PGD Opposite

[nuthinbutpink]

Hi Dr P.

This is has been a tough couple of weeks for HT. There have been 2 reported cases of PGD opposites and both seem to be the result of a day 3 aCGH biopsy.

I know you are "with" GSN but you recommend day 3 for GSN so I want to ask how accurate gender is with a day 3 biopsy. I have seen the confidence levels quoted but with gender, it seems either there is an X and a Y or XX so why would there be any confidence level associated with those chromosomes other than 99%?

I don't have a great understanding of the GSN or CGH process- how the chromosomes are analyzed. I know that there is a lot to look at using one cell though. Is gender something we have to now worry about when using PGD? I know with old school FISH, either you see XX or XY or not. Human error was the only cause of an opposite but with these new testing methodologies, is it due to human error or is it a real possibility?

[Dr. Potter]

Hi Dr P.

This is has been a tough couple of weeks for HT. There have been 2 reported cases of PGD opposites and both seem to be the result of a day 3 aCGH biopsy.

I know you are "with" GSN but you recommend day 3 for GSN so I want to ask how accurate gender is with a day 3 biopsy. I have seen the confidence levels quoted but with gender, it seems either there is an X and a Y or XX so why would there be any confidence level associated with those chromosomes other than 99%?

I don't have a great understanding of the GSN or CGH process- how the chromosomes are analyzed. I know that there is a lot to look at using one cell though. Is gender something we have to now worry about when using PGD? I know with old school FISH, either you see XX or XY or not. Human error was the only cause of an opposite but with these new testing methodologies, is it due to human error or is it a real possibility?

We have never had a gender opposite using GSN and neither has any of of our collaborators. This represents thousands of cases at this point. The aCGH process has a particularly hard time with small chromosomes (such as y and 22) and also has real problems with accuracy unless it is done on day 5. Based on data recently presented at our annual meeting, aCGH is not a good choice for day 3 biopsy and does not work well with single cells. I am with GSN but all the other people that are presenting data are also with their own companies with similar potential proprietary biases. What I think is very clear at this point is that GSN is a superior technology in terms of accuracy (as compared with aCGH and other microarray based platforms) on day three. GSN's real advantage is the ability to get accurate results from a single cell. FISH can also be used reliably to detect gender only on day three but does not help with embryo selection. We never had a FISH gender opposite and I am not aware of any of my competitors having an opposite with FISH. On day 5, GSN's advantage over aCGH in terms of accuracy is minimal as they are both very accurate. GSN is still the superior technology on day 5 because is at least as accurate as aCGH and provides you with more information. Remember, GSN is able to detect polyploidy, uniparental disomy and determine the parental source for any aneuploidy (on both day 3 and day 5) where aCGH cannot. I hope that this helps. Great question!

[nuthinbutpink]

Thank you. It is upsetting that knowing that we are doing this only for GS that a clinic would recommend something that is less than 100%. I guess that is where experience with the technology really matters.