Ask Our Doctors – Archive
Our Medical Directors are outstanding physicians that you will find to be very personable and compassionate, who take care to ensure that you have the most cutting-edge fertility treatments at your disposal. This is your outlet to ask your questions to the doctors.
I am a 39- old woman with 5 failed FETs from one extraction. My doc put me on an estrogen priming protocol before the extraction cycle; even though I do not have DOR; instead have mild PCOS. In theory, this approach does not seem bad..however are there disadvantages to being on a estrogen priming protocol when you do not have DOR
I cant say there are real disadvantages. However, in my opinion there are no advantages in doing so.
Geoff Sher
Dr. Sher,
I am entirely grateful for your earlier reply to my questions. In your reply you wrote:
“I try to avoid using such protocols/regimes (especially) in older women and those with DOR, favoring instead the use of the agonist/antagonist conversion protocol (A/ACP), a modified, long pituitary down-regulation regime, augmented by adding supplementary human growth hormone (HGH).”
If I might ask some followup questions, I hope I’m not imposing too much on you? Starting from the end of your comment and working my way backward:
I actually asked my RE a few days ago about HGH and she told me that it is no longer allowed to be prescribed for IVF. Do you know anything about what she means?
And then, you mentioned an A/ACP protocol — I don’t know what that is. Could you describe it so I know better what to be asking for? Similarly, what kind of drugs are involved in a long-pituitary down-regime protocol, being new to all this I have no idea what that means either. 🙂
You mentioned LH in older women being an issue — I do know my LH on the three day FSH / LH test is 2.0.
Thank you for all your help to the IVF patient community —
Lori
HGH ism not available in NY but otherwise it is.
The use of GnRH antagonists as currently prescribed in ovarian stimulation cycles, i.e. the administration of 250mcg daily from the 6or 7th day of stimulation with gonadotropins is in my opinion problematic when used in women who have diminished ovarian reserve (DOR) (i.e. are “poor responders” to gonadotropins),. In such cases the commencement of pituitary LH suppression with GnRH antagonists 6-7 days into the stimulation fails to suppress high tonic pituitary LH in the first few days of stimulation and it is at this time , formative (early) stage of follicle/egg development early on in the most the vulnerable stage. One of the roles of LH is to promote androgen (mail hormone) production which in turn is essential (in modest amounts) for optimal follicular growth to take place. In women with high LH and/or ovarian stromal hyperplasia, the failure of conventional GnRH antagonist protocols to address this issue, results in the inevitable excessive exposure of follicles to androgens (mainly testosterone). This can adversely influence egg/embryo quality and endometrial development.
The likely reason for the traditional approach of commencing GnRH- antagonist 6-7 days after stimulation with gonadotropins commences, is to try to block the release of LH (later in the cycle) so as to try to prevent the occurrence of the so called “premature LH surge” (syn; premature luteinization), which is most commonly seen in women with DOR, who tend to be susceptible to LH-induced “follicular exhaustion” resulting in poor egg/embryo quality. But if truth be known, the term “premature LH surge” is a misnomer. Contrary to popular belief, the concept of LH rising as a “terminal event” late in the cycle is, erroneous. In fact rather than representing an isolated event, the so called “premature LH surge” is the end point of a progressive escalation in LH (“a staircase effect”) which results in increasing ovarian stromal activation with commensurate growing androgen (mainly testosterone) production. A more appropriate term would be …”Premature Luteinization”. So, trying to improve ovarian response and protect follicular exhaustion by administering Ganirelix/Cetrotide/Orgalutron starting during the final few days of ovarian stimulation is like trying to prevent a shipwreck by collision, through removing the tip of an iceberg. The use of such late GnRH-antagonist protocols in women who have a normal ovarian reserve (i.e. are “good responders”) will probably not produce such adverse effects because the tonic endogenous LH levels are low (normal) and such women are unlikely to have ovarian stromal hyperplasia.
It is my opinion that some form of pituitary blockade, either in the form of a GnRH agonist (e.g. Lupron, Buserelin, Superfact or Decapeptyl) or a GnRH antagonist (e.g. Orgalutron Cetrotide, and Ganirelix) 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 often adversely affect follicle/ egg development, resulting in compromised embryo quality. However, when a GnRH antagonist is used in women with DOR, it is my belief (for reasons cited above) that it should preferably be administered from early in the cycle, at the time that gonadotropin stimulation starts and NOT 6-7 days later, as is traditionally done. In such cases, the dosage of the GnRH antagonist can in my opinion be reduced to 125mcg daily.
