PR Research Thread - NO CHIT CHAT!!!!!

[TryMeditate]

VIAGRA AND IVF

Dr Sher and Dr Fish from USA reported that three out of four women became pregnant after taking the drug Viagra while undergoing IVF treatment. These women had already experienced many failed IVF treatments. The reason beyond the use of Viagra was to increase the blood flow to the uterus and to improve both the pattern and thickness of the endometrium. Viagra suppositories rather than oral tablets were used in order to reduce the side effects such as headaches and low blood pressure because it deliver the drug near the proximity of the uterus. A large randomized study needs to validate the efficacy and  safety of this treatment which, if proven, may offer hope for some women who can not conceive because of the poor quality of their endometrium.
A longer interview with Dr Sher on the use of Viagra
http://www.storknet.com/cubbies/infertility/exgs1.htm

Viagra used to thicken lining in the uterus – BBC article
http://news.bbc.co.uk/1/hi/health/741125.stm
 
As always I'm thinking about women with POF.  I wonder if "increasing the blood supply" to the uterus could help with follicle development?  I think I'll add this to my list of things to try on myself..... now if only someone would hand me some Viagra suppositories :-)
 
 
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[FertilityFriends]

[theodora]

I've emailed a few compounding pharmacies to find out what's in the viagra suppositories, no answers yet. It's not good science for folks to be publishing papers that cannot be reproduced because they don't say what is actually in the pills! However I suspect that will change as this treatment catches on a bit.

Wanted to add this article to the research listing, I was able to download it & it is kinda interesting. They ADDED Viagra to the treatment, & treated all the women differently depending on what their other problems were (so some got prednisone, some got that + IV Ig, etc), so again not reproducible...

But anyway, they conclude:
"The present data shows the effects of vaginal sildenafil on NK-cell activity and endometrial thickness in women with a history of RM. According to our knowledge, these data suggest for the first time that sildenafil might be a useful therapy in RM patients. The data suggest that sildenafil has no detrimental effect on NK-cell activity; on the contrary, NK-cell activity was significantly decreased after vaginal sildenafil therapy in the study women. The mechanism of sildenafil’s influence on NK cells is unknown; however, it can not be excluded that improvement in uterine artery flow has efficient influence on the local endometrial NK-cell population, and the diminished NK cell activity may promote successful pregnancy outcome. Additionally, sildenafil significantly improves endometrial thickness, which is especially important in successful implantation. Therefore, sildenafil citrate introduced vaginally might be a novel therapy improving the quality of the endometrium and the immunologic environment in recurrent miscarriage patients."

http://www.ncbi.nlm.nih.gov/pubmed/18440513
"Sildenafil citrate decreased natural killer cell activity and enhanced chance of successful pregnancy in women with a history of recurrent miscarriage" (Jerzak M, Kniotek M, Mrozek J, Gorski A, Baranoswi W )
ABSTRACT
OBJECTIVE: To   evaluate the effect of sildenafil on peripheral natural killer (NK)   cell activity in women with a history of recurrent miscarriage (RM).
DESIGN: Observational study.
SETTING: University teaching hospital.
PATIENT(S): Thirty-eight nonpregnant women with a history of RM and 37 healthy women with previous successful pregnancy outcomes.
INTERVENTION(S): Patients self-administered sildenafil suppositories (25 mg intravaginally, four times a day) for 36 days.
MAIN OUTCOME MEASURE(S): Peripheral   blood NK-cell activity before and after vaginal sildenafil therapy in   the RM women was measured using flow cytometry. In addition, the   influence of 10 microg and 400 ng sildenafil on NK-cell activity after   in vitro culture were determined. Uterine artery blood flow and   endometrial thickness were recorded using Doppler ultrasound with an   intravaginal probe.
RESULT(S): The   NK-cell activity was significantly decreased after vaginal sildenafil   therapy. Endometrial thickness was significantly increased after such   therapy.
CONCLUSION(S): Vaginal sildenafil might be an interesting therapeutic option before conception in women with histories of reproductive failure.
 
