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.
Dr.Sher,
Which two embroyos would you transfer as these were the results
1-bs 45,xx,-6,+7,-14 ab
2-bs 48,xx,+3,+21 ab
3-bs 45,xx,-11(mos)
4-bs 46,xx,dup(6)(p11,2p25)
5-bs complex ab (mos)
Probably # 3 (preferentially) and perhaps also #4.
Geoff Sher
Hi Dr Sher
I am 37 years old and have a 5 year old daughter and 3 year old son. In the past year I have had 3 miscarriages (currently going through my 3rd). The first occurred naturally and started bleeding at 6 weeks, the second was a missed miscarriage at 10 weeks (baby showed growth to 7. 5 weeks) and this one was at 8 weeks (baby seems to have stopped growing at 6 weeks). I am so devastated and confused. I want to have extensive tests done at this point. I conceived all of the first 4 pregnancies very easily but this last one took 6 months to conceive (my second miscarriage took about 6 weeks to be complete and may have affected my system?).
I am desperate for any advice you could offer me.
Thank you so much,
Eleanor
Hello Dr. I have hidradenitis supporativa and i am in my 2 week wait. I am having a flare up which is causing low grade fever and chills. I know this is due to an infection stirring up in my body. I was prescribed minocycline to take daily for this condition over a year ago and it has worked, however Ive stopped taking it recently while trying to conceive. Thus, causing the flare up i am having now. My question is can this infection interfere with implantation? Would infection cause my uterus to reject my embryo? Would my immune system attack my embryo because it is already up in arms due to the infection in my body? And should i start back taking the minocycline to get through this flare up or would this antibiotic interfere with implantation? It seems either option can end badly. Thank you!
I don believe that this inflamation alone (if treated) will adversely affect implantation!
Good luck!
Geoff Sher
Hi, Dr. Sher!
I’m wondering your thoughts on the Lupron trigger (80 units) along with 1,000 units of HCG and its affect on the quality of eggs. I had 17 eggs retrieved; 11 mature; 7 fertilized. In my previous cycles I had 9 retrieved-6 mature-5 fertilize-1 blastocyst and then 13 retrieved-11 mature-9 fertilize-5 blastocysts. These previous cycles were triggered with 10,000 units of HcG. I know that nothing can go back and change it now, but I’m just so curious if you think the drop off in mature eggs to fertilization was due to the Lupron trigger, or if this is statistically pretty standard. It feels like I lost more eggs than usual, and now I’m nervous that the 7 embryos I have now (on day 3: 1@ 6 cells, 1@7 cells, 2@8cells, 3 @ 9cells) won’t be strong enough to make it through for PGT testing.
Thank you so much for any thoughts.
I’m sorry…I should have mentioned that the reason we used the Lupron trigger was due to my estradiol levels (3837 on day 10 of antagonist) and risk of OHSS. I also began taking cabergoline at that time.
The problem with the Lupron trigger is there is no way to gauge the magnitude of the induced pituitary flare of LH. Adding 1,000U hCG is in my opinion better than nothing but falls far short of the mark.
Ideal egg development sets the scene for optimal egg maturation that occurs 36-42h prior to ovulation or egg retrieval. Without prior optimal egg development (ovogenesis), egg maturation will be dysfunctional and most eggs will be rendered “incompetent” and unable upon fertilization to propagate viable embryos. In IVF, optimal ovogenesis requires the selection and implementation of an individualized approach to controlled ovaria stimulation (COS). Thereupon, at the ideal time, maturational division of the egg’s chromosomes (i.e. meiosis) is “triggered” through the administration of hCG or an agonist such as Lupron, which induces an LH surge. The, dosage and timing of the “trigger shot” profoundly affects the efficiency of meiosis, the potential to yield “competent (euploid) mature (M2) eggs, and as such represents a rate limiting step in the IVF process .
