31 Year Old With DOR Advised To Keep Trying: Adjust Protocol To "Mixed" FSH & FSH/LH

QUESTION:

Hi Dr Ramirez

I am on my first round of IVF and my day 9 scan showed no follicles on left ovary and 3 tiny follicles on right. I am on 375 menopur which has now been upped to 450. Priot to starting treatment i was on the combined pill for irregular periods. I am 31 years old with FSH level of 6. My question is, can being on the pill interfere with follicles growing and am i on te right meds? When they scanned me prior to starting treatment i had more follicles than when doing IVF which doesn't make sense to me? I am having treatment in London, England.

Thanks, N. from England

ANSWER:

Hello,  N. from England,

With your age and FSH level, I would have expected a much better stimulation response. I think you are not being adequately stimulated. Menopur is not adequate. There needs to be more FSH in my opinion, but keep in mind that each doctor does things differently and one way is not necessarily better than another. If you were my patient, my preference is to use a "mixed" protocol using both FSH (Follistim or Gonal-f) and FSH/LH (Menopur or Repronex). I would have started at 300IU Follistim and 150IU Menopur (450IU total of FSH), then possibly decreased to the dosage you started at. But, that is my personal preference (and of course something that makes each clinic different with different results).

The pill should not and does not interfere with ovarian stimulation. I presume that you are also on a Long lupron protocol? Lupron will suppress the ovaries as well.

I have also been surprised by the lack of stimulation in a younger patient, such as your doctors were pretty surprised. Sometimes it is hard to predict what will happen. If the cycle fails, then I greatly increase the medications in the next cycle. Such a finding is called a "poor responder". But keep two facts in mind:

(1) each cycle is unique and the stimulation results can vary from cycle to cycle. One does not necessarily predict the next.

(2) it only takes one good embryo to be successful.

Good Luck!

Follow-Up Question:

Hi Dr Ramirez,

Thank you so much for your prompt reply. I carried on with the 450 Menopur until day 16 and they decided to cancel the cycle as the one follicle was not responding as they would have liked. The consultant at the IVF clinic told me that my chances of conceiving are zero per cent even with IVF. To say I was shocked was an understatement. I spoke to him about the possibility of a different protocol or different meds but he was adamant that I shouldn't try again. I don't quite know where to go from here. I have been under the care of a gynae at my local hospital for fertility investigations for 5 years and he kept telling me IVF was the answer. I got pregnant with Clomid two years ago but now I am at zero fertility, I mean not even 1% according to the IVF consultant.

My question to you would be, in America do you do things differently? I spoke to him about Gonal F and he said it wouldn't have made a difference. I also said about Synarel and he said it wouldn't have made a difference. I have low ovarian reserve and that is that. He is a highly regarded doctor here in England (Mr Tim Child) so I am sure he wouldn't have said zero if he didn't believe it. I know it's hard for you to give an opinion without knowing my full history, but have you seen seomeone with such a poor first reposne go on to do better second time around or should I just draw a line under it all?

Thank you so much for your guidance on this, as my husband and I are a bit shell-shocked. Over here in the UK we always consider the Americans to be further forward in medicine and cutting-edge treatments. We would be prepared to travel if we thought it was worth it. If only one follicle is growing very slowly under high stimulation, would you be inclined to say zero chance too? I appreciate your honesty.

Kind regards, N.

Follow-up Answer:

I am sorry for all the grief you have had to endure. I am afraid that I don't completely agree with your doctor. First of all 450IU is not the maximum dose of medication. You certainly have "decreased ovarian reserve", which means that your ovaries don't stimulate well, but given your age, I would expect you to have a good chance even with only ONE egg. So I would recommend trying with a higher protocol and even if there are only a few follicles, you should continue the cycle and give it a try. It stands to reason, if the cycle is cancelled you certainly won't get pregnant, so in my opinion if there is a follicle present the patient deserves to give it a chance.
In terms of decreased ovarian reserve, there have been several studies, including one that was just published, that showed that ovarian response will vary even in patients with decreased ovarian reserve. Therefore, it is still recommended to continue trying in a patient with decreased ovarian reserve. The next cycle may be completely different than this one, especially if a different protocol is applied.

