Upcoming Frozen Embryo Transfer #4: Do I Transfer 1, 2 or 3????

Question:

Hello,

I have a son via FET. I have now had three cycles of FET total. The first did not work, the second we got my son, and this last one worked- however I had a miscarriage at 6.5 weeks pregnant. I now have 4 embryos left frozen and am starting my next IVF cycle. They are frozen in vials of 2 each. I am so concerned if only one survives: do I only implant only one and pray it works, or do I thaw the last two we have and implant all 3? I obviously want the ultimate outcome: a pregnancy. 

 

My doctor is NO help when I ask what he recommends.  I am scared to only implant one.  Yet I am scared to use all of them in this one last attempt we have.  Is only implanting one pointless? Can you give me a recommendation on what is best if this situation were to happen on the day of transfer? The transfer is only a couple weeks away so I am so nervous.

 

Thank-you so much.

 

S. from Illinois. Nervous mom!!!!!!!

Answer:

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

Since you haven't given me your age, I can't give you specific recommendations but will have to answer your question in more general terms.  Also, another significant piece that would help answer the question is whether your embryos were frozen on day#3 (cleaved) or day#5 (blastocyst).

We always consider age when counseling patients on the number to transfer because this affects the quality of the embryos and therefore their chances of implantation.  Of course, the younger you are, the higher your chances of implantation and pregnancy per embryo.  Because the technology has gotten so much better over the years, pregnancy rates have gone up and we have realized a problem; namely, an increase in multiples, especially those over twins.  As a consequence, every IVF Physician is wary of putting to many back for fear of getting too many in return.  As a result, the American Society for Reproductive medicine and the Society for Assisted reproduction, its subgroup, have produced recommendations or guidelines for transfer.  these of course are dependent on the age and the stage of development.  Their recommendations are as follows:

 Cleaved embryos:   
                             35    35-37    38-40  40 years old

   Favorable         1-2       2         3        5+

   Unfavorable        2        3         4        5+

 Blastocyst         

   Favorable          1        2         2        3

   Unfavorable      2        2         3        3

I have my patient sign a counseling for that they have been informed regarding these guidelines and either choose to follow them or choose a different number.  I do let my patients decide within reason.  Because you have gotten pregnant with these embryos before, that would be an additional piece of information making me more cautious.

So here's the decision.  Unless you are over 35, I would recommend no more than 2 if they are blastocysts.  If these are cleaved embryos, then I would recommend 2-3.  But, the risk is of getting multiple implantations leading to at least twins.  With blastocysts and transferring 2, my twin rate is 56%.  With cleaved and transferring 3, my twin rate is 35%.  Are you willing to take the risk of having twins?  The pregnancy is harder and there is an increased risk of fetal loss.  If you are not willing to take the risk of twins then you would only transfer 1 no matter what stage.  If you are not willing to take the risk of triplets, then you would not transfer more than 2.  I do not recommend triplets.  The fetal loss rate can be as high as 50%.  The down side of transferring less than 2 is a decrease in pregnancy rates per cycle, but not necessarily over all.  It make take more attempts to get pregnant doing single embryo transfer.

I hope this gives you the information you needed to help with the decision.

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.

 

38 Year Old Has Five Failed Fresh IVF Cycles But Has Frozen Embies: Should She Try FET?

Question:

Hello - I have been reading you blogs for some time now and am so thankful that you take the time you do with such thoughtful answers.

I am 38 and husband is 41. My history is as follows: 2009 wasted time on clomid prescribed by my obstetrician, 2010 saw RE (reproductive endocrinologist) and began the real journey. Major issue is male factor morphology but I suspect with my age quality may be issue too.

In 2010 we had 2 Fresh IVF (in vitro fertilization) cycles, first was a failure 3 eggs collected, thankfully 3 fertilized and implanted 2 (1 frozen) but no pregnancy, cycle 2 doubled my stim meds to 300 gonal f and 150 repronex, collected 13 eggs but transferred 2 "decent" but beta was very low around 70 the pregnancy continued to around 11 weeks saw heartbeat but clearly there was issues as the size kept loosing ground until miscarriage and D&E. Cycle 3 same meds, 13 eggs, transferred 2 on day 5 and then arrived my beautiful baby girl delivered 12/29/2011.  Fast forward to 2013 where I have done two more fresh cycles same protocol, birth control, 10 lupron, to 5 lupron when stimming, retrievals after 9-10 days of stims. Cycle 4 resulted in collecting 20 eggs, 2 "decent" transferred on day 5 (blastocyst and morula) very low beta resulted in loss about a week later.  Cycle 5 same protocol except menopur instead of repronex, collected 18 eggs, 14 fertilized and transferred 2 blastocysts on day 5. This was a negative. BTW all cycles are ICSI and included medrol, baby aspirin, antibiotics, vivelle patches and  progesterone in oil injections. 

My question is what are your thoughts on FET (frozen embryo transfer).  I have 4 frozen embryos 1 from cycle 1, 1 from cycle 4 and 2 from cycle 5. RE and hubby think I should take a break and try for FET. I and concerned as I don't want to "waste" a cycle insurance will cover on the lower cost option but the meds did really affect me this time and see their point about giving my body a rest. I am at a very reputable clinic in Boston and doc said 4 frozen is a lot due to their strict freezing criteria so am optimistic although obviously embyro age has no advantage. Would FET also be something you would recommend at this point? Fresh cycles are a big logistical challenge as my husband travels 70% of the time.

Also if I go back to fresh cycle is there anything significantly different you would do (btw I am also doing acupuncture). Thank -you in advance for your time. I also want to say I am very grateful for my daughter and don't want to seem selfish but I would really like her to grow up with a sibling. 

