Mini-IVF In A Woman Over 40 Years Old

Question:

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

Answer:

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
www.montereybayivf.com
Monterey, California, U.S.A.

40 Year Old IVF Patient In Vietnam On Low Protocol Fails First Cycle: Has Many Questions, Concerns

Question:

Dear Dr. Ramirez,

My name is A. from Vietnam, 40 years old by end of March 2011. Just give you some information about me regarding Infertility/IVF. My menstruation cycles are different every month: 28 days in Feb, 26 days in March and 31 days in April. So, average: 26 days. Period in March was especially longer; maybe it was caused by hormone therapy in March. My FSH on March 6 (2.day of period) was 10.6mIU/mL and AMH on April 9 was 0.8ng/mL.

I started my first IVF cycle on March 6 2011 (2. day of period) and ended it with 2 embryos transferred on March 22. Unfortunately, it failed. On March 6, I got 1 Decapeptyl 0.1mg. However, I reacted allergic to this and the doctor stopped Decapetyl and gave me 2 days later on March 8: 1x Gonal F 300 i.u. each day and for 8 days until March 15. One day later on March 16, I got Pregnyl at 8.30pm. 2 day later on March 18 at 8.30am, I had my egg retrieval. 6 eggs were collected and 4 were fertilized. On Day 3 after retrieval at 8C stage I had 2xnormal embryos with grade 1, 1x embryo with grade 2 and 1 embryos with Monosomy 21. On day 4, 2 embryos were transferred. My husband semen test result shows 25% normal form (morphology) with total live count of 341 million sp/vol and has anti-sperm antibody. So, I used IVF, ICSI and PGD (for down’s syndrome) in March.

For the next IVF: One clinic suggested to give me on the 3.day of my menstruation 1x300 i.u. Gonal-F mornings and 1x 150IU Menopur nights for 4 days first. Based on the follicle count and size in the ovaries, they will decide on further dose. They are likely to follow a step-down protocol. They will not use any drugs like Decapeptyl this time.

Another clinic suggested to give me on the 2nd day of my menstruation 1x300 i.u. Gonal-F for 5 days and will see based on the ultrasound result.

Could you please kindly answer my following questions and tell me what would you do differently?

1. Do I need birth control pills? Why or why not? I think I need it, because my monthly cycles are different. So, with the birth control pills, the embryos will be implanted on time. What do you think?.

2. Which dosage and drugs would you use except for the 2 dosages of 2 clinics?. Which dosage of these 2 clinics does make more sense to you? Which one will give me more eggs with good quality? Last IVF, I just had 6 eggs, 4 fertilized and just 2 healthy embryos transferred at the end. As I know, I need 3 embryos for my age.. Do I need such kind of drugs like Decapeptyl? Why or why not?.

3. On which day would you start the IVF (2. or 3.Day of period)? Why?.

4. Will acupuncture and Chinese herbs support the success of IVF? Or will it be contra productive? If recommended: before or before and during the IVF? I am taking prenatal multi vitamin and 400mcg folic acid. Do the unfreezing eggs have the worse quality compared to fresh eggs?

5. Was the embryos’ transfer late (at the Murola stage) last time? Should it be transferred earlier this time at 8C stage? I will not use PGD this time. Did I have enough eggs (6 eggs last IVF) at my age? Do I need to increase them next time? Does one embryo have 9% success rate for women at 40?

Thank you very much for your time. Best wishes.

Answer:

Hello A. from Vietnam,

It is interesting for me to see that IVF is being done in Vietnam, proving that this is a procedure that spans the world. Keep in mind that protocols used are highly variable between clinics and doctors. No one protocol is better than another so the recommendations I give are based on my knowledge, experience and preferences.

I always use the birth control pill preceding an IVF cycle. I believe the studies that show better response to stimulation by using the BCP. In addition, it causes the ovaries to essential shut down so that they will be more responsive to the stimulation and so that the follicles will start out somewhat evenly when the stimulation is started.