The long Pituitary agonist down-Regulation approach: With the long Lupron down regulation protocol the administration of the GnRH agonist begins several days in advance of commencing gonadotropin stimulation. As such, by the time gonadotropin stimulation commences, most LH has been expunged from the pituitary gland thereby avoiding over-production of ovarian androgens. However, this protocol involves continued administratio0n of the GnRH agonist throughout the stimulation phase and this is not ideal for women who have DOR where prolonged administration of GnRH agonists could blunt follicular response to ovarian stimulation with gonadotropins (perhaps by competitively binding with ovarian FSH receptors).
The agonist-Antagonist conversion protocol (A/ACP). I introduced the A/ACP for women with DOR, in order to counter the suppression effect of the traditional long Pituitary agonist down-regulation protocol.. With the A/ACP, low dose GnRH-antagonist (Ganirelix/Cetrotide Orgalutron) is commenced at the onset of menstrual bleeding that follows initiation of GnRH agonist therapy using a long-down-regulation protocol approach or at the onset of spontaneous menstruation. I currently prescribe the A/ACP to most of my IVF patients who have DOR. Results suggest that this is an optimal approach in such cases. In such cases I augment the stimulation with human growth hormone.
There is one potential draw back to the use of the A/ACP, in that the sustained use of a GnRH antagonist 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 an agonist (e.g. Lupron) alone is used or where a “conventional” short GnRH antagonist protocol is employed. Rather than this 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. For this reason I avoid prescribing the A/ACP in “high responders” who are predisposed to the development of severe ovarian hyperstimulation syndrome (OHSS) where accurate measurement of plasma estradiol plays a very important role in the safe management of their stimulation cycles.
The A/ACP with Estrogen priming: In women who have severe DOR (AMH=<0.1 ng/ml) I modify the A/ACP The A/ACP through incorporation of “estrogen priming” with injections of estradiol valerate (Delestrogen), given twice weekly for about a week following the initiation of the A/ACP, and prior to commencing FSH-dominant gonadotropin stimulation. I then continue this through gonadotropin stimulation. Estrogen Priming appears to further enhance ovarian response….presumably by up-regulating ovarian FSH-receptors. ”.
“Flare Protocols” in women with DOR: With the “Flare” approach, GnRH agonist (e.g. Lupron/Buserelin/Superfact/Decapeptyl) is started with the initiation of gonadotropin stimulation. The agonist causes an immediate surge in pituitary gland LH release. Thus the follicles/ eggs of women on GnRH-agonist “flare protocols” are exposed to an exaggerated Lupron-induced LH release, (the “flare effect” The increased androgen production early on in the stimulation has a deleterious effect on egg development and thus on subsequent embryo quality.
The Traditional GnRH-antagonist , ‘short protocol” in women with DOR: 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). While this might not be problematic in in women who have normal ovarian reserve (i.e. “normal responders”), it could be decidedly prejudicial in women with DOR (“poor responders”) where endogenous tonic LH activity is usually raised and the ovaries may be inordinately sensitive to LH. In such cases excessive exposure of follicles and eggs to androgens (mainly testosterone) could severely compromise egg development and thus embryo quality.
Use of the Birth Control Pill to set up ovarian stimulation with gonadotropins: In my practice, patients are placed on a birth control pill for 10-40 days (depending on circumstance), before commencing a long antagonist protocol (whether conventional or the A/ACP). With this approach, the agonist is overlapped with the BCP in the last few days of its usage. Thereupon daily agonist administration continues until menstruation ensues a few days later at which point, the dosage of the agonist is halved and this is continued throughout stimulation until the hCG “trigger”.
The rise in FSH that occurs in ovulating women 5-6 days prior to menses, initiates recruitment of follicles available for the upcoming cycle. The BCP by suppressing ovulation (and FSH) precludes this premenstrual rise in FSH, suppressing follicle recruitment. Premenstrual GnRH agonist administration overcomes this by inducing a premenstrual FSH surge which then serves to recruits follicles in a timely manner…for the upcoming COH cycle. Following use of the BCP (without prior overlap with agonist) the first 4-6 days of FSH administration must first recruit follicles before growing them.
