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 have my embryo transfer Thursday, but just got TSH back that says it’s 2.06. Is that too high to go forward with the transfer.
Looks fine to me!~
Geoff Sher
Hi Dr. Sher,
Last week I spoke with you about the possibilities of transferring PGD tested abnormal embryos. I was considering transferring the high grade monosomy embryos , but have since decided to move on to donor eggs. I am now faced with making the decision whether to PGD test the donor embryos. I have had multiple miscarriages and I am afraid I might transfer aneuploid embryos. I could just skip the testing and transfer 2 untested embryos,but then multiples scares me. What are your thoughts about this dilemma?
Personally, I see no benefit in doing PGS on blastocysts derived from fertilization of DEs with normal sperm. 50% of the blastocysts would be PGS normal and thus by transferring 2 (given a 25% risk of twins) you would have the same chance as with a PGS-tested blastocyst.
Geoff Sher
Hello, I had a cancelled cycle in December due to poor response on antagonist (i only had 6 measurable follicles after 6 days). I am 36 years. My FSH and LH are good (both below 3 and ratio 1:1). My AMH is about 1.6 ng/l. This is my first time with IVF as we are doing it for PGD so we will a lot of eggs to retrieve. I will like to know, given that we are doing PGD, will you advice that I do the Lupron Flare protocol, or the A/ACP protocol (L(A)-6 ). We really need a protocol that will produce the highest number of eggs/embryos. Thank you for your time
I am not a protagonist of the flare protocol. Since you have borderline reserve, I would suggest the A/ACP.
Conventional GnRH Antagonist (GnRHa) Protocols:
GnRH antagonists (e.g. Ganirelix, Cetrotide, and Orgalutron) are currently used with many controlled ovarian stimulation (COS) protocols. The conventional approach is to administer 250mcg antagonist, daily starting from the 6th-8th day after commencing ovarian stimulation with gonadotropins. This traditional approach is in my opinion, best suited to younger patients who have normal ovarian reserve (AMH>2.0ng/ml or 15pmol/L) and are “good responders” to COS, provided that the stimulation cycle is launched with a spontaneous menstrual cycle and is not launched coming off a birth control pill (BCP) or following prolonged premenstrual hormonal suppression (see Use of BCP in IVF”, elsewhere on this blog). However, this approach can in my opinion be decidedly disadvantageous when used in older women (>39y), women with diminished ovarian reserve (DOR) or women with polycystic ovarian syndrome (PCOS) who all tend to have increased LH bioactivity.
Background information: An important role of LH is to promote male androgen hormone (testosterone, androstenedione and DHEA) production by ovarian connective tissue (stroma or theca) that surrounds follicles. While androgens (predominantly testosterone) represent the building blocks from which follicle granulosa cells manufacture estrogen and are thus essential for optimal follicular growth and egg development, too much LH activity can lead to over-production/exposure to ovarian androgens which might compromise follicular/egg development. Accordingly, when it comes to older women and those DOR and PCOS who tend to have excessive LH-induced ovarian testosterone, it is (in my opinion) essential to maintain LH activity at a subliminal level. Thus LH suppression needs to be in place from the very start of COS…not much later as when antagonist suppression is commenced 6-8 days into the COS process. Accordingly, I believe that GnRH antagonist treatment should be commenced from the very initiation of ovarian stimulation…and that is the concept upon which the agonist/antagonist conversion protocol (A/ACP) is based….see below.
Bear in mind that the main reason for using antagonist suppression is to avoid the “Premature LH Surge”. This is a condition where high ovarian LH activity propagates androgen-induced “follicular exhaustion” and egg dysmaturity. The term “premature LH surge” is a misnomer since it does not involve a sudden “surge” or sporadic rise in LH. In actuality it occurs as a steady rise in LH activity (a “staircase effect”) which elicits a progressive increase in ovarian stromal androgens that ultimately exhausts follicle development and compromises egg “competency”. A more accurate term might be “premature luteinization.” Such poorly developed eggs will often respond to the hCG trigger by becoming aneuploid (a numerical chromosomal abnormality
Thus, trying to avoid “premature luteinization” by administering GnRH antagonist 6-8 days into the COS cycle, is like” shutting the gate after the horse has already left the stable”.
The long pituitary down-regulation COS protocol:
Here, administration of a GnRH-agonist (Lupron, Superfact, and Buserelin) several days before COS is initiated, expunges all LH from the pituitary gland, exhausting it of reservoired LH. Thereupon, agonist administration is continued until the hCG “trigger”. In this way, developing follicles and eggs are protected throughout COS, from over-exposure to LH-induced androgens…thereby avoiding “premature luteinization”. In my opinion, this approach is ideally suited to younger women who have normal LH, normal or increased ovarian reserve (e.g. those with PCOS) and those who have DOR. The downside of this approach is that the GnRHa (Lupron/Buserelin) can competitively bind with ovarian follicle stimulating hormone (FSH) receptors and suppress ovarian response to gonadotropins, something that is more likely to occur with older women and those who have DOR. I introduced the Agonist/Antagonist Conversion Protocol (A/ACP) more than 15 years ago to try and counter this effect.
