A Step By Step Guide To The IVF Process: Step One -- Stimulation

Dear Readers,

This is the second 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 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 ONE: STIMULATION

As explained in the natural process, the first step in your body is for the hypothalamus and pituitary to send a hormone to the ovary to stimulate the growth of a follicle and maturation of the egg within.

The hypothalamus sends a hormone called GnRH or gonadotropin releasing hormone to the pituitary. This in turn, causes the pituitary to give off follicle stimulating hormone (FSH) and a little luteinizing hormone (LH). For now, I won’t go into detail regarding LH since it is not as important in this stage of the process. The FSH, or follicle stimulating hormone, stimulates the growth of a follicle, hence the name. The ovaries already have all the follicles they are going to have from birth. These follicles are in a dormant state until they are stimulated. In a natural cycle, several follicles are stimulated but only one is designated to grow to ovulation. The FSH goes through the blood stream and makes its way to the ovary. The ovary then picks up this hormone from the blood. It then processes the hormone and a follicle grows causing the production of estradiol and progesterone, and maturing the egg within. The egg is normally in an immature state in the dormant follicle.

In the IVF process, we take over the function of the hypothalamus and pituitary. In fact, we shut down the natural process so that we can control how the process goes and to help with timing. Timing is critical in IVF, as it is in the natural process. Many programs use birth control pills to shut down the ovaries and thereby shut down the hypothalamic-pituitary axis. Some clinics use leuprolide acetate or Lupron, Synarel or a similar drug, to shut down this axis. These drugs are known as GnRH (gonadotropin releasing hormone) agonists which is essentially adding GnRH but the brain monitors the levels of this hormone and if it reaches a certain threshold, shuts down production in the hypothalamus. Using Lupron from the luteal phase of the previous cycle is known as the “long protocol”. Some programs will go into IVF directly from an natural menstrual cycles and this is sometimes called “Natural cycle” IVF.

As I was explaining, in the IVF process we take over this step by giving FSH and LH hormone directly. These are known as injectable fertility drugs, but in actuality are not “fertility” drugs but merely the hormones your body would naturally produce to induce follicle growth in the ovary but at a higher dosage. So in reality, these drugs don’t increase your fertility or make you more fertile, they actually just give you more of an opportunity to become pregnant. Some of the medication used in IVF, such as Gonal-f or Follistim are now recombitant, or genetically produced FSH (in the old days, all FSH used to be natural FSH that was extracted from elderly women’s urine). These medications are pure FSH and have no LH within. There are other medications such as Pergonal, Menopur, Repronex that contain both FSH and LH. These are still derived from urine. Some clinics will use only FSH but most will use a “mixed” protocol, meaning they use both an FSH only drug in combination with an FSH/LH drug taken together.

The amount of medication given is what determines how many follicles your ovaries grow, and is dependent on how aggressive your doctor wants to be, i.e. how many follicles they want to try to get, and how well he/she thinks your ovaries are functioning or going to respond to the stimulation. We call the latter “ovarian reserve”. A younger patient will usually, but not always, have a very good ovarian reserve and therefore require less medication, whereas as a woman ages, her ovaries become more resistant or less likely to pick up the FSH from the blood, i.e. decreased ovarian reserve. Logically you can see that if the ovaries are more responsive, less medication is required and vice versa. The best way to picture this, as I explain to my patients, is to imagine a golf “wuffle” ball. If you don’t know golf, this is a practice ball with lots of holes in it so that it doesn’t fly far. Imagine that all the holes are open and you put the ball in a bowl of fluid (which is the FSH). The wuffle ball readily admits the fluid into its center. Now imagine that you block off most of the holes in the ball. You can see that less fluid gets into the ball (you also have to imagine that you have a time limit as to how long the ball gets to sit in the bowl of fluid). That is ovarian resistance. No matter how much drug you give, the ovary will only pick up as much FSH as it can and thereby only stimulate as well as it is going to stimulate. There is no technology that can change this. That leads to a lower ovarian response to the stimulation, and less follicles and eggs to work with. It is called “ovarian resistance” once stimulation has been attempted and only a few follicles grow. That is different from “ovarian reserve” which is the anticipated ovarian response or ovarian response potential before stimulation. “Ovarian resistance” is what you see once the stimulation is done and the ovary does not stimulate well.

