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.
Not sure where to see the answer to my question, which I asked the doctor yesterday.
Please re-post it and I will respond!
Geoff Sher
What are the pros and cons of using birth control pills versus estrogen priming for IVF? What does an estrogen primed protocol look like?
Denise,
Estrogen priming is an approach that I only use in women with VERY severely diminished ovarian reserve. I administer estrogen in the form of estradiol Valerate injections from the start of the period for about 8 days before initiating gonadotropin stimulation. The estrogen is given to enhance follicle granulosa cell response to gonadotropins and so, hopefully improve response.
The BCP is used to lead into a cycle of stimulation. It is not used to i mprove follicle response.
A.Antagonists with and without Estrogen priming:
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 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. ”.
B) The BCP:
One often hears the expressed opinion that the BCP suppresses response to ovarian stimulation. This is not the case, provided that the BCP is overlapped with administration of an agonist (e.g. Lupron, Buserelin, Superfact) for several days leading up to the start of menstruation and the initiation of ovarian stimulation cycle with gonadotropin drugs. If the latter precaution is not taken, and the cycle of stimulation is initiated coming directly off the BCP the response will often be blunted and subsequent egg quality could be adversely affected. The explanation for this is that in natural (unstimulated) as well as in cycles stimulated with fertility drugs, the ability of follicles to properly respond to FSH stimulation is dependent on their having developed FSH-responsive receptors . Pre-antral follicles (PAF) do not have such primed FSH receptors and thus cannot respond properly to FSH stimulation with gonadotropins. The acquisition of FSH receptor responsivity requires that the pre-antral follicles be exposed to FSH, for a number of days (5-7) during which time they attain “FSH-responsivity” and are now known as antral follicles (AF). These AF’s are now able to respond properly to stimulation with administered FSH-gonadotropins. In regular menstrual cycles, the rising FSH output from the pituitary gland insures that PAFs convert tor AF’s. The BCP (as well as prolonged administration of estrogen/progesterone) suppresses FSH. This suppression needs to be countered by artificially causing blood FSH levels to rise in order to cause PAF to AF conversion prior to COS commencing, otherwise pre-antral-to –antral follicle conversion will not take place in an orderly fashion, the duration of ovarian stimulation will be prolonged and both follicle and egg development may be compromised. GnRH agonists (e.g. Lupron, Buserelin, Superfact) , cause an immediate surge in release of FSH by the pituitary gland thus causing conversion from PAF to SAF. This is why, women who take a BCP to launch a cycle of COS need to have an overlap of the BCP with an agonist. By overlapping the BCP with an agonist for a few days prior to menstruation the early recruited follicles are able to complete their developmental drive to the AF stage and as such, be ready to respond appropriately to optimal ovarian stimulation. Using this approach, the timing of the initiation of the IVF treatment cycle can readily and safely be regulated and controlled by varying the length of time that the woman is on the BCP.
Since optimizing follicular response to COS requires that prior to stimulation with gonadotropins, FSH-induced conversion from PAF to AF’s first be completed and the BCP suppresses FSH, it follows when it comes to women launching COS coming off a BCP something needs to be done to cause a rise in FSH for 5-7 days prior to menstruation heralding the cycle of CO S.This is where overlapping the BCP with an agonist (e.g. Lupron/Superfact/Buserelin) comes in. The agonist causes FSH to be released by the pituitary gland and if overlapped with the BCP for several days and this will (within 2-5 days) facilitate PAF to AF conversion…. in time to start COS with the onset of menstruation. Initiating ovarian stimulation in women taking a BCP, without doing this is suboptimal
I believe it to be essential regardless of the protocol of COS protocol being contemplated, for women who launching ovarian stimulation coming off a BCP to overlap with an agonist for several days in advance of initiating ovarian stimulation with the onset of menstruation,
ANNOUNCEMENTS:
1.About my Retirement by mid-2018:
After > 30 years in the field of Assisted Reproduction (AR), the time has finally come for me to plan on retiring from full-time clinical medicine within a year. If you are interested in my medical services prior to my retirement, 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.
2.The 4th edition of my newest 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. Sher – thank you for taking the time to read my comment. I have had 2 failed FET PGS “BB” grade transfers (1 embryo per transfer). I was hoping you could give me your advice on how to proceed to discover what could be wrong.
* I had hysteroscopy’s both times before transfer; the first one had 3 polyps removed — the second one looked great.
* I had 10mm triple stripe at transfer both times.
