* Author Topic: PR Research Thread - NO CHIT CHAT!!!!!  (Read 62824 times)

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Offline TryMeditate

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PR Research Thread - NO CHIT CHAT!!!!!
« on: 5/03/10, 22:03 »
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!!!

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    Offline TryMeditate

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    Re: PR Research Thread - NO CHIT CHAT!!!!!
    « Reply #1 on: 5/03/10, 22:05 »
    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.
     

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


    Offline TryMeditate

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    Re: PR Research Thread - NO CHIT CHAT!!!!!
    « Reply #2 on: 6/03/10, 11:39 »
    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

    Offline TryMeditate

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    Re: PR Research Thread - NO CHIT CHAT!!!!!
    « Reply #3 on: 6/03/10, 11:40 »
    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

    Offline TryMeditate

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    Re: PR Research Thread - NO CHIT CHAT!!!!!
    « Reply #4 on: 6/03/10, 11:41 »
    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

    Offline TryMeditate

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    Re: PR Research Thread - NO CHIT CHAT!!!!!
    « Reply #5 on: 6/03/10, 11:42 »
    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

    Offline TryMeditate

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    Re: PR Research Thread - NO CHIT CHAT!!!!!
    « Reply #6 on: 6/03/10, 11:43 »
    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

    Offline TryMeditate

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    Re: PR Research Thread - NO CHIT CHAT!!!!!
    « Reply #7 on: 6/03/10, 11:44 »
    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

    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

    Offline Jumanji

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    Re: PR Research Thread - NO CHIT CHAT!!!!!
    « Reply #8 on: 8/03/10, 04:58 »
    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.  


    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

    Offline dimsum

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    Re: PR Research Thread - NO CHIT CHAT!!!!!
    « Reply #9 on: 10/03/10, 16:29 »
    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.