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

[TryMeditate]

I wanted to start this thread to save our research only.  Please do not post anything but research on this thread.  For chit chat or any questions, please go to the usual PR Thread!!!

[FertilityFriends]

[TryMeditate]

CHR does a different protocol than over here called estrogen priming which apparently gets a better egg rate .


Also see

http://www.highfshinfo.com/
Pregnancies in women with FSH (mIU/ml) of 143 and 127 using estrogen priming.

http://www.ncbi.nlm.nih.gov/pubmed/10920090?dopt=AbstractPlus
Three pregnancies despite elevated serum FSH and advanced age: case report.Check JH, Check ML, Katsoff D.

The University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School at Camden, Cooper Hospital/University Medical Center, USA. [email protected]

Although the transfer of fertilized donor oocytes is the most efficacious mode of conception for infertile women with hypergonadotrophism associated with incipient or apparent ovarian failure, there are many individuals who, for religious, ethical, or personal reasons, would prefer to try to conceive with their own oocytes. The three cases presented here represent extremes to date for (i) highest serum FSH concentration in a woman with incipient ovarian failure (n = 2), and (ii) the oldest woman with apparent overt ovarian failure (n = 1) to have successful pregnancies. All three cases were treated for only a short time with pharmacological dosages of ethinyl oestradiol with luteal phase support with progesterone. The peak FSH (mIU/ml) in cases 1 and 2 was 143 and 127 respectively. The precedents set in these cases can help physician-patient consultation when patients enquire whether there is a certain critical FSH concentration above which pregnancy is not possible or an age over which successful pregnancy could not be achieved even if ovulation despite ovarian failure was possible.

Estogen Priming
http://www.ncbi.nlm.nih.gov/pubmed/15672973?dopt=AbstractPlus

Very high FSH, no periods, failure to have withdrawal period after progesterone, no antrals on scan, small ovaries "extremely" high FSH - estrogen priming protocol resulted in a baby.

PURPOSE: To attempt ovulation induction in a woman with premature ovarian failure who had very high serum follicle stimulating hormone (FSH) levels (e.g., 164 mIU/ml) by merely using ethinyl estradiol without gonadotropins. METHODS: Ethinyl estradiol (20-40 microg) was used to lower serum FSH. Monitoring of follicular maturation was performed using sonography to determine follicle size and serum estradiol. Progesterone vaginal suppositories (200 mg twice daily) were used following demonstration of oocyte release from the follicle. RESULTS: Follicle maturation and ovulation was achieved in six of ten treatment cycles. A clinical pregnancy occurred in the ninth treatment cycle and a live delivery of a healthy baby occurred.

CONCLUSIONS: Despite small ovaries, amenorrhea, and failure to have withdrawal menses following progesterone, absence of antral follicles on initial ultrasound, and consistently extremely high serum FSH, ovulation and pregnancy is possible by merely lowering the serum FSH
---------------------------------------
Estrogen Priming

http://ridgefieldacupuncture.com/blog/?p=16
Link to estrogen priming protocol study done by SIRM clinic. 137 women, 37% pregnancies, All these women were poor responders, but does say 14% (1 out of 7) for women with diminished ovarian reserve.    It does not say what it defines as diminished ovarian reserve, but they only had 7 out of 137 women with diminished ovarian reserve.  Though another link to the same study says these 7 women had antral FCounts of <5.
 

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Link to 42year old woman with one ovary who had failed IVFs, did estrogen priming at SIRM, got 5 eggs and is pregnant.
http://www3.fertilethoughts.com/forums/archive/index.php/t-445138.html

Estrogen Priming Protocol used in 2006 study SIRM
They only had 7 women in the study with diminished ovarian reserve, defined as AFC<5, and of those 1 had an ongoing pregnancy or 14%.  
1. pill 1 to 3 weeks,
2. last 5 to 7 days GnRH antagonist (lupron0.5mg/per day) overlapping the pill
3. Stopped with onset of period
4. CD2 - low dose 0.125mg GnRH antagonist
5. Estradiol valerate, 2 mg, was given intramuscularly every 3 days for two doses (Note: not oral, reasons given in study)
6. Estrogen suppositories were used to maintain the endometrium until at least one follicle measured 15 mm.
7. Follicular development was then stimulated using recombinant FSH in initial doses of 600 or 750 IU/day, decreasing to 225 IU/day after 5 days.  (Note: Found min 600FSH better than 450 for these women, felt the risk of OHSS was neglible for these PRs)
8. After the first 2 days, hMG at 75 IU/day was substituted for the 75 IU/day of recombinantFSH.
9. Transvaginal ultrasound monitoring began after 7 days of stimulation. The average patient needed 13 days of stimulation before hCG administration.

From SIRM website
http://www.haveababy.com/SIRM/ivfpreparation/customstimulation.html
For several years, we have advocated the use of a "modified LP" (which we refer to as an "Estrogen priming LP", for women over 40yrs and those with ovarian resistance as evidenced by low Inhibin B levels and/or an FSH level of >9.0MiU/ml in association with a plasma estradiol level of <70pg/ml on the 3rd day of a natural cycle. With this protocol, estrogen is administered from the onset of menstruation to "tweak" or "prime" ovarian receptor response to FSH. This we have shown, at least in part, to counter the suppressant effect of GnRHa on FSH receptors. Through early "priming" with estrogen we also hope to improve initial endometrial response to the estrogen produced by ovarian stimulation by exposing the early endometrium to a relatively high concentration of exogenous (administered) estrogen.
SIRM's "Estrogen Priming LP" involves the initial administration of GnRHa for a number of days to effect pituitary down-regulation. Upon menstruation and confirmation by ultrasound blood estradiol measurement that adequate ovarian suppression has been achieved, the dosage Lupron is drastically lowered for the duration of follicular phase (until hCG is given), or it is replaced by Antagon or Cetrotide and the woman is given twice-weekly injections of estradiol for a period of 7-10 days. Ovarian stimulation with a relatively high dosage of FSH-dominant gonadotropins such as Follistim, Gonal F or Bravelle is then initiated for a few days whereupon the gonadotropin dosage is reduced significantly. The combination of FSH, GnRHa or antagonist and estrogen therapy is continued until approximately the 7th day of stimulation with gonadotropins, whereupon estrogen is gradually reduced or immediately withdrawn and the agonist or antagonist/gonadotropin therapy is continued until the day of hCG administration. Using this approach we have been able to significantly improve ovarian response and produce many viable pregnancies in numerous cases where all hope had been abandoned.
While use of the "modified Estrogen priming LP" does NOT guarantee improved follicle development, it does in our experience, optimize the response of women with ovarian resistance. We have been using such protocols successfully for several years.