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[theodora]

I found a recent article where they finally explain: "The sildenafil suppositories were prepared from the oral tablets. The tablets were mashed and dissolved in Hosco S-55 (25 mg sildenafil/1.35 g Hosco S-55)"(from: "Endometrial growth & uterine blood flow: a pilot study for improving endometrial thickness in the patients with a thin endometrium," Fertility & Sterility April 2010, vol 93 issue 6, pages 1851-8.)
So basically a compounding pharmacy could easily do this for you -- they'd just put it in a gel-like base which helps to keep it from going away too fast. That's probably why the pills themselves are supposedly not as useful, they aren't absorbed as well (but there is no proof yet so who knows).

In this study, they used vitamin E, L-arginine, & Viagra for ladies with thin linings & not good blood flow, & all methods were better than doing nothing & much better than placebo. The sample sizes were pretty small so validity of the science is limited, but they were very enthusiastic about vit E treatment & also about Viagra. I'm just wondering what happens if you take them all -- is your blood flow too much? do they cancel each other out?


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[TryMeditate]

1. Exposure to Chemicals in Environment Associated with Onset of Early Menopause
 
Exposure to perfluorocarbons associated with lower concentrations of the hormone estradiol
A recent study accepted for publication in The Endocrine Society’s Journal of Clinical Endocrinology & Metabolism (JCEM) found that higher levels of perfluorocarbons (PFCs) in the body are associated with increased odds of having experienced menopause in women between 42 and 64 years old. Women in this age group with high levels of PFCs also had significantly lower concentrations of estrogen when compared to women who had low levels of PFCs.
PFCs are man-made chemicals used in a variety of household products including food containers, clothing, furniture, carpets and paints. Their broad use has resulted in widespread dissemination in water, air, soil, plant life, animals and humans, eve in remote parts of the world. A probability sample of U.S. adults, found measurable concentrations of PFCs in 98 percent of the participants tested.
“The current study is the largest ever to be done on the endocrine-disrupting effects of perfluorocarbons in human women,” said Sarah Knox, PhD, of the West Virginia University School of Medicine in Morgantown and lead author of the study. “Our data shows that after controlling for age, women of perimenopausal and menopausal age in this large population are more likely to have experienced menopause if they have higher serum concentrations of PFCs than their counterparts with lower levels.”
In this study of 25,957 women aged 18 to 65 years, researchers ascertained menopausal status of participants and then measured their serum concentration levels of PFCs and estradiol. They found that there was an association between PFC exposure, decreased estradiol and early menopause in women over age 42.  There was also an inverse association between PFC levels and estradiol in women of child bearing age but this association was not statistically significant.
“There is no doubt that there is an association between exposure to PFCs and onset of menopause, but the causality is unclear,” said Knox. "Part of the explanation could be that women in these age groups have higher PFC levels because they are no longer losing PFCs with menstrual blood anymore,  but, it is still clinically disturbing because it would imply that increased PFC exposure is the natural result of menopause.”
PFCs are known to have multiple adverse health outcomes including increased cardiovascular risk and impairment of the immune system.
“Our findings suggest that PFCs are associated with endocrine disruption in women and that further research on mechanisms is warranted,” said Knox.
Other researchers working on the study include: Timothy Jackson, Beth Javins, Stephanie Frisbee, Anoop Shankar and Alan Ducatman of the West Virginia University School of Medicine in Morgantown.
The article, “Implications of Early Menopause in Women Exposed to Perfluorocarbons,” appears in the June 2011 issue of JCEM

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[TryMeditate]

The Bright Side of PCOS - PCOS may make fertility last longer
 
An extraction from the article below, full article at
 
http://www.smh.com.au/lifestyle/diet-and-fitness/bright-side-to-pcos-paradox-20111017-1lt1w.html
 
"There is perhaps a evolutionary twist to the prevalence of PCOS among women. Since the condition causes women to ovulate less regularly, they tend to have better fertility than other women later on in their reproductive years. In a manner of speaking, their bodies hold on to their eggs, so they last for longer. One evolutionary explanation is that female bodies adapted to times of famine by increasing insulin resistance to save calories and extend the reproductive years.
 