The agonist/antagonist conversion protocol (A/ACP):
With the A/ACP, GnRH antagonist (Ganirelix, Cetrotide, and Orgalutron) is administered by daily injection from the onset of COS. The A/ACP COS-cycle is launched with the woman coming off a monophasic birth control pill that was administered starting in the 1st 5 days of the preceding cycle and continued for at least 10 days. The BCP is then overlapped with an agonist (e.g. Lupron/buserelin) for three days, whereupon the BCP is stopped and the agonist (Lupron/buserelin) is continued until the onset of menstruation. At or around this point, the agonist (Lupron/Buserelin) is supplanted by an antagonist (Cetrotide/Ganirelix/Orgalutron) and concurrently COS is initiated using an FSH-dominant bias (mainly Follistim/Gonal-F/ Puregon + a small dosage of a menotropins such as Menopur). The combined antagonist/gonadotropin therapy is continued until the hCG trigger. For the reasons cited above, I prescribe some form of the A/ACP for my older IVF patients and those with DOR. ]
A/ACP with estrogen priming: The A/ACP can be modified for women with very severe DOR through incorporation of “estrogen priming”. We have reported on the fact that the administration of intramuscular estradiol starting about a week prior to commencement of COS. This often markedly enhances ovarian response (presumably by “estrogen priming” enhancing the sensitivity of ovarian FSH-receptors).
There is one draw-back to the use of the A/ACP. This is the fact that prolonged administration of GnRH antagonist throughout the stimulation phase of the COS cycle compromises the predictive use of serial plasma estradiol measurements as an indication of ovarian response to COH. The blood estradiol levels tend to be much lower in comparison with cases where GnRHa alone is used.The reason for the lower blood concentration of estradiol seen with prolonged exposure to GnRH-antagonist might be due to the result of subtle, antagonist-induced alterations in the configuration of the estradiol molecule, such that currently available commercial test used to measure estradiol levels are rendered less sensitive/specific. Accordingly, when the A/ACP protocols are employed, we rely much more heavily on the measurement of follicle growth by ultrasound than on the estradiol levels. Because of this downside, I refrain from using this approach in “high responders” who may be at risk of developing of severe ovarian hyperstimulation syndrome (OHSS) and in whom the accurate measurement of plasma estradiol plays a very important role in the safe management of their COS cycles.
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.
Please call or email Julie Dahan, my patient concierge. She will guide you on how to set up an in-person or Skype consultation with me. You can reach Julie at on her cell phone or via email at any time:
Julie Dahan
•Email: Julied@sherivf.com
•Phone: 702-533-2691
?800-780-7437
Geoff Sher
I also suggest that you access the 4th edition of my book ,”In Vitro Fertilization, the ART of Making Babies”. It is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.
Geoff Sher
Dear Dr Sher,
We have currently had a brutal end to our 4th IVF round yesterday. I was preparing for transfer when my clinic called and advised all my embryos had arrested and there was nothing to transfer.
I am not sure which way to progress and have a follow up with my FS on Friday. I know my results are not good but was hoping you could shed some light.
My AMH in 2015 was 6.9 I am currently 37 – this is the Australian count
1st IVF Round NOV 15 Me 36 – short protocol
I was on 225 Gonal/ Cetrotide then trigger Ovidrel
We got 2 eggs/ 1 fertilised IVF/ Transferred Day 4
Good looking embryo and then became a Chemical Pregnancy
2nd IVF Round FEB 16 Me 36 – short protocol
I was on 300 Gonal F/ Cetrotide then trigger Ovridrel
We got 3 eggs/ 3 fertilised IVF/ Transferred Day 4 poorer quality embryo a bit behind with fragmentation Dr said about a 25%. All other embryos have arrested
Negative result
Dr performed a hysteroscopy inbetween rounds everything seemed normal
3rd IVF Round JUL16 – Me 36 – short protocol – Signed up for Blastogen Trial
I was on 350 Gonal F/ Cetrotide then trigger Ovridrel
We got 6 eggs/ 3 fertilised IVF/ Transferred Day 5 worse quality embryo was actually asked if I wanted to transfer it. I did because it was still growing but given a 5% chance. All other embryos had arrested
Negative result
4th IVF Round NOV16-JAN17 – Me 37 – long protocol – Signed up for Blastogen Trial
I was on Synarel and had a surge response grew a follicle triggered then had time intercourse. Late period so did a hpt + clinic tested and I had beta at 20 and progesterone at 68. A few days later went for another BETA and all levels had dropped. Went back on Synarel straightaway same issue another follicle. The clinic left it over christmas period went back in and it was 30mm triggered time intercourse then negative result. I changed from Synarel nasal spray to decapetyl injections and was only on them for about 5 days before period came. Day 2 started stimming.
Gonal F 350/ Luveris/ Decapetyl and triggered with Ovridrel.
We got 8 eggs/ 5 fertilised IVF/ Day 3 update 2 on time 3 behind/ Yesterday was transfer I was called an hour before and told all arrested and nothing to transfer.
This is not good results but for my age 37 and partners at 39 this is really bad. Is there anything I can do to improve my embryo quality. What should I ask my Dr to do differently?
I appreciate your time and your presence here.
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”.
Women who (regardless of age) have DOR have a reduced potential for IVF success. Much of this is due to the fact that such women tend to have increased production of LH biological activity which can result in excessive LH-induced ovarian male hormone (predominantly testosterone) production which 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, https://www.drgeoffreysherivf.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
I invite you to arrange to have a Skype or an in-person consultation with me to discuss your case in detail. If you are interested, please contact Julie Dahan, at:
Email: Julied@sherivf.com
OR
Phone: 702-533-2691
800-780-7437
I also suggest that you access the 4th edition of my book ,”In Vitro Fertilization, the ART of Making Babies”. It is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.
Hi Dr Sher, Is Bravelle as good as Gonal-f? I am supposed to start treatment next week but there is a shortage of gonal-f in my area. My RE has suggested I use Bravelle instead (adding Menopur towards the end).
Hi Sherley,
Many would say that it is..but frankly in my opinion, Bravelle is not as effective. It is a urinary derived product whereas Gonal-F, Puregon and Follistim are recombinant DNA prosucts and in my opinion, much purer and more effective.
Geoff Sher