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.
Hi Dr. Sher,
I wanted to know the physiology behind why a cycle is cancelled with a functional cyst and elevated estrogen. I can understand that the remaining follicles will be suppressed due to the high estrogen, but if one was to try Clomid or letrozole, I would think the anti-estrogen activity would decrease the serum estradiol, allow for more follicles to grow and catch up, and therefore once the medication is stopped, the estrogen will then rise causing an LH surge. Obviously, there must be something else to this since I have never heard of a cycle with oral meds continuing with a baseline higher estrogen (in my case I had a 15mm cyst with a serum estradiol of 103). Would you mind explaining this to me?
The elevated estradiol caused by the cyst will interfere with the pituitary-ovarian interaction that is needed to cause the antral follicles to develop in an orderly fashion. In addition, any follicular development that would occur would be discordant and not result in even follicular growth. Finally, the cyst might enlarge and even rupture.
Functional ovarian cysts are literally nothing more than ovarian follicles that become enlarged, dilated and distended with fluid. They acquire special relevance when detected in women about to undergo controlled ovarian hyperstimulation(COH) with gonadotropins where they can literally, “throw a wrench in the works,” causing a slight delay, postponement or even a cancellation of the cycle of treatment.
Ovarian cysts may be either “functional cysts” or “cystic tumors”. Functional cysts grow in response to a sustained elevation in blood levels of luteinizing hormone (LH) and/or follicle stimulating hormone (FSH), whether produced by their own pituitary glands or administered to them. By definition, tumors (in contrast with “functional” ovarian cysts) are capable of independent growth, thus cystic ovarian tumors do not respond to gonadotropin stimulation. It is this that distinguishes them from “functional” ovarian cysts. It follows that “functional” ovarian cysts may develop as a result of non-physiological, sustained pituitary gonadotropin stimulation or as a result of prolonged administration of gonadotropins (e.g. Folistim, Gonal F, Puregon, Bravelle, Menopur or Repronex).
Aside from causing menstrual dysfunction such as a delay in the onset of bleeding, irregular cycles, and mild lower abdominal discomfort, unruptured “functional” cysts are usually relatively non-problematic. In some cases, such functional cysts undergo rapid distention (often as a result of a minor degree of bleeding inside the cyst itself) and the woman will experience a sharp or aching pain on one side of her lower abdomen and/or deep seated pain during intercourse. They may even rupture, causing the sudden onset of severe lower abdominal pain, which may simulate an attack of acute appendicitis or even a ruptured ectopic (tubal) pregnancy. While very unpleasant, a ruptured “functional” cyst hardly ever produces a degree of internal bleeding that warrants surgical intervention. The pain, which is made worse on movement, almost always subsides progressively over a period of four to five days.
Whenever an ovarian cyst is detected (usually by ultrasound examination), the first consideration should be to determine whether it is a “functional” cyst or a cystic ovarian tumor. The reason is that tumors are subject to a variety of complications such as twisting (torsion), hemorrhage, infection and even malignant change, all of which will require surgical intervention.
Gonadotropin releasing hormone agonists (GnRHa) such as Lupron, Buserelin, Nafarelin and Synarel, administered daily, starting a few days prior to menstruation, all elicit an initial and rapid, out-pouring (“surge”) of pituitary LH and FSH release. This “surge” lasts for a day or two. Then, as the pituitary reservoir of FSH and LH becomes depleted, the blood FSH and LH levels fall rapidly, reaching near undetectable concentrations within a day or two. At the same time, the declining FSH results in a drop in blood estradiol (E2) concentration, leading to a withdrawal bleed (menstruation).
The progressive exhaustion of pituitary FSH/LH along with the decline in blood E2 is referred to as “down-regulation.” The continued daily administration of GnRHa or its replacement with a GnRH antagonist (e.g. Ganirelix, Cetrotide or Orgalutron) results in blood LH concentrations being sustained at a very low level throughout the ensuing cycle of controlled ovarian hyperstimulation (COH) with gonadotropins, thereby optimizing follicular maturation and promoting E2 induced endometrial proliferation.
