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.
Hello Dr Sher! I just had a question re estradiol. Can too much testosterone cause elevated estradiol levels?
It’s so amazing you have given so much of your time to help other women. I am 40.8 years old. I have been TTC naturally now for 2.5 years and it hasn’t worked. I have had a hycosy, a hysterscopy and all is clear. I have been told it’s my age. No male factor infertility either. My AMH is 0.96 ng/ml, what protocol do you recommend for me?
Thank you kindly,
Based upon your AMH you have diminished ovarian reserve (DOR). In my opinion, the protocol used for ovarian stimulation, against the backdrop of age, and ovarian reserve are the drivers of egg quality and egg quality is the most important factor affecting embryo “competency”.
Older women as well as those who (regardless of age) have (DOR) tend to produce fewer and less “competent” eggs, the main reason for reduced IVF success in such cases. The compromised outcome is largely due to the fact that such women tend to have increased LH biological activity which often results in excessive LH-induced ovarian testosterone production which in turn can have a deleterious effect on egg/embryo “competency”.
Certain ovarian stimulation regimes either promote excessive LH production (e.g. short agonist/Lupron- “flare” protocols, clomiphene and Letrozole), augment LH/hCG delivered through additional administration (e.g. high dosage menotropins such as Menopur), or fail to protect against body’s own/self-produced LH (e.g. late antagonist protocols where drugs such as Ganirelix/Cetrotide/Orgalutron that are first administered 6-7 days after ovarian stimulation has commenced).
I try to avoid using such protocols/regimes (especially) in older women and those with DOR, favoring instead the use of a modified, long pituitary down-regulation protocol (the agonist/antagonist conversion protocol-A/ACP) augmented by adding supplementary human growth hormone (HGH). I further recommend Staggered IVF with embryo banking of PGS (next generation gene sequencing/NGS)-normal blastocysts in such cases. This type of approach will in my opinion, optimize the chance of a viable pregnancy per embryo transfer procedure and provide an opportunity to capitalize on whatever residual ovarian reserve and egg quality still exists, allowing the chance to “make hay while the sun still shines”.
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.
•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 Aproach
•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.
•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?
•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
•Implications of “Empty Follicle Syndrome and “Premature Luteinization”
•Premature Luteinization (“the premature LH surge): Why it happens and how it can be prevented.
If you are interested in seeking my advice or services, I urge you to contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com You can also apply online at http://www.SherIVF.com .
*FYI
The 4th edition of my book,”In Vitro Fertilization, the ART of Making Babies” is now available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.
Geoffrey Sher MD
Hello Dr.Geoffrey Sher. I’m 32 year old women.My AMH levels are 1.2 ng/ml. I had 4 cycle of IVF, one with agonist and three with antagonist and got pregnant only once. I had oocytes retrived between 9-20 each cycle.I always had LH below 10 after lupron trigger in antagonist cycles. I had ovarian hyperstimulation syndrome with agonist protocol. Could you please let me know why I always have OHSS with HCG trigger even though I have low ovarian reserve.Could you also let me know my chances of getting pregnant.
That clearly suggests that the diagnosis of OHSS is not accurate. I would repeat FSH/LH/E2 and AMH in day 3 of your cycle.
Typically, women with irregular ovulation/menstruation, young women, those with high ovarian reserve (AMH=>6ng/ml) and those who have polycystic ovarian syndrome (PCOS) who undergo ovarian stimulation with fertility drugs are at increased risk of developing severe ovarian hyperstimulation syndrome (OHSS), a life endangering condition. In cases of OHSS egg “competency” (quality) is often severely compromised.
The fear of OHSS developing often prompts RE’s to trigger egg maturation prematurely with hCG in the hope of arresting the process before ovarian stimulation spirals out of control, increasing physical risk and causing a high percentage of harvested eggs to end up being “incompetent”, (“immature/dysmature).
