Preimplantation genetic diagnosis (PGD) is a prevention technique used in assisted reproduction in order to detect abnormalities in the genetic material of embryos. It is, therefore, a complementary technique that will help to choose the best embryo to transfer in an in vitro fertilisation (IVF) treatment.
Thanks to PGD, it is possible to avoid the transfer of embryos with genetic or chromosomal alterations and, in this way, increase the probability of having a healthy child.
This technique can be applied to all patients who have undergone IVF treatment and obtained embryos. However, there are situations in which PGD is more recommended in order to obtain a better prognosis of the reproductive treatment.
The different sections of this article have been assembled into the following table of contents.
Although, in general, the term preimplantation genetic diagnosis or PGD is used to refer to the use of this technique, the truth is that two concepts are distinguished depending on the purpose :
Depending on whether genetic or chromosomal alterations are to be detected, the techniques for analyzing the DNA of the embryos will be different.
In general, PGD is an advantageous method, and for this reason, it is indicated in the following cases:
Like with any other treatment, the use of PGD has some legal limitations that vary from country to country. In Europe, for example, main IVF destinations such as Spain have restricted PGD to be applied only in the following cases:
To get detailed information about the disorders that can be detected through PGD, please do not miss the following article: Genetic diseases and PGD.
In order to perform PGD on the embryos, the couple or woman must be undergoing IVF treatment. Therefore, the first step is to perform ovarian stimulation that allows obtaining a high number of eggs to fertilize.
After an ovarian puncture, the ovules are fertilized using the ICSI technique (intracytoplasmic sperm microinjection) to obtain embryos.
PGD can be done on both 3-day-old embryos in culture and 5-day-old blastocysts. In the latter case, it is possible to extract a greater number of cells from the trophectoderm to carry out the genetic study.
The steps to perform PGD in each of the embryos are as follows:
Lastly, the quality of the embryos that are genetically viable is assessed in order to transfer them to the mother's uterus. On the other hand, the remaining embryos will be vitrified for future attempts.
For further information, we recommend you to have a look at the following post: About the PGD process.
PGD applied to the prevention of serious hereditary diseases has a clear benefit, as it avoids the couple having to decide whether or not to terminate the pregnancy because they are carrying a sick baby.
On the other hand, PGD to treat infertility and increase success rates does give rise to debate between proponents and opponents of the technique because of the ethical considerations involved.
In the following, we will discuss the advantages and disadvantages of PGD, as well as some ethical and legal aspects.
People who decide to do a PGD while trying to get pregnant can achieve the following benefits:
As previously mentioned, applying the PGD technique reduces the number of IVF treatments. In addition, this also has the advantage of reducing the financial cost involved. It is true that PGD means having to pay an additional amount of money, but it is also possible that pregnancy may occur earlier than if the genetic analysis were not applied. Therefore, in this case, the cost of future embryo transfers would be reduced or avoided.
The application of PGD also has, like the rest of assisted reproduction techniques, some drawbacks:
The remaining drawbacks of PGD have to do with ethical and moral issues, which will be discussed in the next section.
Using PGD as a method for gender selection is subject to a number of legal restrictions and controversy, and for this reason, it is not allowed everywhere across the world.
Currently, sex selection is permitted in the UK, but only in cases where a genetic disease is linked to one sex rather than the other, such as Duchenne muscular dystrophy, a disease that affects males.
When done for medical reasons, the embryo is tested to find out its sex. Then, only the embryos of the non-affected sex are selected for the transfer. This way, we prevent children from having serious medical conditions.
The process of PGD for gender selection works as follows:
In the United States, the regulations governing PGD allow gender selection for social reasons (a phenomenon known by many as "designer babies"), and this is why it is the main destination for fertility tourists from the UK, Australia, and Canada above all.
The unused embryos of the appropriate sex can be cryopreserved (embryo freezing) for later use, although not all embryos biopsied may be suitable for vitrification. Those of the different sex can be destroyed or donated to science.
It should be clear that this test is not 100% reliable. Also, there is the risk that no embryo is suitable for transfer because all embryos obtained are of the opposite gender.
With PGD, some embryos are considered "viable", i.e. the healthy ones, while others are ruled out and considered to be "non-viable", as they carry a genetic abnormality. This has created a debate in which opponents ask themselves to what extent is it respectful of the morality and ethics of the process. The main arguments are:
The controversy surrounding this technique is precisely the reason why it has not been legalized in a number of countries. If allowed, the law contemplates a number of legal restrictions as well.
Preimplantation genetic diagnosis is an additional complexity to the usual process of in vitro fertilisation, so the economic cost is higher.
PGD may add up to €3,000-4,000 to the process of IVF with ICSI. These additional fees depend on whether one wishes to have only the most common chromosomes analyzed by FISH (13, 15, 16, 17, 18, 21, 22, X, and Y), the common ones with some additional chromosome, or all of them.
It also varies depending on factors such as advanced female age, the method used for genetic testing, etc.
