Cgh And Pgd On Older Women
Posted 16 November 2008 - 04:34 AM
I saw this blog on another site, is this true, that CGH and PGD is not advisable on older women!!
Whats your opinion?
For good measure, I will post a recent exchange from Dr. Zhang's blog. In addition to being an RE, he is also a PhD in embryology, and was the first IVF center in the US to use vitrification for eggs and embryos:
I am in my early 40s and I am thinking about the pros and cons of PGD and CGH. Does the risk of mosaicism work in both directions - if one blastomere tests positive for aneuploidy, can the embryo still be good? If one blastomere tests negative for aneuploidy, can the embryo still be bad? What percentage of embryos have this kind of false diagnosis?
This is the major reason why PGS for aneuploidy is out of favor. It is generally believed that at least 5% of negatives will actually be aneuploid (abnormal), and at least 5% of positives will actually be euploid (normal). Why would you want to risk throwing away a good embryo with abnormal results from CGH or FISH, especially in your age group? From a mathematical perspective - if you do PGS on embryos from a 40 year old woman, when you already know that no less than 80% of those embryos will be abnormal, it is a waste of time and money, and far too risky for that age group. Overall, the more embryos you produce and transfer, the more chance for a successful pregnancy. More testing will not change the outcome - PGS cannot correct abnormal embryos, and in fact it has the potential to damage them, and to result in the discarding of viable embryos which at your age you cannot afford to do.
How about Polar Body’s biopsy? Is the risk of biopsy could be justified by the better way to select euploid eggs?
When banking embryos how do I know when to stop?
The risk of damage to an embryo with polar body biopsy is small, as for a blastomere biopsy. The risk of mosaicism with polar biopsy is the same as with blastomere biopsy. However, polar body is a degenerating structure of the egg and the infomation from it does not tell that much about the future of the embryo. As far as blastocyst biopsy, the risk for damage is diminished in experienced hands, but the risk of mosaicism is increased. Overall, in some cases the risks of PGS (whether CGH or FISH) might be justified, but that would be dependent on the history, age of the patient, the number of embryos produced, the ovarian reserve, and any known genetic factors.
It's difficult to comment on when you should stop banking embryos without knowing the specifics of your case. It would depend on your history, your age, your financial situation, and your tolerance for repeat cycles. Obviously, the more embryos you have, the higher the chance to achieve live birth. Generally speaking, for a patient less than 38 it would be good to have a minimum of 4 developed blastocysts to optimize the chance for one live birth. For a patient over 38, you should aim for at least 6 developed blastocysts for one live birth. But please bear in mind this is only an estimate based on generalized statistics, and for each person it may be different. Also this is based on the assumption that embryos are banked using vitrification, which has a much higher rate of survival than slow freezing.
Posted 16 November 2008 - 09:53 AM
We published in May, 2007 (Fertility and Sterility) on a STRONG LINEAER CORRELATION between egg, 1st and 2nd polar body (PB-1, and PB-2) and day 3 embryo (blastomere) CGH (in cases of non-male infertility). The reported findings clearly demonstrated the reliability of single cell metaphase CGH (mCGH) in accurately diagnosing egg/embryo aneuploidy. We calculated the false +ve and/or false-ve results to be <5%. Since then we are now around >150 successes and our data can be readily substantiated. In contrast, array CGH (aCGH) for multicell blastocyst trophectoderm biopsy is believed (based upon recently presented data) to yield >15% false +ve results.
In my opinion the issue is less about differences in reliability between mCGH and aCGH than it is about the inaccuracy of multicell blastocyst CGH versus single cell egg (PB) and embryo (blastomere biopsy) CGH.
Edited by Geoffrey Sher, MD, 16 November 2008 - 10:07 AM.
Posted 16 November 2008 - 11:42 AM
How did you calculate the false positive rate? If an embryo tested positive for aneuploidy, how did you calculate that in fact it is euploid?
If an older woman can expect that 5% of her embryos will be normal, why take the risk of the same 5% (you and Zhang both used 5%) for a false positive result? She could end up discarding the one good embryo she has left. I think that is Zhang's point - do you disagree?
Do you disagree that CGH is not advisable for some patients and some circumstances?
Posted 16 November 2008 - 02:07 PM
If you need more specifics we will need to talk. This venue does not lend itself to debate when it gets down to details.
Posted 16 November 2008 - 02:33 PM
Posted 16 November 2008 - 07:39 PM
Posted 16 November 2008 - 08:00 PM
Thism is in the articles.
I am afraid that is that is the best I can do!
Edited by Geoffrey Sher, MD, 16 November 2008 - 08:02 PM.
Posted 17 November 2008 - 06:06 AM
"The literature attests to the fact that (due to technical error, misdiagnosis, mosaicism or a combination of these factors) there is at least a 5% risk of false positive and false -ve results associated with all forms of Preimplantation Genetic Testing (PG)-based testing."
Yet above you say this:
"We calculated the false +ve and/or false-ve results to be <5%. "
Can you explain the discrepancy? Is the false diagnosis rate at least 5%, or less than 5%?
Posted 17 November 2008 - 08:19 AM
Posted 17 November 2008 - 08:22 AM