One thing I noticed about the protocols you have been on is the fact that they are low dose protocols. My highest protocol is a total of 600IU of FSH and I prefer a "mixed" protocol using pure FSH and an FSH/LH mixed compound. The preferred medications I use are Follistim (pure FSH) and Menopur (FSH/LH) in an approximately 2:1 ratio. So, my highest protocol, which is what I would use with you, is Follistim 450IU and Menopur 150IU taken every evening. My highest protocol is a continuous protocol, meaning you stay at the same dose all the way through, but it will really depend on your stimulation. Sometimes, if the patient stimulates more strongly than expected, I will drop the dose but most patients with an elevated FSH like yours (decreased ovarian reserve) will stay at the same dose. I do think that you were understimulated and the number of eggs retrieved and resultant embryos was low. In your age group I would prefer to have 4-6 embryos to transfer.

I cannot comment on the two clinic's protocols specifically, as I mentioned earlier. I can only give you my opinion regarding the protocol that I use.

In my center, I start the IVF cycle on an arbitrary day called "cycle day #2" irregardless of when your period actually starts on that cycle. This is because having used the birth control pill, I am in total control of the cycle and don't have to rely on the natural cycle timing.

I do recommend acupuncture as some studies have shown it to be beneficial with IVF.

I do think that the transfer should have been on D#5 post retrieval if PGS was done (blastocyst) but if PGS is not going to be done, then D#3 is better because I believe the uterus to be a better culture environment that the lab. Frozen embryos tend to have a decreased pregnancy rate, mainly because the best embryos are used to do the fresh transfer and the second best left to freeze. Also, the freeze/thaw have a little effect on the embryos but if done right, this should not be significant.

Finally, pregnancy rates are highly variable between doctors, clinics and countries. I cannot compare them exactly. In my center, your chances of pregnancy per cycle is 70% with 60% continuing. The U.S. does tend to have higher pregnancy rates than most other countries. At 41 years old, this decreases to 47% pregnancy and 29% continuing. Since we batch pregnancy rates into a 38-40 yo category, the rate I gave for 40 years old might be a little higher than it should be.

"Chúc may mắn"....Good luck on your next cycle!

Dr. 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.

After Failing IVF Three Times 45 Yr Old Wonders, Higher Stim or Lower Stim? Use BCP?: I Recommend A High Stim Mixed Protocol & BCP

Question:

Hi Dr. Ramirez,

I am 44 turning 45 this June. I have had 3 failed IVFs - 1 didn't go beyond retrieval because I pre-ovulated so no eggs to retrieve. My recent failed ivf cycle I had 3 follicles 19mm, 18mm and 16.5mm. The biggest follicle had no egg, the second largest had a degenerative cell and the third an immature egg. I took 300 iu's of follistim and 1 vial of menopur increased to two mid cycle.

Can taking too little or too much meds (follistim/menopur) cause this outcome?

We are trying a gentler dose and using follistim instead of gonal f. My first few cycles I was taking 600 iu's of gonal f and 150 iu;s of menopur. They had me doing this protocol for months and I started to respond poorly to it. I insisted on changing the meds or trying a gentler dose.

We interviewed with a new doctor here and his approach is less is more, less meds and get better quality vs. quantity eggs. And is it true that the smaller follicles esp. women my age will have bad eggs? My last cycle debunked that whole theory because the dominant follicle or the two largest didn't have any eggs. The smallest follicle did have an egg but it was immature.

I know that on the average I produce 5-8 follicles per cycle. I think it's important to save as many of the follicles we can, we can't afford not to even if they have bad eggs in them. I am not young and producing 20 follicles. How much do you recommend women my age take in meds (follistim/menopur)? The new doctor wanted to put me on 150iu's of follistim every other day or maybe everyday? That did not seem enough? He only wants to stimulate the dominant follicle or larger follicles. I don't want to take so little that it doesn't stimulate enough or take too much that I can get overstimulated and not respond well. I know my body and I am very sensitive to the drugs. I have also used micro-dose lupron and I responded poorly to it.