“Triggering meiosis with Urine-derived (hCGu-Pregnyl/Profasi/Novarel) versus recombinant hCG-(hCGr-Ovidrel): Until quite recently, the standard method used to “trigger” egg maturation was through the administration of 10,000 units of hCGu. Subsequently,, a DNA recombinant form of hCGr (Ovidrel)was introduced and marketed in 250 mcg doses. But clinical experience strongly suggests that 250 mcg of Ovidrel is most likely not equivalent in biological potency to 10,000 units of hCG. It probably only has 50%-70%of the potency of a 10,000U dose of hCGu and as such might not be sufficient to fully promote meiosis, especially in cases where the woman has numerous follicles. For this reason, I firmly believe that when hCGr is selected as the “trigger shot” the dosage should best be doubled to 500 mcg at which dosage it will probably have an equivalent effect on promoting meiosis as would 10,000 units of hCGu. Failure to “trigger” with 10,000U hCGu or 500mcg hCGr, will in my opinion increase the likelihood of disorderly meiosis, “incompetent (aneuploid) eggs” and the risk of follicles not yielding eggs at egg retrieval (“empty follicles”). Having said this, it is my personal opinion that it is unnecessary to supplant hCGu with hCGr since the latter is considerably more expensive and is probably no more biopotent than the latter.
Some clinicians, when faced with a risk of OHSS developing will deliberately elect to reduce the dosage of hCG administered as a trigger in the hope that by doing so the risk of critical OHSS developing will be lowered. It is my opinion, that such an approach is not optimal because a low dose of hCG (e.g., 5000 units, hCGu or 250mcg hCGr) is likely inadequate to optimize the efficiency of meiosis particularly when it comes to cases such as this where there are numerous follicles. It has been suggested that the preferential use of an “agonist (Lupron) trigger” in women at risk of developing severe ovarian hyperstimulation syndrome could potentially reduce the risk of the condition becoming critical and thereby placing the woman at risk of developing life-endangering complications. It is with this in mind that many RE’s prefer to trigger meiosis by way of an “agonist (Lupron) trigger rather than through the use of hCG. The agonist promptly causes the woman’s pituitary gland to expunge a large amount of LH over a short period of time and it is this LH “surge” that triggers meiosis. The problem with using this approach, in my opinion, is that it is hard to predict how much LH will be released in by the pituitary gland. For this reason, I personally prefer to use hCGu for the trigger, even in cases of ovarian hyperstimulation hyperstimulated, with one important proviso…that being that is she underwent “prolonged coasting” in order to reduce the risk of critical OHSS, prior to the 10,000 unit hCGu “ trigger”.
The timing of the “trigger shot “to initiate meiosis: This should coincide with the majority of ovarian follicles being >15 mm in mean diameter with several follicles having reached 18-22 mm. Follicles of larger than 22 mm will usually harbor overdeveloped eggs which in turn will usually fail to produce good quality eggs. Conversely, follicles less than 15 mm will usually harbor underdeveloped eggs that are more likely to be aneuploid and incompetent following the “trigger”.
Geoff Sher
Hi Doctor. Thanks for creating this blog and providing great support to all of us. I am 39, mother of a 7 year. After failed to conceive our 2nd baby, we approached IVF. My first IVF resulted in 7 follicles, 5 eggs, 3 embryos, but all of them failed in genetics testing. I had my 2nd round of retrieval yesterday. I was also given Omnitrope to provide additional egg quality. So we were hoping better quality eggs. This cycle I had 8 follicles in good ranges but only 3 eggs were retrieved. We are very heartbroken , still waiting to hear back from doctor today and but feeling very negative about everything. Please advice.
The importance of the IVF stimulation protocol on egg/embryo quality cannot be overstated. This factor seems often to be overlooked or discounted by t IVF practitioners who use a “one-size-fits-all” approach to ovarian stimulation. My experience is that the use of individualized/customized COS protocols can greatly improve IVF outcome. While no one can influence underlying genetics or turn back the clock on a woman’s age, any competent IVF specialist should be able to tailor the protocol for COS to meet the individual needs of the patient.
