What is preimplantation genetic screening, and should I get it

What is preimplantation genetic screening, and should I get it?

I had a condition as a young adult which affected my hypothalamus and I was told then that it may have been genetic. Even though the condition no longer affects me, when we started our IVF journey it made me think about genetics and genetic testing and this is what I found about preimplantation genetic screening.

Preimplantation genetic screening or PGS testing is performed on embryos from IVF at day 3 or day 5 post retrieval. It tests for abnormalities in the chromosomes of the embryo which could lead to a miscarriage or non-viable pregnancies using techniques including FISH, microarray and SNP to increase the chance of clinical pregnancy.

Is Preimplantation genetic screening (PGS) the same as preimplantation genetic diagnosis (PGD)?

Often within the IVF and infertility circles you will see PGS and PGD terms used interchangeably, however this shouldn’t really be done as they are distinctive tests and are used for differing reasons.

PGS – These are genetic tests which look at the number of chromosomes in an embryo to ensure that they will be viable.

PGD – This looks at a specific gene or genes to identify a specific disease or trait. A non-exhaustive list of areas it can identify are: –

  • Translocations of genes (exchange of chromosomal materials or other structural rearrangements), which can cause birth defects, learning disabilities, or miscarriage
  • Huntington disease
  • Marfan syndrome
  • Recessive genetic diseases such as cystic fibrosis or Tay-Sachs disease
  • Genetic diseases carried on the X chromosome, such as haemophilia or Duchenne muscular dystrophy
  • Gender, which allows you to avoid an X-linked genetic disease (mostly boys have those) or balance your family – the ethical considerations of these need to be thoroughly considered and it is not common practice in the UK.

This article looks specifically at PGS however if you want to read more about PGD then please check out Human Fertilitsation adn Embryology Authority page on PGD

What does preimplantation genetic screening look for in embryos?

PGS testing looks at the number of chromosomes in an embryo. In a healthy embryo there are 23 pairs of chromosomes or 46 single chromosomes. It uses a day 3 (blastomere biopsy) or day 5 (blastocyst biopsy) embryo and it removes a cell which is then analysed in a lab using one or more of the techniques discussed below. As a note it is more common to do day 5/6 testing as this has been proven to reduce the risk to embryo vs a day 3 biopsy. It then identifies whether the embryo is aneuploid (A cell with the incorrect number of chromosomes) or not. Most embryos with the incorrect number of chromosomes either don’t implant or lead to miscarriages, the most common is Trisomy 16 (Trisomy means a condition in which an extra chromosome is present) – this was found in about 6% of all miscarriages. Some other specific conditions including Down’s, Edwards and Patau’s can be detected through PGS and will be discussed in detail in the conditions section of the article.

What techniques are used in PGS testing?

PGS can only be performed in clinics which special licence authorising the use of these services and has very strict regulations around its use.

Blastomere biopsy – this is performed during the cleavage stage and normally during day 3 on cells which have reached the 8-cell division. The zona pellucida which you can learn more about in our has a hole made in it either through mechanical, chemical or laser techniques and 1-2 blastomeres containing nuclei are removed. The benefits of day 3 are that they give more time for analysis to be performed, especially if multiple runs need to be performed before the embryo is implanted. However, evidence demonstrates there are much higher risk of day 3 PGS vs day 5 PGS and as such HFEA do not recommend this except in specific circumstances.

Blastocyst Biopsy – The hole in the zona is still usually made on day 3 of an 8-cell division however, extraction of the cells waits till day 5. Using a small glass needle or laser energy 4-5 cells are removed from the blastocyst for testing. This method has some advantages that more cells make testing easier than single cell testing techniques. This method means that tests must be performed quicker, especially if the implantation is being done with no embryo freezing. It can also be problematic as embryos develop into viable blastocysts. However, evidence clearly shows that this is less likely to damage the embryo.

FISH (Fluorescent in situ hybridisation) – This used to be the most common technique used however, one of the older techniques and has predominantly been replaced by new techniques. The cells are fixed to a glass slide and are mixed with florescent DNA probes which are specific to certain section of a certain chromosome. This creates a hybridisation (this means that they bind) of the cells and DNA probes which can then be viewed as shown in the image are analysed to identify additional or missing chromosomes. The drawbacks of FISH are that only about 70% of anomalies are detected, the error rate is around 7-10% of false positives, false negatives and the high rate of mosaicism (different chromosomal arrangements in different cells in same embryo) in day 3 cells reduce the diagnostic accuracy.

Microarray CGH (comparative genomic hybridisation) – This is one of the more recent techniques used. This is a more automated process, which allows for quicker and more efficient testing. It shares a similar principle with FISH in that it hybridises the cells with DNA probes, this time it uses a probe for every single chromosome. This is then placed into an array which contains a reference DNA. This is then analysed through a computer and shows a graphical output identifying loss of, the same amount or extra chromosomes. This still has some drawbacks including it cannot detect and areas of DNA not covered by the probes.

