spontaneous pregnancy, recurrent miscarriage and now a poor responder for IVF

[AndreaD]

I am 33 years old have had 5 spontaneous pregnancies, most recently in October 2008. My first pregnancy resulted in my daughter (now turning 4) without any difficulties. Of my 4 losses, one was due to amniotic band syndrome. I have been extensively investigated for recurrent miscarriages with no abnormal results on imaging or bloodwork.

My fertility specialist suggested I try IVIG, and because I do not live near a fertility clinic we decided to try IVF maximize my chances of achieving a pregnancy and to facilitate the timing of the IVIG. Now I have encountered a new problem. I am a poor responder to the stimulation drugs.

This is actually my second IVF cycle, having tried once before (July 2008) when my husband had a transiently low sperm count. In the first cycle I was lupron/200 puregon (increased to 250 on day 8) and had 4 follicles, 3 eggs, 2 good quality embryos transferred on day 3, no pregnancy. For this cycle we are using a GNRH antagonist (orgalutron), menopur 150 and puregon (starting at 150, now increased to 250) and I am on day 10 of the cycle with only 2 follicles of adequate size.

This was very unexpected as I have achieved spontaneous pregnancies recently. Is there a link between me being a poor responder to stim meds and my recurrent miscarriage? Is this an indication that my ovaries are 'older' than expected for my age, and I have poor quality eggs leading to the pregnancy losses? Does this alter my prognosis? I've read that poor responders do not have a good prognosis for IVF, yet I have had several spontaneous pregnancies. I guess I am hoping that makes me somehow different, all though I am finally starting to lose hope.

a.

[Dr Jeffrey Fisch]

There is indeed a link. Egg quality is determined at ovulation when the egg finishes dividing it's chromosomes. If this occurs abnormally, as it does with increasing freqency as you get older, then the egg will be genetically abnormal. In some cases a bad egg can result in a baby, like Down's syndrome. Most abnormal pregnancies cannot survive and that is why they fail. In fact we believe that 70-90% of all miscarriage in the first 12 weeks of pregnancy is caused by an abnormal egg. This is also related to poor embryo development and poor response to stimulation.

Since egg quality is not determined untilt he time of ovulation, the period of time between when they become reactivated and when you ovulate is a time where the hormone environment the follicles see can influenece the development of the maturing eggs.

In the natural cycle, estrogen promotes growth and LH gives the egg a signal it is supposed to die. We believe poor responders, (among others, including those with high FSH levels, unexplained infertility, endometriosis, decreased ovarian reserve) have become overly sensitive to the male hormones in the stimulation medications as well as the natural amounts of male hormone your body makes on its own.

For this reason our protocols are designed to maintain "estrogen dominence" in the follicles. We believe this will help to proect the egg quality. We don't like protocols with a lot of Menopur or the standard antagonist approach. We have a different approach called agonist antagonist conversion with estrogen priming that may work better for you and is certainly an alternative to consider before oocyte donation.

If you contact me directly, I would be happy to review your case with you in more detail. We do have many patients travel from around the world to have treatment with us in Las Vegas.

Jeffrey Fisch
jfisch@sherinstitute.com

[AndreaD]

I've read the abstract of your paper (2008) on the agonist/antagonist cycle with estrogen priming. It appeared as though the live birth rate did not differ significantly amongst the groups. Are there subgroups of patients that you think might benefit the most from this approach? The pregnancy rate also remained low ~25%. I assume this goes along with the poor prognosis for poor responders. Is it at all possible to do parallel cycles in the recipient and egg donor so that my very few, possibly poor quality embryos could be transferred along with one good donor blast? My husband is having a very difficult time with the disappointment of my poor response, and if we do another IVF intervention would like me to proceed directly to a donor cycle to optimize the chance of success. I think that there is no doubt that a embryo from a 20 something donor will have a better chance than my almost 34 year old, poor responder embryos.

[Dr Jeffrey Fisch]

If you like I can discuss the options with you. Both groups in that study got the protocol. There were two different doses. We reported almost 30% ongoing pregnancy in both groups (<38, 38-42). Everyone in the study was told by a prior doc that they had less than 5% chance of delivery. Egg donor does have a 60% delivery rate per transfer.

Jeffrey Fisch