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Tenacious B, I need input on genetic testing approaches

May 16 2012 at 7:54 PM
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MIR  (Login miraclex2)

 
If I remember correctly, you are doing biopsy on day 3 embryos and CGH, and then grow blast and freeze them at SIRM, right?

My clinic offered me to do the following:
1) thaw blast, biopsy and then CGH, freeze. Need to thaw again when doing transfer. My RE doesn't really like this approach because the blast needs to be thawed and frozen twice.
2) biopsy on d2, not d3, embryos, then let them grow to blast and freeze the normals. My RE is trying to push this approach.

However, I am a bit concerned if the biopsy on d2 4-cells will actually do more harm than good. So I have been doing quite a bit of reading over the last few days, and I found some research that stated that 5% of the normal embryos biopsied on day 3 couldn't make it to blast and arrested before then. Theoretically they should, but there is suspicion that the biopsy process may have hurt them at the early stage (or culture, or a combination of factors). I have also read quite a few cases of normal blasts not making it after CCS at CCRM.

So I'd like to know if SIRM believes that CGH on a day 3 embryo is considered safer than blast freezing and thawing and freezing and thawing?

Here is the way that I look at it:
I don't mind early miscarriages, it does little harm to the carrier. I do mind 20 week abortion because of the harm to the body of my GC, and all the cost involved. It seems like with biopsy on a pre-blast embryo, there is a 1/20 (5%) chance of loss for normal embryo. But the ratio of Down and other rarer disease is about 1/64. Since that risk is lower than the loss of embryo, shouldn't I opt for the lower risk 1/64 and push ahead with CVS (loss ratio of 1/300) instead of taking the 1/20 risk?

 
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Jamie
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barge to MIR

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May 16 2012, 11:57 PM 

MIR, all I can say is that my RE was not worried about thaw, biopsy, freeze and eventually thaw again someday. Both my embies survived the thaw and biopsy process. I would be petrified of taking a cell from a day 2 embryo and that disruption, versus taking a few from a blast. With a blast they can grab cells from the area that will develop into the placenta rather than the baby. With vitrification I think the freeze part at least is pretty negligible. If the lab is skilled the thaw should be fine.

Does your RE have a comment on mosaicism? I have read that that is a concern with earlier embryo biopsies.

 
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MIR
(Login miraclex2)

My clinic just started offering this

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May 17 2012, 12:18 AM 

I am also petrified at taking ONE out of FOUR cells, so I prefer not to do that at all. Two-time freezing-thawing could be a problem at my clinic because it is new for their lab. So in a way, I will be part of the earlier skill-building patients, which is something I don't want. If I were with an established lab doing this two-time freeze-thaw, I would have felt more comfortable.

 
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LadyG
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Another Barge

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May 17 2012, 12:13 AM 

Having just been thru the decision of whether to freeze our 3 blasts and bank for future CCS testing with the next batch we learned the following:

*CCRM were not fond of the two time freezing and thawing, more because they have only done this about 25 times and do not have any long term data on whether this has any impact on babies born from such embryos

*They recommended freezing at day 3, then pooling that batch with the next by unfreezing the day 3 group and letting them all grow to blast together and testing the blasts that make it. They will not biopsy even on day 3 as one cell from an 8 cell embryo is 12% of that embryo - too stressful on the embryo for their liking. This still would involve freezing twice those that make it to blast from the first batch, which I forgot to ask them about, but I will inquire about that next time I speak with them.


 
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MIR
(Login miraclex2)

Thanks and further questions

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May 17 2012, 12:25 AM 

Why do they freeze at day 3 and then thaw to grow to blast instead of growing blast straight from the beginning? Does it have something to do with switching culture medium from d3 to d5 which is a labor intensive practice? I can understand that if they are one of the practices using different culture, batching frozen d3 embryos would make a lot of sense operation wise. I believe my clinic uses only one culture from d3 to d5, and every lab has their proprietary culture medium/approach.

As of 2011, a couple of my friends who went to CCRM reported that they were still doing growing blast straight from the start and biopsy before freezing. So what you mentioned sounded like a deviation of the practice they were doing. I am sure a cutting edge clinic like CCRM updates its practice all the time based on the feedback.

 
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LadyG
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not sure

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May 17 2012, 12:55 AM 

about whether they do a culture change at day 3-5. i am wondering if the two time/freeze has less impact on a day three 8 cell less complex embryo (at least for the first freeze/thaw) than twice freeze/thaw on a blast? i need to ask them.

 
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TenaciousB
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That's a tough one

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May 17 2012, 1:49 PM 

Hi MIR! That's is a tough one. This kind of testing (Array CGH, Micro-array CGH, CCRM CCS, 3-Day, 5-Day)...is all so new, it's hard to know what's safest/best for the embryos. I am not up on the statistics, but I think you should go for whatever scenario your lab recommends. My sense is you don't want to push their skill set or have your embryos be the "guinea pigs."

SIRM-NY's embryologist is currently doing 3-Day biopsies (removing 1 cell from a 6-10 cell embryo). That way, they can send the biopsies out to the Reprogenetics lab to get the results by day 5 (& either do a 5-6 day fresh transfer or vitrify 5-6 day blasts). I believe they do it that way because the embryologist feels very comfortable with Day 3 biopsies. Personally, I want to do whatever you embryologist feels is most within his/her skill set.

Is a Day 2 biopsy called a "polar body" biopsy?

Regarding Day 5 CGH testing, Dr. Sher prefers that method over Day 3 (per his blog ivfauthority.com --- another good place to search for CGH info). However, I think his Vegas embryolgist usually biopsies prior to freeze, then vitrifies (the 5-day results take a couple of weeks to come back).

With regard to double-freezing, I think Sher would recommend freezing earlier (day 2 or 3), then growing to blast before biopsying, then vitrifying again. They don't like thaw and freeze them again on the same day.

Dr. Sher is pretty active in answering questions through his Vegas discussion board on haveababy.com. Maybe you could ask him for advice there. Dr. T doesn't check the NYC discussion board as frequently, but it couldn't hurt to ask him, too.

Wish I could be more helpful. Please keep us posted about your research and what you decide!!



 
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