Genetics is the branch that studies genes and the transmission of hereditary characters. Genetics is especially important in assisted reproduction to analyze and prevent the transmission of certain diseases and also determines some infertility problems. At IVI, we have a Reproductive Genetics Unit, which aims to diagnose and prevent chromosomal abnormalities and monogenic diseases in the embryo before implantation. In this way, repeated abortions, implantation problems and the development of genetic diseases are avoided. These diseases are an important cause of infertility and infant and adult mortality, which is why it is essential to identify couples with a high risk of having offspring with these diseases. But… What are genetic tests and how are they applied in assisted reproduction? We explain everything to you in this post
What is Preimplantation Genetic Diagnosis for?
The Preimplantation Genetic Diagnosis (known by the acronym DPI) detects and prevents the transmission to offspring of serious diseases caused by genetic and chromosomal alterations in embryos, before being transferred to the uterus. Through the DPI we achieve that babies are born free of hereditary diseases. Within the PDI there are variants depending on the type of problem to be detected.
There are many types of chromosomal abnormalities, but we can classify them as numerical or structural. Numerical abnormalities have one more chromosome or one fewer chromosome than the normal pair (23 pairs of chromosomes) would be, and structural abnormalities occur when a part of a particular chromosome is missing, overdone, or transferred to another. it is reversed.
Until now, we distinguished these two situations:
- PGS o Preimplantation Genetic Screening for aneuploidies, in Spanish PGD for aneuploidy screening: This technique is indicated in patients where all the chromosomes of each of their embryos are going to be analyzed, in order to rule out abnormalities in any of them. These indications can be:
- Advanced maternal age: 35 years or older
- Women who have suffered two or more miscarriages
- Two or more failed IVF cycles
- Alterations in sperm meiosis
- Couples with previous gestation with chromosomal abnormality
- Recurring implantation failures
- PGD o Preimplantation Genetic Diagnosis, and that in Spanish we called by the generic DGP. In this case, the technique allows us to address two types of alterations:
- Monogenic diseases: Both patients, one of them or their family antecedents with a specific disease and look for those embryos free of suffering from it.
- Structural alterations: Patients in whom it is known that in one of their chromosomes there is an alteration of its shape (let’s say that a piece of the chromosome breaks or changes its place).
Change of nomenclature in genetic tests
At the end of 2017, the most relevant Assisted Reproduction associations worldwide agreed on a new glossary (The International Glossary on Infertility and Fertility Care, 2017) published in Fertility and Sterility, where a new term appears that replaces the others, and pretends to be more exact: the Preimplantation Genetic Testing or PGT. And to be more specific, the initials of the type of anomaly that it describes are added, leaving it thus:
- PGT-A (Preimplantation Genetic Testing for aneuploidy): It would be exactly equivalent to old PGS and it serves to detect numerical anomalies, which is the same as aneuploidies. Its definition would be “Preimplantation genetic diagnosis technique to detect chromosomal losses or gains in embryos”. If we have 23 pairs of chromosomes (22 plus the sexual pair: XX or XY), these are the diseases where the number is altered. For example, Down syndrome, in which instead of having two chromosomes of each, for number 21 there are three (trisomy 21). In addition to trisomy 21, the most common chromosomal aneuploidies in live-born babies are: trisomy 18, trisomy 13, 45X (Turner syndrome), 47XXY (Klinefelter syndrome), 47XYY, and 47XXX.
- PGT-SR (Preimplantation Genetic Testing for structural diseases): In addition to the numerical anomalies, as we mentioned, there are structural anomalies. This means that the structure of one or more chromosomes is altered, that is, abnormalities caused by the breakage or incorrect union of chromosome segments. Several of the structural chromosomal abnormalities result in disease. There are many types of structural alterations: translocations, deletions, duplications, insertions, ringings, or inversions.
The PGT-M and its variants
- PGT-M (Preimplantation Genetic Testing for monogenic diseases): Monosomies are inherited diseases caused by the mutation or alteration in the DNA sequence of a single gene. They are also called Mendelian hereditary diseases, because they are transmitted to the offspring according to Mendel’s laws. They are divided into three types:
- Autosomal recessive disease: For the disease to manifest itself, two copies of the mutated gene are needed in the genome of the affected person, whose parents normally do not have the disease, but each carry a single copy of the mutated gene, so they can pass it on to their offspring. It is transmitted by non-sex chromosomes. The probability of having a child affected by an autosomal recessive disease between two people who carry a single copy of the mutated gene (who do not have the disease) is 25%. An example would be Cystic Fibrosis or Sickle Cell Anemia.
- Autosomal dominant disease. Only one mutated copy of the gene is needed for a person to be affected by an autosomal dominant disease. Normally one of the two parents of an affected person suffers from the disease and these parents have a 50% probability of transmitting the mutated gene to their offspring, who will suffer from the disease. Examples would be Huntington’s disease or Marfan’s disease.
- X-linked disease. The mutated gene is located on the X chromosome. These diseases can be transmitted in a dominant or recessive way. For example, Hemophilia A or Fragile X Syndrome.
PGT-SR and PGT-Mtogether, they would be equivalent to PGD.
