Picture of a high quality blastocyst 5 days after fertilization
The cells in the 10 o'clock area comprise the inner cell mass (ICM) - precursor of the fetus
Trophectoderm cells (TE) that will form the placenta surround the fluid cavity
What is PGD vs. PGS?
Preimplantation genetic diagnosis, PGD, is a term that is often loosely used to refer to any testing done on in vitro fertilization embryos prior to transferring them to the uterus
For example, PGD can be done on embryos from a couple with both partners known to be carriers for a specific genetic disease such as cystic fibrosis
They can then have embryos transferred that will not be affected with cystic fibrosis
The term PGS (preimplantation genetic screening) is often used when referring to testing done looking specifically at chromosome number abnormalities (karyotype testing, or aneuploidy testing)
Negatives about blastomere biopsy on day 3 instead of trophectoderm biopsy on day 5 or 6
On day 3 human embryos usually have about 6-10 cells. The cells are large and have significant cell to cell attachments.
Therefore, blastomere biopsy requires a large hole in the shell - and that cell must be pulled (torn) away from its neighbors
Depending on the total cell number, about 1/6 to 1/10 of that embryo has been removed (if only 1 cell is taken)
The embryo gets somewhat "beat up" and loses a significant part of its total mass
The blastomere biopsy procedure on day 3 is traumatic to the embryo and has been shown to reduce its developmental potential (strength). Therefore, day 5 or 6 trophectoderm biopsy at the blastocyst stage has been developed in order to minimize trauma to the embryo.
Advantages of trophectoderm biopsy and PGD success rates
The advantage of trophectoderm removal is that the embryo is much less traumatized by the procedure compared to blastomere removal done on day 3
Since the embryo has many more cells (about 100) at the blastocyst stage than on day 3 (about 6-10), we can remove about 5 cells with trophectoderm biopsy with little or no impact on its potential
Trophectoderm biopsy allows the potential to increase IVF live birth success rates by screening for chromosomally normal embryos prior to transfer back to the uterus
Well controlled studies of blastomere biopsy on day 3 with PGS have repeatedly shown lower IVF success rates as compared to IVF without biopsy and PGS
At this time (2013) there are very few published studies on IVF with trophectoderm biopsy and PGS
More studies are needed and will likely be done soon
Disadvantages of trophectoderm biopsy
At this point performing the genetics techniques for chromosomal or genetic analysis on the cells requires 24-48 hours
So a day 3 biopsy can be done with the information about the chromosomes or genetics coming back in time to do transfer on day 5 with fresh embryos
However, when the cell removal is done on a day 5 embryo the genetic or chromosomal results will not be back in time to do a fresh transfer procedure
So we must do the trophectoderm removal, then freeze the embryos, and wait to get the genetics results back before we thaw and transfer back blastocysts to the uterus
The disadvantages of this approach are:
Increased cost from adding a frozen embryo transfer cycle
Delay of about a month before the transfer can be done
The need for development to the blastocyst stage to do a biopsy procedure. Not all couples will have embryos develop to blastocyst stage.
A very small hole is made in the outer shell of the embryo with a laser
A pipette is used (with help from the laser) to detach a few cells off of the trophectoderm component - the precursor to the placenta (see blastocyst picture above)
The cells that will become the fetus itself (inner cell mass) are not disturbed
After trophectoderm removal, all biopsied embryos are frozen
How is preimplantation genetic screening, PGS, done with blastocyst IVF embryos?
Trophectoderm removal is done as described above
The biopsied trophectoderm is sent off for chromosomal (and/or genetic) analysis
The chromosomal (or genetic) test results come back within several days
The appropriate embryo (or embryos) are thawed and transferred back to the uterus
It is quite possible that in the future technology will advance so that we can assess chromosomal competence and/or genetic specific genetic defects within a few hours. This would allow day 5 trophectoderm removal with transfer of fresh embryos the same day.
We are doing trophectoderm biopsy and embryo freezing (vitrification) and subsequent frozen transfer for cases needing genetic evaluation for single gene defects (cystic fibrosis, etc.) and for couples that want PGS screening for normalcy of chromosomes (aneuploidy screening).
Eventually, studies will be done and published that will determine to what degree IVF with preimplantation genetic screening increases chances for pregnancy and live birth for couples with advanced maternal age, recurrent IVF failures and/or recurrent pregnancy loss.