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.
I had my first beta HCG today and am 8 days past five day frozen transfer. The level was 46. Is that a good first number?
Yes! It is promising. However, it needs to double in the next 48h.
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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it comes to management, strategy, protocol and implementation of treatment, my advice and recommendations are always superseded by that of the hands-on treating Physician”.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
I have been told that I am having twins and I’m wondering about the selective reduction procedure…could someone give me more info or call me please!!!!
The introduction of ovulation induction drugs such as clomiphene citrate and urinary-derived gonadotropins (menotropins) in the 60’s, followed about 15 years later by in vitro fertilization (IVF), markedly improved the success of infertility treatment, but at the same time it heralded a virtual explosion in the incidence of multiple gestations. In spite of this, the likelihood in any given case of achieving a viable pregnancy by these methods still remains somewhat unpredictable.
The high cost of IVF treatment in the United States (>$12,000 per cycle) coupled with a relatively low birth rate per embryo transferred to the uterus has resulted in an unfortunate tendency for couples undergoing IVF as well as doctors performing IVF to transfer multiple embryos to the uterus in hopes of maximizing success potential. The downside to such practice, of course, is the risk multiple gestations , especially “high order multiples” (triplets or greater) with their serious incumbent medical risks to both the mother and babies as well as the substantial toll it takes on and on the healthcare system. The short and long-term health risks that the babies face is also a tremendous financial burden to the family and to society, as many of these babies face the prospect of “cradle to grave” medical care due to prematurity-related medical conditions. The cost of providing such care now exceeds two billion dollars per year in the United States alone.
It has been reported that in about 40% of high order multiple pregnancies, one or more of the babies will either not survive the neonatal period or will suffer chronic from physical and/or neurologic complications associated with premature birth. The magnitude of the problem is further evident from statistics’ that show that from 1980-2006 the number of annual live babies born from twin gestations rose > 50%, while the incidence of high-order multiple gestations (triplets or greater) increased by > 400%.
It is the prospect of such disaster that often prompts prospective parents to consider selective fetal reduction in the case of a high-order gestation (SFR). Though a heart-rending decision, SFR is a relatively safe procedure whereby it is possible to reduce the number of concepti in the uterus without harming the remaining one(s). It involves the injection of a lethal chemical under guidance by ultrasound, directly into the heart chamber(s) of one or more developing concepti around the end of the first trimester of pregnancy. This results in the conceptus immediately succumbing whereupon it is slowly absorbed over a number of weeks, without doing harm to the surviving concepti. Provided that it is not done to reduce “monozygotic” (identical) multiples that share the same blood supply, and that the procedure is conducted by an expert, selective fetal reduction rarely (i.e. in less than 5% of cases) will result in loss of the entire pregnancy. The procedure is performed in the early second trimester (after the 12th week).
The only sure way to avoid the risk of high order multiple pregnancies is to insure that no more than one embryo reaches the uterus. With IVF this can be achieved by limiting the number of embryos transferred. However, when it comes to methods of ovulation induction that do not involve IVF (e.g. the use of fertility drugs alone or in combination with intrauterine insemination), it is not possible to prevent this problem from occurring.
It is my intent to rapidly move to single embryo (blastocyst) transfers (SET). Blastocysts are much more viable than day 2 or day 3 embryos. Besides, embryos that do not reach the blastocyst stage in culture are almost always “incompetent” (chromosomally abnormal) and unworthy of being transferred, anyway. Thus I believe that it would be prudent, to transfer the first blastocyst fresh and then vitrify all left over embryos. Thereafter, if this does not result in a live birth, the remaining frozen blastocysts could be transferred one at a time in ensuing cycles until a pregnancy results or all are used up. Most important is the fact that such an approach would yield the same overall baby rate per egg retrieval conducted as would the transfer of all available multiple births.
Since embryo quality declines with the age of the egg provider age, a SET policy might not be suited to women over 39 years of age. In such cases a double embryo (blastocyst) transfer (DET) policy conducted along the same lines, might be more appropriate.