J. from Boston

Answer:

Hello J. from the U.S. (Boston),

It sounds like you are in good hands.  Your clinic has accomplished several pregnancies, which is an IVF success.  Keep in mind that IVF can only give you the "opportunity" to become pregnant.  It can't make you pregnant because the last three steps (embryo hatching from its shell, attachment to the endometrial lining, and lining growing around the embryo are natural processes that are in God's hands.  That fact that you got a pregnancy (positive bHCG) shows that those steps occurred.  Continuation of the pregnancy is then based on pregnancy factors and not IVF factors.  Because of your age, your chances of a miscarriage are high due to abnormal embryos.  You've shown that you can get pregnant, and your ovaries stimulate very well.  Now it is just a matter of finding the perfect egg/embryo which will then lead to a successful pregnancy.  I wish all my 38 year olds responded as you do.  So hang in there!

I think I would advise proceeding with the FET cycle before another fresh cycle.  It is a much easier cycle on your body, and some newer studies are showing better pregnancy rates than fresh, probably because of the lack of overstimulation of the endometrial lining.  I don't completely agree that FET is "better" but it certainly gives a good chance.  If they fail, you can certainly try fresh cycles again.  I would advise two FET cycles consecutively.  In fact, I always advise my patients to do an FET cycle, if they have frozens, before trying a fresh cycle again.  You never know. . . the frozen might work.
In terms of additional protocol changes, you are doing everything that I have my patients do in terms of supplemental medications, but I also add low dose heparin (2000 U per day).  Not all RE's agree with this protocol, but it is an accepted protocol for recurrent pregnancy loss so you might want to ask your RE.

Thanks for following my Blog.

Good Luck,

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

www.montereybayivf.com

Monterey, California, U.S.A.

Comment: Thank you much for the quick and thoughtful answer. I have several time contemplated seeking a more aggressive clinic despite my comfort level. Your response puts many of my worries at ease. You are truly a huge help to those of us in a constant state of limbo. Thanks again.

 

Egyptian Fails One Fresh & One Frozen IVF Cycle: Advice On How To Improve Lining Thickness

Question:

Hi, I am 28 years old, married since 3 years, trying to get pregnant since 2 years. I had ectopic pregnancy since 15 months which ended by right laparoscopic salpingectomy. Then I tried clomid for 3 cycles, HMG induction for 2 cycles and I tried fresh IVF (in vitro fertilization) with long protocol.

I took 1 amp menogone , 1 amp fostimon 75 mg, 1 amp fostimon 150 mg/d. there was 36 mature follicles , all fertilized well, then 4 good embryos were transferred on 3rd day but ended badly on 5th week by blighted ovum.

Then I tried frozen embryo transfer by thawing the embryos and let them grow to the blastocyst stage. We got 14 good blastocyst from 19 embryos, then 2 hatched blastocysts were transferred. I took estrogen valereate 6 tab/d till endometrium thickness 8cm, then progesterone supp 800 mg/ d , aspirin 75 mg/d. but again a negative BHCG on due time.

Some history:

a) semen analysis is good with no abnormal forms or motlity
b) patent left tube by hysterosalpigogram
c) history of endometriosis discovered during laparoscopic salpingectomy.
d) good hormonal profile FSH, LH, TSH, prolactin, anti-phospholipid tests

Now I am planning to repeat but I still have 12 frozen blastocysts, but I need your advise because we thawed the 3rd day embryos from the first ivf , then let them grow till the blastocyst stage , then did the transfer the last time , then refreezed them again.

My question:

I am undergoing a new frozen cycle now. I take 6 tablets oral estrogen valereate/ day, 200mg sildenafil (viagra) vaginally/ day and vitamin e, aspirin, and after the endometrium reached 8.5 mm thickness on the 10th day stimulation, it decreased on the 13th day to 6 mm although I still take the same dose with no discontinuation, sure of the expiry date.

What is your explanation please, and what can I do to prevent cancellation of the cycle? If I continued the same dose is there any hope for restoration the thickness?

Please answer me because I am frustrated and breakhearted.

N. from Egypt

Answer:

 Hello N. from Egypt,

This is a protocol question, which I do not answer because protocols can vary widely and there is not only one way to do things. That being said, there is some general information that I can provide.

First, keep in mind that you have been pregnant with IVF and so can get pregnant again. IVF only gives you the opportunity to become pregnant, it cannot make you pregnant because there are still some natural steps that must occur on their own. Studies have shown that if you have gotten pregnant in the past, your chances of getting pregnant with IVF are higher. Also keep in mind that, just like trying to get pregnant on your own each month, it does not always work. Sometimes it can take several attempts before it is successful.

Second, it is well documented by studies that the best way to deliver hormones for IVF is either by injection, by patches or by vaginal delivery. Oral tablets can be used vaginally (you just push them to the very back). This helps with maximum absorption of the hormone and delivery to the uterus. Oral intake has been shown to be the worst way to give hormones for IVF because most of it is lost when it passes through the liver. I personally use patches, which most US doctors use, but tablets used vaginally is also a good option.

I would not necessarily cancel the cycle, because time can be taken to develop the endometrial lining further. It is only finalized once the progesterone is started. That is what determines the timing of the transfer, which for a blastocyst, should be on the 6th day after starting the progesterone. If you have not started the progesterone yet, you can keep using an increased amount of estrogen to get the lining to 9 mms.

Good Luck,

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

Australian Undergoing Natural Cycle FET: Timing Is Everything!!!

Question:

Hi Dr Ramirez, I am 32 from Australia. I am about to embark on my first Frozen Embryo Transfer, using my natural cycle. I have one child (5yrs old) who was conceived spontaneosly after removing my endometriosis 3 months earlier. My doctor will be conducting ultrasounds and blood tests to determine ovulation and progesterone levels. This starts on day 12. My embryos (which were all top rating) were frozen on day 2.

