Monday, December 10, 2012

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

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
Monterey, California, U.S.A.


  1. Hello Dr. Rameriz,
    I'm not sure how to ask you questions, as I'm on my phone, and can't see your entire page. So I hope that you can find the time to answer my question in your comment section. I am desperate. I've asked countless doctors, and done hours and hours of research, and still can't find a simple answer.
    Okay, I have suffered through 5 losses, and have one healthy daughter. It all happened in this order: chemical pregnancy, miscarraige at 6 weeks (started bleeding & no heartbeat found on ultrasound, baby measured the same two weeks later), a missed miscarriage at 8 weeks followed by d&c, my daughter, and then 2 chemical pregnancies in a row. All of these happened with my husband.
    I had all of the testing after my 3rd loss, and everything came back normal. I couldn't accept that, so I tried thinking of everything... that's when I thought of the Adderall my husband and I are both prescribed.
    See, we always took it, even while trying to conceive, but I would stop it immediately when I got a positive test. The funny thing is, when I became pregnant with our daughter, we weren't taking it much that month, as there was a shortage. I mean, could this really be a coincidence? I thought using an over the counter progesterone cream after getting my positive test was what made her thrive. Now I'm beginning to think otherwise. Especially because I went back on my adderall after having her, and had the two losses even though I used the same cream.
    Here are my questions:
    1. Can adderall affect fertility, and should it be taken while trying to conceive?
    2. Can adderall affect sperm quality, egg quality, or uterine lining?
    3. Did stopping my prescription cold turkey possibly have an affect on the baby?
    4. Do you know anything else about getting pregnant while taking prescription adderall?

    My husband and I have both stopped taking it this month in hopes to have another healthy child. In the mean time, I'm still so desperate for answers.
    Thank you so incredibly much in advance. You have no idea how much an answerv would mean to me.

    1. Hello,

      Sorry for the delay in my reply. Somehow I missed your question.

      "Addreall" is an amphetamine and considered a category C drug. Basically that means there are no tests in humans during pregnancy to determine whether it is safe or not but in mice there are fetal abnormalities. It also means that it has been taken by patientd during pregnancy and not adverse effects have been reports (these are not studies however).

      My recommendation to all my patients undergoing fertility treatments is to not take any exogenous chemicals other than what I prescribe because there is no way to predict what effects it might have. As you know, people's bodies can respond to chemicals differently.

      There is no way to know if this was the cause of your miscarriages. You don't mention your age, but age plays a significant factor in miscarriage rates, especially from 35 years old and on. Since this drug has not been studied or tested at the egg, sperm or uterine lining levels, or any other reproductive level for that matter, I can't give an answer regarding that part of your question.

      Good Luck

  2. hello edward
    i want to contact you
    how can i it?
    do you have mail? please tell me

  3. Hi Dr Edward,
    my name is Mos. I had my embryo transfer on the 8th December 2012 and I had a slightbrownish spotting on day 3 after the ET. On the 15th Dec(a week after ET)I started spotting and the spotting has continue since till today 23rd december. I did a urine PT yesterday 22nd dec and it was positive and also a blood test which shows a weak positive result. Am kind of worried abt d cramps and spotting for over a week. what do u advise. thanks. Mos

    1. Hello,

      I have found that spotting or bleeding in early pregnancy can be a relatively normal occurrance. Why it occurs is not necessarily known. It could be vaginal progesterone, if you are using this. There is some cervical erosion or irritation from vaginal progesterone.

      However, it could also be a bad sign that the pregnancy is not progressing well. There is no way to know what exactly is going on so all you can really do is wait and see how things progress. I have seen many patients have such bleeding and have very successful pregnancies so all is not lost.

      Good Luck

  4. I am 32 and have had 10 chemical pregnancies (naturally and 2 ivf and 2 iuis). Thin utterine lining of 5-7mm. Treated for high uterine killer cells which are now normal. Just had ivf again using cyclogest, lining was 7.4 on egg collection. Positive bhcg at 57.9 8 days after embryo transfer. Started bleeding day later lining was 5mm. Now not pregnant.Always fails just after ppositive pregnancy test. Do you think its my lining or my immune system? I have chromosomes checked and all OK.

    1. Hello. By definition, you have recurrent pregnancy loss and should undergo a complete evaluation for this. Potential reasons include anatomical, genetic, immunological, infectious disease and hormonal. Since you've not given me the details of any testing you have done, or the medication protocols you've used, I can't tell you what might be the problem, what needs further testing or what would be an appropriate treatment. I'd be happy to do that for you as a personal consultation. Just go to my website and contact me there to set up the consultation. If you then send me all your records, I will review them and make specific recommendations. There is a fee for that service.

  5. Hello Doctor Adward

    I am 33 and have undergone 2 IVF cycles which failed despite embroyes were A grade in quality with 4-6 cell division .The endometrium grew till 11mm on day of trasfer in both cycles. I had E-coli infection for which I had taken a course of 10 days antibiotic injection before my second IVF cycle. I had chemical pregnancy resulting second IVF. Now I will be on Frozen cycle and my doctor has prescribed down regulation from 14th day of my previous cycle and with EMGRAST 300 mcg injection to be inserted during second day of my cycle which is due tomorrow. Please advise how safe is EMGRAST 300 mcg injection for my health ? What is the success rate of using this type of medication ?

    1. First, 4-6 cells is not good if these are D#3 embryos. Ideally they should be in the 7-8 cell range. Certainly you could get pregnant with 4-6 cells but that may indicate that there is some type of embryo development problem going on OR that the lab has a problem so the embryos are not growing well.

      I'm sorry that I can't comment on the "Emgrast". I've never seen nor used that medication before and from reviewing it on the web it is only described for use in cancer and not fertility. So, basically, I don't know what your doctor is using it for. It would be great if your doctor could explain it to you and then you can share that information with me.

    2. It is not something that is being used in the U.S. for fertility purposes so maybe your doctor is trying something rather new?

  6. Hello Dr. Ramirez.......

    I am preparing to do my third ivf transfer and I am 37. Do have any suggestions to help this be a success procedure? My two previous transfers have been a fail. One fresh and one frozen.

    1. I'm afraid you would need a formal consultation for such recommendations as I would need ro review your records to see what was done and why you might be failing. Age is certainly a factor, but there could be something else as well. Also keep in mind that pregnancy rates vary from clinic to clinic. If you decide that you want a formal consult, please contact me via my website. It can be done via email or Skype if you are not in my area.



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