Ovulation Induction With Follistim Keeps Failing & Estradiol Remains Low


Question:

We are currently TTC our 2nd baby. My daughter who is 2 was conceived on our second cycle of follistim75iu. We are currently on our 4th cycle of Follistim 75iu. Each cycle I'm told my estradiol is low and they end up increasing my dose of Follistim to 150 iu and even by the time I trigger it's still on the low side.

I understand that ideally estradiol should be 200-250per mature follicle. But this cycle it is 110 with follicle sizes of a 14 and a11. So at this point of my cycle what should it be since they are not mature follicles? Also last cycle they had me do hcg booster shots after ovulation because I had a low estradiol (it was 80) 7 days after ovulation the cycle prior. The boosters helped increase my estradiol to 354. My concern is do the boosters really help achieve pregnancy or are they just masking a bigger problem?? Thanks in advance, S. from Pennsylvania, U.S.A.

Answer:

Hello S. from the U.S. (Pennsylvania),

There is no fixed protocol when using gonadotropins such as Follistim. Basically, these medications are the hormone FSH which is the hormone that your brain produces to stimulate the ovary to produce a mature follicle for ovulation. If the amount of hormone is insufficient to do this, then it has to be increased and this is usually done on an incremental basis.

For example, it may be started at 75IU but every three to four days, and estradiol level can be drawn and checked to see if it is increasing. If it is increasing then starting on cycle day #9, an ultrasound is done to evaluate the ovaries and see how many follicles are present, what their sizes are and when to trigger. In your case it sounds like that is not being done. For some reason, your doctor is fixated on keeping the same dosage. I'm not sure I understand why.

You are correct about the estradiol level of a mature follicle. If your follicle does not reach the mature size18-20 mms, then the estradiol level will not reach the appropriate size either. Basically the follicle increases in size by increasing the number of cells. Think of it as a chain of cells in a circle. These cells to increase in size, rather, more cells are added to the chain and each cell produces some estradiol. That is why as the follicle increases, more estradiol is emitted. In order for the follicles to grow more cells, increasing amounts of FSH is required. So, if your doctor stops the dosage at 150IU and it is not enough FSH to stimulate follicular growth, then nothing will happen. He needs to keep increasing the dosage until the follicle grows appropriately. Once the follicle reaches the ovulatory size of 18-24 mms, then ovulation can be triggered with HCG (a substitute for the LH surge you would produce in a natural cycle).

The "HCG booster shots" do nothing to help the estradiol rise. Rather, this was merely a coincidence. The growing follicle causes the increased estradiol. The HCG can be used after ovulation to help prime the enodmetrial lining for ovulation. Some clinics use this instead of progesterone. It is also used to trigger ovulation, as I've mentioned previously.

Based on the information you have given me, I'm wondering if you are seeing the right doctor. Your doctor may be comfortable with using Follistim, but is he really an infertility specialist i.e. have a thorough knowledge of the gonadotropins to use them for IVF (in vitro fertilization) if he has to? There are many Ob/Gyn docs that feel comfortable with ovulation induction and use gonadotropins like Follistim on a protocol basis, but in reality, don't know what they are doing. Could you be in that type of situation? Maybe it is time for a second opinion. The best way to find an infertility specialist is to simply ask the clinic or doctor, "Do you do IVF?".

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/
Monterey, California, U.S.A.

Jamaican Woman Doing 1st IVF Confused About Meds: Possible PCOS Misdiagnosis



Question:

I am about to do my first ivf with a clinic and I got a lsit of medications that I will have to use/purchase. I am a litte uncertain about one of them - menopur. The list has over 40 vials of 75iu. I am certain that this is a mistake.

I will of course be asking the clinic but I wanted to be certain. I have had two iui - failed previously. one on clomid with three follicles gretaer than 10mm and one with menopur 150 with about 4 or 5 follicles. This is why I am uncertain about the quantity of menopur on the list.This medication represents the most expensive item on the list and I wouldn't want to order this many at once.

