# G-CSF helps build Endometrium



## ellesters

*G-CSF can help women improve endometrial thickness, according to new study from Center for Human Reproduction*

New research at a leading New York fertility center, Center for Human Reproduction, confirms that endometrial perfusion with G-CSF can dramatically improve endometrium in IVF cycles for patients with treatment-resistant endometrium.

For immediate release

November 15, 2012 (New York, NY) - Direct perfusion of the endometrial cavity with granulocyte colony-stimulating factor (G-CSF) improves the thickness of the endometrial lining in IVF patients with too thin endometrium even after treatments, according to a new study just published online in the medical journal Human Reproduction1.

In the study, 21 women undergoing in vitro fertilization (IVF) cycles at the Center for Human Reproduction (CHR) in New York City successfully expanded their initially inadequate endometrium after uterine perfusion with G-CSF. Specifically, in the 5 days between G-CSF perfusions and embryo transfers, patients increased their endometrial thickness from 6.4 ± 1.4 mm to 9.3 ± 2.1 mm. The result offers confirmatory evidence to an earlier, smaller report by the same research group on the positive effects of G-CSF on IVF patients with treatment-resistant, thin endometrium.

In natural menstrual cycles, endometrium develops on its own in preparation for embryo implantation. In IVF cycles, endometrium of at least 7 mm at the time of embryo transfer is considered necessary to achieve superior pregnancy rates. When endometrium is too thin and does not respond to conventional treatments, embryo transfer is often cancelled and embryos are frozen for transfer in a later cycle.

"Treatment-resistant thin endometrium is a fortunately rare, but frustrating, problem in IVF," explains Norbert Gleicher, MD, Medical Director and Chief Scientist of CHR, the lead author of the study. "Affected patients, until now, at minimum, faced treatment delays and, not infrequently, if their endometrium could not be improved even in subsequent cycles, had no choice but to use a gestational carrier (surrogate)."

David H Barad, MD, MS, Director of Clinical ART and Senior Scientist at CHR, and another senior author of the study, adds: "This is why when in 2011 we reported our initial four cases in the literature, patients and colleagues took notice. One can still transfer embryos into the uterus with endometrial thickness under 7mm, but IVF success rates will be very low. G-CSF perfusions really offer affected patients the opportunity to drastically improve IVF pregnancy chances."

1Gleicher N et al. A pilot cohort study of granulocyte colony-stimulating factor in the treatment of unresponsive thin endometrium resistant to standard therapies. Hum Reprod 2012; (http://humrep.oxfordjournals.org/content/early/2012/10/17/humrep.des370.abstract)

Located in New York City, CHR (http://www.centerforhumanreprod.com/) is a leading research and clinical fertility center in the world, having contributed many important innovations to the treatment of infertility. As "fertility center of last resort," CHR treats patients worldwide, with, during 2011, over half coming from outside the New York tri-state area, approximately a quarter from overseas. Drs. Gleicher and Barad are available for further comments.

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## Mistletoe (Holly)

Yes - but not without side-effects.
G-CSF is used after cancer chemotherapy to return a patient's white cell count levels to normal after the chemo has suppressed them.

Given to a normal person with an already normal blood count it can put the white cell counts up to very high levels.

One lady on here I know tried it and had success, amongst many other drugs, but her white cell count went up to 4 times highest normal levels and she had abnormal cells in the blood. She had to see a haematologist and it was quite scary for a while.

If anyone is considering this treatment you should discuss the risks and benefits of unlicensed treatment.


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## ellesters

My understanding is that white blood cell count is not affected in the same way by the uterine wash - which this study is referring to.  Neupogen injections, which I believe are usually used in conjunction with other immune treatments, does have that risk and most ladies who have been prescribed it need to have their WBC monitored.  

This treatment, while relatively new in Europe, has been in use by Dr. Braverman (USA) for a number of years now.  Lots of info/experiences available on the subq injections on the Yahoo immunology forum.  