In addition, I am a firm believer that there is a difference between a mixed protocol (using FSh + FSH/LH such as is found in Gonal-F or Follistim (pure FSh) and Menopur (FSH/LH). I know that there is no standard protocol and studies contradict each other, but FSH is the hormone that stimulates follicle growth (that is why it is called follicle stimulating hormone)and LH is not. In a normal natural cycle, the LH does not rise until just before ovulation whereas the FSh is rising all of the first half of the cycle.

I would encourage you not to give up.. . at least not yet anyway. It is possible that down the road you might have to resort to using donor eggs, for instance if your ovaries shut down completely (premature menopause/premature ovarian failure) or you have failed several attempts with your own eggs, but until then, hope is not lost, every cycle is a new and different cycle and every egg is a new and different egg; all with their own potential. I will never tell a patient that there is "zero" chance because there are always exceptions to the rule and I also believe in miracles. I've seen them happen many times. If you wish to come to California, I would be pleased to assist you in the best of my abilities.

Good Luck,

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

Secondary Infertility: Decreased Ovarian Reserve And Low Morphology May Be The Culprits

Hello,

I just turned 33 and I have one beautiful 18 mo little girl who is the love of my life. She was conceived on our 3rd iui using 5mg of Femara. My husband has low morphology (6%) and I have no regular periods. We both exercise / eat as we should and have no other health issues. We are considered unexplained infertility.

For the past 6mos we have been trying to conceive. I just had a large polyp removed and my fsh levels were tested. 2 1/2 years ago they were 7.0. 6 weeks ago they were 12.1. We are trying to figure out what to do next. We definitely want another child (And we would be open to 3). My questions are:

1) What do you recommend for medication? Is Femera a good starting point? Should we use the same dosage or higher?

2) Should we try an IUI or go straight to IVF?

3) Are there any "rules of thumb" for why FSH increases and how quickly it increases? I've heard stress can impact it. Thanks in advance for your help. C. from Washington State

Answer:

Hello C. from the U.S.,

Congratulations on achieving your first baby relatively easily. You do not have "unexplained" infertility as you have two reasons: sperm abnormality/low motility and irregular periods (ovulation dysfunction). Those are reasons enough to prevent spontaneous pregnancies.

In terms of your FSH level, I have to presume that it was drawn on cycle day #2 or 3, because that is the proper time to do this test and the only way that it an be interpreted. If it was, the elevated FSh level of 12.1 is not a good finding. This is called "decreased ovarian reserve", which basically means that your ovaries will be more resistant and less productive if stimulated with fertility medications. It is not an indication of ovarian function, but is somewhat of a time clock. Once the FSH level reaches 15, most IVF clinics will require you to use donor eggs. When it reaches 20, it means you are in menopause, which in your young age would be classified as premature ovarian failure. So from a time perspective, that means you don't have a lot of time to waste.

Certainly IUI is an option for you, and somewhat reasonable since it worked before. The FSH level will have no bearing on its chances of success. Chances of success depends on age and the sperm problem. If you wanted to do IUI first, I would limit it to no more than 4 attempts. You can use Femara, Clomid or injectables for these attempts and even alternate them, but don't waste a lot of time. Keep in mind that the chances of pregnancy with IUI in your age group is 20% per attempt. By four attempts you should be pregnant, otherwise the statistical chances drop dramatically after that.

If the IUI's fail, then you need to progress aggressively and quickly, especially if you want to have more than one more child. In that case I would recommend proceeding to IVF with ICSI. This will give you a 74% chance of pregnancy per attempt in my clinic (and is the treatment level that most infertility specialists would recommend with an FSH level above 10. Most would recommend not even to try the IUI).