Notwithstanding the above, the occurrence of high order multiple pregnancies are and will for some time remain a harsh reality. And when that happens, I would respectfully submit that given the gravity of the risks associated with high order multiple pregnancies, SFR, rather than being decried from the bully pulpit as being unethical, might better be described as a moral decision whose purpose it is to optimize the quality of life after birth. Furthermore, given the heart- rendering nature of such a decision, it should perhaps even be regarded as a brave and laudable attempt to optimize the quality of life after birth.
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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!
Dr Sher,
Have you ever come across centromere-antibodies and scleroderma as a reason for early embryo arrest and multinucleation after IVF and ICSI? Could immune treatment before ovulation address this?
I know of no relationship.
Geoff Sher
Hello dr. Sher,
1 month ago my wife had a laparoscopy and was diagnosed with endometriosis early phase, small fibrom (that was removed) and chlamydia (which was spread to the liver). For 14 days we both have taken doxycycline 2 x 100 mg daily. For her impryl and for me proxeed. The doctor suggested to try again naturally this month. I have read your blogs and articles about IID, do you suggest to try on their own? Do you think chlamydia is a reason for our recurrent chemical pregnancies (7 in total)? Should you recommend sildenafil and prednisolone? she has MTHFR mutation homozigote and anti-phospholipid antibodies syndrome. We are both 32 years old and very hopeless.
Thank you if you respond to my post
Chlamydia inflammation does not cause chemical pregnancies.
When women with infertility due to endometriosis seek treatment, they are all too often advised to first try ovarian stimulation (ovulation Induction) with intrauterine insemination (IUI) ………as if to say that this would be just as likely to result in a baby as would in vitro fertilization (IVF). Nothing could be further from reality It is time to set the record straight. And hence this communication!
Bear in mind that the cost of treatment comprises both financial and emotional components and that it is the cost of having a baby rather than cost of a procedure. Then consider the fact that regardless of her age or the severity of the condition, women with infertility due to endometriosis are several fold more likely to have a baby per treatment cycle of IVF than with IUI. It follows that there is a distinct advantage in doing IVF first, rather than as a last resort.
So then, why is it that ovulation induction with or without IUI is routinely offered proposed preferentially to women with mild to moderately severe endometriosis? Could it in part be due to the fact that most practicing doctors do not provide IVF services but are indeed remunerated for ovarian stimulation and IUI services and are thus economically incentivized to offer IUI as a first line approach? Or is because of the often erroneous belief that the use of fertility drugs will in all cases induce the release (ovulation) of multiple eggs at a time and thereby increase the chance of a pregnancy. The truth however is that while normally ovulating women (the majority of women who have mild to moderately severe endometriosis) respond to ovarian stimulation with fertility drugs by forming multiple follicles, they rarely ovulate > 1 (or at most 2) egg at a time. This is because such women usually only develop a single dominant follicle which upon ovulating leaves the others intact. This is the reason why normally ovulating women who undergo ovulation induction usually will not experience improved pregnancy potential, nor will they have a marked increase in multiple pregnancies. Conversely, non-ovulating women (as well as those with dysfunctional ovulation) who undergo ovulation induction, almost always develop multiple large follicles that tend to ovulate in unison. This increases the potential to conceive along with an increased risk multiple pregnancies.
So let me take a stab at explaining why IVF is more successful than IUI or surgical correction in the treatment of endometriosis-related infertility:
1.The toxic pelvic factor: Endometriosis is a condition where the lining of the uterus (the endometrium) grows outside the uterus. While this process begins early in the reproductive life of a woman, with notable exceptions, it only becomes manifest in the 2ndhalf of her reproductive life. After some time, these deposits bleed and when the blood absorbs it leaves a visible pigment that can be identified upon surgical exposure of the pelvis. Such endometriotic deposits invariably produce and release toxins” into the pelvic secretions that coat the surface of the membrane (the peritoneum) that envelops all abdominal and pelvic organs, including the uterus, tubes and ovaries. These toxins are referred to as “the peritoneal factor”. Following ovulation, the egg(s) must pass from the ovary (ies), through these toxic secretions to reach the sperm lying in wait in the outer part the fallopian tube (s) tube(s) where, the sperm lie in waiting. In the process of going from the ovary(ies) to the Fallopian tube(s) these eggs become exposed to the “peritoneal toxins” which alter s the envelopment of the egg (i.e. zona pellucida) making it much less receptive to being fertilized by sperm. As a consequence, if they are chromosomally normal such eggs are rendered much less likely to be successfully fertilized. Since almost all women with endometriosis have this problem, it is not difficult to understand why they are far less likely to conceive following ovulation (whether natural or induced through ovulation induction). This “toxic peritoneal factor impacts on eggs that are ovulated whether spontaneously (as in natural cycles) or following the use of fertility drugs and serves to explain why the chance of pregnancy is so significantly reduced in normally ovulating women with endometriosis.
