41 Yr. Old South African Woman Fails IVF: Needs Higher Stim Protocol, Menopur Dose Too Low

Question:

Hi Dr Ramirez,

I am 41 (42 in March) and have just come through a failed IVF cycle (our 1st attempt). I'm not sure what my FSH levels are but know that I only have 4 and 5 antral follicles left and an AMH of 0.94.

I was put on an 11 day course of 5 amps of menopur a day. I produced 4 eggs, 2 of which fertilised. On day three I had a 6 cell and a 10 cell (neither of which were fragmented) and so the transfer went ahead. Neither took and our result was negative.

I have a 13 month old daughter that we conceived naturally so am reluctant (at this stage) to use a donor egg. The reason we have to go the IVF route is that I have severe Ashermans Syndrome as a result of bad placente accreta from my pregnancy. We are therefore using the services of a surrogate.

I understand that the odds are against us but if we have the means do you think it is worth another attampt or two with my own eggs, and are there any other protocols which may produce a better egg result?

Thanks, M. from Johannesburg, South Africa.

Answer:

Hello M. from South Africa,

As you well understand, IVF pregnancy rates are very dependent on the age effect on eggs. As a woman ages, more and more of her eggs become debilitated leading to poor quality or abnormal embryos. This is the most likely reason for failure after the age of 40 years old. If you absolutely want to have a genetic child, then the only option you have is to continue trying as many times as it takes to be successful. The only things that may stop that plan are if you run out of money (i.e. cannot afford to continue) or the quality of the embryos is consistently poor. Otherwise, persistence can sometimes yield success.

There is a fairly good pregnancy rate at 41-42. In our clinic it is 55% pregnancy/32% deliveries. Miscarriages are increased because of the higher chance of genetically abnormal embryos. The oldest pregnancy to date in a woman using her own eggs was 49 years old in the U.S., but it took her 2 years of trying. Since you have been able to conceive about two years ago, there is already evidence that you do have good eggs. In your case there is the added factor of using a surrogate, but I assume you have selected one that has had successful pregnancies.

In terms of your protocol, every clinic is different and every doctor is different and prescribes/uses different protocols. It does not mean that one is better than the other. In my opinion, however, your protocol is too low for your age. In order to increase the chances of finding a good egg, a lot more eggs need to be recruited and retrieved. 5 amps of Menopur is only 375IU of FSH. As an example, my highest protocol, which is pretty consistent with other clinics in the U.S., uses 450IU of Follistim (pure FSH) + 150IU of Menopur (FSH/LH) for a total of 600IU per day. The bottom line is that the clinic you are working with and their protocol is highly influential on your outcome. You should check and see what their 41-42 year old pregnancy and delivery rates are, then compare them to other clinics. You may find that another clinic is better than the one you are attending.

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.

Comment: Thanks very much! It was great to receive such a quick and informative response.

"What FET Protocol Do You Use For Difficult PCOS Patients?" UK Patient Asks

Dear Dr Ramirez,

Firstly, thank you so much in advance for taking the time to read my question.

Brief History: Dx with PCOS at 17 y/o. HSG clear. My husband has severe m/f, so our only chance of conceiving is through IVF with ICSI. On my fresh cycle in 2008, I had 30 eggs retrieved and due to OHSS, couldn't have an Embryo Transfer. We had 13 embryos, all of which were frozen at the 2PN stage. I have gone through six FET cycles since, but only got to transfer three times, b/c the drugs used to suppress my ovaries (ProstapSR, Buserelin, Synarel) have actually stimulated my ovaries, leading to OHSS a further three times!

My treatment is in the UK and I cannot switch clinics b/c a) my treatment is free and b) since it's free I can't choose where to have my IVF/FET's. The Drs at my clinic have put their heads together to try to come up with an individualized protocol for me, since I keep suffering these rare responses to the suppression meds. I am naturally frightened and sceptical about this new protocol since it hasn't been tried and tested in the UK as yet (but apparently it has in other countries with good success for challenging PCOS patients).

