Wednesday, February 29, 2012

Canadian Is Nine Weeks Pregnant, Has Enlarged Yolk Sac And No Fetal Pole: Is There A Problem?


Hi Dr Ramirez,

I was prescribed Clomid this cycle and am now pregnant. I am currently 9 weeks along. I went for an ultrasound at 8 weeks, 1 day pregnant and my measurements indicated that I was 8 weeks, 6 days pregnant. There was no fetal pole found. The yolk sac is measuring 8.6 mm. I am doing HCG/progesterone testing every other day -- so far all levels are within range. I am going for a follow up ultrasound at 10 weeks pregnant. Is the enlarged yolk sac a bad sign, even though my measurements and bloodwork are good?

Thanks, E. from Canada.


Hello E. from Canada,

Assuming that your dates are correct, the yolk sac size is not a problem but the fact that there was no fetal pole or fetal heart motion at 8 weeks is bad. Usually by 6.5 weeks gestational age, a fetal pole and heart beat can be detected. This is seen for sure by 8 weeks. An empty gestational sac is called a "blighted ovum" and basically means that the sac developed but the fetus did not. You should not have to wait until 10 weeks gestational age to make the diagnosis. Your doctor should make that diagnosis already and recommend treatment.

If you wait too long, then a D&C (surgery) would be required to clear the uterus. At an earlier stage it can be done using medication alone. I should not be the one to be the bearer of bad news so I am sorry that this answer is not reassuring. You need to talk with your doctor right away and don't let them put you off or avoid the issue, like they seem to be doing.

Take care and good luck,

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

Thursday, February 23, 2012

40 Yr Old Wonders: Should I Use Donor Eggs After Failing Five IUIs?


Dear Dr. Ramirez,

I would like your opinion on whether I should move on to donor eggs. I am 40 yr and I have 5 failed IUI (intra uterine inseminations), 3 of the IUI was with Menopur injections. The last IUI, my RE (reproductive endocrinologist) prescribed 22 vials where I used 3 vials for 7 days. Each IUI, I have one matured follicle whether its clomid, clomid combo injections or injections only.

One of the IUI resulted in pregnancy but I miscarried at 7 weeks 4 days in 2011 at age 39. Previous to my 5 IUIs, I was able to conceive naturally and got pregnant but miscarried at almost 10 weeks in 2010 at age 38. My FSH is 12 in 2012 but was 20 in 2010. My amy level was 0.5 in early 2011 and 0.25 in feb 2012. I have not tried IVF (in vitro fertilization) yet but I would like to know if the different protocol will make any difference producing more matured follicle. My RE doctor states that he needs at least 3 matured follicle to transfer, if there is not one, the cycle will get cancel and change to IUI. I have already find a donor but i found myself going back and forth to see if its worth going to a IVF cycle or not.

Please help! Thank you, D. from Texas


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

I think I would have recommended IVF back when you were 38 years old. In general, if a patient is 37 years old or older, I strongly recommend IVF rather than IUI. The main reason is that the chances of pregnancy with IUI at 37 is 5-10% per cycle vs 60% for IVF. In addition, seeing that your FSH level was already elevated at 12, that would have made a strong argument that time was critical so I would not have wasted it on a low yield treatment plan. But that is "spilled milk" as they say.

Now, you have two things going against you in terms of trying with your own eggs. One is that you are 40 years old so your chances of pregnancy are decreased, but still around 50% per attempt. More critical is that your FSH level is very very high and your AMH level is low. These are not good and indicate that the ovaries would probably not stimulate well. Sure, it only takes one good embryo to achieve pregnancy, which is what I tell my patients, but at the same time, the only way to increase your chances because of your eggs is to try to get a lot of eggs (it is know that the number of good eggs decreases with age). If only a few eggs are retrieved, then the chances of having a good egg, decreases. By the way, I don't agree with your doctor's policy to change to IUI if you have less than three follicles. IVF is clearly better than IUI because more of the steps are accomplished, bringing you closer to implantation, whereas IUI requires that your body go through ALL the steps naturally. In addition, I and many others in the assisted reproductive speciality have experiences with only one embryo leading to a pregnancy. Why give up IVF when it is your best option in such a cycle?

However, given your age, FSH level and AMH, I think that if you are willing to consider donor eggs, that is now the best way to go. I do let my patients try IVF despite these adverse factors because many desire to try at least once with their own eggs before giving that up. If you can afford it, that is an option. But you should clearly understand and be prepared for a failure and be ready to go to IVF with donor eggs.

Thank you for writing and good luck,

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

Thursday, February 16, 2012

Hope And Encouragement During IVF: Is It Necessary?

Dear readers old and new,

The main purpose of my blog, Facebook entries, Twitter entries and All Experts advice are to give people hope; to urge them to continue their quest to have a child; to give them explanations and to help them in their quest.

I and my staff are my patient’s cheerleaders. We want the very best for them and hope and pray with them. We feel sadness when they fail and are overjoyed when they are successful. We put our hearts into them. This is a closeness that most large IVF clinics do not have the time or energy to do. This is personalized care, and it affects us because of the stresses it puts on us. Nameless, less personal and faceless care would be a lot easier for us. It would be less stress. It also would be less sadness for us, but that is not the type of care I or my staff like to give.