Also in an attempt to reduce the risks of OHSS, some RE’s trigger egg maturation using a reduced dosage of hCG or through inducing an outpouring of pituitary LH an agonist such as Lupron or Buserelin. While such approaches indeed reduce the risk and severity of OHSS, they often result in many eggs failing to mature. Thus lowering risk by reducing the dosage of hCG or by using an agonist “trigger”, often comes at the expense of egg “competency”.
In women with PCOS, poor egg “competency” is also often attributable to high ovarian LH-induced testosterone. Such eggs have reduced fertilization potential, often yielding “poor quality embryos”. While poor egg “competency” in women with PCOS can be due to the fact that such eggs are more prone to having intrinsic quality deficits, it is (in my opinion), more commonly attributable to aberrant intra-ovarian hormonal changes brought about by severe ovarian hyperstimulation. This effect, can be prevented or curtailed through implementation of individualized or customized ovarian stimulation protocols that minimize over-exposure to excessive LH-induced ovarian male hormones (androgens) which can best be accomplished by limiting the use of LH-containing gonadotropins such as Menopur and by using a procedure that I introduced in 1989, known as “prolonged coasting” (see below).
Approaches to preventing or containing OHSS include:
1.PROLONGED COASTING: My preferred approach is to use a long pituitary DR protocol coming off up to 2 months on the BCP, overlapped in the last 3 days with the agonist, Lupron. The BCP is intended to lower LH and thereby reduce stromal activation (hyperthecosis) in the hope of controlling ovarian androgen (predominantly, testosterone) production and release. I then stimulate with low dosage recombinant FSF-FSHr (Follistim/Gonal-F/Puregon) to which I add a smidgeon of LH/hCG (Luveris/Menopur) from the 3rd day. Then, starting on day 7 of ovarian stimulation, I perform serial blood estradiol (E2) and ultrasound follicle assessments, watching for the # of follicles and [E2]. If there are > 25 follicles, I keep stimulating (regardless of the [E2] until 50% of all follicles reach 14mm. At this point, provided the [E2] reaches at least >2,500pg/ml, I stop the agonist as well as gonadotropin stimulation and track the blood E2 (without continuing US, follicle measurements) ) daily. The [E2] will almost invariably increase for a few days. I watch the E2 rise (regardless of how high a blood concentration it reaches) and then track it coming down again. As soon as the [E2] drops below 2500pg/ml (and not before then), I administer a “trigger” shot of 10,000U hCGu (Profasi/ Novarel/Pregnyl) or hCGr (Ovidrel/Ovitrel-500mcg) and perform an egg retrieval 36 hours later. ICSI is a MUST because “coasted” eggs usually have no cumulus oophoris envelopment and eggs without a cumulus will not readily fertilize naturally. Moreover, they also tend to have a “hardened” envelopment (zona pellucida), making spontaneous fertilization problematic in many cases. All fertilized eggs are cultured to blastocyst (up to 6 days) and are then either vitrified and preserved for subsequent transfer in later hormone replacement cycles or up to two (2) fresh blastocysts are transferred transvaginal under US guidance.. The success of this approach depends on precise timing of the initiation and conclusion of “prolonged coasting”. If you start too early, follicle growth will stop and the cycle will be lost. If you start too late, you will encounter too many post-mature/cystic follicles (>22mm) that usually harbor abnormally developed eggs. Use of “Coasting” avoids unnecessary cycle cancellation, severe OHSS, and optimizes egg/embryo quality. The worst you will encounter is mild to moderate OHSS and this too is uncommon. The obvious remedy for these adverse effects on egg and endometrial development is to employ stimulation protocols that limit ovarian over-exposure to LH and allowing the time necessary for the follicles/eggs to develop optimally, prior to administering hCG through the judicious implementation of “Prolonged coasting” (PC).
