Sunday, June 23, 2013

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

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

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
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.


  1. Dr. Ramirez,

    I am a 38 year old woman; my husband is 37. I have DOR & poor responder to stimulation and my husband has a low sperm count. Also, my AMH was undetectable a year ago. My day three labs come back well within normal levels -- E2, P4, LH and FSH. I menstruate regularly with clear signs on ovulation, cervical mucus and rise in temperature. I am overweight and am a well-managed diabetic (for a year now).

    We have had one failed IUI, which was a converted cycle from IVF, because I only had one follicle, but there were multiple follicles that "popped up," but went away. I was on 300 FSH/150 Menopur with Ganirelix. We triggered with ovidrel, with clear signs of ovulation, but sperm count was low so chances were not good. I felt ovulation, but think my levels of progesterone were too low to support implantation and pregnancy -- they only had me on endometrim suppositories three time per day; I think I needed injectables too and to have P4 level monitored, but this clinic didn't do that until you got a positive preg. test. BFN.

    We've had two failed IVF cycles. First one, I had two follicles but only retrieved one immature egg, which was matured by IVM from GV to M2 and fertilized with ICSI. Tranferred 4-cell embryo -- not sure why we didn't wait for 6-8 cell. BFN. Dr. thinks he went in too soon by 12-24 hours. I also think I needed another booster shot of HCG. Additionally, there was no good signs of ovulation, in fact, I was quite dry vaginally. For this cycle I was on 900-1450 of Follistim, HGH, ganirelix and novarelle. I had one booster of novarelle after ET because P4 was 5 and should have been 20 or higher. The entire time, though, from retrieval to transfer, I felt like I was going to start my period. BFN.

    Second one, we used 1800 Follistim, HGH, ganirelix, actos and ovidrel. We had four follicles, but no eggs retrieved. Dr. claims empty follicles or they eggs died early. I think that we went in too early and the trigger was insufficient to induce ovulation because, again, no signs of ovulation. We had intended to add 2-3 boosters of novarelle for P 4 with suppositories.

    I am now on EPP -- estradiol and prometrium -- for one month. Dr. says it will sensitize me to the stimulation drugs, but I am dubious. I have normal numbers, with no indication of egg quality issues. I think the the stimulation protocol is not optimal and the ovulation trigger is insufficient as well as the timing being too soon. But, I'm not a MD; so, I don't want to conflate my disappoint with his potential error.

    My questions are:

    1. Why did ovidrel work well to stimulate ovulation with the IUI, but ovulation has been sub-optimal with the higher doses of stimulation drugs? Was the LH in menopur the key to better ovulation for me?
    2. Should we switch clinics? Two failed attempts with the same doctor have made me very wary.
    3. Does HGH do more harm than good? Or, is it worthless -- we pay for it out of pocket, $500 to $670 each time.
    4. Is my poor response linked to my weight?
    5. Any thoughts for ways to improve my chances??

    1. Hello,

      You've asked some very interesting questions but I don't think there is an answer to all of them. I think the second question is the most important one and the answer to that question is YES.

      I don't use HGH, although there are many doctors that do. I don't think it is useful based on multiple studies.

      Weight does not affect response to stimulation.

      You have two major inhibiting factors and some smaller ones. The major ones are your age, which reduces your chances because of egg quality issues, and decreased ovarian reserve/response, which reduces the number of eggs you have to use with each cycle. There is no treatment to improve egg quality. The way IVF helps is by being able to extract multuple (lots) of eggs in the hope that you will find one that is still good, but if you don't stimulate well and lots of eggs are not reteived, then your chances are not increased.

      Finaly thought, you should never cancel an IVF cycle and go to IUI. IVF, even with only one follicle, will always be better than an IUI because it helps with the sperm problem but also many more of the steps required to become pregnant, whereas IUI depends almost completely on all the steps in the natural process.

      At some point, you may have to seriously consider using donor eggs. Only you can decide when that point is.

      Good Luck

  2. Thanks for your response to my many questions, Dr. Ramirez. Your suggestion of changing clinics makes good sense, as we've lost "faith" in this doctor.

    We are glad to know that weight does not impact response to stimulation; it must be the DOR.

    We have been told that we should/could consider donor eggs, but we think that we nearly got four eggs this time but because of errors did not -- though, I guess it is possible that the quality of the eggs were so poor that they were irretrievable, but my FSH is always normal...


    1. What indicates to you that we should find a new doctor? That is, what aspect of our history indicates that a change is necessary? We'd like to know in order to assure that we are making a very sound decision as looking for doctors and going through the work-ups are quite extensive.
    2. How many more attempts should we make before we move on to donor egg or accept that we are child free? We are not interested in donor eggs -- we prefer a genetic child.

  3. 1. You had doubts regarding your doctor's advice and explanations such as whether you had enough progesterone and whether the retrieval was done at the correct time due to the lack of eggs being retrieved. IVF is a very elaborate and draining experience and confidence in your doctor has to be high. They need to meet your expectations.
    2. The discussion between no child and a donor egg child is one I have often. Certainly, you can try as many times as you feel you need to, as long as you can tolerate the procedures, emotional let downs and can afford it. If you don't try, certainly it will not happen. On the other hand, you can save yourself a lot of time, emotional cost and financial cost by going to donor eggs which will give you a higher chance. Keep in mind that although the child would not be yours "geneticallly" it will still be your biologically, have your husbands genetics and will be nutured in utero by you. In addition, what is so important about having your genetics? Did you ever check to see if your genetics are the same as your parents' or is there something special about your genes that it has to be yours. I know that a lot of people put a great deal of value on carrying on their genetics, but did you realize that all humans share genetics? We all came from the same source! Sure we have special characteristics, that MIGHT be unique, but we also have characteristics that we might not want to pass on. Finally, I have had husbands say they want a child that will look like their wife, but that is not a for sure thing. Genetics is a funny thing in that certain characteristics are passed on and activated, and others aren't. The child could look more like the husband, more like the wife or a combination ofthe two. So it is not something that you can count on. Don't rule out donor eggs so quickly. Having a biologic child is hundreds of times better than having no child. It is a unique gift, and no experience can take its place.

  4. Thanks for your thoughts and information -- we have appreciated your insight. We will consider it, especially the distinction you make between biologic and genetic children. We are familiar with epigenetics (both of us have advanced degrees/PhDs), but are still somewhat wary and want genetic children.

    I am on the second month of EPP with estradiol and prometrium; my husband is recovering from his fifth bout of MRSA. We learned today that clindamycin and Bactrim could have majorly impacted his sperm count this past year.

    If we do not switch clinics, the doctor wants to use 1800 of Menopur for five days for moving to 1800 Follistim for the rest of the stimulation -- we are also interviewing two other REIs in our area.

    If you have any other thoughts, please share them.



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