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.
Hello Dr. Sher,
I am 42 years old, currently still in the IUI phase, expecting to start IVF early next year.
My AFC/AMH/FSH is not horrible (at least for my age: 15/2.03/9.7), but my uterine lining is a bit thin. For the first IUI is was 6.9mm on the day of the trigger, for the second one it was 5.34 – the first IUI was cancelled (for practical reasons, nothing medical) and the second yielded no positive pregnancy test.
My doctor decided to give vaginal sildenafil a try: 25mg twice a day (CD3-day of trigger). I do have very low blood pressure (80-90/as low as in the 40s) and the RE team at the clinic is not able to make a decision whether it is safe for me to start this treatment or not. My family doctor has not heard of this use of Viagra and she is unwilling to commit to saying either way and I was supposed to start the first dose this morning and the second dose is scheduled for right now.
I read your papers where you do state that in your practice you saw “virtually no clinical side effects”. Can you comment on whether you saw any blood pressure changes?
Thank you!!
Not when used in women with normal cardiovascular status.
More significantly, I believe the use of IUI in a woman of yourv age to be relatively contraindicated. The chance of success is about 1: 30 and you don’t have the time to waste.
Many infertile patients, are erroneously advised by their physicians to first try IUI several times before resorting to IVF. Additionally many misguided insurance providers often, purely for economic reasons, require that infertile female enrollees who have at least 1 patent Fallopian tube, first undergo several attempts at IUI before doing IVF. It is important for infertile women to be aware that such an approach is often ill-advised as there are circumstances where IUI is very unlikely to be successful and where IVF should be the primary approach.
While IUI is well indicated for women undergoing controlled ovarian stimulation for ovulation dysfunction, cervical mucus hostility, male impotence and when artificial insemination with pre-frozen sperm, there are several situations where in spite of tubal patency it is (in my opinion) relatively contraindicated:
•Moderate or severe male Infertility: Intrauterine insemination (IUI) and in-vitro fertilization (IVF) are both often touted as being equivalent treatments for male factor subfertility. This is a fallacy. The success rate with a single IVF treatment using intracytoplasmic sperm injection is actually 8-10 times greater than a single attempt at IUI. Thus when it comes to moderate or severe male infertility such patients will ultimately require IVF anyway. Those who argue that because a single cycle of IUI is much less expensive than a single attempt at IVF and for this reason, several attempts at the former should be tried before resorting to IVF. A recent study conducted by the Department of Public Health in the UK compared outcomes (live birth-producing pregnancy) and the cost-effectiveness of offering IVF as a primary approach as compared with first trying IUI and only resorting to IVF if this fails. The results confirmed that in cases of male factor infertility it is far less costly and much more cost-effective to go directly to IVF as the primary treatment than to start with IUI and then only resort to IVF, should this fail.
•Older women and those with Diminished ovarian reserve (DOR): For the vast majority of women, over 35y of age, an inevitable irreversible and accelerated advancement of the biological clock takes place, such that by age 40y there is only about a 2-3% per-cycle, chance of IUI success. Conversely IVF afford many such women a far greater opportunity to have a baby. Thus such women simply do not have the time to waste on ineffectual treatments such as IUI. Rather, they need (in my opinion) to “make hay while the sun still shines” and go directly to IVF.
•Endometriosis: All women with endometriosis have toxins in their pelvic secretions. This compromises the ability of sperm to fertilize eggs that pass from the ovary (ies) to reach sperm in the fallopian tube(s).This dramatically reduces egg fertilization potential by a factor of 4-6 fold. It in large part serves to explain why potentially all women with endometriosis have reduced fecundity (reproductive potential) and why tubal surgery, the use of fertility drugs and/or intrauterine insemination (IUI) does not improve fecundity over no treatment at all. The only way to improve the chance of having a baby through extracting eggs before they are exposed to toxic pelvic secretions…i.e. through IVF. I am not suggesting that all women with endometriosis should go directly to IVF. In fact most ovulating younger women with early endometriosis have time and should consider trying to conceive on their own. Rather, what I am saying is that women over 35y, regardless of age, those who have DOR and those women who for whatever reason feel a compelling sense of urgency to conceive ASAP, should preferentially consider doing IVF.
