Genetic testing to prevent disease

• When sterility/infertility is suspected to be due to genetic abnormalities in the embryo that make implantation, gestation or the birth of a healthy child unfeasible.
• When you want to select an embryo that is histocompatible with one of the couple's children so that it can be a donor for the other.

Due to suspected genetic abnormalities in the embryo

An embryo with genetic abnormalities will result in implantation failure (no pregnancy), recurrent miscarriages and/or the birth of children with malformations or mental retardation due to chromosomal abnormalities (Down syndrome, Edwards syndrome, etc.).

The reasons for suspecting that there is a genetic abnormality in the embryo are:

• Altered karyotype: one partner in the couple has alterations in their peripheral blood karyotype: the carrier has a balanced karyotype but there is some type of chromosomal restructuring (inversion, reciprocal translocation, Robertsonian translocation, etc.) that causes unbalanced gametes to form (eggs and sperm that are missing or have excess genetic material). This would mean that many of the embryos formed would be altered.
• Altered meiosis: meiosis is the process by which sex cells reduce the number of chromosomes from 46 to 23 so that when they unite with the sex cell of the partner, which has 23 chromosomes, they give rise to an individual with 46 chromosomes. If this chromosome reduction mechanism fails, the resulting embryo will have aneuploidy (alterations in the number of chromosomes). These alterations in meiosis can occur even if both partners have normal peripheral blood karyotypes. A testicular biopsy must be performed to diagnose whether a man has meiosis abnormalities. In women, diagnosis is more difficult and can only be done indirectly by performing PGD testing on embryos produced after an IVF cycle. This information obtained by PGD will be from the embryo (46 chromosomes), so depending on the couple's reproductive history and the results of the male's tests, we will be able to deduce some of the female's information.
• Implantation failure after several IVF cycles: the most common cause of implantation failure after several IVF cycles in which good-quality embryos have been transferred may ultimately be explained by meiotic abnormalities. PGD testing of embryos allows only balanced embryos to be transferred, thereby increasing the chances of success.
• Recurrent miscarriages: in these cases, when the couple is examined, it is usually found that one of the partners has an altered karyotype or meiosis abnormalities. This results in embryos that can implant but at a certain point in their development cease their activity and result in a miscarriage.
• Advanced maternal age: as maternal age increases, the mechanism by which chromosomal reduction occurs during meiosis is altered, increasing the number of embryos with chromosomal abnormalities with age.
• Severe male factor: sperm with chromosomal abnormalities are found in 70% of severe male factor cases.
• Monogenic disease: this is the case of couples who are carriers of a disease that their offspring may be at risk of developing. This would be the case, for example, with haemophilia, cystic fibrosis, Duchenne muscular dystrophy, etc. Through PGD, embryos can be studied and only healthy embryos (those that do not carry the disease) can be transferred.

For selection of histocompatible embryos

This selection has recently been authorised by law. This is the case for families who have a child with a specific condition that requires a tissue transplant. In these cases, the family may request to seek a new pregnancy in order to have a child who is tissue-compatible with their sibling so that they can act as a donor. This would be the case, for example, of a family with a child suffering from leukaemia. The couple could achieve a new pregnancy by undergoing IVF treatment with PGD in order to have a child with the same histocompatibility characteristics as the brother with leukaemia, so that he can act as a bone marrow donor.

How is it carried out?

The couple must undergo a normal IVF cycle: ovarian stimulation, ultrasound-guided oocyte retrieval, ICSI or oocyte puncture with sperm, and embryo retrieval if fertilisation occurs. The only difference is that instead of performing the transfer on day +3, as is usual, it will be delayed by one or two days until the results of the embryo study are available.

On day +3, which is when the embryo usually has 6-10 cells, the embryo biopsy is performed. A hole is made in the embryo's outer layer (the zona pellucida) and one or two cells are removed for testing. The rest of the embryo remains in incubation while awaiting the result. Normal embryos will be selected for transfer.

At this stage, all the cells in the embryo are ‘totipotent’, in other words, as cell differentiation has not yet occurred, each of the cells would be capable of giving rise to a complete embryo and, therefore, the removal of one or two cells from the embryo does not compromise its viability.

The survival rate after embryo biopsy is over 99%. Therefore, the risk of embryo loss due to handling is very low.

Genetic counselling is the study of the transmission of a hereditary disease to offspring. It is carried out through clinical assessment and specialised tests, including biochemical, cytogenetic, molecular tests, etc.

The most common reasons why couples seek genetic counselling are when there is a history of one or more cases in the family of disorders that may be hereditary, either to prevent their occurrence, or when there is already an affected child, to learn about the management of the disease itself, its progression and prognosis.

What are the objectives of genetic counselling?

• Providing information about the diagnosis, prognosis, and treatment of the genetic disorder.
• Understanding the transmission mechanism and its probability.
• Proposing reproductive options to prevent transmission.
• Facilitating adaptation to the problem and its transmission risk.
• Encouraging individual choice of acceptable options based on risk, objectives and values.

Geneticists will explain to the couple how the disorder they carry is inherited and the probability of it being passed on to their children. They will also consider aspects such as the cost-benefit ratio of performing the test and the possible decisions and psychological consequences that such information may entail.

This visit is scheduled by the Assisted Reproduction Unit, where you will be informed of the documentation that the geneticists need in order to carry out a proper assessment.