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.
Dear Dr. Sher,
I have written to you before (early this year) and benefited greatly from your advice and insights. Sadly I have to turn to your help again. I am a heatlhy (just turned) 44 year old with AMH of 2,00 ng/ml and a 4cm endometrioma on my right ovary (as well as a couple of non-cavity-deforming 2-3 cm fibroids). My hormones were in balance as far back as the April (all within normal ranges and FSH and LH around 7, AMH also measured then). My healthy ovary had AFC of about 10 back in April. I say back in April because since then I have been put on OCP first as prep for an IVF cycle, then as treatment for endometriosis. With breaks I have used about 5 boxes of Mycroginone since April, with at a bit over two months continuously ending in September. During that time I could follow my left ovary dwindle in real time from 10 to 0 AFC and of course the right one as well (though I do not count on it much even though it always has a 1-4 AFC on its own next to the endometrioma). When I stopped the pill in hope to start the short antagonist protocol, my FSH blew up top 31 (CD 2) and immediately in the cycle a polyp and a 4cm follicular cyst appeared (for the first time that I know) on the right ovary next to endometrioma. After bleeding I measured FSH again it fell to 4 on day 2, a 5 cm polyp was confirmed and I had a polypectomy several days later and waited for the cyst to reabsorb. On day 19 of that cycle I had a scan with 7 antrals on the left and 4 on the right and the cyst was gone. I was put on diphereline 0,1 starting the next day (CD 20) in order to begin the long protocol . On day 33 of that cycle (and normally my cycles are 27-28, at least that’s what they used to be before this OCP business) I bled, next day I had a scan and there was a 19mm cyst detected on the left healthy ovary. (I should mention perhaps that I had a separate scan mere 3 days after diphereline and there was already a 14 mm follicle detected on that ovary even though I ovulated several days before (also detected on the scan)). The hormones were measured and they were : E2 = 52 pg/ml and LH=4. The doctor decided to extend diphereline for another couple days and wait so he could see whether the cyst was growing and not. When I came 4 days later the cyst wasn’t there, but there were two lead follicles 11mm and 9mm on the left ovary and 3 smaller ones, and endometrium was about 3 mm. E2 was 65 pg.ml and LH was 2,8. I was advised to continue diphereline and even double it the next day and get back in 3 days. When I did the scan in 3 days (which was two days ago and is day 21 of diphereline already), I had two lead follicles -13 and 14 mm, endometrium was trilaminar (5,1 mm) and E2 was 112 pg/ml. Do you think there is any salvageing this cycle? Why do you think this is happening? What are my options now? Can I witch to IUI? Continue with suppression? I read somewhere that if this “escape” happens, then one can do a PIO shot and wait for withdrawal bleeding and start again (but do I continue the diphereline throughout?). I am going to see the doc today and will probably have to make a decision immediatly becasue follicles have probably grown to 16-17 mm by now. You know, I am so dumbfounded because I would think after such long use of OCP I would maybe be oversuppressed with starting a cycle so early. I stopped the pill on Sep 18. I don’t know if my body is totally crazy responding to diphereline so it is not sufficient to shut my brain or is this batch of diphereline they’ve been using deficient or has just my doc missed the beginning when E2 was 52 pg/ml even though there was a 19 mm cyst? I already had one cycle in February which I cancelled thanks to your insights, and then also I had 3 huge follicles of 10,5 mm on baseline ultrasound the day after bleeding which happened about 10 days after starting diphereline. Except that time around the doctor (another one) just went with it (E2 was about 110 pg/ml also) and of course the follies were all over the place regarding the sizes and the stimulation was over in 4 days. It seems to me like I can’t even make it to the stimulation phase, everything happens only with diphereline 🙁 Maybe a new kind of protocol? Honestly I have no idea what’s happening I am desperate as my time is running out. Please advise (your advice regarding my age and endometrioma notwithstanding – they simply don’t do sclerotherapy here and we have – as you can see – very bleak options here regarding medical care. I don’t dare do laparoscopy nad egg donation is not an option yet). Thank you ever so much, eternally greatful. Yours, Dana
Hi Dana,
I know you wont want to hear what I have to say, but at 44y, given your response in the past and the endometrioma, I believe that you are really wasting your time continuing to try with own eggs. You need an egg donor.
G-d bless!
Geoff Sher
Hi Dr Sher, you talk about LH being elevated in PCOS women and how clomid/Femara are not ideal for women with increased LH levels. Why are these women prescribed clomid/Femara when they increase the bioavailability of LH??
Many doctors are unaware of the fact that Clomiphene and Letrozole, markedly increase LH and also becauase of the lower cost of performing ovulation with such oral agents as compared to gonadotropin injections, commonly try such an approach first.
Geoff Sher
Hello Dr Sher
I am hoping you can provide some answers and advice on the likely cause of empty follicles on egg retrieval. I am 43 going on 44 and recently had my first IVF treatment with a short antagonist cycle starting with the birth control pill for 52 days and five days after stopping starting gonal f (Follitropin alpha) and day 6 on gonal f starting ganirelix befor triggering with Ovitrelle (HCG) 250mcg after 12 days of stimulation. I hade six follicles on egg retrieval but only two eggs were retrieved both of which fertilized but arrested on day 4.
My RE is now recommending that I repeat the exact same cycle but without BCP, is this a good plan given the previous poor response?
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.
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 diminished ovarian reserve (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
•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
Dr Sher, what is your live birth rate for women aged 40-41 using A/ACP (not A/ACEP)? And do you have a refund program?
The success rate without PGS is probably around 20% and with PGS at least double that! we have a variety of plans…some (I believe, but am not certain) do include a refund. Please call 7020892-9696 and ask the administrative people.
Geoff Sher
Hi Dr Sher, I know you like to use BCP with an agonist overlap, but what is your personal opinion with the mid-luteal Lupron cycle where you inject lupron on day 21 of your cycle and then start stimulation on day 1 or 2 of menstrual cycle? What, in your view, are the disadvantages of this cycle, which does not use BCP and does not reduce the dose of lupron? Do you use this at all?
I think it is another good way to go!
Geoff Sher