The stimulation step is important because part of the success of IVF is an enhanced statistical chance by having lots of eggs to work with. Take for instance, if you have one dice and you want the number five. You have a 1 in 6 chance with each roll of the dice. Of course, your chances increase with rolling the dice more times, which is a different statistical chance and the statistic that changes as you attempt IVF repetitively. But taking just one roll into consideration, as in one IVF cycle, your chance is 1 in 6. Now, if you add three, four or five dices to that one roll, you can see that you have increased your chances 3, 4 or 5 fold. That is the same with each IVF cycle. In a natural cycle, you give off only one egg, so if that egg doesn’t go through each step perfectly, you don’t get pregnant. IVF increases your chances of pregnancy by accomplishing more of the steps of the process for you, but more importantly, you still need to have a perfect egg that forms a perfect embryo. If you only have one egg, the chances of having a perfect egg are significantly decreased. It increases by having more eggs to work with. That is how IVF increases your chances of pregnancy statistically. So the goal of stimulation is to try to maximize the number of eggs that you have available in order to increase your chances of getting/finding the perfect egg/embryo.

Now there is a caveat to this. You don’t necessarily want too many eggs because over stimulation can not only cause a major illness, but the egg quality may suffer. This is where the “art” of IVF lies. It is up to the doctor to try to make an educated guess as to how much stimulation would be ideal for each patient. Under-stimulate and you decrease the chances. Over-stimulate and you also decrease the chances, as well as, risk making the patient sick. Doctors get better at making this decision through experience. And this is part of what makes each doctor and each clinic different.

We will continue this discussion soon with the next installment, "Step Two: Follicle Growth and Egg Maturation". 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/

31 Year Old With DOR Advised To Keep Trying: Adjust Protocol To "Mixed" FSH & FSH/LH

QUESTION:

Hi Dr Ramirez

I am on my first round of IVF and my day 9 scan showed no follicles on left ovary and 3 tiny follicles on right. I am on 375 menopur which has now been upped to 450. Priot to starting treatment i was on the combined pill for irregular periods. I am 31 years old with FSH level of 6. My question is, can being on the pill interfere with follicles growing and am i on te right meds? When they scanned me prior to starting treatment i had more follicles than when doing IVF which doesn't make sense to me? I am having treatment in London, England.

Thanks, N. from England

ANSWER:

Hello,  N. from England,

With your age and FSH level, I would have expected a much better stimulation response. I think you are not being adequately stimulated. Menopur is not adequate. There needs to be more FSH in my opinion, but keep in mind that each doctor does things differently and one way is not necessarily better than another. If you were my patient, my preference is to use a "mixed" protocol using both FSH (Follistim or Gonal-f) and FSH/LH (Menopur or Repronex). I would have started at 300IU Follistim and 150IU Menopur (450IU total of FSH), then possibly decreased to the dosage you started at. But, that is my personal preference (and of course something that makes each clinic different with different results).

The pill should not and does not interfere with ovarian stimulation. I presume that you are also on a Long lupron protocol? Lupron will suppress the ovaries as well.

I have also been surprised by the lack of stimulation in a younger patient, such as your doctors were pretty surprised. Sometimes it is hard to predict what will happen. If the cycle fails, then I greatly increase the medications in the next cycle. Such a finding is called a "poor responder". But keep two facts in mind:

(1) each cycle is unique and the stimulation results can vary from cycle to cycle. One does not necessarily predict the next.

(2) it only takes one good embryo to be successful.

Good Luck!

Follow-Up Question:

Hi Dr Ramirez,

Thank you so much for your prompt reply. I carried on with the 450 Menopur until day 16 and they decided to cancel the cycle as the one follicle was not responding as they would have liked. The consultant at the IVF clinic told me that my chances of conceiving are zero per cent even with IVF. To say I was shocked was an understatement. I spoke to him about the possibility of a different protocol or different meds but he was adamant that I shouldn't try again. I don't quite know where to go from here. I have been under the care of a gynae at my local hospital for fertility investigations for 5 years and he kept telling me IVF was the answer. I got pregnant with Clomid two years ago but now I am at zero fertility, I mean not even 1% according to the IVF consultant.

My question to you would be, in America do you do things differently? I spoke to him about Gonal F and he said it wouldn't have made a difference. I also said about Synarel and he said it wouldn't have made a difference. I have low ovarian reserve and that is that. He is a highly regarded doctor here in England (Mr Tim Child) so I am sure he wouldn't have said zero if he didn't believe it. I know it's hard for you to give an opinion without knowing my full history, but have you seen seomeone with such a poor first reposne go on to do better second time around or should I just draw a line under it all?

Thank you so much for your guidance on this, as my husband and I are a bit shell-shocked. Over here in the UK we always consider the Americans to be further forward in medicine and cutting-edge treatments. We would be prepared to travel if we thought it was worth it. If only one follicle is growing very slowly under high stimulation, would you be inclined to say zero chance too? I appreciate your honesty.