From a response Dr SHER – SIRM posted to someone on his website.
Estrogen priming protocols: Older women (over 40 yrs), women who have demonstrated a prior reduced ovarian response to COH and those who by way of significantly raised cycle day 3 FSH and reduced Inhibin B levels are considered likely to be “poor responders”, are first given GnRH agonist for a number of days to effect pituitary down-regulation. Upon menstruation and confirmation by ultrasound blood estradiol measurement that adequate ovarian suppression has been achieved, the dosage of GnRH agonist is drastically lowered (or the agonist is replaced with a GnRH antagonist) and the woman is givens twice-weekly injections of estradiol for a period of 7-10 days. COH is then initiated using a relatively high dosage of FSH-dominant gonadotropins such as Folistim or Gonal F that is continued along with daily administration of GnRH agonist/antagonist until the “hCG trigger”. A recently completed study has demonstrated the efficacy of this protocol and the ability to significantly improve ovarian response to gonadotropins in many of hitherto “resistant patients

The GnRH Agonist/Antagonist Conversion Protocol (A/ACP) : It is our position that some form of pituitary blockade, either in the form of a GnRH agonist (e.g. Lupron, Buserelin, Nafarelin, and Synarel. Decapeptyl) or a GnRH antagonist (e.g. Antagon, Cetrotide, Cetrorelix, and Ganarelix) is an essential component in ovarian stimulation of “poor responders” undergoing IVF. If this is not done, a progressive rise in LH –induced ovarian androgens (male hormones ….mainly testosterone) will inevitably affect follicle/ egg development, resulting in compromised embryo quality.
The follicles/ eggs of women on GnRH-agonist “flare protocols” are exposed to an exaggerated Lupron-induced LH release, (the “flare effect” while the follicles/eggs of women, who receive GnRH antagonists starting 6-8 days into the stimulation cycle are exposed to endogenous LH -induced ovarian androgens( especially testosterone). This might not be problematic in “normal responders” but could be decidedly prejudicial in “poor responders” and older women where endogenous basal LH levels are often raised and the ovaries may be inordinately sensitive to LH and where excessive exposure of follicles and eggs to testosterone could severely compromise egg development and thus embryo quality.
exhausted of its LH and residual minimal LH is present in the circulation by the time stimulation with gonadotropins begins, the above mentioned adverse testosterone-effect is largely negated. On the down side is the fact that prolonged administration of GnRH agonists such as Lupron (such as with the GnRH agonist down-regulation protocol could suppress subsequent ovarian response to ovarian stimulation with gonadotropins, by competitively binding with ovarian FSH receptors. We introduced of our Agonist/Antagonist Conversion Protocol (A/ACP) more than a year ago in an effort to counter this effect.
With the A/ACP, low dose Antagon/Cetrotide is commenced at the onset of spontaneous menstruation or following bleeding that follows initiation of GnRH agonist (e.g. Lupron) therapy using a long-down-regulation protocol arrangement. We currently prescribe the A/ACP to most of our IVF patients regardless of whether they are “normal responders” or “poor responders”. Preliminary results suggest a significant improvement in egg number, egg/embryo quality as well as in implantation and viable IVF pregnancy rates. The A/ACP has however, proven to be most advantageous in “poor responders” where additional enhancement of ovarian response to gonadotropins may be achieved through incorporation of “estrogen priming”. We have reported on the fact that the addition of estradiol for about a week following the initiation of the A/ACP, prior to commencing FSH-dominant gonadotropin stimulation appears to further enhance ovarian response, presumably by up-regulating ovarian FSH-receptors.
There is one potential draw back to the use of the A/ACP, in that the sustained use of a GnRH antagonist ( e.g. Antagon/Cetrotide) throughout the stimulation phase of the cycle, appears to compromise the predictive value of serial plasma estradiol measurements as a measure of follicle growth and development in that the estradiol levels tend to be much lower in comparison to cases where agonist (Lupron) alone is used or where a “ conventional” GnRH antagonist protocol is employed ( i.e. antagonist administration is commenced 6-8 days following initiation of gonadotropin stimulation). Rather than being due to reduced production of estradiol by the ovary(ies), the lower blood concentration of estradiol seen with prolonged exposure to GnRH-antagonist, could be the result of a subtle, agonist-induced alteration in the configuration of the estradiol molecule , such that currently available commercial kits used to measure estradiol levels are rendered much less sensitive/specific. Thus when the A/ACP is employed, we rely much more heavily on ultrasound growth of follicles along with observation of the trend in the rise of estradiol levels, than on absolute estradiol values. Thus we commonly refrain from prescribing the A/ACP in “high responders” who are predisposed to the development of severe ovarian hyperstimulation syndrome (OHSS) and accordingly where the accurate measurement of plasma estradiol plays a very important role in the safe management of their stimulation cycles.
It is remarkable, that while using the A/ACP + "estrogen priming " in “poor responders “ whose FSH levels were often well above threshold limits, the cycle cancellation has consistently been maintained below 10% ( i.e. much lower than expected). Many of these patients who had previously been told that they should give up on using their own eggs, and switch to ovum donation because of “poor ovarian reserve”, have subsequently achieved viable pregnancies at SIRM using the A/ACP with “estrogen priming”.



