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.

 

Second IVF Fails Despite Implantation: Thin Lining? Embryo Issue?

Question: Dear Dr. Ramirez,

I am here to seek your advice once again. I just found out my second IVF (in vitro fertilization) attempt finished with a chemical pregnancy. I tested HCG levels at 11dp2dt and it was 19,2 miu/ml (pretty low), and 48h later it was already 4,7 miu/ml.

I am nearly 37yo, have high FSH levels and my antral follicle count was 12 for this past cycle, 8 follicles grew, 6 were collected and 4 eggs retrieved. We got 100% fertilization and we transferred two 8-cell embryos with perfect morphology and no fragmentation.

I think my biggest problem is my endometrium. It is usually very thin. Although I still have 2 frozen embryos from my first IFV, two transfer cycles were cancelled due to thin lining that would never pass 6.9mm. I tried estradiol patches, vaginal estradiol (creme and pills) which resulted in poor endometrial growth (estradiol levels reached 3500pg/ml in one cycle) even after 3 weeks of use. I also tried vaginal viagra, vitamin E, baby aspirin, prednisone, and nothing worked... the endometrium would grow up to 5.5 to 6mm in the first 8-9 days of the cycle and then would take 14-21 days to reach 6.9mm. In one of the cycles it even decreased 1mm in one week.

Before my first IVF I did a hysteroscopy and everything looked fine. I have a couple small intramural fibroids, none projecting into the uterine cavity. I had a big fibroid removed 4 years ago, but it was intramural and the endometrium was not touched during surgery.

So, in my last IVF that turned out as a chemical pregnancy, my endometrium was 7.1mm at the 6th day of stimulation with FSH (Bravelle), which was really encouraging. However, 2.5 days later, it decreased to 6.4mm... Because at that time I already had bid leading follicles, my doctor wanted to triger that night. He then injected into the uterine cavity, using a catheter, 300 ug of filgrastim (G-CSF), since there are two papers from Dr. Gletcher that mention it as a possible treatment for thin lining. My RE explained to me it was experimental and I agreed to try it.

48h latter and on the time of egg retrieval, my endometrium was 7.6mm. Still not ideal, of course, but the best I got in a long time, so my RE advised us to carry on with the transfer (2 beautiful 8-cell embryos).

So my questions are:

1)What is more likely to be the cause of the chemical pregnancy: genetically abnormal embryo or my thin lining?? I know my age is a factor, but I have been taking Coq10 for nearly a year now. My embryos always look good and I have 100% fertilization rate.

2) Also, I wanted to know if it is normal to have a 8-cell embryo at the end of day 2 (I collected the eggs on Mon 9am and the embryos were transferred Wed 6pm).

3) Is it normal for the endometrium decrease during stimulation phase? What could have caused mine to go from 7.1 to 6.4mm in a little over 60h?

3) Do you think I should try filgrastim on my next transfer cycle? I don´t think my body likes synthetic estradiol though, it never responded well... so maybe a natural cycle (in which I usually reach 7mm) with filgrastim could work?

Taking my history into account, what would you recommend for my next FET in order to be suscessful in overcoming thin lining? Should I start to look into surrogacy?

As always, I really appreciate your time and expertise, and most of all the beautiful work you do here at your blog (for which I am a subscriber :)  C. From Brazil

Answer:
Hello C. from Brazil, Thank you for your kind words and for following my blog! Let me answer your questions in sequence to make it easier.

1. If endometrial thickness were the problem, implantation would not have occurred. Technically, the minimum endometrial thickness required is 6.5 mms so your lining was adequate for implantation to occur, which did happen. The miscarriage was most likely a genetic issue considering your age. Unfortunately, we do not have a technology to evaluate internal egg quality nor change the quality. Keep in mind that the CoQ 10 study was in mice and not humans so we don't know if that will work or not.

2. An 8-cell embryo on D#2 is not normal. That is a rapidly dividing embryo and may indicate that it is genetically abnormal, as has been found on preimplantation genetic studies in the past. Division rate is one of the criteria I use to evaluate embryos, in addition to the external quality.

