Infertility Specialist Incompetent: Cancelled IVF Cycle Prematurely

Dear Doctor,

I am 40. I had two missed abortions at 37, both in the ninth week after heart beat was felt. Subsequently I did not conceive and my RE suggested IVF. I have regular 29 day cycle.

My Day 3 FSH is normal. My RE put me on Lupron (0.5cc) from day 17. On day 2 of the period, she started with 600IU of HMG and 0.25 cc of Lupron for 3 days (cd 2-4). On reviewing after on CD 5, she said no follicle and no endometrium growth is seen. She continued the medication for two more days and (cd 5, 6) and examined me cd 7 and said that there are no follicles or endometrium and cancelled the cycle.

I stopped all medications and on cd 12, I checked with a local ultra sound center. The Ultrasound specialist said there are about 12 follicles on both ovaries, the largest being 10mm.

I checked my FSH and E2 on the same day and the FSH was 12.76 and the E2 is 58.00.

On Cd 16 I checked again and the Ultrasound specialist informed me that one follicle is 13 mm and others are still small.

Can I do anything at this stage to get a multiple ovulation in this cycle so that I can try naturally in this cycle (Like one or two doses of clomid or letrozole)?

What do you infer from my endometrial thickness of 10mm though my follicle size is only 13mm.

What is your advice for future IVF cycles? Thanking you in anticipation. R. from India

Answer:

Hello R. from India,

It may be too late to rescue this cycle but if you have any Menopur, you could use it but the dosage would need to be significantly reduced to minimize the number of follicles that grow to ovulatory size. Unfortunately, the reality is that the eggs will not continue to grow and mature if it does not receive enough FSH hormone and will proceed to atrophy (wilt). If your natural FSH production kicks in then you might still have one follicle ovulate as you would in a natural cycle. I guess that is what you will have to hope for.

An endometrial lining of 10 mms is adequate and appropriate for implantation. It is also a sign that you have adequate estrogen levels because endometrial growth is dependent on Estrogen. Did your doctor ever check your estrogen levels?

My second piece of advice is for subsequent cycles. Your age is a factor from this point on so I would advise you to find a competent specialist. Your doctor is incompetent and does not know what she is doing so I would dump her (find a new doctor). It is expected, and usually the case, that there will not be much follicular growth by CD#7 of stimulation. Some people take longer,as you have shown. In IVF cycles, you have to continue to follow the Estradiol levels to see if they are rising, which is proof of follicular growth (stimulation), and measure the follicle. Most people do not have ovulatory sized follicles until CD#10-12.

I often wonder, do doctors in India have to train to be specialists? Your doctor cancelled the cycle prematurely and just wasted your money. I would demand a refund!

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.

A Step By Step Guide To The IVF Process: Step Two -- Follicle Growth And Egg Maturation

Dear Readers:

This is the third part in the series I have begun to help answer what In Vitro Fertilization (IVF) is and how it works with my world-wide Blog audience. What you read here is what I also provide my patients with on a daily basis. I plan on going into some detail but in a way that is understandable to the normal (lay) audience, and not the medical or scientific one. I also hope that this will not only clarify what you will go through, but explain why things are done a certain way and what the goals of each step are. I also want to convey that IVF is actually a replacement for some of the “natural” steps required to get pregnant and not some miraculous high tech fertility treatment that gets patients pregnant artificially, as many think it is. It is somewhat of a miracle that we can do as much as we can, but there are still lots of things/steps that we cannot do or influence. I hope this discussion will benefit you. This series will be posted over the next few weeks in installments.

STEP TWO: FOLLICLE GROWTH AND EGG MATURATION

Under the influence of FSH (follicle stimulating hormone), dormant follicles within the ovary start to grow. Measurement of the dormant follicle number is called the “antral follicle count (AFC)” and also measured by the “Anti-Mullerian Hormone (AMH)”. Both these measurements are used to give one an idea of the ovarian capacity to be stimulated, also known as ovarian reserve, similar to the FSH level. They are additional indirect measurements. Many physicians and patients believe that these two measurements actually tell them how many eggs are left within the ovaries, but that is too broad an interpretation. We do not have the technology to know how many eggs are present without doing a careful dissection of the ovaries. So these are indirect measurements that serve to give warning about your fertility. Their only use is to help predict, as much as possible, whether the ovaries will yield many follicles upon the hyperstimulation that occurs with giving increased amounts of FSH.