Assisted procreation, as any other medical treatment, requires that you rely on the professionalism of the doctors and staff of the clinic you choose. Obviously, each clinic is different. Get now your Fertility Report, which will select several clinics for you out of the pool of clinics that meet our strict quality criteria. Moreover, it will offer you a comparison between the fees and conditions each clinic offers in order for you to make a well informed choice.
Patients are recommended to ask fertility clinics for providing them with a detailed cost estimate including all fees so that couples are able to see the price of embryo biopsy, standard genetic screening, and all tests done as complementary testing.
Even though the overall cost can vary from clinic to clinic, in general, the cost of IVF-ICSI with PGD ranges from €8,000 to €9,000.
In the following video, Dr. Jon Díez Alcántara, gynaecologist at Fertility Madrid, talks about PGD and its chances of success.
The main benefit we have with the PDG is knowing in advance which embryo is correct and avoid and we avoid transferring the bad ones.
At present, it is not possible to perform PGD on eggs. This technique would damage the eggs and it would not be possible to fertilize them to obtain embryos.
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The time in which the results of the PGD are provided is usually between 2 and 4 weeks, although these may vary depending on the technique, the genetic laboratory, etc. Also, some laboratories offer the possibility of making a diagnosis in 24 hours, although these cases are usually studied, both because of the costs and the associated risks.
An important aspect is the case in which a previous genetic study is required to analyze hereditary diseases. These cases involve a variable prior study depending on the pathology and knowledge of the disease that can take up to 2 months. After this period of time, the assisted reproduction treatment must be carried out, which will conclude with the genetic diagnosis. In other words, this process can take up to 4 months.
From a reproductive point of view, if we take as advanced maternal age women seeking pregnancy from 40-41 years of age, the clinical data are clear and reveal that the eggs of these women present an increased risk of chromosomal alterations, especially trisomies such as chromosome 21 or Down's Syndrome.
Clinical data from the main medical groups that apply PGD show that its use for this group of women favors the gestation rate and decreases the miscarriage rate.
Today, PGD has become an intrinsic part of reproductive medicine and adds to the preventive options offered to couples with a personal or family history of severe hereditary diseases. It is also useful as a tool for improving reproductive options in specific groups of couples with subfertility or increased risk for chromosomally altered embryos.
The future of PGD seeks to integrate new knowledge and developments in high-throughput genetic methodologies, such as next-generation ultrasequencing platforms, together with advances in assisted reproductive techniques (ART) to improve reproductive options for all couples attending assisted reproduction clinics.
Answer by Crea Centro médico de Reproducción Asistida:
The PGD technique is indicated in the following cases:
In the case of couples carrying a genetic alteration or monogenic disease, a study is needed prior to PGD to locate the mutation and be able to look for it in the cells of the embryo to be analyzed
As explained above, we put the embryo at risk of being seriously damaged after the biopsy to the point that the embryo transfer has to be cancelled, even though it was a healthy embryo. Also, the result of the genetic screening might show that all embryos are genetically altered, in which case the transfer would be cancelled as well, and a new IVF-ICSI cycle restarted. Moving to donor eggs and/or sperm is another feasible option.
The eggs of these women are no longer of good quality and have an increased risk of chromosomal abnormalities. Therefore, PGD can increase the pregnancy rate, decrease the miscarriage rate and prevent the baby from having a genetic disease such as Down syndrome.
Yes, since the sex chromosomes are analyzed for any alteration, it is possible to know if the embryo is male or female. This is very useful in case the couple presents some genetic disease linked to sex, since only those embryos of one of the sexes, which are healthy, could be chosen for transfer.
There is no minimum number of embryos for PGD. However, as it is an expensive procedure, couples who have obtained a low amount of embryos in a single cycle are advised to undergo more cycles in order for a higher number of embryos to be gathered (normally 5 or over) before PGD.
If preimplantation genetic diagnosis is not done, the only option left would be fetal or prenatal resting through amniocentesis or chorionic villus sampling (CVS). The main disadvantage of this type of genetic testing is that the woman would have no alternative but to choose to terminate her pregnancy in case a genetic disease was detected, given that she has to be already pregnant for these techniques to be carried out.
Alternatively, prospective parents can decide not to use their oocytes and/or sperms to avoid the transmission of genetic diseases to their offspring. In such case, donor gametes would be used.
Since this is a very early stage of embryonic development, the embryo will compensate for the absence of the extracted cell and continue to multiply naturally. Therefore, performing PGD on the embryo does not imply any alteration in its genetic endowment.
However, this technique involves the manipulation of the embryo, which may affect its ability to evolve. This is the reason why PGD is generally recommended only in the necessary cases and not in a generalized way.
As we have said, PGD is a complementary technique that is carried out during in vitro fertilization. If you want to know what this treatment consists of, you can enter the following post: What is In Vitro Fertilization (IVF)? - Process, Cost & Success Rates.
For more detailed information on PGD results and probability of success, you can continue reading in the following article: Understanding the results of Preimplantation Genetic Diagnosis.
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