3. The endometrium does not decrease. The difference in widths are variations in ultrasound measurements. Because we are dealing with mms, the difference between 7.1 and 6.4 (0.6) is within the margin of error and not significant.

4. I cannot comment regarding the "filgrastim" as I am not familiar with this medication or its usage. I would recommend that you consider the frozen embryo transfer in a natural, unmedicated cycle, but I would follow a natural cycle without transfer first to evaluate if your body growth the endometrium to adequate width. Then if it does, I would schedule to make do the transfer in the next cycle. I would still use supplemental hormones after the transfer, namely progesterone to help support implantation and the early pregnancy.

5. If the FET fails, despite everything that has been done, the only other recommendation I could make, if you are still going to try your own eggs, is to have preimplantation genetic screening done (trophectoderm biopsy) on a Day #5 embryo. Some studies have shown increased pregnancy rates in older patients when embryos are screened for normal genetics. That will at least give you an indication on the genetic health of the embryos you are making and whether or not you should consider donor eggs. I would only recommend surrogacy if you are absolutely sure that you cannot get implantation and in your case, you've had implantation. I think it might be more of an embryo issue.

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.

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.

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.

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

Woman In Tasmania Has Done 14 IVF Cycles At One Center And Now Faces An FET: What Advice Can You Give Me?

(**If the blog-talk radio starts up, go to the October 1st blog post below & pause it...I will be keeping the show up for the month of October.)

Question:

Dear Dr Ramirez,

Someone wrote a comment on my blog suggesting I ask you. Basically, I was asking what questions to ask my RE. This is the post she was responding to:

Here’s where I am: I’ve been doing IVF/ICSI since July 2006. We started because my husband had a vasectomy many years ago, so it’s not like we’d been trying for years and didn’t know what was wrong and needed a diagnosis. We knew we’d need IVF if we wanted any hope of having a child.

I live in Hobart, Tasmania. There’s one clinic with only 2 REs: one who is part-time (he’s mainly an obsetrician) and one who is full-time. We started off with the part-timer but have been with the full-timer for a few years now. I would say they pretty much don’t have individualised treatment. They have a few standard protocols, but mainly seem to pride themselves on keeping treatment costs low so patients can have many cycles. Quantity, not quality. If you have repeated failures, they don’t do investigations; they just suggest you keep on going on.

To go to another clinic would cost us money, time, more stress, and be logistically difficult. That’s not to say I’m not up for it if need be. However my husband gave me the ‘I’m tired of treatment and would rather not pursue it, but I’m doing it for you’ bombshell the other night. So I don’t know if I could drag him by the testicles to an interstate clinic to try to get different treatment. I’m willing to go without him though. Having a child has become muchmore important than my marriage.

The only investigations I’ve had are a laproscopy, hysteroscopy, hydroscopy a couple years ago (I had endo, which was removed, and the hydroscopy as inconclusive as fluid didn’t move through my tubes but they looked OK). My obstetrician ordered a bunch of blood tests after Blobby’s miscarriage: protein C, protein S, AT 3, Anticardiolipin antibodies, LAC, Factor V Leiden, Prothrombin G20210A mutation MTHFR C677T mutation, MTHFR C677T mutation, and Karyotyping.I find it unbelievable that after so long, they still don’t try to find out WHY we’re having the problems we’re having. They never check hormone levels (not even during stim cycle – he just relies on ultrasounds to tell him what’s happening), they don’t check for implantation issues, there’s been no renothing. Hearing about the testing that goes on in other clinics has really opened my eyes. I would welcome finding out I had a problem because then we’d know whether it would be likely to be able to be fixed or if we had no hope.

Questions I’ve come up with are:

1. As one of our embryos is a 3 day and the other two are 4 day, can the 3 day be thawed used this time and thawed a day ahead? That way if it doesn’t thaw we still have 2 more we can attempt thawing.