What protocol do you at your clinic use on women my age? My recent baseline fsh is 8.6, E2 is 30 and my AMH 0.27. It started low and increased up to 0.7 taking dhea and in the last few months started to decrease. I have no other issues other than my age and thyroid disease but it's under control. Do you change dosage depending on blood levels, number and size of follicles? The doctors I went to never did that.

Do you use clomid or birth control pills? I am not fond of either of them but I have heard and read that if you are on clomid you third ivf cycle will be successful? I prefer to use estrace or patches over the birth control pill to suppress. Why do clinics use birth control pills? I have read clomid was found to give cancer to lab rats?

Your help is greatly appreciated. I don't have time to waste anymore.

Thank you, C. from New York

Answer:

Hello C. from New York,

In general I don't comment on specific protocols because each doctor has their personal preferences and there are none that are perfect or better than others. However, I don't think I like your new doctor's recommendations or protocols and I'll explain why.

The biggest hurdle that you are facing is an age related decline in egg quality AND a decreased ovarian reserve. There is nothing that can be done about the egg quality but the goal with IVF is to increase the number of eggs recruited and available in the hope that a good egg is still present and we can find it. So, the protocol is always to try to stimulate an increased number of follicles and hopefully eggs.

I have read studies where the argument is if you use a natural cycle (no stimulation or decreased stim cycle), the egg quality will be better, but I believe that to be nonsense. Why would decreasing the number of follicles or relying on a natural cycle (only one follicle) produce better eggs? That is illogical. The quality of the eggs are already predetermined. Stimulation or lack thereof does not influence its quality. Again, I believe that the only way to overcome the age factor is to try to get the maximum number of eggs out at a time. For this I use a high protocol or mixed protocol that is 450IU of follistim and 150IU of Menopur. I also Do Not Use Lupron (called the long protocol) because I think it is inhibiting the ovaries too much at the time of follicle recruitment. Instead I use an antagonist protocol where the antagonist is given for only 1-3 days.

The only time I will decrease the amount of medication is if the patient has gone through one or two IVF cycles and still the number of follicles encountered or eggs retrieved are few. I decrease the protocol because I don't want her to spend lots of money on medications if the increased amount is really not doing too much. The ovaries do get to a point where they won't stimulate much despite increased dosage of medications. Unfortunately, your ovaries sound like they are there already. Again, the reason for doing this is to reduce the cost of medications.

I do alter my dosages as the cycle goes on, but only if I am starting from a lower dose and the patient is not stimulating, in which case I increase the dosage, or if I start on a higher dosage protocol and she is stimulating too strongly, in which case I decrease the dosage. Other than that, the dosage stays the same for most of the cycle without alterations.

I would not even consider Clomid for an IVF cycle. Some clinics do again to decrease the cost of medications but multiple studies show that the injectables are superior to Clomid.

Finally, in terms of the birth control pill, I do use it. Several studies have shown a better response if preceded by birth control pills. It suppresses the ovaries in the cycle preceding the IVF cycle and there may be a rebound effect so that the ovaries stimulate better. Estrogen does not suppress the ovaries unless given in very high amounts such as with the birth control pill. I have read of clinics trying to do IVF after a natural "unsuppressed" cycle, but I don't think it makes much difference. The other reason to use the birth control pill is that it allows us to take control of your cycle so that we can be sure that timing is correct. Timing is absolutely critical with IVF. There is a very small window of opportunity for the embryo to implant and if you miss it, then the cycle will fail. Also, using the birth control pill helps with scheduling if you batch patients (put them in the same group).

