What is preimplantation genetic diagnosis or PGD?

By (embryologist), (expert in clinical diagnostics), (gynecologist), (gynecologist), (embryologist) and (psychologist).
Last Update: 02/25/2022

Preimplantation genetic diagnosis (PGD) is a prevention technique used in assisted reproduction in order to detect abnormalities in the genetic material of embryos.

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.

PGD ​​is also often called PGD (for the acronym in English, preimplantation genetic diagnosis) and is considered a complementary technique that can be applied in the course of in vitro fertilization (IVF).

Provided bellow is an index with the 9 points we are going to expand on in this article.

What is PGD?

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 :

Preimplantation genetic diagnosis or PGD
allows the early detection of serious genetic diseases, which can be transmitted to offspring if the parents are carriers or sick. In general, these are monogenic hereditary diseases such as Fragile X syndrome, Huntington's disease and muscular dystrophy.
Preimplantation genetic screening or PGS
also called screening for aneuploidy. In this case, alterations in the number or structure of chromosomes are identified. The best known chromosomal disease is Down syndrome.

Depending on whether genetic or chromosomal alterations are to be detected, the techniques for analyzing the DNA of the embryos will be different.

When is PGD used?

In general, PGD is an advantageous method, and for this reason, it is indicated in the following cases:

  • When the intended parents, or at least one of them, are carriers of some hereditary genetic disease, and decide to visit a genetic specialist.
  • When the intended parents, or at least one of them, have their karyotype altered (chromosomal testing) due to the presence of a chromosomal abnormality, such as translocations or chromosome inversions.
  • After repeated conventional IVF or ICSI failure
  • After recurrent embryo implantation failure (RIF)
  • Recurrent pregnancy loss
  • Advanced maternal age (especially indicated for women over 38-40 years old)
  • History of fetal aneuploidy (abnormal number of chromosomes in a cell) in previous pregnancies
  • Certain cases of male sterility, such as those when the semen sample is collected directly from the epididymis or the testis.

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:

  • Prevention of severe, early-onset hereditary diseases for which there exists no postnatal cure.
  • Prevention of abnormalities that may compromise the viability of the embryo.
  • As a therapeutic method to heal or cure a sick child (savior baby or savior sibling): by selecting the human leukocyte antigens (HLA) of future offspring, the newborn can help cure a sibling's genetic disease.

To get detailed information about the disorders that can be detected through PGD, please do not miss the following article: Genetic diseases and PGD.

Procedure

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:

  1. Embryo biopsy: a hole is made by means of a laser or chemical substances in the zona pellucida of the embryo to extract one or two cells, if the embryo is 3 days old, or several cells of the trophectoderm in the case of blastocysts.
  2. Tubing or intubated: the extracted cells are placed in a tube with great delicacy. Subsequently, the genetic material that each cell contains inside will be extracted.
  3. Analysis of the extracted DNA: there are several techniques such as FISH, array CGH, PCR, or sequencing.
  4. Assessment of results: genetically healthy embryos and those with alterations in their genetic material are identified, which will be discarded.

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.

What are the pros and cons?

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.

Benefits of PGD

People who decide to do a PGD while trying to get pregnant can achieve the following benefits:

Best embryo selection
Obviously, the main objective of PGD is to detect genetically healthy embryos. Therefore, those with mutations or aneuploidies that, without this genetic analysis, could be confused and transferred to the mother, which would lead to implantation failure, miscarriage, or birth of a sick child, can be directly ruled out.
Lower risk of abortions
some chromosomal alterations allow the embryo to implant, but after several weeks of development they end up in a spontaneous abortion due to not having the correct genetic makeup.
Higher pregnancy rate
since embryos that lead to repeated implantation failures are avoided.
Less number of IVF treatments
PGD allows "getting it right" in the selection of the embryo with greater implantation capacity and that can give rise to a healthy baby. Therefore, the number of failed transfers is reduced, as is the time to achieve a pregnancy.
Greater peace of mind for patients
PGD manages to eliminate the uncertainty of whether the embryo will be good or not. In addition, once the positive is obtained, the woman also feels more relaxed knowing that the embryo is viable and the risk of miscarriage is much lower.

DGP drawbacks

The application of PGD also has, like the rest of assisted reproduction techniques, some drawbacks:

Handling the embryo
embryo biopsy is an invasive procedure that involves making a hole in the zona pellucida and, furthermore, allowing it to spend more time outside the incubator. Some embryos do not support this process and stop their development.
Cancellation of the cycle
PGD implies having to discard several embryos due to the anomalous result. If the couple did not have many embryos after fertilization, the risk of having to cancel the transfer is greater.
Mosaicism
some embryos present a mixture of normal cells and altered cells. Therefore, when only one cell of the embryo is biopsied, it is possible that a non-viable mosaic embryo is taken as healthy, or vice versa.