What is the latest time (post ovulation) they could transfer these soon to be 3 day old embryos? I'm just worried because 3-4 days post ovulation would most likely be on a Saturday or Sunday and the lab is not open on a Sunday. Is delaying it or doing it too early acceptable?

Thank you for your time. Kind Regards, Z. from Australia

Answer:

Hello Z. from Australia,

First let me say that I am very surprised that your doctor has chosen to do this with a natural cycle. Implantation is very time sensitive, meaning the timing of the transfer has to be pretty exact. If the development of the lining is out of sync with the embryo stage, then implantation will not occur. The timing of the endometrial lining development is very dependent on progesterone stimulation and that cannot be measured by blood tests because the blood levels do not reflect the endometrial levels or the endometrial architecture.

In terms of your question, I cannot believe that an IVF center would not be open on a Sunday if they have to be because of timing. Again, I know I'm being redundant, timing is EVERYTHING in a frozen embryo transfer. The embryos can be transferred at any cell stage, as long as it coordinates with the stage of endometrial development. In a normal cycle, the embryos are transferred one more day than the number of days you have been on progesterone. For example, for a Day 3 embryo, it is transferred on the 4th day of progesterone. For a Day 5 embryo, it is transferred on the 6th day of progesterone. What I would suggest for you, if the 3rd day falls on a Sunday and the clinic cannot do a transfer on that day, culture out the embryos until Day #5 and transfer at that time. They will have developed into blastocysts by then which might help your chances for implantation since the embryos will be closer to the stage they need to be in for implantation.

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.

How Can I Overcome Implantation Failure After Failing Multiple Fresh & Frozen Cycles?

Dear Dr Ramirez,

I'm a 43 years old female (from Australia) and for the last 2 years have been unsuccessful with IVF (in vitro fertilization) after 3 stimulated cycles and 10 Embryo transfers. I produce a good number of eggs (approx 18) with a stimulated cycle of 300iU/day of Gonal F. This egg number usually decreases at each stage; eg of 19 eggs, 13 are mature to fertilise, 6 fertilise and finally 1 or 2 reach day 5 blastocysts which can be transferred or frozen. All frozen eggs have always thawed well and transferred.

The pattern each cycle is similar however I'm finding that in this latest cycle only one embryo was transferred and the 2 remaining did not reach an acceptable stage for freezing. Implantation has always failed, even with the use of progesterone pessaries after transfer. I've also tried implanting 2 embryos with no positive result.

My specialist has resigned to the fact that my eggs are not of good quality due to my age. No testing on this has been suggested.

In terms of health I have PCO's and have a BMI of 30 (90kgs). I find it difficult to lose the weight which has been gradually gained in the last 8 years, have mild anxiety on the odd morning upon waking and trouble getting quality sleep 2 -3 nights per week. At times I suffer from low mood but put it down to the drugs and loss of hope. But I pull though with the support from family but use no medication. I do take a prenatal multivitamin 150mg of CoenzQ10 and fish oil. In your experience are there other treatments that could be explored for recurring implantation failure? Thank you, S. from Australia

Answer:

Hello S. from Australia,

Based on your embryo development and transfer of at least one good blastocyst, the cause of your failures is not determinable. We classify this as implantation failure but in reality there are two steps that have to occur naturally after the embryo is transferred. These are embryo hatching and attaching to the uterine wall and the endometrium growing around the attached embryo (implantation). We have no way to confirm that these steps are occurring. For that reason, there are no specific therapies to overcome failure at this point, but there are many suggestions for things to try. I say "things to try" because these are not proven remedies either. Also keep in mind that IVF success is not only dependent on embryo quality/normality and endometrial processes, but also on the doctor's transfer technique.

I think that what I would do if you were my patient is:

(1) Abandon the blastocyst transfer. Blastocyst culturing does not guarantee a quality embryo or success. Laboratory techniques, media, etc are not perfect. I wholly believe that the uterus is a better culture media and environment than the lab. Also, some embryos that might be the normal and healthy ones may not develop to blastocyst, as has been shown by numerous studies looking at preimplantation genetic screening.

(2) You could consider PGS to determine which embryos are genetically normal, and therefore have the highest chances for success.

(3) I empirically add low dose aspiring 81 mg per day, Medrol (Prednisone) 16 mg per day and Heparin 2000 Units twice per day starting at the beginning of the IVF cycle in my patients that have had repetitive failures. This is a formula that has been proven to decrease recurrent miscarriages with the thought that adequate micro blood flow and immunological factors may be leading to failure. I also increase my progesterone supplementation by using both injectable and vaginal supplementation, and add estrogen supplementation after the transfer by patch. Acupuncture has also been found to increase success in some studies, possibly by increasing blood flow or by reducing stress. All of these latter treatments are, as I said earlier, unproven. We call it "throwing the kitchen sink in" which basically means trying everything under the sun.

Finally, if you really suspect that it is an embryo problem, then donor embryos would be the remaining option, or you could consider using a surrogate if you think your embryos are okay but the uterus is not hospitable (my presumption is that a diagnostic hysteroscopy was already done to make sure of this).

Keep trying and 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.

Woman Wonders: Natural FET Cycle Vs. Controlled FET Cycle?

Question:

Dr. Ramirez, I have some embryos frozen. I have adenomyois and endo and chronic endometritis diagnosed.

Have done antibiotic treatment with uterine lavages and IVs.

After depot lupron treatment, is it better to do a natural FET (frozen embryo transfer) or medicated FET. Since it takes about 2-3 months to wait for period to arrive is it better to do a medicated FET? I am concerned about medicated FET as the last time I did a medicated FET I had fluid in the uterus although nearer to transfer it disappeared and I did go on to transfer although BFN (big fat negative).