2. Is there a wait list for donor semen? (There wasn’t a few years ago when I did 7 DI/IUI cycles, but I think there is now. Want to know just in case.)

3. Might DHEA help my embryo quality?

4. Any news on the egg donor wait list (Australia's)? (This is probably a stupid question; I know other women in Australia on the wait list and we all seem to get difference answers to our questions. Someone who is 27 was told recently she should have a donor by January 2011 – sorry, but that’s a HUGE porky she’s been told!)

5. The best embryo we’ve had was from a down regulation cycle. Is this just a coincidence, or should be try down regulation cycles again?

6. What sort of implantation failure testing can be done?

If you are interested, my blog "Riding The IVF Roller Coaster" is at http://tasivfer.wordpress.com/. I am writing from Hobart, Tasmania, Australia. Australia's island state - and a long way from any clinic other than the one I've been with for soooooo long. . .Cheers,TasIVFer

NOTE: As of 2012, TasIVFer is a MOM! "After 4 1/2 years, 14 fresh IVF cycles, 7 donor inseminations, 4 FETS, and the loss of my dear son Blobby at 14 weeks 2 days, we tried (half) an egg donor. Blood test 10 December 2010 = BFP. Little Spark was born 6 August 2011!!! He LIVES! Now the journey continues with an FET in November 2012 with our last embryo. Perhaps our last ever?" Good for her!!!

Answer:

Hello TazIVFer from Australia,

Let me take your questions in sequence and answer them the best that I can.

1. The Day #3 frozen embryo certainly can be thawed and cultured to align with the Day #4. My recommendation would be to thaw both, one day apart, and allow them to culture to blastocyst if your home lab has that capability. That may give the embryos a better chance of implantation. You don't mention what the cell # and grade was at the time of freezing but that is an important factor. As the saying goes, bad in-bad out. That means that if the embryo is poor quality, culturing further does not make it better quality. It may not survive the culture.

2. I cannot answer your questions regarding donor sperm wait lists. In the U.S., there are no donor sperm wait lists. Donor sperm are readily available. I guess that's because there are more men in the U.S. than Australia.

3. DHEA will do nothing and is not recommended. However, I would recommend that you consult my blog where I addressed the issue of implantation failure. I do have my own, specific protocol that I use for patients that fail IVF. Because I don't have any precise information from your cycles, I cannot give any specific recommendations.

4. Again, no egg donor wait lists in the U.S.

5. Coincidence probably but I would have to look at your cycle information to do a detailed analysis.

6. There are no specific tests for implantation failure.

I hope this answers your questions adequately. It is unbelievable that you have gone through so many cycles. I don't know of many women and their husbands that could manage the stress and frustration of prevailing through IVF for so long. I wish you the very best of luck with your FET cycle!

Keeping my fingers crossed! Good Luck,

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

High Prolactin Levels Can Interfere With A Successful IVF Cycle

Question:

Hiya,

I'm 28 years old and had the first cycle of ICSI done a month ago. The reason for ICSI was that my husband has a very low sperm count and motility. My test date was 26th August and I started bleeding on the 24th of Aug. I went for a beta hcg which was 4.73.

I had a high prolactin level (35) for which I was given Dopergin (Bromocriptine) until Embryo transfer which was on the 12th of Aug. I was not told to continue it and I was stupid enough not to ask about it. I had 3 Grade A embroys transferred but there was no implantation. I had my prolactin test done on the 25th of Aug and it was 48.

My question is, could the high prolactin have been a reason for implantation failure? I'm not trying to play a blaming game but I need to know if this could've been avoided particulary as have nine day 2 frozen embryos and I plan on going for FET after my next cycle in September.