Kind regards, N.

Follow-up Answer:

I am sorry for all the grief you have had to endure. I am afraid that I don't completely agree with your doctor. First of all 450IU is not the maximum dose of medication. You certainly have "decreased ovarian reserve", which means that your ovaries don't stimulate well, but given your age, I would expect you to have a good chance even with only ONE egg. So I would recommend trying with a higher protocol and even if there are only a few follicles, you should continue the cycle and give it a try. It stands to reason, if the cycle is cancelled you certainly won't get pregnant, so in my opinion if there is a follicle present the patient deserves to give it a chance.
In terms of decreased ovarian reserve, there have been several studies, including one that was just published, that showed that ovarian response will vary even in patients with decreased ovarian reserve. Therefore, it is still recommended to continue trying in a patient with decreased ovarian reserve. The next cycle may be completely different than this one, especially if a different protocol is applied.

In addition, I am a firm believer that there is a difference between a mixed protocol (using FSh + FSH/LH such as is found in Gonal-F or Follistim (pure FSh) and Menopur (FSH/LH). I know that there is no standard protocol and studies contradict each other, but FSH is the hormone that stimulates follicle growth (that is why it is called follicle stimulating hormone)and LH is not. In a normal natural cycle, the LH does not rise until just before ovulation whereas the FSh is rising all of the first half of the cycle.

I would encourage you not to give up.. . at least not yet anyway. It is possible that down the road you might have to resort to using donor eggs, for instance if your ovaries shut down completely (premature menopause/premature ovarian failure) or you have failed several attempts with your own eggs, but until then, hope is not lost, every cycle is a new and different cycle and every egg is a new and different egg; all with their own potential. I will never tell a patient that there is "zero" chance because there are always exceptions to the rule and I also believe in miracles. I've seen them happen many times. If you wish to come to California, I would be pleased to assist you in the best of my abilities.

Good Luck,

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

Third Failed IVF Cycle: New Protocol Needed? Compare SART Stats?

Question:

Dr. Ramirez,

I just had my 3rd failed IVF cycle and I'm looking for some guidance. A little history:

I am 31 have a short luteal phase but PIO and estrace seem to do the trick. Day 3 testing normal. My husband has low morphology.

My 1st IVF attempt I responded very well (long lupron) to low doses of meds. Stimmed for 7 days. They obtained 10 eggs and 9 fertilized with ICSI... all were very good quality on Day 3. Transfered 1 and 5 frozen on Day 3.

2nd IVF attempt- Antagonist Protocol- very slow to respond on highest doses of meds. Didnt have any measureable follicles until Day 10... stimmed for 15 days. Obtained 6 eggs and only 3 fertilized with ICSI. Transfered 2 embryos on day 3. Negative beta 10dp3dt and stopped meds. Discovered 2 weeks later that I was pregnant and miscarried.

3rd IVF attempt- back to Long Lupron- very slow to respond again on highest doses. Stimmed for 15 days- obtained 8 eggs- 4 fertilized and only 2 were viable on Day 3. Beta negative.

Questions:Any thoughts on why I would have such a different response from cycle #1? All 3 cycles were done in 2011.Would you suggest trying a different protocol? Do you think I may be a good canidate for Micro-Flare Protocol?In both 2nd and 3rd cycles my e2 level was 22 and 24 at suppression check compared to 59 in cycle 1. Any insight? Could this mean that I am oversuppressed? Also AFC was lower in past 2 cycles.How much time do you suggest in between fresh cycles?Any thoughts that you would be willing to share would be greatly appreciated. I am getting very discouraged and you have been so helpful in the past. Thank you, D. from Massachusetts

Answer:

Hello D. from the U.S.(Massachusettes),

It is difficult to critique protocols and I generally do not. There are many different ways to accomplish the same thing so any one particular protocol may not be better than another.I do not favor the long protocol, however, for two reasons. I think there is too much ovarian suppression at the beginning of the stimulation and you have to take many more injections. For that reason I use the antagonist protocol, which usually only required 2-3 injections. So, I would not go back to the long protocol. There is not question that the long protocol is the classic method, in fact, most REI's use this protocol because they are not familiar with the antagonist protocol.