When the BCP is overlapped with a GnRH agonists towards the end of the BCP cycle, it triggers a pre-menstrual pituitary release of endogenous FSH (and LH). This results in recruitment of follicles to the antral follicle stage, whereupon the initiation of gonadotropin stimulation, while continuing agonist or supplanting this with low dose antagonist (i.e. A/ACP) to prevent further LH release, will induce an uninhibited and prompt follicle growth and development.
Given that FSH is so important to antral follicle “recruitment” , since the BCP suppresses FSH, it is essential (in my opinion) that the contraceptive pill be overlapped with an agonist during the last 3 days of its use to promote FSH production. If this is omitted optimal antral follicle development will not occur, and the response to subsequent ovarian stimulation with gonadotropins will in my opinion, be suboptimal. This could result in discordant egg/follicle development, a longer period of ovarian stimulation and compromised egg/embryo quality. I believe that unless the use of a long pituitary down regulation approach is contemplated, launching ovarian stimulation coming off a BCP is best be avoided.
Geoff Sher
Hi Dr. Sher,
I’m 37 years old with DOR. High FSH and AMH .6 . I conceived successfully in 2013 through IVF, and then again in 2015 with a frozen embryo from the same cycle (2 healthy boys today)! I tried another round of IVF last year, where only 4 eggs were retrieved and 1 made it to GoodBB and was hatching, but that embryo came back after PGS as missing one of chromosome 18 so was not transferred. I would like to try one more time! I started taking 75mgs of DHEA daily a couple of weeks ago and have already begun experiencing severe skin breakouts and suspected hair loss. I am second-guessing the DHEA after stumbling upon your site. My questions are:
-Would you recommend DHEA for me?
-Out of curiosity, have you ever seen an embryo that was missing one of chromosome 18 transferred and resulted in a healthy baby? I am considering not getting the PGS this time.
Thank you for your time and for your very helpful site!
In my opinion, an autosomal monosomy 18 is worthy of transfer. It could be a mosaic.
Dehydroepiandrosterone (DHEA), is steroid hormone produced by the adrenal glands and ovary. It is involved in producing the male hormones, androstenedione testosterone and also estrogen. DHEA blood levels tend to decline naturally with age.
Under the effect if luteinizing hormone (LH), DHEA is metabolized to testosterone in ovarian connective tissue (theca/stroma). Thereupon the testosterone is transported to the granulosa cells that form the innermost layer of the ovarian follicles where, under the influence of follicle stimulating hormone (FSH)-induced desmolase and aromatase enzymatic activity the testosterone is converted to estradiol. As this happens, granulosa cells multiply, follicle fluid volume increases along with estrogen output and egg development is promoted.
It is recognition of the essential/indispensable role that male hormones (mainly testosterone) play in follicle and egg development that prompted the belief that by giving DHEA and boosting ovarian testosterone production might benefit follicle/egg development. This belief was given some credence by an Israeli study that in 2010 reported on improved fertility when a group of infertile women were given the administration of 75mg of oral DHEA for 5 months. However, this study was seriously flawed by the fact that it did not separate out women who had diminished ovarian reserve, older women and those with PCOS, all of whom have increased LH-induced production of testosterone. In fact, we recently completed a study (currently being processed for publication) where we conclusively showed that when follicular fluid testosterone levels exceeded a certain threshold, egg quality was seriously prejudiced as evidenced by a marked increase in the incidence of egg chromosomal defects (aneuploidy).
Consider the following: Ovarian testosterone is needed for follicular development. However, the amount required is small. Too much ovarian testosterone spills over into the follicular fluid and has a deleterious effect on egg/follicle development. Some women (women with diminished ovarian reserve –DOR, older women and those with polycystic ovarian syndrome-PCOS) who tend to have increased LH biological activity, already over-produce testosterone. To such women, the administration of DHEA to such women, by “adding fuel to the fire” can be decidedly prejudicial, in my opinion. Young women with normal ovarian reserve do not over produce LH-induced ovarian testosterone, and are thus probably not at significant risk from DHEA supplementation. It is noteworthy that to date, none of the studies that suggest a benefit from DHEA therapy have differentiated between young healthy normal women with normal ovarian reserve on the one hand and older women, those with DOR and women with PCOS on the other hand.
