What information does the PGT-A test provide? What are aneuploidies? Do I have to start fertility treatment in order to take the test?
Depending on which genetic alterations needs to be detected, one of three tests is used. In today’s article, however, we will focus on the PGT-A, the pre-implantation genetic test for detecting aneuploidies.
Aneuploidies – what are they?
In order to determine chromosomal abnormalities, it is important to understand what chromosomes are. They are DNA structures that contain our genetic information. Normal or euploid human embryos have 23 pairs of chromosomes. The mother and father each pass on one copy of each pair of chromosomes to their child.
An abnormal number of chromosomes in embryos (also called aneuploidy) usually stems from certain alterations during the early development of eggs, sperm or embryos and in many cases leads to miscarriages or genetic disorders.
What are the details of a PGT-A test?
The Preimplantation Genetic Testing for Aneuploidy (PGT-A) is a technique of reproductive medicine that allows us to genetically analyse the embryo in the laboratory before implantation. Through this genetic analysis, it is possible to transfer only healthy embryos and to detect disorders caused by chromosomal abnormalities, as it is the case in Down syndrome, Turner syndrome or Klinefelter’s syndrome, etc.
In order to perform a PGT-A, the patient must undergo in vitro fertilisation treatment.
To make the test as safe and reliable as possible, an embryo biopsy is performed between the 5th and 6th day of embryonic development, when the embryos have reached the blastocyst stage. During this biopsy, a small incision is made with a laser and aneuploidy screening is performed. This screening shows us which embryos are genetically normal and can be used to achieve a successful implantation that will lead to pregnancy.
What disorders can be detected through PGT-A?
Since we know that a normal number of chromosomes consists of 23 pairs (22 plus the XX or XY sex-chromosome), we can use the Preimplantation Genetic Testing for Aneuploidy to detect disorders caused by an abnormal number of chromosomes, such as Down syndrome, in which the 21st chromosome is triplicated (also known as trisomy 21).
Other conditions that can be detected through PGT-A are Edwards syndrome (trisomy 18) and Patau syndrome (trisomy 13).
In the case of abnormalities of the sex chromosome, the PGT-A test can detect disorders such as Klinefelter syndrome. This syndrome occurs when a boy is born with an extra X chromosome. It manifests itself in abnormal development of the testicles and abnormal testosterone production. In girls, the absence (partial or complete) of the same chromosome is known as Turner syndrome and it affects the development of affected children.
When is a genetic screening like PGT-A recommended?
In cases where patients have suffered repeated miscarriages or multiple implantation failures after IVF, or in cases of severe male factor, it is recommended to perform a PGT-A test, as there could be a possibility that the patient suffers a specific alteration of the gametes causing problems in the development of the embryo.
Many patients aged around 40-45 years who undergo treatment with their own eggs undergo PGT-A because it is very common for aneuploid embryos to be found as the patients get older. The reason for this is that the percentage of aneuploidy increases drastically with age.
“In the IVF-Spain clinic in Madrid alone, 41% of patients in 2020 underwent PGT-A, in addition to PGT-M for very specific diseases with a known gene mutation that has been detected in the family, such as cystic fibrosis, osteogenesis imperfecta or sickle cell anaemia”.
Although PGT-A is usually recommended for women of advanced maternal age, it is also very informative for couples or women with a history of genetic disorders in their family, karyotype alterations in one or both parents or for women who have suffered repeated miscarriages.
In our group of clinics, we generally recommend the PGT-A test to improve the chances of success in any assisted reproduction treatment, as it reduces the risk of miscarriage and increases the chances of conceiving a baby without chromosomal disorders.
How is the PGT-A test done?
Every treatment at IVF-Spain Madrid begins with an initial consultation . This first visit can be done either online or in person. One of our specialists will analyse your complete medical history and previous experience with other fertility treatments, if it’s the case.
If the initial consultation takes place on-site at our clinic, a complete gynaecological examination of the patient and medical diagnosis is carried out, as well as a sperm analysis if the patients are a heterosexual couple. In our clinic group, we place great emphasis on a personalised treatment plan for each of our patients in order to be able to achieve our common goal: the birth of a healthy child.
The ovarian stimulation begins once the detailed diagnosis has been completed and a date for the start of the treatment has been set together with the patient.
Ovarian stimulation usually lasts 10-15 days. During this period, the patient receives daily injections to stimulate follicular growth to obtain more than one mature egg in the same cycle. That way, we are able to increase the ovarian response and the production of eggs, thus increasing the number of fertilised embryos. The more eggs obtained in one cycle, the higher the chance of obtaining high-quality eggs and the process will not need to be repeated.
The size and number of follicles are monitored by ultrasound and hormone analysis to determine the best time to induce ovulation. The final date set for the follicular puncture depends on the progress of the stimulation. The procedure takes place in the operating theatre and the patient is placed under light anaesthesia while the follicular fluid containing the eggs is aspirated.
The mature eggs obtained previously are then combined with the partner’s or a donor’s sperm. Fertilisation is carried out by in vitro fertilisation (IVF) or by ICSI (intracytoplasmic microinjection).
The embryo culture and development of the embryos is now monitored by our experts in the IVF laboratory until they reach the blastocyst stage on the fifth or sixth day of embryo development. Now they are classified according to their quality in a process called embryo selection.
Embryos with adequate quality are subjected to an embryo biopsy and are frozen using the cryopreservation technique in which the embryos are submerged in liquid nitrogen with the help of cryoprotectants to prevent them from being damaged. This way the embryos are stored securely until the results of the genetic analysis arrive.
The biopsy is an important part of embryo selection, as it is here that cells are taken from the embryo and genetically analysed thanks to massive parallel sequencing technology (NGS, Next Generation Sequencing), the most advanced in the field of reproductive medicine, to determine whether a chromosomal abnormality (aneuploidy) is present.
What is done with the results of the PGT-A?
We receive the results of the analysis after about 20 days. Depending on whether a chromosomal abnormality is detected or the number of chromosomes in the embryo is normal, it is determined whether the embryo is discarded or considered a candidate for devitrification and transfer to the mother’s uterus.
According to Spanish law, aneuploid embryos are not allowed to be transferred after PGT-A or PGT-M analysis.
In conclusion, our embryology experts review all the data from the patient, the embryo, the result of the genetic analysis and the vitrification-device in which the embryo is frozen before it is discarded in order to find the best embryo for transfer.
The Preimplantation Genetic Testing for Aneuploidy is becoming more and more common among patients and, for our embryology experts, it is something already a very common procedure in the laboratory: “We perform this very specific technique practically every day, which allows us to be highly trained and at the forefront in this field”.