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/

42 yo U.K. Woman, SWF, Low FSH, Low LH, High TSH, No Periods For 16 Years: What Is Wrong? What Are Her Reproductive Options?

Question:

Dear Doctor, I am a single, white female, aged 42. I have high prolactin and started having no periods at age 26 following cessation of pill. There has been no return of periods despite shrinking of prolactinoma found. Many consultants scratched their heads over the years. I am now using HRT (hormone replacement therapy) to guard against osteoporosis.

I have been told I would just need a little help conceiving, clomide maybe. I went off HRT for 6 months whilst exploring potential IVF (in vitro fertilization) clinics using donor sperm. I looked at adoption but did not proceed as few babies for single white people in the UK. Had ORT (ovarian reserve test) at clinic. FSH at 0.8. e2 under 44. AMH low at 0.83. tsh normal/borderline at 4.36. It was suggested that I get tested for response with gonatrophins, then if follicles appear I can try with donor eggs. Donor eggs and sperm may be a bit too far for me.

Any thoughts? Feels like end of road for me. But as clinic is going to seek advice from endocrinologists, I thought I would start to ask wider. Thank you! J. from the U.K.

Answer:

Hello J.from the U.K.,

There are several problems that you report. Let me take them one at a time.

You mentioned that you hve not had periods since the age of 26 and now your are 42 years old. There must be some explanation for that and the only explanation I can see is that your FSH level is very very low (0.8). I presume the LH (lutenizing hormone) level is similarly low. We call that "hypogonadotrophic hypogonadism". It means that your hypothalamus is dysfunctioning and not producing adequate FSH (follicle stimulating hormone) to stimulate the ovaries to work. The treatment for a woman that wants pregnancy is to give FSH and LH (Menopur or Repronex) to stimulate the ovaries to work. This can be done with a reproductive endocrinologist, not a medical endocrinologist, also known as an infertility subspecialist.

Secondly, I noticed that your TSH (thyroid stimulating hormone) level, albeit is within the normal limits, is higher than we like to see it. In general, and U.S. endocrinologists have now adjusted their tolerances as well, we like to see the TSH at less than 2.2. So your thyroid is functioning but it is a little hypothyroid. A little thryoid replacement hormone (synthroid) would probably help to bring that down.

Thirdly, I presume that your prolactin levels are normal now? If not, then need to be treated to get them down to less than 20.

Now, let's talk about your options to get pregnant assuming all the above findings. The one very significant problem that you have, in addition to those above, is your age. At 42 years old, your natural chances for pregnancy have diminished significantly. For example, a 26 year old would have an 85% chance of pregnancy per year. A 42 year old has a 1% chance of pregnancy per year. Therefore, as a single, white female, you need to think outside the envelope of getting pregnant by natural means i.e. just having intercourse or injecting sperm (IUI). IVF will be the treatment of choice, and the medications used to stimulate your eggs will be FSH and LH so that covers the hypothalamic problem.

You might want to consider a gonadotropin stimulation test (trial of using the meds to see if your ovaries respond), but that is not necessary. If you enter the IVF cycle path and your ovaries don't stimulate, then you just cancel the cycle, so the IVF cycle will be test enough. At 42 years old, in my clinic, your chances of pregnancy would be 44% per cycle. That's significantly better than your natural chances. You certainly have the option of using donor eggs. Because donor eggs are taken from a younger woman, and pregnancy rates are dependent on the age of the eggs, you will have a greater chance of pregnancy no matter what age you are as long as your uterus is normal. That means the chances of pregnancy would be the same at 42 as at 45 years old. So that is a backup option that you will always have. If you wanted the best chances for pregnancy, then donor eggs would give you a 60-79% chance of pregnancy per attempt. In the U.S., we do allow donor egg cycles in single women.

So I hope that gives you some food for thought. I have written more extensively on this subject in my blog so you might want to use the search bar to look up more information.

Good Luck,

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.