PGS / PGD and Embryo Biopsy
- More than 25% of all miscarriages are due to embryo aneuploidy.
- Aneuploidy is common and early embryos are naturally aneuploid. About 20% of human eggs and 9% of human sperm are thought to be naturally aneuploid.
- It is the most common cause of implantation failure in IVF. Studies suggest that over 55% of blastocysts are genetically abnormal / aneuploid (Journal of Fertility and Sterility) which if transferred to the uterus usually result in miscarriage. A few may survive to birth presenting genetical abnormalities, the most common of which is Down’s syndrome (Trisomy 21).
- Embryo biopsy and genetic screening are invaluable techniques in ART which assist in the selection of the ‘best’ most viable embryo for transfer.
Read on to find out more about embryo aneuploidy, how it affects conception & pregnancy, what genetic tests are available and for whom they may be recommended in order to improve the chances of a successful pregnancy and healthy newborn.
KEYWORDS: Human embryo, Chromosome, Euploid, Aneuploid, In vitro fertilization, Preimplantation genetic screening,
What is embryo aneuploidy?
Aneuploid embryos don’t have the correct number of chromosomes, either they have extra (trisomy) or missing (monosomy) chromosomes and this is considered abnormal. Such embryos are a relatively frequent occurrence in both natural and assisted human reproduction. In nature they are believed to be one of the major limitations of human reproduction, accounting for approximately 50% of early pregnancy losses.
Most aneuploid embryos are lost through implantation failure, and a woman has a negative pregnancy test. Those that survive may result in spontaneous miscarriage and the few that grow might result in a stillbirth, or a baby born with congenital birth defects. Down Syndrome (Trisomy 21) and Turner Syndrome, where an x chromosome is missing, are examples of aneuploid embryos or aneuploidy.
As such aneuploidy is a major obstacle in achieving successful pregnancies in in vitro fertilization (IVF) procedures. They are the most common cause of implantation failures. In practice, more than 50% of preimplantation embryos are aneuploid and unable to achieve viable pregnancy.
Preimplantation Genetic Screening (PGS)
How do we select chromosomally normal embryos?
In assisted reproduction we need to be able to find the healthy chromosomally normal (euploid) embryos for the best chance of a successful pregnancy and healthy newborn. These embryos are have 46 chromosomes in 23 pairs. These are the embryos suitable for embryo transfer.
It may be recommended to carryout a technique called preimplantation genetic screening (PGS) to test your embryos before your embryo transfer procedure. It is the most effective way to find the best embryos for transfer to avoid abnormalities that could affect your pregnancy or a healthy birth. It is sometimes also called preimplantation genetic testing for aneuploidies (PGT-A).
PGS/PGT-A is a generalised test that screens for general chromosome abnormalities of the embryos (i.e. looking at the number and arrangement of chromosomes). It does not screen for genetic diseases. It is the preferred method for selecting euploid embryos for transfer in couples who do not carry a specific inherited disease. For this reason, it is widely used as a monitoring tool before embryo transfer.
There are many possible reasons to recommend PGS testing, including advanced maternal age, recurrent implantation failure, severe male factor, and couples with normal karyotypes who have experienced repeated miscarriages.
Preimplantation Genetic Diagnosis (PGD)
PGD testing is used when a couple is looking to diagnose or screen for a specific genetic disease.
This technique allows couples who are single-gene carriers or carriers of chromosomal abnormalities to choose normal embryos for embryo transfer, thereby avoiding risks such as genetic transmission of abnormalities to their children, human leukocyte incompatibility and recurrent miscarriages. Currently, there are several types of the method available depending on the needs of each couple all of which are provided at Life Clinic.
PGD essentially involves the collection and genetic analysis of not only early stage embryos (about three days old) but also embryos at the blastocyst stage. Healthy embryos with normal genetic and chromosomal structure are selected and transferred to the uterus for implantation.
Over 4,000 monogenic abnormalities are identified, the most common of which are Cystic Fibrosis, Tay-Sachs, Fragile X Syndrome, Myotonic Dystrophy and Thalassemia. PGD does not in any way involve manipulation of the genetic material of the embryos, it only allows the selection of normal ones over those that show aneuploidy.
The embryo biopsy
The PGD / PGS process begins with egg collection and fertilisation in our laboratory as part of IVF or ICSI. The embryos are allowed to develop in culture up until the blastocyst stage (Day 5 or 6) at which point our embryologist performs an embryo biopsy where a small sample of cells are collected from the outside layer of the blastocyst embryo to be genetically screened. The biopsied material is sent to a genetic testing laboratory for PGS / PGD that specializes in examining the DNA of these cells. After receiving the results from the genetic testing laboratory, those embryos which have a normal karyotype are selected for transfer. Other normal embryos can be kept frozen for future use.