Again, I will be clarifying but I needed additional research/opinion. I have pcos and was diagnosed with endo, had a laporoscopy, ovarian drilling, suppression after lap etc etc

Thank you. KL from Jamaica

Answer:

Hello KL from Jamaica,

I cannot tell you if this is the right dose or not because it depends on the protocol your doctor has you on. But I can make the following comments:

1. PCOS patients tend to be very sensitive to medication and therefore require less medication to stimulate. For that reason alone, I would be skeptical, as you are, of the amount of medication ordered.

2. Menopur is NOT a good medication for PCO patients (if that is a correct diagnosis) because PCO patients already tend to have an increase LH level and the additional LH in Menopur is not needed and will lead to the risk of ovarian hyperstimulation syndrome (OHSS). I will usually either use only Follistim or will use a very low dose of Menopur less than or equal to 75IU. However, given that you only had 4-5 follicles with Menopur 150IU before, I wonder if maybe the PCO diagnosis is not correct?

You definitely need to ask your doctor regarding these concerns.

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.

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.

Diminished Ovarian Reserve, First Time IVF: Low Estradiol (E2) Levels During IVF Stim Cycle


Question:

K. from NYC:

So, I took your advice and immediately wasted no time, and moved directly to IVF (in vitro fertilization). Dx: DOR (diminished ovarian reserve) @ age 35, one previous live birth 2 years ago, natural conception, (baby came from left ovary) after 12 months of trying @ 32 years old.

My recent HSG showed tubes open, but right tube slightly dilated. RE said not to worry about it at this time, as it was only slightly dictated and still spilling. Always have right ovary pain w/ ovulation, never left. I had b/w done on day 3 of my cycle before my ivf. FSH 10.4, e2 45, AFC 10, AMH 0.87. I started bcp's (birth control pills) for 21 days prior to stims. My AFC (antral follicle count) dropped to 6! ugg. For the last year i monitored my cycles very closely. 26 day cycles when i had ovulation pain on my right ovary, and 30 days when I had no pain from my left ovary. In my humble opinion I don't think my right ovary functions like it should.

Last month was my left ovary's turn, the month I had an AFC of 10 (6 antrals in left and 4 in right). This month it is my right ovary's turn and I only have 3 AFC in each #small too!~bcp's?. I also ovulate on cd 18 with my right ovary and cd 16 with my left, not sure if that is relevant.

My stims are NOT going well. I am on 300 follistim and 150 Menopur, I took no meds between ending BCP's and starting Follistim/Menopur 3 days later. On my the morning after my day 3 stims my e2 was a whopping 32.5! My clinic said to continue on my meds, no changes. Come back in 3 days for b/w and u/s. Per the nurse, "some people take a little time to get going". My questions are: why didn't they increase my meds? Did they expect a low e2 because I am DOR? Could this be over suppression with bcp's? Since I normally ovulate later in my cycle and not earlier like most DOR, could this just be my norm~my body taking it's time to develop the eggs? My cd3 e2 have always been between 30-45, I thought that was good for stimming? Could this be due to decrease blood flow to ovaries? I was told to stop my fish oil/baby asa/vitamin e before stims b/c they are blood thinners, but i thought these could help during stims?

This is my first IVF. Do you think they are just riding this out to see how I stimulate for next time? I am waiting for RE to call me back, but I want all the opinions I can get.

ANSWER:

Hello K. from New York.,

If I am understanding you correctly, your CD#3 E2 with this cycle was 32.5. That would be your baseline E2 for this cycle and does not necessarily indicate that you are not stimulating. The first estradiol level to check for stimulate would be four to five days after starting the stimulation (Follistim/Menopur) and you would be monitored approximately every three days after that to determine your progress. It is at the second E2 that you doctor might adjust your protocol and increase it if their protocol is not already at the highest. Some clinics use 450IU of medication (300IU Follistim/150IU Menopur) as their highest protocol. I go a little higher with 450IU of Follistim and 150IU Menopur. Because of your decreased ovarian reserve, it is expected that your ovaries will probably not stimulate strongly, but you will have to wait and see how things go. The goal is to have a peak E2 of around 2000 (when the follicles are ready to trigger).