So the real interpretation of a low AFC or AMH is that there might be a lower number of follicles produced, and consequently less eggs retrieved. As explained previously, these are additional measurements of “ovarian reserve.” They only predict success from a statistical point of view because part of how IVF enhances your chances of fertility is by increasing the number of eggs that are available for fertilization and hence the number of embryos and hence the increased chance of finding the perfect embryo that will lead to a pregnancy as explained in the previous segment. It is a total misunderstanding or misinterpretation to say that a low AFC or low AMH indicates that you are infertile, that your ovaries won’t stimulate or that you won’t have good eggs! Taken together with an elevated FSH, these measurements serve as red flags from a time point of view. It means that you may not have as much time to get pregnant using your own eggs as you might have thought. Since we cannot predict when you will run out of time, time becomes a critical consideration.

Currently, transvaginal ultrasound is used to monitor the follicular growth by simply measuring the follicles. This measurement is usually an average diameter taken from a horizontal and vertical measurement of the follicle and reported in millimeters (mms). As the ovary is stimulated with FSH, some of the follicles will grow. Follicles grow approximately 2 mms per day so there is some predictability of when the follicles will reach the appropriate size for ovulation or retrieval. As the follicle expands, Estradiol hormone is produced in increasing amounts by the growing follicle and so estradiol levels can be monitored to also help determine progress as well. With IVF, the goal is to have 15-20 total follicles and estradiol levels between 2000-4000. Each mature follicle will produce approximately 150-250 of estradiol. In IVF, we want to keep the estradiol level at less than 4000 because if there are more than 20 growing follicles and the estradiol level goes above 4000, there is an increased risk for an illness called “ovarian hyperstimulation syndrome”. That is a whole other topic so it won’t be explained here. Suffice it to say that OHSS has the potential to cause death in its worst form. A competent physician with experience doing IVF will take appropriate precautions to prevent this from occurring.

It is known that the follicle has to reach an average diameter of a minimum of 15 mms for the egg within to be mature. We cannot see the egg because it is microscopic size. Therefore, maturation is assumed by the size of the follicle, as has been shown in early IVF studies. With most IVF clinics, a follicle is deemed to be mature size and appropriate to trigger once it has reached at least 18 mms, but it can be as low as 15 mms based on previous studies. Because the follicles will grow unevenly, meaning there will be some that grow faster and some that grow slower, most physicians will trigger with HCG when the largest 2-4 follicles reach maturity size, or when the highest number are between 15-24 mms. My preference is for the larger follicles to be 20-24 mms which I have decided to use based on my long term experience. I don’t necessarily trigger when the largest ones reach that size but, rather, I want to get as many follicles into the mature stage as I can without losing the larger ones or have too many smaller ones. The problem with smaller sized follicles is the eggs within them will not have had adequate time to mature and so will be unusable. Also, follicles that grow to over 24 mms tend to have eggs that are over-mature and therefore not viable. Once the majority of the follicles reach a size of 20-24 mms, then you are ready for the “trigger” shot. The decision of when to give this shot is determined by the experience of the doctor part of the art of IVF. If given too soon, you may lose eggs because they will not be mature. Too late and you may lose them because they will be over-mature. The goal is to try to get the majority number of mature eggs as possible because only mature eggs will fertilize.

Until the trigger shot is given (or the body goes through an LH surge if allowed to occur naturally) the egg within the follicle does not go through its final phase of maturation, meiosis stage 2. Eggs within the follicle are usually in the “germinal vesicle (GV)” stage. Once stimulation occurs, they then go through meiosis phase 1 (M1) and then are mature at meiosis phase 2 (M2). In the natural reproductive process, the “trigger” occurs under the influence of a hormone called LH (luteinizing hormone) and is known as the LH surge. This is what is being checked when you use an ovulation detector kit. There is a sudden rise in the LH hormone which then signals the ovary to begin the ovulation event.

In IVF, HCG (human chorionic gonadotropin) hormone, which is chemically similar to LH, is substituted for the LH to make the eggs go through their final maturation phase and begin the process of ovulation. There are three sources for this medication:

(1) Urinary HCG extracted from human urine,
(2) Recombitant HCG (synthesized HCG) and
(3) Lupron, another drug that has a similar chemical structure to LH.