Thank you. A. from Spain

Answer:

Hello A. from Spain,

It is our protocol in the U.S. to check all the hormones prior to starting any infertility treatment cycle. This is so that we can eliminate anything that might interfere with the success of the IVF cycle. Of course, we check other things as well, and thus, have the highest pregnancy rates in the world. Traditionally, prolactin levels were measured in ng/ml, and normal prolactin levels in women are less than 20 ng/ml. (The new units now are pmol/l and to convert you need to multiply by 44. This means a normal level is less than 700 pmol/l.)

Since your prolactin was found to be elevated prior to the IVF cycle, and 35 is not very elevated, you were been placed on the Bromocriptine ahead of time in order to get the level back to normal prior to starting the cycle. There is no question that an elevated prolactin level can interfere with fertility.

My recommendation would be to get your level back to normal prior to your FET cycle!

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.

"What FET Protocol Do You Use For Difficult PCOS Patients?" UK Patient Asks

Dear Dr Ramirez,

Firstly, thank you so much in advance for taking the time to read my question.

Brief History: Dx with PCOS at 17 y/o. HSG clear. My husband has severe m/f, so our only chance of conceiving is through IVF with ICSI. On my fresh cycle in 2008, I had 30 eggs retrieved and due to OHSS, couldn't have an Embryo Transfer. We had 13 embryos, all of which were frozen at the 2PN stage. I have gone through six FET cycles since, but only got to transfer three times, b/c the drugs used to suppress my ovaries (ProstapSR, Buserelin, Synarel) have actually stimulated my ovaries, leading to OHSS a further three times!

My treatment is in the UK and I cannot switch clinics b/c a) my treatment is free and b) since it's free I can't choose where to have my IVF/FET's. The Drs at my clinic have put their heads together to try to come up with an individualized protocol for me, since I keep suffering these rare responses to the suppression meds. I am naturally frightened and sceptical about this new protocol since it hasn't been tried and tested in the UK as yet (but apparently it has in other countries with good success for challenging PCOS patients).

The new protocol would not involve the usual suppression medications. On day 3 of my period, I would inject a long acting Cetrotide shot (sub-q) and also commence 6mg Progynova (estradiol valerate). On Day 5, I would commence daily Cetrotide shots, whilst continuing daily with the Progynova. All in all, this protocol should only take around 13days, then I would commence Progesterone, 3-4days before Embryo Transfer. I am terrified of hyperstimulating again. Is this likely to happen with the Cetrotide at all? Have you had any PCOS patients who have ever responded like I have to suppression medications?

If you were my Dr (I wish you were :D ), what protocol would you suggest for a FET? It may be helpful to add that I have always been a slim PCOSer (BMI 21) and have an AMH of 98.5. I also got pg on our first FET with twins, which I sadly miscarried at 8 weeks. My subsequent two transfers resulted in a negative beta. Thank you so much for reading and for any input you may be able to give! G. from the U.K.

Answer:

Hello G. from the U.K.,

I have never heard of such as thing as OHSS with an FET cycle. I'll have to do some research on that and see if that actually happens. If not, your docs might want to write your case up as an unusual case. Since you have been using GnRH "agonists (stimulators)" in your previous cycles, it sounds like maybe the dosages were not high enough to suppress the hypothalamus (which is what they are supposed to do and prevent ovarian function), but instead stimulated FSH production and ovarian stimulation leading to the OHSS.

I think the change to an "antagonist" is certainly the best way to go. I converted to using the antagonist, Cetrotide and now Ganerelix, over 5 years ago (mainly because it is less injections). I have not used it with an FET cycle (because it is more expensive), but it can work just as well with the protocol you have outlined. The antagonist will definitely suppress any ovarian function, so you should not be able to mount an OHSS response. This is definitely a good plan.

I thank you for the compliment :) and wish that you could be my patient as well. For many reasons, such as the fact that some like you can get IVF for free where they live, patients feel that they are stuck in the clinic near their home. This cannot be further from the truth. I have a patient from Serbia and South Korea in my IVF cycle this month. I have patients come from out-of-state, one from as far as Montana, which is like the difference between the UK and Poland. You can travel to the best center to do your IVF, thereby saving you years of frustration & grief. I had one patient who failed five times at a Los Angeles center only to succeed the first time with us. It is not that difficult to do or arrange IVF afar. There are additional costs involved, which is the biggest factor, but heck, you could plan a vacation at the same time. The IF community calls this "Reproductive Tourism" or "Cross-Border IVF", I believe.