SNP Array (single nucleotide polymorphism) – This is like other array’s except that they use even more specific probes known as allele-specific oligonucleotide which identify very small sections of DNA code. This technique allows for a unique DNA fingerprint for embryo’s to be developed and a more specific understanding of the DNA sequence and mechanism of disease inheritance. This is a very expensive technology.

What conditions can preimplantation genetic screening identify?

The most important three conditions which PGS can identify are

Trisomy 21 – Also known as Down’s syndrome, this is a third chromosome number 21. This is a survivable genetic condition which occurs in 1 in 1000 babies born, however, maternal age does change this substantially as shown by a 2002 research piece which showed the chances of women at age 20, had a 1 in 1441; at age 30, it is 1 in 959; at age 40, it is 1 in 84; and at age 50 had a 1 in 44 chance. Down’s causes a range of challenges including low IQ, physical differences including stunted growth, specific facial features, heart problems and many others. The CDC states that about 5% of those with Downs Syndrome die within the first 12 months, however the average life expectancy has risen hugely in recent years and in the UK it is currently 58 years old.

Trisomy 18 – Also known as Edwards’ syndrome this is an additional 3rd Chromosome 18. It occurs in about 1 in 5000 live births, however many foetuses with Trisomy 18 don’t make it to term. Sadly, only about 7.5% survive to their first birthday and a tiny percent survive to their teens. These individuals have severe disabilities and require full time care. If preimplantation genetic screening picks this up the embryo won’t be implanted, if it is picked up during pregnancy you will be offered counselling to explore your options.

Trisomy 13 – Also known as Patau’s Syndrome this has a 3rd copy of chromosome 13. About 1/5000 births have Patau’s Syndrome, however many don’t survive to full term. For those that are born about 9 in 10 don’t make it to their first year of life and have serious health problems. If this is picked up in PGS then the embryo won’t be implanted, if it’s found in pregnancy you will be offered counselling to decide on how to progress.

Is the IVF or ICSI process any different for me if I have PGS?

The simple answer to this is no. However, there are some things to consider, if you have a low number of blastocysts then the chance of having no embryos which are appropriate for transfer is much higher. Overall the IVF process and timeline are exactly the same for you as the patient.

What are the risks associated with PGS testing?

There are 2 key risks associated with PGS in addition to IVF they include: –

  1. PGS is an invasive procedure for the embryo and as such there is a chance that the removal of the cells from the developing embryo can lead to damage, which can cause the embryo to stop developing and destroying the embryo.
  2. The next risk is those found within the results of PGS – this is because the limits of the technology mean that you can get false positives and false negatives, this means that a good embryo may be ruled out and therefore reducing the number of embryos per cycle or conversely an embryo with chromosomal abnormalities can be implanted which can lead to a failed pregnancy.

Will PGS testing improve my IVF chances of becoming pregnant?

It is very difficult to say for certain either way which is why PGS is rated as red for day 3 testing and amber for day 5 testing on HFEA. Both the NHS and Cochrane suggest more research and trials are required before it can be determined the impacts of PGS.

Cochrane did a review of 9 trials in 2006 and had this conclusion.

“PGS as currently performed significantly decreases live birth rates in women of advanced maternal age and those with repeated IVF failure”

However, I hear you say, this was performed 13 years ago, and the technology has progressed a long way with new array technologies and another gold standard Cochrane review hasn’t been performed on this yet. It is important to note that other more recent studies appear to be showing similar results so at this current point having reviewed the research I will say that it appears that PGS doesn’t improve live pregnancy rates. 

Should I pay for preimplantation genetic screening testing?

Firstly if you are considering having preimplantation genetic screening or diangnosis then I would advise you to seek genetic counselling. We have a overview of this on or aritcle infertility and genetic counseling – Don’t underestimate the emotional impacts

Let me state that PGS is not available on the NHS other than for very specific conditions, so if you want this then you will have to pay for it and this is very expensive.  They also have complex pricing structures which are normally packages for a specific number of embryos with additional cost for each embryo over this amount, some do this per cycle. But it usually starts at £2,000 and can run in excess of £4,000 if you need a lot of embryo’s tested and frozen. With the evidence leaning towards no impact on live birth rates when compared to high quality embryos if you are doing it to improve your chances to get pregnant then I would seriously advise against this treatment. If you have genetic challenges within your family including down’s and you are of an advanced age older than 40 and you just want to rule out embryos with genetic anomalies, then only you can decide whether the cost is worth it, but this would be for peace of mind rather than an increased chance of pregnancy.

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