PGD info

[Mondayschild]

I review Dr. Licciardi blog on occassion, it is very informative. Here is some info on PGD. The website is www.infertilityblog.blogspot.com

The PGD Paradox
The next couple of blogs will be about the downside of PGD.

PGD: Pre-Implantation Genetic Diagnosis, otherwise known as Embryo Biopsy.

A day 3 embryo is ideally 8 cells. One of the cells can be removed and the DNA in the cell can be analyzed. If the cell is normal, we can transfer the embryo into the woman’s uterus. If it is abnormal it will not get transferred. Now it can be a little more complicated. Some centers are biopsying polar bodies, and some talk of testing blastocysts; but the great majority of the biopsies are done on day 3.
PGD is mostly performed for 2 indications. One is to look for genetic diseases. Here, one or both parents carry genes that will lead to illness in the child, so they undergo PGD to identify the embryos without the abnormal gene or genes.
The second is to look for aneuploidy, which means an abnormal number of chromosomes. This is the problem that occurs with age related infertility and miscarriage. You’ve heard of Down’s syndrome, which is when the child has an extra chromosome 21. But we have 23 pairs of chromosomes, so if an embryo gets one too few or one to many of any of the chromosomes, the embryo may be abnormal. In these cases, the embryo may just not implant, or it could grow early on and miscarry, or in rare cases it could turn into an abnormal baby.
Aneuploidy testing is the most common indication for PGD, and for good reason. Women who want to increase their chances of becoming pregnant, or want to reduce their chance of miscarrying an abnormal fetus, can do in vitro fertilization, get their embryos tested using PGD, and transfer the good embryos.
The problem is that PGD for aneuploidy has not been as helpful in improving pregnancy rates and reducing miscarriage as we had hoped, thus the paradox. If you were a patient undergoing IVF, had a good stimulation, normal uterus, nice embryos and no pregnancy, what explanation would you get from your doctor? He or she would probably tell you that although they looked good, your embryos were probably genetically abnormal. This tells me that if you were to do PGD, and had only the normal embryos transferred, you should expect a very very high pregnancy rate. Unfortunately, this is not the case. I’ll talk about possible reasons why next time. As usual, please read disclaimer 5/17/06.
Dr. Licciardi
More About PGD
So should you have PGD? Well, this is between you and your doctor. Hopefully this blog will help you in your discussion with him/her. Let me start by saying that there is a place for PGD. There are some patients that are clearly candidates, and many children have been born as a result. I am very happy for those of you who have had PGD successfully. The problem is in saying that if it’s good for some, it’s good for all.
We already said that PGD is not all it’s cracked up to be. How could that be? Isn’t IVF science cutting edge? Yes it is, but it’s not perfected and here are some of the pitfalls.

Mosaicism. In basic biology it is taught that the cells of the early embryo are identical. Since it all starts from the DNA of the fertilized egg, as the cells divide they all have the same DNA. Well, this is usually the case, but often enough, there is mosaicism, meaning that some cells have one type of DNA and other cells have different DNA. For example, in an 8 cell embryo, it’s possible to have some cells that cause Down’s Syndrome (this is an extra chromosome 21) and some cells can be normal. Just to back up, almost all of us have 23 pairs of chromosomes, for a total of 46. If an embryo is missing at least one, or had an extra 1, we generally call this aneuploidy. Aueuploidy is the genetic problem related to aging. Down’s is an extra chromosome 21, but any of the chromosomes affected in the same way, either an extra or missing. Getting back to PGD, if the embryo has 2 normal cells, and 6 abnormal cells, and the biopsy plucks off a normal cell, this mostly abnormal embryo will be transferred, probably producing no pregnancy. If the embryo is mostly normal and an abnormal cell is tested, that embryo will not get transferred, yet it may have produced a normal child.

Embryo Damage. This is very hard to quantitate, but embryo biopsy is a rather invasive procedure. So it may be that removing 1/8 of the embryo reduces its viability.

Testing Error. Even when done correctly in experienced hands, error happens. Meaning the lab says the cell is normal when it is abnormal, and visa versa. The error rate is low, but if many embryos are tested the chance of an error per case increases.

These pitfalls get magnified when a woman produces few eggs. The biggest risk here is that the one good embryo gets damaged or is misdiagnosed as abnormal.
So the most important question you have to ask is, “will PGD increase my chances of having a baby?” If your doctor says, “Yes, absolutely”, or “most of our patients are getting PGD”, get another opinion.
The bottom line is that the medical community is not so sure yet if PGD increases pregnancy rates. Theoretically it should, but in practice nothing has been proven yet. It is possible that PGD will reduce the chance of miscarriage, and there are some studies to show this is the case, but there is other research showing it may not.
And what about the cost? My partner Dr. Berkeley brought up a great point. For the extra cost of 2 PGDs, you can pay for another IVF cycle.
Just to repeat, I have patients who do PGD, but they make the choice after getting whatever information I can give them.
Please read disclaimer 5/17/06.
Dr. Licciardi

p.s. I have recently heard of programs that freeze the embryos of poor responding patients over a few cycles to get a batch big enough to biopsy all at once. It sounds a little extreme to me, but I can't really comment until I see the results published. Just remember, a frozen embryo is not a good as a fresh.

