What is the Preimplantation Genetic Diagnosis (PGD)?

By (embryologist), (gynecologist) and (babygest staff).
Last Update: 07/05/2019

Preimplantation genetic diagnosis or PGD is an embryo analysis technique that differentiates between embryos that carry a genetic abnormality and those that are genetically normal.

The final objective of this technique is to avoid the birth of children with chromosome abnormalities, as embryos that are diagnosed as abnormal after genetic analysis are discarded for transfer. This increases the probability of embryo implantation and therefore the probability of success.

Steps in genetic diagnosis of embryos

PGD is a complementary technique to the IVF process (in vitro fertilization). It consists of analysing the genetic sets of embryos obtained in the laboratory before they are transferred to the uterus. To do this, these are the steps to follow:

  • Fertilization of the eggs: this is done by using the ICSI technique (intracytoplasmic sperm injection) and not conventional IVF. In this way, we avoid the possible interference of the spermatozoa that adhere to the egg membrane in conventional IVF.
  • Embryo culture: the embryos are left in culture until day 3, at which time they have between 6 and 8 cells. It is also possible to extend the culture until day 5-6, when the embryo is in the blastocyst stage, formed by two cell groups: the internal cell mass (which will give rise to the embryo) and the trofoectoderm (which will form the placenta).
  • Embryo biopsy: with laser or chemical components, a small hole is made in the zona pellucida and one or two cells (embryos on day 3) or a small set of trofoectoderm cells (blastocyst) are extracted through it. This is what is known as biopsiing the embryo. It is important to see that the analysed cells have a single nucleus (where the DNA is stored) in order to avoid alterations in the results.
  • TubingIt consists in depositing, with special delicacy, the cells obtained from the embryo in a specialized tube for this process.
  • Genetic diagnosis: the cells in the tube are analysed using molecular biology techniques such as PCR, FISH, CGH array or NGS.

The results obtained will indicate whether the embryo analysed has a normal chromosome dotation or whether, on the contrary, it presents any genetic alteration likely to give rise to any disease.

It is necessary to keep in mind that at this time, the embryo is at a very early stage of development. Their cells are totipotent stem cells, i.e. they can differentiate into any type of cell in the human body to form a complete organism, so the extraction of one or two cells will not affect further development.

Nor it should not be forgotten that specialists analyse the genetic sets of one or a few embryo cells. Therefore, the reliability of the result, although approaching, is not 100%. This is known as mosaicismwhich is the fact that some cells have different genetic information than others.

When is PGD applied?

PGD technology is applied as a complement to the ICSI process, mainly in the following situations:

  • When one or both members of the couple (those who provide the eggs and sperm) are carriers of some disease or genetic abnormality.
  • When one or both members of the couple have an altered karyotype, that is, some alteration in the number of chromosomes.
  • Repeated implantation failures
  • Repeated miscarriages.
  • Advanced maternal age The likelihood of genetic abnormalities in the embryo increases proportionally with the age of the mother. Thus, from the age of 35, it increases the proportion of morphologically normal embryos presenting aneuploidy, i.e. genetic abnormalities. This percentage is even higher in women over 40.
  • Family history of disease or genetic alteration

It is important to note that genetic diagnosis of embryos prior to implantation involves manipulation of the embryos, which can be a risk. For this reason, it is important to assess the risk-benefit balance and to carry out the procedure only when it is necessary and can lead to an improvement in the probability of success.

Pros and cons

As we have pointed out before, genetic diagnosis of embryos before implantation makes it possible to avoid the transfer of embryos with genetic abnormalities that could give rise to children with serious illnesses.

There are genetic alterations incompatible with life that, in case of transfer, would result in failure of implantation or miscarriage. However, there are other abnormalities that can lead to the birth of children with development disorders. To give an example, there is the chromosomal syndromes such as Down Syndrome (trisomy 21), Patau Syndrome (trisomy 13), Edwards Syndrome (trisomy 18), etc.

The great benefit of PGD lies precisely in this type of case, although it is also important for cases of recurrent miscarriage or implantation failures. Generically speaking, we can say that PGD increases the probability of pregnancy, especially in elderly women, something more common every day.

On the other hand, it is also possible to find the negative consequences.

  • We have indicated that the PGD process involves the manipulation of the embryo. During the biopsy, the embryo is outside the incubator and this may alter its qualities. On many occasions, there are embryos that are incapable of supporting the process and end up stopping its development, despite being genetically normal.
  • On the other hand, we may be forced to cancel the transfer because none of the embryos obtained is healthy. It is important to keep in mind that there are genetic alterations with mild symptoms or that do not pose a great risk to life. However, we would not transfer these types of embryos.
  • In addition, the fact of doing PGD does not eliminate the need for prenatal testing in the most serious cases (family history of genetic disorder, parents with some abnormality, etc.).
  • Finally, we found the ethical issues. Especially those who believe that life begins from the very moment when fertilization takes place, consider that to discard embryos for transfer is to impede their life.

The new techniques of embryo manipulation and the advances in this sense allow the effect on embryos to be less and less harmful. However, it is still a risk.

What does the law say about PGD?

United Kingdom and United States of America do not have the same vision about PGD process use.