Regardless of whether down-regulation with GnRHa is initiated while the woman is taking birth control pills (BCPs) or by starting treatment on day 20-23 (the mid luteal phase) of a natural cycle, the initial FSH/LH “surge” sometimes so accelerates follicular growth that it leads to the development of one or more “functional” ovarian cysts. These cysts release E2 and cause the blood E2 often to remain elevated (>70pg/ml). Depending on the extent of this effect, it sometimes leads to a delay in the onset of menstruation and thus also in the initiation of ovarian stimulation with gonadotropins. While in most cases, further continuation of GnRHa therapy (with sustained suppression of FSH/LH) would ultimately (within a week or two) lead to absorption and disappearance of functional cysts followed by menstruation, delaying COH can have drawbacks. This is because prolonged uninterrupted GnRHa therapy can blunt subsequent ovarian follicular response to gonadotropins. Thus, it is not good policy to continue GnRHa administration for much longer than 14 days prior to initiating COH.
Failure of menstruation to commence within 4-7 days of initiating treatment with GnRHa suggests a potential underlying “functional”ovarian cyst and calls for an ultrasound examination to make the diagnosis. Once diagnosed, there are two therapeutic options, depending upon the number and size of cysts detected 1) wait to see whether the cyst will absorb spontaneously within a few days or, 2) immediately resort to needle aspiration of the cyst(s) under local anesthesia. My preference is to perform needle aspiration, sooner rather than later in such cases. Menstruation will usually follow a successful aspiration within 2-4 days. Upon menstruation, a blood E2 level is measured. Provided it is less than 70pg/ml, COH can be initiated.
Functional ovarian cysts do not present a serious health hazard. Almost without exception, they will spontaneously resolve within 4 to 6 weeks, while “cystic tumors” will not. Accordingly, the persistence of any ovarian cyst for longer than 6 weeks should raise suspicion that you are dealing with a tumor rather than with a “functional” cyst. Since ovarian tumors can be malignant (or might later undergo malignant change), all ovarian cysts that persist for longer than 6 weeks (whether in non-pregnant or pregnant women), should be treated by surgical removal, followed by pathological analysis.
Geoff Sher
My husband and I are moving to embryo donation through our clinic after 4 early losses attributed to poor egg quality due to age (42-43 during pregnancy/losses) after many tests my husband and I had including kereotyping. We have been offered 3 6 day blasts 2 are 4BB and 1 4BC. They were frozen in 2013 using vitrification. I have found conflicting information on the grading. From what I can gather 4BB are good? And the 4BC is fair? What is your take on the odds when transferring 6 day 4BB embryos? I do realize there are many factors including lab procedures etc., but based on grading does this seem to have a decent chance of implantation success?
They could well be chromosomally normal and propagate a pregnancy!
I wish you well!
GEoff Sher
Hello Dr. Sher, what would you suggest for a woman who is trying to conceive and has a TSH of 4, free T of 1.1?
Talk to your primary care physician and you probably should repeat the TSH and if it remains that high, go on to thyroxin (low dosage) sufficient to bring the TSH down to 1-2.5 and keep it there. I also suggest that you have yourself tested for antithyroid antibodies (ATA) and if this is positive you be evaluated for uterine natural killer cell activity hich will be elevated in 50% of women who have ATA.
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.
Feel free to call or email Julie Dahan, my patient concierge. If you are interested in discussing your case with me , Julie can guide you on how to set up an in-person or Skype consultation . 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.
Hello Dr. Sher. I have two children 3.5 and 1.5. Both conceived naturally and very easily. I am 38. I had my second miscarriage on 11/29/16. First one sept 2016. My period returned 1/5/17 after the loss. However my hcg still is at 69 as of today 1/12/17. My husband and I have decided to go the IVF route. Our current doctor says I need to wait till my hcg is down to 0 before she will do an ultrasound for the AFC. And I would have to wait until my cycle starts to do this US.
aMH .4
3 day FSH 13
Estradiol 45
It seems odd first that I would have to wait for my next cycle. My cycles are not regular. Who knows when the next one will be. And that she would put me on 4-6 weeks of BCP beforehand to start IVF. That just seems like a very long period of BCP. What do you think? Also do you think IVF would even work for me with my low AMH? And would banking embryos and doing PGS be a good idea?
I totally agree with your RE.
You clearly have severely diminished ovarian reserve and time is a crucial consideration as is the approach taken to 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”.
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,
Do you have any thoughts for or against using low dose HCG (Pregnyl in my case) for stimming? My estrogen at baseline was 9, which only came up to 50 after three days of Follistim 225 and Lupron 5. AFC was 14, all follicles still below 10mm. We also plan to use full dose Pregnyl for trigger shot. Thank you!
Pregnyl (hCG) mis like LH so it caused ovarian testosterone production. I personally do not use it during stimulation but provided you do not have DOR, low dosage Pregnyl supplementation probably won’t do harm.
Geoff SWher