An IVF cycle can be done so that you only have to come here for the minimum necessary time, which for an FET cycle would be 1 week or less or 10 days for a fresh cycle. Also, remember the old adage, "you get what you pay for." Free cycles are all well and good, but as you mentioned above, you are stuck with one center, one protocol, one embryology lab (and there quality can differ greatly), governmental restrictions and that is unfortunate. In the U.S., particularly in California, we have few restrictions and can do embryo donation, donor egg, donor sperm, frozen eggs, surrogacy, and are given leeway on the number of embryos we can implant. I wish that I could just outfit a 747 jet with an IVF clinic and jet all over the world where patients want to see me. I think that would be fun as well :D !!!

Good Luck,

Edward J. Ramirez, M.D., FACOG

Executive Medical Director

The Fertility and Gynecology Center

Monterey Bay IVF Program

www.montereybayivf.com

Monterey, California, U.S.A.

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

IVF Patient With Positive Beta On Immunoglobulins (IVIG) & Has Questions

Question:

Good day Dr Ramirez,

I wrote to you a while ago. We just completed our 3rd IVF (in vitro fertilization cycle) and 2 , 5-day frozen blastocysts were transferred.

I had a blood test on day 10 post transfer and the result was positive. I suffer from rheumatoid arthritis. My doctor gave me 5ml immunoglobulin (integram) on day 2 of my cycle and 5ml again 10 days post transfer. I am also on 600mg cyclogest as well as folic acid , baby asprin, omega 3 & 6 and staminogro.

I am still concerned about the arthritis and worry about the anti bodies - is the immunoglobulin sufficient - what is the protocol, what do you suggest?

My second question is. From the day of the FET I felt this twitch on my left side of my uterus . From 7 days post transfer I have lower back and stomach pains.

Should I worry? I have heard that it is normal for FET patients to get pains and cramps and it is good pains. I have no spotting though. My first beta on day 10 was 198 and my second beta on day 12 was 416 .Can you please advise. Thank you. V.

Answer:

Hello V.,

I believe the immunoglobulin is sufficient from a fertility point of view, but I don't know in regards to the arthritis. You would need to consult a rheumatologist to get the answer to that question.

The pains you are having are probably normal. Many women experience some uterine cramping or pains in the early pregnancy. We call these "growing" pains. Your bHCG levels are good so things look good. At this point, you just have to hope for the best. Congratulations and stay positive!

Follow-Up Question:

Thank you so much for your reply. Do I understand correctly that the dosage of the immunoglobulin that I got is sufficient for the duration of the whole pregnancy and I don't need to get additional imunoglobulin again? The reason why I ask is that I had a miscarriage 7 years ago ( a natural cycle without any meds)- due to the antibodies of the athritis and I am concerned that it might happen again.

Follow-Answer:

Hello Again,

Because the use of Immunoglobulin in IVF is controversial, there are no set protocols or dosages. Therefore, I cannot comment on the dosage or times of delivery. In my experience, however, it is given at the beginning of the cycle, after the transfer and if pregnant again at that time. I would recommend that you look up the Reproductive Immunology Associates website (www.rialab.com/ivf_immunotherapy.php). They are immunologists that have geared their practice specifically to reproductive issues. They will have more specific information regarding the use of immunoglobulins. They will also answer email questions.

Good Luck,

Edward J. Ramirez, M.D., FACOG

Executive Medical Director

The Fertility and Gynecology Center

Monterey Bay IVF Programwww.montereybayivf.com

Monterey, California, U.S.A.

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

Secondary Infertility, High Responder PCO Patient: Why Did I Fail Two IVF Cycles?