My RE seems to want to wait for a period before transfer but would not that waste 2-3 months since you said the endo can return in 6 months? Will the cycle be regular and as in ovulation or will it be not regular when I do FET. At the moment my cycles are regular. I have also heard of high dose progesteone treatments treating endo and adeno. Can you explain how this works?

I am confused what to do as we have limited embryos and want to do everything as possible as once the embryos are used up we are done.

Thank you. R. from Rhode Island

Answer:

Hello R. from the U.S. (Rhode Island),

Your RE should have explained that one of the critical steps in getting pregnant, natural or with IVF, is the state of the uterine lining at the time the embryo reaches it for implantation. We know that there is a very limited time that the embryo can implant and the endometrial lining has to be in a very specific and correct microscopic state for implantation to occur. This is where timing is absolutely essential. If you miss this "implantation window", then it will fail.

Conceivably you could do this with a natural cycle, but then there is a wider margin of error because we don't know exactly what the timing is or what is going on microscopically in the uterus. For this reason, we do not do this in FET cycles. FET cycles are always done as a controlled and programmed cycle. With this protocol, you can have a period induced artificially with medication and then start the cycle, but most clinics will want their patients to be on the birth control pill for at least two weeks period to the FET cycle in order to suppress the ovaries, which then allow complete control of the FET cycle.

If this is in fact gong to be your last attempts at getting pregnant, then I would make absolutely certain that you are in the best clinic that you can be in and that it will give you the highest chances of success. A good clinic would be able to answer these questions and make sure everything is clearly laid out.

Finally, in terms of progesterone treatment with endometriosis and adenomyosis, progesterone has suppressive action or counteracts estrogen in estrogen receptors. AS you probably know, endometriosis/adenomyosis are stimulated by estrogen and therefore, will be somewhat suppressed by progesterone. However, there is still some small amount of stimulation so progesterone is not the perfect treatment. Estrogen receptor blockers such as Lupron are better at suppressing endometriosis. Progesterone is used mainly to slow down the recurrence of the endometriosis after they have been treated with surgery or Lupron.

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 Little Miracle...Seven Years In The Making

I want to share a special story with you, my readers, about a couple who went through a recent IVF (in vitro fertilization) cycle with us. This couple had come to us back in 2004 for infertility treatment. After the normal trial of IUI's (intra uterine insemination) did not work, they opted to do IVF with us. The cycle went well, the retrieval went well and there were three embryos to transfer. While doing the transfer of all three embryos, one embryo "floated" (aspirated) back out of the catheter. This was an unusual event for me and my staff. The couple decided to freeze that one reluctant embryo. Unfortunately, the patient did not become pregnant with that cycle. As it so happens, she soon became pregnant naturally and in the ensuing years, as sometimes happens, they had no trouble conceiving again, having three children in all.

In the meantime, the frozen embryo remained in our cryobank storage facility. The couple elected to leave the embryo there for the last seven years until recently. Grappling with the options of either continuing to pay for storage, dispose of the embryo or put it up for adoption, the couple opted to go forward with a frozen embryo transfer. We transferred the one embryo successfully and crazy as it may seem, the patient is now pregnant! This child will be both the "oldest" and the "youngest" sibling by virtue of this unusual series of events.

I am a spiritual man, if you have not guessed already. For us, every child is special, but I have a feeling that this child will truly be a special one, for it is my belief that for some divine reason his or her birth was delayed. How often I feel defeated when a cycle does not succeed and yet when something like this happens, I know that we can only do what we can up until a certain point, at which time the final steps of creation are taken out of our hands. Which brings me to one of my favorite quotes from Deepak: "When you live your life with an appreciation of coincidences and their meanings, you connect with the underlying field of infinite possibilities."

Right After A Cancelled IVF Cycle, Try Naturally Or IUI?

Question:

Dear Dr. Ramirez,

I write to you from Los Angeles, California. I am 38 and just started an IVF (in vitro fertilization) cycle after two FETs (frozen embryo transfers) that did not take. Those embryos from the FET were from an IVF I did when I was 36 that resulted in my wonderful son. I am on Bravelle and went in for my first ultrasound and they saw only two developing maturing follicles, one on each side, that were outpacing all the rest. Previously, they had seen about five on each side. My doctor has cancelled this cycle but recommended continuing on the Bravelle for two more nights and then trigger ovulation and timed intercourse. My questions is, should I do IUI instead of just timing intercourse? I know that my chances are very low of conceiving anyway, but my feeling is that if we are paying for the meds and these ultrasounds, that perhaps we should optimize our chances, even though they are very low. The doctor was trying to minimize our costs and suggested timed intercourse instead of the IUI.

I am hoping that these two years that have passed since my son was born haven't led me to be a 'poor responder.' The doctor said that sometimes this happens and that we can try a fresh ivf cycle next month and he would increase the amount of the stimulation drugs.Any thoughts on IUI versus timed intercourse or anything else?

Answer:

Hello S. from California,

I don't recommend canceling IVF cycles normally because you never know if the perfect egg is in one of those follicles. In addition, despite the fact that two have outgrown the others, that does not mean you can't get mature eggs from the other follicles. There have been studies that have retrieved mature eggs from follicles as small as 10 mm. So even if there is only one follicle, I like to give it the best chance that we can. I know that this is a more expensive way to go, but I've had numerous pregnancies from just one follicle. Bear in mind that IVF has a significantly higher pregnancy rate, even with only one egg, than any other method at your age, per cycle. In my center it would be 70% pregnancy with 40% continuing with IVF vs 7-10% with IUI.