PGD for gender selection

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:

  • Patients undergo normal IVF treatment to create the embryos
  • Embryos are cultured in the laboratory for a number of days
  • Some cells are removed from the embryo(s) selected
  • The chromosomes are examined to identify which ones are male and which are female
  • The embryos of the desired gender are transferred to the patient's uterus

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.

Ethical issues and controversy

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:

  • How ethical is it to select an embryo in vitro so that it becomes a savior baby once born?
  • Is it ethical to choose the gender of your baby for social purposes (physical features such as eye color)?
  • To what extent am I acting in an ethical way if I select only the viable embryos and allow the affected ones to perish?
  • If a couple undergoes IVF, do they have the right to find out the genome of their embryos?
  • How ethical is it to use PGD in the case of late-onset diseases?
  • Where should the limits to embryo selection by genetic testing be set?

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.

What is the cost of PGD?

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.

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.

To perform a PGD, one should undergo IVF as the main treatment. If you are looking for a clinic to get started, we recommend that you generate your individual Fertility Report now. It is a useful, simple tool that, in just 3 steps, will give you a list of the clinics that have passed our rigorous selection process. You will receive an email in your inbox with a report that contains tips and recommendations to get started.

FAQs from users

Is it possible to perform PGD on eggs?

By Xinxin Lin MD (gynecologist).

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.
Read more

How long do PGD results take?

By Álvaro Martínez Moro B.Sc., M.Sc. (embryologist).

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.

To what extent is the application of PGD important in women who decide to become mothers at an advanced age?

By Julio Martín (expert in clinical diagnostics).

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.

What is the present and future of the DGP?

By Julio Martín (expert in clinical diagnostics).

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.

By Zaira Salvador B.Sc., M.Sc. (embryologist).

Answer by Crea Centro médico de Reproducción Asistida:

The PGD technique is indicated in the following cases:

  • Couples who are carriers of a genetic disease, such as cystic fibrosis or osteogenesis imperfecta
  • Alterations in the karyotype of one of the members of the couple
  • Men with FISH in altered spermatozoa or severe male factor
  • Implantation failures in IVF
  • Advanced maternal age
  • Repeat abortions

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

What are the main risks of PGD?

By Andrea Rodrigo B.Sc., M.Sc. (embryologist).

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.

Why is PGD indicated for women 40 years of age or older?

By Zaira Salvador B.Sc., M.Sc. (embryologist).

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.

Is sex selection possible with PGD?

By Zaira Salvador B.Sc., M.Sc. (embryologist).

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.

How many embryos are necessary for PGD?

By Andrea Rodrigo B.Sc., M.Sc. (embryologist).

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.

Is there any alternative to PGD to prevent the transmission of genetic diseases?

By Andrea Rodrigo B.Sc., M.Sc. (embryologist).

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.

Can embryo biopsy cause abnormalities in the embryo?

By Zaira Salvador B.Sc., M.Sc. (embryologist).

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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References

Bick, D.P. y Lau, E.C. (2006). Diagnóstico genético preimplantacional. Pediatr. Clin. N. Am., 53: 559 – 577.

Buster, J.E. and Carson, S.A. (1989) Genetic diagnosis of the preimplantation embryo. Am. J. Med. Genet., 34, 211–216.

Carson, S.A. and Buster, J.E. (1994) Biopsy of gametes and preimplantation embryos in genetic diagnosis. Semin. Reprod. Endocrinol., 12, 184–195.

Delhanty, J.D.A. (1994) Preimplantation diagnosis. Prenat. Diagn., 14, 1217–1227.

Delhanty, J.D.A. and Handyside, A.H. (1995) The origin of genetic defects in the human and their detection in the preimplantation embryo. Hum. Reprod. Update, 1, 201–215.

Dokras, A., Sargent, I.L., Ross, C. et al. (1990) Trophectoderm biopsy in human blastocysts. Hum. Reprod., 5, 821–825.

Egozcue, J. (1996) Preimplantation diagnosis in older patients. To biopsy or not to biopsy? Of course not. Hum. Reprod., 11, 2077–2078.

Findlay, I. (2000). Pre-implantation genetic diagnosis. British Medical Bulletin, 56 (No 3) 672-690.

Florensa, M. (2011). Diagnóstico genético preimplantacional para enfermedades de aparición tardía. Rev. Asoc. Est. Biol. Rep., Vol. 16, Nº 1, pág. 45-46.

Gleicher, N., Kushnir, V.A. & Barad, D.H. (2014). Preimplantation genetic screening (PGS) still in search of a clinical application: a systematic review. Reproductive Biology and Endocrinology, 12:22.

Grifo, J.A., Tang, Y.X., Cohen, J. et al. (1992) Pregnancy after embryo biopsy and co-amplification of DNA from X and Y chromosomes. J. Am. Med. Assoc., 268, 727–729.

Grifo, J.A., Tang, Y.X., Munné, S. et al. (1994) Healthy deliveries from biopsied human embryos. Hum. Reprod., 9, 912–916.

