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Infertility/Fertility/Spontaneous pregnancy following 15 failed IVF cycles.

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Dear Dr Ramirez,

I'm writing to you from Melbourne, Australia. I would be appreciative of your opinion regarding my fertility issues.

I am now 34 years old, however my husband (37) and I began trying to conceive nearly four years ago. We are both healthy with no medical or previous gynaecological problems for myself. I ovulate regularly, with a 28 day cycle and my husband was found to have no issues after a number of semen analyses.

We tried naturally for approximately 12 months before seeking the advice of an experienced fertility specialist at a well regarded clinic in Melbourne. I work in the health care industry and I sought the opinions of gynaecological colleagues before engaging this specialist.

I had a HSG, which showed my tubes were patent and serial blood tests which showed that I did indeed ovulate regularly. I also undertook testing for autoimmune factors.

From there we undertook 3 cycles of IUI with no success. We turned to IVF.

I responded well to an Antagonist Cycle, collecting 19 eggs, which resulted in 9 high grade embryos. We transferred 4 embryos over the next four cycles using progesterone without any sign of implantation. I then had a laparoscopy and D&C which revealed a small amount of endometriosis, mainly affecting the uterus, left ovary and bowel. The endometriosis was all removed bar the small amount on the bowel. My specialist believed that this remaining endometriosis was insignificant.

The remaining embryos were grown onto blastocyst. All embryos made it to blastocyst and remained good quality. They were transferred singularly over the next few cycles with no sign of implantation.

We had several more pickups, again resulting in good numbers and good quality embryos over the next few months. We also tried Down regulation cycles. We continued to grow to blastocyst and began transferring two at a time. The progesterone was increased to 800mg per day and I had a number of cycles using clexane and prednisolone having read about NK cells.

I then had another pickup and had three embryos sent for PGD using micro array. All three embryos were normal chromosomally and made it to transfer which again resulted in failed implantation.

I then sought the opinion of a well renowned specialist at a different clinic. He suggested that my treatment had been appropriate and he could not suggest where the problem lay.
I changed to a third specialist, again very well renowned and head of the IVF department at Melbourne's biggest clinic.
He undertook a number uterine biopsies which indicated that there may have been a phase delay. I had two more transfers increasing the progesterone from the day of pickup, without success.

I am aware of your opinion on the importance of transfer technique and I believe given these practitioners reputations and success rates that this is not where the problem lay. The transfers were always straight forward without any issues.

His opinion was that since we produce good quality euploid embryos, I must therefore have a uterine defect and should consider surrogacy.
We had a willing surrogate and after many months preparation were approaching transferring an embryo to her when I spontaneously fell pregnant. The pregnancy is proceeding well.

I had read studies on aspirin and implantation failure which showed negligible but increased implantation rates nonetheless. So I began taking 100mg per day. I had been taking it for two cycles when I fell pregnant on the second.

I would be interested to know if you feel the aspirin had any influence or where you think the problem lay.
In summary I had 3 IUI cycles and 16 embryos transferred, both a number of fresh and frozen, and never a pregnancy.

Thank-you for your time,
Christine

Answer
Hello Christine from Australia,

First, CONGRATULATIONS!  God does work in mysterious ways.

It was very interesting reading such a well written letter from a highly intelligent source.  You seemed to have done lots of research and showed that you have been thinking from every angle.  You even posted my answer at the end, regarding transfer technique, which showed that you have researched me as well.  

It is difficult for me to do a comprehensive review and find a potential source of failure without reviewing every facet of your medical records.  But assuming that the transfer techniques were not an issue, I'm not sure of the cause, but it is very interesting that you got pregnant spontaneously after adding aspirin to your regimen.  That indicates that there might have been some type of subclinical immunological issue going on, which is the theory behind endometriosis.  Because the last three steps of the reproductive process in an IVF cycle are "natural" steps (egg hatching and exiting from the shell, attachment to the endometrial lining and lining growing around the embryo (implantation), there is no way or technology to determine why well transferred good quality embryos did not complete those steps.  Those are the steps that I attribute to God.  We may never know what it was that didn't work or why.  

I will share with you, however, that in my patients I place all of them on low dose aspirin, low dose Medrol (prednisone), extra progesterone and extra estrogen to help reduce the inflammatory/immunological response and increase blood flow to the endometrium.  In patients that fail two IVF cycles, I also add low dose heparin.  I still do get some cases of implantation failure but not that often.  Maybe that would have helped several cycles ago.

Congratulations and Good Luck,

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

Monterey, California, U.S.A.

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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