Third Failed IVF Cycle: New Protocol Needed? Compare SART Stats?

Question:

Dr. Ramirez,

I just had my 3rd failed IVF cycle and I'm looking for some guidance. A little history:

I am 31 have a short luteal phase but PIO and estrace seem to do the trick. Day 3 testing normal. My husband has low morphology.

My 1st IVF attempt I responded very well (long lupron) to low doses of meds. Stimmed for 7 days. They obtained 10 eggs and 9 fertilized with ICSI... all were very good quality on Day 3. Transfered 1 and 5 frozen on Day 3.

2nd IVF attempt- Antagonist Protocol- very slow to respond on highest doses of meds. Didnt have any measureable follicles until Day 10... stimmed for 15 days. Obtained 6 eggs and only 3 fertilized with ICSI. Transfered 2 embryos on day 3. Negative beta 10dp3dt and stopped meds. Discovered 2 weeks later that I was pregnant and miscarried.

3rd IVF attempt- back to Long Lupron- very slow to respond again on highest doses. Stimmed for 15 days- obtained 8 eggs- 4 fertilized and only 2 were viable on Day 3. Beta negative.

Questions:Any thoughts on why I would have such a different response from cycle #1? All 3 cycles were done in 2011.Would you suggest trying a different protocol? Do you think I may be a good canidate for Micro-Flare Protocol?In both 2nd and 3rd cycles my e2 level was 22 and 24 at suppression check compared to 59 in cycle 1. Any insight? Could this mean that I am oversuppressed? Also AFC was lower in past 2 cycles.How much time do you suggest in between fresh cycles?Any thoughts that you would be willing to share would be greatly appreciated. I am getting very discouraged and you have been so helpful in the past. Thank you, D. from Massachusetts

Answer:

Hello D. from the U.S.(Massachusettes),

It is difficult to critique protocols and I generally do not. There are many different ways to accomplish the same thing so any one particular protocol may not be better than another.I do not favor the long protocol, however, for two reasons. I think there is too much ovarian suppression at the beginning of the stimulation and you have to take many more injections. For that reason I use the antagonist protocol, which usually only required 2-3 injections. So, I would not go back to the long protocol. There is not question that the long protocol is the classic method, in fact, most REI's use this protocol because they are not familiar with the antagonist protocol.

In terms of your stimulation, there can be significant differences from one cycle to the next. For example, I have a patient who only produced one follicle in her first cycle with the maximum dosage of medication, yet in the second cycle, with a reduced protocol, she produced 8 follicles. This shows that each cycle is unique and the ovaries will respond differently. You don't mention of these cycles were done back to back i.e. consecutive months, but in general there should be a one month rest period between IVF cycles to allow the ovaries to recover. A stimulation of 12-14 days is not unusual and sometimes preferable. Sometimes a short stimulation phase leads to less quality eggs. Also keep in mind that you were successful in the second cycle, which means that you can be successful again. You have to be persistent. You are lucky that you are in an insurance mandated State for IVF.

I would strongly recommend against the Micro-flare protocol. This has been shown to not be of any benefit.Finally, there are other reasons for failure of an IVF cycle. You are young and had good embryos to transfer. So maybe it was something else? Implantation failure can occur if the transfer technique is not good by the Physician, as an example. Or you may need some additional meds to reduce your immune response or increase blood flow. There are differences between IVF clinics/centers. We are not all the same and therefore pregnancy rates differ.

Follow-Up Question #1:


Thank you so much for your thorough response. I have a few more follow up questions if you do not mind...What are your thoughts on the Estrogen Priming Protocol? Do you usually use a FH and FSH while stimming? I have read that adding Menopur in too soon can effect egg quality. The article that I read suggested adding it in after 4-5 days of stims and then lowering the FSH dosage. Any thoughts on this? My current RE had me starting Menopur on the 2nd day of stims.The past 2 cycles fertilization was only 50% with ICSI compared to 100% my 1st cycle. The embryologist noted that my eggs were "brownish". Any thoughts on this? Do you think it was due to egg quality? Lab issues?You mentioned additional meds to reduce your immune response and increase blood flow... what type of meds do you usually prescibe?How much emphasis do you put on SART scores.