In terms of your stimulation, there can be significant differences from one cycle to the next. For example, I have a patient who only produced one follicle in her first cycle with the maximum dosage of medication, yet in the second cycle, with a reduced protocol, she produced 8 follicles. This shows that each cycle is unique and the ovaries will respond differently. You don't mention of these cycles were done back to back i.e. consecutive months, but in general there should be a one month rest period between IVF cycles to allow the ovaries to recover. A stimulation of 12-14 days is not unusual and sometimes preferable. Sometimes a short stimulation phase leads to less quality eggs. Also keep in mind that you were successful in the second cycle, which means that you can be successful again. You have to be persistent. You are lucky that you are in an insurance mandated State for IVF.

I would strongly recommend against the Micro-flare protocol. This has been shown to not be of any benefit.Finally, there are other reasons for failure of an IVF cycle. You are young and had good embryos to transfer. So maybe it was something else? Implantation failure can occur if the transfer technique is not good by the Physician, as an example. Or you may need some additional meds to reduce your immune response or increase blood flow. There are differences between IVF clinics/centers. We are not all the same and therefore pregnancy rates differ.

Follow-Up Question #1:


Thank you so much for your thorough response. I have a few more follow up questions if you do not mind...What are your thoughts on the Estrogen Priming Protocol? Do you usually use a FH and FSH while stimming? I have read that adding Menopur in too soon can effect egg quality. The article that I read suggested adding it in after 4-5 days of stims and then lowering the FSH dosage. Any thoughts on this? My current RE had me starting Menopur on the 2nd day of stims.The past 2 cycles fertilization was only 50% with ICSI compared to 100% my 1st cycle. The embryologist noted that my eggs were "brownish". Any thoughts on this? Do you think it was due to egg quality? Lab issues?You mentioned additional meds to reduce your immune response and increase blood flow... what type of meds do you usually prescibe?How much emphasis do you put on SART scores.

I am contemplating switching clinics and I am looking for some guidance. Mass General has the highest success ratings in my age group but I have heard that they are very focused on scores, etc. I have heard great things about a RE at Boston IVF but there SART scores are lower. Would this be a deciding factor for you?Yes, I agree... I am very lucky to have insurance coverage! Again, I really appreciate your help. This process is so stressful and I am so overwhelmed!

Follow-up Answer #1:

Hello Again,

Let me take your questions sequentially for ease.

1. I don't have any feelings one way or the other regarding estrogen priming. I don't use it because I don't think it has been shown to be of any benefit. By I lack the experience to know for sure.

2. I am a believer in the "mixed protocol" which uses both pure FSH and a combination FSH/LH (my preference is Follistim/Menopur). Many studies have shown benefit to having LH present in the follicular phase. It has been found to increase the egg quality although there is not real technology to determine egg quality. I was trained on this method and my experience has been that the stimulation is better i.e. higher number of follicles. My pregnancy rates are pretty good as well. I don't agree that it will decrease egg quality. That has not been my experience.

3. Brownish or discolored eggs signify a basic egg quality issue. This may be why the fertilization rate was not as good. The minimum fertilization rate should be 50% and will vary from cycle to cycle because the eggs will be different each time. I don't think anyone has any explanation for why the eggs would have a "brownish" or "discolored" appearance.

4. I use low dose aspiring (81mg), Medrol (16 mg) and low dose heparin (2000 units twice per day). These all start with the start of the stimulation and continue through the cycle. The aspirin and heparin are stopped on the day of the trigger injection and not restarted until the day after the retrieval.

5. SART scores are certainly one thing I would look at. The problem with SART scores or the CDC scores is that they only look at one year, not cumulative scores which is more revealing. That's because clinics can have a good year and bad year depending on the types of patients they have, embryology problems, change in personnel, etc. But since these two organizations don't give cumulative statistics, you might have to ask the clinics if they have them. If you are going to use SART scores, then try to look at the last three years and compare. Also the problem with these scores is that they are 2 years behind and IVF technology is ever-changing.

Also, if you are going to look at the SART/CDC stats, the only one you should look at is the implantation and pregnancy rates per cycle and transfer in patients under the age of 35. Don't necessarily look at your specific age group. Those two statistics are the important ones and we use under 35 years old as the gold standard because those are inherently the most fertile patients (ie no age factor). Certainly your age group statistics are also important because you want a clinic that does well with your age group. If I were going to a new area and had no idea which clinic to go to, I would use the SART/CDC statistics to help me decide. Then I would go check them out, ask about their program and see how personal the care is (just like you would if you were buying a car). I don't recommend going to a factory type program. You want a program where you have one doctor attending you through the entire process and don't get a different doc for the transfer, which is one of the most critical steps. Sometimes smaller clinics are better than larger ones because of this, as long as the pregnancy rates are equivalent. Try to get the clinic's current statistics if you can or the most recent ones, and not necessarily the ones from two years ago submitted to SART. Most clinics will have the previous year's stats.


