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The · Psychohistorian

IVF, endometriosis, and the paleo diet

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This post is mainly for my own reference, setting down some thoughts on IVF, endometriosis, and the paleo diet before I forget them.

greyautumnrain and I recently had a "miracle" pregnancy after 7 years of infertility punctuated by 3 unsuccessful and 2 successful IVF cycles. The pregnancy appears at 8 weeks to be headed towards a miscarriage; statistically, this is most likely due to trisomy 16 or some other nonheritable genetic defect. Naturally we've been googling like mad to try to figure out what's going on and how to make things work better next time we try for the third child.

Endometriosis comes into the picture because that was diagnosed as the cause of the infertility. The paleo diet comes into the picture because we started the paleo diet 3 years ago on the birth of our first child, and since that time the most obvious symptom of endometriosis - painful periods - has disappeared. We attribute the lack of painful periods to the paleo diet rather than to pregnancy because those I've polled on line with endometriosis all report that their postpregnancy periods became painful again.

The reason to think of these three factors together is that the "miracle" pregnancy occurred on our first carefully timed attempt - our third attempt overall - since the birth of our second child over a year ago, a pregnancy rate that seems quite typical for fertile couples, and quite atypical for us up to this point, especially compared to the period when we made lots of very carefully timed natural attempts before we first resorted to IVF. The question is, does this pregnancy represent a lucky result from a single large population of low probability attempts from when we first started trying to conceive seven years ago, or does it represent a normal result from a new population of normal probability attempts after the birth of our second child. If the latter, where do the several admittedly haphazard attempts between the two children fit in, since they were also postpaleo?

On to the research data.

The first interesting piece of research data is a paper looking at the mechanism by which endometriosis may cause infertility.[1] This paper documents an experiment in which mouse ova were bathed in either normal or endometrial human peritoneal fluid - simulating the environment seen by human ova in normal and endometrial humans - during the later stages of meiosis, specifically metaphase II, the stage to which ova develop immediately after ovulation and in which they arrest while awaiting fertilization. Ova in normal human peritoneal fluid were normal, with microtubules forming normally between the centrosomes and the chromosomes, pulling the chromosomes into a normal equatorial plane in preparation for separation of the chromatids to be used in the zygote and those to be ejected in the second polar body. Ova in severely endometrial peritoneal fluid are missing the microtubules and the chromosomes are scattered randomly, perhaps due to the highly inflammatory and oxidative nature of the fluid; presumably these ova will never eject a polar body and never successfully divide. Ova in moderately endometrial peritoneal fluid show intermediate microtubule development; even if they eject a polar body, one might posit that insufficient and poorly distributed microtubules would increase the chance of aneuploidy - excess or missing chromosomes - due to errors in separating the chromatids. ncreased aneuploidy is found in endometriosis[2], albeit not to levels sufficient to fully account for the observed infertility.

That suggests that endometriosis causes infertility by reducing egg quality, in addition to or instead of affecting implantation. IVF helps by providing more eggs - more "lottery tickets", as it were - but also by allowing meiosis II, including metaphase II, to happen outside the woman's body in a more benign artificial environment. Of course, meiosis I still occurs inside the body before the eggs are retrieved[3], and can still be affected by endometriosis, perhaps explaining why IVF has a lower success rate in patients with the disease - and incidentally suggesting that in vitro egg maturation might help in cases of endometriosis. If the paleo diet helps with the infertility effects of endometriosis as well as with the cramps - likely, since it is a very noninflammatory diet - it should be expected to help in both meiosis I and meiosis II. Reduced problems with meiosis I could also explain how we still got a child out of our second successful IVF cycle despite only half the eggs of the first successful IVF cycle, though that of course could just as well be luck. It would be at odds with how none of our few natural cycles between the two children worked, though as mentioned, our timing on those cycles was haphazard.

That brings us to the next question. The ova are suspended in prophase I of meiosis for decades, from before birth to shortly before ovulation. What happens during those decades?

I haven't found any direct research on that yet, but I did find one relevant fact: ovarian folliculogenesis requires, not just a couple of weeks in the first half of the cycle, but approximately 13 months. It can be even longer if a pregnancy intervenes.[4] Most of this time is spent accumulating granulosa cells in the developing follicle around the egg.[5] Presumably endometriosis affects these cells just as it affects ova. Even if they are affected only by incorporation of peritoneal fluid into their cytoplasm, that cytoplasm then surrounds the ovum during completion of meiosis. That would be consistent with our successful natural cycle being more than a year after the birth of our second child - between our first child and the start of the IVF that led to our second child, there was less than the year that would have been required for all formerly maturing follicles to be cleared.

Finally, I should address the likely inviability of the current fetus. It's not that unexpected, as genetic defects in the ova happen more than half the time with women over 40. There's a small possibility that we could expect some reduced egg quality due to lingering effects of endometriosis, but those effects would likely have to come from exposure of the ova while suspended in prophase I. From a practical standpoint, that means any such effects would affect both IVF cycles as well as natural cycles.

[1] http://www.clevelandclinic.org/reproductiveresearchcenter/docs/agradoc329.pdf
[2] http://humrep.oxfordjournals.org/content/25/9/2374.full
[3] the IVF "trigger shot" causes egg maturation through meiosis I and the ejection of the first polar body prior to retrieval - see for example http://www.advancedfertility.com/immature-ivf-eggs.htm
[4] see for example http://www.biolreprod.org/content/66/2/266.full
[5] see for example http://www.embryology.ch/anglais/cgametogen/oogenese02.html or http://www.endotext.org/female/female1/femaleframe1.htm
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On January 10th, 2012 11:30 pm (UTC), psychohist commented:
Just to track the data, here's a record of attempts after the miscarriage. Elizabeth's normal cycle is 31 days.

- first menstruation happened about two months after the miscarriage.
- a 28 day cycle that we suspect was anovulatory; we tried assuming ovulation on day 17, which clearly wasn't what happened.
- a 31 day cycle where we tried assuming ovulation on day 14, unsurprisingly no pregnancy
- a 31 day cycle where we tried assuming ovulation on day 17; no pregnancy
- a 31 day cycle where we tried assuming ovulation on day 17; positive pregnancy test and heartbeat, though we could easily have another miscarriage.

Positive tests on 2 out of 3 carefully timed cycles, as opposed to 0 out of dozens of such cycles before paleo, strongly suggests that there is indeed a major difference here.
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