PGD abnormalities and frozen TESE sperm
7 Replies
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Dear Dr Smith
My husband and I just had our first PGD cycle. We were told that the abnormalities found were suggestive of post-zygotic chromosome abnormalities.
I have 2 questions.
1) What exactly does this mean?
Does this mean that something happened to the chromosomes after fertilisation? Does it mean that the chromosomes in the sperm and egg were OK but then something happened? Or does it mean that chromosomes were abnormal in the egg and/or the sperm?
2) Is this pattern likely to be predictive of any future cycles?
For information my husband's azoospermia is believed to be from an obstruction deep in the pelvis. Hormone profiles, karotype, CF mutations etc all normal.
Many thanks
Regards, Torrin
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Post zygotic means that the abnormality occurred after fertilization. This implies that the sperm and egg were genetically normal, but during the subsequent division process something went wrong.
Testicular sperm are not completely mature and they often have an abnormal shape. In TESE cases, it is very hard for the embryologist to choose a morphologicallly normal sperm for ICSI. Accordingly, there is a higher incidence of genetic abnormalities in embryos generated from testicular sperm. I'm not genetist, but I wouldn't rule out that the problem came from the sperm.
Every sperm-egg combination is genetically unique, so it is difficult to predict the chance of this occuring on a subsequent cycle.
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Dr Smith
Many thanks for your reply. It's thrown up a few more questions.
!) If freshly retrieved/frozen epididymal sperm were available would that be preferable? Blockage is suspected in the vas so I'm wondering if we should seek an epididymal retrieval?
2) Is it worthwhile doing PGD again or would we have the same chance by going for a D5/D6 blast transfer? I've recently read about a small retrospective study that suggested with retrieved sperm that PGD makes the most difference if going for SET. Would appreciate your views.
I am 41 (yikes) and we do have a 2 year old son from out first ICSI/TESE cycle. Since then one missed m/c at 11 weeks and 3 chemical pgs. So frustrating that we've done it once!
Regards, Torrin
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Now you've stirred maternal age into the soup. At 41, it could have been a problem with the eggs as well. The other miscarriages were probably a combination of sperm and/or eggs and/or bad luck. Have you considered immune testing? When we see succesively earlier and earlier miscarriages it can be indicative of elevated NK cells and/or abnormal NK cell activation. I would recommend testing to rule that out before trying again.
Yes, the succes rate is higher when epididymal sperm (frozen or fresh) are used for ICSI rather than testicular sperm. It might be a little easier on your husband too.
Day 5-6 transfer does not exclude the possibility of genetic abnormalities. Most aneuploidies are weeded out on Day 3, but not all. On the other hand, PGD is not 100% correct and aneuploidies can slip though there as well. In addition, the embryo biopsy required for PGD may also compromise the developmental capacity of the embryo. I'm not a big fan of performing PGD for advanced maternal age or TESE. Personally, I think it causes more damage than good, but thats just my opinion. I haven't seen any convincing data that shows a big advantage for performing PGD for advanced maternal age or TESE. Perhaps if you are electing for single embryo transfer, there may be a rationale, but I imagine that you will want to put back more than one embryo to increase your odds of a term pregnancy anyway.
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Many thanks. Yes, it is a veritable soup. :)
We are in the UK and some of the best clinics have been slow to adopt immune testing. My clinic don't believe in it ........ but we are having a consult soon with another excellent clinic who do do immune testing. I intend to leave no stone unturned!
We will also explore the possiblity of epididymal retrieval. Luckily for my husband he's had just one TESE from which 8 vials were frozen.
I have mixed feelings regarding PGD too and really struggled with the decision. But now I feel that the genie is out of the bottle, having done it once. Plus our normal and abnormals all developed similarly despite multiple chromosome abnormalities - that kind of freaks me out a bit too.
Here in the UK, the decision on the number of embryos to transfer is not one that is agreed between doctor and patient but by our (nannying) government. >:( Max of 2 if <40 and max of 3 if >40. (Rant over).
Regards, Torrin
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Dear Dr Smith
Just thought I'd update this post. Well, we had our consult (fabulous!) and I had a full thombophilia panel taken and also NK cells. Guess what? NK cells are raised and I'm told that I will need steroids during next tx. (Please don't let me become fat and hairy ;D )
I know it's just one piece of the jigsaw but so relieved that I had these tests.
Regards, Torrin
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I wish more doctors would test for NK cells ad thrombophilia BEFORE IVF, not just after a failed cycle. The steroid treatment (Solu-Cortef in the US) is gaining poplarity as an NK treatment because of its low cost and equivalent efficacy to IVIg. It does, however, make you hairy and gives you a strong desire to howl at full moons. Its only for few months before you have the litter. Just kidding. Hope things work out on the next cycle.
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