Too many abnormal embryos and ? about chromosomal blood test

[jpper]

Hi, am hoping there are others who might be able to comment about possibilities for such high number and varied abnormal embryos, with no known genetic abnormalities in the mother and father (currently waiting for chromosomal blood test results).

Am feeling really gutted and confused and unsure what the future will hold. This is compounded by the fact that 1) I have very few people to turn to since my husband prefers to keep it a secret that we are going through IVF, and 2) the day after our failed 2nd attempt (that ended in no transfer) he found out his father was in the hospital with a possible brain tumor which has yet to be confirmed. Although he is extremely stable and positive, he has been very preoccupied with his father and work, and has little left over to offer me in the way of support. So the last week has been really really rough on me, especially since I'm here all alone in Bangkok, away from our much beloved pets and home overseas, and isolated from my normal support network of friends that I have to keep this a secret from. It's not just my husband, but I don't exactly feel comfortable with revealing these genetic questions about our condition with others, at least, not just yet.

The background is, we have gone through 2 IVF cycles now. I am 35 with no previous pregnancies but normal hormone levels, and my husband is 45 with very good quality sperm. Together we have no known genetic or physiological abnormalities. We've gone through 2 IVF attempts, both with higher than normal % of abnormal embryos using 5 probe PGD for 1st attempt (5 out of 17 embryos normal), and then 7 probe for 2nd (1 out of 13 embryos normal).

The first attempt used long protocol and combo of gonal-f/monoper (about 300-something units) but ended in negative pregnancy test after having collected 33 eggs (22 mature, 17 fertilized, and 5 normal according to 5-probe PGD of X, Y, 13, 18, & 21).

The 2nd attempt used short protocol and only gonal-f (about 220 units for 1st 3 days, then reduced to 187.5). 16 eggs were retrieved, 15 mature, and 13 fertilized. Because of the high # and variety of abnormals we got during the previous attempt, we decided to do 5-probe PGD again with the option to retest any embryos that came back abnormal but that had good morphology, and reprobing any normals with an additional 2 markers for chromosomes 16 and 22.

Unfortunately I am using an IVF clinic in Thailand (Srisiam) and 7 is the maximum they can do, and doing CGH (which tests full spectrum of all chromosomes) is not available in this country. We were sure to have any retesting done using the originally biopsied cell and not a new one to reduce the risk to the growing embryos. However I am regretting doing this since we may have been able to eliminate confusing results due to mosaicism if we had taken a new cell. We also could have taken the new cell from the placenta part of the embryo (as is done for CGH testing) thereby reducing risk to the growing embryo.

We were surprised by the low number of normals during the 1st cycle, but the Dr. suggested that my ovaries may have been overstimulated (hence the high number of 33 retrieved eggs) which may have resulted in lack of pregnancy, even after transferring 3 pretty good quality embryos, altho only 1 was had just hatched. (Unfortunately during this 1st attempt, the embryo that was the most developed and furthest along in the hatching stage also came back as trisomy 21).

The Dr. explained he tried me on a higher than normal dose of ovarian stimulation because he thought he'd have to counteract the effects of the ovarian suppression caused by the initial long protocol shot. He said the next attempt he would put me on a lower dose of stimulation.

We went back 2 months later to do the 2nd attempt and changed to short protocol with lower dose of gonal-f. We were devastated and shocked to learn that out of 13 that fertilized only 2 were normal for the 5-probe test. However, there were 4 with beautiful, advanced morphology that initially tested abnormal. So we decided 1) to have the previously biopsied cell from those 4 rewashed to remove the old markers and reprobed with the 5 markers to see if the abnormal results could be verified; and 2) to to have the 2 normal (an XY and XX) tested for an additional 2 probes for chromosomes 16 and 22. Unfortunately, out of those 2 initial normals, only the XX came back normal and the XY came back monosomy 16. The rest had exactly the same abnormal results as before. (This, along with other issues of poor and delayed reporting due to "being too busy" makes me kind of made me doubt whether they had bothered to do the 5-probe retest at all, even though we definitely got charged for it.)

Has anyone ever heard of redoing PGD results on a previously tested cell by washing out the old markers? How reliable is this? How much can a cell's DNA have degraded which could cause different results from the same cell?

The Dr. suggested we take a blood test to do karyotyping to see if we have any chromosomal abnormalities. Unfortunately it will take another 2.5 weeks to get back any results, and he doesn't seem to know much more about it, or the test, or even its implications. So we had to make the difficult decision to freeze the one healthy girl we got and delay transfer until we knew more about our individual chromosomal status.