In Some countries DHEA treatment requires a medical prescription and medical supervision. Not so in the U.S.A where it can be bought over the counter. Since DHEA is involved in sex hormone production, including testosterone and estrogen, individuals with malignant conditions that may be hormone dependent (certain types of breast cancer or testicular cancer) should not receive DHEA supplementation. Also, if overdosed with DHEA some “sensitive women” might so increase their blood concentrations of testosterone that they develop increased aggressive tendencies or male characteristics such as hirsuites (increased hair growth) and a deepening voice. DHEA can also interact other medications, such as barbiturates, corticosteroids, insulin and with other oral diabetic medications.
BUT the strongest argument against the use of routine DHEA supplementation is the potential risk of compromising egg quality in certain categories of women and since there is presently no convincing evidence of any benefit, why take the risk in using it on anyone.
Finally, for those who in spite of the above, still feel compelled to take DHEA, the best advice I can give is to consult their health care providers before starting the process.
Addendum: One potential advantage of DHEA therapy if used appropriately came from a study conducted by Washington University School of Medicine in St. Louis, MI and reported in the November 2004 issue of the “Journal of the American Medical Association” which showed that judicious (selective) administration of 50mg DHEA daily for 6 months resulted in a significant reduction of abdominal fat and blood insulin in elderly women.
Women who (regardless of age) have diminished ovarian reserve (DOR) have a reduced potential for IVF success. Much of this is due to the fact that such women tend to have increased production, and/or biological activity, of LH. This can result in excessive ovarian male hormone (predominantly testosterone) production. This in turn can have a deleterious effect on egg/embryo “competency”.
While it is presently not possible by any means, to reverse the effect of DOR, certain ovarian stimulation regimes, by promoting excessive LH production (e.g. short agonist/Lupron- “flare” protocols, clomiphene and Letrozole), can in my opinion, make matters worse. Similarly, the amount/dosage of certain fertility drugs that contain LH/hCG (e.g. Menopur) can have a negative effect on the development of the eggs of older women and those who have DOR and should be limited.
I try to avoid using such protocols/regimes (especially) in women with DOR, favoring instead the use of the agonist/antagonist conversion protocol (A/ACP), a modified, long pituitary down-regulation regime, augmented by adding supplementary human growth hormone (HGH). I further recommend that such women be offered access to embryo banking of PGS (next generation gene sequencing/NGS)-selected normal blastocysts, the subsequent selective transfer of which by allowing them to capitalize on whatever residual ovarian reserve and egg quality might still exist and thereby “make hay while the sun still shines” could significantly enhance the opportunity to achieve a viable pregnancy
Please visit my new Blog on this very site, www. SherIVF.com, find the “search bar” and type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly
•Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
•IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation(COS)
•The Fundamental Requirements For Achieving Optimal IVF Success
•Ovarian Stimulation for IVF using GnRH Antagonists: Comparing the Agonist/Antagonist Conversion Protocol.(A/ACP) With the “Conventional” Antagonist Approach
•Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
•The “Biological Clock” and how it should Influence the Selection and Design of Ovarian Stimulation Protocols for IVF.
• A Rational Basis for selecting Controlled Ovarian Stimulation (COS) protocols in women with Diminished Ovarian Reserve (DOR)
•Diagnosing and Treating Infertility due to Diminished Ovarian Reserve (DOR)
•Controlled Ovarian Stimulation (COS) in Older women and Women who have Diminished Ovarian Reserve (DOR): A Rational Basis for Selecting a Stimulation Protocol
•Human Growth Hormone Administration in IVF: Does it Enhances Egg/Embryo Quality and Outcome?
•The BCP: Does Launching a Cycle of Controlled Ovarian Stimulation (COS). Coming off the BCP Compromise Response?
•Blastocyst Embryo Transfers Should be the Standard of Care in IVF
•Frozen Embryo Transfer (FET) versus “Fresh” ET: How to Make the Decision
•Frozen Embryo Transfer (FET): A Rational Approach to Hormonal Preparation and How new Methodology is Impacting IVF.
