related ones. This is where PGT-A stands. Additionally, we can also find HLA-compatible embryos in very special cases.
There are various types of genetic tests. For example, there’s preimplantation genetic testing for monogenic diseases (PGT-M). This is for diseases that affect a single gene, such as Huntington’s disease. These diseases can be recessive or dominant. If someone is affected by a dominant disease, they have a 50% chance of transmitting it to a child. If it’s a recessive disease, the risk only exists if both partners are carriers of the same mutations. In those cases, there is a 25% chance of transmitting the disease.
PGT-A stands for Preimplantation Genetic Testing for Aneuploidy and it is used for testing embryos for aneuploidies, and numerical chromosomal abnormalities. There’s also preimplantation genetic testing for structural rearrangements (PGT-SR). It’s used to screen for chromosomal structural rearrangements caused by balanced translocations or inversions, and it’s intended for patients known to carry these abnormalities. Some people have chromosomes that swap parts, meaning a part of a chromosome is exchanged with another. Generally, these individuals have a balanced amount of DNA, leading to no health issues. However, problems can arise during gamete formation, potentially leading to imbalances transmitted to their children.
Then there’s the test for HLA compatibility, a situation where a child is affected by a severe genetic disease, and another child is needed to donate cells to treat the condition. Medicine uses genetic testing in scarce situations to aid in this treatment.
PGT-A is a test performed on embryos to screen for numerical chromosomal abnormalities. If an embryo is aneuploid, it has an extra or missing chromosome. Embryos with such abnormalities often fail to implant, leading to negative pregnancy tests or miscarriages.
Embryos found to be chromosomally normal are called euploid and are more likely to lead to successful pregnancies. This is why we identify these good-prognosis embryos; it saves time in pregnancy and reduces the need for frozen embryo transfers, hence saving patients’ money. At Ferticentro and Procriar, Next Generation sequencing is used for PGT-A, which allows the analysis of all 24 chromosomes. This is now routine worldwide, and there are even more accurate techniques available, improving the quality of genetic testing.
When we conduct PGT-A, we detect chromosomal abnormalities before embryo transfer, enabling patients to make informed treatment decisions. It’s essential to understand that PGT-A doesn’t improve embryos; it provides information and the ability to select the best embryos. By transferring the best embryos, we reduce the number of cycles needed for pregnancy, ultimately saving money. This should be assessed on an individual basis; if a patient only has one embryo, it’s more about information than cost-saving. However, if a patient has 10 embryos, PGT-A will likely save a lot of money, as it’s improbable that all 10 embryos are viable.
The graph shown on the slide from Igenomix, a significant international genetics lab, presented the probability of having an abnormal or aneuploid embryo. When dealing with patients under 35, only 36-40% of embryos carry genetic abnormalities. As maternal age increases, more embryos have abnormalities not compatible with life. For example, between 38 and 40, there’s a 64% chance of an embryo being abnormal. In Portugal, we conduct PGT-A without restrictions for those above 39. Below 39, we only perform PGT-A in specific cases, like multiple failed embryo transfers, previous pregnancies with abnormal embryos, or maternal age equal to or higher than 39.
Another graph from Igenomix demonstrated the probability of implantation for embryos with PGT-A across different age groups, showing stability and high probabilities. Conversely, unselected IVF samples show declining implantation probabilities with age. This reinforces the importance of transferring only the best embryos for patients.
After stimulation with 300 IU of HMG per day, 9 day-9 blastocysts were obtained. We conducted PGT-A and had 2 transferable embryos, 1 euploid, and 1 mosaic with a 30% abnormal cell line. Research now considers this type of mosaic as essentially irrelevant. If we hadn’t done PGT-A, we might have transferred 2 embryos, resulting in a pregnancy out of one. Instead, we transferred 1 embryo and achieved a successful pregnancy. It was crucial, especially considering the patient’s age, as it’s a discussion we have with patients when they’re 42.
We conducted a PGT M, a test for a monogenic disease present in one gene. After stimulation, we retrieved 5 eggs, then, with an increased dosage, in the second stimulation, we had 29 eggs. From these, we obtained 22 embryos, of which 13 were blastocysts. After conducting the PGT-A test, 7 embryos were not carriers of the mutation. Of these, 6 were euploid, and transferring 1 resulted in the birth of a healthy child with five good prognosis blastocysts still available.
The only solution for her existing child was a bone marrow donation, which led her to seek a genetically compatible sibling. With a theoretical probability of finding a compatible donor at 20%, we needed special permission to perform an HLA compatibility selection. We conducted 2 ovarian stimulations, resulting in a total of 56 eggs, from which we got 14 blastocysts. Three of these were HLA-compatible and chromosomally normal embryos, leading to a successful birth after a precise embryo transfer.
Despite excellent results in the lab, all embryos were aneuploid. This led to a discussion about double donation treatment due to the unavailability of the embryos. In these cases, PGT-A has proved instrumental in making informed decisions and significantly impacting the outcomes for the patients.- Questions and Answers