2.The Immunologic Factor: About one third of women who have endometriosis will also have an immunologic implantation dysfunction (IID) linked to activation of uterine natural killer cells (NKa). This will require selective immunotherapy with Intralipid infusions, and/or heparinoids (e.g. Clexane/Lovenox) that is much more effectively implemented in combination with IVF.
3.Surgical treatment of mild to moderate endometriosis does not usually improve pregnancy potential:. The reason is that endometriosis can be considered to be a “work in progress”. New lesions are constantly developing. So it is that for every endometriotic seen there are usually many non-pigmented deposits that are in the process of evolving but are not yet visible to the naked eye and such evolving (non-visible) lesions can also release the same “toxins that compromise fertilization. Accordingly, even after surgical removal of all visible lesions the invisible ones continue to release “toxins” and retain the ability to compromise natural fertilization. It also explains why surgery to remove endometriotic deposits in women with mild to moderate endometriosis usually will fail to significantly improve pregnancy generating potential. In contrast, IVF, by removing eggs from the ovaries prior to ovulation, fertilizing these outside of the body and then transferring the resulting embryo(s) to the uterus, bypasses the toxic pelvic environment and is therefore is the treatment of choice in cases of endometriosis-related infertility.
4.Ovarian Endometriomas: Women, who have advanced endometriosis, often have endometriotic ovarian cysts, known as endometriomas. These cysts contain decomposed menstrual blood that looks like melted chocolate…hence the name “chocolate cysts”. These space occupying lesions can activate ovarian connective tissue (stroma or theca) resulting in an overproduction of male hormones (especially testosterone). An excess of ovarian testosterone can severely compromise follicle and egg development in the affected ovary. Thus there are two reasons for treating endometriomas. The first is to alleviate symptoms and the second is to optimize egg and embryo quality. Conventional treatment of endometriomas involves surgical drainage of the cyst contents with subsequent removal of the cyst wall (usually by laparoscopy), increasing the risk of surgical complications. We recently reported on a new, effective and safe outpatient approach to treating endometriomas in women planning to undergo IVF. We termed the treatment ovarian Sclerotherapy. The process involves; needle aspiration of the “chocolate colored liquid content of the endometriotic cyst, followed by the injection of 5% tetracycline hydrochloride into the cyst cavity. Such treatment will, more than 75% of the time result in disappearance of the lesion within 6-8 weeks. Ovarian sclerotherapy can be performed under local anesthesia or under conscious sedation. It is a safe and effective alternative to surgery for definitive treatment of recurrent ovarian endometriomas in a select group of patients planning to undergo IVF
I am not suggesting that all women with infertility-related endometriosis should automatically resort to IVF. Quite to the contrary…. In spite of having reduced fertility potential, many women with mild to moderate endometriosis can and do go on to conceive on their own (without treatment). It is just that the chance of this happening is so is much lower than normal.
IN SUMMARY: For young ovulating women (< 35 years of age ) with endometriosis, who have normal reproductive anatomy and have fertile male partners, expectant treatment is often preferable to IUI or IVF. However, for older women, women who (regardless of their age) have any additional factor (e.g. pelvic adhesions, ovarian endometriomas, male infertility, IID or diminished ovarian reserve-DOR) IVF should be the primary treatment of choice. I strongly recommend that you visit 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: •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! •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 •How Many Embryos should be transferred: A Critical Decision in IVF? •Endometriosis and Immunologic Implantation Dysfunction (IID) and IVF •Endometriosis and Infertility: Why IVF Rather than IUI or Surgery Should be the Treatment of Choice. •Endometriosis and Infertility: The Influence of Age and Severity on Treatment Options •Early -Endometriosis-related Infertility: Ovulation Induction (with or without Intrauterine Insemination) and Reproductive Surgery Versus IVF •Treating Ovarian Endometriomas with Sclerotherapy. •Effect of Advanced Endometriosis with Endometriotic cysts (Endometriomas) on IVF Outcome & Treatment Options. •Deciding Between Intrauterine Insemination (IUI) and In Vitro Fertilization (IVF). •Intrauterine Insemination (IUI): Who Needs it & who Does Not: Pro’s & •Induction of Ovulation with Clomiphene Citrate: Mode of Action, Indications, Benefits, Limitations and Contraindications for its use •Clomiphene Induction of Ovulation: Its Use and Misuse! ___________________________________________________ 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!