•Staggered IVF: An Excellent Option When. Advancing Age and Diminished Ovarian Reserve (DOR) Reduces IVF Success Rate
•Embryo Banking/Stockpiling: Slows the “Biological Clock” and offers a Selective Alternative to IVF-Egg Donation.
•Preimplantation Genetic Testing (PGS) in IVF: It Should be Used Selectively and NOT be Routine.
•Preimplantation Genetic Sampling (PGS) Using: Next Generation Gene Sequencing (NGS): Method of Choice.
•PGS in IVF: Are Some Chromosomally Abnormal Embryos Capable of Resulting in Normal Babies and Being Wrongly Discarded?
•PGS and Assessment of Egg/Embryo “competency”: How Method, Timing and Methodology Could Affect Reliability
•Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas:
•Traveling for IVF from Out of State/Country–
•A personalized, stepwise approach to IVF
•How Many Embryos should be transferred: A Critical Decision in IVF.
•The Role of Nutritional Supplements in Preparing for IVF
•Premature Luteinization (“the premature LH surge): Why it happens and how it can be prevented.
•IVF Egg Donation: A Comprehensive Overview
My final IVF cycle at SIRM-LV commences on March 19th and concludes on April 2nd. If you are interested in undergoing a fresh IVF treatment cycle with me or if you have embryos cryopreserved at SIRM-LV and wish to undergo a Frozen Embryo Transfer (FET) prior to my departure, please contact me immediately….. My March cycle is likely to be very much in demand…….So, time is of the essence!
Following my departure from SIRM in mid-April, 2019, I will continue to provide comprehensive consultations to those of you that wish to have my guidance. Upon scheduling a SKYPE consultation with me, you will promptly receive a detailed questionnaire, along with a request that you submit available medical records for my review prior to our consultation. Additional tests and records can/will be requisitioned later, as needed. Your +/- 1 hour comprehensive SKYPE consultation will be followed by a detailed written report which you can also share with your personal Fertility Physician.
I will soon be posting a list of internationally regarded Fertility Specialists whom I endorse and who will have expressed a willingness to implement my suggested approaches, at their discretion. It is to one of these doctors that I would selectively refer you…upon request.
CONTACT INFORMATION:
•Online: Go to sherivf.com and Schedule a Skype Consultation. Upon doing so, you will be able to download a free copy of my new eBook ” Recurrent Pregnancy Loss (RPL) and Unexplained IVF Failure: The Immunologic Link”
•Phone
oIf you live in the USA or Canada: Please call 1-800-780-7437 or 702-533-2691
oIf you reside elsewhere Abroad: Please call 702-533-2691
oEmail: concierge@SherIVF.com
Please monitor this website for future announcements on further developments.
Geoff Sher
Hello. I am 31 and i just went through my first IVF cycle but i had empty follicle syndrome and I’m wondering what your opinion is.
I have a diminished ovarian reserve FSH 19.1 U/L (unfortunately i do not know my AMH levels but when they were first taken i was told my chances of IVF being successful were 10% but after my AFC which showed better results – 5 and 4 – my doctor said we should try IVF).
For 2 months prior to my cycle i was on the birth control pill and also did one pump (1.25 g of gel) AndroGel 1% daily while i was on the pill. I did this for two cycles.
When i started IVF, i started on January 3 with Microdose Lupron (400/mcg/ml) 10 units or 0.1ml twice a day. I did Lupron for my whole cycle.
On January 5 i started Gonal-f 450 IU daily, continued my Lupron twice a day and also started Dexamethasone 1mg daily.
I did this until January 16th when i was instructed to do my trigger shot.
On January 16 i did Lupron in the morning, stopped the Dexamethasone and did 300 IU Gonal-f that night.
On January 16 i also did my trigger shot at 9pm which was 1000 IU hCG.
Egg retrieval was scheduled for 9 am on January 18 but then I had empty follicle sydnrome.
On January 16 my follicles measured
Right ovary – 14mm, 19mm, 20mm
Left ovary – 19mm, 8mm
I was sent for bloodwork following the retrieval and my HCG was 233 U/L which i was told was normal.
I also take synthroid 0.05mg and have taken this for 3 years.
Can you please let me know your thoughts. I am 31, health, 126 lbs, 5’4 and do not smoke.
Thank you,
Amanda
There are 3 issues: 1.”empty follicle syndrome; 2.your diminished ovarian reserve (DOR) and 3. Hypothyroidism and the possible link to autoimmune implantation dysfunction.
a. Empty Follicle Syndrome:
Frequently, when following vigorous and often repeated flushing of follicles at egg retrieval they fail to yield eggs, it is ascribed to “Empty Follicle Syndrome.” This is a gross misnomer, because all follicles contain eggs. So why were no eggs retrieved from the follicles? Most likely it was because they would/could not yield the eggs they harbored.
This situation is most commonly seen in older women, women who have severely diminished ovarian reserve, and in women with polycystic ovarian syndrome (PCOS). In my opinion it is often preventable when an optimal, individualized and strategic protocol for controlled ovarian stimulation (COS) is employed and the correct timing and dosage is applied to the “hCG trigger shot.”
Normally, following optimal ovarian stimulation, the hCG “trigger shot” is given for the purpose of it triggering meiosis (reproductive division) that is intended to halve the number of chromosomes from 46 to 23 within 32-36 hours. The hCG trigger also enables the egg to signal the “cumulus cells” that bind it firmly to the inner wall of the follicle (through enzymatic activity), to loosen or disperse, so that the egg can detach and readily be captured at egg retrieval (ER).
Ordinarily, normal eggs (and even those with only one or two chromosomal irregularities) will readily detach and be captured with the very first attempt to empty a follicle. Eggs that have several chromosomal numerical abnormalities (i.e., are “complex aneuploid”) are often unable to facilitate this process. This explains why when the egg is complex aneuploid, its follicle will not yield an egg…and why, when it requires repeated flushing of a follicle to harvest an egg, it is highly suggestive of it being aneuploid and thus “incompetent” (i.e., incapable of subsequently propagating a normal embryo).
Older women, women with diminished ovarian reserve, and those with polycystic ovarian syndrome, tend to have more biologically active LH in circulation. LH causes production of male hormone (androgens, predominantly testosterone), by ovarian connective tissue (stroma/theca). A little testosterone is needed for optimal follicle development and for FSH-induced ovogenesis (egg development). Too much LH activity compromises the latter, and eggs so affected are far more likely to be aneuploid following meiosis.
Women with the above conditions have increased LH activity and are thus more likely to produce excessive ovarian testosterone. It follows that sustained, premature elevations in LH or premature luteinization (often referred to as a “premature LH surge”) will prejudice egg development. Such compromised eggs are much more likely to end up being complex aneuploid following the administration of the hCG trigger, leading to fruitless attempts at retrieval and the so called “empty follicle syndrome.”
The developing eggs of women who have increased LH activity (older women, women with diminished ovarian reserve, and those with PCOS) are inordinately vulnerable to the effects of protracted exposure to LH-induced ovarian testosterone. Because of this, the administration of medications that provoke further pituitary LH release (e.g., clomiphene and Letrozole), drugs that contain LH or hCG (e.g., Menopur), or protocols of ovarian stimulation that provoke increased exposure to the woman’s own pituitary LH (e.g., “flare-agonist protocols”) and the use of “late pituitary blockade” (antagonist) protocols can be prejudicial.
The importance of individualizing COS protocol selection, precision with regard to the dosage and type of hCG trigger used, and the timing of its administration in such cases cannot be overstated. The ideal dosage of urinary-derived hCG (hCG-u) such as Novarel, Pregnyl and Profasi is 10,000U. When recombinant DNA-derived hCG (hCG-r) such as Ovidrel is used, the optimal dosage is 500mcg. A lower dosage of hCG can, by compromising meiosis, increase the risk of egg aneuploidy, and thus of IVF outcome.
There is in my opinion no such condition as “Empty Follicle Syndrome.” All follicles contain eggs. Failure to access those eggs at ER can often be a result of the protocol used for controlled ovarian stimulation.
2. Diminished Ovarian Reserve:
Women who (regardless of age) have diminished ovarian reserve (DOR) have a reduced potential for IVF success. Much of this is due to the fact that such women tend to have increased production, and/or biological activity, of LH. This can result in excessive ovarian male hormone (predominantly testosterone) production. This in turn can have a deleterious effect on egg/embryo “competency”.
While it is presently not possible by any means, to reverse the effect of DOR, certain ovarian stimulation regimes, by promoting excessive LH production (e.g. short agonist/Lupron- “flare” protocols, clomiphene and Letrozole), can in my opinion, make matters worse. Similarly, the amount/dosage of certain fertility drugs that contain LH/hCG (e.g. Menopur) can have a negative effect on the development of the eggs of older women and those who have DOR and should be limited.
I try to avoid using such protocols/regimes (especially) in women with DOR, favoring instead the use of the agonist/antagonist conversion protocol (A/ACP), a modified, long pituitary down-regulation regime, augmented by adding supplementary human growth hormone (HGH). I further recommend that such women be offered access to embryo banking of PGS (next generation gene sequencing/NGS)-selected normal blastocysts, the subsequent selective transfer of which by allowing them to capitalize on whatever residual ovarian reserve and egg quality might still exist and thereby “make hay while the sun still shines” could significantly enhance the opportunity to achieve a viable pregnancy
3. Autoimmune Thyroid Disease:
Between 2% and 5% of women of the childbearing age have reduced thyroid hormone activity (hypothyroidism). Women with hypothyroidism often manifest with reproductive failure i.e. infertility, unexplained (often repeated) IVF failure, or recurrent pregnancy loss (RPL). The condition is 5-10 times more common in women than in men. In most cases hypothyroidism is caused by damage to the thyroid gland resulting from of thyroid autoimmunity (Hashimoto’s disease) caused by damage done to the thyroid gland by antithyroglobulin and antimicrosomal auto-antibodies.
The increased prevalence of hypothyroidism and thyroid autoimmunity (TAI) in women is likely the result of a combination of genetic factors, estrogen-related effects and chromosome X abnormalities. This having been said, there is significantly increased incidence of thyroid antibodies in non-pregnant women with a history of infertility and recurrent pregnancy loss and thyroid antibodies can be present asymptomatically in women without them manifesting with overt clinical or endocrinologic evidence of thyroid disease. In addition, these antibodies may persist in women who have suffered from hyper- or hypothyroidism even after normalization of their thyroid function by appropriate pharmacological treatment. The manifestations of reproductive dysfunction thus seem to be linked more to the presence of thyroid autoimmunity (TAI) than to clinical existence of hypothyroidism and treatment of the latter does not routinely result in a subsequent improvement in reproductive performance.
It follows, that if antithyroid autoantibodies are associated with reproductive dysfunction they may serve as useful markers for predicting poor outcome in patients undergoing assisted reproductive technologies.
Some years back, I reported on the fact that 47% of women who harbor thyroid autoantibodies, regardless of the absence or presence of clinical hypothyroidism, have activated uterine natural killer cells (NKa) cells and cytotoxic lymphocytes (CTL) and that such women often present with reproductive dysfunction. We demonstrated that appropriate immunotherapy with IVIG or intralipid (IL) and steroids, subsequently often results in a significant improvement in reproductive performance in such cases.
The fact that almost 50% of women who harbor antithyroid antibodies do not have activated CTL/NK cells suggests that it is NOT the antithyroid antibodies themselves that cause reproductive dysfunction. The activation of CTL and NK cells that occurs in half of the cases with TAI is probably an epiphenomenon with the associated reproductive dysfunction being due to CTL/NK cell activation that damages the early “root system” (trophoblast) of the implanting embryo. We have shown that treatment of those women who have thyroid antibodies + NKa/CTL using IL/steroids, improves subsequent reproductive performance while women with thyroid antibodies who do not harbor NKa/CTL do not require or benefit from such treatment.
I strongly recommend that you visit http://www.DrGeoffreySherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.
•The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
•Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
•IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation (COS)
•The Fundamental Requirements for Achieving Optimal IVF Success
•Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
•Ovarian Stimulation in Women Who have Diminished Ovarian Reserve (DOR): Introducing the Agonist/Antagonist Conversion protocol
•Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
•Human Growth Hormone Administration in IVF: Does it Enhances Egg/Embryo Quality and Outcome?