But today, I was criticized for something completely different. I had two patients give us feedback that we were “too encouraging” so their feeling of failure was worsened. They were angry at us for this. We were criticized for giving too much compassionate care, so that we enhanced their expectations and hence their fall when they received the negative result. I am mystified as to when good care or good service is no longer acceptable. Should we create more of a distance from our patients? Is giving hope to patients really just fueling false hope and subsequent depression? Is the anonymous factory-type care that many large centers provide, better than our approach? Is this really what infertility patients want? Are my efforts actually more destructive than they are constructive? I’d love to hear from readers of this blog about their thoughts.

As infertility specialists, we deal with a very personal issue. So personal and private that most patients won’t even acknowledge us to their friends or family. For example, I was at a B’nai Mitzvah recently for twins that, not only did I help conceive, but I also delivered. It was a celebration of the children, and there were acknowledgements of everyone in their lives, including their teachers, rabbi, friends, travel partners, etc. but, alas, there was no mention of me; the one who not only made it possible for their mother to have them, but who physically brought them safely into their world (I delivered these twins as well).

I have accepted the fact that what I do is highly personal and private. I have accepted the fact that many patients will not acknowledge me in mixed company, or in the store or on the street. Being a “fertility specialist” can have a negative impact on their standing among friends. That is certainly something that all fertility specialists have to accept. I do accept that. Unlike many other medical specialties, the praises we receive are received in private. We don’t mind that because we know that in their hearts, they appreciate the care and gift that we gave them.

It can be a bit disheartening though, at times.

Edward Ramirez, MD, FACOG

Saturday, February 11, 2012

38 Year Old With One Fallopian Tube: Miscarriage With 2nd IVF


Hello Dr. Ramirez!

I am 38 and trying to conceive my 2nd child. I did 2 rounds of IVF at 35 and had a healthy daughter at age 36. We just went through another round of IVF and got pregnant, however it ended up in a miscarriage at 10 weeks. We can't afford another IVF so we're trying a few rounds of IUI with Clomid 100 mg. I'm now going for my second round.

My issues are stemmed from a ruptured appendix at 16 which left one of my fallopian tubes badly scarred. I did have a laparoscopy and had that one closed and my other one is totally open. In all the testing for my IVF, everything came back good..."for my age". My husband has a fantastic motility and count, so there's no issues there. My questions are:

1. My RE says that follicle growth is completely random and that they do not alternate sides every month. What are your thoughts on this? I hate to waste the time and money if the follicles grow on the bad side.

2. Have you seen much success with clomid/IUI at my age? Everything is totally normal with me and my husband. We eat good, (I was a smoker from 16-30 but haven't smoked in 8 years) and I rarely drink.

3. If this doesn't work, any suggestions on where to go from here?

BTW, I'm writing from Milwaukee! Thanks!


Hello L. from the U.S. (Wisconsin),

First of all, it is wonderful that you were able to already have one child via IVF! This is encouraging.

1. Yes, your RE is correct that it does not alternate but is random. Also, your assumption that the side that it ovulates on is the side where it enters the tube is not correct. In fact, the ovary, being three dimensional, can have a follicle rupture at any part of its surface, even the side that is opposite where the tube is located. So how then does it get to the tube? Well, when the ovary ovulates the fluid surrounding the egg rushes out taking the egg with it and flow down-hill into a space called the culdesac. The culdesac is like a little bowl. The fluid collects here and then with simple fluid motion, it moves around. In normal anatomy, the end of the tube that picks up the egg, called the fimbria, is located in the culdesac, so it you are lucky, the egg contacts the fimbria of one tube and is brought into the tube (like an elevator) where it meets the sperm. This is why a woman who only has one tube on one side and one ovary on the opposite side can get pregnant.

2. Pregnancy rates at 38 years old are around 5% per cycle, which is not very good but it is not zero.The pregnancy rates are less with Clomid than IVF because you and your body still need to go through the 9 step process to achieve a pregnancy whereas with IVF, steps 1-7 are done by the IVF procedure and there is only two steps left to contend with.

3. Monterey, California :) I'm only kidding. You have already shown that IVF can work. The reason that you miscarried is because the embryo was probably abnormal, which is a risk that you have because of your egg. The goal is to eventually get a perfect egg that will give you a perfect and healthy baby. That is probably just a matter of time. The only alternative, which gives you a higher chance for pregnancy per cycle and less chance of a miscarriage, is using donor eggs. But you can do that at any age, so I would try again with IVF if you are not successful with your Clomid cycles, although I understand that finances are an issue. You don't have much time, though. If you do manage another IVF cycle and it fails, then you can always do donor eggs. I recently had a patient who tried IVF in her early 40's, miscarried then failed, and then gave up. At 55 she decided she wanted to try again and went with donor eggs. She now has a beautiful daughter. With donor eggs, your age is not a significant factor.

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

Tuesday, February 7, 2012

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


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


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
Monterey, California, U.S.A.

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


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