aromatase inhibitors

carnelian

14 Posts
Reply Posted on: Mar 2, 2012 at 2:01am
Hi Dr Braverman

I've been reading about aromatase inhibitors being used for repeat implanation failure particularly for patients who have been diagnosed with a deficiency of beta3 integrin in the uterine lining - and you've mentioned them previously in your posts about resveratrol having an effect as an aromatase inhibitor.

In this study http://humrep.oxfordjournals.org/content/27/3/881.abstract

using letrozole for 5 days during the follicular phase seemed to correct the deficit in about 2/3rds of patients suggesting that inhibiting aromatase and reducing ovarian estrogen production must help improve expression of b3 integrin.

As far as I understand it, repeat implantation failure patients, especially those with mild/moderate (but not severe) endometriosis and those with other inflammatory problems like hydrosalpinges.

In the study, for OE IVF patients with RIF associated with the deficit adding letrozole for 5 days during the early part of stimulation seemed to raise the pregnancy rate a lot.

Presumably a similar protocol of 5 days letrozole could be used during the lining prep phase for medicated FET or DE.

I've been trying to understand the mechanism of letrozole better so I could understand whether there would be any downside to letrozole treatment and whether it would be sensible to try it for ladies with RIF who hadn't actually done the biopsy for b3 integrin.

I couldn't find anything to suggest that including a 5 day course of letrozole for RIF patients would have a downside (except that high responders would presumably need their stimms doses adjusting downwards because of the ovarian stimulatory response of letrozole).

Are you aware of anything that would make adding letrozole to the IVF protocol more widely for unexplained RIF patients - ladies who already feel they have tried 'everything else' without success?

Thanks again!

Dr. Braverman

2017 Posts
RE: aromatase inhibitors Posted on: Mar 2, 2012 at 5:04am
you are correct. I have used letrazole in both my FET cycles and fresh cycles without complications. The unpublished studies that were posted at the last ASRM conference showed benefit to those patients with endometriosis who used letrazole during an FET cycle and no benefit(but no harm ) to those that did not have endometriosis but used the letrazole. We have expanded that on our own to fresh cycles and as you have suggested , we modified the need for gonadotropins when using letrazole.
Dr. Jeffrey Braverman MD FACOG
Medical Director
Braverman Reproductive Immunology P.C.

carnelian

14 Posts
Reply RE: aromatase inhibitors Posted on: Mar 2, 2012 at 8:43am
Thank you. I found the titles to those presentations but nothing seems to have published in journals yet.

Although, it did lead to an interesting detour about the Egyptian study where 500 IU of HCG was infused into the uterus 7 minutes before ET. For good prognosis (young, no fibroids, 1st cycle of IVF only etc) patients, it seemed to lift the pregnancy rate from 60% to 75%.... and when 100 or 200 IU of HCG was used there was no benefit - so that does seem to confirm that the HCG must actually do something rather than the benefit being purely from the infusion of liquid....so I am wondering whether we would expect poor prognosis i.e,. RIF patients to benefit more or less from trying this - as you can probably tell, I get really excited when I read about low cost, low tech advances. Do you have a view on the HCG infusions, or do we just need to wait until there are some confirmatory studies?

Anyway, back to the letrozole, I guess what I am thinking is that there may be ladies with RIF who might have mild undiagnosed asymptomatic endometriosis and therefore benefit from letrozole in the protocol - and its probably not justifiable to do a laproscopy to see if they do have endometriosis given the risks of scarring from unnecessary surgery.

So for diagnosed endometriosis patients who have RIF adding letrozole to their IVF/FET/DE protocol seems like a 'no-brainer'

but for RIF patients who are asymptomatic and have never had a laproscopy I am not quite sure why 5 days of (very cheap!) letrozole isn't thrown in automatically just in case they happen to have undiagnosed endometriosis?

Thanks again for being such a fabulous and interesting doc!

Dr. Braverman

2017 Posts
RE: aromatase inhibitors Posted on: Mar 2, 2012 at 8:47am
One you are correct about the letrazole this is why we use it here(you might think of applying for a job here!). No need for laparoscopy if not desired we just add the letrazole as I had the same thinking as you , and early on I like the results.

I read the Egyptian study and you are correct it proves by higher doses it really is a cause and effect. We are treating our first patient this week with this protocol just for what you stated, it is less expensive and as I have stated previously must have similar mechanisms to G-CSF.

Good Luck , let me know if you need me.
Dr. Jeffrey Braverman MD FACOG
Medical Director
Braverman Reproductive Immunology P.C.