Dear Dr. Sher,
Thank you for the job your are doing. I read frequently your blog in the past 2 years, and it has made a difference for me. I am 40 years old, I gave birth to my son 4 years ago, with whom I remained pregnant on the first month of trying. My husband is 6 years younger and I have been trying to get pregnant with a second child for the last 2 years. I had to pregnancies ending in miscarriage over that time. I had also 2 IVF attempts, the first one, on a short protocol, resulting in what is sometimes called “empty follicle syndrome” and subsequent cancellation; and a very recent one, on a long procotol resulting in 7 eggs retrieved, 5 were fertilized and were looking good on day 2. One was transferred the other were cultivated to the 5. None made it. Is there anything I can do to increase my chances, besides lifestyle improvements and taking supplements? Do you have any suggestions to these course of action?
Thank you very much in advance.
The potential for a woman’s eggs to undergo orderly development and maturation, while in large part being genetically determined can be profoundly influenced by the woman’s age, her “ovarian reserve” and proximity to menopause. It is also influenced by the protocol used for controlled ovarian stimulation (COH) which by fashioning the intra-ovarian hormonal environment, profoundly impacts egg development and maturation.
After the menarche (age at which menstruation starts) a monthly process of repeatedly processing eggs continues until the menopause, by which time most eggs will have been used up, and ovulation and menstruation cease. When the number of eggs remaining in the ovaries falls below a certain threshold, ovarian function starts to wane over a 5 to10-years. This time period is referred to as the climacteric. With the onset of the climacteric, blood Follicle Stimulating Hormone (FSH) and later also Luteinizing Hormone (LH) levels begin to rise…. at first slowly and then more rapidly, ultimately culminating in the complete cessation of ovulation and menstruation (i.e. menopause).
One of the early indications that the woman has entered the climacteric and that ovarian reserve is diminishing DOR) , is the detection of a basal blood FSH level above 9.0 MIU/ml and/ or an AMH level og <2.0ng/ml.
Prior to the changes that immediately precede ovulation, virtually all human eggs have 23 pairs (i.e. 46) of chromosomes. Thirty six to forty hours prior to ovulation, a surge occurs in the release of LH by the pituitary gland. One of the main e purposes of this LH surge is to cause the chromosomes in the egg to divide n half (to 23 in number) in order that once fertilized by a mature sperm ends up having 23 chromosomes) the resulting embryo will be back to having 46 chromosomes. A “competent” mature egg is one that has precisely 23 chromosomes, not any more or any less. It is largely the egg, rather than the sperm that determines the chromosomal integrity of the embryo and only an embryo that has a normal component of 46 chromosomes (i.e. euploid) is “competent” to develop into a healthy baby. If for any reason the final number of chromosomes in the egg is less or more than 23 (aneuploid), it will be incapable of propagating a euploid, “competent” embryo. Thus egg/embryo aneuploidy (“incompetence”) is the leading cause of human reproductive dysfunction which can manifest as: arrested embryo development and/or failed implantation (which often presents as infertility), early miscarriage or chromosomal birth defects (e.g. Down’s syndrome). While most aneuploid (“incompetent”) embryos often fail to produce a pregnancy, some do. However, most such pregnancies miscarry early on. On relatively rare occasions, depending on the chromosome pair involved, aneuploid embryos can develop into chromosomally defective babies (e.g. Down’s syndrome).
Up until a woman reaches her mid- thirties, at best, 1:2 of her eggs will likely be chromosomally normal. As she ages beyond her mid-thirties there will be a a progressive decline in egg quality such that by age 40 years only about 15%-20% of eggs are euploid and, by the time the woman reaches her mid-forties, less than 10% of her eggs are likely to be chromosomally normal. While most aneuploid embryos do appear to be microscopically abnormal under the light microscope, this is not invariably so. In fact, many aneuploid embryos a have a perfectly normal appearance under the microscope. This is why it is not possible to reliably differentiate between competent and incompetent embryos on the basis of their microscopic appearance (morphologic grade) alone.
The process of natural selection usually precludes most aneuploid embryos from attaching to the uterine lining. Those that do attach usually do so for such only a brief period of time. In such cases the woman often will not even experience a postponement of menstruation. There will be a transient rise in blood hCG levels but in most cases the woman will be unaware of even having conceived (i.e. a “chemical pregnancy”). Alternatively, an aneuploid embryo might attach for a period of a few weeks before being expelled (i.e. a “miscarriage”). Sometimes (fortunately rarely) an aneuploid embryo will develop into a viable baby that is born with a chromosomal birth defect (e.g. Down’s syndrome).
The fact that the incidence of embryo aneuploidy invariably increases with advancing age serves to explain why reproductive failure (“infertility”, miscarriages and birth defects), also increases as women get older.
It is an over-simplification to represent that diminishing ovarian reserve as evidenced by raised FSH blood levels (and other tests) and reduced response to stimulation with fertility drugs is a direct cause of “poor egg/ embryo quality”. This common misconception stems from the fact that poor embryo quality (“incompetence”) often occurs in women who at the same time, because of the advent of the climacteric also have elevated basal blood FSH/LH levels and reduced AMH. But it is not the elevation in FSH or the low AMH that causes embryo “incompetence”. Rather it is the effect of advancing age (the “biological clock”) resulting a progressive increase in the incidence of egg aneuploidy, which is responsible for declining egg quality. Simply stated, as women get older “wear and tear” on their eggs increases the likelihood of egg and thus embryo aneuploidy. It just so happens that the two precipitating factors often go hand in hand.
The importance of the IVF stimulation protocol on egg/embryo quality cannot be overstated. This factor seems often to be overlooked or discounted by those 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 in patients at risk – particularly those with diminished ovarian reserve (“poor responders”) and those who are “high responders” (women with PCOS , those with dysfunctional or absent ovulation, and young women under 25 years of age).
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.
During the normal ovulation cycle, ovarian hormonal changes are regulated to avoid irregularities in production and interaction that could adversely influence follicle development and egg quality. As an example, small amounts of androgens (male hormones such as testosterone) that are produced by the ovarian stroma (the tissue surrounding ovarian follicles) during the pre-ovulatory phase of the cycle enhance late follicle development, estrogen production by the granulosa cells (cells that line the inner walls of follicles), and egg maturation.
However, over-production of testosterone can adversely influence the same processes. It follows that protocols for controlled ovarian stimulation (COS should be geared toward optimizing follicle growth and development (without placing the woman at risk from overstimulation), while at the same time avoiding excessive ovarian androgen production. Achievement of such objectives requires a very individualized approach to choosing the protocol for COS with fertility drugs as well as the precise timing of the “trigger shot” of hCG.
It is important to recognize that the pituitary gonadotropins, LH and FSH, while both playing a pivotal role in follicle development, have different primary sites of action in the ovary. The action of FSH is mainly directed towards the cells lining the inside of the follicle that are responsible for estrogen production. LH, on the other hand, acts primarily on the ovarian stroma to produce male hormones/ androgens (e.g. androstenedione and testosterone). A small amount of testosterone is necessary for optimal estrogen production. Over-production of such androgens can have a deleterious effect on granulosa cell activity, follicle growth/development, egg maturation, fertilization potential and subsequent embryo quality. Furthermore, excessive ovarian androgens can also compromise estrogen-induced endometrial growth and development.