* I was on steroids & antibiotic leading up to transfers
* I was on PIO shots for first transfer (had a reaction) — second transfer I was on oral and vaginal Progesterone
* I was on Estrogen pills and patches
* I was on Lovenox & Baby Asprin 3 days after transfer
Transfer #1 – HCG – 6 (11d5dt)
Transfer #2 – HCG – 1.4 (11dp5dt)
Infertility Diagnosis – Female – PCOS (age 33) // Male – High Morphology (age 33)
Thank you for your time and advice!
Grateful,
Linda
Dear Dr Sher,
I am planning to undergo IVF soon where BCP or estrace will be used before the cycle starts. However I am MTHFR homozygous C677T. I was told this is the worst kind and that estrogen/BCP should not be taken by people who have this as it may increase the risk of getting blood clots.
a) is it safe to take estrace/ BCP/ ethinyl estradiol when you have this?
b) Should I take aspirin as a precaution? If so how much? ( I undestand Lovenox is a good idea at embryo transfer but I am wondering more about taking the BCP/ estrace before the IVF cycle)
c) Is it ok to fly long flights when on BCP/ estrace when having this condition?
I read controversial things about this on google and also speaking to various doctors. I will greatly appreciate hearing your advice and expertise. Thank you in advance.
Adriana
a) is it safe to take estrace/ BCP/ ethinyl estradiol when you have this?
A: Yes: But I would stop the BA about 5 days prior to projected ER…and then only restart after the ET.
b) Should I take aspirin as a precaution? If so how much? ( I undestand Lovenox is a good idea at embryo transfer but I am wondering more about taking the BCP/ estrace before the IVF cycle)
A:Lovenox would only commence with the biochemical diagnosis of pregnancy…in my opinion.
c) Is it ok to fly long flights when on BCP/ estrace when having this condition?
Yes!
Good luck!
Geoff Sher
Hi Dr. Sher,
I am a 39 year old dealing with secondary infertility. My first child was delivered via C- Section when I was 34. I had no issues conceiving, but since then, I have had 4 miscarriages and have never been able to carry past 9 weeks.
My last miscarriage was 3 weeks ago with twins (Baby B’s heart stopped at 8 weeks, Baby A’s heart stopped at 9 weeks). We did a D&C and Baby A was found to be Normal and Baby B had Trisomy 13 & 15. This was an “AN3 Antagonist” IVF cycle which was converted to an IUI due to low follicle response to Stims (Details below).
We would like to do an IVF cycle with PGS next go round, and are having problems finding the right protocol. We have done 2 stim cycles with different results.
First Stim Cycle: we had an IUI cycle in October 2016 which started with 11 antral follicles, resulted in 8 mature follicles, all close in size and in the optimum range 1.5-2.0cm. (Unfortunately I ovulated early on my own and the IUI was canceled). Details below:
Canceled IUI Cycle – Oct 2016
Gonal-F 150 (CD 4-9)
Menopur 75 (CD 4-9)
HCG 10,000 (CD 11)
Ovulated (CD 12) – Canceled IUI
Starting Antral Follicles: 11
Day before HCG Trigger (CD 10) – 8 Follicles (Left:1.7, 1.5, 1.6, 1.7; Right: 1.9, 1.8, 1.7, 1.5). Estradiol: 2019, Progesterone: 0.65, Endometrial Thickness: 1
Second Stim Cycle: in January 2017 we did an IVF cycle similar to the canceled IUI cycle, same dosage Menopur, higher dosage of Gonal-F, and added an antagonist (Ganirelix). We started with 3 weeks of BC. Of the 14 antral follicles, we ended up with only 7 mature follicles, not close in size, a couple didn’t grow much and several grew super fast and ended up being very large, with a leading follicle.
Converted IVF to IUI Cycle – Jan 2017
3 weeks BC
Gonal-F 225 (CD 1-8)
Menopur 75 (CD 1-8)
Ganirelix 250 (CD 5-8)
HCG 15,000 (CD 9)
IUI (CD 11)
Starting Antral Follicles: 14
Day before HCG Trigger (CD 8) – 7 Follicles (Left: 1.9, 1.7, 1.1; Right: 2.4, 1.9, 1.8, 1.8). Estradiol: 2005, Progesterone: 0.77, Endometrial Thickness: 1
Day after Trigger (CD 10) – 7 Follicles (Left: 1.9, 1.8, 1.4; Right: 2.8, 2.3, 2.1, 2.1). Estradiol: 2495, Progesterone: 4.90, Endometrial Thickness: 0.9
Stats: I am 39 (turn 40 in September), have a high AMH (around 7), low FSH (around 5-6), but only 9-14 antral follicles per cycle.