I think it is meritorious that you are trying to achieve pregnancy with your own eggs at 45 years old, but you have to understand that pregnancies rarely occur after 43 even with IVF unless donor eggs are used. However, I always remind my patient that the oldest woman to achieve pregnancy through IVF using her own eggs was 49 years old. It did take her two years of doing IVF, so persistence can count if you can afford it and want to wait that long to have a child. But you also have to be realistic and not let your expectations be too high. I hope that your journey will go well nonetheless, and that you achieve your goal of having a child.

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.

40 Year Old U.K. Woman With One Miscarriage Feels Time Is Running Out For Her: More IUI's, More IVF Or Donor Eggs?

This post concerns a woman in England who has written to me several times regarding her infertility journey. I would like to publish the entire correspondence for those of you who have a similar dilemma, that is, what to do if you have gone through multiple intra uterine inseminations, actually get pregnant naturally but miscarry, but because of your age, needed to consider IVF as the next step. Unfortunately, the first IVF cycle you do fails. What next? You can read my final response and advice at the very bottom. It is interesting to see how women in the U.K. receive infertility treatments through the National Health Service and the limitations of this government sponsored health care.

Question:

Hello Doctor Ramirez,

Hope you are well. It's L. from England again! I have added my previous questions below and your answers below as I didn't know how to add a link to my history. I have had my first round of IVF (NHS) and it did not go well. First I down regged with Buserelin Spray and this did not work after 3 weeks I was switched to the injection which then worked after another 2 weeks so all in all 5 weeks of down regging. I was then given Menopur 300 ui (Maximum dose at my clinic) after 12 days of stimming this has only produced 2 follies ( I have had 4 follies on puregon at a much smaller dose) at my scan today they have said the they will convert me to IUI as they need 3 min for IVF.

I am now so confused about what my next step should be if the IUI does not work. Unfortunately I am only really able to afford one more go at IVF, at a push with the help of family maybe 2 and wanted to ask what you thought my best option was. I have heard that mild/mini IVF may be better for me at my age however I am worried about my response, but then can't help thinking that my response was poor because I down regged for too long.

My niece has agreed to be a donor for me but im not sure she will be accepted by the clinic as her BMI is high and she is only 21 (she has a 1 year old daughter). My clinic said usually the lower age limit is 23. (I could possibly look at other European clinics with not as strict egg donation guidelines).

Or should I try again with my own old eggs? I have read about the benefits of taking DHEA to improve egg quality but feel that here in England I would need to self medicate this as I don’t think doctors here have taken this approach on board yet. What would you suggest I take if you indeed think it is appropriate. I am already taking the low dose aspirin and of course folic acid. Basically what I am trying to ask is if you were me what would you do in view of my low follie count on this IVF cycle. What regime would you put me on if I were at your clinic? or is it better to give up on my eggs and do down the donor route? Thank you in advance for your response. I always feel much better when I receive your advice. L. from the U.K.

PREVIOUS LETTERS:

Question: Hi, I am having IUI in England. My first attempt was cancelled as I ovulated myself before the follicle was large enough. My 2nd attempt I took 50 puregon every other day from day 5 and then had IUI on day 17 (I have a short cycle of 24 days), my period came on day 24 as usual. My 3rd attempt I again took 50 puregon every other day from day 5 and had IUI on day 14, again my period came on day 24. After reading many forums on the internet a lot of people seem to be having a larger dose every day from earlier in their cycle. Is it better to try and carry out IUI within my natural cycle or should the puregon be making my cycle longer? Should I be injecting earlier in order to have a follicle that is the correct size by my natural ovulation day of day 10? I have tried to contact my consultant but he never returns my calls and unfortunately I am starting to lose confidence in him. Thank you for your time. L. from the U.K.

Answer:

Hello L. from England,

First, if your doc does not return your calls, then find a new doc. He is not helping you. For example, my patients have access to me via by cell phone and via email, which I receive on my cell phone.