This post contains an unconfirmed link/information and readers are reminded that fertilityfriends.co.uk or its owners are not responsible for the content of external internet sites

[TryMeditate]

dhea cont:


The following is a summary of conclusions about CHR's DHEA data, as we
presented them at these events, and as we understand them to be reflected
by the clinical experience we have witnessed so far in our patients:

>>DHEA increases in older women oocyte numbers to a statistically very
significant degree.

>> DHEA also increases egg and embryo quality in older women to a
statistically very significant way.

>> DHEA appears to increase pregnancy rates with IVF in older women;
however, while we are observing a very strong trend towards
significance for this finding, the data have not yet reached
statistical significance.

>> We have observed preliminary evidence, which has not reached
statistical significance, and needs to be viewed with extreme caution,
that DHEA may reduce the degree of chromosomal abnormalities in eggs
and embryos of older women.

We are, therefore, to day in a position where we can state with
considerable conviction that treatment with DHEA benefits older women, as
reflected by their IVF- cycle outcomes.

We have also considerable evidence, though not as much as in older women,
that DHEA treatment has a similarly beneficial effect on younger women
with prematurely aging ovaries.

>> We also confirmed the initial observation in our index patient that
the effectiveness of DHEA usage peaks after approximately 4 months of
use.

>> Moreover, we strongly suspect (though do not yet have absolute proof)
that co-treatment with gonadotropins further amplifies the positive
DHEA effect on the aging ovary.

The conclusions we report here are based on what is called observational
studies. The quality of results obtained from such studies is not equal
to results obtained from prospectively randomized and blinded studies. We
have, indeed, instigated such a study protocol for DHEA; however, because
it involves the randomization of patients to placebo we have experienced
considerable recruitment problems into the study since patients with
"older" ovaries are usually hesitant to take the risks of prolonged
placebo treatments.

Our observational study is, however, of rather high quality because it
involves patients pre- and post-DHEA treatment in unselected fashion and,
indeed, also involves by now a large enough number of patients who serve
as their own controls in that they, themselves, underwent pre- and post-
DHEA cycles.

Finally, we are extremely confident of our data because, even, when we
statistically corrected for the increased egg numbers, we observe after
DHEA treatment, we still maintain high significance for improved egg and
embryo quality.

We are on purpose not publishing our DHEA treatment protocols because we
want to discourage self-treatment with DHEA. We, however, encourage
colleagues to contact us with questions and will, on such occasion, gladly
share our clinical experiences in more detail and describe our treatment
protocols.

Patients who wish to consider treatment through CHR should contact us for
a consultation for an appointment. Patients who live outside of the
United States may request an appointment for a telephone consultatio


with a CHR physician. CHR is routinely cooperating on patient care with
physicians from all over the world.


Treatment Findings - 5/19/05
The happy mother of a newborn 8lbs., 2oz. boy was 41 years old at time of
her successful IVF cycle in July of 2004 which had been preceded by seven
weeks of DHEA treatment. A prior IVF attempt in June of 2004 had to be
cancelled after lack of ovarian response to ovarian stimulations. With
identical ovarian stimulations and the DHEA treatment, we were able to
produce 8 oocytes and 4 embryos, respectively. To date, five women waiting
to go into IVF cycles have conceived spontanelously.

Previous Treatment - 5/05
DHEA not only increases egg numbers but also appears to improve egg/embryo
quality. Our experience with DHEA has now reached 45 women with previously
diagnosed impaired ovarian reserve. They have used the medication for
various time intervals at a range form 4 to 48 weeks before starting an
IVF cycle. Based on these patients we are so far able to compare 43 IVF
cycles before with 33 cycles conducted after DHEA start. The following
findings were noted:

Baseline FSH and ESTRADIOL levels did not change with treatment
Egg production increased significantly from an average of 4.4 to an
average of 8.6 oocytes (confirming further our previously reported update
data
Eggs after DHEA treatment produced high quality embryos at a significantly
higher rate than eggs prior to treatment (35% vs. 16%).
This latter observation provides the first evidence ever reported that
DHEA treatment not only increases egg quantity but apparently also
improves egg quality. If further investigations should confirm these early
and, therefore, preliminary data, then DHEA could truly be seen as an
"ovarian rejuvenator" by beneficially affecting two of the classical signs
of ovarian aging, poor egg numbers and poor egg quality. Anecdotally, such
an interpretation of these data is further supported by our observation of
a small number of totally unexpected spontaneous pregnancies in women with
clear evidence of diminished ovarian reserve after they started DHEA
supplementation.
Previous Treatment Findings - 3/05
Our experience with these over 30 patients, therefore, suggests the
following:

In women, ages 40 to approximately 44, DHEA, indeed, appears to increase
oocyte yield. This increase is not observed in all women but in a
horizontal assessment it is significant for the whole group studied.
The data is not yet adequate to assess the value of DHEA in younger women,
with evidence of prematurely aging ovaries, but preliminary trends suggest
that DHEA may have similar benefits in these patients.
We confirmed that the benefit of DHEA increases with time of use and peaks
after approximately 4 months of use. Whether the plateau reached after 4
months DHEA use is time limited, and, if so, for how long before a decline
is observed, is unknown.
DHEA appears to enhance spontaneous fecundity/fertility. We make this
statement based on the observation that, in this very unfavorable group of
patients, 4 (!!) conceived spontaneously while on DHEA treatment and
waiting to enter an IVF cycle. This is, of course, anecdotal evidence in
view of the small numbers; however, our expectation for spontaneous
pregnancies in these patients is extremly low.
DHEA use probably lowers baseline FSH levels. We cannot make this
statement with absolute certainty because only one, out of two,
statistical analyses performed on these data showed statistical
significance so far.
We do not know yet whether, in addition to oocyte quantity, DHEA also
effects oocyte quality.
Next Step
The first step is easy, simply complete the Prematurely Aging Ovaries
Qualification Form to determine if you qualify for our DHEA Treatment
Program.