I use low dose aspirin in all my IVF cycles, but not the Vit E or Fish oil. There is no problem with that.

It is certainly difficult to know how a person is going to respond in the first IVF cycle. There is a little guess work in determining how much medication to use with each patient. Your doctor has probably chosen this protocol as a good place to start and may make adjustments henceforth. You'll have to be patient and wait and see how things turn out. You may want to ask your doctor if you are on their highest protocol.

Follow-Up Question:

I never asked what my baseline e2 was, but the 32.5 was after 3 nights of stimulation. I had an u/s today (after 6 nights of meds) and NO CHANGE to baseline u/s, 6 unmeasurable follies. Waiting on new e2, but suspect it is going to be the same. I feel like I was completely suppressed. My cycle prior to this my CD3 u/s showed 10 juicy follicles, 6 in left and 4 in right. I know that this is a low count but I can't help to think that if i started my stims on that cycle I would have produced some eggs.

I am sure I will be cancelled on Monday. I hope my ovarian function returns. When they call w/ my e2's from this AM and if they don't increase my dose, I will ask why. I was told not to take any blood thinners (and listed: ASA, VitE, Foil due to risk of bleeding w/ ER.) When I suggested not using BCP's next time if needed they said ok, switch to Lupron, but wouldn't that suppress me too? Why can't we just start meds on CD3?? Thank you so much for your time!

Follow-Up Answer:

Hello Again,

Thanks for the clarification. The E2 on the third day of stimulation is called the CD#5 E2 level. It is the first check to see how you are stimulating, and you are correct, it shows that you are not stimulating at all. I don't do an ultrasound on that day because it is too early and the follicle sizes will still be small. The next check is usually done on CD#9 and an ultrasound is done with that visit. If you were in my clinic and the E2 were only 32 on CD#5, I would have increased your Follistim to 450IU. That is my maximum protocol (450IU Follistim/150IU Menopur). Then we would see how it goes from there. However, you have to understand that every clinic and every doctor is trained differently and uses different protocols. No protocol is better than any other. Your doctor's max protocol may only be 300/150. So you'll have to ask.

In terms of your decreased response, I don't think that it is due to the birth control pill, but there are some studies that show a decreased response if not enough days are given after the last pill and the start of stimulation. Basically, not enough time is given for it to leave your system.

In DOR (diminished ovarian reserve) patients I will usually want 6-7 days off the pill before starting stimulation. Again, you are correct that Lupron would also suppress the ovaries (this is known as the long protocol), and in fact, it will suppress the ovaries stronger than the birth control pill. I don't think that is any better.

The non-pill cycle that you are referring to is following the IVF cycle after a natural cycle. There are some clinics that do that but scheduling and making sure everything is suppressed appropriately, stimulated appropriately and timed appropriately is harder after a natural cycle. Some older studies also showed a better response if the ovary has been suppressed with the birth control pill for at least three weeks in the preceeding cycle. I always precede a cycle with birth control pills. That allows me to control the ovarian response. Decreased ovarian reserve or DOR basically means that your ovaries will not respond well to stimulation. That is to be expected. But, you should have had at least one follicle developing and that may mean that you are not being stimulated hard enough.

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.

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.

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

Follow Up Question From 30 Yr Old Austrian Who Failed 5 IVF Cycles & Is Trying Once Again


This is a follow-up question from a young woman with possible PCOS in Austria, who first wrote me in March. Please view the first two questions she posed in order to fully understand the problems she and her husband face. See the March 18th blog post: http://bit.ly/cqXqAp

QUESTION:

Dear Dr. Ramirez,

I had asked you a couple of questions two months ago, and thought of you now as we are preparing to do another IVF. I copy below what you suggested in terms of protocol for me (PCO-like stimulator), since I discussed it with my doctor and he is not sure that this kind of protocol can be done with the medicines available in Austria. You said:"Patients start at a low dose of Follistim 150IU for three days then the estradiol level is checked for response. If there is not a high response then I step up the dosage to Follistim 150IU + Menopur 75. We continue the same pattern of checking and adjusting the dosage as needed. I don't use Lupron agonist suppression (long protocol), but instead use the Antagonist Ganerelix. When the follicles are appropriate sized, I trigger with Lupron 0.5 mg instead of Ovidrel. These combination and protocol has been shown to be effective in preventing hyperstimulation syndrome"

