How reliable is PGS testing?
Dear Professor Winston,

The service you are providing here is much appreciated – thank you.

When I was 41 I conceived naturally (by accident) but miscarried at week 6. I then looked into IVF, was said to be a good candidate for IVF given my AMH and ovarian reserve, and have just (at age 42) finished two rounds of egg collection via IVF – heavily medicated!

In total I produced 26 eggs, of which 22 fertilised and 16 made it to day 5 / 6 blastocysts. I opted for PGS testing understanding that due to my age a high number of these blastocysts would be abnormal and I wanted to make sure we (as far as we can tell with currently available technology) put the best one back and hopefully have some reserves as of course not every egg works.

Unfortunately only one egg was Euploid, graded A, 2 had no results due to insufficient DNA (of which 1 egg is graded B – the other said to be poor quality) 1 was low level mosaic, but Chromosome 21, and the rest abnormal (5 blastocysts) or complex abnormal (7).

I wanted to ask your thoughts on how reliable PGS testing is, in particular I wanted to get your thoughts on what the science says around the possibility of the abnormal blastocysts self correcting as they grow?

I may have one of the no result blastocysts re-biopsied – I don’t want to waste time on an embryo that will abort if it is chromosomally abnormal – would you recommend that? Even though there is more potential for damage given the thawing- biopsy- freezing process, of which I think little is known especially of the long term effects.

I wanted to get more opinions on this before considering a further round of egg collection. My previous two rounds were fine – but I worry that injecting high volume of hormones isn’t the best thing I can do to my body and the financial cost is huge.

Many thanks

L

 

Dear Lucy,

Thank you for your enquiry. I do not want to sound arrogant, but seeing as it was the Genesis Research Laboratories which pioneered embryo biopsy and funded the research as well as the first PGS, I think I can speak with a degree of confidence.

I regret to tell you that PGS was never intended to pick out good embryos in this way.  In our service it was originally designed to help those couples who were known to carry chromosomal defects and pass them on to a foetus.  In these patients miscarriage or an serious abnormality after birth were what we were trying to avoid. But I do not know of any really well conducted study which clearly shows PGS can identify embryos from so called “normal” couples no matter what their age is.  Regrettably it is widely used in some private clinics, sometimes makes them a great deal of money, but no properly controlled trial has clearly shown that it improves pregnancy rate.  Indeed, it is even possible it may decrease it. This is because a huge proportion of human embryos are mosaic – that is to say some cells are normal, but others are chromosomal abnormal or aneuploid.  So it is certainly possible to sample a number of abnormal, aneuploid, cells from a perfectly normal embryo and then mistakenly discard it.

Your case is most interesting as well because you produced 26 eggs – a very high number for somebody of your age and probably too high. This over brisk response to ovarian stimulation is very likely to increase aneuploidy so although you may think you are lucky to have produced so many embryos, this is not to your advantage.  You are right that where there are some cells which are chromosomal abnormal there may be some correction as these abnormal cells die out and do not produce a lineage but this is extremely unlikely to be helpful where there has been an exaggerated response to stimulation.

As it happens, I think PGS should not be done to improve “embryo quality”. There is, in my view, enough to suggest that invading the embryo in this way is far from ideal and given the the lowered pregnancy rate that a number of centres have reported, it doesn’t seem like a great idea.  I certainly would personally not want to do this in the frozen/thawed embryo that you are considering.

As it happens, at Genesis a colleague and I are now working on a project to identify the most viable embryos which does not involve major manipulations like biopsy and is far cheaper. We are testing different aspects of embryo development and with a bit of luck I think we have a good chance of a much more effective and far less expensive way of choosing embryos. Our problem has been two-fold. Covid has held up doing the key laboratory work we need and secondly, there are only two of us. Genesis needs to raise more funds to employ research assistants but at the present time there are people around who could certainly move this research forward but we need funds, like all charity at present, to employ people.

Finally, I absolutely agree with you. Using high doses of hormones probably isn’t that good for your body and it a most certainly is not likely to be good for your eggs.

My best wishes,

Robert Winston