That is because, if you image how the natural cycle process works, it takes 10 steps for your body to accomplish a pregnancy:
(1)Brain sends FSH to stimulate the ovary to grow follicle
(2) Ovary grows follicle
(3) Follicle ruptures out of ovary (ovulation)
(4) egg is pulled into the culdesac with the fluid from the follicle and finds (or has to find) tube within 12-24 hrs
(5)Egg is picked up by the fimbria of the tube
(6) Sperm and Egg meet within the tube and fertilization occurs
(7) Egg travels down the tube and divides into blastocyst
(8) Embryo enters uterine cavity
(9)Embryo hatches and exits from its shell
(10) Inner mass attaches to the uterine lining and the lining grows around the embryo (implantation)

With IVF, steps 1-8 are accomplished for you and only two steps left up to chance/nature/God, whereas with IUI, only steps 1 and 2 are accomplished for you. The rest occurs naturally.

In any case, there are several issues you have brought up and questions that correspond. One is whether you should do IUI vs try naturally right after a cancelled IVF cycle. Statistically, IUI has a better chance of pregnancy than pregnancy (7-10% vs 5%), so for that reason alone, I would go with IUI. I would recommend following the exact same protocol as you would of with IVF except that retrieval and transfer will not occur. I would do the same progesterone supplementation.

The other issue is regarding your stimulation. It is obvious that you were not stimulated with the max protocol if you doctor commented that they are going to increase it. You may have a decrease in response but without getting maximum stimulation, you don't know that for sure. So, you may not be a poor responder. You just did not get stimulated adequately.

The good news is that you have had one successful pregnancy. It is a good thing that you are pursuing having the second at 38 yr.s, before you become much older and the rate of success drops dramatically.

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.

Patient Fails One Fresh, One Frozen IVF Cycle: Will Another FET Work?

Hello,

My name is S. from Boston. I am writing with a question regarding what I am going to be undergoing next week, a second frozen transfer. Just to give you some history, I had a first attempt successful IVF (in vitro fertilization) cycle in 2008 and delivered a healthy baby. We are now trying for baby #2 and had an unsuccessful fresh cycle, and an unsuccessful frozen cycle in the last few months. I still have several frozen embryos so my insurance is mandating that we use them prior to doing another fresh cycle.

I know the success rate is lower with frozen embryos but I wanted to know another opinion, if I should proceed with a fresh cycle if this one is negative. I have 3 frozen embryos left, that are all 6 cell and high implantation potential. I am not optimistic that this one will work, because the other two cycles they put in 2 8 cells and they didn't take. My doctor says there is no difference between 6 and 8 cell embryos, but if that is the case, then why do they always choose to transfer the 8 cells first? I know I could also lose some cells in the thawing process, so does that lower my chances more, and are there are risks associated with the baby, if I do become pregnant this cycle? Thank you so much!

Answer:

Hello S. from the U.S.,

These are very good questions that you should direct to your doctor. It is his/her responsibility to keep you informed.

Let me take the easy questions first. The reason why we use the 8 cell embryo first is because embryos are graded based on their appearance. Yes, that is we give them a higher grade, the better they look, just like a beauty contest. The cell number is the number of cells the embryo has divided into by that particular day, which I presume to be post-retrieval day#3. Again, we prefer embryos with more cells than less cells. That does not necessarily mean the embryos with more cells are BETTER than the embryos with less cells. In fact, preimplantation genetic testing often shows the opposite. So a higher number of cells does not guarantee a good embryo. The factors that make a good or perfect embryo are not things that we have the technology or knowledge to apply at this point in time. Maybe in the future. My preference is for my embryos to be between 6 cells and 8 cells at this point. Most pregnancies will result from embryos within this range, either grade I or grade II.

Frozen embryo transfers have a lower pregnancy rate probably because the lesser embryos are left to be frozen and the better embryos are transferred fresh. Also, it may be because of the freeze and thawing of the embryos, but the technique has gotten so good that I don't think that is much of a factor any more. But, that does not mean that a frozen embryo can't implant and produce a good pregnancy. I would still recommend that you use them first before another fresh cycle because the medications required are less, AND there are some studies that show that implantation is better if there is no ovarian stimulation, as in Donor cycles. That might be an advantage. You just have to hope that the embryos are still good enough.

I might suggest that you ask your doc to culture the embryos remaining to blastocyst stage. That will be a further validation of the embryos, and may lead to fewer embryos to transfer, but they will be at a stronger stage. That does not necessarily give you a better chance at pregnancy, but the assumption is that if the embryo can survive further culturing then it has a better chance of continuing to implantation. That way, you can further screen the remaining embryos that you have. The ones that don't make it to this point will be discarded, then you will need to move to a fresh cycle. If you have extra blastocysts, you should only transfer two max at this stage, they can be frozen and are in a better stage for the freezing.Finally, there are no added risks for a normal baby if by frozen eggs or embryos. If the embryos are abnormal they usually will not work (implant) or will end in miscarriage. You have not given your age, but this can be a factor in terms of embryo quality, success and genetic risks as well if you are 35 years old or older.

Good luck,

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

45 Year Old Woman With FSH Of 13, Fails Four IUI Cycles: Go To IVF With Her Own Eggs Or With Donor Eggs?

Question:

Hello Dr. Ramirez,

I'm writing to you from Texas. I just turned 45 and in the past 4 months I have gone through 4 IUI cycles (3 w/Femara) and one natural. None worked, but my fertility specialist thought it was worth a try because there is no problem with me (other than my age) or my husband and our ability to conceive. He did mention that there was a small amount of endometriosis, but nothing to be concerned about. We had been trying for over 3 years before I finally went to a specialist. I know I should have gone much sooner.