Handyside, A.H., Lesko, J.G., Jarin, J.J. et al. (1992) Birth of a normal girl after in vitro fertilization and preimplantation diagnostic testing for cystic fibrosis. N. Engl. J. Med., 327, 905–909.

Hardy, K., Martin, K.L., Leese, H.J. et al. (1990) Human preimplantation development in vitro is not adversely affected by biopsy at the 8-cell stage. Hum. Reprod., 5, 708–714.

Harper, J.C. (1996) Preimplantation diagnosis of inherited diseases by embryo biopsy: an update of the world figures. J. Assist. Reprod. Genet., 11, 132–143.

Harper, J.C. and Handyside, A.H. (1994) The current status of preimplantation diagnosis. Curr. Obstet. Gynecol., 4, 143–149.

Lissens, W. and Sermon, K. (1997) Preimplantation genetic diagnosis: current status and new developments. Hum. Reprod., 12, 1756–1761.

Mastenbroek S, Twisk M, van Echten-Arends J, Sikkema-Raddatz B, Korevaar JC, Verhoeve HR, Vogel NE, Arts EG, de Vries JW, Bossuyt PM et al. (2007). In vitro fertilization with preimplantation genetic screening. N Engl J Med; 357: 9– 17.

Moreno, J.M. (2007). Biopsia embrionaria. Aspectos técnicos. ASEBIR, 12: 17-21.

Rodrigo, L.; Rubio, C.; Mateu, E. y Buendía, P., 2014. Capítulo 14: El laboratorio de diagnóstico genético preimplantacional. Instituto Universitario IVI Valencia. Máster en Biotecnología de la Reproducción Humana Asistida. 9ª Edición (2014-2016). 1213-1277

FAQs from users: 'Is it possible to perform PGD on eggs?', 'How many embryos are transferred after PGD?', 'When is PGD recommended?', 'How long do PGD results take?', 'To what extent is the application of PGD important in women who decide to become mothers at an advanced age?', 'What is the present and future of the DGP?', 'When is PGD recommended?', 'What are the main risks of PGD?', 'Why is PGD indicated for women 40 years of age or older?', 'What do statistics show with PGD?', 'Is sex selection possible with PGD?', 'Can autism be prevented through preimplantation genetic diagnosis?', 'How many embryos are necessary for PGD?', 'Would an amnio test become unnecessary if PGD is done?', 'Which genetic diseases are most commonly analyzed through PGD?', 'Is there any alternative to PGD to prevent the transmission of genetic diseases?' and 'Can embryo biopsy cause abnormalities in the embryo?'.

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Authors and contributors

 Álvaro  Martínez Moro
Álvaro Martínez Moro
B.Sc., M.Sc.
Embryologist
Álvaro Martínez Moro has a degree in Biology from the University of Granada and a Masters in Advanced Biotechnology from the University of A Coruña. He also holds his own Masters in Human Reproduction from the Complutense University of Madrid and another in Medical Genetics from the University of Valencia. In addition, he is a postgraduate specialist in Clinical Genetics from the University of Alcalá de Henares. More information about Álvaro Martínez Moro
 Julio  Martín
Julio Martín
Expert in clinical diagnostics
Expert in clinical and laboratory generic development. Development of new tests and analysis of single gene genetic disorders. Laboratory manager at IVIOMICS and currently working in the IGENOMIX laboratory. More information about Julio Martín
 Miguel Dolz Arroyo
Miguel Dolz Arroyo
M.D., Ph.D.
Gynecologist
Bachelor's Degree in Medicine and Surgery from the Medicine Faculty of the University of Valencia (UV) and Doctor in Medicine, finished in 1988 and 1995, respectively. Physician specialized in Obstetrics & Gynecology. Expert in Reproductive Medicine, with more than 20 years' experience in the field. He is the Medical Director and founder of FIV Valencia. More information about Miguel Dolz Arroyo
License: 464614458
 Xinxin Lin
Xinxin Lin
MD
Gynecologist
Dr. Xinxin Lin has a degree in Medicine from the University of Barcelona and is a specialist in gynecology and assisted reproduction. More information about Xinxin Lin
Colleague number: 48324
 Zaira Salvador
Zaira Salvador
B.Sc., M.Sc.
Embryologist
Bachelor's Degree in Biotechnology from the Technical University of Valencia (UPV). Biotechnology Degree from the National University of Ireland en Galway (NUIG) and embryologist specializing in Assisted Reproduction, with a Master's Degree in Biotechnology of Human Reproduction from the University of Valencia (UV) and the Valencian Infertility Institute (IVI) More information about Zaira Salvador
License: 3185-CV
Adapted into english by:
 Cristina  Algarra Goosman
Cristina Algarra Goosman
B.Sc., M.Sc.
Psychologist
Graduated in Psychology by the University of Valencia (UV) and specialized in Clinical Psychology by the European University Center and specific training in Infertility: Legal, Medical and Psychosocial Aspects by University of Valencia (UV) and ADEIT.
More information about Cristina Algarra Goosman
Member number: CV16874

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