I did a lot of research online about the karyotyping test, and have concluded that since my husband and I have never been diagnosed with any genetic or physiological problems, it stands to reason that a balanced translocation may be a possibility. How else can he or I have seemed normal yet also seem to have problems creating chromosomally normal embryos? Yet one question really bothered me: assuming there is an issue with balanced translocation(s), how can this one or maybe max 2 translocations account for the wide variety and number of abnormal embryos we saw? Almost every embryo tested abnormal for either 1 or more of the 5-7 tested probes. I find it hard to believe that we might be carriers of 5-7 balanced translocation for just those chromosomes that happened to be tested for (X, Y, 13, 16, 18, 21). I assume that if one has a balanced translocation, that abnormality will show up in a consistent fashion in some % of embryos for those chromosomes involved in the translocation, and not cause mutations in unrelated chromosomes. Or not? Can anyone with more experience comment on that?

We consulted another dr at a different facility here in Bangkok (called BNH) who concurred with me. He basically said that even if the blood test comes back positive for some maternal/paternal abnormality, that still wouldn't explain the results we got. We're in limbo now until we get the blood karyotyping results back, but now I'm at the point where I'm thinking maybe:

a) my ovaries just didn't like the brand of hormones used for egg stimulation and may like it better if I use a different brand;
b) my ovaries just don't like being pushed with stimulating hormones period, and IVF will never work for me; or
c) the blood test will come back with some weird diagnosis that will magically explain all this and point the way to how we can modify the next treatment protocol.

I'm also in the difficult stage of blaming myself for being the likely one with abnormal chromosomes, because my husband used to be a top sperm donor for a prominent sperm bank and they must have done all this testing for him already. He has been really supportive and willing to posit that it could also be a problem with him, and how, if I find that out, will I still love him and accept him? I immediately responded of course I will, without question. However, this was kind of a ploy of his to make me realize that I should feel the same way about myself if I find out it is me. But ploy or not, all the same I'm grateful.

Any help or advice would be extremely appreciated, thank you!

[barren-bipolar]

Sorry, I can't give you any technical help. Just wanted to reach out to you and say I'm thinking of you. I lived and worked in China for 2 years after college (1 year in Beijing) and also spent time in Thailand. I know how difficult it is to be separated from your support system. I also know what it's like to have a husband who doesn't want to discuss infertility struggles with others. It's great that you're coming to this board to get support. I've found that it really helps me a lot. I'm sorry about your father-in-law.

We've done one (failed) IVF cycle so far with an unusual amount of embryos fertilizing abnormally. It's frustrating. Both my husband and I have been tested genetically and nothing showed up, so that is reassuring. I hope your genetic testing comes back fine. I really think that CGH is a good way to go. I can tell that you are a determined, intelligent woman and I think you will find a way. It only takes one good embryo.

[waitinginpa]

I do not have time right now to type the long reply that i'd like but wanted to say I am 38, after 2 BFN and 2 M/C me and DH did the Karyotyping, thinking maybe one of us had a balanced translocation. Both of our blood tests came back totally normal. However our last IVF cycle, we did PGD using 12 probe. Sent 10 to PGD only 4 came back normal. 60% of our embies were abnormal from 2 chromosomally normal parents, I found that very interesting. we are now in the 2WW to see if that helped our situation any

[jpper]

Need to update and correct background info:

I stated we have no known genetic or physiological diseases. But I *forgot* (!) to mention that I was diagnosed as having Hashimoto's Thyroiditis last January 2009 after the first round of fertility hormone testing came back with borderline low thyroid and twice the normal levels of TSH. Further testing showed I had thyroid antibodies levels of 10 and 200 times the normal for thyroid peroxidase AB and Thyroglobulin AB respectively. Full thyroid panel results are below.

I've been on 25 micrograms/day of levothyroxin since early Feb 2009 and have had normal thyroid levels since April 2009. My T3 and T4 are still at the same level as before (kind of on the lower side of normal) but my TSH has dropped by half. So the levothyroxin is working brilliantly and I guess my body just likes the T3 and T4 levels where they are.

Anyway, that's a twist to the tale, but every Dr. I've spoken to has said that shouldn't make a difference as long as I continue taking the levothyroxin thyroid hormone supplement. And that it's completely safe to use during pregnancy and breast feeding.

However, I do wonder about the autoimmune component and how much that will raise the risk of miscarriage for me. But we are still at the stage of getting a healthy embryo and attaining pregnancy. I suppose we will learn more when we get to that particular hurdle of maintaining a pregnancy.




TSH-3rd generation 1.98 (Reference Range 0.40-4.50 mIU/L)
T4 Free 1.5 (Reference Range 0.8-1.8 ng/dL)
T3 Uptake 31 (Reference Range 22-35%)
T3 Total 116 (Reference Range 97-219 ng/dL)
Thyroid Peroxidase AB 355 (Reference Range <35 IU/mL)
Thyroglobulin AB >3000 (Reference Range <20 IU/mL) Further results using a different test showed Thyroglobulin AB levels of 4000.

[jpper]

Thanks waitinginpa, it is reassuring to hear about a couple with normal karyotyping who also had high, unexplained #'s of abnormal embryos. When we were asking the docs and nurses here (in Bangkok) if they'd ever seen results like these, they all started hemming and hawing and shaking their heads.

