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QUESTION: Dear Dr. Ramirez,

I am here to seek your advice once again.
I just found out my second IVF 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 donīt 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 and at your blog (for which I am a subscriber :)

Cindy

ANSWER: Hello Cynthia from Brazil,

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.  The 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 D#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.

for additional information check out my blog at http://womenshealthandfertility.blogspot.com check me out on twitter with me at @montereybayivf and facebook @montereybayivf.  Skype and internet comprehensive consultations now available via my website for those who want a more extensive evaluation that this site can accommodate

---------- FOLLOW-UP ----------

QUESTION: Dear Dr. Ramirez,

Thank you so so much for your input!
I would like to know if you think itīs worthwhile to try estradiol valerate intravenously in order to get a better lining. This is the only form of estradiol I had not tried. Iīve heard it hurts a lot but what is the dosage and frequency one has to take it during FET?

Thanks again for all your help!
Cindy

ANSWER: Hello again,

No I would not recommend it.  It would not be better than vaginal estrogen.

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.

for additional information check out my blog at http://womenshealthandfertility.blogspot.com check me out on twitter with me at @montereybayivf and facebook @montereybayivf.  Skype and internet comprehensive consultations now available via my website for those who want a more extensive evaluation that this site can accommodate




---------- FOLLOW-UP ----------

QUESTION: Hello Dr. Ramirez,
Iīve meant to write back to you for a while now, but I donīt have a question this time around. I just wanted to tell you my beautiful baby boy will be one year old in early September :)
Last time I wrote to you (Dec/12) I was already naturally pregnant and I didnīt know about it.
I just wanted to thank you for your time, kindness and support during my journey to motherhood, even though I was not your patient.  What you do for people like me is truly amazing!
All the best and may God bless you!
Cynthia

Answer
How wonderful!  Congratulations and you are sincerely welcome.  Have fun being a mom.

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.

for additional information check out my blog at http://womenshealthandfertility.blogspot.com check me out on twitter with me at @montereybayivf and facebook @montereybayivf.  Skype and internet comprehensive consultations now available via my website for those who want a more extensive evaluation that this site can accommodate

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Edward Joseph Ramirez, MD, FACOG

Expertise

I am a specialist in infertility and advanced gynecological care. I can answer questions about infertility, gynecology related ills, menopause...virtually anything that affects women's health. PLEASE tell me where you are writing from as I am always interested.

Experience

I have been practicing as an Ob/Gyn and Infertility Specialist for over 23 years. Gynecology, advanced laparoscopic surgery, basic infertility, IUI's, IVF, reproductive surgery, and ovulation induction are all areas of my expertise. I am Board Certified. I have been doing In Vitro Fertilization in my clinic for 19 years.

Organizations
American College of OB/GYN, American Board of Obstetrics and Gynecology, American Society of Reproductive Medicine, Society of Assisted Reproductive Technology, American Association of Gynecologic Laparoscopists, Fellow of The American College of Obstetricians & Gynecologists,Resolve-National Chapter, Open Path - Northern California, Board of Directors Monterey Medical Society

Publications
American Journal of Obstetrics and Gynecology, Wall Street Journal, Monterey Herald, SERMO, Women's Health and Fertility Blog

Education/Credentials
Medical Degree from Stanford University, Residency at Tripler Army Medical Center, Reproductive Training at Pacific Fertility Center, San Francisco

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