The protocol he gave me last time (Dec. 2009) (starting on day 3 of cycle) was:Day 3-5 Gonal-f (150IU)Day 6 Gonal-f (112 IU)Day 7 Gonal-f (112 IU) + Cetrotide (one shot 0,25 mg)Day 8 Cetrotide (0,25mg) + Pergoveris shotDay 9 Cetrotide (0,25 mg) + Pergoveris shotDay 10 Cetrotide (0,25 mg) + Pergoveris shotDay 11 Cetrotide (0,25 mg) + Pergoveris shot Triggering with OvitrelleEven though this protocol was substantially reduced in quantity of medication, I still had 15 eggs and mild-hyperstimulation (enough for being 3-4 days uncomfortable to breathe and in pain and swollen all around).

The doctor is now proposing a similar protocol to this, but reducing from 150 IU to 112 IU to start and see what happens. I showed him your suggestion and he was receptive but I don't know if the medicines you suggested can't be found here or if what he is suggesting is similar to what you suggested. We are thinking of not having a treatment here anymore and moving onto a treatment in the States. In an ultrasound on day 19 of my cycle, he saw that I had ovulated recently and noted that I have/had around 15 follicles (or left overs of follicles) in my two ovaries. I was really shocked since I have been medication free for 6 months, so I didn't expect that's normal to have so many follicles on a natural cycle, he said that could mean I have a high ovarian reserve and could be a sign of why I hyperstimulate every time no matter what medicine they have given me.

My questions:

Is the protocol he proposes similar to what you wrote above?
What do you think about this empty follicles in my ovaries now?

Also, he has me taking Thyrex for my thyroid (one pill of 50 mg per day) since I started treatment with him over 10 months ago because my TSH level was over 4, and he wants to keep it at around 1, but am I supposed to take this pill forever? for Hypothyroidism? That's what he said, that until I achieve a pregnancy and give birth, I should be taking that pill.

Another question: What do you think about that? My TSH has been at around 1 since i started taking the pill. Regarding my husband's sperm (CF gene), they have been using his frozen samples for all treatments, saying that the freezing and thawing act as natural selection, whatever survives is better for ICSI than trying with fresh sperm. Do you think is better to use fresh sperm for ICSI? or frozen?

Finally, we are thinking of going to a US clinic because in Austria PGD is prohibited, and for us they have been doing polar biopsy of my eggs to only transfer the embryos which fertilized with the better eggs, but as you noted in your previous emails, the embryos should be checked as well to eliminate any effect by my husband's sperm...correct?

So thank you so much for your answers, we are about to cancel the cycle here which starts in one week and move on to make an appointment in the States with you or another clinic which can take us.

Receive my warm regards, L. from Austria


Answer:

Hello Again,

I am happy, yet surprised to hear that your doctor was receptive to my suggestions. I do not dispense recommendations with the expectation that patients will share it with their Physicians. It is mainly for patient knowledge. I do not mean to intrude on that doctor-patient relationship, nor your doctor's judgement, since they usually know you better, and many doctors will be offended.

The medications Gonal-f and Follistim are the same, but made by different companies. Cetrotide is the same as Ganerelix. Gonal-f and Cetrotide are made by Serono, whereas, Follistim and Ganerelix are made by Organon. They are interchangeable. Based on the protocol you showed me, you were already on a pretty low dose protocol. Since, despite this, you hyperstimulated, I would reduce the dose further to a starting dose of 75IU or 37IU Gonal-f. I would probably fight the inclination to increase the dose above this because you seem pretty sensitive and 75IU may be all that you need to get an adequate number of mature eggs.