Lupron can only be used if you are on an antagonist protocol, with Ganerelix or Cetrotide, and not in a long Lupron protocol. This trigger shot will also cause the ovary to begin the ovulation process but because we don’t want the ovulation to occur, and thereby lose the eggs into the pelvis, the egg retrieval procedure is timed to occur before ovulation will take place. This is usually scheduled for 35-36 hours from the trigger shot.

We will continue this discussion soon with the next installment, "Step Three And Four: Egg Retrieval". Thank you for joining me today!

Edward J. Ramirez, M.D. F.A.C.O.G.
Medical Director, Monterey Bay IVF
Monterey, CA
http://www.montereybayivf.com/

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. Please see how I do ovulation inductions here: "Ovulation Induction".

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.

Kuwaiti Woman Asks: How To Thicken My Endometrium Lining?

Question:

Hi Dr. Ramirez,

I feel am really blessed to find someone very expert and caring like you :)

This is N. from Kuwait, I am very concerned about my endo thickness (was between 6.5 to 7.9 on CD14). On the other hand, I don’t want to take medicine that may harm me. The dr. is giving me Duphaston and Progyluton. The Norgestrel is combined with Estradiol valerate in one pill that comes in medicine call Progyluton (I don’t know if you know it). 11 white tablets each containing Estradiol valerate and 10 light brown tablets to be taken from CD16, each containing Estradiol valerate and Norgestrel). You have said previously that the Norgestrel is not used in the USA to treat endos.

What about the Duphaston which is Dydrogesterone 10 mg- Orally – 2 times a day from CD14? Should I take it Vaginally? Does it hurt? What do you suggest? Should I take natural Progesterone instead of the Duphaston? If yes, would you please give me name of the medicine?

Unfortunately it seems there are not that good doctors over here, they are RE and Gyno. This is the 3rd doc. The 2nd doc believes that clomid will increase the endo because it produces eggs; and she sees endo thickness 7 or 8 mm is not bad!!! Dr. Ramirez, If you don’t mind to give me Online Consultancy and I will PAY for it (I can call). Write me a prescription with what should I take and when and how? For example estrace from CDx to CDx, and then XXX medicine from CDxx. (I can order them online)

I know that it sounds weird, but with the globalization and the existence of internet the behaviors and habits are changing. I will go to the doctor on CD14 (or whenever you think is the best) to do the ultrasound and then will let you know about the size of eggs, endo and so on :)

Thank you!

Answer:

Hello N. from Kuwait,

The Duphaston can be used vaginally. Progesterone is important to help with implantation. I would NOT recommend the Progyluton. It is used from hormone replacement therapy and cycle control. It is not used in infertility because of the Norgestrel. Although the Estradiol component is okay, and necessary to increase the uterine lining, the Norgestrel (progesterone) will compete with the estrogen and keep the lining thin. With this combination women don't usually have periods, which is the reason why it is used for menopausal hormone replacement therapy. In fertility cycles, the first half of the cycle needs to have unopposed estrogen stimulation so that the lining will grow. Then once ovulation occurs, the progesterone is introduced to help the lining convert to a luteal phase lining so that implantation can occur.

Your proposal for an internet consultancy is interesting, I will send you an email. I'll have to think about that one. In terms of your supplementation, I use the following protocol:

1. I use the estrogen patch for estrogen supplementation such as the Climara patch. I use two 0.1 mg Climara patches beginning at the start of the cycle and continuing until the pregnancy test. If it is positive, then I continue it until you are 10 weeks pregnant.

2. For progesterone, I use a product called Endometrin 100 mg vaginal tablets. You place 1 vaginally twice per day beginning on cycle day # 16, or beginning with the HCG injection if you use an HCG trigger for ovulation. You would then continue this until the pregnancy test or 10 weeks gestational age if you get pregnant. Other forms of progesterone that you can use in the same way are Prometrium 100 mg or Crinone/Procheive 8% cream.

If you look up my blog regarding how I do Clomid ovulation inductions, it will give you directions on how I recommend doing Clomid cycles. Normally, as the follicles are stimulated and grow, they produce increasing amounts of estrogen. This then goes to the uterine lining and increases it. The problem with Clomid, however, is the way it works. It blocks estrogen receptors in the reproductive system and tricks the brain into thinking that it is not producing enough estrogen. So the brain responds by increasing the amount of stimulation of the ovary, hence ovulation is stimulated or multiple eggs are stimulated. By blocking the receptors, however, it can cause the uterine lining (endometrium) to no grow sufficiently.