Effect of dehydroepiandrosterone on oocyte and embryo yields, embryo grade and cell number in IVF
David Barad 1 * and Norbert Gleicher 2
BACKGROUND: The aim of this study was to investigate the effect of treatment with dehydroepiandrosterone (DHEA) on fertility outcomes among women with diminished ovarian reserve. MATERIALS AND METHODS: This is a case-control study in an academically affiliated private infertility centre. Twenty-five women with significantly diminished ovarian reserve had one IVF cycle before and after DHEA treatment, with otherwise identical hormonal stimulation. Women received 75 mg of DHEA daily (25 mg three times daily) for an average of 17.6 ± 2.13 weeks. We performed a comparison of IVF outcome parameters, before and after DHEA treatment, including peak estradiol (E2) levels, oocyte and embryo numbers, oocyte and embryo quality and embryo transfer statistics. RESULTS: Paired analysis of IVF cycle outcomes in 25 patients, who underwent cycles both before and after DHEA supplementation, demonstrated significant increases in fertilized oocytes (P < 0.001), normal day 3 embryos (P = 0.001), embryos transferred (P = 0.005) and average embryo scores per oocyte (P < 0.001) after DHEA treatment. CONCLUSION: This study confirms the previously reported beneficial effects of DHEA supplementation on ovarian function in women with diminished ovarian reserve.

/links

[TryMeditate]

dhea cont:

In demonstrating these facts, this patient provides confirmation for our
DHEA work which has suggested that DHEA substitution in older ovaries
increases egg yield and egg as well as embryo quality. Since DHEA levels
are known to decrease significantly with advancing age, the aging ovary
can be seen as akin to that of a DHEA deprived ovary, where the cause of
that deprivation, as in this patient, appears not age-related but due to
an adrenal defect. In other words, this patient confirms that DHEA
deprivation, if corrected, improves ovarian function. In doing so, this
case validates the treatment of aging ovaries with DHEA.

Maybe more importantly, however, this case also may point towards a better
understanding of the prematurely aging ovary and here is why:
approximately 10% of women suffer from prematurely aging ovaries. They
usually reach menopause prematurely and this condition is familial; i.e.,
it means that if your mother had early menopause, you, as her daughter,
are at significantly increased risk for early menopause, as well. The
diagnosis of prematurely aging ovaries is, as we have repeatedlydescribed
in these pages, at times difficult to make, requires a high level of
suspicion and, at times, cannot be made without taking patients into an
IVF cycle. It is, therefore, no surprise that many women with this
diagnosis go undiagnosed for long periods and are frequently misdiagnosed
as so-called "unexplained infertility."

All of this applied to this patient. She went undiagnosed for years. Only
after her FSH levels became significantly abnormal was the problem
recognized. And with great likelihood, will she experience early
menopause, though she is currently attempting another pregnancy. This
patient was, however, unique in one aspect: she was diagnosed with an
adrenal enzyme deficiency which prevented the normal conversion of
precursor hormones into DHEA.

This, of course, immediately raised in our minds the question whether
there might not be other patients, like her? Indeed, one could speculate
that this kind of an adrenal enzyme defect may be quite frequent. Many
patients then could be expected to have, as a consequence of such a
defect, low DHEA levels and these adrenal enzyme defects may, then,
indeed, represent a significant cause for the premature aging of ovaries.
In other words, the prematurely aging ovary may be an adrenal disease!

Such a finding would, of course, have huge significance for our field
because it would give us, for the first time, tools to diagnose women with
this condition early and then treat them correctly. Moreover, DHEA
substitution may also allow us to delay their premature menopause.

We are looking for volunteers:
However, one swallow does not make spring, yet! We have a lot of work to
do

--------------------------------------------------------------------------------

to confirm this very exiting theory and have, therefore, already
instigated a study of young women with proven prematurely aging ovaries.
In order to have very clear study criteria for our patients with
prematurely aging ovaries, we have set strict criteria for patient
selection for this study.

If you want to participate in this study, you have to be under the age of
35 and you have to have had an elevated FSH level on at least one
occasion. If you believe that you qualify, please complete the Prematurely
Aging Ovaries Qualification Form.

Once confirmed to qualify for the study, you will be asked to spend a few
hours at our Center on either the 2nd or the 3rd day of your menstrual
period, at which time you will undergo a so-called ACTH stimulation test.
This is a routine test for adrenal function.

What it means is that you will have some baseline bloods drawn; then you
have a small amount of the hormone ACTH injected intravenously, followed
by two more blood draws at 30 and 60 minutes after injection. How several
of your hormones respond to the injection of ACTH, defines your adrenal
function.

Treatment Findings - 6/27/05
Because women who potentially can expect benefits from DHEA treatment are
usually at an age, and on a time-line, that do not allow for delays, we
have made it a practice to publish on our website periodic updates on
CHR's DHEA experience, as the data become available.

CHR is, of course, pursuing in parallel the scientific publication of
these data; however, the scientific publication process is very slow and
many patients do not have the time left to wait for such formal
publications. For example, the first report on the CHR's index patient,
who gave us the idea to pursue the investigation of DHEA, over a year and
a half ago, appeared in print in Fertility & Sterility, the official organ
of the American Society for Reproductive Medicine (ASRM) in its September
2005 issue. Another manuscript, describing CHR's DHEA experience over the
first year of treatment, will be submitted for publication soon.