Gonadotropins (LH and FSH), whether produced by the pituitary gland or administered by way of fertility drugs, have different “targeted” sites of action in the ovary. FSH targets cells that line the inner wall of the follicle (granulosa cells) and also form the cumulus cells that bind the egg to the inner surface of the follicle. Granulosa cells are responsible for estrogen production.
LH, on the other hand, targets the ovarian connective tissue (stroma/theca) that surrounds ovarian follicles resulting in the production of male hormones such as testosterone (predominantly), androstenedione and DHEA. These androgens are then transported to the granulosa cells of the adjacent follicles in a “bucket brigade fashion”. There FSH converts testosterone to estradiol, causing granulosa cells to multiply (proliferate) and produce estradiol, follicles to grows and eggs to develop (ovogenesis) It follows that ovarian androgens (mainly testosterone) is absolutely indispensable to follicle/ egg growth and development.
However, the emphasis is on a “small” amount of testosterone. Over-exposure of the follicle to testosterone can compromise egg development and lead to an increased likelihood of chromosomal irregularities (aneuploid) following LH/hCG-induced egg maturational division (meiosis) and compromise embryo “competency/quality.
Ovarian androgens can also reach the uterine lining where they sometimes will compromise estrogen receptor -induced endometrial growth and development.
Many older women and those who have diminished ovarian reserve (DOR) have increased LH activity is increased. Such women either over-produce LH and/or the LH produced is far more biologically active. Chronically increased LH activity leads to overgrowth of ovarian connective tissue (stroma/theca). This condition, which is often referred to as Stromal Hyperplasia or hyperthecosis can result in excessive ovarian androgen/testosterone production and poorer egg-embryo quality/competency, Similarly, women with polycystic ovarian syndrome (PCOS), also characteristically have Stromal hyperplasia/hyperthecosis due to chronically increased LH activity. hus they too often manifest with increased ovarian androgen production. It is therefore not surprising that “poor egg/embryo quality” is often also a feature of PCOS.
In my opinion, the over-administration of LH-containing menotropins such as Menopur, [which is comprised of roughly equal amount of FSH and hCG which acts similar to LH)], to older women, women with DOR and those who have PCOS can also lead to reduced egg/embryo competency. Similarly, drugs such as clomiphene or Letrozole that cause the pituitary gland to release excessive amounts of LH, are also potentially harmful to egg development and in my opinion, are best omitted from IVF COS protocols. This is especially the case when it comes to older women and those with DOR, who in my opinion should preferably be stimulated using FSH-dominant products such as Follistim, Puregon, Fostimon and Gonal-F.
Gonadotropin releasing hormone agonists (GnRHa): GnRHa such as Lupron, Buserelin, Superfact, Gonopeptyl etc. are often used to launch ovarian stimulation cycles. They act by causing an initial outpouring followed by a depletion of pituitary gonadotropins. This results in LH levels falling to low concentrations, within 4-7 days, thereby establishing a relatively “LH-free environment”. When GnRHa are administered for about 7 days prior to initiating gonadotropin stimulation (“long” pituitary down-regulation”), the LH depletion that will exist when COS is initiated, will usually be protective of subsequent egg development. In contrast, when the GnRHa administration commences along with the initiation of gonadotropin therapy, there will be a resultant immediate surge in the release of pituitary LH with the potential to increase ovarian testosterone to egg-compromising levels , from the outset of COS. This, in my opinion could be particularly harmful when undertaken in older women and those who have DOR.
GnRH-antagonists such as Ganirelix, Cetrotide and Orgalutron, on the other hand, act very rapidly (within hours) to block pituitary LH release. The purpose in using GnRH antagonists is to prevent the release of LH during COS. In contrast, the LH-lowering effect of GnRH agonists develops over a number of days.
GnRH antagonists are traditionally given, starting after 5th -7th day of gonadotropin stimulation. However, when this is done in older women and those (regardless of age) who have DOR, LH-suppression might be reached too late to prevent the deleterious effect of excessive ovarian androgen production on egg development in the early stage of ovarian stimulation. This is why, it is my preference to administer GnRH-antagonists, starting at the initiation of gonadotropin administration.
