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February 4th, 2014, 10:57 PM #1IVF Advice Coach
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Day 3 accuracy of aCGH for gender
Hi Alyssa!
Let me preface my question with the background knowledge that we have had people give birth to opposite gender children on here after using day 3 CGH. It was over a year ago when it happened but it has happened and since then, we as a community looked into the issue and tried to go right to the source- Dr Sher of SIRM who is responsible for the aCGH test. He told us that Day 3 aCGH is not always reliable for gender detection because the "Y" chromosome is so small, during the analysis, the "computer" does not see it and since CGH does not actually look for 2 XX chromosomes and compares DNA found to a sample, it incorrectly can label the embryo as a normal XX embryo when in fact it is a normal XY- that is my "non-medical background" synopsis!
SO, we have people consult with doctors that say they use day 3 aCGH when doing 23+gender testing and they think it is just fine to use. Many clinics have gone to day 5 only because as we have also seen on here, embryos that initially test "abnormal" with day 3 testing can retest normal on day 5 with a re-biopsy and have resulted in pregnancies on here. That is compelling enough for me to not use day 3 testing but when people are trying to choose clinics, not all clinics have day 5 biopsy capability and then travel becomes as issue and it just makes the process hard.
My questions-
1. How reliable in your opinion is day 3 aCGH testing- particularly for gender.
2. Is day 5 testing done using one cell just like day 3 with aCGH? If so, is it any more reliable than day 3?
2 things that sway my opinion with Day 3 CGH from Dr Sher of SIRM-
Array CGH vs. Metaphase CGH in IVF: Which is Best & When to Test | IVF Authority
and
http://genderdreaming.com/forum/ivf-...h-testing.html
Thanks!!Mom to
and my IVF/PGD
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April 12th, 2014, 06:30 PM #2Banned
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Can these questions be answerd? Is there more information about it after using it more often?
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April 22nd, 2014, 05:54 PM #3
Dear Nothinbutpink,
Thank you for your message. In our experience, aCGH testing is very accurate for both Day 3 and Day 5 biopsies. It is true that for a Day 3 biopsy, only a single cell is taken, and so there is less DNA to start with than a Day 5 biopsy, where several cells can be safely taken. DNA from both Day 3 and Day 5 biopsies is amplified (copied many times) until there is enough to use for analysis, so in the end, a similar amount of DNA is used for both biopsy types. If the DNA sample is insufficient (happens only 0.01% of the time) to give a reliable call, our lab will report "No Results" rather than report ambiguous or low-confidence results. We do see a slightly higher "no call" rate for day 3 biopsies (5%, probably due to an anucleated cell) than we do for day 5 biopsies (2%). These are reported as “No DNA detected,” but if a result is obtained for a Day 3 biopsy, we are as confident as we are with a Day 5 biopsy.
Rates of mosaicism may be different between Day 3 (up to 40%) and Day 5 biopsies (~4%), which can affect the likelihood of misdiagnosis. However, misdiagnosis of gender resulting from purely XX/XY mosaicism is rare. Misdiagnosis resulting from mosaicism is more likely to involve other chromosome abnormalities.
Even on the Y chromosome, there are hundreds of probes, and so the computer analyzer is reliable in detecting Y when it is present. We do in fact look for the presence of two X chromosomes. aCGH looks for the amount of genetic material present, and for each test, a male and female control is used as a reference. If the embryo has two X chromosomes, then we get 100% match with female reference, 0% match with male reference, and we know it is a girl. If the embryo has one X and one Y, we get 50% match with female reference and 50% match with male reference, and we know the gender of the embryo is a boy.
Our regular aCGH platform is 98-99% accurate for all chromosomes analyzed, including the sex chromosomes. In our experience, we do not have a higher rate of misdiagnosis for the sex chromosomes than for any other chromosomes, even though the Y is small. Still, 98-99% accuracy means that 1-2% of the time, there could be a misdiagnosis. Our GenderSure test adds an additional step that increases the accuracy to nearly 100% (99.999%) for the sex chromosomes.
Sincerely,
AlyssaAlyssa C. Snider, MS, PhD, LCGC
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