The new protocol would not involve the usual suppression medications. On day 3 of my period, I would inject a long acting Cetrotide shot (sub-q) and also commence 6mg Progynova (estradiol valerate). On Day 5, I would commence daily Cetrotide shots, whilst continuing daily with the Progynova. All in all, this protocol should only take around 13days, then I would commence Progesterone, 3-4days before Embryo Transfer. I am terrified of hyperstimulating again. Is this likely to happen with the Cetrotide at all? Have you had any PCOS patients who have ever responded like I have to suppression medications?

If you were my Dr (I wish you were :D ), what protocol would you suggest for a FET? It may be helpful to add that I have always been a slim PCOSer (BMI 21) and have an AMH of 98.5. I also got pg on our first FET with twins, which I sadly miscarried at 8 weeks. My subsequent two transfers resulted in a negative beta. Thank you so much for reading and for any input you may be able to give! G. from the U.K.

Answer:

Hello G. from the U.K.,

I have never heard of such as thing as OHSS with an FET cycle. I'll have to do some research on that and see if that actually happens. If not, your docs might want to write your case up as an unusual case. Since you have been using GnRH "agonists (stimulators)" in your previous cycles, it sounds like maybe the dosages were not high enough to suppress the hypothalamus (which is what they are supposed to do and prevent ovarian function), but instead stimulated FSH production and ovarian stimulation leading to the OHSS.

I think the change to an "antagonist" is certainly the best way to go. I converted to using the antagonist, Cetrotide and now Ganerelix, over 5 years ago (mainly because it is less injections). I have not used it with an FET cycle (because it is more expensive), but it can work just as well with the protocol you have outlined. The antagonist will definitely suppress any ovarian function, so you should not be able to mount an OHSS response. This is definitely a good plan.

I thank you for the compliment :) and wish that you could be my patient as well. For many reasons, such as the fact that some like you can get IVF for free where they live, patients feel that they are stuck in the clinic near their home. This cannot be further from the truth. I have a patient from Serbia and South Korea in my IVF cycle this month. I have patients come from out-of-state, one from as far as Montana, which is like the difference between the UK and Poland. You can travel to the best center to do your IVF, thereby saving you years of frustration & grief. I had one patient who failed five times at a Los Angeles center only to succeed the first time with us. It is not that difficult to do or arrange IVF afar. There are additional costs involved, which is the biggest factor, but heck, you could plan a vacation at the same time. The IF community calls this "Reproductive Tourism" or "Cross-Border IVF", I believe.

An IVF cycle can be done so that you only have to come here for the minimum necessary time, which for an FET cycle would be 1 week or less or 10 days for a fresh cycle. Also, remember the old adage, "you get what you pay for." Free cycles are all well and good, but as you mentioned above, you are stuck with one center, one protocol, one embryology lab (and there quality can differ greatly), governmental restrictions and that is unfortunate. In the U.S., particularly in California, we have few restrictions and can do embryo donation, donor egg, donor sperm, frozen eggs, surrogacy, and are given leeway on the number of embryos we can implant. I wish that I could just outfit a 747 jet with an IVF clinic and jet all over the world where patients want to see me. I think that would be fun as well :D !!!

Good Luck,

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.

In Vitro Fertilization Gives You The Opportunity To Become Pregnant But It Is Never A Guarantee: Perseverance Is Key!

Something I have been thinking about as I read through infertility blogs & remarks on Facebook, which I think needs to be clarified and clearly understood by all fertility patients. There is a general misconception that In Vitro Fertilization, or IVF, is the "be all" fertility treatment. It is the ultimate "magical" treatment that will get everyone or anyone pregnant. This could not be further from the truth. IVF CANNOT make you pregnant. It can only give you the OPPORTUNITY to become pregnant, by making and placing embryos into the "womb". From that point on, it is in God's or Nature's hands. IVF also CANNOT give you a baby. That is propaganda that has been propagated by SART and the CDC through the use of their "delivery rate" statistic.

