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Understanding High FSH and Estradiol Levels: Causes & Options


Question
Dear Dr. Ramirez,

I am forty-one year old professional woman living in Youngstown, OH, and I desperately want another child (I have a 16 year-old and a five year-old that were conceived with no problem at all).  Before trying to conceive this time, my dr. ran day 3 FSH and estradiol testing, with an FSH result of 15.9 and an estradiol result of 207.  What does all of this mean for me?  I've heard that I should take Clomid to stimulate ovulation, but since Clomid raises the FSH, isn't that counterproductive?  How does Femara (sp?) work?  Is there any hope for me without donor eggs?

Thank you so much,
Melissa

Answer
Hello Melissa from the U.S.,

FSH stands for Follicle Stimulating Hormone.  It is the hormone that the pituitary (brain) produces to stimulate the ovary to grow and ovulate an egg.  Think of the ovary as a ball with lots of holes in it (sort of like a practice golf wiffle ball).  Imagine this ball at the end of your blood vessel and the holes let the FSH in.  When the FSH reaches the inside, the ovulatory process is stimulated.  Now, imagine the same ball with much less holes because over time the holes have blocked off.  So now less of the FSH is entering the ball and stays in the blood stream.  That is your cycle day# 2 or 3 level.  If the ovary is picking up a lot of the fSH, the level is low, but if it is picking up less, the fSH is high.  When then level reaches 20, that signifies that the ovary is not picking up the fSH anymore, which is menopause.  From a fertility point of view, we want the fSH to be less than 10.  When it is higher than 10, that signifies "ovarian resistance", which simply means that if we stimulated the ovary with fSH (fertility medications), the ovary will not respond very well i.e. not increase the number of eggs that it ovulates.  The main purpose of fertility drugs, in someone who is ovulatory, is to increase the number of eggs that are ovulated in order to increase the chances that one egg will find and get into the tube to be fertilized, etc.  So if the ovary is "resistant" to being stimulated, then more eggs will not be ovulated or available to be retrieved (as in IVF).

When the fSH level is 15 or above, that is significant ovarian resistance and very close to menopause.  It is very very unlikely that we would get more than one egg, if any at all, which means that the IVF cycle would be wasted.  That doesn't mean it won't work, after all, it only takes one good egg and one good embryo to become pregnant (and I have had several of these types of patients), but merely that the chances are less.  For this reason, many IVF clinics use 15 as their cutoff for a patient to use their own egg.  However, it is not an absolute and the choice is ultimately yours.

Clomid and Femara work by stimulating the ovary indirectly.  They are both estrogen receptor blockers, and in doing so, trick the brain into thinking that it is not producing enough estrogen (which occurs from the ovulation process in the ovary).  As a result, the brain increases the amount of fSH in the blood to stimulate the ovary.  As you can see, if you have ovarian resistance already, meaning that the ovary will not pick up more fSH anyways, then using Clomid or Femara will not help. In fact, using high dose injectable fSH won't do much either.  

Finally, the way that IVF helps with the age factor, what I call the "age related egg factor", is by stimulating the ovary to get lots of eggs out at a time.  The assumption is that there are still some good eggs left in the ovary.  By taking many many eggs out at a time, we are hoping that we will have a good egg in that group, and thereby increase the chances of pregnancy.  We do not have the technology to make eggs better.  If we can't get a lot of eggs out at a time, then then IVF is helping a little more than trying naturally but not by much.  I still think that IVF is better, however, than trying naturally because more of the process required to become pregnant is accomplished with IVF, whereas you natural process is less exact.

I have had and have patients will high FSH levels, such as yours, attempting IVF.  Again, it is your choice, and my role is to be your advisor, not your parent.  Most patients want to try at least once, to convince themselves that they gave their best effort.  Also, as I mentioned previously, I have had some successes with only one egg.  One can make a good argument for not using fertility stimulation in these cases, since a natural cycle will produce one egg on its own if the ovary is still functioning normally, however, we can't know that until we try, so I still use high dose stimulation.  

By the way, having such a high estradiol level on cycle day#3 does not make sense.  The estradiol should be at its lowest level.  Having a high level like that means that something else is producing estrogen, such as a cyst, or that the timing of the test is wrong.  Therefore, I would recommend that you repeat the test after another natural cycle.

I know this is a long answer, but I hope it gave you some relevant information.  

Good Luck,

Edward J. Ramirez, M.D., FACOG
Executive Medical Director
The Fertility and Gynecology Center
Monterey Bay IVF Program
www.montereybayivf.com

Monterey, California, U.S.A.

for additional information check out my blog at http://womenshealthandfertility.blogspot.com check me out on facebook and twitter with me at @montereybayivf