Monday, April 28, 2014

Understanding my infertility: four years in retrospect

When I had my first miscarriage and then my second in rapid succession, I had no idea what was going on, and I made truly valiant efforts to understand. I went off on a lot of tangents, and some of them (the Vitamin D deficiency, understanding the connection between Vitamin D and AMH, the thyroid autoantibody issue) yielded a lot of valuable information. There were some indicators that all of these (the vitamin D deficiency combined with the TPO antibodies, often seen in women with PCOS) may be indicative of a very low level of autoimmunity that may have interfered maybe oh-so-slightly with the progress of a pregnancy, but at the end of the day, I think these things were not my central problem.

There are two aspects to egg quality, both of which decline with maternal age. One is the state of the egg cytoplasm, which has all the mitochondria and the nutrients required to survive, divide, and thrive for the first 8 days of life by itself. The second is the chromosomes itself, and this is governed by the meiotic division process where your 46 chromosomes are divided into two sets of 23 chromosomes each. I talk about how one or both of these may be affected in the "Science of Infertility" section.

What was my problem? My cytoplasm quality was, by all accounts, really gosh darned good. It may be that I have an issue with the meiotic chromosomal division process, as a result of which a high number of my eggs are aneuploid, and I may have come into this problem (which is usually seen in women in their 40s) ten years or so too early. Compounding the problem may have been my "superfertility," which may have caused my rather stupid uterus to implant embryos that a "normal" person's uterus may have rejected. I have come to these conclusions based on the following statistics:

  • My pregnancy rate was 75% (3 out of 4 unmedicated cycles), which is FAR higher than the figure (20%) reported in "normal" women. Two of my three embryos were shown to be aneuploid, and one of these aneuplodies was a Trisomy 4, which is extremely rare because embryos with a trisomy of this ginormous chromosome almost always fail to make it to the blastocyst stage, or after, fail to implant or grow. 
  • Normally, the implantation rate for high-grade blastocysts is around 40-50% (i.e., 1 out of 2 blasts is likely to implant). The implantation rate for my high-grade blasts in women with "normal" fertility (the two surrogates) was far lower (1 out of 5 blasts, from 3 transfers).  
This suggests that most of my embryos were abnormal, and I kept implanting them anyway. This pregnancy may have come about because J's uterus could perform the selection that mine could not.

Had I not the "superfertility" issue, I may have just taken much longer to get pregnant, but may have stayed pregnant when I finally got knocked up. That would have been so much better, but as I gaze at my baby girl, I'm still fine with this version of events.

Now WHY I had the meiotic division problem is really the gzillion dollar question, that remains completely unknown. There appear to be no biomarkers or tests to indicate this. One has to wonder if the common problems seen in infertile women (The MTHFR mutation, the PAI variant, various autoantibodies) are biomarkers (indicators) for this issue, or are linked to it in some way, but nobody has ever looked at these particular questions, I think.

The other thing I wonder if there is a "cross talk" between my embryos and uterus that was messed up, and a developmental "brake" that malfunctioned in my embryos. Each time I ever got pregnant, it was an ovulation from my left ovary. The one time I failed to get pregnant was a right ovary ovulation, and honestly, I fail to see how that embryo could have been more messed up than the left ovary-derived Trisomy 4 embryo that implanted in my next attempt.

During IVF, I asked the embryologist to culture the eggs from my right and left ovaries separately, and the results were interesting. Normally, around 40% of fertilized eggs become blasts, and I saw this in my right ovary eggs. In contrast, over 70% of the fertilized eggs from my left ovary became blasts, which is far higher than normal. My daughter (feels SO amazing to say that), came from a right ovary egg. All this makes me wonder if the fault (for the messed up crosstalk between the uterus and the embryos) is a problem that is a problem specifically in the eggs of my left ovary. Of course, this last bit is wild speculation (even more so than the first bits, which are a lot more likely). 

There...the last 3 paragraphs will probably give everybody a headache, but I had to put down my thoughts for posterity. There is a part of me that wants to go back and do research on this issue, because I feel so passionately about it. I've actually been thinking about whether there are openings at RMA-NJ (because they are such a research-oriented fertility group).

Anyway...all is well that ends well, and I hope this recounting will be of use to somebody someday.


  1. I'm glad that you have your beautiful daughter after all of this ordeal. The human body sure is strange. Sometimes I think it is amazing that anyone is ever born.

  2. I think your analysis is very interesting. After my early miscarriage almost a decade ago, I had no confirmed implantations (though a couple suspected starters). I think by the time I had a good doctor and things figured out supplement and nutrition-wise, I was playing with few good eggs. I definitely don't think I had awesome egg cyctoplasm... I echo what Nell said - so glad you have your daughter and it is amazing!

  3. I've wondered similar things about my fertility and the ones that made it and the ones that didn't. I know my first miscarriage and my chemical pregnancy were from the same ovary. I can't remember if my second miscarriage was as well, or whether my two successful pregnancies were. Regardless, I know that I have a similar problem with developing crappy embryos past the point they should grow--and I also conceived 2/3 iuis, so I sometimes suspect that I also have an undiscriminating uterus that will implant anything, so long as sperm can get to egg.

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