Follow-Up Question #2:

Thank you very much for your response. The info that you provided re: the SART scores is very helpful. I appreciate the tips!!One more follow up question re: the "mixed protocol". Do you usually start the Menopur at the same time as Follistim? Or do you wait a couple of days.Also, would you reccomend that I try any supplements? I have done some reading about DHEA? What are your thoughts?

Follow-Up Answer #2:

Hello Again,

The Menopur (FSH/LH) is started at the same time as the Follistim (FSH). I don't recommend any supplements. There are none, especially DHEA, that have been proven to work but I did see a recent article touting DHEA is older women. They claimed it increased embryo quality, but I am doubtful. That shouldn't be a problem for you because you are young.

Things that I do add in patents that have failed a previous cycle:
1. Acupuncture (it is not proven, but some studies show benefit and it doesn't hurt to try everything after failures.)
2. Low dose aspirin - 81 mg orally per day starting at the beginning of the cycle.
3. Low dose heparin - 2000 units SQ twice per day starting at the beginning of the cycle.
4. Medrol 16 mg orally per day starting at the beginning of the cycle and decrease to 8 mg on the day of transfer (you would stop this at the time of the pregnancy test).
5. Both progesterone injections and progesterone suppositories. I don't start the suppositories until the day after the transfer.

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.

Comment: Dr. Ramirez is always very kind and helpful. I am very thankful for all of his help.

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.

45 Year Old Danish Couple On Sixth IVF Attempt: Should They Alter Meds & Blastocyst Transfer?

Question:

Dear Dr. Ramirez,

We are a 45 year old couple from Denmark on our sixth IVF attempt. The first three attempts produced 5/5/9 eggs with 225-275 units of Gonal-F and a fertility rate of 100%/60%/60% respectively. Eggs for transfer were three 8-cells on try one on day three, two 8-cells and one 10-cell on try two on day three and two morulas and a 10-cell on the third attempt on day five.

We then increased Gonal-F to 375 units and got 12 and 13 eggs in the next two attempts and a fertility level of 85%-100% and decided to go for Blastocysts and had two BC's and a Morula in the fourth attempt on day six and one BC and a Morula transferred the last time on day six. On the recent attempts we've been supplementing with Ovitrelle prior to aspiration (as well as folic acid, acupuncture and considerate food and no alcohol of course). After aspiration a dose of 16mg Medrol was administered for four days, then 8mg and then 4mg, as well as 81mg of Aspirin for the duration.

Our questions are: 1)should we continue to go for Blastocysts for transfer, and 2) do you have any suggestions as to an altered protocol perhaps in terms of increasing the dose or frequency of Medrol or any other meds that might help us?

Thanks in advance for your reply. T. From Denmark

Answer:

Hello T. from Denmark,

The good news is that your wife's ovarian response is still good and strong. She has done very well on her current stimulation protocols. The problem that you have is not so much the external quality of the embryos formed, they have been good, but the internal quality of the embryos. We know that with age, the quality of the eggs and thus the embryo quality deteriorates. That is probably what is leading to your failure. We rarely see pregnancies after the age of 43 in a woman using her own eggs. However, there was a case in New York of a woman who was successful at 49 years old, and is currently the oldest to become pregnant with her own eggs using IVF. It did take her two and 1/2 years of trying, however. Statistically, your chances of pregnancy with IVF are less than 1% per attempt based on age factors alone.

In terms of whether to do D#3 or D#5 transfers, I don't think it makes any difference. One is not better than the other. The embryos that would make it to blastocyst would still have done so in the uterus. In fact, I think the uterus is a better culture environment than the lab. I generally transfer at D#3 for this reason. In fact, in your case if you were my patient, I would transfer ALL embryos back on D#3 to maximize your chances.

In terms of what other protocols, I use Medrol starting at the beginning of the cycle (D#2) taken as 16 mg until the transfer then decreasing to 8 mg thereafter. I stop with the pregnancy test. I also use aspirin 81 mg per day starting at the beginning of the cycle and heparin 2000 units twice per day injections starting at the beginning of the cycle. I also use a "mixed" protocol of Gonal-f or Follistim + Menopur/Repronex for a total FSH dose of 600IU to start. In most cases, the patients stay at that level but some will decrease based on their response. In your case, your wife does not need more meds since she stimulated well, but a mixed protocol might be advised.

Your only option is to keep trying or move to donor. I am amazed that you have done so many cycles already. Most in the U.S. will not do that many cycles due to cost issues.

Good luck with this upcoming cycle & never lose sight of your goal...it can be achieved if you are open to options.

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.