[crazydiamond]

We are using PGD now and did some research into this.

It was explained to us by our doctor that with any specialty medical issue - some hospitals/doctors/labs get great results – some not. The technology, knowledge, and skills of medical professionals vary from place to place. This is the same with PGD -it depends on the lab doing PGD - some are better than others and some are not. The results we reviewed with our doctor and PGD lab seem to support the increase in pregnancy rates and reduction in miscarriages and things like downs that we are looking for - link below

Reprogenics

[BeccaMichelle]

I totally agree with this info. I did pgd in May and all 8 of my embryos came back as abnormal. I did not get a transfer and that was so difficult. I'm 25 with no history of family diseases or disorders. I highly doubt this was the case and that all my embryos were abnormal. I'm about to do my second IVF and this time not doing PGD. I will post back the results that will hopefully prove PGD was wrong and my eggs are normal. I wish I would've done more research because I thought PGD would raise our chances and I was very wrong. It lowered them completely. Waste of $5000.

[BabyPrayers09]

I too did PGD.

I was 34 or 35 at the time.
I used 2 frozen embryos from my first IVF cycle and 16 fresh from my second IVF cycle.

ALL OF THEM came back abnormal.

I was devastated, to say the least. I was told it was "egg quality" and have since moved to DE.

My RE said it was not impossible to say that they would possibly find a few good eggs in me, but time and $$$ was a greater consideration for me.

All this research does make me wonder if they pulled the wrong cell or something. Overall, I think that b/c I had embryos from 2 different cycles, and countless other cycles that did not produce a child ~ I just needed PGD for closure. If that makes sense at all.

[jpper]

To BabyPrayers09: my heart goes out to you. I am wondering, did your Dr. suggest doing a blood test to see if either you or your husband have any chromosomal abnormalities?

I have had 2 failed IVF cycles because of high number of abnormal embryos, even though neither my husband or I have any diagnosed genetic or physiological abnormalities that could account for such a result. We are currently waiting for the results of the blood karyotype tests to see if we might have a balanced translocation or something like that which might explain how we might seem normal but have problems producing normal gametes (eggs and sperm).

I will be really stumped if the blood tests come back normal though. Am wondering if maybe my ovaries just don't like being stimulated or if it might help to try a different brand of hormone stimulation? (I used a combo of monoper+gonal-f for the 1st try, and lower dose of just gonal-f the 2nd.)

[BabyPrayers09]

jpper:

Thanks for your concern. Dh always tested just fine. We had done every blood test imaginable. We even did SCSI testing on the sperm. The only real definitive testing was the PGD. With all abnormal embryos, it was easy to blame egg quality. So in that case it was worth it.

Unfortunately, there are soooooo many possibilities to consider when dealing with infertility. Often more questions than answers. You just have to navigate through it the best you can, making the choices that seem appropriate to your own personal situation. I hope this round of testing provides you with some answers, instead of more questions. If the blood tests come up with nothing, I would consider PGD if at all possible. At least you would get some piece of mind. It was worth every penny for us b/c it led us to donor egg and eventual success.

Good luck and God bless.

[jpper]

Thanks BabyPrayers09! It appears you are very close to your due date? Congratulations and good luck!

Yes, we did in fact do PGD for both attempts. We were only able to test for 5 probes the 1st time (X, Y, 13, 18, 21) but then the 2nd time the lab was able to test for 2 more chromosomes, 16 and 22. Unfortunately more full testing e.g., CGH, that gives comprehensive analysis of every chromosome is not available in Thailand yet. So we are basically waiting for the karyotype results back, and then will try to find a clinic in a different country (USA?) that can do CGH and will tell us the sex of the baby, and will implant at least 3 embryos.

Any suggestions for such a clinic? We're wiling to travel anywhere we need to.

All the best again!

[BabyPrayers09]

Wow! Didn't realize you were in Thailand!

General PGD testing here is what they call for aneuploidy. This tests a wide variety of chromosomal abnormalities. Here is the link for the facility I used for PGD. (However, it's not the same as the IVF clinic ~ your embryos just get sent here).


http://www.reprogenetics.com/about.html

A clinic may be another story. I can only speak for my little neck of the woods here on the East coast. If you are willing to travel anywhere, that's a lot of research you'll be needing to do!!!

Let me know how it goes!