Don't stress too much over all this, please take your time and copy these instructions. Take the time to discuss this thoroughly with your physician and good luck!

Sincerely,

Edward J. Ramirez, M.D., FACOG

Executive Medical Director

The Fertility and Gynecology Center

Monterey Bay IVF Program

http://www.montereybayivf.com/

Monterey, California, U.S.A.

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.

41 Year Old With High FSH, High Estradiol - Can I Still Get Pregnant?

Question:

Dear Dr. Ramirez,

I am forty-one year old professional woman living in OH, and I desperately want another child (I have a 16 year-old and a five year-old that were conceived with no problem at all). Before trying to conceive this time, my dr. ran day 3 FSH and estradiol testing, with an FSH result of 15.9 and an estradiol result of 207.

What does all of this mean for me? I've heard that I should take Clomid to stimulate ovulation, but since Clomid raises the FSH, isn't that counterproductive? How does Femara work? Is there any hope for me without donor eggs?

Thank you so much, M.

Answer:

Hello M. from Ohio,

First of all, thank you for your questions. They have relevancy with a topic which I have addressed lately, which is how to approach infertility at +40 and beyond.

So, how does Femara work? Well, FSH stands for Follicle Stimulating Hormone. It is the hormone that the pituitary (brain) produces to stimulate the ovary to grow and ovulate an egg. Think of the ovary as a ball with lots of holes in it (sort of like a practice golf wiffle ball). Imagine this ball at the end of your blood vessel and the holes let the FSH in. When the FSH reaches the inside, the ovulatory process is stimulated. Now, imagine the same ball with much less holes because over time the holes have blocked off. So now less of the FSH is entering the ball and stays in the blood stream. That is your cycle day# 2 or 3 level. If the ovary is picking up a lot of the fSH, the level is low, but if it is picking up less, the fSH is high. When then level reaches 20, that signifies that the ovary is not picking up the fSH anymore, which is menopause. From a fertility point of view, we want the fSH to be less than 10. When it is higher than 10, that signifies "ovarian resistance", which simply means that if we stimulated the ovary with fSH (fertility medications), the ovary will not respond very well i.e. not increase the number of eggs that it ovulates.

The main purpose of fertility drugs, in someone who is ovulatory, is to increase the number of eggs that are ovulated in order to increase the chances that one egg will find and get into the tube to be fertilized, etc. So if the ovary is "resistant" to being stimulated, then more eggs will not be ovulated or available to be retrieved (as in IVF). When the fSH level is 15 or above, as yours is, that is significant ovarian resistance and very close to menopause. It is very, very unlikely that we would get more than one egg, if any at all, which means that the IVF cycle would be wasted. Here's the catch: That doesn't mean it won't work, after all, it only takes one good egg and one good embryo to become pregnant (and I have had several of these types of patients), but merely that the chances are less. For this reason, many IVF clinics use an fSH of 15 as their cutoff for a patient to use their own egg. However, it is not an absolute and the choice is ultimately yours.

Regarding your question re Clomid/Femara. Clomid and Femara work by stimulating the ovary indirectly. They are both estrogen receptor blockers, and in doing so, trick the brain into thinking that it is not producing enough estrogen (which occurs from the ovulation process in the ovary). As a result, the brain increases the amount of fSH in the blood to stimulate the ovary. As you can see, if you have ovarian resistance already, meaning that the ovary will not pick up more fSH anyways, then using Clomid or Femara will not help. In fact, using high dose injectable fSH won't do much either. Finally, the way that IVF helps with the age factor, what I call the "age related egg factor", is by stimulating the ovary to get lots of eggs out at a time. The assumption is that there are still some good eggs left in the ovary. By taking many, many eggs out at a time, we are hoping that we will have a good egg in that group, and thereby increase the chances of pregnancy. We do not have the technology to make eggs better. If we can't get a lot of eggs out at a time, then then IVF is helping a little more than trying naturally but not by much. I still think that IVF is better, however, than trying naturally because more of the process required to become pregnant is accomplished with IVF, whereas your natural process is less exact.

I have had and have patients will high FSH levels, such as yours, attempting IVF. Again, it is your choice, and my role is to be your advisor, not your parent. Most patients want to try at least once, to convince themselves that they gave their best effort. Also, as I mentioned previously, I have had some successes with only one egg. One can make a good argument for not using fertility stimulation in these cases, since a natural cycle will produce one egg on its own if the ovary is still functioning normally, however, we can't know that until we try, so I still use high dose stimulation. By the way, having such a high estradiol level on cycle day#3 does not make sense. The estradiol should be at its lowest level. Having a high level like that means that something else is producing estrogen, such as a cyst, or that the timing of the test is wrong. Therefore, I would recommend that you repeat the test after another natural cycle.

