Preimplantation genetic screening (PGS), refers to removing one or more cells from an IVF generated embryo to test for chromosomal abnormality. PGS screens the embryo for normal chromosome number. Humans have 23 pairs of chromosomes. Down syndrome has an extra chromosome 21, referred to as trisomy 21. This can be detected by PGS. PGS does not test for a specific disease – such as cystic fibrosis, thalassemia. Detection of disease such as cystic fibrosis, thalassemia through embryo biopsy is known as Preimplantation Genetic Diagnosis (PGD)
Many studies have shown that about 60% of human preimplantation embryos from IVF are chromosomally abnormal. The rate of abnormalities to a large extent is affected by the female age. Chromosomes in eggs from older women have a significantly increased rate of abnormalities.
chromosomal abnormalities are mostly responsible for the failure of the implantation of IVF embryos. Chromosomal abnormalities are also responsible for about 70% of miscarriages in early pregnancy.
PGS in IVF embryo for aneuploidy (an abnormal number of chromosomes) has been used since the mid-1990s. However, studies showed that performing embryo biopsy on day 3 and performing the genetic analysis using FISH technology (fluorescent in situ hybridization) did not result in an increased pregnancy rate.
Advances in the field have led to the utilization of improved genetics technologies that allow assessment of all 23 pairs of chromosomes.
There are currently 4 technologies that can be utilized for assessment of normality of all 23 chromosomes :
Comparative Genomic Hybridization (often referred to as CGH, or a CGH) is microarray technology that is often used now instead of the older and far less comprehensive FISH. With microarray CGH, the actual DNA in the embryo is compared to a known normal DNA specimen utilizing thousands of specific genetic markers. This gives a more accurate result, with far fewer false normal or false abnormal results.
Some studies have determined that the error rate using array CGH technology is about 2%. FISH has an error rate of about 5-10%. Additionally, many other abnormal embryos would be reported by FISH as normal because the abnormality was in a chromosome that was not part of the FISH panel being used.
Next-Generation Sequencing (NGS) is a newer technology that has been increasingly utilized for testing IVF embryos since about 2015. NGS appears to be better at detecting smaller segmental changes compared to aCGH. It is also thought to be better at detecting partial aneuploidy and small unbalanced translocations. Mosaicism is probably more likely to be discovered using Next-Generation Sequencing.
Trophectoderm biopsy is done at the blastocyst stage on day 5 and 6. At this stage, there are many more cells present in the embryo. This allows multiple cells to be removed from the trophectoderm which is precursors to the placenta and the inner mass cells which are precursors to the fetus can be left undisturbed during the biopsy. With trophectoderm biopsy, about 4-5 cells are snipped off for testing. This does not significantly weaken the embryo because it has about 100 cells at this stage.
The combination of these two modifications (advanced genetics and trophectoderm biopsy) has led to significantly improved pregnancy success rates for patients that want to utilize PGS for their IVF treatment.
We are seeing substantially improved ongoing pregnancy rates in patients that are having trophectoderm biopsy performed at the blastocyst stage with subsequent freezing of their embryos.
A frozen-thawed transfer cycle is done after the chromosomal analysis results come back.
There is some interesting speculation that the uterine lining could be less receptive during a stimulated cycle as compared to the controlled or “artificial” embryo replacement cycle.
Transferring embryos in a controlled cycle (using frozen embryos) gives a higher pregnancy rate than in a “fresh cycle”.
The improved success rate seen following blastocyst biopsy and comprehensive chromosomal analysis is also due to the benefit of transferring chromosomally normal embryos.
This is currently an evolving issue in the field of reproductive medicine
Some potential candidates could be :