In addition, we are presenting our DHEA data on an ongoing basis at
international scientific meetings. For example, Norbert Gleicher MD, our
Medical Director, presented updated DHEA data at the invitation of the
organizers at the World Congress for ART in Istanbul, Turkey in May, and,
just recently in June, at the Annual Meeting of the European fertility
Society (ESHRE) in Copenhagen, Denmark. At both of these meetings the data
received disproportionate attention from the community of fertility
specialists. To keep the local New York Ob/Gyn community informed, David
Bard, MD, presented the data at one of CHR's Grandround events in June.



/links

[TryMeditate]

dhea cont:

we have encountered the expected difficulties in recruitment, since most,
not surprisingly, do not want to take the risk of being blindly assigned
to four to five months of placebo. We, therefore, have to work with the
best evidence we are able to develop and that this, as of this time, the
kind of LTA we are in the process of preparing.

While we have no final data yet available, our preliminary f indings came
as a surprise, even to us! We have seen so far, in addition, to the DHEA
pregnancies with IVF, TWELVE (12) post-DHEA pregnancies in women who have
not yet reached IVF treatment and approximately two third of these
pregnancies are ongoing.

Considering who the patients are who we have placed on DHEA, these numbers
are truly remarkable and exceed even our own, most optimistic
expectations. We in principle recommend DHEA treatment only to two patient
groups: The first group is older women, usually over age 42.5 years, with
no prior IVF experience, or over age 40, if a prior IVF experience yielded
only small numbers of good quality eggs/embryos. A second group is younger
women, always under age 40, who have indisputable evidence of prematurely
aging ovaries. Both of these patients groups, without treatment, have, as
many studies in the literature have shown, only a minimal chance of
spontaneous pregnancy. Indeed, most IVF programs will not even accept
patients from either of these two groups because, even with IVF, their
chances of conception are extremely poor.

In approximately 50 such patients, our data show that over 30% have so far
conceived and over two-thirds of those who have conceived are either
carrying ongoing pregnancies or have already delivered, if spontaneously
conceived and pregnancies, conceived through IVF cycles, are added up.

As noted above, these preliminary numbers are truly remarkable and exceed
even our own expectations. It is important to note that these numbers are
preliminary! We will publish an "Update" on our website with final numbers
as soon as those have become available. Because of the importance of this
issue to so many women with aging ovaries, we want to make absolutely sure
that our data are correct in their last detail and we are, therefore,
currently re-reviewing the charts of all DHEA patients.

However, because time is of so much essence for women with aging ovaries,
we have made it a policy to offer data to CHR's own patients, and to the
readers of our website, as soon as reliable data become available to us.
Research is slow and the publication of research data in scientific
journals is even slower. As an example, the report on our index patients,
which led CHR into the research of DHEA over a year ago, will only now, in
September, be published in Fertility & Sterility, the official organ of
The American Society
 
--------------------------------------------------------------------------------

for Reproductive Medicine (ASRM). We are, however,
planning on presenting the finalized LTA of our DHEA experience at the
upcoming annual ASRM meeting in Montreal , Canada , which will take place
in October. Our paper has been accepted for oral presentation for the
first day of the meeting.

Treatment Findings - 8/12/05
For a number of reasons this month's update is quite remarkable and
unusual: A first reason is that, once again, we can report on a very
significant DHEA-related advance which was served to us on a platter by a
patient. Most of you will recall that it was one of our patients at CHR
who brought DHEA to our attention in the first place. This time, it wasn't
even one of our own patients but a patient elsewhere who, through the
internet, had become aware of our DHEA work and contacted us to tell us
about her truly unique history. And in telling us, and documenting, her
history in excruciating detail, she allowed us not only to correct her own
presumptive diagnosis but, more importantly, provided us with convincing
proof of the importance of DHEA for normal ovarian function and, possibly
most importantly, may have pointed us into a direction which will allow us
to understand, diagnose and treat the prematurely aging ovary better.

So what is this all about?
This patient, after a number of years of infertility, decided to
investigate the medical literature to see what else she could do to better
her obviously prematurely aging ovarian function with elevated, very
abnormal FSH levels. Like our initial patient, she came across the one
paper in the literature that suggested that DHEA may improve ovarian
function to a small degree. She took this, however, a step further and
asked her medical endocrinologist to investigate her adrenal glands, which
produces DHEA. And, low and behold, this testing revealed that she,
indeed, had very low DHEA levels in conjunction with certain other low sex
hormones. Her medical endocrinologist correctly concluded that she, most
likely, suffered from an adrenal enzyme defect which blocked the normal
production of DHEA in her adrenal glands and prescribed DHEA substitution.

Even though this medical endocrinologist was apparently wrong in the exact
enzyme defect he had diagnosed (that defect actually results in elevated
DHEA levels), her treatment with DHEA, indeed, corrected, as was well
documented, all of her hormonal abnormalities. Her DHEA returned to normal
levels and so did her production of other hormones which are produced from
DHEA, such as estradiol. In addition, in her first IVF cycle, after
approximately 6 months of DHEA substitution, she produced more eggs and
better eggs and embryos than in prior IVF cycles, conceived a triplet
pregnancy and delivered, at age 39, a healthy son after six years of prior
unsuccessful attempts.

So what does all of this mean?
First and foremost this patient is an experiment of nature which suggests
that low DHEA levels may, indeed, be cause for infertility and, possibly,
premature ovarian aging and that DHEA substitution may reverse some of
these effects successfully.



/links

[TryMeditate]

dhea cont:

Such a treatment offered itself when one of our patients, without our
knowledge, started to take the mild male hormone, DHEA, and, subsequently,
greatly increased her oocyte yield in IVF cycles. Indeed, this 43 year old
woman, after approximately four months of DHEA treatment, featured ovaries
which in function and sonographic appearance were indistinguishable from
ovaries one would expect in much younger females.

Because of the extremely dramatic improvement in ovarian response by this
patient after DHEA use, we felt ethically obliged to publicize this
finding as quickly as possible since, in older women, time is, of course,
of essence. A more formal scientific report of this case appeared in
Fertility and Sterility, the official organ of the American Society for
Reproductive Medicine (ASRM).