We are on the hunt now for a place that can do a full chromosomal analysis on the embryos using CGH. Unfortunately Thailand seems to only able to do max 7 markers for X, Y, 13, 16, 18, 21, and 22, and they can't do CGH yet. So that means going for treatment to a different country if we want to do another round of IVF, not sure where yet though. I'd be willing to try Sydney ART, but they won't transfer more than one or maybe max, 2, embryos, and they won't tell you the sex. We're looking for somewhere that will transfer at least 3 and tell us the sex so we can make sure to get a mix of male and female.

I posted another thread asking about where the best IVF clinics currently are. If you or anyone has suggestions can you please post on http://www.fertilethoughts.com/forum...48#post6823448? Thanks!

As a sidenote that has to do with posting on this forum: I apologize for not knowing all the abbreviations that people use on this site which make reading and writing a lot faster. Is there a glossary of abbreviations somewhere which I can learn and use for deciphering other people's posts? Like, what's a BFN and 2WW? I figured out M/C and RE means miscarriage and reproductive endocrinologist.

Barrenbipolar: I am very grateful to hear your words of encouragement and empathy, especially with your experience of living overseas in Asia. The more foreign the language, the more isolated one can feel, so thank you for your kind thoughts

I noticed your signature says you are borderline low thyroid. So am I! Or actually, I'm Euthyroid now as I have no symptoms of hypothyroidism and have normal thyroid levels after being on Levothyroxin 25 micrograms/day for most of this year now.

Your recommendation from a different thread to find a good RE is extremely helpful. Have you ever spoken to one about how your thyroid levels might affect fertility and egg quality?

Thanks so much everyone....mood has brightened considerably since getting replies

[barren-bipolar]

jpper-

I know- all the abbreviations are confusing, but you'll get used to them soon. Look at the top of the page. Next to New Users, there is a header that says "acronyms." Click on that. Hope that helps!

Also, when I spoke to my RE about my thyroid, he just said that hypothyroidism is associated with miscarriages. I don't know how it affects egg quality, but it does seem that my eggs are not the best.

[TTCyears]

jpper, reading your post is what I imagine my post might be like. You obviously have educated yourself well on the subject, and yet there are still no answers.

My DH and I have "unexplained" IF and RPL. Our Karoty was normal. The only slightly abnormal result we have is DH's sperm analysis, and my MTHFR. The RE believes our lossses are genetic, although for various reasons it's unconfirmed. He recommends PGS and your story sounds a lot like what he warned me of (except that he also warns me that a genetically normal embie could "arrest" following the test, which would be my luck).

I wanted to do DNA testing on DH's sperm, but the RE said that since we're not going to do donor sperm then it's not worth the money. As you know genetically abnormal embies have long been associated with the age of the woman and recently associated (duh!) with the age of the man. But perhaps you both are young. I was when I started all this, but that was long ago. It's frustrating that there's nothing to "do" about it - although we keep half-heartedly trying - newest on the list is Zinc for him.

I hope you get to visit home at some point!

Hugs,
~Sharon

[linden]

jpper: did you end up getting karyotyping done on you and DH? I know someone who had 3 miscarriages in a row at age 28 and it turns out that she has a mosiac form of Turner's syndrome which was never diagnosed previously and she had absolutely no symptoms of Turner's. It was only until she had the karyotyping done that she found out that it was cause of her RPL. Her first IVF w/ PGD yielded lots of embryos and all were abnormal. Her 2nd ivf w/ PGD yielded one normal embyro who is now her son!

[jpper]

Hi Linden! Yes we got the karyotype results a few weeks after my initial post and they are both normal. In fact, we did the test at a separate hospital using a different lab and the same normal result came back.

So it's good to eliminate one possibility, but we still had very high #'s of abnormal embryos which are unexplained.

I got 2nd opinions of 4 other Bangkok Dr's and 2 suggested I may have undiagnosed polycystic ovaries (PCOS), which could account for why I was overstimulated in the 1st attempt, and we had so many abnormal embryos. Apparently they were saying that when an egg doesn't get released properly, it can get old and the dna can degrade. It also causes a buildup of immature eggs. Then when they are stimulated into maturation by the IVF cycle, an inordinate # of eggs get harvested with high rates of abnormalities to boot.

However, the problem with PCOS hypothesis is, I had at least 7 ultrasounds done with as many Dr's in the year prior to any IVF attempt and not a single one suggested I might have PCOS. I also don't seem to have any of the attending symptoms, like irregular periods or excess hair. I am quite thin as well and have no history of glucose insensitivity...although I know from looking at the message boards that there are women who are thin and have PCOS.

Anyway, I have to wait another few weeks for my ovaries to go back to normal after the IVF stimulation, before I can do another ultrasound to check.

My husband maybe thinks if I have PCOS, IVF stimulation might be good because it causes all the "backlogged" undeveloped eggs to be flushed out. It will then make it possible for a future IVF round to stimulate fresher, healthier eggs. However, I am not too sure about this line of reasoning!