The Pergoveris is the same as Menopur (FSH/LH). If it is added, as your doctor did previously, he might want to reduce the dose to 37.5 IU (half-dose), but it isn't absolutely necessary. Some studies have shown decreased hyperstimulation in PCO patients when the FSH/LH is left off because PCO patients tend to have an elevation in LH production.

Once your lead follicles reach 15 mms (at least 20% of the follicles), Cetrotide should be started at 0.25 mg per day and continued until the trigger shot. The Gonal-f may need to be increased because of this ovarian suppression, and you should expect a decrease/drop in the estradiol level initially because some of the smaller follicles will stop developing due to the suppression and stop producing estradiol. That is okay and the cycle should be continued (this is contradictory to current thought, where if the estradiol drops the cycle is usually cancelled).

The trigger should NOT be HCG or Ovidrel. Instead, Lupron 0.5mg (50 mcg) should be used subcutaneously as the trigger. This has been shown, in European studies, to be just as effective as HCG but because of a shorter 1/2 life (the amount of time the drug is in your system), there is a decreased incidence of hyperstimulation.

In addition, to the above, I will also sometimes use "drifting/coasting" if it looks like the estradiol level will go above 4000 before the lead follicles are at a mature size. This requires that the doctor predict the levels on a daily basis and the drift/coast is not started until the lead follicles are at least 16 mms. You doctor should understand what this technique is. But, just in case he is not familiar with it, it is where the stimulationn with Gonal-f and/or FSH/LH is stopped but the ultrasound surveillance continues until the lead follicles reach 18-24 mms, then the trigger is given.

Finally, your doctor is correct that the TSH (thyroid hormone) levels have to be in the normal range, otherwise this can have an adverse effect on your pregnancy chances. As I said previously, PGD is the only way to rule out your husband's CF gene from the embryo, as egg polar body biopsy only evaluates the egg (your genes), and frozen sperm is just as good as fresh sperm. I am flattered that you would consider us for a second opinion, thank you. If you do decide to come to the U.S. I would certainly enjoy meeting you and your husband and be assured that our center would do anything that it can to accommodate you and help you succeed.

In closing, tell you doctor that I have had patients where I even start the Gonal-f/Follistim at 37.5IU and step up to 75 or 150IU, so he might want to consider that in you since you are so sensitive.

The very best of 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.

38 Year Old TTC’r With Factor V Lieden, MTHFR, High BMI, High FSH & Good Embryos Has Done 3 IVF Cycles: I’d Throw In The Kitchen Sink!


Question:

I am a 38 yo female in the Northeast US. I started menstruating when I was 10 yo and due to irregular (too frequent) and heavy periods, went on BCP's at age 15 thru 35 - after stopping BCP's, my periods are very regular. We started TTC 3 years ago, and after no success, initial tests showed my H had good sperm count but low motility. We started w/ an RE in Jan 09. For me, my problem areas are age, high BMI, hypothyroid (well controlled) and + for MTHFR (Methylenetetrahydrofolate reductase) & Factor 5 Leiden. No PCOS, no endometriosis, tubes are open, endometrial lining develops well, FSH 9.

We were advised to go right to IVF to increase our chances of conception. IVF#1 5/09 Lupron/Gonal F protocol - 13 retrieved, 7 fertilized, 3 day transfer of 3 embryos - all Grade 2 (8, 7, 6 cells), resulted in pregnancy that ended in m/c at 8 weeks due to triploidy. IVF#2 8/09 Lupron Flare protocol - 13 retrieved, 2 fertilized, 3 day transfer of 2 embryos - Grade 2 (6 & 5 cell) BFN. Dec 09 - had a d&c and a month of antibiotics & estrace to prepare for IVF. IVF #3 1/10 w/ acupuncture, Lupron/Gonal F/Menopur - 13 retrieved, 5 fertilized, 3 day transfer of 3 embryos - all Grade 1 (8 cells) another BFN. All IVF's had ISCI and last 2 w/Assisted Hatching and no embryos made it to freeze. My E2 levels were consistent for all 3 - always between 1900-2300. My meds are always prenatal vits, folgard, baby asa, and levoxyl (thyroid). Lovenox only during pregnancy. My RE says that my age is the problem & that although I respond well and fertilize well, my eggs are of poor quality and arrest several days after transfer. I have no more covered IVF's, but do have 6 IUI's. His recommendation was to try 4 IUI's and if I do not get pregnant, to move onto other options, like DE (donor eggs).