I know this is a long answer, but I hope it gave you some relevant information.

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.

Follow-up comment: Thank you so much for your honest and clear answer. You did not have to put so much time into answering by question, and I truly appreciate it that my question was important enough to you for you to do so.

44 Yr. Old Has Clomid Challenge Test

Question:

Hi Dr. Ramirez,

I'm 44 yrs. old and recently had a clomiphene citrate challenge test with two ultrasounds. I took 100 mg. of Clomiphene Citrate from days 5-9.

The results are as follows: Before Clomiphene Citrate: FSH 5.5, Estradiol 131, with a baseline vaginal ultrasound showing one follicular at 4.2mm in right ovary(I believe) and endometrial lining 4.39, could not locate left ovary. Then, after taking last cc pill another blood test on 11/14 showing FSH of 27.6 and Estradiol of 90. Then, another ultrasound on 11/16 showing two follicles, 10.0 mm, 10.2 mm, in right ovary and 6mm in left ovary, with endometrial lining of 8.2 mm.

What are my options? Should I pursue taking HCG shots or other fertility drugs using my own eggs? Should I pursue donor eggs? My sister is willing to donate her eggs, she recently had a normal, healthy baby boy 10 months ago and she is 41 years old. Thank you in advance for your answers.

Answer:

Thank you for your question.

The purpose of the Clomid challenge test is to evaluate if the ovaries will respond well to stimulation. The Clomid is used for stimulation. A "positive" test is when there is an elevation of the FSH level on cycle day# 11. This shows that there is significant resistance to stimulation and the ovary will probably not stimulate well. The only way to overcome the "age" factor is to get lots of eggs from the ovary. If only a few eggs are retrieved, then the chances for success decrease significantly. Your ovaries are still working, which means that you can be stimulated to get a few (1-3) eggs, but the chances for pregnancy are not good. I do have patients try this but it is with this clear understanding. Most patients do want to try at least once on their own. As I tell them, there are always exceptions to the rule and you only need one good egg, so from an emotional and psychological point of view, it might be worth the try. Expect the worst, however.

Donor eggs is probably your best chance for pregnancy from a statistical point of view. Although your sister was recently successful, she is not the best donor candidate. IVF pregnancy rates are very dependent on the eggs retrieved. If you are going to use a donor, you want the best eggs that you can get. For that reason, we recommend donors that are under the age of 35 years old. The other problem with older eggs is the risk of genetic abnormalities, such as Down's syndrome. You would have a risk of 1:50 for this syndrome with your sister's eggs. I am sure that both you and she would be crushed if that happened. Therefore, I would recommend that you consider an anonymous donor under the age of 35.

I hope this helps,

Sincerely,

Edward J. Ramirez, M.D., FACOG

Executive Medical Director

The Fertility and Gynecology Center

Monterey Bay IVF Program

www.montereybayivf.com

30 Yr. Old TTC'r With Elevated Estradiol Levels- May Be Physiological Cyst

Question:

I am 30 years old and have been trying to get pregnant for 3 years. I have had 4 cycles of Clomid including 3 cycles of IUI. I ovulate on my own, have regular painless periods, and no apparent endometriosis. HSG shows clear tubes.

Bloodwork done 7 months before shows estradiol, FSH and progesterone within the normal range. My husband who is 32 has low sperm motility (about 47%) and morphology shows 71% abnormal sperm heads. We decided to go ahead with IVF+ICSI and since my RE thought I may not need to supress my ovaries too much, I was on birth control pills for only 2 weeks starting in the luteal phase. For my baseline appointment and bloodwork they discovered that I had elevated levels of estrogen (about 190) so I was called in after 4 days.

I did my second set of bloodwork today (had taken my lupron shot before going in) and my level was 185 which they thought was still high so they have canceled my IVF this month. Since I live in a small town and we have just one RE I have been scheduled for November. I am very disappointed and I wonder what went wrong. Can you please help me understand why the levels went so high.

Answer:

Hello, to answer your question as best I can without being able to evaluate your condition myself, an elevated Estradiol level is an indication of ovarian hormone production. The ovary needs to be down regulated prior to starting the stimulation medications. Usually a persistent elevated Estradiol occurs because there is a persistent cyst present in the ovary.