Second, I presume that your doc is monitoring you by ultrasound to determine the optimal day for trigger. Is he not? If not, then he is not the right person to see. If he is, you should be forming at least 3 follicles per cycle in order to optimize your IUI's. That's my goal and the number that studies have shown to increase pregnancy rates per cycle. In addition, you should be going on Progesterone the day following the IUI to supplement your luteal phase. The fact that your cycles are short, despite ovulating on CD#14-17, means that you have an inadequate luteal phase (luteal phase defect). Without adequate progesterone support, implantation will not occur or the pregnancy will not continue. With the additional progesterone, you will not have a period until the progesterone is stopped, which should be after a negative pregnancy test is done 12-14 days after the IUI. If it is positive, then the progesterone would be continued until you are 10 weeks gestational age.

I hope this helps, Good Luck. Edward J. Ramirez, M.D.,

Follow-Up Question:

Hi, I wonder if you could please give me your advice once again.

After your last reply I spoke to my fertility nurse and she indicated that I may have luteal phase defect but said that they did not use progesterone to help in IUI she basically said there was nothing I could do, I then managed to speak to the consultant who was very angry with the nurse as he did not think I have luteal phase defect. I argued with him about this but he was adamant. (I agree with you that I do have LPD) Just so you know my consultant has the best success rate in the country for IUI !My consultant was monitoring me with ultrasounds to check the size of the follicles and at my next scan I had 4 follicles he usually aims for 2 (The rules are different in England regarding multiple births, I had also been injecting a higher dose of puregon than the consultant recommended) He advised me to cancel the IUI as the risk of multiples was too high and told me to use contraception. Against his will I took my pregnyl trigger shot that night and had sex. I also purchased Pro-Gest progesterone cream (on the internet as it is not readily available in England without a prescription, is the cream as effective as pessaries?) and used it a couple of days after the trigger shot.Imagine my surprise and delight when I became pregnant!! Unfortunately at 9 weeks I had a missed miscarriage leaving myself and my partner devastated, I took pills at the hospital to expel the foetus rather than have a D&C.

I now have a dilemma as I can stay with the Consultant. I currently have another 4 cycles of IUI for free or I can go to a new clinic and receive 1 cycle of IVF free on the NHS. I realise that its great I can have this free treatment but there are drawbacks in that you cannot choose your doctor, you have to go to the clinic that your GP refers you to and each time you visit the clinic you may see a different doctor.

So in your opinion what is my best chance of getting pregnant? I am 40 in December 2010 and time is running out should I take the 4 rounds of IUI using higher doses and progesterone cream (as at least now I know I can get pregnant) or is the 1 round of IVF with a new consultant my best option?Which ever option I choose if it doesn’t work I will find the money to have at least 1 round of IVF at a private clinic even if I have to put it on my credit card then possibly look at donor eggs.Im sorry this is so long and hope it makes sense. Thanks very much in advance. L. from England

Follow-Up Answer:

Hello L.,

I presume that your consultant does not do IVF and therefore is not a fertility subspecialist? In any case, you have proven that you can get pregnant by natural means, so indeed you have a dilemma. Let me see if I can help you sort it out but ultimately, you will have to make the decision. Your age is a significant factor. Your natural chances of pregnancy is only about 10% per year of trying, or less than 1% per month. With IUI it is only slightly higher than that. This is mainly because (1) your body has to go through the entire natural process to become pregnant (there are 9 steps) and it does not do this perfectly every time, and (2) you have an age related quality of egg issue, I call "age related egg factor", that diminishes your chances as well. The probably cause of your miscarriage was an abnormal embryo. IUI will not help that.

IVF, on the other hand, has a much higher pregnancy rate than IUI because (1) it is not a natural process and does not necessarily rely on the body to do each of the steps except for the last two steps: embryo extrusion from the shell and implantation. For this reason, your chances of pregnancy with IVF runs about 40-65% per month in the U.S. (it is 68% in my program). This also reduces the chances of miscarriage because more eggs are recruited, giving a higher chance of finding a healthy normal embryo. There is still a miscarriage risk but as you can imagine, that risk is reduced. In addition, because you have gotten pregnant previously, you have shown that implantation can occur and all you need is a good healthy embryo. So, in my clinic I would advise you to do IVF, but with the caveat that it may take more than one attempt (remember the last two steps are still "natural" steps that we cannot control.