•My preferred Protocols for Controlled Ovarian Stimulation (COS):
1.“Long” GnRHa (Lupron/Buserelin/Superfact/Gonopeptyl) Pituitary Down-regulation Protocol: The most commonly prescribed protocol for GnRHa/gonadotropin administration is the so-called “long protocol”. Here, GnRHa is given, starting a week or so prior to menstruation. This results in an initial rise in FSH and LH , which is rapidly followed by a precipitous fall to near zero. It is followed by a withdrawal bleed (menstruation), whereupon gonadotropin treatment should commence, while daily Lupron injections continue, to ensure a “low LH” environment. A modification to the “long protocol” which I prefer prescribing for older women and in cases of DOR, is the Agonist/Antagonist Conversion Protocol (A/ACP) where, upon the onset of a GnRHa-induced bleed, the agonist is supplanted by an antagonist (Ganirelix/Cetrotide/Orgalutron) and this is continued until the hCG trigger. In many such cases I often supplement with human growth hormone (HGH) in such cases in an attempt to enhance egg mitochondrial activity and so enhance egg development. This approach is often augmented with preimplantation genetic screening (PGS) of all embryos that reach the expanded blastocyst stage of development by day 5-6 post-fertilization. I also commonly recommend blastocyst banking to many such patients.
2.Short (“Flare”) GnRHa Protocol: Another GnRHa usage for COS is the so called “(micro) flare protocol”. This involves initiating gonadotropin therapy commensurate with initiation of gonadotropin administration. The supposed objective is to deliberately allow Lupron to elicit an initial surge (“flare”) in pituitary FSH release in order to augment FSH administration by increased FSH production. Unfortunately, this “spring board effect” constitutes “a double-edged sword”. While it indeed increases the release of FSH, it at the same time causes a surge in LH release. The latter can evoke excessive ovarian stromal/thecal androgen production which could potentially compromise egg quality, especially when it comes to older women and women with DOR. I am of the opinion that by evoking an exaggerated ovarian androgen response, such “(micro) flare protocols” can harm egg/embryo quality and reduce IVF success rates, especially when it comes to COS in older women, and in women with diminished ovarian reserve. Accordingly, I do not prescribe such protocols to my IVF patients.
3.Estrogen Priming – This is the approach I sometimes prescribe for my patients who have virtually depleted ovarian reserve , as determined by very low blood anti-Mullerian hormone AMH levels (<0.2ng/ml or 2 pmol/L) and are thus likely to be very “poor responders”. It involves a modified A/ACP. We start with the birth control pill (BCP) for 10 days or longer, overlap it for 3 days with a GnRHa whereupon the BCP is stopped. Th GnRHa is continued until the onset of menstruation (usually 5-7 days later) to cause pituitary LH, down-regulation. Upon menstruation and confirmation by ultrasound and measurement of blood estradiol levels that adequate ovarian suppression has been achieved, the dosage of GnRHa is stopped and is immediately supplanted by daily administration of GnRH antagonist. The patient is given twice-weekly injections of estradiol valerate (Delestrogen) for a period of 8 days whereupon COS is initiated using a relatively high dosage FSH-(Follistim, Fostimon, Puregon or Gonal F), which is continued along with daily administration of GnRH antagonist until the “hCG “trigger.” This approach is often augmented with HGH administration throughout the process of COS and by preimplantation genetic screening (PGS) of all embryos that reach the expanded blastocyst stage of development by day 5-6 post-fertilization. I also commonly recommend blastocyst banking to many such patients.
Estrogen Priming has succeeded in significantly enhancing ovarian response to gonadotropins in many of otherwise very poor responders.