"PCOS might have been a good thing to have in times of food scarcity because it allowed the window of fertility to be extended and it allowed women to survive and preproduce in low fuel environments. Today we have calories all around us, and yet the body's possible adaptation to another time still remains for some women. One way to look at PCOS is as a past adaptation gone astray." Dr. Sarah Berga says, speaking on PCOS at a recent conference."
 ---------------------------
   FYI - a lot of fertility clinics prescribe Glucosophage for women with PCOS which helps control blood sugars allowing them to fall pg more easily.
 
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[Apple Orchard]

I found this. In principle it sounds very interesting. If anyone understands it properly, I'd be very grateful for a translation!

http://humrep.oxfordjournals.org/content/23/6/1355.full

Thank you in advance!


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[Apple Orchard]

I have read about people taking Melatonin and Inositol for poor responders. Has anyone heard of this? The research has been carried out in the US and apparently, the UK.

This is from September 2010, so a while ago, but still relevant.

http://www.news-medical.net/news/20100915/Hormone-melatonin-improves-egg-quality-in-IVF.aspx


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[TryMeditate]

For all those with POF and very low AMH this is interesting research.  It's a small study, that shows something we have long suspected.  Just because a woman has POF doesn't mean she doesn't have ovarian activity from time to time.  In this study in shows 24% of the women with POF showed ovarian activity - I'm guessing in order to predict "when" they must have used some kind of regular ultrasounds.  By the way, a recent UK study now believes the number of woman under 40 affected by POF is more likely to be around 7 or 8%, not the 1% previously thought.
 
http://www.menopausematters.co.uk/newsitem.php?recordID=125/Intermittent-Ovarian-Activity-May-Follow-Premature-Ovarian-Failure

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[TryMeditate]

A very very interesting breakthrough.  Maybe women are not born with a limited number of eggs after all.  Human stem cells generate new eggs in human ovarian tissue. 

http://www.nature.com/news/egg-making-stem-cells-found-in-adult-ovaries-1.10121

http://gma.yahoo.com/stem-cell-finding-could-expand-womens-lifetime-supply-190304876.html

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[wehavethreecats]

Apple Orchard
Just come across this thread and saw your post about the "Flexible GnRH antagonist versus flare-up GnRH agonist protocol in poor responders treated by IVF: a randomized controlled trial"   by Lainas et al. 

I looked at the statistics they report in the abstract, and it doesn't actually show very promising results (at least not in terms of statistically significant terms). Their results show that the outcomes weren't much better than chance... 

They say that "Ongoing pregnancy rate, the primary outcome measure, was significantly higher in the antagonist group compared with the agonist group (12.2 versus 4.4%, P< 0.048; difference 7.8%, 95% CI: 0.2 to 14.0)".  What the numbers mean is that, yes it was a bit higher, but when you do stats tests on the numbers, it isn't much better than chance.  the P value should be 0.05 or less...  so, it is just on the brink of statistical significance.  The CI numbers refer to the 'confidence interval'.... ideally here you don't want a very big range and 0.2 - 14.0 is really big (basically they are saying 95% of their sample scored within that range. really you'd want 95% scoring within a range of one or two points for this kind of outcome measure).

The second bit of findings they report: "Estradiol levels on the day of hCG administration were lower in the antagonist protocol [median (interquartile range): 572 (325–839) versus 727 (439–1029) pg/ml, P = 0.018]. "  is also not terribly promising

Sorry if its diappointing news... i guess i'd rather know myself (boring old realist when it comes to chances of sucess). 
x


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