My questions:

1. Do you agree with this diagnosis? Would it be worth trying another IVF with another RE? I have been very happy w/ my experience w/ this group.

2. I've read about Natural Killer cells & antibodies & immunology treatments - my RE says the studies do not support this type of treatment and this will not help. Do you agree?

3. I've had my first IUI on 3/31 and am awaiting a beta on 4/13. Do you think trying several IUI's is worth it or are the chances of success so low that I am wasting my time?

4. Is moving onto Donor Eggs my best next step?

Thank you so much for taking the time to read and reply. I really enjoy reading your answers on this site. A. from the U.S.A.

Answer:

Hello Alyssa from the U.S.,

1. In reviewing your history, out of three IVF cycles, you were successful with one (the first one), but in each, you stimulated well, had a good number of eggs retrieved and, except for the second cycle, had decent embryos. So that means that your ovaries are functioning well and stimulating well despite your high FSH level, and you seem to make good embryos. Of course, since embryos are rated only based on how they look, we cannot know if they are normal or not. Your first pregnancy was genetically abnormal and that is the "age factor" i.e. poor quality eggs leading to abnormal embryos. It is possible that the embryos in cycles #2 and 3 were genetically abnormal as well and that is the reason they did not implant. So, I agree that egg quality might be the issue, leading to imperfect embryos. That is the hurdle that you need to overcome and is totally based on your age. You may not necessarily need to change doctors, but it just may take more tries to become pregnant, since the majority of your eggs are not good quality and the goal is to get a good one.

However, pregnancy rates do vary by physician and protocols, and that could possibly make a difference. For instance, I do not use the Long (lupron) protocol or flare protocol. I use a combination (Ganerelix (antagonist) + Follistim + Menopur) protocol. That could possibly make a difference in your stimulation and the number of eggs retrieved, thereby increasing the chances of finding a good egg. Also, a lot of it is just luck of the draw, so to speak. Each cycle is unique and has the potential to yield a different outcome.

2. You have a +MTHFR and Factor V Leidin. That puts you at increased risk immunologically. For that reason, low dose aspirin, Medrol, and possibly Heparin or Lovenox, might make a difference and would be a good idea. I automatically place my failed patients on this protocol. My reasoning is that, despite the studies showing no value to this regimen, it is like stress reduction, acupuncture or any number of other adjuncts that have not been clinically proven in that, it doesn't hurt and it might help. The American Society of Reproductive Medicine does not advocate the use of immunological therapies, so your RE is correct. However, if you keep failing multiple times and that is something you want to try, then go for it. Basically I throw the kitchen sink in to try to overcome the failures. So, what's the harm?

3. If your IUI is positive, great. If negative, then you need to understand that you are doing them because you have the benefit and not because it is a better treatment. It is not. It certainly has a chance of working that is better than trying naturally, but that chance is not that good. At 38 yo, the chances are about 7-10% per cycle, which is much less than the 60+% with IVF per cycle. But, that doesn't mean it can't work. The goal would be to make sure that you are ovulating as least three eggs with each cycle. It should preferably be 5. Use injectables if you have to. It is the ovulation of multiple eggs that increases the pregnancy rate with IUI.

4. Donor eggs is certainly an option and an option that you will have until you are 50 years old. It certainly gives you the best chances of success because it eliminates the egg factor and reduces the risk of miscarriage. It's your ace in the pocket. Whether or not to proceed with it at this time is your personal decision. Because your ovaries stimulate well, there is still the opportunity for you to get pregnant with your own eggs. There should still be some good ones left inside. It will just be a matter of time. But, if you would rather not keep trying until you find that good egg, and increase your chances of success in the shortest time, then donor eggs would be the logical option. There was a report in the NY Times about a patient who is now the oldest patient to get pregnant successfully with her own eggs at age 49. She was very persistent and dedicated to being successful, and it took her two years of doing IVF.

