Preimplantation Genetic Diagnosis (PGD)

By detecting whether the embryo is affected by a hereditary disease, we successfully guarantee healthy offspring and definitively prevent the disease from being transmitted to future generations

Types of pre-implantation genetic diagnosis

PGD for monogenic disorders/PGT-M

The advantage of PGD applied to genetic diseases affecting a single gene is clear and its usefulness is widely accepted. It is the only means of avoiding transmission of a genetic disorder without the partner having to face the possibility of the child she is carrying being affected and, therefore, having to deal with the decision of terminating the pregnancy.

PGS/CCS/PGT-A

This technique allows us to rule out embryos that have classically been classified as ‘good quality’ embryos based on their appearance but that do not implant correctly or that lead to pregnancy loss during the first few weeks of pregnancy because they have chromosome abnormalities.

When is PGD performed?

PGD for monogenic disorders/PGT-M:

PGD is recommended in couples who have a genetic disorder or who are carriers of a genetic disorder and who wish to have a child that is free from it. Couples can be assured that they will give birth to children who are free from the disorder.

PGS/CCS/PGT-A:

PGS is recommended when the mother is of an advanced age, following recurrent pregnancy loss, if IVF has previously failed and when patients have chromosomal abnormalities.

What does PGD entail?

PGD for monogenic disorders/PGT-M

In order for PGD to be carried out, the future parents need to undergo genetic testing. The first step, therefore, is the genetic analysis. In other words, a process that identifies the error in the gene (mutation) which causes the disorder. Based on the results obtained, the most appropriate way of diagnosing future embryos when they are in the in vitro fertilisation laboratory (informativity) needs to be designed.

Once the phases prior to PGD (genetic and informativity study) have been completed, the PGD cycle can proceed with confidence. The couple can then begin in vitro fertilisation (IVF). It is important to wait until the embryos from the treatment have divided so that several embryo cells can be extracted (embryo biopsy). The biopsies are then analysed in the molecular biology laboratory in order to find out if the biopsied embryos are free from the disorder in question. The aim is to transfer healthy and viable embryos which will lead to a healthy pregnancy.

PGS/CCS/PGT-A:

The external layer of the embryo (the future placenta) is also biopsied in this case during blastocyst stage. This time, however, we analyse the chromosomal make-up in order to be able to select the embryos that have the correct number of chromosomes. 

Which disorders can be analysed using PGD?

In theory, if we know which gene is responsible for a hereditary disease, the disease can be analysed using PGD.

PGD can be used irrespective of the type of inheritance:

• One partner has a genetic disorder with dominant inheritance (50% of children are born with the disorder).
• The mother is a carrier of a genetic disorder which may or may not be passed on depending on the sex of the child (50% of her children will have the disorder).
• Both partners are carriers of a genetic disorder with recessive inheritance (25% of children are born with the disorder). 

The advantages of PGS/CCS/PGT-A

There is some disagreement regarding the degree to which studying chromosomal abnormalities (PGS) improves success rates in assisted reproduction techniques. The main advantages and disadvantages of both points of view are explained below.

Improved embryo selection

Only embryos with no abnormalities in the number of chromosomes will lead to the birth of a healthy child. Therefore, when we work with good embryos and apply PGS techniques, we are able to select chromosomally normal embryos and rule out those that would never lead the birth of a healthy child even when their appearance suggests that they are good quality embryos.

Transfer of embryos that will not implant can be avoided

Certain chromosomal abnormalities are incompatible with life and prevent embryos from developing during the early stages and even from implanting in the mother's uterus. PGS means that embryos of this kind can be ruled out, thus optimising the number of transfers.

Transfer of embryos that will lead to pregnancy loss or the birth of children with a variety of syndromes can be avoided

Within the range of possible chromosomal abnormalities, some are less harmful to the embryo and allow it to implant. However, they do stop the pregnancy from developing correctly and can lead to pregnancy loss or the birth of a child with a number of possible syndromes such as Down's syndrome, Patau's syndrome or Edwards' syndrome. PGS means that embryos that will lead to situations of this kind can be ruled out.

The time taken to get pregnant is reduced

By using PGS, we are able to avoid transferring embryos that will not lead to the birth of a healthy child since they will have been ruled out using the technique. Since we know which embryos will give rise to a full term pregnancy, 'time is not wasted' transferring embryos that will undergo embryo arrest during development and will not lead to the birth of a healthy child.

The financial burden is reduced

Adding a new analysis to the process could be indicative of an increase in the cost. However, an in-depth knowledge of the characteristics of each embryo means that embryos that would appear to be healthy but which, in fact, are not healthy from a genetics point of view are not frozen and stored. Additionally, we are able to remove the cost of transferring embryos that will not lead to a pregnancy.

A positive impact on psychological wellbeing

Using PGS means that patient uncertainty is diminished. On the one hand, they have the guarantee of a healthy embryo and the assurance that the very latest technology has been used to achieve it. On the other, the risk of pregnancy loss is reduced and this reduces emotional stress, particularly in the case of patients who have already experienced it.

The disadvantages of PGS/CCS/PGT-A

An invasive procedure

PGS means that the embryo needs to be biopsied in order to carry out the genetic test. However, significant progress in reducing the possible damaging effect of the biopsy has been made over the last few years. Carrying out the embryo biopsy on day 5 of development rather than on day 3 has been key. Nowadays, we can say that the embryo biopsy does not have a negative impact on embryo viability.

A cycle without transfer

In some cases, patients are at a high risk of having abnormal embryos. This is the case, for example, with mothers of an advanced age. In these cases, PGS analysis could determine that all the embryos are chromosomally abnormal and unsuitable for transfer. As well as the upset caused by calling the treatment off, there is also a significant emotional impact.

Embryo mosaicism

It is commonly accepted that human embryos have a certain degree of mosaicism. However, diagnosis used to be difficult. Nowadays, thanks to the development of genetic analysis techniques, we are able to see if there are both normal and abnormal cells in the embryo (mosaic). What we need to know is if this affects the embryo in any way. Several pieces of research work that aims to assess this issue have been carried out at Instituto Bernabeu.

PGS as a means of screening

PGS analyses the external part of the embryo with the aim of leaving the part that will give rise to the baby (the internal cell mass) intact. Scientific research has shown that there is a significant correlation between the two. As such, we accept that the biopsy sample that is taken is representative of the entire embryo.

A difficult decision

Many couples find taking the decision to analyse their embryos difficult for ethical and emotional reasons. Psychological and professional support is available to guide the patients at our clinics and the decision to go ahead is always up to the family.