As we have emphasized from the beginning, one case in medicine may give
hope but is certainly not enough to reach far reaching conclusions of any
kind. We have emphasized this fact from day one; not only to our patients,
but have also stressed it in our writings. At the same time we, however,
have mounted a strong effort to investigate the use of DHEA as a potential
extender of female fertility and have done so in two distinctive formats..

The ultimate study format for any clinical trial is the double blinded,
prospectively randomized study. Such a study has been approved by our
Institutional Review Board (IRB) and is under way. This study, however,
mandates the use of a placebo, a sugar pill, in half of all patients. In
practical terms this means that one half of all patients in this study
will receive no treatment for up to four months. To give no treatment to
an older woman who, maybe, has only a few months of reproductive life
left, would not be considered ethical. We, therefore, had to restrict this
study to a relatively young patient population, between the ages of 35 and
40 years. Women above age 40 will not be enrolled in this study.

They, however, are given the option of using DHEA, anyhow, by serving as
their own controls. In this study, we compare patients' IVF outcomes,
before they started using DHEA, to IVF cycle outcomes after the use of the
medication. This form of a study is, of course, not as well controlled as
a double blinded, prospectively randomized study, but, as this case so
well demonstrates, such studies are not always possible in medicine and,
sometimes, we have to accept a second best study format.

Two other IVF centers, one in New York and the other in Chicago, have
joined us in the prospectively randomized study and we hope to be able to
report results within a reasonably short time period. Finding infertility
patients who agree to be randomized to possible placebo for four months
is, of course, not always easy. We have, however, so far been able to
place over 30 patients into the second study and are, therefore, already
in a position to report further

--------------------------------------------------------------------------------

Finding infertility
patients who agree to be randomized to possible placebo for four months
is, of course, not always easy. We have, however, so far been able to
place over 30 patients into the second study and are, therefore, already
in a position to report further preliminary results. These results are
currently being summarized for another formal scientific publication.
However, because of the obvious time pressures involved in older women, we
feel an ethical obligation to pass these preliminary results on as soon as
we become aware of them.

Treatment Findings To Date - 10/20/05
At the annual meeting of the ASRM which took place between October 17-19
in Montreal, Canada. Drs Gleicher and Barad presented a number of research
papers and, amongst them, the DHEA Update received considerable attention.
This presentation by Dr. Gleicher offered the most recent update of CHR's
DHEA data and also represented the first presentation of these data
(except for CHR Grandrounds) on U.S. soil. Dr. Gleicher had presented
earlier talks on the subject at the World Congress for IVF in Istanbul, at
the ESHRE meeting in Copenhagen and on recent lecture tour through Japan
and Taiwan. To a packed house, the presentation involved outcome data on
DHEA patients who had completed IVF cycles and, for the first time, a life
table analysis of all patients who had been started on DHEA which,
therefore, also included the many spontaneous pregnancies we have
witnessed in this patient population. This kind of analysis allows
separating prognostic factors by such patient characteristics as age and,
therefore, represents a very useful tool in counseling patients. What this
analysis demonstrated is that women with prematurely aging ovaries, under
age 38 years, have excellent pregnancy chances with the use of DHEA. Women
with prematurely aging or physiologically aged ovaries, between ages 39
and 42 years also still have surprisingly good pregnancy rates, though
lower than the former group. Above age 42, the establishment of pregnancy
is difficult, even with DHEA, though our oldest ongoing pregnancy is in a
patient who was age 45 years at time of conception.

Treatment Findings - 9/1/05
In this month's update we want to inform you about yet another remarkable
observation we have made in patients who have started using DHEA:
Spontaneous pregnancies, while patients wait to go into IVF cycles.

We are currently in the final stages of calculating what is called a life
table analysis (LTA) for all patients who, over the last year, have been
placed on DHEA. The purpose of such a LTA is to document all pregnancies
that have occurred, whether spontaneously or through IVF, so that this
overall rate can be compared to what would be expected from such a patient
population.

Such a statistical comparison is not ideal because under best study
conditions one would, of course, like to compare patients who were blindly
given DHEA or a placebo. While such a placebo-controlled study is also
underway, considering the patients who are candidates for DHEA treatment,



/links

[TryMeditate]

Dhea - taken from a public email forwarded by chr to whoevers interested

-------------------------------------------------------------------------------

1: J Assist Reprod Genet. 2007 Dec 11
Update on the use of dehydroepiandrosterone supplementation among women with diminished ovarian function.
Barad D, Brill H, Gleicher N.
Department of Epidemiology and Social Medicine, Albert Einstein College of Medicine, Bronx, NY, USA.
OBJECTIVE: We assessed the role of DHEA supplementation on pregnancy rates in women with diminished ovarian function.
DESIGN: This is a case control study of 190 women with diminished ovarian function. The study group includes 89 patients who used supplementation with 75 mg daily of oral, micronized DHEA for up to 4 months prior to entry into in vitro fertilization (IVF).
The control group is composed of 101 couples who received infertility treatment, but did not use DHEA. The primary outcome was clinical pregnancy after the patient's initial visit.
We developed a Cox proportional hazards model to compare the proportional hazards of pregnancy among women using DHEA with the controls group.
RESULTS: Cumulative clinical pregnancy rates were significantly higher in the study group (25 pregnancies; 28.4% vs. 11 pregnancies; 11.9%; relative hazard of pregnancy in study group (HR 3.8; 95% CI 1.2-11.8; p < 0.05).
CONCLUSIONS: DHEA treatment resulted in significantly higher cumulative pregnancy rates. These data support a beneficial effect of DHEA supplementation among women with diminished ovarian function.
PMID: 18071895 [PubMed - as supplied by publisher]

Prematurely Aging Ovaries Overview
Older women (generally above age 38), and younger women with so-called
prematurely aging ovaries, will often find it harder to get pregnant. We,
here at CHR, have a special interest in the "aging ovary" and have been
conducting a lot of research on this topic. See Ovarian Aging: is there a
"Norm" in Contemporary ObGyn. Our program has become known in the
community as the program of "last resort" and we, therefore, have probably
proportionally more "older ovaries" under treatment than any other
infertility center in New York City.