Question:

Hi, I am 28 years old and my husband and I have a naturally conceived 3 year old son. We are dealing with secondary infertility. We have gone through 2 IVF cycles.

1st IVF/ICSI cycle-21 eggs--11 fertilized (70% fert. rate)--transferred 2 great 8 cell embryos. None to freeze. Negative result

2nd IVF/ICSI cycle

19 eggs--(85% fert. rate)--8 embryos on day 3

1-8 cell grade 1 (best)

2-8 cell grade

21-8 cell grade

32-7 cell grade

22-5 cell grade 2

No transfer because of lining issues. Did one FET--ended in a chemical pregnancy.

My question--do I have poor egg quality? Lab results said some eggs were abnormal, with thicker zona. Any hope to go through IVF again?

I'm from Fargo, ND. Thanks in advance!

Answer:

Hello M. from North Dakota,

From the number of eggs retrieved, I presume you also had a high number of follicles (>20). That indicates that you are responding like a PCO patient, or have PCOD. Studies have shown that there is a decrease in pregnancy rates with PCO patients, probably due to a high number of immature eggs retrieved. It also seems to affect egg quality. That is not because you have abnormal eggs, it is probably because the PCO causes an inefficiency in egg maturation.I would not give up hope. In fact, I would encourage you to continue trying because you will be successful. It may take some more tries, and hopefully, your doctor will adjust your protocol to try to reduce your stimulation. It would be better to have fewer follicles with good eggs than lots of follicles with poor eggs.

By the way, I just had a patient from your end of the country, Montana, that previously went to a clinic in Washington state and had two failed IVF cycles. She was a secondary infertility patient as well. Well, the change in weather or location or clinic did the trick because she became pregnant with one attempt, and with twins. Infertility Physicians and clinics are not all equal. That may have a bearing on your success as well. I am worried about the fact that despite all the eggs, your embryo quality rate and number to freeze were so low. That might also indicate a laboratory issue.

In any case, don't give up hope. You will eventually be successful.

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.

Comment: Thank you for your insight! Very much appreciated! :)

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

New IVF Patient Mixed Up Suppositories & Took Progesterone Early - What Now?

Question:

Hello Doctor,

I am one day before fresh embryo transfer and I'm really worried. I'm currently on my first IVF. Two days before my egg retrieval last week I was instructed to use Clindamycin suppository at night for 3 nights last night being the day of my egg retrieval. Well, I mixed up the suppository bags and inserted 50 mg of Prog suppositories for first 2 nights instead of Clindamycin. I didn't realize this mistake till the day of my egg retrieval. So I ended using 2 Prog suppositories for 2 nights before my egg retrieval.

I told my doctor and he said this is a problem in that my uterus was exposed to progesterone too early therefore lining is not optimal for transfer...and that we need to freeze my embryos and do a frozen embryo transfer next month! I was just devastated to hear the news and asked for any alternatives. To make the long story short we are going ahead with a fresh single embryo transfer tomorrow with hopes that not too much damage was done. Given my history what are the chances of me actually getting pregnant? Would it take a miracle?

R. from the U.S.

Answer:

Hello R. from the U.S.,

Keep in mind that miracles do happen.

I'm afraid that I agree with your doctor's response. Progesterone converts the endometrium from its growing state to its implantation phase. If the endometrium is out of phase with the embryo, then implantation will not occur. There is a very small (2 day) window for implantation. It is likely that the progesterone changed the internal architecture (cellular structure) of the endometrium, which will make it inhospitable to the embryo and implantation will not occur. But there is no way to know that for sure. You will just have to wait and see.

If you want to be absolutely sure, then you should postpone the transfer and freeze the embryos. Then do a frozen embryo transfer the next month. If you don't mind risking an embryo, then given it a try. I normally prescribe antibiotics on the day of the retrieval, but all clinics have their own protocols specific to how the physician prefers to tweek their cycles. Like I said at the beginning, miracles do happen.

I'm sorry and stay positive!

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.

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.

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.