Preimplantation Genetic Screening (PGS)
Preimplantation Genetic Screening (PGS) refers to biopsy and genetic screening that is performed on embryos prior to transfer to the uterus.
PGS is used in the field of assisted reproduction for aneuploidy screening, that is, the detection of abnormal numbers of chromosomes
When PGS is requested the embryo has to be biopsied at Day 5, the blastocyst stage. The biopsy is taken from the area that is predestined to become the placenta (trophoblast) which may contain a mixture of normal and abnormal or aneuploid cells (mosaicism) even though the fetus itself may be normal.
If more abnormal cells are captured, by chance, in the sample then a diagnosis of abnormality may occur despite the fetus being normal. In otherwords there is a potential false positve rate that could be as high as 20%, meaning “good” embryos could potentially be disgarded. Vice versa so called euploid or “normal” embryos may fail to implant also due to mosaicism.
The very presence of this mixture of normal and abnormal cells makes a single trophectoderm biopsy very difficult to interpret (Scot R. “The Challenge of embryonic mosaicism in preimplantation screening”Fertility and Sterility Vol 105 No 5 may 2016)
The problem is especially hard if you have fewer blastocysts, where there is the potential for discarding normal embryos and therefore reducing the possibility of an ongoing pregnancy from the retrieval cycle.
There is added increased cost (approximately $7000) also for this procedure and although on the positive side there a greatly reduced miscarriage rate and higher pregnancy per transfer the pregnancy per retrieval cycle is not increased.
The alternate scenario is to have sequential frozen embryo transfers knowing that some may not implant. It is considered to be a controversial area due to these factors.
Preimplantation Genetic Diagnosis (PGD)
PGD is done for specific gene abnormalities identified from one’s family history of potential carrier states.
Essentially the process is the same as for PGS except PGD involves the following additional steps:
- Genetic counselling where the couple and all relevant family members, will be identified for testing which involves collecting DNA material from mouth swabs.
- The swabs are sent to the genetics reference lab which then genetic results to develop a “genetic probe” specific for the gene in question.
- The same process of embryo biopsy is undertaken as for PGS and the biopsied cells are sent to the same genetics reference lab to identify affected embryos with the genetic probe.
- Finally the disease free embryo(s) can be transferred back to the mother in a subsequent frozen-thawed embryo transfer.
- Women of advanced maternal age (over 35)..more
As a woman’s eggs age they are more prone to genetic abnormality specifically aneuploidy or abnormal numbers of chromosomes. PGS attempts to screen for this to reduce the risk of transferring back an ‘abnormal’ embryo.However the downside is that in some cases and particularly for older women IVF often yields very few Day 5 embryos and therefore there is a risk of nothing to transfer. In addition there is a risk of potential damage to the embryo or a mis reporting of false positives or false negatives.
- Couples with recurrent miscarriages that are otherwise unexplained
- Couples who have experienced several failed IVF cycles
- Couples who have had a prior pregnancy with a chromosome abnormality
- Men with infertility requiring intracytoplasmic sperm injection (ICSI)
- Men with positive aneuploidy sperm screening
- Couples where at least one partner has aneuploidy mosaics
- Couples where at least one partner is a carrier of an X-linked disease but the exact genetic mutation is not known
- Couples where at least one partner is a carrier of a structural chromosomal rearrangement
- Couples who desire to have a child that would provide a bone marrow match for sibling
These indications can be categorized differently as:
- PGD for single gene mutations PGD for determination of chromosome number (aneuploidy)
- PGD for structural chromosome abnormalities (translocations) PGD for Tissue Typing
PGD utilizes IVF often with ICSI, where multiple eggs are matured and retrieved; the oocytes are fertilized and the resulting embryos are grown in culture until the 6-8 cell stage (day 3 of embryo development). At this point, the embryo is biopsied with the removal of 1-2 cells.
The isolated cells are evaluated for the specific genetic condition.
In order to obtain results of the biopsy, the cells removed must contain a nucleus, as the nucleus contains the genetic information necessary for testing. Embryos that are determined to be unaffected by the genetic mutation (PGD) or are chromosomally balanced (PGS) are transferred back to the woman’s uterus on day 5 of embryo development.
Embryos that have both a normal test result and have continued on in development may be transferred.
Sometimes embryos that have normal genetic tests will have a physical problem that prevents them from growing normally.
Occasionally embryos that have abnormal genetic tests will appear to be physically normal. The combination of normal genetic testing with normal physical appearance indicates the highest chance of becoming a healthy pregnancy.