Pre-implantation genetic screening (PGS)

Pre-implantation genetic screening is used as part of some in vitro fertilisation cycles to determine whether the embryos produced will be affected by a genetic disease that is known to run in one of the parent’s families. Regulations on how pre-implantation genetic screening can be applied vary throughout the world, but the scientific techniques used are more standardised.

Our article on pre-implantation genetic diagnosis gives an overview of the genetic diseases that can be screened for, and the circumstances in which you might consider these tests.

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Pre-implantation genetic screening and embryo biopsy

The first step to screening embryos for a genetic disease, or to determine their sex, involves taking at least one cell away to be tested. Obviously this is a delicate and intricate procedure that needs to be done without damaging the embryo.

Pre-implantation genetic screening can be carried out on embryos at different stages of development:

• Unfertilised eggs: not embryos, but destined for use in IVF to create embryos.
• Fertilised eggs: these contain only one cell, so this is one of the trickiest techniques.
• 3-day embryos: these have 6–8 cells, so removing one cell for testing is possible.
• Blastocysts: these are embryos that are allowed to develop for 5–6 days after in vitro fertilisation to see if they develop into balls of cells that contain about 120 cells.

The fertility specialist doing the biopsy for pre-implantation genetic screening first breaks the outer layer of the embryo or the egg, the zona pellucida. In an unfertilised egg, or a fertilised egg, one of the polar bodies is removed for analysis. These contain genetic material from the mother only, so can show if the mother has passed on a genetic disease that she has or that she carries. It provides no information about a genetic condition passed on by the father. This method of pre-implantation genetic screening is used in only 6 % of fertility clinics around the world. It is the only form allowed in Germany, due to regulations on eugenics.

In a 3-day or 5-day embryo, the zona pellucida is penetrated and then one or two cells containing a complete cell nucleus are removed. This PGS technique is more popular and well accepted, being done by 94 % of clinics around the world that offer pre-implantation genetic screening.

Genetic analysis techniques used in pre-implantation genetic screening

Two main genetic techniques allow the genes of the embryo to be examined in detail:

• The polymerase chain reaction (PCR): this amplifies the tiny amount of DNA available from the embryo, making hundreds of thousands of copies of each stretch of the embryo’s genome. This larger amount of DNA can then be tested and sequenced to detect the presence of known gene faults that lead to genetic diseases such as cystic fibrosis.
• Fluorescent in situ hybridisation (FISH): in this technique the cell taken in the embryo biopsy in fixed onto a glass slide and then treated with various fluorescent probes. These are specific for known genes within chromosomes and can be used to determine the sex of the embryo fairly easily, and to detect various chromosomal abnormalities and genetic diseases.

Limitations of pre-implantation genetic screening

Both of the main techniques used in pre-implantation genetic screening to analyse the material extracted from the embryo have their drawbacks and problems. One of the main ones is that a single cell from an embryo, or a piece of genetic material from the polar body, may not be truly representative of the final human being that would grow from that embryo.

Researchers have discovered that many embryos can be considered as mosaics of different cell types. Some of these are destroyed in the process of development after implantation. So, if the pre-implantation genetic screening is performed on one of these cells, the embryo could be discarded even though it would eventually have been made up of healthy cells.

Recent research has shed many doubts on the reliability of pre-implantation genetic screening, and its use declined for a time. However, there is a demand for it and new techniques are being developed, so it will play a role in fertility treatment in the future.

New techniques in pre-implantation genetic screening

New developments are adding to the way DNA can be manipulated and it is likely that new, more reliable techniques will be developed in the future. A technique called pre-implantation genetic haplotyping was developed by researchers at Guy’s Hospital in London in 2006, based on the technique of DNA fingerprinting.

Ethical considerations and the results of pre-implantation genetic screening

The use of PDS itself is fraught with ethical problems, and policies on what can be done vary from country to country. The risk of killing a healthy embryo by the process of biopsy is significant but the results obtained following a successful biopsy present ethical dilemmas of their own:

• The main objection to PDS is that it can be used to select embryos for qualities other than the absence of genetic disease. The path to eugenics is a short one.
• Some embryos may be discarded when they would have been healthy and could have lived a useful life.
• The opposite is also true: just because an embryo appears healthy, there is no guarantee that something will not go wrong with the pregnancy or the birth, or that the child will not have a genetic condition.
• Some tests on an embryo may reveal a genetic condition that must be present in one of the parents but of which they are unaware. Huntington’s chorea is the main example; the presence of the faulty gene can be detected by pre-implantation genetic screening, but the symptoms do not reveal themselves until early middle age. In these cases, the results of PGS are, with agreement, withheld from the parents but embryos who do not carry the disease are chosen for transfer.