•Triggering egg Maturation prior to egg Retrieval: hCG versus GnRHa
With ovulation induction using fertility drugs, the administration of 10,000U hCGu (Pregnyl; Profasi, Novarel) or 500mcg hCGr (Ovidrel/Ovitrel) “trigger”) sends the eggs (into maturational division (meiosis). This process is designed to halve the chromosome number, resulting in mature eggs (M2) that will have 23 chromosomes rather that the 46 chromosomes they had prior to the “trigger”. Such a chromosomally numerically normal (euploid), mature (MII) eggs, upon being fertilized will (hopefully) propagate euploid embryos that have 46 chromosomes and will be “: competent” to propagate viable pregnancies. In my opinion, the key is to always “trigger” with no less than 10,000U of hCGu or 500mcg hCGr (Ovidrel/Ovitrel). Any lesser dosage often will reduce the efficiency of meiosis and increase the risk of the eggs being aneuploid. I personally do not use the agonist (Lupron) “trigger”, unless it is combined with (low dosage) hCG. The supposed reason for using the agonist, (Lupron) “trigger” is that by inducing meiosis through compelling a surge in the release of LH by the pituitary gland, the risk it reduces the risk of OHSS. This may be true, but it comes at the expense of egg quality because the extent of the induced LH surge varies and if too little LH is released, meiosis can be compromised, thereby increasing the likelihood of aneuploid and immature (MI) eggs. And there are other better approaches to preventing OHSS (e.g. “prolonged coasting”), in my opinion.
•Use of the Birth Control Pill (BCP) to launch IVF-COS.
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 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 a GnRHa 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 strongly recommend that you visit www.SherIVF.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
•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.
•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)
•Ovarian Stimulation in Women Who have Diminished Ovarian Reserve (DOR): Introducing the Agonist/Antagonist Conversion protocol
•Controlled Ovarian Stimulation (COS) in Older women and Women who have Diminished Ovarian Reserve (DOR): A Rational Basis for Selecting a Stimulation Protocol
•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?
•Staggered IVF
•Staggered IVF with PGS- Selection of “Competent” Embryos Greatly Enhances the Utility & Efficiency of 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.
•IVF: Selecting the Best Quality Embryos to Transfer
•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
•IVF outcome: How Does Advancing Age and Diminished Ovarian Reserve (DOR) Affect Egg/Embryo “Competency” and How Should the Problem be addressed.
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ADDENDUM: PLEASE READ!!
INTRODUCING SHER FERTILITY SOLUTIONS (SFS)
Hitherto I have personally performed IVF- treatment and related procedures on patients who, elected to travel to Las Vegas to be managed by me. However, with the launching of Sher-Fertility Solutions (SFS) in April 2019, I have taken on a new and expanded role. Now, rather than having hands-on involvement I confine my services to providing hour-long online Skype consultations to an ever-growing number of patients (emanating from >40 countries), with complex Reproductive problems, who seek access to my input, advice and guidance. All Skype consultations are followed by a detailed written report that meticulously describes and explains my recommendations for treatment. All patients are encouraged to share this report with their personal treating doctor(s), with whom [subject to consent and a request from their doctor] I will, gladly discuss their case with the “treating Physician”.
Through SFS I am now able to conveniently provide those who because of geography, convenience and cost, prefer to be treated at home or elsewhere by their chosen Infertility Physician.
“I wish to emphasize to all patients with whom I consult, that in the final analyses, when it comes to management, strategy, protocol and implementation of treatment, my advice and recommendations are always superseded by that of the hands-on treating Physician”.
Anyone wishing to schedule a Skype consultation with me, can do so by: Calling my concierge (Patti Converse) at 1-800-780-7437 (in the U.S.A or Canada) or 702-533-2691, for an appointment. Patients can also enroll online on my website, http://www.SherIVF.com, or email Patti at concierge@SherIVF.com .
I was very recently greatly honored in receiving an award by the prestigious; International Association of Top Professionals (IAOTP). For more information, go to the press release on my website, http://www.sherIVF.com .
PLEASE HELP SPREAD THE WORD ABOUT SFS!
Geoff Sher