I can't tell you why the fSH is elevated. That is an unknown.

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.

Diminished Ovarian Reserve: I Have Failed 3 IVF Cycles, Blighted Ovum -- Where Should I Go Next?

Question:

Dr., I am 34 and have been diagnosed with diminished reserve.

I have done three IVF cycles. In the first, we got 5 eggs, after fertilizing all had testing and all found to have some anomoly, none transferred. Second, the clinic let me ovulate...didn't even get to extract eggs. Third got 2 eggs, only 1 fertilized, only a 4 cell with a lot of fragmentation, & I knew it was not going to work. Just found out I have a blighted ovum.

My question: Obviously my chances are not very good on my own and I realize donor eggs are my best option but I am finding it difficult to give up.

I am in health care and I guess my question if you can offer any advice is: For example in certain types of cancer there are certain centers that are more leading experts than others for certain types of cancers. Is that possibly the case with this disease? Is there a center that is the leading expert at diminished ovarian reserve that can help me? I had these 3 IVF at 2 different clinics and neither were very compassionate and treated me just like a number taking a shot in the dark at my protocol.

The last clinic the MD REALLY got my hopes up and now that it hasn't worked has dropped off the face of the planet. So my question is, are there leading experts in this arena that maybe know more specifics about what type of protocol might work best for me??

Answer:

Hello B. from the U.S.,

First of all, let me say that diminished ovarian reserve is NOT a disorder and is not a cause of infertility. It simply means that the patient's ovaries don't stimulate well and is often indicated by a high cycle day #2 or 3 FSH level. It is not an indication of egg quality in any way. Secondly, you are still young. You still have a good chance of pregnancy with your own eggs even if only a few are retrieved. I would still expect your pregnancy rate to exceed 50% per cycle (ours is 73%). I would not have wasted any of the cycles because there is no way to know if the good egg was in that batch. Even normal women do not ovulate good eggs all the time, and that is why it can take several months of trying to get pregnant. It is the same with IVF. Even if my patient has only one follicle I still try for this reason.

In terms of your question regarding the best center for your problem, I'm afraid there is no one center that is best for this problem. All IVF clinics have patients with decreased ovarian reserve, and each IVF center has different statistics and different ways of taking care of their patients. We all use different protocols as well. One question I would ask is what was your protocol? Were you given the max stimulation (600IU of FSH in either pure FSH (gonal-f, follistim, bravelle) or a combination (one of the previous with Menopur, Pergonal, Repronex). These latter medications have FSH in them as well so for instance if you took 450IU of Follistim + 150IU of Menopur, you would have a total dose of 600IU of FSH. I use this as my highest protocol.

In addition, timing is critically important. If the HCG trigger was given with the follicle size of 18 mms, it is possible that the egg did not have adequate time to mature, whereas 20 mms or 24 mms would have been better. As you can see, there are many variations in treatments. That is why there is no one center that is better than any other.

In my center, for example, I have extensive experience with low responders and use a high protocol for those patients. I also am a smaller, boutique-type center that prides itself and excels in providing one-on-one personalized care from beginning to the end. I am the only doctor, involved with my patients' progress from day one. That is what makes us different from some of our competitors in the big cities that operate more impersonally and do not give you access to the RE as much. All of these are facts and qualities that a patient should look for and seek out. They are paying a LOT of money for this treatment so they should demand their money's worth in all aspects.

With all that said, low responders are difficult because part of the success of IVF comes from having a large pool of eggs to work with. We know that in all cycles, there are going to be good eggs and bad eggs, so if we have an increased number, then there is a higher likelihood of getting a good egg. For low responders who don't stimulate well, and hence, don't give a lot of eggs to work with, that just means it may take more attempts before that good egg emerges. I would recommend that you NOT give up. After all, you have really only done two IVF cycles since the second one was cancelled. I am confident that you will be successful if you can continue to try. If you want a quicker solution, then donor eggs would be the option, only because a donor with normal ovarian function will yield more eggs to work with. Since you have had a blighted ovum, it means that the IVF cycle worked (remember, IVF only can produce embryos. The pregnancy, because of the last implantation step, still has to occur naturally). This confirms that you can get pregnant, and it is just a matter of getting a good egg/embryo into you. If you were 40, I would advise differently and lean more toward donor, but at your young age, you should keep trying.

