Wow, the medical community loves its acronyms. PGD, PGS, FISH, CCS – I often get asked to explain the differences and options for genetic testing of embryos prior to transfer. So, in sort-of layman terms, here’s my explanation.
The terms PGD and PGS are often used interchangeably – the “d” technically stands for diagnosis, the “s” for screening – but they are both types of preimplantation genetic testing.
PGD – preimplantation genetic diagnosis.
In the past, this was the “catch-all” used for any genetic testing of embryos. But, practically speaking, if we are using it to prevent transferring a known genetic defect/mutation of a specific gene or balanced chromosomal rearrangement – for example, single gene defects such as cystic fibrosis, hemophilia, Tay-Sachs, etc. then we are testing for a known genetic mutation. The SART/ASRM says the term PGD applies when “one or both genetic parents carry a gene mutation or a balanced chromosomal rearrangement, and testing is performed to determine whether that specific mutation or an unbalanced chromosomal complement has been transmitted to the oocyte or embryo.”
PGS – preimplantation genetic screening.
This is a newer term for screening embryos for the correct number of chromosomes and look for any abnormalities in the chromosomes. It is also sometimes called aneuploidy screening (which is a fancy way of saying we’re looking for competent embryos). Aneuploidy embryos have chromosome defects. SART/ASRM says PGS term is to be used when “the genetic parents are known or presumed to be chromosomally normal and their embryos are screened for aneuploidy.”
Now, before we go any further, we need to talk about the fact that there are several different ways of testing embryos before implantation.
FISH Methods– This is the older method that has been widely used until recently. It typically only tests between 5 – 10 chromosomes, rather than all of the chromosomes. So, it is possible to pass testing with FISH method and still have some chromosomal abnormalities. These biopsies in the past have been typically done on day 3, and only biopsy a single cell. Although this can be the better choice for select PGD situations, for standard PGS (where we are not testing for a specific defect but testing for overall competency), the concern is that that not allchromosomes are evaluated. Also, some experts believe that there may be some false positives or uncertain results, or even that in some cases an embryo that tests positive for a defect on day 3 might have been able to self-correct by day 5. The added concern with a day 3 biopsy is that some feel there is possibly a higher risk of damaging the embryo (since they are typically only around 8 cells by day 3). With the day 3 biopsy, the results are typically back in time for a fresh blastocyst transfer on day 5.
CCS – Comprehensive Chromosomal Screening. CCS is a form of PGS and simply means you are screening all pairs of human chromosomes rather than a limited set tested with FISH methods. Now, just to make it more confusing, there is also more than one way of evaluating all chromosomes with CCS – common methods are CGH (also known as array CGH or aCGH), SNP and qPCR.
With CCS, you can do a day 3 biopsy (again, only a single cell like is often used with FISH testing) or also a day 5 biopsy, which allows you to biopsy a few cells, giving them more material to analyze. The experts are still uncertain as to whether a day 3 or day 5 biopsy is better, but some feel that the embryo may be better able to tolerate the day 5 biopsy. An advantage of day 3 biopsy is that most labs can have the results back in time for a fresh blastocyst transfer on day 5. The disadvantage to day 3 biopsy is having only one cell to evaluate; whereas with day 5 biopsy there are a few cells to help re-verify any positive or unclear result. When doing a day 5 biopsy, many clinics are then immediately freezing the embryos (typically with vitrification so that the thaw rate is 95+%) and then waiting for the CCS results, and then doing the transfer in a later frozen cycle.
There are a few clinics that can do a day 5/blastocyst biopsy and have the results back in time for a fresh day 6 transfer, but again, experts are mixed on which option may be the better solution. Also, when trying for a fresh day 6 transfer, you run the risk that if the embryo is not at blastocyst stage by day 5, you are forced to wait until it is a blastocyst on day 6, biopsy, then freeze anyway and wait for a result, because outcomes of day 7 transfers are not very good. Anecdotal evidence seems to support that currently many clinics are preferring the day 5 biopsy with a freeze/vitrification and transfer in a separate cycle. But, for patients traveling from afar for treatment, it may not always be the preferred choice since it requires at least two separate visits.
There are two potential additional advantages to freezing the embryo after a day 5/blastocyst biopsy and doing a frozen transfer. The first is in an own egg cycle, if waiting for a frozen transfer the woman’s body can recover from the stimulation medication and be in a more natural hormonal state at the time of transfer which is thought to possibly enhance the likelihood of implantation and recent studies indicate that it may improve overall pregnancy outcomes. That benefit doesn’t necessarily extend to a donor egg cycle, since the medications are similar to the recipient for a fresh or frozen transfer. The second potential benefit is that by batching embryos together, the overall cost of testing may be lower.
PGS/PGS Costs – In the US, costs for PGD/PGS vary by clinic and type of testing, but the typical cost of CCS ranges from around $4000 – $8000 for up to 6 or 8 embryos, with additional fees per add’l embryo tested. I haven’t seen much difference in the CCS pricing at US clinics regardless of whether they are getting the results back for a fresh transfer, or vitrifying and waiting for results. Some clinics do charge an additional FET fee for the transfer (adding to overall cost), while others waive the FET fee since they didn’t do a transfer in the fresh cycle. At some European clinics, I am seeing some benefit of lower costs by batching embryos for testing (day 5 biopsy/vitrification and transfer in FET cycle). For example, where a European may charge around 2350 Euro (approx. $3100 US) for CCS with array CGH testing of up to six day 5 biopsies with STAT results in time for a fresh transfer; if they biopsy and freeze, then test as part of a larger batch, they offer it on a per embryo basis for around 370 Euro (approx. $500 US).
This option is particularly attractive for women of advanced maternal age who many not be producing as many embryos and are at a higher risk of aneuploidy embryos (experts say as many as 60% of miscarriages are due to aneuploidy). Whereas paying $5000+ to test one or two embryos might not be cost effective; paying $500 for testing a single embryo to improve success rates and reduce miscarriage rates seems like a reasonable and affordable consideration.
For a more technical discussion of PGS, CCS methodologies and comparisons of FISH and CCS, an informative article published in the March 2012 Journal of Assisted Reproduction and Genetics can be found at: