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Thread: Should I be tested for endo?

  1. #1
    Join Date
    Feb 2014

    Default Should I be tested for endo?

    Hi Dr. Saleh-
    Thank you for your time, this is a wonderful service.

    -38 years old
    -AMH .39
    -ATA elevated over 8,000
    -NK cell activity was slightly elevated at 10.5 with <10 normal range suppressed to 7.9 with IL in lab
    -APA, ANA, Immunoglobulin panel, embryo toxicity assay, Repro Immuno Pheno all normal (except CD 4 T-Helper slightly elevated).
    -TSH in 2012 was 2.4, now in 2014 1.34 (I am not on thyroid meds the drop happened on its own)

    One failed donor cycle:
    -infused with IL 10 days before transfer
    -10mg Prednisone pre and post transfer
    -lining 8.2mm
    -the two blastocysts were grade 1
    -my saline ultrasound prior showed no fibroids or scarring

    We are sad and unsure of why this didn't work for us. We are about to have a subsequent FET from the same donor. If this second attempt fails, are there any other tests you would recommend I have, aside from further immunological testing? From reading your earlier posts, it actually sounds like you wouldn't recommend being tested for endometriosis, especially since I am already treating elevated NK cells, is this correct?

  2. #2
    Join Date
    Oct 2008


    The low AMH suggest decreased ovarian reserve, rather than immunological issues are the problem. Even though an embryo looks good, it may not be chromosomally normal. It would be important to adjust the protocol accordingly and consider genetic testing. See below:


    It is age rather than FSH level which is the predominant determinant of egg/embryo quality. At age 30 yrs, approximately 30% mature eggs/embryos will have structural and numerical chromosome abnormalities (aneuploidy) at age 40yrs the incidence is about 60%, at age 43yrs-+/- 75% and at 45yrs, about 85%. So, if four (4), “healthy looking” embryos were to be transferred to the uterus of a woman of say 43yrs, only about one could be expected to be chromosomally normal. A progressive increase in the incidence of embryo aneuploidy lies at the root of declining IVF success rates, increasing miscarriage rates and the increase in the incidence of birth defects such as Trisomy 21 (Down's syndrome) with advancing age. As an example, at age 43ys, under the very best circumstances, the IVF birth rate would be 10- 20% per cycle. Contrast this with a 50-60% success rate in a woman of similar age, who undergoes embryo transfer with embryos derived from a young fertile egg donor.

    Often, in spite of this realization, the desire to give birth to progeny that carry the mother’s own genetic code drives many women to try with their own eggs as long as the opportunity still avails itself to them.

    In an attempt to increase the number of follicles/eggs produced by older and sometimes younger women with “ovarian resistance”, some practitioners advocate the use of the so-called GnRHa (e.g. Lupron) “microflare (MCF) protocol”. The MCF protocol involves the administration of GnRHa therapy along with gonadotropins, virtually at the same time. The stated benefit of this approach is that it causes the woman’s own pituitary gland to release large amounts of FSH immediately, adding to the injected dosage of FSH and augmenting or even synergizing the follicular response. The problem is that there is no way to cause the administered GnRHa to selectively elicit an FSH response. LH is unfortunately also released along with FSH, in high concentrations in the pelvic blood system. The target of LH is largely the connective tissue (stroma/theca) in the ovaries which responds to LH by producing male hormones (predominantly, testosterone). While small amounts of testosterone (and therefore LH too) are indispensable to follicle growth and development and estrogen production by the follicles, exposure to too much testosterone compromises egg/embryo quality and down-regulates estrogen receptors in the uterine lining (endometrium), reducing the subsequent potential for the embryo(s) to implant. To make matters worse, as the menopause draws nearer and the ovaries become more “resistant” to FSH stimulation, the woman’s own pituitary LH becomes more bioactive as her FSH becomes less so. At the same time, her ovarian stroma undergoes thickening (hyperplasia) and becomes more sensitive to LH. The fact that ovarian production of testosterone increases with age is often evidenced by the appearance increased facial hair in menopausal women.

    It follows that older women (40yrs of age and beyond) as well as those with proven “ovarian resistance” require a customized approach to ovarian stimulation in an attempt to offset some of the consequences of excessive and undue exposure to LH. Such protocols should be aimed at minimizing ovarian exposure to LH (body's own pituitary LH as well as LH present in high concentration in some fertility drugs such as Pergonal and Repronex), without eliminating the presence of LH altogether. As previously stated, a small amount of LH is needed for follicle growth and estrogen production. Over-exposure to body's own LH can be best prevented by avoiding protocols such as MCF because the administration of the Lupron early in the cycle of stimulation, exposes developing follicles and endometrium at their most crucial stage of development (at the beginning) to too much testosterone. In addition, FSH-dominant products such as Folistim, Gonal-F and Brevelle should be prescribed preferentially.

    In the so called “Long Protocol (LP)”, which is the mainstay of ovarian stimulation in IVF, GnRHa (Lupron) is given, 5-7 days so prior to menstruation. This precipitates an initial rise in FSH and LH level, which is rapidly followed by a precipitous fall to very low FSH/LH blood levels by the time of withdrawal bleeding (menstruation), whereupon gonadotropin treatment is initiated while daily GnRHa injections continue, to ensure that FSH stimulation of follicles can take place in a “low LH environment. The main criticism of this approach to ovarian stimulation is that prolonged exposure to GnRHa could suppress (“blunt”) ovarian FSH receptor response to FSH stimulation, and thereby compromise follicular growth and development. To minimize this effect, the Lupron dosage must be drastically reduced from the onset of menses or be replaced with a GnRH antagonist such as Cetrotide or Antagon, from the onset of menstruation to the triggering of ovulation with hCG. It is thought that GnRH antagonists are less likely than agonists, to compromise FSH receptor response.

    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.


  3. #3
    Join Date
    Feb 2014

    Default Donor eggs....

    Hi Dr. Saleh-
    Sorry, I don't think I made it clear that we used DONOR eggs for our failed cycle and are about to use another donor egg for our FET, so I don't think my AMH would be affecting the outcome. Just curious what you would recommend for testing if this second donor cycle doesn't work?

  4. #4
    Join Date
    Oct 2008


    Ah ok. In that case, I would make sure you get treated for the NK hyperactivity. See below:


    Intralipid (IL), is a synthetic product composed of 10% soybean oil, 1,2% egg yolk phospholipids, 2.25% glycerin and water. Based on research performed at SIRM and elsewhere, infusion of IL lowers Natural Killer cell activation (Nka) as effectively as does, intravenous gammaglobulin (IVIG.) When indicated IL (as with IVIG) is infused 7-10 days prior to ET and one more time again after a positive pregnancy in women whose Nka is due to an autoimmune causes (antiphospholipid antibodies and/or antithyroid antibodies). In cases of alloimmune implantation dysfunction (DQa and/ HLA matching between the embryo recipient and the male partner) the same applies but in this situation the infusion is repeated at 2-4 week intervals until the 24th week of pregnancy.
    We have supplanted IVIG with IL therapy in a significant number of women undergoing IVF , and who had immunologic embryo implantation dysfunction. The results thus far have been excellent, way beyond our initial expectations.
    At last we now have a safe and inexpensive alternative to IVIG therapy…Intralipid! What is more, IL costs about 10 times less than IVIG, is not a blood product and is without significant side effects.

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