My questions are:
1. Comparing the two cycles using similar stims, do you think I was over-suppressed by the BCP in the second cycle, resulting in only 7 of the 14 follicles responding, versus the non-BCP cycle where 8 of the 11 follicles responded? The BCP also did not help keep the follicle sizes close together, without leading follicles. It seemed to have an opposite effect on my cycle compared to my first stim cycle without BCP.
Is it better for me to do a natural start IVF without BCP? Or use something other than BCP (estrogen priming, testosterone, progesterone, etc)?
2. What is your ideal follicle size range before trigger? (I’ve read 1.5-2.0). My doctor thinks 2 to 2.5 or bigger is fine. Could these be over-ripe? How many follicles in your ideal range do you think is best to end up with at least 2 good embryos for IVF/PGS success?
3. What protocol would you recommend to get more of the follicles responding to the stims? Should I be doing a “poor responder” protocol based on these cycles? My doctor thinks my response was good and wants to repeat the same thing.
4. Could there be scar tissue from the C-section preventing proper implantation, embryo growth which would cause a normal embryo to miscarry?
5. Any other reasons for miscarrying a normal-tested embryo? If so, what are other tests (killer cells, hysteroscopy, etc) you would do before attempting IVF with PGS?
6. What is the minimum number of eggs you like to see on ultrasound in a cycle for an IVF cycle with PGS testing?
We may only get one chance at IVF and feel that with the right protocol, we could be getting a better response. Thank you in advance for your help and expertise!
AMH:
Jan 2017 – 7.12
Feb 2016 – 7.06
Cycle Day 2-4 FSH:
Ranges between 4.7 – 6.49
Jan 2017 – 6.17 (CD 3)
Nov 2016 – 5.81 (CD 2)
Oct 2016 – 6.49 (CD 4)
Aug 2016 – 5.15 (CD 2)
May 2016 – 5.53 (CD 5)
April 2016 – 5.05 (CD 5)
Mar 2016 – 6.4 (CD 4)
Feb 2016 – 4.7 (CD 4)
Estradiol:
Jan 2017 – 21.06 (CD 3)
Nov 2016 – 26.40 (CD 2)
Oct 2016 – 32.46 (CD 4)
Aug 2016 – 22.40 (CD 2)
May 2016 – 35.30 (CD 5)
April 2016 – 27.99 (CD 5)
Mar 2016 – 22.4 (CD 4)
Feb 2016 – 17.9 (CD 4)
HSG – normal
SIS – normal
Genetic Tests on me and my huband: Normal
Blood Disorders:
Thalassemia Beta Minor
Occasional anemia
PAI 4G / 5G
+MTHFR
Meds:
Baby Aspirin
Folgard / Folbic tablet
Ferrex 28
Methyl Folate 1000mcg
Synthroid 50mcg
Prenatal
DHEA 25
Myo-inositol 2000mg
Ubiquinol 400mg twice daily
Melatonin 3mg
Frankly, This is too complex to adress comprehensively here. I think we should talk.
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.
•Optimizing Response to Ovarian Stimulation in Women with Compromised Ovarian Response to Ovarian Stimulation: A Personal Approach.
•Egg Maturation in IVF: How Egg “Immaturity”, “Post-maturity” and “Dysmaturity” Influence IVF Outcome:
•Commonly Asked Question in IVF: “Why Did so Few of my Eggs Fertilize and, so Many Fail to Reach Blastocyst?”
•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?
•Secondary Infertility: Addressing the Root Causes
•Recurrent Pregnancy Loss (RPL): Why do I keep losing my Pregnancies
•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
•Cervical Ureaplasma Urealyticum Infection: How can it Affect IUI/IVF Outcome?
•Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas
•Should IVF Treatment Cycles be provided uninterrupted or be Conducted in 7-12 Pre-scheduled “Batches” per Year
•A personalized, stepwise approach to IVF
•My Retirement in the Year Ahead: A letter of Thanks From me to You!
ANNOUNCEMENTS:
1.About my Retirement by mid-2018:
After > 30 years in the field of Assisted Reproduction (AR), the time has finally come for me to plan on retiring from full-time clinical medicine within a year. If you are interested in my medical services prior to my retirement, 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.
2.The 4th edition of my newest 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
5320 S. Rainbow Blvd. Suite 302. | Las Vegas, NV 89118 |office: 702-478-1024
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