My question is this: We have decided to try IVF . My big concern is the age of my eggs. My FSH was 13. Is there any greater chance of my becoming pregnant if I use my eggs and my husbands sperm to create an embryo, or if I use a donated embryo from a younger couple? I get somewhat different answers depending who I ask at my fertility clinic and it's quite frustrating. I don't want to change clinics if I can help it, because my doctor is top notch. His staff knows their stuff, but they seem to be too busy to give me any real in depth answers. I look forward to getting your opinion on this issue. I've found all kinds of websites that deal with donated embryos - are there any that you would recommend? Thank you! J. From Texas

Answer:

Hello J. from the U.S.,

I am very, very surprised that your "top notch" doctor recommended you to try IUI's (intra uterine inseminations) that many times based on your age and elevated FSH. Did he tell you that your chance of pregnancy was less than 0.5% per month? Did he tell you that your FSH was elevated and give you the diagnosis of decreased ovarian reserve, which essentially means time is critical for you. You may already be in a pre-menopausal state!

Unless my patient absolutely demands it, I do not recommend IUI in my 42+ year old patients or patients with FSH levels greater than 10. In my opinion, in order to have the best chances of pregnancy in the short time that you have left, IVF is the treatment of choice. At least there is a pregnancy rate at 45 years old that is about .5%, and for this reason I will let them try with their own eggs (many clinics do not), but it is with the understanding and plan that if it does not work then they will proceed with donor eggs. I have also had a few patients decide to mix their eggs with frozen donor eggs so that they don't know which resulted in the pregnancy (they preferred to not know that it was absolutely a donor). These eggs are purchased from an egg bank and are slightly less expensive than going the fresh donor egg route.

I think that based on your age of 45, and the elevated FSH of 13, I would strongly recommend that you proceed with donor eggs and IVF (in vitro fertilization). That will give you a pregnancy rate of 75% per attempt in my clinic and many other clinics.

In terms of finding a donor, there are three options: (1) finding your own donor that is either your family member, friend, acquaintance, which is the least expensive because you don't have to pay the donor but there could be some social issues, or (2) use a donor that is registered with that IVF center if the center has donors registered. This is usually the second least expensive way to go but there may be limited donor choices (3) Purchase frozen eggs from an egg bank or (4) go through an agency. There are many agencies across the country and you have to be very careful which agency to use. Some are reputable and some are not. This is the most expensive way to go and can double the cost of IVF because of the agency fee. We have worked with several agencies in the past, although most of my patients elect to use an egg donor in our registry.

Donor cycles are fairly easy to do from your side and will require a minimal amount of time at the IVF center. Because of this, many patients will travel to an outside clinic for a donor cycle due to price or the location of the donor. Many clinics, such as ours, can even arrange for preliminary and initial cycle visits to be done at a local clinic or IVF center so that the only travel required would be at the time of embryo transfer. So don't be limited by where you are. You have lots of options open to you. You just need to decide how you want to proceed from here.

I don't mean to be critical of your current clinic and I'm sure your doctor appreciates that you have a high opinion of their clinic. However, keep in mind that infertility clinics, doctors and treatments differ greatly. The fact that the staff at your center seem to be "too busy to give you any real in depth answers" should not be acceptable to you, considering the urgency of your situation. For example, our clinic is only one-on-one. Each patient is handled individually, and there is only one doctor that sees you, does your ultrasounds, does your procedures and makes recommendations. My patients have 24/7 email and phone access to me or my key staff. There are no mid level providers. We pride ourselves on being a boutique IVF center. It is what sets us apart from other, high volume, IVF centers that tend to make you feel more like a number. I hope this helps.

Follow-Up Question:

Hello again Dr. Ramirez, After reading your response I felt pretty emotionally bad, for lack of a better way of putting it. I was aware of the limitations with the IUI, the reason I did it is because my doctor felt there was nothing "wrong" with me or with my husband's sperm, and he assumed sluggish motility may have been part of the problem. I was planning on doing IVF next month, either using my own eggs (which I'm not entirely comfortable with) or a donor embryo rather than donor eggs, because of the price disparity. I don't live in CA where infertility treatments are covered under alot of insurance plans.

I said my doctor was top notch, in part because of the high ratings and recognition he has received in his field. That being said, I've never had a true one on one relationship with anyone at the clinic - although I tend to deal w/the same nurse and doctor. The clinic does offer an egg donor program, but based on your answer, I'm not so sure if I should continue on with them, since I don't believe their database is that comprehensive. In fact, I believe they go outside the clinic for donors, and the cost of the IVF with an egg donor is somewhere around 18,000. I asked you about FET (frozen embryo transfer), but you did not comment. I would like to get your opinion about this and if you have any recommended facilities that house frozen embryos. Unfortunately, the clinic I'm working with does not have any recommendations for embryo donors. After reading your answer, I'm not so sure about anything anymore. Thanks for answering, J. from Texas.

Follow-Up Answer:

Hello J.,

I apologize for causing you this strife. I don't want you to give up, rather, I am just here to give you advice and opinion. Certainly you can see that my opinion is greatly different from your doctor's.

California is not a mandated state in terms of infertility, so many of the insurances don't cover it here either. So I am very aware of the costs of treatments. It is a dilemma in my clinic as well where we lose 10-15 patients per cycle because of finances. Yes, I know that egg donor cycles can cost $18,000 or more per attempt.

Embryo donation is a fairly new option. I would recommend that you look at the web and you will find several organizations that assist with embryo donation. Keep in mind, however, that there are not a lot of embryos out there that are donated. Many parents do not want siblings all over the country. This certainly could be a lower cost than standar IVF because the transfer procedure is fairly simple. The medication cost is less and the procedure cost is less involved. Our clinic would charge $3500 for an FET (frozen embryo transfer). That is about what it costs in most of the clinics in our state. I don't know what the cost of these embryos would be, however, and most IVF clinics do not have embryos to donate. Most of the embryo banks are Christian organizations that either facilitate the process or have their own storage facility so that the embryos are not destroyed.