There's also a new to the market culturing medium using G-CSF called Embryogen which looks promising as well. 

xx Ellie


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## devitt

Has there been any recent update on this? I can find that they were doing a randomised controlled trial (http://clinicaltrials.gov/show/NCT01202643), but no results published, and any reference to G-csf and thin endometrium have been removed from the Center for Human Reproduction website. I would really like to know whether it is worth trying or not. Anyone has any news?

Thanks,
d


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## ellesters

Hi Devitt,

They haven't published the full results of the trial but the interim results were published in a journal called Human Reproduction in Dec 2012.

http://humrep.oxfordjournals.org/content/early/2012/10/17/humrep.des370.abstract

In this study they were successful in increasing endometrium from less than 7mm to 9mm+. Small sample size (only 21 women) and about 20% clinical pregnancy rate, which I thought rather disappointing in contrast to the earlier pilot study of 4 where all the women got pregnant! But in all cases it allowed the cycle to go ahead when otherwise it would have been cancelled. I think it's worth a try.

Good luck!

xx Ellie


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## Dudders

I just thought I'd come back with a little update on this one for anyone interested .....

I'd had one fresh cycle and one FET where my lining failed to get above 6mm - the fresh resulting in a freeze all because of the lining issue and the FET only went ahead because I insisted.

Following these I went for a follow up and although I had read this article, I hadn't really given it too much more thought - it didn't appear to be widely available and I feared it would be very expensive anyway.  So I was pleasantly surprised when the consultant suggested it and also when it was less than £100 to do.  As my lining hadn't responded to anything else and little else could be done, I felt it was a reasonable choice to make.

So we went ahead with a further fresh cycle, and this time my lining didn't even reach 6mm.  The uterine wash is carried out on the day of trigger and if required, repeated on the day of egg collection.  At the time of the first wash my lining was 5.5mm and on ec day I was disappointed to hear that it was only 5.4mm.  Therefore the wash was repeated.  We managed to reach blastocyst and although I wasn't hopeful, 5 days after ec my lining had reached 7.4mm.  In fact it was described as a lining that you wouldn't have spent the last 3 weeks worrying about - which is in reality what had been happening!

I appreciate that this is an off label use of this drug but I honestly believe that I wouldn't be sat here now able to say that the cycle resulted in a positive test for us.  So in my book, definitely worth a shot, but of course everyone has to make their own decisions.


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## devitt

Hi Dudders - 

Congratulations! And thank you so much for posting your news. 

I had 5 cycles with unresponsive lining. I am currently undergoing a mock cycle with GCSF to see if it can kick-start my lining into action.

Enjoy your pregnancy.

d
x


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## Dudders

Thanks devitt  

Really hope it makes a difference for you


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## krolland70

Hi Dudders interesting info , where did you have GCSF wash done was it the lister I am trying to have treatment at Serum in Athens but June cycle was cancelled due to thin lining of only 5.5mm, however they only started Cyclacur on day 9 of cycle by Day 14 no improvement and lead follince dropped form 13mm on day nine to a few at 7mm. I am having double donor and also have elevated NK Cells as well as Thrombophila issues.

Unsure if I should trackk a couple of cycle with scans?? does Oestrogen sometimes not work with some people??


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## Dudders

Hi krolland70,

I did indeed have the GCSF wash done at the Lister.

I'm guessing that you were originally planning to do a natural cycle hence the mention of follicles etc and that the oestrogen was introduced as an attempt to rescue the cycle.  If this is your first cycle, I wouldn't suggest diving straight in to things like GCSF as it may have just been a bum cycle for you.  From what I know of Serum, they close for August so I certainly don't think it would hurt to track a cycle whilst you wait over the Summer.  Though for control it would make more sense to do a medicated cycle in my humble opinion, so would make sense to get another prescription and do a mock cycle and check out what happens to your lining then, with starting the oestrogen at the beginning of your cycle.

There are many treatments that can be tried for thin lining - take a look at Agate's immunes FAQ under L for lining.  GCSF was only used in my case as my lining is considered treatment resistant.  And on occasion yes oestrogen doesn't work for some people - my oestrogen level was through the roof on the latest fresh cycle and yet still no real lining growth.


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