I hope this helps, you have the potential to get that one good embryo & it may only be a matter of time and changing up the treatment protocol a bit. I find it heartening that you are willing to stay open to all possibilities, so I know you will succeed!

Good Luck,
Edward J. Ramirez, M.D., FACOG
Executive Medical Director
The Fertility and Gynecology Center
Monterey Bay IVF Program
www.montereybayivf.comMonterey, California, U.S.A.

Confused Canadian IVF Patient Told She Is PCOS & Ovarian Resistant: Not Possible! What Is The Right Approach?


Question:

Hello Dr. Ramirez,

I am a 36 year old woman who has just attempted my first IVF cycle after 5 unsuccessful IUI's. I have been diagnosed with PCOS and ovarian resistance even thought my FSH has always been low on my day 3 blood work. I do not have a regular period and have needed clomid and Puregon injections in order to ovulate for the IUI's.

This past IVF cycle my numbers were as follows: Day 3 - FSH 5.7, Estrogen 112, Progesterone 3.5 and LH 7.6. I commenced 150 of Puregon on Day 3 and continued on Day 4 and 5. On Day 6 my blood work results were: Estrogen 334, Progesterone 3 and LH 4 and I had many follicles at 1.0. I upped my Puregon to 200 for Day 6 and 7. On Day 8 my blood work was Estrogen 717, Progesterone 2.7 and LH 2.7 and none of the follicles were progressing. I went back in on Day 9 for a follow-up ultra sound and there was no change in follicle size. My IVF cycle was cancelled.

My question is what would the IVF protocol be for someone who has a history of ovarian resistance? Would my dosage need to be increased or combined with other medication? I have had a egg reserve blood test done and I apparently have a very high number of eggs for someone my age. I would assume that would be because I do not ovulate on a regular basis. The question then comes down to egg quality. If I do not ovulate, does that compromise egg quality? Any advice or light you can shine on my situation would be very helpful.
B. from Canada

Answer:

Hello B. from Canada,

First of all, having BOTH PCOS and Ovarian resistance does not compute. Ovarian resistance is when the ovaries do not respond well to stimulation. PCOS patients tend to over-respond to stimulation. Somehow, I'm not sure your doctors have it right. You should be one or the other.

You do not have ovarian resistance based on your description of having "many follicles". You were also on a low protocol, probably in anticipation of being a high responder due to PCOS. Based on your estradiol levels, you were progressing well, but your follicles were small as is characteristic of PCOS patients. They tend to stimulate and grow a lot of follicles, which progress more slowly, instead of selecting a few and growing them more rapidly. Keep in mind that 200IU or Puregon is a low dose. My highest protocol is 600IU. I don't know why your doctor canceled your cycle. Maybe he/she felt uncomfortable with number of follicles you had and did not want to risk hyper-stimulation syndrome. Obviously, your doctor is not used to treating PCOS patients. Also, you were only cycle day #8 which is still early in the cycle. Most patients will go to cycle day #12 or 14 before the follicles are ready. Since your estradiol was only 717, you were not at risk for hyper-stimulation syndrome as yet. Patients that develop hyper-stimulation syndrome tend to have estradiol levels over 2000 by cycle day # 9.

Also, you should keep in mind that at 36, you are still young and most of your eggs should still be at good quality. You have a good FSH. Age is not an issue for you yet.

In terms of protocols, I cannot give you a standard protocol because every program and doctor has different protocols and combination of protocols. I prefer to use a "mixed" protocol which combines both FSH and FSH/LH (I use Follistim for FSH and Menopur for FSH/LH). In your case, you just were not stimulated enough, and the doc should have kept going and increasing the dosage, whether you use the single agent protocol like you did or use a mixed protocol.

I hate to say this, but I might suggest that you consider seeking out a different clinic or doctor, because I am leery about how your first cycle went. Again, I don't think you are a "low responder" so you might want to discard that label for yourself. Low responders barely respond to 600IU or more of medication and often the estradiol doesn't get much above 300-400.

Keep trying and 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.