Friday, March 4, 2011

After Failing IVF Three Times 45 Yr Old Wonders, Higher Stim or Lower Stim? Use BCP?: I Recommend A High Stim Mixed Protocol & BCP


Hi Dr. Ramirez,

I am 44 turning 45 this June. I have had 3 failed IVFs - 1 didn't go beyond retrieval because I pre-ovulated so no eggs to retrieve. My recent failed ivf cycle I had 3 follicles 19mm, 18mm and 16.5mm. The biggest follicle had no egg, the second largest had a degenerative cell and the third an immature egg. I took 300 iu's of follistim and 1 vial of menopur increased to two mid cycle.

Can taking too little or too much meds (follistim/menopur) cause this outcome?

We are trying a gentler dose and using follistim instead of gonal f. My first few cycles I was taking 600 iu's of gonal f and 150 iu;s of menopur. They had me doing this protocol for months and I started to respond poorly to it. I insisted on changing the meds or trying a gentler dose.

We interviewed with a new doctor here and his approach is less is more, less meds and get better quality vs. quantity eggs. And is it true that the smaller follicles esp. women my age will have bad eggs? My last cycle debunked that whole theory because the dominant follicle or the two largest didn't have any eggs. The smallest follicle did have an egg but it was immature.

I know that on the average I produce 5-8 follicles per cycle. I think it's important to save as many of the follicles we can, we can't afford not to even if they have bad eggs in them. I am not young and producing 20 follicles. How much do you recommend women my age take in meds (follistim/menopur)? The new doctor wanted to put me on 150iu's of follistim every other day or maybe everyday? That did not seem enough? He only wants to stimulate the dominant follicle or larger follicles. I don't want to take so little that it doesn't stimulate enough or take too much that I can get overstimulated and not respond well. I know my body and I am very sensitive to the drugs. I have also used micro-dose lupron and I responded poorly to it.

What protocol do you at your clinic use on women my age? My recent baseline fsh is 8.6, E2 is 30 and my AMH 0.27. It started low and increased up to 0.7 taking dhea and in the last few months started to decrease. I have no other issues other than my age and thyroid disease but it's under control. Do you change dosage depending on blood levels, number and size of follicles? The doctors I went to never did that.

Do you use clomid or birth control pills? I am not fond of either of them but I have heard and read that if you are on clomid you third ivf cycle will be successful? I prefer to use estrace or patches over the birth control pill to suppress. Why do clinics use birth control pills? I have read clomid was found to give cancer to lab rats?

Your help is greatly appreciated. I don't have time to waste anymore.

Thank you, C. from New York


Hello C. from New York,

In general I don't comment on specific protocols because each doctor has their personal preferences and there are none that are perfect or better than others. However, I don't think I like your new doctor's recommendations or protocols and I'll explain why.

The biggest hurdle that you are facing is an age related decline in egg quality AND a decreased ovarian reserve. There is nothing that can be done about the egg quality but the goal with IVF is to increase the number of eggs recruited and available in the hope that a good egg is still present and we can find it. So, the protocol is always to try to stimulate an increased number of follicles and hopefully eggs.

I have read studies where the argument is if you use a natural cycle (no stimulation or decreased stim cycle), the egg quality will be better, but I believe that to be nonsense. Why would decreasing the number of follicles or relying on a natural cycle (only one follicle) produce better eggs? That is illogical. The quality of the eggs are already predetermined. Stimulation or lack thereof does not influence its quality. Again, I believe that the only way to overcome the age factor is to try to get the maximum number of eggs out at a time. For this I use a high protocol or mixed protocol that is 450IU of follistim and 150IU of Menopur. I also Do Not Use Lupron (called the long protocol) because I think it is inhibiting the ovaries too much at the time of follicle recruitment. Instead I use an antagonist protocol where the antagonist is given for only 1-3 days.

The only time I will decrease the amount of medication is if the patient has gone through one or two IVF cycles and still the number of follicles encountered or eggs retrieved are few. I decrease the protocol because I don't want her to spend lots of money on medications if the increased amount is really not doing too much. The ovaries do get to a point where they won't stimulate much despite increased dosage of medications. Unfortunately, your ovaries sound like they are there already. Again, the reason for doing this is to reduce the cost of medications.

I do alter my dosages as the cycle goes on, but only if I am starting from a lower dose and the patient is not stimulating, in which case I increase the dosage, or if I start on a higher dosage protocol and she is stimulating too strongly, in which case I decrease the dosage. Other than that, the dosage stays the same for most of the cycle without alterations.

I would not even consider Clomid for an IVF cycle. Some clinics do again to decrease the cost of medications but multiple studies show that the injectables are superior to Clomid.

Finally, in terms of the birth control pill, I do use it. Several studies have shown a better response if preceded by birth control pills. It suppresses the ovaries in the cycle preceding the IVF cycle and there may be a rebound effect so that the ovaries stimulate better. Estrogen does not suppress the ovaries unless given in very high amounts such as with the birth control pill. I have read of clinics trying to do IVF after a natural "unsuppressed" cycle, but I don't think it makes much difference. The other reason to use the birth control pill is that it allows us to take control of your cycle so that we can be sure that timing is correct. Timing is absolutely critical with IVF. There is a very small window of opportunity for the embryo to implant and if you miss it, then the cycle will fail. Also, using the birth control pill helps with scheduling if you batch patients (put them in the same group).

I think it is meritorious that you are trying to achieve pregnancy with your own eggs at 45 years old, but you have to understand that pregnancies rarely occur after 43 even with IVF unless donor eggs are used. However, I always remind my patient that the oldest woman to achieve pregnancy through IVF using her own eggs was 49 years old. It did take her two years of doing IVF, so persistence can count if you can afford it and want to wait that long to have a child. But you also have to be realistic and not let your expectations be too high. I hope that your journey will go well nonetheless, and that you achieve your goal of having a child.

Good Luck,

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

Monterey, California, U.S.A.

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