I would now like to try and dispel the following misconceptions regarding IUI:
i.The per-cycle cost of IUI is significantly lower than IVF and thus IUI represents a “cost saver”: Given the fact that IVF is at least 3-4 times more likely to be successful, when one looks at cost per baby (rather than cost per procedure) this turns out to be a fallacy. Moreover, cost also comes in the form of emotional currency and this needs to be measured in terms of the much lower chance of success with IUI.
ii.Success in ovulating women who undergo natural-cycle IUI and those women undergoing ovulation induction with clomiphene citrate is equivalent to success rates when gonadotropins are used: Quite to the contrary….,with the exception of IUI performed using thawed sperm (usually donor sperm), spontaneously ovulating women undergoing natural-cycle IUI does not improve the chance of pregnancy over regular timed intercourse. Also, when compared with IUI performed following induction of ovulation with gonadotropins, the use of clomiphene citrate is associated with a 30% lower success rate.
iii.”IUI is less invasive than IVF”… ….This is true, however aside from the surgical egg retrieval which (when done in the right setting) is a safe procedure, IUI with gonadotropins requires largely the same drugs, preparation and monitoring as does IVF and the success rate is several fold lower than for IVF.
iv.IUI is a viable option when at least one Fallopian tube is patent: Most tubal damage is due to prior pelvic inflammatory disease and this almost always affects both Fallopian tubes. What this means is that when only one tube is damaged or blocked the other (whether patent or not) is almost invariably affected as well. For a viable intrauterine pregnancy to occur following IUI, a healthy intra-tubal environment is an absolute necessity. This serves to explain why the chance of successful pregnancy following IUI is severely compromised in such cases. It also serves to explain why the chance of pregnancy is markedly reduced and why the risk of a tubal (ectopic) gestation is markedly increased in such cases. It is therefore my opinion, that IVF should be considered preferentially when one tube is damaged and this is deemed to be the likely consequence of tubal infection.
v.The chance of a multiple pregnancy can be controlled with IUI: When compared with IVF, IUI has another major disadvantage. This is because in women with ovulation dysfunction (e.g.; those who have irregular or absent menstruation such as with PCOS) ovarian stimulation often results in the release of multiple eggs at a time and it is not possible to limit number of embryos that reach the uterus. This is why when, undergoing IUI, such women are very likely to have multiple pregnancies (triplets or greater) which is associated with serious perinatal and long term complications. It is only through IVF that by regulating the number of embryos transferred to the uterus that the risk of multiple pregnancies can be limited.
In my opinion, we as physicians need to rethink the basis upon which we recommend IUI as an alternative to IVF and educate our patients accordingly.
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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
Today I am 4 weeks 5days pregnant I found out early I was pregnant. Last week Friday The 15th I had blood taken and and ultrasound my levels were at 80. Ultrasound showed nothing. Monday my blood level was 360 but my blood from weenesday went down to 290 today Friday I had more blood take (waiting on results) and had a. Ultrasound where a gs sac was seen is there any possible way with my levels going down the one time this can turn out to be a healthy pregnancy ?
Yes..that could happen if > 1 embryo was transferred, and took…followed by the spontaneous absorption of one. I would repeat the blood hCG test to see if it continues to drop or picks up and starts to rise appropriately…hoping of course, for the latter to happen.
Geoff Sher
Hi Dr. Sher.
I just turned 36. I have been trying to get pregnant for 16 months. In September 2018, my AMH was 0.4. In November 2018, it was undetectable (not sure if it matters, but it was a different clinic. Either way, it is very low!). In November 2018, we tried a mini IVF. The one follicle had no egg (used Menopur and Antagon). We then took a break for a few months.
In April 2019, we tried IVF again with another clinic. This time we did birth control for 11 days with Lupron overlapping the last three days. The lupron continued for the rest of the cycle (until trigger). After 11 days of Lupron, we started stimulation with Gonal F and HCG. There were 4 follicles, which turned into 3 eggs which turned into 3 excellent quality blasts (we opted out of genetic testing. They were graded 5AA, 5AB and 5AB).
We did a fresh transfer that failed. We did a frozen transfer the following month that also failed. We now have the 5AA frozen and don’t want to touch that until we get more embryos.
Since then we have tried to replicate the last cycle but had a poor response to stimulation. My doctor then tried a cycle with a shot of Lupron Depot, and then three weeks later, stimulation with Puregon and Menopur. Again, I had a poor response to the stimulation medication. I believe I had side effects from Lupron Depot (really bad cramps etc.). I’m not sure if I was oversupressed? I don’t want to try to the Lupon Depot ever again.
We are at a loss of what to do in terms of our next cycle. Do you have any recommendations? I have heard about estrogen priming for people with DOR, or priming with HGH. We have also been hearing about PRP.
Could you provide any suggestions for the next cycle. We will not use donor eggs/embryos.
Women who (regardless of age) have diminished ovarian reserve (DOR) have a reduced potential for IVF success. Much of this is due to the fact that such women tend to have increased production, and/or biological activity, of LH. This can result in excessive ovarian male hormone (predominantly testosterone) production. This 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, www. SherIVF.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
___________________________________________________
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!
I had 3 failed IVF and in forth ivf I got my baby stillborn in 20 week so again childless. And idea why stillborn happpen in healthy pregnancy.
Thank you
I would require a great deal more information to respond authoritatively.