This cyst is producing the estrogen. If then continued the cycle, you would not stimulate well, and pregnancy would not ensue. I would have cancelled the cycle as well. I'm sorry that you have to wait until November, however.

I presume that your RE put you back on OCP's so technically you would be ready to start the cycle in September.

Follow Up Question:

Thank you so much Dr.Ramirez, however I have not been diagnosed with PCOS and my ovary did not seem to have a cyst during any ultrasounds. I was always told that the ovaries looked great and the lining was great.

Do you think it might have been missed?? :-( I have been reading on the internet and came across an article about how a weak liver can not filter the estrogens. I have had malaria thrice and maybe the meds I took made my liver weak? I have also worked in a research lab and handles a lot of teratogenic material..do you think that might have affected something?

I know I sound paranoid, but it's the first time I have had a test report that was not normal.

Follow Up Answer:

The cyst I was referring to is a physiologic cyst, not the cysts of PCOS. If there was no cyst at the time of your baseline ultrasound, then something is producing estrogen. There are very few things that produce estrogen. It is not from your history of malaria. The liver has to be in failure before it significantly affects the processing of hormones and medications. You would know if you were in liver failure!

Your history of working with teratogenic materials would also have no impact. Something else is producing hormones. You might want to ask your doc what it could be. Hormones can only be produced from hormone producing structures and the ovary is the only structure that produces estrogen. You are not taking estrogen from another source such as medication are you? The only non-ovarian source would be certain types of tumors.

If the estrogen level goes down after your course of birth control pills, then that would rule out any type of tumor. In that case you should be good to go.

Good Luck!

Edward J. Ramirez, M.D.

Executive Medical Director

The Fertility and Gynecology Center

Monterey Bay IVF Program

http://www.montereybayivf.com/

Monterey, California, U.S.A.

Fertility Possible After Chemo and Radio Therapy

Question:
Hi, I am a 29 year old women who suffered 5 years ago colorectal cancer. I went trhough radio/chemo treatment, and I also got my ovaries moved up to avoid direct exposure to radio, I also got a monthy injection to protect my overies from chemo, finally I got surgery with result of a permanent colostomy. I got recently interested in knowing my possibilities of pregnancy, and just made hormonal blood test. That was made on the first day of my menstruation, and results are: LH 7.17 mUI/ml, FSH 12.5 mUI/mL; Beta Estradiol 29.2 pg/mL and prolactina 13.4 ng/mL. I have not gone to my ginecologist yet, but seems like my FSH is a little bit too high. Can anyone give me a glimpse if I am allright?
Cheers, CE from Spain

Answer:

Hello CE from Spain,

Based on your hormone tests, you still have normal ovarian function. That is, you are still ovulatory. However, the FSH level is elevated from a fertility point of view. We generally like the FSH level to be 7 or less. We worry when it reaches 10 or above. This elevated FSH level normally indicates that the ovaries would be resistant to stimulation if IVF were performed. What that means is that even with high dose fertility medications (which is FSH), the ovary may not stimulate well and few eggs would be retrieved. It is also an indication that time is not on your side so if you are going to get pregnant, you should do it soon.

The analogy I use for patients to explain FSH levels is like this: Imagine that the ovary is a ball with lots of holes in it (like a golf practice ball) so that it allows fluid to easily pass through into the center. That fluid is FSH. Now, imagine that more and more of those holes get blocked, so that less and less FSH can get into the middle. That would then leave more and more FSH on the outside (your blood), so that the levels increase. That is basically what is happening.

The other worry I would have with your history is the egg quality. Although precautions were taken to try to preserve the eggs from harm from radiation, chemotherapy can also damage the eggs, so that may be a major deterrent to getting pregnant.

