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 am 30 years old doing second round of IVF after 4 years. I am working with a new Dr and I’m not sure he is going the right route with me after reading and hearing so many different opinions and wanted to here your thoughts. I started on Gonal F 300 IU 8 days ago with my scan showing 7 follicles on the one side the largest nearly 7mm and 7 on the other side, largest at 6.5mm.My E2 was 200pmol/L and LH4.7 U/L. I stayed on 300IU for 4 days and on the 5th day had another scan and bloods and my E2 shot up to 2067 pmol/L and LH1.1 and the follicles amount hasn’t changed just the size on each side largest been right 14x16x19 mm and left 12x19x22mm . The Dr stressed about the E2 jump and I coasted that evening. Now I have been put on Gonal F75IU, Menopur 75 and Cetrotide and will be on this for the next 3/4 days till trigger but am going for another E2 today. My concern is will this not affect the size of my “eggs” all these injections and I am so confused because some people are saying that a high E2 is actually only over 4000, and I’m.just simply confused and obviously worried about OHSS. Please give me some of you thoughts and a bit of guidance so I know which way to steer this at my next appointment. Thank you.
In my opinion, given your modest E2 (2o67pmol/L) and only about 15-17 follicles (in total), you would not have been at risk of developing OHSS. In my experience, OHSS does not occur with <25 follicles and a peak E2 of <7500pmol/L (and with that number of follicles your E2 would in my opinion never have got that high). Personally would not have initiated "coasting" in your case. See below:
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.
Geoffrey Sher MD
Hello Dr Sher, At what stage do you recommend to come off progesterone pessaries? And should we wean off or just stop? I’m currently 13 weeks and my doctor told me I could stop. I’m on 400mg at night. Does this sound ok? Also shouldn’t I be having a blood test soon after to check natural progesterone levels? Obviously I’m a bit nervous about stopping. Thank you
I stop my patients cold turkey at 10 weeks!
Geoff Sher
Dear Dr. Sher,
I just returned home from my baseline appointment for our second round of IVF. We completed our first round with another clinic that only starts batched cycles on BCP. I responded poorly to the stims and the doctor had actually recommended cancelling our cycle since my response was so poor compared to my blood work and follicle count. We ended up moving forward anyway, ended up with three 6-day embryos (two of which we transferred) and got a positive pregnancy test. We miscarried at 9 weeks after seeing the fetal heartbeat at 6 1/2 and 7 1/2 weeks.
Each time my follicles have been checked over the past almost year and a half (including in January of this year), my total count has been between 17 and 19 follicles. Today, when we went in, I was devastated to hear that I only had four to five follicles on each side – a reduction by about half! We have been doing everything the same with the exception of adding DHEA about six weeks ago (which I stopped one week ago, per doctor’s instruction to stop one week before stims) and starting this cycle with estrogen priming instead of BCP. I’m on day 14 of 2mg of Estradiol two times per day (will take my last dose tonight and start Follistim and micro-HCG tomorrow night).
Could the DHEA or the estrogen have reduced my follicle count? Is it possible that the sudden, drastic reduction is simply a matter of my age (I am turning 38 this year)?
I would really appreciate your input.
Most sincerely,
Whitney
I really advise against using DHEA in women with diminished ovarian reserve.
The older a woman becomes, the more likely it is that her eggs will be chromosomally/genetically “incompetent” (not have the potential upon being fertilized and transferred, to result in a viable pregnancy). That is why, the likelihood of failure to conceive, miscarrying and of giving birth to a chromosomally defective child (e.g. with Down Syndrome) increases with the woman’s advancing age. In addition, as women age beyond 35Y there is commonly a progressive diminution in the number of eggs left in the ovaries, i.e. diminished ovarian reserve (DOR). So it is that older women as well as those 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 age-related effect on the woman’s “biological clock, certain ovarian stimulation regimes, by promoting excessive LH production (e.g. short agonist/Lupron- “flare” protocols, clomiphene and Letrozole), can 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 older women and those 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 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, http://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
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 newest 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.
Geoffrey Sher MD
Hello Dr Sher,
1) If I wanted to do prolonged coasting and I only ended up with 23 follicles and 50% were at or above 14mm (and my E2 was 5000pg/ml) should I still wait for E2 to drop bellow 2500pg/ml before triggering? I ask because in your article you say “provided there are >25 follicles” so I wasn’t sure if 23 follicles would be a different scenario.
2) what’s your opinion about Dostinex/Cabergoline to prevent OHSS? In you’re opinion does it compromise egg/embryo quality and is there any benefit in taking it?
1). If it were up to me I would allow the E2 to fall below 2500pg/ml before a 10,000U hCG or 500mcg Ovidrel trigger
2) I am not convinced it works, but it wont do harm, in my opinion.This having been said, if you were coasted correctly you probably would not need it anyway!
Geoff Sher
(Apologies if I’ve posted this twice – having ‘technical’ difficulties!)
Dear Dr Sher,
Thank you so much for your blog, and for sharing your time and expertise.
I am 43, turning 44 next month. I have a healthy son, conceived naturally when I was 40. I had two natural pregnancies over 3 months at 42 which ended at 7 and 8 weeks. Full repeated miscarriage test panel done, with no problems indicated.
I had 5 PGD normal embryos collected over 10 egg collections over 1.5 years, but have lost 2 in unsuccessful FETs. My first failed FET last October was with a 6AA hatching blastocyst using an artificial cycle (progesterone injections and pessaries, plus microgynon), and have just this month had another unsuccessful FET with a 5AA blastocyst in a natural cycle with 10mg prednisone and supplemental progesterone pessaries..
Prior to my first FET, my then specialist did an ERA test, which found my uterus receptive for a day 6 transfer (although the FET failed).
My current specialist performed a hysteroscopy and biopsy and found my uterus to be sound, without problems, and did a blood test showing have high serum NK cells (a reading of 19 against a high reference of 12), hence the 10mg prednisone this FET.
I only have 3 precious frozen PGD normal embryos left (a 5AA, 5AB and 5BC(?) blastocysts) collected when I was 43.5, and am anxious to maximise my chances, as I see little hope of collecting any more after turning 44. So, I am seeking your opinion on how I should best proceed witb these precious embryos. Thank you again for your time.