Certainly if you attempt the several IUI tries, for which your consultant has not been very cooperative mind you, you could get pregnant but I would be prepared for more miscarriages. In addition, at your age, I would try for 5 ovulatory sized eggs to increase your chances. The chances of a multiple are slim at your age. But I think IVF will give you a better chance, ultimately.In terms of donor eggs, I would not consider than unless you fail several IVF attempts (3-4), or you reach 43 years old, whichever comes first. You can do donor eggs at almost any age so time is not critical.

Most Recent Answer:

Hello L. from England,

Thank you so much for inserting your previous questions. As you probably can surmise, I get lots of questions and can't remember everyone.

I still think that you have a chance for pregnancy with your own eggs. I know that financial issues preclude that, but I am not convinced that you need donor eggs yet. That being said, if I were you I would find a different clinic. Go out of country if you have to. Your clinic is NOT giving you the best chances. 300IU of Menopur is an inadequate stimulation dose in your case. I am also concerned about your down regulation. I have not seen anyone need 5 weeks of down regulation. I would certainly do things differently.

First of all, my highest protocol is 450IU of Follistim and 150IU of Menopur, which is the highest protocol used in the U.S. Again the goal is to get the maximum stimulation so that we can retrieve the maximum number of eggs. That is the only way to overcome the "age factor."

Secondly, I NEVER cancel cycles even if I have only one follicle. That is because I have had many cycles with only one follicle, resulting in one egg retrieved and one embryo transferred, AND it may be the perfect egg that you just wasted.

Thirdly, we will allow directed donors (donors that you find and use) as long as they are over 18 years old (legal age).

Remember, as I mentioned before, you can do donor eggs at almost any age. So time is not an issue, whereas, it is an issue using your own eggs because of your age. What I mean by that is if you fail with an IVF cycle or two using your own eggs (in a good clinic), then you can save up your money for a year or two then do donor eggs. Of course if you don't want to wait and want the maximum chance of getting pregnant quickly, then donor eggs would be the way to go, and I would go elsewhere. I feel for you and hope that all goes well.

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.

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.

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

33 Yr. Old Low Responder Trying For A 5th IVF Cycle, One Stillbirth But Not Ready For Donor Eggs Yet

Question:

Dear Dr. Ramirez:

I've just recently gone through my 5th IVF Cycle. Yesterday at retrieval they got 11 eggs but said that 6 of them were empty. The embryologist called today to say that none of the eggs fertilized and they are not sure what is going on. To give you a brief synopsis of my history:I'm 33, my husband is 46. We have been together for 6+ years. I was first diagnosed with blocked tubes back in 2005. I had bilateral tubal repair which successfully opened both tubes. Since I did not get pregnant we moved to IUI, which most of those got cancelled due to relationship difficulties. In 2008 I had a chemical pregnancy using donor sperm. My RE didn't count it because my AF started the next day after the beta. We then found out that my husband had a low sperm count. He was not tested prior to this because he has a child from a previous relationship years ago.

We did our first IVF in May 2008 with the transfer of 3 day 3 embryos. I conceived on this first attempt. However, my son was stillborn when I was 25 weeks along. We don't know the reason why because an autopsy was not performed. All I know is that I had an amnio at about 19 weeks and things were never quite the same after that. After meeting with my RE a month later he said we could try again soon because I have a high FSH which normally measures around 10 or so. The last two cycles my FSH was 9.9 and 8.8. We have done 4 IVF cycles in 2009 and all have failed.

1/09--bcp for 1 week, lupron, follistim 450, and menopur 150. 5 Eggs retrieved, 3 fertilized only one made it to day 3 transfer. Result=BFN3/09--same protocal as above, retrieved around the same amount of eggs but none fertilized.