Sincerely,

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

Monterey, California, U.S.A.

check me out on facebook and twitter with me at @montereybayivf

Empty Follicle Syndrome

Question:
Sorry for the long question but I wanted to make sure you had a good picture.....
I am 38 year old and have been trying to get pregnant for a while. I got pregnant using clomid and HCH shot but had a pregnancy lost in 2007 at approx 24 weeks. I did a thrombophilia work up and one of my clotting factors was borderline so the action that I was to go on blood thinners with a next pregnancy. High FSH has been a problem as it peaked at 20.23 during one cycle when I was doing the IUIs. I had to date 3 unsuccessful IUIs and two cancelled IVF due to empty follicles. The first IVF cycle I had two follicles after using Lupron in the beginning and then repronex and gonal F for several days and finished with Novarel HCG shot.
　　
The second attempt my RE did a different approach. I was placed on birth control for one cycle and the next cycle I start with clomid and then repronex and gonal followed by ganirelix and the last norvarel shot before retrieval. Note that my FSH was 8.8 but estradiol was high at about 90 so that made my FSH skewed. I had four follicles (the most I had have) and they were all empty. I was concerned that the shot was given properly but my RE said that does not have anything to do with them being empty. After the miscarriage I was always taking baby aspirin but no heparin.
　
Mentally I am not ready for donor eggs and my husband has flat out said no. I want to exhaust all options before I give up. As you would say, "pull out the full court press". I want to try one more cycle but I have doubts whether I should try again with this RE or try someone else. Can you shed some light on the empty follicle syndrome and if I have a chance? I am so desperate that I am trying acupuncture and herbs while I am on "ovary rest" break.
　
Answer:
Hello Patrice from the U.S.,
　
"Empty follicle" syndrome is a description/name of a condition that is found when no eggs are retrieved from obviously adequate sized follicles. It can occur at any age, but seems to be more prevalent the older one gets. So, a woman in her 40's could still have regular menstrual cycles and ovulation, but no egg will be ovulated so pregnancy does not occur. With IVF, we find this when we go to retrieve and get no eggs back. It is thought that this is the "normal natural condition" in the aging ovary. A woman essentially runs out of eggs. However, that does not seem to be the case in younger woman, since younger women stil have a full complement of eggs. So, "running out of eggs" does not seem to be the whole answer.
　
I have had several cases of empty follicles in both younger and older women. In the younger patients, I have concluded that they did not get adequate HCG stimulation. Previously I had used a generic HCG and worried that it was not produced properly or suffered some type of inactivation in shipping or storage. I therefore switched to Ovidrel. Since then, the incidence of empty follicles has been resolved except in a couple of exceptions. I had two moderately obese young woman have a very poor retrieval despite lots of follicles (both were PCOD patients). By poor retrieval, I mean that there were either no eggs or we only retrieved 1 or 2 eggs despite 25+ follicles. They had given the Ovidrel as instructed, into there belly. In the subsequent cycle, I had then give it in the back of the arm where there was some fatty tissue but much less than the abdomen. They then had good retrievals. This lead me to suspect that HCG stimulation was the problem, and that the increased fatty layer of the abdomen did not allow adequate absorption of the HCG, therefore the eggs did not release to be retrieved.
　
In your case, with an elevated FSH level, your age and poor ovarian stimulation, the problem may actually be a lack of eggs. However, you did not mention your weight so you might want to look at that possibility. In addition, you may not be stimulating well if you are not getting a large enough dosage of medication. For example, I use a total of 600IU of gonadotropins in the combination 450IU of Follistim and 150IU of Menopur. Are you using that much? If you are, then the poor stimulation is because of ovarian resistance as manifest by an elevated FSH level.
　
You certainly have the option of continuing to try with your own eggs if that is your only choice (per your husband) and you can afford continuing to try, AND you doctor agrees to allow you to keep trying. However, based on the cycles you have had, realistically Donor eggs is your best option, and the most cost effective since you would probably get pregnant quickly. Using your own eggs is a long shot.
　
If you don't think that your doctor is giving you an adequate chance, or being aggressive enough, then you certainly can consider changing doctors. The Doctor-Patient relationship is based on TRUST. If you don't have that trust, then you need to move on. If you trust your doctor's abilities then stick it out, albeit, every clinic and doctor have different protocols and treatments for difficult cases so that must be a consideration as well.
　
　
If you were my patient, as I mentioned, I would have you on 450IU follistim/150IU Menopur from the start, Aspirin 81mg per day from the start, Medrol 16mg per day from the start, Heparin 2000U twice per day from the start, Estrogen patches and progesterone from retrieval on and I use Ganerelix once the follicles reach 16 mms, NOT Lupron which will inhibit the ovaries from the start (called the long protocol).

I hope this gives you some information to think about.
　
Sincerely,
　
Edward J. Ramirez, M.D., FACOG
Executive Medical Director
The Fertility and Gynecology Center
Monterey Bay IVF Program
http://www.blogger.com/www.montereybayivf.com