Geoff Sher
Hi Dr. Sher,
I am 39 and my husband is 43. My partner has two biological children with his previous partner. I have never been pregnant, but always on birth control (a non-hormonal IUD from 24-33 after that, nothing as I was with my current partner), and nothing significant showed abnormal in all my tests (AMH=10.6 pmol/L, FSH=5). My cycles have always been very regular, and I’ve never had any issues whatsoever with endometriosis, PCOS, etc. I am not overweight, do not smoke, am active, and live a very healthy lifestyle. I have been taking Opti Ova, Vitamin D, Vitamin B, MTHF, and prenatal vitamins, in addition to eating a healthy diet and eliminating almost all caffeine and alcohol. I do not have a family history of infertility or birth defects.
I have one small fibroid but it is a type 2, mostly submucosal with only a very small amount impacting the uterine cavity. Due to the location, I was told it would not be necessary to remove it as it is highly unlikely that it would affect implantation.
My partner had a vasectomy that we had reversed in November 2017. While at first, the surgery was successful, we weren’t getting pregnant. We found out that my partner’s sperm had a high titre of anti-sperm antibodies, so IUI was suggested. After a few months of tests, etc., we attempted IUI in January 2019, but the day of sperm collection we found out the reversal had failed and there was no sperm in the sample. At that time, we were told IVF was our only option to have our biological child. We retrieved my husband’s sperm through a PESA process and froze nine vials for ICSI during IVF.
Our first IVF used the antagonist protocol and we retrieved 12 eggs, but only 6 fertilized and only 2 made it to day 5, neither of them full blastocysts. Our first transfer was on April 4, 2019, with two morulas, and that failed. We were told that it was an egg quality problem, so we changed up the protocol and used the testosterone flare protocol the next time. I also made more lifestyle changes (eliminated all plastics, phthalates, parabens, white carbs, etc. [basically all the information in the “It Starts with the Egg” book I’m sure you’re familiar with]). We had our second egg retrieval on July 27, 2019. Again, we got 12 eggs, but this time 10 fertilized and 6 made it to day five. We transferred two on day five, but they weren’t full blastocysts yet. One was an early blast and the other was a morula. That transfer also failed. On day 6, we froze four blastocysts: two graded 3BB and two 2BB. We attempted an FET with the 3BB blastocysts and that too has failed. We are now waiting for the results of the 2BB transfer but I’m not hopeful. We find out Monday.
We are a bit frustrated, as I have never had any issues with anything that would indicate why we are unable to make this work using my own eggs. My naturopath, GP, and OBGYN also do not have any answers, though all have attempted to help.
I have sought and received different physicians’ recommendations, and they are:
1) go straight to egg donation as my eggs are clearly not creating good embryos
2) do the same process, the testosterone flare, get PGS testing, and get the fibroid removed
3) do a long agonist process and get back up egg and sperm donors to be sure (we can do a “combination cycle” but have to go overseas for this one, due to the cost)
Could you tell me which one (if any) you would recommend? I would ideally like to use my own eggs, but as time goes by and we suffer one disappointment after another, I am feeling really disheartened. I am not opposed to using donor eggs, but did want to give myself one more try.
Some further questions for you:
1) If I decide to do the third option and go overseas, would it be possible to do DHEA treatment prior to the long agonist cycle to get a better result? What would the dosage and recommendation be for that? Or what about HGH?
2) Would you recommend I remove the fibroid, regardless of the protocol? I was not recommended to do that prior to my second cycle, but that was when my doctor was sure that I would be able to make an embryo “stick.” Now that it appears I cannot, maybe that is one reason? My doctor still hasn’t recommended that, but it’s an option.
3) What are your thoughts on a testosterone flare cycle vs a long agonist cycle?
4) Do you recommend PGS testing? My current doctor doesn’t recommend it but since we’ve had so many failures, I’m wondering if we should.
4) Do all the supplements and lifestyle changes really make enough difference?
Thank you for any guidance you can offer. I appreciate it more than you know!
You have diminishing ovarian reserve and in my opinion, in such cases, the protocol used for ovarian stimulation needs to be carefully modified. 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. Thus 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.
3.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.
4.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.
Second, I based upon the above, I would oppose the use of testosterone or DHEA as too much ovarian testosterone will often prejudice egg quality and thus embryo competency.
I would suggest that you try IVF with own eggs again. However, given your diminishing ovarian reserve, consider the following: Women who (regardless of age) have diminished ovarian reserve (DOR) have a reduced potential for IVF success. Much of this is due to the fact that such women tend to have increased production, and/or biological activity, of LH. This can result in excessive ovarian male hormone (predominantly testosterone) production. This 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
I would definitely recommend PGS testing
I respectfully disagree that submucosal fibroids can be disregarded. If they are encroaching on the uterine cavity, they can compromise implantation and in my opinion should be removed hysteroscopically prior to embryo transfer.
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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