One of our patients, not too long ago, indeed, taught us a very important
new lesson, which we, since, have diligently investigated with an
increasing number of our patients. She, without our knowledge, had started
taking the over the counter available, mild male hormone, DHEA and, as a
consequence, greatly increased her oocyte (egg) yield in IVF. Indeed,
after approximately four months of DHEA usage, her 43-year old ovaries
behaved like those of woman in her 20ies.

Treatment Qualifications
If you are older than 40 and are unable to get pregnant after trying for
six months, complete the Prematurely Aging Ovaries Qualification Form to
determine if you qualify for our DHEA Treamtment Program. This new
treatment may improve the patients' inherently limited preg nancy chances.



/links

[TryMeditate]

Dhea links



CHR link DHEA usage for fertility issues: http://www.centerforhumanreprod.com/about_chrupdate_0808.html


I think the Greece study is a bit “lucky”, I know a lot of women on DHEA and it is far from a 100% success rate.
Greece clinic – 5 women with POF pregnant. Dr. Mamas protocol.  Older research:   http://messageboards.ivillage.com/n/mb/message.asp?webtag=iv-ppttcaf40&msg=15712.1  

newest abstract of Greece clinic> http://www.neogenesis.gr/en/publications/dhea-in-assisted-reproduction.html

-----------------------------------------------------
http://www.ivfwales.co.uk/default.asp - IVF wales carrying out a study into dhea

http://www.nutros.com/nsr-0202n.html


http://boards.babycenter.com/bcus1143741/messages/3590/5914
Story copied below
Hi Ladies -
I can't remember who was asking about DHEA a few weeks ago, but I came across this information from someone on another board I belong to.  Found it interesting.  I'll be looking for information on the progesterone creme too!
I realize the DHEA subject is controversial and I only add this to increase awareness (and to follow-up on my previous post).

After taking DHEA for four+ months, at the instruction of my RE, my antral follicle count went from 6 to 19; my AMH went from 0.6 (borderline) to 0.9 (good). I am now on the aggressive AACEP IVF protocol, but the protocol did not kick in in time for it to be responsible for my increased AFC or AMH. My FSH was not measured becaues I had taken Lupron for suppression and that messes up the FSH value. My RE thinks the AMH increase indicates a real improvement in ovarian reserve. I have 11 follicles after 5 days of stimming compared to 6 in May.

By the way, my RE also recommended DHA supplementation (along with a mega prenatal vitamin).

Just wanted to share my positive developments. We can't be sure it's the DHEA, but I haven't done anything else differently. Well, actually, I've done some things differently but they should work in the opposite direction: this time, I did not cut down caffeine; I have not stopped drinking wine during stims; I am not soaking feet. And I still have way more follicles. It's all about the ovaries!
Sounds like it might've really helped the follies for her!
Kim S

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[Jumanji]

Following on from Sam's posts on DHEA here is some information on AMH.  Can I respectfully ask the mods not to delete any links?

AMH reamins a fairly new test and there is still a LOT of confusion about AMH and what is "normal" and, to be honest, I don't think even the best in the medical profession have enough data yet to know what it all means.  Hence I really do not think anyone should panic over the results of one test.  However, a lot of less experienced doctors now place a lot of reliance on this test and will be very "doom and gloom" if yours is anything less than perfect.

The first thing anyone should find out is what scale their AMH result is on.  The pmol scale has higher numbers than the ng/ml scale and the conversion factor is 7.14.  Hence, if your result is 1 ng/ml that is 7.14 on the pmol/ml scale.  The pmol/l scale is more commonly used in the UK and Australia but elsewhere, notably the US, the ng/ml scale is the one used.

The assay kit link (next but one link below) is the source of the "original" AMH ranges which everyone jumped on as representing the "norms".  They are 2-6.8 on the ng/ml scale and 14.28 - 48.55 on the pmol/l.  This is the scale which had people with AMH of say 1 (or 7.14) being told they had "low ovarian reserve".  It was also the source of the statement that "optimal fertility" is about 28-48.55 pmol/l (3.92-6.8 ng/ml), while "satisfactory" fertility is 15.7-28 pmol/l (2.2-3.92) - see this link for details of this scale - http://www.tdlpathology.com/index.php?option=com_content&task=view&id=201&Itemid=73. This sample also gave a mean AMH of 4.  

However, take a look at the next link which details the sample they got this from.  First, the size is small (335) and ALL the women are under 38 so chances are we know they probably mostly in their 20s!  (I remember reading elsewhere that a lot were college students and thus 18-23 or so but I can't find the link now!).  To be fair on the assay manufacturers, they clearly never intended their results to be taken as "norms".  They do point out that AMH decreases with age and that suggest labs should find their own ranges.  The trouble is many have not done that and simply trot out this reference range, with no idea where it comes from.    

http://www.mbl.co.jp/diagnostic/products/amh/AMH_nousho.pdf

Other research has found that in women of 37 the average AMH was 10 pmol/l (1.4ng/ml).  This has 238 subjects but I don't know the numbers in age ranges.  Anyway, it did find that AMH remained at about 20-25 pmol/l from age 18-29 (so satisfactory but not optimal according to the first link above!!) and then started to drop.  Again, this is beginning to show lower AMH is still ok, especially for those over 30 and that even in those in their 20s, the average still looks lower than first thought.  See the next link.      

http://www.ingentaconnect.com/content/bsc/ajo/2005/00000045/00000001/art00006;jsessionid=o9h2pdwmbk56.alice?format=print