In conditions such as polycystic ovarian syndrome (PCOS), which is characterized by increased blood LH levels, there is also increased ovarian androgen production. It is therefore not surprising that “poor egg/embryo quality” is often a feature of this condition. The use of LH-containing preparations such as Menopur further aggravates this effect. Thus we recommend using FSH-dominant products such as Follistim, Puregon, and Gonal-F in such cases. While it would seem prudent to limit LH exposure in all cases of COS, this appears to be more vital in older women, who tend to be more sensitive to LH
It is common practice to administer gonadotropin releasing hormone agonists (GnRHa) agonists such as Lupron, and, GnRH-antagonists such as Ganirelix and Orgalutron to prevent the release of LH during COS. GnRH agonists exert their LH-lowering effect over a number of days. They act by causing an initial outpouring followed by a depletion of pituitary gonadotropins. This results in the LH level falling to low concentrations, within 4-7 days, thereby establishing a relatively “LH-free environment”. GnRH Antagonists, on the other hand, act very rapidly (within a few hours) to block pituitary LH release, so as achieve the same effect.
Long Agonist (Lupron/Buserelin) Protocols: The most commonly prescribed protocol for Lupron/gonadotropin administration is the so-called “long protocol”. Here, Lupron is given, starting a week or so prior to menstruation. This results in an initial rise in FSH and LH level, which is rapidly followed by a precipitous fall to near zero. It is followed by uterine withdrawal bleeding (menstruation), whereupon gonadotropin treatment is initiated while daily Lupron injections continue, to ensure a “low LH” environment. A modification to the long protocol which I prefer using in cases of DOR, is the Agonist/Antagonist Conversion Protocol (A/ACP) where, upon the onset of a Lupron-induced bleed , this agonist is supplanted by an antagonist (Ganirelix/Cetrotide/Orgalutron) and this is continued until the hCG trigger. In many such cases I supplement with human growth hormone (HGH) to try and further enhance response and egg development.
Lupron Flare/Micro-Flare Protocol: Another approach to COS is by way of so-called “(micro) flare protocols”. This involves initiating gonadotropin therapy simultaneous with the administration of GnRH agonist (e.g. Lupron/Buserelin). The intent here 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” represents “a double edged sword” because 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 androgen production which could potentially compromise egg quality, especially in older women and women with PCOS, whose ovaries have increased sensitivity to LH. 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 in older women, and in women with diminished ovarian reserve. Accordingly, I do not prescribe them at all.
Estrogen Priming – My approach for “Poor Responders” Our patients who have demonstrated reduced ovarian response to COS as well as those who by way of significantly raised FSH blood levels are likely to be “poor responders”, are treated using a “modified” long protocol. The approach involves the initial administration of GnRH agonist for a number of days to cause pituitary down-regulation. Upon menstruation and confirmation by ultrasound and measurement of blood estradiol levels that adequate ovarian suppression has been achieved, the dosage of GnRH agonist is drastically lowered and the woman is given twice-weekly injections of estradiol for a period of 8. COS is thereupon initiated using a relatively high dosage of FSH-(Follistim, Bravelle, Puregon or Gonal F) which is continued along with daily administration of GnRH agonist until the “hCG trigger.” By this approach we have been able to significantly improve ovarian response to gonadotropins in many of hitherto “resistant patients”.
The “Trigger”: hCG (Profasi/Pregnyl/Novarel) versus Lupron: With ovulation induction using fertility drugs, the administration of 10,000U hCGu (the hCG “trigger”) mimics the LH surge, sending the eggs (which up to that point are immature (M1) and have 46 chromosomes) 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 it had prior to the “trigger”. Such a chromosomally normal, M2 egg, upon being fertilized by mature sperm (that following maturational division also has 23 chromosomes) will hopefully propagate embryos that have 46 chromosomes and will be “:competent” to propagate viable pregnancies. The key is to trigger with no less than 10,000U of hCGu (Profasi/Novarel/Pregnyl) and if hCGr (Ovidrel) is used, to make sure that 500mcg (rather than 250mcg) is administered. In my opinion, any lesser dosage will reduce the efficiency of meiosis, and increase the risk of the eggs being chromosomally abnormal. . I also do not use the agonist (Lupron) “trigger”. This approach which is often recommended for women at risk of overstimulation, is intended to reduce the risk of OHSS. The reason for using the Lupron trigger is that by inducing a surge in the release of LH by the pituitary gland it reduces the risk of OHSS. This is true, but this 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 percentage of chromosomally abnormal and of immature (M1) eggs. The use of “coasting” in such cases) can obviate this effect
.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