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jmr67 - January 6th, 2007 6:21 PM

Hello Dr. Smith – need I repeat how invaluable you are/have been to myself and so many scared uncertain couples trying desperately to have a child. I am at a point where I am not sure what to do next. I will be as brief as possible but need to give you all the details. I am 39, DH 40. Age is an issue for me (obviously) and after my most recent FSH of 9.3 I am getting close to borderline ovarian reserve. (Right?) DH had an 18yr vas reversal. Previous 2 children 1 normal son and 1 Downs Syndrome daughter – determined to have come from the mother’s side as he is negative for translocation or any chromosome disorders and mother has 2 Downs Syndrome relatives. DH sperm count post reversal btw 15-26million washed, Motility >50%, Morphology 7% (strict so they say). DH had prior chemical exposure in Gulf War and at your suggestion SCSA resulted surprisingly at DFI 12% (excellent range) and HDS 11.8%. We had 2 unsuccessful IUIs. Our IVF history is as follows…all microdose lupron flare protocol…..

IVF/ICSI #1 Feb/06- On birth control 32 days prior to stims - 14 eggs retrieved, 11 mature, 11 fertilized. 2 high grade day 3 embryo’s xferred – result blighted twins. Missed miscarriage 10wks (misoprostol).
IVF attempt #2 Jul/06– Birth control 44 days prior to stims – cycle cancelled only 9 follicles but growing slowly only 3-5 possibly mature and E2 very low. (RE feels anything over 6wks on BCP could result in oversupression and this was likely my problem)
IVF/ICSI #3 Oct/06 – Birth control 24 days prior to stims – 11 eggs retrieved (dysynchrony noted) 6 mature, 3 fertilized. 2 medium grade and 1 low grade embryo xferred. Note 1 medium embryo slightly oblong – result 2 fetuses 1 appeared to have arrested around 6wks and 1 arrested w/in days of 8wk u/s based on size. Doc said there must have been a heartbeat but it stopped. Missed miscarriage 9wks (misoprostol)

My RE feels another try is warranted. He will do autoimmune testing and advises use of baby aspirin although I have a possible aspirin allergy which will be confirmed prior to use. He does not suggest any change in protocol. Previously I had asked you about MDL protocol w/ regards to older women and high levels of androgens possibly being detrimental to egg quality but you said the androgen theory was not ready for prime time :) .

If you are still reading thank you! I would appreciate any thoughts you have or advice you could give me. Do I have an egg quality issue with 4 implanted embryo’s but no continuing pregnancies? Do I still have a chance? Could enough tries to get the right egg/sperm combination result in a live birth? Is there anything you would do differently? Thank you so much for your time.

Dr Smith - January 8th, 2007 4:41 PM

Yes, I read your entire infertility manifesto - just kidding.

I think the autoimmune testing is important. If nothing more than to rule out automimmune issues as a contributing factor. The baby asprin protocol is pretty common, so, as long as you are not alergic to asprin, it can't do any harm and it may do some good.

From your description, I'm beginning to suspect a genetic "problem" with the embryos. Not necessarily from your eggs, but likely so. Its not the number of miscarriages per se, its the nature of the miscarriages. I'm not a big fan of the use of preimplantation genetic diagnosis (PGD) as a panacea for recurrent miscarriage, but you might want to give it some thought. Especially if the autoimmune testing is normal. Quite a bit of data has now accumulated to support the use of PGD in cases such as your own. Speak with you doctor about it. Even if they don't routinely perform embryo biopsies for PGD, they can bring someone in to do it (of course, at added expense to you).

I would also suggest growing the embryos to the blastocyst stage (what a surprise) because embryos that result in a "blighted ovum" can be spotted prior to transfer. They have a small/inadequate inner cell mass (to few stem cells to make a baby). Considering your history, that alone is a pretty good reason. If you are a frequent visitor to this board, you know my position on blastocyst culture and transfer, so I won't get on that soap box again.

jmr67 - January 8th, 2007 9:14 PM

Sorry for the book :) Just thought it would help to know the details.... Thanks again and I will take your advice and consider the PGD. I asked about it before my last cycle but the doc felt it did more damage than good.... I do know and respect your position on blastocyst culture and transfer :) My biggest concern is does the lab have adequate experience with it and I really don't know how to confirm that. One follow up confirmation if you will....do you agree with not changing the MDL flare protocol to something w/out the high initial LH such as GnRH Agonist/Antagonist Conversion Protocol (A/ACP) with estrogen priming? If this is not a question for you could you possibly ask Dr. Jane?

Dr Smith - January 10th, 2007 4:07 PM

Its a clinical question. I prefer to leave these questions to Dr. Miller. I'll forward your post. She's doing a chat room tonight, so she won't reply until tomorrow.

jmr67 - January 15th, 2007 9:08 PM

I was wondering if perhaps Dr. Miller might have missed this one? Could I possibly get her opinion regarding the protocol question above? Thanks again.

Dr Smith - January 17th, 2007 8:34 AM

I forwarded it again. We're very busy right now (lots of IVF cases). I'm sure she'll answer as soon as she gets a chance.


Dr Jane - January 17th, 2007 4:47 PM

Hello-
Here's my take on it all: I agree with Dr. Smith that it may be the genetics of the embryos that are causing the px. to miscarry. Remember: you are not old - but you are "older". Genetically abnormal embryos that cannot "go the distance" are more common as we age. This phenomenon happens sooner in some than in others. It's a raw deal !! Now, in answer to your question: I don't think that there is a known detriment from the initially high LH in the microdose flare protocol. It's 6 of 1, half a doz. of the other if you repeat this stimulation or use gonadotropins and GnRh antagonists. Estrogen priming may help slightly. Using the OCP as you have is just fine. I strongly believe that 2 things would give you more information and may be helpful in directing your treatment. The first is a complete autoimmune workup including natural killer cell analysis. Recurrent px. loss may be secondary to increased NK call # or activation. The second thing is blastocyst culture of all your embryos. (You've heard the benefits of this from Dr. Smith.) I do not believe that PGD will add much at this time - except a hefty addition to the pricetag.
Good luck!
Dr. Jane

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