Tuesday, May 10, 2011

Mini-IVF In A Woman Over 40 Years Old


I am from Canada and will turn 42 in a few weeks. I am trying to conceive my second baby after already having a baby boy with a previous IVF cycle. My first cycle for baby number two was unsuccessful. It consisted of Lupron from day 21 then Gonal F and Repronex. This was not successful as they retrieved only 5 eggs from fourteen follicles. All five fertilized but only 1 made it to the 5 day transfer. This cycle my RE has me on Clomid from day 3 to 7 with Gonal F and Menapur starting on day 7. I will be taking Cetrotide at some point. I have tried to find this protocol on the web and couldn't find it anywhere. I will be taking 100 mg of Clomid, 150 Gonal F and 75 Menopur. It seems like these amounts appear to be very low. I am so worried that this protocol does not seem very aggressive. Do you have any experience with this type of protocol for someone with my age?? I assume that egg quality is the issue. My FSH is low after three months of DHEA. Thank you, S. from Canada


Hello S. from Canada,

The protocol you are using is a "mini-IVF" protocol and mainly used to help reduce the cost of medications. It is probably reasonable in a young woman that responds well to stimulation, because the Clomid will be adequate to recruit sufficient follicles, but I think it is not appropriate for you at your age. 

(Readers: Since the writing of this blog post there has been a Yale University study published in April 2012 showing that Mini-IVF is highly overrated and results in lower pregnancy rates as well as take home baby rates. See article "Mini IVF Yields Mini Success" and the study brief  "A case-control pilot study of low-intensity IVF in good-prognosis patients".)

This is a very low protocol. You would be at high risk of having a minimal stimulation and very few follicles. In truth, I can't believe your RE is planning this. Since you didn't give me the amount of medications you used on the first cycle, I can't tell whether you were adequately stimulated or not, but if you were my patient (and keep in mind that protocols vary widely amount doctors and no one protocol is better than another), I would be stimulating you aggressively with a high dosage. Namely 450IU Follistim and 150IU Menopur (or Repronex) in a continuous dosage.

In terms of your previous cycle, you had fourteen follicles and that is a very respectable number. I am worried about the fact that only 5 eggs were retrieved. Without looking at your records, I cannot know for sure, but I am inclined to think that you were probably triggered (with HCG) a little too early. If the eggs within do not have time to begin maturing, they do not release from the follicle wall and don't get retrieved. I expect to have at least a 60% retrieval rate in my clinic, so that would mean that you should have gotten at least 8 eggs retrieved. Since all 5 of your eggs fertilized, that means that they were all mature, which is a good maturity rate. The lack of development was due to the "age factor", which is the decline in egg quality that occurs with age. I would NOT have taken them to blastocyst, as that puts them through an unnecessary extra step, and instead, would have opted to transfer all at D#3. I believe the uterus is a better incubator than the laboratory.

Because of your age, keep in mind that it is going to be harder to become pregnant, but not impossible. Since your ovaries are still responding well, you still have the opportunity to become pregnant with your own eggs. You will just have to be resigned to having to go through several attempts to become successful. The only alternative is donor eggs, and you will always have that option as it takes away your age as a factor.

Follow-up Question:

Thank you so much for your response. As predicted the cycle was a bust. I had four follicles only and at one point they decreased in size (after my Cetrotide shot) I have been told that my lead follicle that reached 1.4 (which is when I was instructed to take my Cetrotide) may of been a cyst that they saw on day three. Anyway, I have a couple of questions about my upcoming cycle. So far I have had two awful cycles when taking Cetrotide. My first cycle before conceiving my son my Estrogen dropped significantly after Cetrotide. Do you think I should do another cycle with Cetrotide or do you think I should go back to Lupron?? Is it possible to just start Lupron the same day as my injections instead of going back to CD21.

I am at a loss as what would be the best plan for me given my age. As far as medication amount, you were accurate that I was on 450 of Lupron and 150 of Repronex. I believe the cycle that I had my son my Lupron was stopped as soon as I started my medication but he doesn't seem to be wanting to do that. Could you please give me advice on what protocol would be best given my age?? Thanks

Follow-up Answer:
Hello Again,
If you are going to use Lupron, then you have to start from CD21 of the preceding cycle. It is called the "long protocol". I would not recommend it in you.

I use the antagonist protocol almost exclusively in my practice. The problem that I see from what you told me is that you started the Cetrotide too early. If you do that, you suppress the follicle growth and get what you saw. The antagonist (Cetrotide or Ganerelix) should only be started when the follicles have reached 16-17 mms. The rule of thumb is that at least 30% of the follicles should be this size. I will sometimes wait until the lead follicle is 18mms if the other follicles are not sufficient enough size. With that, I do see an estradiol drop so I don't pay attention to it much any more. I think it is showing a decrease in activity of the smaller follicles that have been stunted. Using the antagonist is where the art of medicine comes into play because there are no hard and fast rules. It is very dependent on the experience and judgement of your doctor.

As I mentioned previously, if you were my patient, I would use the antagonist Cetrotride, not Lupron,and use the highest protocol of 450IU Follistim and 150IU Menopur continuously (no adjustments).
Good Luck,

Dr. 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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