I’m obsessed with numbers. So I liked this article, which had a lot of good information about the numbers people see during the monitoring process:
Some of my take-aways from this article (and take with a grain of salt) follow.
Measurement of E2 is based on follicle size
My doctors certainly seemed to think that my E2 measurement had some relationship to the number of follicles, and this article proves that. These authors actually have an E2 formula depending on the sizes of the follicles! Here it is:
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.
Okay, that’s a little complicated, but they do give a rule of thumb (much more helpful for most of us):
“E2 level is approximately 400 pg/ml per large follicle.”
Also, as we all know, the authors indicate that there is a risk of OHHS with “extremely high levels of E2 (over 3000 pg/ml).”
It’s not good if E2 is rising too fast or two slow, or falling
The article suggests, “It is inadvisable to give hCG to patients in whom the serum estradiol level is seen to increase rapidly (i.e. doubling in 24 hours).” The article suggests that a “linear” E2 growth is best. It says “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.”
Whaaaaa? I get that you don’t want your E2 to double, but I’m not sure what the optimal amount of increase is.
I charted my E2 measurements. My E2 growth (as opposed to the E2 measurement itself) was not doubling every day—it was rising about 64% per day (and was always rising in the 60%s). So I *think* that’s “linear growth” (and thus optimal) as the authors define it.
Here’s my E2 measurements for this cycle:
Stim day
|
Estradiol
|
E2 Growth
|
Follicles
|
0
[not stimming yet]
|
<12
| ||
3
|
108
| ||
5
|
328
|
~9 follicles
| |
7
|
853
|
ave 61.35% [over 2 days]
|
~3 mature, ~11 follicles total
|
8
|
1449
|
69.87%
|
~8 mature, ~11 follicles total
|
9
[trigger shot]
|
2376
|
63.98%
|
I put my data on a graph (with the “x” or horizontal axis being my “stim” day and the “y” or vertical axis being my E2 measurement) but, unfortunately, I don’t know how to make it visible on this blog. It looks something like this:
3000
2500 x (2376)
2000
1500 x (1449)
1000 x (853)
500 x (328)
0 x (108)
0 2 4 6 8 10
Stim Day
It’s hard to tell from the little mini-chart above, but my E2 measurements were growing exponentially. (My E2 “growth” [or increase] in measurements was linear, while my E2 measurements themselves were growing exponentially. If it’s been a while since you had… whatever level math this kind of stuff was taught in… think about it like this. If you gain 10% of your body weight a year, you will actually gain MORE weight year after year. So if you start at 100lbs, the next year you’ll be at 110 (gained 10 lbs or 10% of 100lbs), and the next year you’ll be at 121 lbs (gained 11 lbs, or 10% of 110 lbs), and the next year you’ll be 133.1lbs (gained 12.1lbs), and so on. So your weight gain GROWTH is linear (always 10%) but your weight GAIN is exponential (you gain more pounds each year).) Anyway, the formula showing my E2 measurements (y) as compared to my stim day (x) is: 24.024e0.5119x
Aaaand if we put in on a log scale (so that the axis showing E2 is on a logarithmic scale—ie. Increases in increments of 10x). It looks approximately like this:
10000 x (2376)
x (1449)
1000 x (853)
x (328)
100 x (108)
10
0
0 2 4 6 8 10
Stim Day
Okay! That looks like a pretty straight line! (It’s better on the real graph—it’s seriously a straight line.) My “B” value from above (“the slope of the least square line corresponding to the semilogarithmic plot of E2 values versus time”) appears to be 0.5119. (The number from the formula above.) Which means that my EGR from above (e-B -1) is 0.40. Right in the range of optimal above.
About 20 years ago I was pretty good at math (I took a number of advanced engineering math classes in college), but it’s been a looooong time so it’s possible I totally messed this all up. Since my calculated number appears normal (I didn’t calculate an EGR of 750, when the optimal range is 0.31 to 0.41) and indeed is “optimal,” I’m going to call it a victory and move along.
Back to the article. Here are a few more of the authors’ observations on E2…
• Non responders/low responders: E2 levels did not reach 300 pg/ml by day 8 of stimulation, <800 pg/ml on date of hCG shot.
• Slow responders: E2 levels were <300 pg/ml by day 5, but >300 pg/ml by day 8 of stimulation, 800-1500 pg/ml on date of hCG shot.
• Fast responders: E2 levels >300 pg/ml by day 5 of stimulation, >1500 pg/ml on date of hCG shot.
No differences between the three groups in respect to development of mature oocytes and rapidly cleaving embryos, but the pregnancy rate in the low responding group was significantly lower than in the other two groups. “Thus it seems that the receptivity of the endometrium depends at least partially on adequate E2 levels. It also seems that E2 levels do not directly correlate with oocyte maturity and embryonic growth.”
Here’s another article that suggests it is better when E2 grows slowly:
Finally, as we all know, you always want the E2 to be rising: “in good outcome cycles, E2 continued to rise until hCG was administered, but in nonpregnant cycles, E2 plateaued on the day before hCG administration, which suggests that luteinization or atresia of the more advanced follicles had commenced spontaneously.” Mine was always rising, so I guess that’s good. A nurse at my doctor’s office told me, in response to a question, that sometimes they do see a fall in E2, which suggests that the follicles are overripe, and in that situation they immediately trigger. She said “it’s not ideal.” Um, yea.
Stimming too long (unclear how long “too long” is) is not good
Another suggestion from the authors—you want the “active phase of E2 rise to be 6±1 days, and >7 days is not as good.” “They attributed the high incidence of early abortion, when the active phase was >7 days, to be an expression of oocyte overexposure to hMG prior to hCG injection. Such overexposure may result in postmature oocytes and end in early abortion.” (citing http://www.ncbi.nlm.nih.gov/pubmed/1674937) Elsewhere the article suggests “Patients who fail to achieve adequate follicular development after 6-8 days of ovarian stimulation do not receive hCG, and the treatment cycle is cancelled.”
I don’t know what to make of this because I don’t know what the “active phase” is. (I stimmed for 8 days before my hCG shot on day 9, and I’ve read that a lot of people stim for up to 10 days. I don’t think that is too long….) I think I had adequate follicular development with a day 9 trigger shot. Maybe the “first” day of the active phase is day 3? (That’s when my first E2 measurement was.) In which case, my “active phase” was day 3 to day 8, or 6 days? Or is this one of those things where you don’t count the first day? I don’t know. I guess the takeaway is that stimming too long is bad. Unclear how long is “too long.”
Too many mature follicles prior to trigger shot is not good
The article also suggests “It is advisable that hCG not be administered if there are more than 3-4 follicles of 14 mm or more in diameter.” I think I had EIGHT follicles larger than this the day before my hCG trigger day. Hmm.
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