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Monday, October 11, 2010

IVF factors: follicle size, estradiol (E2) levels and endometrium lining

As we travel along this IVF journey, dealing with the highs and lows of each cycle, I find myself obsessively reading and researching the internet. I no longer google "2ww symptoms", but instead, I find myself trying to understand, and find answers as to why our cycles have failed.

It's still a mystery to the medical profession as to why some embryos fail to implant, and after going through the whole numbers, statistics and probability thing, I feel like it would help if I understood a bit more. Yes, I am 40. Yes, the quality of my eggs have started to decline. But so far, our embroys have made it to blastocyst stage, and they have been good quality.

In trying to understand some of the reasons why IVF fails, and in particular, age-related infertility, it's important to understand that a woman is born with all the eggs she will ever produce. When she reaches puberty, a group of follicles is recruited for development every month. In actual fact, they can be recruited 4 months before, during which time they undergo complex development changes. Usually only 1 will continue to grow and becomes the dominant follicle. The ones that don't make it die, a natural process known as egg attrition.

This process of egg attrition continues after birth but at a slower rate. By the time the woman reaches puberty and begins to menstruate and then ovulate, her egg population has dropped from more than 5 million (at 3-4 months post-conception) to less than 1 million on average. The number of eggs present at the time of puberty when the woman’s reproductive potential is launched is genetically determined.

With every 4 month recruitment journey the number of follicles (eggs) that a woman has available declines. For women in their mid-30s, what few she does have left, will also depend heavily on their quality. (see
http://fertilityportal.com/factors-affecting-ivf-outcome/)

So as we go through the beginning of a cycle, and the blood tests start to trickle in, I find myself trying to anticipate what might happen when.
 
(A good basic summary of protocols and "expected" E2 levels, follicle size etc can be found here:
http://www.infobarrel.com/Follicle_Size,_Uterine_Lining_and_Estradiol_Levels_During_In-Vitro_Fertilization )

Summarized from the link above:
During an IVF cycle, there are three things you want to know after every visit to your clinic: follicle size, the thickness of your uterine (endometrium) lining, and your estradiol level. These are the key data that let you and your doctor know how your cycle is progressing.

Estradiol is measured in either pg/mL (picograms per millilitre) or pmol/L (international measurement).
The conversion factor is E2 (pMol/L) = pg/mL x 3.676.

IVF is all about the eggs and one important indicator of your cycle is follicle size. Follicle size indicates how your eggs are developing and when they will be mature enough for retrieval. Follicles grow approximately 2mm a day on average and produce increasing levels of estradiol.

Estradiol levels also affect the uterine lining, with higher levels correlating to a thicker uterine lining. Uterine lining should measure at least 7 to 8 mm in thickness and usually grows 1-2mm a day.


Estradiol Levels During In-Vitro Fertilization:
Just like Goldilocks' porridge, the estradiol level during an IVF cycle needs to be just right. Too high, you're at risk for hyperstimulation. Too low, your response to your doctor's protocol may not be optimal. But what
exactly is a good, low, or high estradiol level? How can you judge the progress of an in-vitro fertilization cycle by the estradiol levels?


It's difficult to give exact numbers because every cycle and body is different, but, in general, a 'good' estradiol level is between 150- 500 pg/ml on day eight of an IVF cycle. Approximate doubling of the day eight
value every 48 hours is a positive sign of continued follicle development.

hCG is administered when the serum estradiol level reaches 200-600 pg/ml per follicle >17-18 mm in diameter
** 700-2000 pMol per mature follicle

I also made my brain work very hard by reading this article:
http://www.gfmer.ch/Books/Reproductive_health/Monitoring_IVF.html

There were waaayy too many words which I didn't know, like:
- exogenous
- concomitantly
- echogenicity
- sonolucent

But I found it fascinating, reducing the creation of life from sperm and cells, to numbers and equations ....
There is no difference in E2 production between follicles measuring 14 mm and those that are smaller, nor between follicles measuring 17 mm and those which are larger (32). The authors devised an equation to determine expected serum E2 levels depending on number and size of follicles in both ovaries. Thus the serum E2 level on the day of hCG injection is:

E2 = 291 pg/ml + 180 (x) + 64 (y) + 18.7 (z)

where x, y and z represent follicles measuring >17 mm, 15 to 16 mm and <14
mm respectively.

The dose of gonadotropin should not be changed as long as serial E2 levels rise between 50 and 100% every other day (32). Dirnfeld et al. (6), showed that very slow or very rapid estrogen growth rates (EGRs), calculated from the 4 days preceding oocyte aspiration in CC/hMG stimulated cycles, were associated with a reduced pregnancy rate. EGRs of 0.31 to 0.41 were associated with optimal pregnancy rates. EGR is calculated by the formula:
EGR = e-B -1

where B is the slope of the least square line corresponding to the semilogarithmic plot of E2 values versus time and e = 2.718.
If I can figure out the equation and get the right answer, then it should work .... right?

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