Preimplantation Genetic Diagnosis (PGD) is an assisted reproductive technology used for the genetic testing of embryos. The first step is carrying out an ICSI cycle, and then the embryos obtained are genetically screened. Finally, those free from genetic abnormalities are selected for being transferred to the mother’s womb.
It should not be confused with PGS or Preimplantation Genetic Screening, which is a similar technique, but for people with recurrent pregnancy loss or infertility. It uses the same technology as PGD to increase their odds for a successful pregnancy.
It involves a greater degree of complexity if compared to the conventional in vitro fertilization (IVF) process, which means the cost of PGD is higher. However, as in any other infertility treatment, the price is not only dependent on the level of complexity, but also the fertility clinic and each particular case.
The different sections of this article have been assembled into the following table of contents.
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.
As 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 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.
Process step by step
PGD can be done with blastocyst embryos, that is to say, day-5 embryos. At this stage, embryos have two types of cells: the inner cell mass, from which the embryo develops, and the trophoblast or trophectoderm, which gives rise to placental development.
The following is an explanation of how preimplantation genetic screening works step by step:
- One or two cells are removed from the embryo through embryo biopsy. By doing this, we can obtain the genetic material contained within.
- Tubing: the cells removed are placed in a tube
- The genetic material obtained is analyzed either by means of PCR, FISH, CGH arrays or Next Generation Sequencing (NGS).
- The embryo is screened to verify whether it is free from genetic abnormalities. In case one of them presented a chromosomal abnormality, it would be discarded for the transfer.
For further information, we recommend you to have a look at the following post: About the PGD process.
Since we are still in the stage of early embryo development, the embryo will compensate the loss of the cell that has been removed, therefore continuing with its cleavage naturally. Thus, performing a PGD on an embryo does not mean its genetic code is going to be altered.
Nevertheless, PGD involves embryo manipulation, something that may have an impact on its development. This is the reason why PGD is only advisable in cases where it becomes necessary, and not used in a generalized manner.
What are the pros and cons?
The risk for human embryos to have some type of chromosomal abnormality increases significantly with age. In this sense, patients of advanced female age (38 or older) in need of IVF can benefit from a PGD because it allows us to:
- Rise the embryo survival rate, as the embryo has an adequate DNA code.
- Reduce the risk of miscarriage and recurrent pregnancy loss, since the possibility that they are due to chromosomal abnormalities disappears
- Get information about the embryo’s chromosomal code
- Increase the overall pregnancy rates
On the other hand, there are some concerns with PGD that should be taken into account. Firstly, there is a chance for the embryos to be damaged by the biopsy procedure, especially when done on day 3.
For this reason, there is evidence that embryo biopsies done on day 5 or 6 of embryo development may not weaken the embryo that much or, if any, damage goes unnoticed, as the number of cells it contains is way higher.
In case you were interested in reading more about this, we suggest you to visit the following article: Results of PGD.
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 Duchenne muscular dystrophy, a disease which 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 a serious medical condition.
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 a 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.
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.
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 with 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.
FAQs from users
How many embryos are transferred after PGD?
The number of embryos to transfer to a patient is not dependent on the technique performed for the genetic analysis of embryos, but on the stage, quality, and particularities of each patient. Preimplantation Genetic Diagnosis is usually performed in cases of advanced maternal age (aneuploidy screening) or when there exist severe genetic pathologies (in many cases, present in the woman). In both situations, a multiple pregnancy would be contraindicated.
So, given all these circumstances, doctors usually recommend Single Embryo Transfers (SETs).
What is PGD used for?
Preimplantation Genetic Diagnosis (PGD) is a technique that complements IVF/ICSI and helps us detect the presence of genetic abnormalities in embryos before their transfer to the maternal uterus.
Currently, it is done by performing an biopsy to the trophoblast of a blastocyst embryo, that is, on days 5-6 of embryo culture. The cells removed can be examined to detect the presence of chromosomal abnormalities using PGS (Preimplantation Genetic Diagnosis), or genetic diseases, such as Duchenne muscular dystrophy (DMD).
Could a blastocyst transfer with PGD help prevent implantation failure?
We talk about implantation failure when pregnancy has not been achieved after three failed cycles of IVF/ICSI using her oocytes, or after two donor-egg cycles, as long as high-quality embryos were selected, no technical issues have occurred during the transfer procedure, and the woman doesn’t have evident uterine anomalies.
Often, couples with implantation failure are referred to PGD (Preimplantation Genetic Diagnosis) to determine whether the cause are chromosomal abnormalities.
What are the main risks of PGD?
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.
What do statistics show with PGD?
With PGD for aneuploidy screening, data show that miscarriage rates are lower after PGD. However, statistical data on the pregnancy and live birth rates is inconsistent.
The same applies in the case of PGD for inherited genetic diseases. For instance, if both partners (male and female) are carriers of a recessive disease such as cystic fibrosis (CF), they would have a 25% chance of having a baby with this disease. With PGD, they can have normal embryos, and therefore a healthy child.
Can autism be prevented through preimplantation genetic diagnosis?
No, it is not yet possible, either through PGD or prenatal testing. To date, only a few specific gene mutations linked to autism have been identified, which makes it impossible for PGD to work with the purpose of avoiding this disease.
How many embryos are necessary for PGD?
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.
Would an amnio test become unnecessary if PGD is done?
In case PGD is indicated, the embryos chosen for the transfer would be free from genetic abnormalities, so the chances for amniocentesis to be necessary are very low, as in principle there is no reason why one should suspect about the presence of genetic diseases when pregnant. So, broadly speaking, we can say that PGD would remove the need for an amnio test to be done.
Which genetic diseases are most commonly analyzed through PGD?
Examples include: Spinal muscular atrophy , beta thalassemias (β thalassemias), Clouston syndrome (or hidrotic ectodermal dysplasia), Gaucher’s disease, cystic fibrosis, osteopetrosis, polycystic kidney disease, non-syndromic congenital sensorineural hearing loss, myotonic dystrophy, muscular dystrophy, tuberous sclerosis (type I and II), neurofibromatosis (type I), Huntington’s disease or chorea, retinitis pigmentosa, haemophilia A, Fragile X syndrome…
Is there any alternative to PGD to prevent the transmission of genetic diseases?
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.
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.
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: 'How many embryos are transferred after PGD?', 'What is PGD used for?', 'Could a blastocyst transfer with PGD help prevent implantation failure?', 'What are the main risks of PGD?', 'What do statistics show 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?' and 'Is there any alternative to PGD to prevent the transmission of genetic diseases?'.