Chromosomal abnormality...
5 Replies
Eyeball - April 10

Hi there

I was wondering if you could provide me with some advice...

I am 35. We have just completed our 2nd IVF cycle. We had 12 eggs of which 8 fertilised. Of these...

3 x 8-cell grade 1 embryos were frozen at Day 3.
1 x 8-cell grade 1 embryo was implanted at Day 3.
No PGD was undertaken.

We managed to get a successful pregnancy, only to find out at 13 weeks that our baby had Trisomy 13.

We were wondering what the chances were of this happening again with our 3 remaining frozen embryos? Do you recommend that we undertake PGD with the remaining embryos? Is there anything else we should be doing, or getting our fertility clinic to do, to give us every possible chance of this not happening again? Should we just start another fresh IVF cycle?

Thank you in advance for your help.


Dr Smith - April 18

There is always a chance that you will loose a pregnancy due to a genetic abnormality. Although PGD does screen for trisomies (including chromosome 13), it does screen for more subtle genetic abnormalites that can also result in miscarriage. It is not a panacea.

I would not recommend performing a biopsy on the reamaining frozen embryos. Embryos frozen on Day 3 often loose one or more cells during the thawing process. To remove another cell for biopsy would not leave enough cells for a viable embryo. You can either transfer the frozen-thawed embryos and accept the possibility of miscarriage or start a new fresh cycle, perform PGD and accept the possibility of miscarriage. Either way, there's no way to eliminate the possibility of miscarriage. Miscarriage is a natural process to terminate abnormal pregnancies. Miscarriages are common among non-fertility and infertility patients.


Eyeball - April 19

Thank you very much for your reply Dr Smith

I hope that your holiday was a good one.

I have some more questions....

1. Is it possible to thaw our Day 3 frozen embryos, wait until blastocyst when there are more cells, and then do PGD? If so, what do you think of this option?

2. After thawing, should we wait until blastocyst to transfer our embryos anyway? Or is it okay to transfer Day 3 thawed embryos? Would waiting until blastocyst also reduce our chances of having a miscarriage?

3. At age 35, how many of the frozen embryos (we have three) would you recommend transferring at once asuming all survive the thaw?

Thank you for your time in advance - much appreciated.


Dr Smith - April 19

A1. PGD is performed on Day 2-3. This is because blastocyst stage embryos have differentiated into two cell types: stem cells and trophectoderm (the fetal portion of the placenta). The stem cells (from which all fetal tissue is derived) cannot easily be biopsied. Theoretically, the trophectoderm could be biopsied, but the results are difficult to interpret because trophectoderm cells may have chomosome abnormalities, but these abnormalities have no developmental consequence. So, the short answer is no.

A2. In terms of reducing the chances of miscarriage, there is no advantage to waiting until the embryos reach the blastocyst stage after thawing because all embryos that result in miscarriage reach the blastocyst stage and implant. HOWEVER, there is an advantage in terms of assessing the developmental potential of the thawed embryos. Most programs that freeze embryos on Day 3 transfer the embryos right after thawing. Waiting for 1-2 days after thawing would identify embryos with arrested development and, therefore, unsuitable for transfer. If they don't continue to develop in the lab, they wouldn't deveop in the uterus either.

A3. All three, assuming they survive the thaw.


DianaEvans2 - May 14

Dear Dr. Smith:
Please forgive me if I am mis-directing this question. I went searching all over the internet, got lots of facts, but had a tough time drawing together a meaningful synthesis of the piles of data.

Very recently received a cytogentics report about my missed abortion of 8 weeks. 20 metaphase cells were analyzed (is this normal protocol?). The resultant findings "47.XY.-22" Abrnormal male Karyotype with trisomy 22". OK, fetus was a boy with an extra chromosome.

I looked up trisomy 22 on the net and it seems it is responsible for a huge laundry list of defects. Whereas Trisomy 21 is Down's syndrome(not my case). I am considering a last and third IVF (third time a charm perhaps.....) cycle, but want to understand the fact of trisomy 22-is there a genetic pre-disposition for this trisomy ? or was it just poor egg quality that caused the fetal arrest/missed abortion. I know the dismal stats at my age (43 now) and am well aware of donor egg stats.

Further, I was told that Trisomy 22 defect occurs during the first cell divisions (before the sperm DNA kicks in at cell 6 plus division??) it seems odd to me that this embryo actually made it through all the additional cell divisions, implanted itself and looked like a viable pregnancy development until the fetal arrest.... If I put myself in an embryo's shoes....why would I go through all the pregnancy trouble if I was carrying around bad DNA instructions? I must be ryhming together something incorrectly......

In advance, thank you very much for any possible clarity or providing direction. Wishing you a marvelous Monday!


Dr Smith - May 16

First, I have to qualify that I am not a reproductive geneticist, so I'm not an expert in these matters. You are right that nature is usually very efficient and, at the first sign of genetic trouble, embryonic/fetal development stops. Some aneuploidies do make it through the first check point at the 4-8 cell stage (apparently, trisomy 22 is one of those). The ones that do get through are usually caught during the 8-11 week gestation period (as in your case). Triploidy 21 (Down's Syndrome) is a notable exception and can make it all the way to term.

I am not aware of any pre-disposition to trisomy 22 that would make it more likely to occur during a subsequent pregnancy, but, like I said, I'm not a geneticist. At 43, you do have a very high pre-disposition to aneuplodies of all kinds. So, if you do decide to try again, brace yourself for the possibility of no pregnancy or another early miscarriage. As an aside, PGD would have identified the trisomy 22 embryo, and it would not have been transferred. However, you still got the same answer, albeit a few weeks later and after raising your hopes of a term pregnancy. If you feel that the emotional price of another miscarriage is too high, you may want to consider PGD.



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