I am contemplating switching clinics and I am looking for some guidance. Mass General has the highest success ratings in my age group but I have heard that they are very focused on scores, etc. I have heard great things about a RE at Boston IVF but there SART scores are lower. Would this be a deciding factor for you?Yes, I agree... I am very lucky to have insurance coverage! Again, I really appreciate your help. This process is so stressful and I am so overwhelmed!

Follow-up Answer #1:

Hello Again,

Let me take your questions sequentially for ease.

1. I don't have any feelings one way or the other regarding estrogen priming. I don't use it because I don't think it has been shown to be of any benefit. By I lack the experience to know for sure.

2. I am a believer in the "mixed protocol" which uses both pure FSH and a combination FSH/LH (my preference is Follistim/Menopur). Many studies have shown benefit to having LH present in the follicular phase. It has been found to increase the egg quality although there is not real technology to determine egg quality. I was trained on this method and my experience has been that the stimulation is better i.e. higher number of follicles. My pregnancy rates are pretty good as well. I don't agree that it will decrease egg quality. That has not been my experience.

3. Brownish or discolored eggs signify a basic egg quality issue. This may be why the fertilization rate was not as good. The minimum fertilization rate should be 50% and will vary from cycle to cycle because the eggs will be different each time. I don't think anyone has any explanation for why the eggs would have a "brownish" or "discolored" appearance.

4. I use low dose aspiring (81mg), Medrol (16 mg) and low dose heparin (2000 units twice per day). These all start with the start of the stimulation and continue through the cycle. The aspirin and heparin are stopped on the day of the trigger injection and not restarted until the day after the retrieval.

5. SART scores are certainly one thing I would look at. The problem with SART scores or the CDC scores is that they only look at one year, not cumulative scores which is more revealing. That's because clinics can have a good year and bad year depending on the types of patients they have, embryology problems, change in personnel, etc. But since these two organizations don't give cumulative statistics, you might have to ask the clinics if they have them. If you are going to use SART scores, then try to look at the last three years and compare. Also the problem with these scores is that they are 2 years behind and IVF technology is ever-changing.

Also, if you are going to look at the SART/CDC stats, the only one you should look at is the implantation and pregnancy rates per cycle and transfer in patients under the age of 35. Don't necessarily look at your specific age group. Those two statistics are the important ones and we use under 35 years old as the gold standard because those are inherently the most fertile patients (ie no age factor). Certainly your age group statistics are also important because you want a clinic that does well with your age group. If I were going to a new area and had no idea which clinic to go to, I would use the SART/CDC statistics to help me decide. Then I would go check them out, ask about their program and see how personal the care is (just like you would if you were buying a car). I don't recommend going to a factory type program. You want a program where you have one doctor attending you through the entire process and don't get a different doc for the transfer, which is one of the most critical steps. Sometimes smaller clinics are better than larger ones because of this, as long as the pregnancy rates are equivalent. Try to get the clinic's current statistics if you can or the most recent ones, and not necessarily the ones from two years ago submitted to SART. Most clinics will have the previous year's stats.


Follow-Up Question #2:

Thank you very much for your response. The info that you provided re: the SART scores is very helpful. I appreciate the tips!!One more follow up question re: the "mixed protocol". Do you usually start the Menopur at the same time as Follistim? Or do you wait a couple of days.Also, would you reccomend that I try any supplements? I have done some reading about DHEA? What are your thoughts?

Follow-Up Answer #2:

Hello Again,

The Menopur (FSH/LH) is started at the same time as the Follistim (FSH). I don't recommend any supplements. There are none, especially DHEA, that have been proven to work but I did see a recent article touting DHEA is older women. They claimed it increased embryo quality, but I am doubtful. That shouldn't be a problem for you because you are young.

Things that I do add in patents that have failed a previous cycle:
1. Acupuncture (it is not proven, but some studies show benefit and it doesn't hurt to try everything after failures.)
2. Low dose aspirin - 81 mg orally per day starting at the beginning of the cycle.
3. Low dose heparin - 2000 units SQ twice per day starting at the beginning of the cycle.
4. Medrol 16 mg orally per day starting at the beginning of the cycle and decrease to 8 mg on the day of transfer (you would stop this at the time of the pregnancy test).
5. Both progesterone injections and progesterone suppositories. I don't start the suppositories until the day after the transfer.

Good Luck,
Dr. 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.

Comment: Dr. Ramirez is always very kind and helpful. I am very thankful for all of his help.