Yes, our goal is for you to have a baby. That is what we and you want. But to think that we have an ability to make that happen, and to use that as a measure of IVF success is misleading. We, as infertility specialists, and IVF as a treatment, have absolutely no control over the pregnancy, its course, its complications or its outcome. That too is in God's or Nature's hands. Any pregnancy, whether it is a chemical pregnancy, miscarriage or continuing pregnancy, is an IVF success because the limit of IVF is to give you the chance to get pregnant. Getting a positive pregnancy test and losing the pregnancy is a sad outcome, but at the same time should give you hope. It showed that the IVF worked, and if it can work once, it can work again and hopefully, result in a baby the next time! Perseverance will get you the baby that you want, although the pathway to that dream may sometimes take you in a different direction from your original intended route.

Edward Ramirez, MD, FACOG
Monterey Bay IVF
www.montereybayivf.com

U.K. Patient Has One More Question: How Would I Go About Egg Donation?

Question:

Dr. Ramirez,

I see that having an operation to fix my tubes would be useless.

My last question concerns egg donation-If I decide (after 1 or more IVFs) that my only option is to try egg donation could you please tell me what I should be considering when I choose a clinic. I have heard that in Valencia, Spain there is a clinic that is connected with the local university and only uses young women, mostly students, to donate eggs after they have been thoroughly screened. Have you heard of this particular clinic? I understand that you cannot recommend a particular clinic.

Most importantly, what should I be making sure is involved in the egg donation operation? Is there anything I can do to ensure that I have a better chance of success?

I can't thank you enough for all your advice. Sincerely, P. from the U.K.

Answer:

Hello again,

I cannot give any information regarding the clinic in Spain, as I have no contacts in that country. I have heard of an organization recently called Global IVF & I think it might be a good place to start (http://www.globalivf.com/).

In terms of finding a clinic, you would need to find a good IVF center. It is one that does an adequate number of IVF cycles per year with good published results. You should in particular examine the Donor IVF pregnancy rates. In the U.S., these rates are over 60% per cycle.

Donors can be obtained from three sources: (1) someone you know or find, like a sibling, friend, acquaintance, etc., (2) a donor registered with the IVF clinic or (3) through a donor agency. Usually the costs increase from source 1 to 3. Almost all clinics or agency recruit donors that are under the age of 33, so I would not consider one older that that age, unless it were someone you personally knew, like a sister. In addition, if the donor had proven fertility such as a previous pregnancy, or previous successful donor IVF cycle, then that would be preferential as well. In the US, we have strict rules regarding eligibility and medical history for donors. They are extensively tested to make sure that they don't have any transmittable diseases or genetic diseases. I don't know about Spain.

In the US, donors are usually selected by the recipient, and not by the clinic. I have had information from other European couples that they have to choose the donor the clinic provides, and have no choice. In the U.S., the donors have a full profile, including pictures for you to choose from. Many patients like to choose someone with the same characteristics, background, education, etc. However, the more criteria you have, the more difficult it becomes to find an appropriate donor.

I hope that gives you the information that you need.

Good Luck, your questions are all relevant ones and I hope you continue to inquire of your physicians as much as you need to!

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.

36 Yr. Old Irish TTC'r With Low AMH & Scar Tissue From Cystectomy Needs IVF

Question:

Hello,

I have a number of queries.

I am a 36 year old female from Dublin, Ireland who has been TTC for 2.5 years. After one year of trying myself and my partner were referred to a fertility clinic. At that time, ultrasound and MRI showed that I had a 4.5 cm dermoid cyst on my left ovary and I was referred for a csytectomy in April 2009. My surgeon chose to do a laparotomy saying that there would be less likelihood of the cyst rupturing during surgery and having to clean up the pelvis so I went with his advice, while I was open he took the cyst on the left ovary but also took what he thought was another cyst on the right ovary as it was hemorrhagic. The histology report showed that the cyst from the right ovary was actually my corpus luteum for that month.

