During this event, Dr José Félix García España, Medical Director of UR El Ángel, explained how Preimplantation Genetic Diagnosis without the need for invasive biopsies works and its current status.
First of all, if we talk about non-invasive or invasive PGT-A, we need to know what chromosomes are and what a karyotype is.
We can identify euploid embryos, indicating normal chromosomes. For instance, consider a typical male: 22 pairs of chromosomes plus the sex chromosomes X and Y. Similarly, a typical female possesses 22 pairs of chromosomes along with the sex chromosomes X and X. Now, contrast this with an aneuploid embryo, such as one with Down syndrome. In this case, observe that in position 23, there is a deviation from the usual pair – instead of two chromosomes, there are three. This abnormality is characteristic of Down syndrome embryos.
In the past, our methodology, illustrated in the second point, involved performing invasive procedures years ago. Specifically, we utilized a biopsy technique during the early stage when the embryo consisted of eight cells.
This method, however, had limitations. It lacked precision because, during the biopsy, we could only extract a single cell. Attempting to obtain more cells posed a risk to the embryo’s viability; obtaining additional cells could potentially lead to the embryo’s demise. Consequently, relying on just one cell for analysis proved insufficient and non-representative of the overall embryo.
In the current scenario, the invasive biopsy is conducted at the blastocyst stage, typically on day six or day five of the embryo’s development. This stage is characterized by a considerable number of cells within the embryo. During this procedure, we can successfully extract a substantial group of cells, usually six to seven cells, enhancing the accuracy of our diagnostic process.
Looking at the graph, we can see on the first line, we see a line here, and then it’s very small, but here is chromosome number one and one, 2, 3, 4, 5, etc., chromosome 22 and the X and Y, and this is a normal, an euploid embryo. When they see that, they say, “Okay, we can transfer this embryo because it’s normal.” You see that all chromosomes in the line are at the same level except the Y, which is smaller has less weight, and comes down a little bit more.
Number two and number three, in red, are aneuploid. They are abnormal, and you can see here there is a defect in chromosomes in pair 22 or in the third one where we see problems in chromosome 15 in pair 15 and chromosome X as well. Therefore, these two embryos should be discarded and not be transferred.
What are the indications for invasive PGT-A? Advanced maternal age because the older the woman, knows that the quality of the eggs comes with more chromosomal alterations, and wants to know which one is normal because the probability of having a miscarriage or other abnormalities is high. Another indication is when we have a patient who has more than 2 miscarriages or failed implantation.
In situations where patients have experienced recurrent miscarriages or failed implantations, there is a demand to understand whether the cause lies within the embryos themselves, particularly due to abnormal chromosomes. Additionally, when there is an issue with male fertility, and the male contributes abnormal sperm, which could be due to factors like DNA fragmentation or alterations in DNA testing, it becomes crucial to explore and identify these factors.
Comparing niPGT-A to the invasive PGT-A, we see its effectiveness. In the graph represented by the yellow line, we observe that over time, the likelihood of achieving a successful pregnancy decreases. However, for women who haven’t undergone PGT-A, or any similar procedure under a different name, there is a significant difference. If a woman, especially one aged 42 or older, undergoes PGT-A through a biopsy of the embryo, and it turns out normal, her chances of pregnancy become equivalent to that of a 25-year-old. This underlines the successful resolution of the age factor in assisted reproductive techniques.
This non-invasive method employs an algorithm to categorize embryos based on their chromosomal characteristics. Group one represents embryos with a probability of more than 85% viability, while group two includes embryos with chromosome alterations, segmental or mosaicism, carrying a 40% probability of viability. The approach helps prioritize the transfer of embryos based on their likelihood of success. The algorithm plays a crucial role in identifying potential issues, such as chromosomal abnormalities, that may lead to conditions like Down syndrome or Edward syndrome.
In conclusion, while the non-invasive PGT-A boasts an 85% concordance with the highly accurate invasive method, it is not yet considered a diagnostic tool. Rather, it serves as a valuable biological marker, aiding in the early selection of embryos and preventing unnecessary transfers. The non-invasive approach allows for a more informed decision-making process, improving the chances of successful pregnancies.- Questions and Answers