Another option is Frozen Egg Banks, which has now become a viable option. I recently had a 45 year old patient use that method. The costs were still higher than an IVF cycle, because the Frozen Egg cost was high, but it was less than using your own egg donor. Unlike embryos, these are unfertilized eggs that were frozen and can be fertilized with your husband's sperm. The protocol you would go through would be like an FET. It is more expensive than a simple FET because you have to purchase the eggs (I think then sell them in lots of two), ICSI would have to be done and the embryology process would have to be done like a regular IVF cycle. The only step that would not have to be done is the egg retrieval step, which is the most expensive part of the IVF cycle.

For both embryo transfer and frozen egg transfer, the pregnancy rates would be very high (75% per attempt in our clinic). It certainly is better than your own eggs.

Again, I apologize for the comments that I made because they deflated your hopes and made you feel emotionally deflated. I hope these new comments will help you more constructively.

P.S. Kelly Preston (John Travoltas wife) just delivered a healthy baby boy at the age of 48. Of course, she doesn't say whether she used any assisted reproductive technology (and I would bet she did), but if not, then there is always a chance. I never say NO to my patients that want to try, I only make sure they understand all their options and their chances up front.

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.

Male Factor Infertility -- IVF Cycle FET Positive But Ended With Miscarriage: Should I Seek A Second Opinion?

Question:

Dr. Ramirez,

My husband and I are a 29yo healthy couple with male factor infertility. Motility is less than 1%, morphology is about 25-30%, and count is pretty low-normal. There are no female issues. We have done 2 IVF/ICSI cycles and one FET (frozen embryo transfer). The first IVF (in vitro fertilization) cycle, I was mildly hyperstimmed. The egg quality wasn't great, and we had about a 50% fertilization rate. We transferred 2 grade A embryos that did not result in pregnancy. No embryos made it to day 5. IVF #2 was much better and had an 80% fertilization rate. 2 day-3 grade A embryos were transferred, but there was no implantation. There were 2 day-6 blasts that were frozen. Both were starting to hatch upon thawing, and the FET resulted in a singleton pregnancy with a heartbeat at about 7 weeks. Unfortunately, I miscarried (no heartbeat) at 8 weeks.

My question to you is when should I seek a second opinion? We had planned on obtaining a 2nd opinion if the FET was unsuccessful, but we feel like technically it was successful. We like the place we go to right now and feel that they are familiar with us. We are planning to do IVF #3 in the near future and are torn as to whether we should stay here or move on. If we stay with the current practice, we will not be changing the protocol since it was successful last time. Although it has been suggested, we are not ready to use donor sperm since we were able to grow 2 blasts and achieve a pregnancy. We are located in Missouri.

Thanks in advance for your time.

Answer:

Hello L. from Missouri,

I agree with your statement that technically the FET was successful. In fact, the FET cycle WAS successful. Remember, IVF can only give you the opportunity to become pregnant. It cannot MAKE you pregnant because the last two steps in the natural process, embryo hatching and implantation, are NATURAL steps and we don't have the technology to make that happen. So, the fact that an embryo did those two steps and the pregnancy went to 7 weeks is a success. And, it is a very good sign because it now shows that what you are doing can work!

I would not give up on that clinic yet. In fact, pregnancy rates with FET are lower than fresh cycles, so a success with an FET is good. They deserve the credit. Now that they have stimulated you twice, know how you react, etc., they are hopefully in a good position to build on that the next cycle. You have to give them some credit for that.

Overall, I would hang in there. You've proven that it can work. Whether or not the pregnancy continues is solely and completely dependent on the embryo. It was probably an abnormal embryo. Now, you just need to get a good one there and you'll go all the way. Don't look back, just look forward. You should now be more encouraged than before because you know that it can work. It is just a matter of time!

On a personal note, I have a patient that I was able to get pregnant on her first try at the age of 36 and she had a beautiful child. She just came back to me for her second child at 39 (worse chances statistically) and became pregnant again, but it was an abnormal pregnancy and ended in a miscarriage. I found out today, that she is planning to transfer to another clinic because they have a "special" research program going on that gives patients a significant discount. You can't believe how heart broken and how I feel rejected by this. I put my heart and soul into my patients, and they get the best care that they can receive. I know that logically the cost is a significant issue, and this is what is driving the patient, but having gotten so close to a success, when we have been successful before, is difficult for me. That is what your clinic will think too. They'll ask themselves, "why is she leaving when we were successful under less odds?"

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.

Twitter with me at @montereybayivf, and follow me on Facebook at http://bit.ly/9Iw9oV

Comment: Dr. Ramirez clearly stated his opinion and seemed to have genuine answers. I appreciate his advice and his providing this service

Estrogen Patches Vs. Estrogen Injections: Which Is Better For Pregnancy Success?

Question:

I have four frozen embryos which I would like to have transferred. My question is what has a better success rate with prepping the uterus, the Vivelle dot 0.1mg patches vs. the delestrogen injections? I had a baby two years ago from a donor egg and how they prepped me was with the delestrogen. I have since moved away from that IVF Clinic who used this protocol. I have recently consulted with a different clinic where I presently live and they would rather use the patches.

This makes me wary since I am not sure if this will hinder my success rate. Please advise.