2.MULTIPLE FOLLICLE ASPIRATION: In some cases, where because of mean follicle size exceeding 16mm or when “coasting” fails to effectively lower the [E2} below 2,500pg/ml within 3 days, the number of developing follicles can effectively and drastically reduced through target transvaginal aspiration, 1-3 PRIOR to planned the hCG trigger. This will almost invariably be accompanied by a rapid and significant drop in the plasma [E2] and in the process will drastically reduce the risk of OHSS occurring without significantly compromising egg/embryo quality. The drawback of this effective approach is the fact that it interjects an additional surgical intervention into an already complex and stressful situation. i
3.TRIGGERING WITH LOW DOISAGE hCG; Because of the fact that hCG augments the development of OHSS (unless preceded by “coasting”), may RE’s prefer to use a lower dosage of hCG for the “trigger. This is either done by administering 5,000U (half the traditional dosage) or by administering, a 250mcg (rather than 500mcg) of DNA recombinant form of hCGr (Ovidrel/Ovitrel. Some clinicians, when faced with a risk of OHSS developing will deliberately elect to reduce the “trigger” dosage of hCG administered (from 10,000U to 5,000U or 250mcg of recombinant hCG-Ovidrel) in the hope that by doing so the risk of critical OHSS developing will be lowered. While this might indeed be true, it is my opinion, that such a reduced dosage is usually insufficient to optimize the efficiency of egg meiosis, e3specially when there are so many follicles present. While the use of a reduced “trigger” dosage of hCG does indeed reduce the risk and occurrence of OHSS-related life-endangering complications, the price to be paid is reduced egg quality/”competency”.
4.“TRIGGERING” WITH A GnRH AGONIST (E.G. “LUPRON/BUSERELIN): More recently, an increasing number of RE’s prefer to trigger meiosis by way of an agonist (Lupron/Buserelin/Superfact () “trigger” rather than through the use of hCG. The idea is to mimic what happens in natural cycles to promote egg maturation (meiosis) and ovulation, namely to have the agonist cause a “surge” in the release of body’s own pituitary LH to trigger egg meiosis (maturation) .But the amount of LH released in by the pituitary gland is often insufficient to optimize meiotic egg maturation and thus, while this approach also lowers the risk of OHSS it again comes at the expense of egg quality/competency.
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.
•Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
•Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas:
•A personalized, stepwise approach to IVF
•Preventing Severe Ovarian Hyperstimulation Syndrome (OHSS) with “Prolonged Coasting.
•“Triggering” Egg Maturation in IVF: Comparing urine-derived hCG, Recombinant DNA-hCG and GnRH-agonist:
•The “Lupron Trigger” to Prevent Severe OHSS: What are the Pro’s and Con’s?
If you are interested in seeking my advice or services, I urge you to contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com You can also apply online at http://www.SherIVF.com .
*The 4th edition of my book,”In Vitro Fertilization, the ART of Making Babies” is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.
Geoff Sher
Hi Dr Sher,
I’m 40 yo and on my third IVF with ICSI cycle. First cycle 2 low grade embryos transferred, negative test. Second cycle 2 blasts transferred, chemical pregnancy. I’m on same protocol as cycle 2 for this cycle, except I’m also taking 200mg of ubiquinol daily. My egg collection is scheduled for Monday. Should I continue taking the ubiquinol after that? Would it do any harm?
Thanks for taking the time to read and answer my questions. It’s much appreciated.
In my opinion, there is no reason to stop taking Ubiquinol.
Geoff Sher
Hi,
I recently transferred a PGS normal embryo and got a BFP. However, I misscarried at 7 weeks. My betas were through the roof. 1st beta 10 post 5 day FET: 798, 13 days post FET: 2,727 and about 20 days post FET: 26, 202. Went in to hear the heartbeat and it was only 81bpm at 6weeks4days. I guess I am looking for answers as to why a PGS normal embryo would fail. I have no known fertility issues other than age, I am 38. This was my 2nd cycle. First cycle was PGS normal but got a BFN, it never implanted. Any suggestions and thank you so much.