This next study was small (only 20) but the mean age was 26 and the mean AMH was 2.4 ng/ml - this again suggests that even in young women typical AMH levels may not be as high as first suggested.  The study also specifically notes that two women aged 33 and 35 had much lower AMH results (1.2 and 0.39) than the rest.  Note that this study was not in infertility populations - just individuals with normal hormones in all other respects, normal menstrual cycle, BMI etc.  See the link below.  

http://humrep.oxfordjournals.org/cgi/content/full/dem101v1

The next one was bascially showing that ladies with PCOS have higher AMH which declines more slowly than in control groups, but look at the control stats.  Again, it's only a small number (41) but the study looked at the decline in AMH over time and consisted of 2 visits.  The mean age at visit 1 was 29.9 and the mean AMH was then 2.1 ng/ml (written as ug/l here but it is the same).  At visit 2 the mean age was 32.9 and the mean AMH was 1.3ng/ml.  So these "control" ladies would have, on average, had low ovarian reserve by their second visit according to the first stats.  Even in their first visit, they are only just "satisfactory" on average!! See below link.

 http://humrep.oxfordjournals.org/cgi/content/full/19/9/2036

Repromedix is a bis US lab and was the original supplier of the "mail order" AMH test to women in the US wanting to see how much time they had!!  It was marketed as the "plan ahead" test or something similar.  Personally I think it is very misleading to suggest a blood test can possibly tell anyone how much "time" they have left!!  But, moving on from that, Repromedix will have got a lot of data from having supplied this.  Take a look at what they consider normal!!  It's right down - bascially from 0.7-3.5 on the ng/ml scale, which is 5-25 on the pmol/l scale is to them "normal" with 0.3-0.7ng/ml (2.14-5 pmol/l) being "borderline low" and 3.5-5 ng/ml (25-35.7 pmol/l) being "borderline high".  This has shifted the goalposts considerably!!!  In this regard, the Glasgow Centre from Reproductive Medicine and some other clinics now regard 5-15pmol/l as normal and 15 and above as high.  This fits in with the Repromedix scale.  I think this demonstrates how experience of AMH ranges (not just reading a supposed "norm" off a sheet with no understanding of its source) is all important.      

http://www.repromedix.com/pdf/AMHbL17CF181.pdf

More recently, CHR in New York has introduced "age specific" AMH levels.  As I noted above, the scale that much of the UK uses is dervied from a very young sample population so women over 35 are judged on a wholly inapplicable scale.  Plus, research clearly suggests AMH declines with age and yet most women are still fertile at 40 so a certain amount of lowering must be entirely normal.  If you see the link you will note that for women under 30 the level should, according to CHR, be 2.1ng/ml or more (14.99 pmol/l or more); for women 31-35 the level should be 1.7 ng/ml or more (12.14 pmol/l or more); for women 36-40 the level should be 1.1 ng/ml or more (7.85 pmol/l or more) and for women 41 or more the level should be 0.5 ng/ml of more (3.57 pmol/l or more).

http://www.centerforhumanreprod.com/about_newsletter.html

This link is from the advanced fertility centre in Chicago and, as you can see, they regard AMH of 0.7-3 ng/ml as being normal (although 0.7-0.9 is low normal).  Plus, it is only below 0.3 ng/ml that they regard AMH as very low (about 2 pmol/l).  This site also makes it clear that AMH probably does not reflect egg quality.

http://www.advancedfertility.com/amh-fertility-test.htm

This lab from Germany regards 1-5 ng/ml as normal and 0.8-1 as redisidual.  However it regards below 0.4 as "menopausal" which we know cannot possibly be correct since loads of women with lower AMH that that have got pregnant!!  

http://www.labmed.de/en/uploads/labmed_letters/amh-engl.pdf

Personally, I think the main message is that it is all too up in the air for anyone to base too much on this one test!!  The goalposts are clearly moving and plenty of clinics are surprised all the time.  Plus the scales in America seem consistently lower than those in Europe so that a lot of women who are told they are "low" here would be fine there, which is ridiculous!  

My last link is from a Swiss clinic warning that AMH use has its limits and advising of natural pregnancies in 2 women with completely undetectable AMH!!

 http://www.ncbi.nlm.nih.gov/pubmed/17562340  

Note also that in 2009 on the poor responder thread there were 3 pregnancies in ladies with AMH of 0.1ng/ml.  One of these was straight after an IVF cycle in which no eggs were collected and another was in a lady who had not seen AF for a few months.  

Whatever your doctors say, AMH is not the be all and end all.  If you have low AMH it is not "the end".  Plus make sure it is really low - many women here are told they have "low" AMH based on the very early scale when subsequent studies have shown it is really fine.  


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[dimsum]

Estrogen priming and clomid

This isn't exactly research but it shares something that made me respond better.

I have found that using 100mg Clomid on days 2 to 4, in addition to 450 Gonal F from day 2 or 3, helps me produce many more follicles and mature eggs. From producing 1 mature egg 3 times I have gone to producing 3 mature eggs 3 times, all of which have fertilised. I've not managed to get pregnant yet but at least my initial chances have increased.

I have also found that using an estrogen patch about one week before I expect AF stops me producing one dominant follicle and helps produce follicles of a more uniform size. Poor responders often have high FSH. One school of thought is that poor responders are more likely to produce a dominant follicle as their FSH levels remain elevated throughout their cycle. This means that, even before the cycle starts, one antral follicle has already been influenced by FSH and, when more FSH is introduced during IVF, that follicle 'runs away'. Estrogen blocks the production of FSH so using estrogen before AF and stims may help ensure that no one follicle is given a head start over the others.

I should say that my use of estrogen and clomid on my last 4 cycles was not prescribed. I self medicated (which I know FF does not condone). But, having done some research, I figured using them might help and I think they have, well at least as far as getting more eggs goes.