Thank you. B. from the United States

Answer:

Hello B. from the U.S.,

There is no difference in pregnancy rates between these two forms of estrogen. Any estrogen can be used. Some clinics will use oral tablets, others will use vaginal suppositories, in addition to the patches or injections. The key is to make sure that enough estrogen is being delivered to form an adequate uterine lining. Certainly protocols can vary, and it is the specifics of the protocols that are important i.e. are they using enough estrogen with the patches vs the injections. Without looking at the two protocols, I cannot tell you if the patch protocol is adequate. You would have to send them to me in order for me to review them and give an opinion on those specifics.

Keep in mind that frozen embryo transfers have a lower pregnancy rate than fresh transfers, so that may affect your chances of pregnancy. The rates are roughly 50% less (30% vs 60%). Let me hear from you if you have further questions.

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, USA

Post IVF Transfer Pain: Implantation Pain or Ectopic?

Question:

My wife says that she was experiencing sharp pain yesterday (10 days after FET) on the area near right side of her stomach. She experienced the pain only yesterday and that was during a 3 mile walk. Today she says she feels some pressure near the right ovaries.

I'm concerned. Could you please let me know your suggestions? Thank you.

Answer:

Thank you for your question. This could be normal, but the main concern would be an implantation that occurs in the tubes called an ectopic pregnancy. I wouldn't jump to this conclusion but it is a possibility. This could also be what we typically call "implantation" pain. Please see my overview of what happens after the IVF transfer including pain and bleeding here: "After Your IVF Procedure".

Let me go into more detail regarding both possibilities.

All patients with infertility are at increased risk for an ectopic, even with IVF. The incidence is low but it occurs. At 10 days post transfer I usually have done my pregnancy test. This can give a better idea of how the pregnancy is doing and whether or not an ultrasound will show anything. Generally, the BHCG level has to be over 3000 to see a pregnancy in the uterus and if it is not there with that level, then an ectopic pregnancy as to be assumed. At only 10 days post transfer, it is unlikely to be an ectopic, however. These usually do not become symptomatic until 6-8 weeks of the pregnancy. At this point, it is probably not anything serious.

Pregnancy can also induce other kinds of pains and discomforts. We call them implantation pain or growing pain. Sometimes women tell us that they "feel" a sharp pain within a week or two post transfer. I cannot discount that sometimes the women who complain of this pain (and I have IUI patients who tell me the same) do have a positive pregnancy test. Another possibility on the right side, of course, would be appendicitis. You can still get other illnesses despite trying for pregnancy. However, appendicitis, is progressive and does not come and go. Once the pain started it would progressively get worst. That doesn't fit your wife's scenario. Without further evaluation it is hard to know what is going on. You should probably bring this up with your doctor.

As a side note, if your wife is actively trying to get pregnant using IVF or FET, then I would not recommend a 3 mile walk right now. She should limit her activity to more sedate activities. A short normal walk would be fine, but power walks are not recommended as are heavy exercises like aerobics, karate, gymnastics, running, etc.

Good luck with your cycle and I hope that this will be a success!

Sincerely,

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.

Empty Gestational Sac After IVF

Question:

Hello, Dr. Ramirez,

Does In Vitro increase the odds of an empty gestation sac? I am 6 weeks pregnant and had an ultrasound with no heart beat detected. I bled just before the ultrasound but there was no bleeding before that.

Two frozen embryos were implanted but only one sac is visible on the ultrasound after the bleeding. The sac is round and empty. What do you think?

Answer:

Hello,

I'm sorry about the news. The answer to your question is no, IVF does not increase the risk of genetic abnormalities in the fetus. An empty gestational sac is due to the lack of development of the fetus. That occurred AFTER implantation, and therefore, after the IVF. It probably occurred due to a genetic defect in the embryo that implanted. It is considered a form of miscarriage, which can occur in up to 40% of pregnancies whether natural or IVF.

Many women who get pregnant naturally are not aware that they are even pregnant before they "lose" the pregnancy. Because we test and ultrasound IVF patients soon after transferring the embryos, they have the opportunity to learn if their pregnancy is proceeding or not proceeding earlier than most. This is not necessarily a bad thing, since actions can be taken to prevent miscarrying in subsequent IVF cycles.

Good luck and keep trying!

Sincerely,

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.

E2 Levels Falling While On Follistim, Why? PCOS Patient Asks...

Question:

Hi, I am a 29/f with PCOS, secondary amenorrhea, non-IR, normal weight. We've done Follistim + Ovidrel + IUI 3 times and it never worked. Upon HCG administration my E2 was around 500 never higher. My RE works at a superbusy teaching hospital clinic.

This cycle we are doing the same thing with injectables. My E2 dropped from 400 to 60 but my follicles are still growing (dose never changed). Why is this? I tried doing some research and journal articles indicate that this is correlated to poor outcomes even in IVF. I also think that I have no LH in my body because before the cycles on Follistim my test line on the OPK's would be half as dark as the control, now I see absolutely no test line on all the days prior to HCG trigger.

Answer:

If the E2 drops despite the follistim, that is an indication that the follicle is either not growing or deteriorating. It is the growing follicle that produces the estradiol. You are correct, this heralds a poorer prognosis. It is possible that you may need some LH in addition to the FSH (follistim).

You should discuss this with your doc. Keep in mind that it is difficult to get a PCOS (polycystic ovarian syndrome) patient to stimulate normally, and at a low rate with injectables. Most will overstimulate and produce too many follicles which necessitates that the cycle be cancelled.

For this reason, 85% of PCOS patients will eventually need to use IVF (in vitro fertilization) to be successful. It is the only way that we can control the number of embryos transferred into the uterus despite the ovaries over stimulating. At your age, your chances at succeeding at IVF with a positive pregnancy are very high and it is possible that there would be embryos to freeze as well for a future (cheaper) frozen embryo transfer if you would wish to have more children.

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.