•The BCP: Does Launching a Cycle of Controlled Ovarian Stimulation (COS). Coming off the BCP Compromise Response?
•Blastocyst Embryo Transfers should be the Standard of Care in IVF
•IVF: How Many Attempts should be considered before Stopping?
•“Unexplained” Infertility: Often a matter of the Diagnosis Being Overlooked!
•IVF Failure and Implantation Dysfunction:
•The Role of Immunologic Implantation Dysfunction (IID) & Infertility (IID): PART 1-Background
•Immunologic Implantation Dysfunction (IID) & Infertility (IID): PART 2- Making a Diagnosis
•Immunologic Dysfunction (IID) & Infertility (IID): PART 3-Treatment
•Thyroid autoantibodies and Immunologic Implantation Dysfunction (IID)
•Immunologic Implantation Dysfunction: Importance of Meticulous Evaluation and Strategic Management 🙁 Case Report)
•Intralipid and IVIG therapy: Understanding the Basis for its use in the Treatment of Immunologic Implantation Dysfunction (IID)
•Intralipid (IL) Administration in IVF: It’s Composition; how it Works; Administration; Side-effects; Reactions and Precautions
•Natural Killer Cell Activation (NKa) and Immunologic Implantation Dysfunction in IVF: The Controversy!
•Endometrial Thickness, Uterine Pathology and Immunologic Factors
•Vaginally Administered Viagra is Often a Highly Effective Treatment to Help Thicken a Thin Uterine Lining
•Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas:
•A personalized, stepwise approach to IVF
•How Many Embryos should be transferred: A Critical Decision in IVF?
•The Role of Nutritional Supplements in Preparing for IVF
My final IVF cycle at SIRM-LV commences on March 19th and concludes on April 2nd. If you are interested in undergoing a fresh IVF treatment cycle with me or if you have embryos cryopreserved at SIRM-LV and wish to undergo a Frozen Embryo Transfer (FET) prior to my departure, please contact me immediately….. My March cycle is likely to be very much in demand…….So, time is of the essence!
Following my departure from SIRM in mid-April, 2019, I will continue to provide comprehensive consultations to those of you that wish to have my guidance. Upon scheduling a SKYPE consultation with me, you will promptly receive a detailed questionnaire, along with a request that you submit available medical records for my review prior to our consultation. Additional tests and records can/will be requisitioned later, as needed. Your +/- 1 hour comprehensive SKYPE consultation will be followed by a detailed written report which you can also share with your personal Fertility Physician.
I will soon be posting a list of internationally regarded Fertility Specialists whom I endorse and who will have expressed a willingness to implement my suggested approaches, at their discretion. It is to one of these doctors that I would selectively refer you…upon request.
CONTACT INFORMATION:
•Online: Go to sherivf.com and Schedule a Skype Consultation. Upon doing so, you will be able to download a free copy of my new eBook ” Recurrent Pregnancy Loss (RPL) and Unexplained IVF Failure: The Immunologic Link”
•Phone
oIf you live in the USA or Canada: Please call 1-800-780-7437 or 702-533-2691
oIf you reside elsewhere Abroad: Please call 702-533-2691
oEmail: concierge@SherIVF.com
Please monitor this website for future announcements on further developments.
Geoff Sher
Hi Dr. Sher,
I recently have experienced 2 miscarriages and one chemical pregnancy all done through FETs. I have one daughter through the same IVF cycle and had a healthy pregnancy. All of the embryos were tested prior to transfer so we know the number of chromosomes were fine. My 1st miscarriage was last Spring at 8 weeks with massive bleeding and after D&C a rare AVM was discovered in uterus. I fully recovered from this after a few months and then did another transfer which resulted in chemical pregnancy. This Fall I did another transfer and heartbeat and measurement looked great at 6 weeks (as it had with Spring pregnancy) but again at 8 weeks miscarried. I did RPL blood panel and everything came back normal. We also tested both embryos after the D&Cs and they both came back healthy with no issues. I just did another round of IVF and my doctor is recommending putting me on a steroid when I begin my FET. I was told and have read there is a very small chance of cleft lip which scares me. If you were my doctor would you put me on a steroid even though we don’t know why I am miscarrying? Thank you !