4/09--bcp, follistim 450, menopur 150, and ganirelix towards the end of stimulation. 7 eggs retrieved, 5 were mature, 4 fertilized, and 2 made it to day 5 transfer. My RE said the day 5 transfer was of morulas (by day 5 they should be blastocyst so they were lagging behind in thier development). Result=BFN. My RE did a hysterosonogram and indicated that my uterus looks fine.

6/09--At this point we've decided to go for a 5th try, although it is now out of pocket as I've maxed out on insurance benefits for IVF. This time around my RE starts me on stimulation day 2 of my cycle with 450 follistim, and 150 menopur. No suppression. I produced more follicles than in my previous cycles. What puzzles me is that as of last Friday I had 16 follicles measuring between 14mm - 18mm and a few that were below 12mm and a few that were less than 10mm. When they did the retrieval yesterday I was a bit surprised that they only got 11 and then more than half of those were empty. The trigger shot I take is two shots of Ovidrel, one on each side. The first cycle when I got pregnant the trigger I took was Novidrel in the butt.

During all of this, after I lost my son with the stillbirth last year, the only person that did any thorough testing on me was my hematologist to find a clue as to what happened. In May 2009 he did an entire work up and discovered I had a Protein S deficiency and something else that may cause my blood to clot along with a positive PPA which he indicated could cause congestive heart failure in a fetus. His recommendation to my RE was that I should be on 81mg of baby aspirin daily and once I conceive I should be placed on Lovenox. Of course this didn't seem like a big deal of concern to my RE. His take is lets get you pregnant first.

My question is, given what I've described above, is there any change in protocol that would be recommended? I'm 33 and not ready for donor eggs but can't afford the cost of more failed cycles. Are there questions I should be asking my RE that I'm not focusing on?

Answer:

Hello,

Boy, you have gone through quite an ordeal, and I'm sorry to hear it. At least you know that you can get pregnant. Despite the fact that you are a poor responder (high FSH), your chances should still be good at your age. I am very surprised that it has failed so many times.

The stimulation protocol that you used recently (Follistim 450/Menopur 150) is my highest protocol as well. I use ganerelix (GnRH antagonist) for 1-3 days prior to retrieval to prevent spontaneous ovulation. I also use Ovidrel to trigger (only 1 shot however). Your stimulation was very good. I am very shocked that there were "empty" eggs. I presumed that meant empty cumulus, not eggs. That is something that we usually only see in Older patients (over 40). That is highly suspicious.

My protocol for patients that fail two IVF cycle is to add the following:

1. Aspirin 81 mg daily beginning at the start of the cycle continue through the pregnancy.

2. Low Dose heparin 2000 units twice per day or Lovenox 30 mg per day starting at the beginning of the cycle. Continue until 10 weeks pregnancy.

3. Medrol 16 mg per day until embryo transfer then decrease to 8 mg per day until the pregnancy test then stop.

4. Both injectable progesterone 50 mg per day beginning after the retrieval and vaginal Endometrin 100 mg vaginally twice per day beginning after the transfer.

I NEVER take low responder patients to blastocyst. I do not believe the blastocyst culturing is perfected and there is still a high embryo loss rate. I only take high responder young patients to blastocyst to decrease the number of embryos to choose from. In most cases, I transfer at day 3.

I don't know if your RE will accept some of these things because they are not well established in studies. But when my patients fail, I pull out all the plugs. The medications are not harmful or dangerous and can only help. The aspirin, heparin and medrol help to decrease the immune response AND decrease the micro clot formation in the early blood vessels going to the implantation site.

Despite all the IVF cycles you have done, at your age I would still want you to continue to try, but certainly donor eggs would be the next option. If you have implantation failure, however, and don't use the above protocol, then even donor eggs might fail. One other option would be to consider trying a different clinic because success rates are highly variable among clinics and doctors within a clinic.

I hope this helps,

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