United Kingdom

European Commission's science and knowledge service in its report about Preimplantation Genetic Diagnosis in Europe says that:

The Since PGD involves creation, storage and use of embryos outside the body, it requires a licence from the Human Fertilisation and Embryology Authority (HFEA), the UK regulatory body for this area.

The HFEA receives its authority from the Human Fertilisation and Embryology Act of 1990 and Human Fertilisation and Embryology Bill of 2007.

PGD is authorized under the following situations:

  • Detection of serious hereditary diseases, of early onset and without postnatal curative treatment.
  • Detection of alterations that may compromise embryo viability.
It appears that ten UK centres are currently licensed to provide PGD.

Indeed, it can be used to select against severe medical conditions or to select a human leukocyte antigen (HLA) match for a sick relative.

United States

On the contrary, in the USA, there are no federal or state laws that regulate the use of PGD. So, the use of PGD is left to doctors' discretion.

According to the Comparative preimplantation genetic diagnosis policy in Europe and the USA and its implications for reproductive tourism present on the website of US National Library of Medicine and National Institutes of Health:

The genetic testing process itself (i.e. the analytic quality of the tests and the qualifications of the technicians who carry them out) are subject to the Clinical Laboratory Improvement Amendments (CLIA).

Thus, in the United States, PGD can be performed for example in order to select the gender of the future baby, that is why, this technique is seen as controversial.

PGD and surrogacy

The surrogacy process is usually performed by in vitro fertilization. For this reason, it is possible to carry out the analysis of the embryo's genes through PGD.

In fact, it is something that is usually done, especially in the United States, the preferred destination for a surrogacy treatment. However, it is important for inteded parents to know both the benefits and disadvantages of PGD when not responding to specific indications.

While it is true that we reduce the likelihood of miscarriage, as well as possible ethical complications, it may be that, as we have already said, the embryos are not capable of surviving the process and we cannot perform the transfer because viable embryos are not available.

FAQs from users

By Dr. Joel G. Brasch (gynecologist).

PGD is recommended to identify embryos that are at risk for a single gene disorder, e.g. cystic fibroses, and for testing for chromosomal structural rearrangements, e.g. translocations, deletions/duplications. PGS or now called PGT, preimplantation genetic testing, is used to detect aneuploidy.

Can PGD be done on frozen embryos?

By Andrea Rodrigo (embryologist).

Yes, it is possible to freeze the embryos, thaw them and then do a biopsy to analyze them genetically. In any case, this is not usual. Generally, what is done is to leave the embryos in culture until the day of the biopsy, either on day 3 or day 5.

The protocol to follow will depend on each laboratory and the personal situation of the patients.

How much does pre-implantation genetic diagnosis cost?

By Andrea Rodrigo (embryologist).

Performing PGD on embryos implies an increase in the cost of in vitro fertilization of between 3,000 and 4,000 euros approximately. Therefore, the total price of an IVF-DGP process is around 9,000 euros.

Would preimplantation genetic diagnosis help prevent the inheritance of cystic fibrosis?

By Andrea Rodrigo (embryologist).

Yes, cystic fibrosis is one of the diseases susceptible to genetic analysis before implantation.

Suggested for you

As we have mentioned, PGD involves the manipulation of embryos as a Assisted Reproductive Technology. If you want to learn more about the techniques performed in Assisted Reproduction, we recommend you to read the following post: Assisted Reproductive Technology (ART) – Techniques Used in Surrogacy.

Some of the most common diseases for which PGD is requested have also been included in the article. In this article you have more explanation about it: What Genetic Diseases Can PGD Test for?

Our editors have made great efforts to create this content for you. By sharing this post, you are helping us to keep ourselves motivated to work even harder.

References

The European Commission's science and knowledge service about Preimplantation Genetic Diagnosis in Europe: [ici]

Comparative preimplantation genetic diagnosis policy in Europe and the USA and its implications for reproductive tourism by US National Library of Medicine and National Institutes of Health [ici]

FAQs from users: 'When is PGD recommended?', 'Can PGD be done on frozen embryos?', 'How much does pre-implantation genetic diagnosis cost?' and 'Would preimplantation genetic diagnosis help prevent the inheritance of cystic fibrosis?'.

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Authors and contributors

 Andrea Rodrigo
Andrea Rodrigo
Embryologist
Bachelor's Degree in Biotechnology from the Polytechnic University of Valencia. Master's Degree in Biotechnology of Human Assisted Reproduction from the University of Valencia along with the Valencian Infertility Institute (IVI). Postgraduate course in Medical Genetics. More information about Andrea Rodrigo
Dr. Joel G. Brasch
Dr. Joel G. Brasch
Gynecologist
Dr. Joel Brasch is the Medical Director of Chicago IVF, founded in 2005. He is board certified by the American Board of Obstetrics and Gynecology, and has over 25 years of direct experience in fertility treatment and reproductive care. He is also the Director of Mount Sinai Medical Center’s Division of Reproductive Endocrinology and Infertility. More information about Dr. Joel G. Brasch
Adapted into english by:
 Marie Tusseau
Marie Tusseau
Babygest Staff
Editorial Director of Babygest magazine in French and English. More information about Marie Tusseau

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