I am just about to finish an IVF cycle I am doing with a lovely couple. They are in one of the best prognosis groups. He has children from a previous marriage as does she. She had a tubal ligation and “only” has blocked tubes (this is the best prognosis group for IVF). She is 37 years old and while not as young as the highest chance group her chances should be outstanding.
So why in heck am I writing this pleasant little musing on them? Where is the technology in the story? Well they decided they wanted PGS (preimplantation genetic screening). This cutting edge technology can be used to screen embryos for genetic diseases and also to test for major genetic abnormalities leading to miscarriage. Approximately 20-30% of early human pregnancies will miscarry due to genetic abnormalities. These are commonly trisomies or monosomies where there is loss of addition of a chromosome (supposed to be only 1 from mom and 1 from dad of each).
In PGS we biopsied each little embryo removing a single cell called a blastomere from an 8 cell day 3 of development embryo. It’s tested overnight and Voila! I got the report today— 10/12 of her embryos were genetically abnormal and incompatible with life! This is the power of this new genetic technology. So luckily 2 of them can lead to a live born baby and I’ll be putting those 2 in tomorrow on day 5 of development.
What’s the controvery DITM?
1) I also get information about the sex of the embryo and people are increasingly requesting this for sex-selection. Should we being doing gender selection? A leading researcher once said last time I checked “gender was not a disease”
2) It has recently been discovered that a “mosaicism” occurs in human embryos. This could lead to high rates of inaccurate results from single embryo biopsies. This is an amazing new discovery–human embryos were thought to undergo orderly cell divisions all equal. NOT TRUE! We know now that every so often (how often we do not know) there is an uneven division of just one cell so its offspring cells are abnormal but all the others are normal- and it may be that those 2 abnormal one will die but the normal cells happily grow! This means that unless we do multiple cell biopsies (and remember there are only 6-10 little cells in an embryo at this stage) we will think it’s abnormal when it is not…
The answers in the future:
1) multiple cell biopsies
2) very large cell number biopsies at the blastocyst stage of development with instant genetic results (day 5 of development cell numbers skyrocket)
This is fascinating. It occurs to me that with a mosaicism, you are as likely to snag normal cells from a partly abnormal embryo, leaving it with fewer normal cells to outnumber the abnormal ones — and not realize that you’d discarded what might actually be viable embryos in favor of non-viable ones. Multiple cell biopsies would seem to be a much more reasonable alternative than trusting single-cell biopsies.
The deciding factor is likely the % cell normal vs abnormal which is clearly related to when in cell division the abnormality occurs and how well the abnormal cells divide. You are 100% correct about the multiple biopsy idea but with current technology this places a signififcant stress on the embryo and seems to reduce viability. In the future we will be biopsying the blatocyst (day 5-6) which has closer to a hundred cells. If we can get the genetic answer instantly (this is coming- today we need a day) then we can just biopsy multiple cells at this stage, get result, & replace normal embryo.
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Mosaicism is quite common in embryos, it is because of the repeated cell division without the proper check of the disjunction of the chromosomes. Anyway, just to point out it is a functional feature that embryos, at the early stage, produce mosaic cells.
Solution for PGS (PGD in UK)? Well, I know University College London takes two cells out of the eight for FISH just to eliminiate mosaicism and false positive. It works well.
Of course, beside false result, there maybe downfall from performing PGD.