Maybe you should consider coming to Monterey :) ! It is a beautiful place to visit as well.

Good Luck and don't give up hope!

Edward J. Ramirez, M.D., FACOG

Executive Medical Director

The Fertility and Gynecology Center

Monterey Bay IVF Program

http://www.montereybayivf.com/

Monterey, California, U.S.A.

Twitter with me at @montereybayivf, and follow me on Facebook at http://bit.ly/9Iw9oV

37 Yr. Old IVF Patient With Decreased Ovarian Reserve or DOR: Continue Trying Or Use Donor Eggs?

Question:

Hi there,

I have just turned 37 years old and this year have been through two IVF cycles both of which were abandoned prior to egg collection due to lack of response to the drugs (only 2 follicles matured and they would only go ahead with 4 min). My consultant has diagnosed low ovarian reserve (DOR, decreased ovarian reserve) without further testing. My FSH level was 7.5 in October when the cycles began and I have not been tested since (they wanted to but I was going on holiday so they used my previous result).

The first IVF converted to IUI but did not work. The next month I fell pregnant naturally but miscarried (very early so was probably a clinical pregnancy). The second cycle we did not convert to IUI as my consultant wanted to wait until I developed a LH surge and then we would have gone to IUI but I didn't surge (probably due to my poor body having had so many drugs!). Anyway, now I am left feeling very down about the whole thing and I think the next meeting I have with the consultant will be the donor egg discussion. I just wanted to know whether you agree with all of this or whether I should try something else first?

Please ask if you need more details but I seem to be rambling on here. Thank you!

Answer:

Dear Adrienne,

Thank you for your question.

You diagnosis of decreased ovarian reserve or DOR is based on the poor response to stimulation during your IVF cycles. We call that "poor responder." Despite a relatively low FSH level, your ovaries did not respond well. This could also be dependent on the amount of medication that you received. I presume you received a high protocol? I go up to 600IU per day with my poor responder patients. Some physicians will not use this high a dose, however.

There are differing philosophies regarding whether or not to proceed with the IVF cycle if there are only a few follicles. Some physicians, like yours, will cancel the cycle if there are not sufficient numbers. I, on the other hand, always complete the cycle. I have had many pregnancies with only 1 egg/embryo. In a natural cycle you only ovulate one egg anyway. IVF is definitely more efficient at achieving pregnancy than a natural method such as IUI so I proceed. I think it gives the patient a better chance for pregnancy. I have heard that in the states where IVF benefits are mandated, such as in Massachusetts, the physicians will cancel because there is a limit on the number of IVF cycles that can be done. In this case it is not the patient's best interest that is being served but economics. That is the problem with government regulations.

Certainly, if your doctor has determined that because you are a poor responder you should not continue trying on your own, then donor eggs is the only option. It is really your choice as to what is the best option for you. I think that each individual has to be emotionally and psychologically ready to go to donor eggs. That is, you have to have resolved that you cannot do it with your own eggs. When my patients have not reached this point, I allow them to continue trying on their own (with their own eggs). You see, my feeling is that I am here to HELP patients achieve their goal, not to dictate what they should or should not do. I don't want to force them into a choice that they are not prepared for or want (some IVF clinics do mandate the choice).

I hope this answers your questions.

Sincerely,

Edward J. Ramirez, M.D., FACOG
Executive Medical Director
The Fertility and Gynecology Center
Monterey Bay IVF Program
http://www.montereybayivf.com/
Monterey, California, U.S.A.