After the recovery period for the surgery my partner and I began to try and conceive naturally with no luck. At this stage (December 2009) we were frustrated with the first fertility clinic we went to so we changed clinics and in February of this year I had an AMH test and pelvic sonogram in preparation for IVF. The AMH results show that I have low ovarian reserve (0.5). The left ovary had no follicles on it at ultrasound and the right one only had four or five. I do know from past ultrasounds that I have been ovulating from my right ovary every month since the surgery (and probably before that since I always had pain on this side every month).

I was also diagnosed with uterine polyps at the sonogram which I am going to have removed via hysteroscopy and d and c prior to starting a cycle of IVF in April.

My questions are these:

- could the removal of the corpus luteum on the right ovary and the cyst on the left have damaged my ovarian reserve?

- do you have any suggestions for maximising my chances of success with IVF given my low ovarian reserve? Would you recommend DHEA?

- since the surgery I have had consistent pain where I perceive my right ovary to be and menstrual like cramping at odd times of the month - could this be related to the surgery. I have asked doctors about it and since they can't see anything wrong with an ultrasound they tell me not to worry about it.

I am very concerned about the effect that the surgery had on my fertility as well as the fact that my surgeon nor the first fertility clinic I was with did not warn me of any risk associated with the surgery.

Thank-you for your time

ANSWER:

Hello N. from Ireland,

The previous surgery would not have had an effect on your ovarian reserve. However, the type of surgery you had (exploratory laparotomy with cystectomy) could have altered and worsened your fertility. Unless a lot of the ovary was removed, however, it should not have affected your ovarian reserve.

In reality, low ovarian reserve is just a description of how you will stimulate with the fertility drugs. AMH (anti-mullerian hormone) is only a test that gives us a measurement of ovarian reserve but it is not an indicator of your fertility. Keep in mind that you only need ONE good embryo to get pregnant. In fact, I did IVF on a patient this month who ended up only having one embryo to transfer, because of low ovarian reserve/low response, and today her pregnancy test is positive!

You are still young so your chances are still good. I would go with a high stimulation protocol (not the flare protocol), then you can only hope for the best. I don't advocate DHEA (which is dehydroepiandrosterone, an endogenous hormone i.e. made in the human body, and secreted by the adrenal gland). Make sure the IVF clinic you go to has a good and high pregnancy rate. You don't want to waste time on one that doesn't.

In terms of your pain, it is possible that you have scar tissue that formed around the ovary as a result of the surgery. Scar tissue cannot be seen by ultrasound. You would need a laparoscopy to see it.If worst comes to worst, you could always come to the US, although I know that is a very expensive proposition. I've had patients from as far away as Serbia on the European side and China on the Asian side.

Follow-Up Question:

Hi Edward,

Thanks for your response, particularly about the impact of low AMH on fertility. I have a couple of follow-up questions:

- how could the type of surgery (laparotomy) I had have adversely affected my fertility?

- what is a decent pregnancy rate for a fertility clinic?

- would you advise a laparoscopy to check for scar tissue prior to the IVF or should I just go forward with my cycle?

Thanks, N.

Follow-Up Answer:

Hello Again,

Whenever surgery is performed abdominally, especially an open surgery and one around the reproductive organs, scar tissue formation can be induced. This will interfere with the passage of the egg from the ovary to the tubes.

In your age group, we are hitting a 68% pregnancy rate per attempt with IVF. I know that in general in the U.S., pregnancy rates are 50-60% per IVF transfer. I don't know what they are in Europe, but you might want to use that as a guide. We break that down into age groups and the statistics I gave you are based on your age, and not across all ages.

I do not recommend laparoscopy to check for scar tissue formation prior to IVF. Only do this surgery if you are dead set on trying to get pregnant naturally. IVF will bypass the pelvis completely, and is the ideal treatment for severe pelvic scar tissue/adhesions, so the surgery is not required.

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.