Preimplantation Genetic Screening
A woman’s fertility and the quality of her eggs progressively diminish with age, making it harder to become pregnant. The natural increase in the rates of genetic mutations in the eggs greatly contribute to the loss of egg quality. This lead to the development of preimplantation genetic screening (PGS) to help improve IVF outcomes by screening for embryos with chromosomal abnormalities and only transferring embryos that are normal therfore increasing chances for live births.
So what is PGS?
PGS is the process of screening the embryos for the correct number of chromosomes and for structural abnormalities in the chromosomes. On day 3 or day 5/6 after the egg is fertilized, the embryologist will take out genetic material from one or more cells in the embryo to test for any chromosomal abnormality. There are many different kinds of techniques used for PGS and each technique has different levels of accuracy and limitations. The most commonly used technique today is PGS 2.0, where genetic material is removed from the cells on day 5/6 (blastocyst stage) when more genetic material is available. PGS is widely used today to help improve the IVF outcome in patients with poor prognosis (i.e. older women or woman with history of multiple miscarriages) and to help select the sex of the child.
What are some concerns with PGS?
Although there are many benefits of PGS as it can test for chromosomal abnormalities of the embryos before the embryo transfer, there are some mistaken thoughts about PGS we need to know:
- PGS primarily examines the number of chromosomes in embryo. This only allows detecting for chromosomal abnormalities rather than specific genetic abnormalities. Preimplantation genetic diagnosis (PGD) is used to describe testing for specific genetic disease, usually single-gene defects like cystic fibrosis and Tay-Sachs Syndrome. There are lots of diseases that are linked to abnormal chromosomal structure but specific gene mutations cannot be reliably detected with PGS.
- PGS is not a reliable predictor for live birth of a chromosomally normal baby. Patients with normal PGS results can experience miscarriages and embryos with abnormal PGS results can progress to a live birth of a chromosomally normal baby. This is due to mosaicism, a normal condition in which there is the presence of two or more populations of cells with different genotypes in one individual. This means that the chosen cells are not 100% representative of all the cells in the embryo.
- PGS can cause damages to the egg. The techniques used in PGS to remove the genetic material can cause some damages to the remaining cells and may reduce the success rates of implantation.
- Not much data to support that overall IVF outcomes are improved. There is limited evidence to show that using PGS in patients with “advanced age”, often older than 37 years of age in many programs offering PGS, show IVF outcomes were improved. Patients who are older have a greater percentage of their eggs having chromosomal abnormalities, which would makes them the perfect candidates for PGS. However, the available data does not seem to support that reasoning.
Who might benefit from PGS?
Patients most likely to benefit from PGS are patients with a history of multiple miscarriages and cases of male infertility where chromosomal abnormalities or abnormal chromosomal structure are likely the reason for the difficulty in becoming pregnant. For patients who are using PGS for “advanced age,” the available data does not strongly support the use of PGS to improve IVF outcomes and may not be cost-effective as PGS can be expensive and are usually not included in the price of the IVF cycle.
The use of PGS to select the sex of the child is a controversial topic and this has lead to restrictions on the use of PGS in some countries by requiring additional documentation to justify using PGS. The degree of restriction is different depending on the country. In some countries, the lack of enforcement of the restrictions make it possible to use PGS for sex selection even though it is not allowed.
There are new PGS techniques currently being developed to improve the accuracy of the screening and make it less invasive when removing the genetic material from the embryo. For those who plan on using PGS, one should inquire whether PGS 2.0 is being used by the clinic and to fully understand the limitations of PGS.
Baird DT. Fertility and ageing. Hum Reprod Update. 2005;May-Jun;11(3):261-76.
Gleicher N, Orvieto R. Is the hypothesis of preimplantation genetic screening (PGS) still supportable? A review. J Ovarian Res. 2017;10:21.
PGDIS Newsletter. PGDIS Position Statement on Chromosome Mosaicism and Preimplantation Aneuploidy Testing at the Blastocyst Stage. Chicago:PGDIS Newsletter;2016.
Handyside AH, et al. Pregnancies from biopsied human preimplantation embryos sexed by Y-specific DNA amplification. Nature. 1990;344(6268):768–770.