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,
i was diagnosed with low ovarian reserve(Amh is 0.53 ng/ml) I ‘m 38 years old with regular cycle, 6 years trying to get pregnant,
I was programmed to do ivf this cycle, but my lh on day 3 was at 7mui/ml, (progeterone at 0.53 and e2 at 56ng), my gynecologist put me on orgalutran 0.25 for four days ( to lower my lh), i repeated the dosage on day 7 of cycle after 4 injection of orgalutran but the level was 8, my gynecologist canceled the cycle and put me on birth control pills( microgynon 30), please what do you suggest, i’m very sad, could you explain for me please?
It is all about the protocol used for ovarian stimulation:
It is primarily the egg (rather than the sperm) that determines the chromosomal integrity (karyotype) of the embryo, the most important determinant of egg/embryo competency”. A “competent” egg is therefore one that has a normal karyotype and has the best potential to propagate a “competent” embryo. In turn, a “competent embryo is one that possesses the highest potential to implant and develop into a normal, healthy, baby.
When it comes to reproductive performance, humans are the least efficient of all mammals. Even in young women under 35y, at best only 2 out of 3 eggs are chromosomally numerically normal (euploid). The remainder will have an irregular number of chromosomes (aneuploid) and are thus “incompetent”. The incidence of egg aneuploidy increases with age such by age 39 years, 3 in 4 are “competent”, and by the mid-forties, at best one in 10 are likely to be aneuploid. The fertilization of an aneuploid egg will inevitably lead to embryo aneuploidy (“incompetence”). As previously stated, an aneuploid embryo cannot propagate a normal pregnancy
Within 38-42 hours of the initiation of the spontaneous pre-ovulatory luteinizing hormone (LH) surge (and also following administration of the human chorionic gonadotropin (hCG) “trigger” shot, given to induce egg maturation after ovarian stimulation with fertility drugs), the egg embarks on a rapid maturational process that involves halving of its 46 chromosomes to 23. During this process, (known as meiosis) 23 chromosomes are retained within the nucleus of the egg while the remaining 23 chromosomes are expelled in a membrane envelopment, from the egg nucleus. This small structure known as the polar body, comes to lie immediately below the “shell” of the egg (the zona pellucida) and is known as the 1st polar body or PB-1. The sperm, in the process of its maturation also undergoes meiosis divides into two separate functional gametes, each containing 23 chromosomes (half its original number of 46 chromosomes). With subsequent fertilization, the 23 chromosomes of the egg now fuse with the 23 chromosomes of the mature sperm resulting in the development of an embryo with 46 chromosomes (the normal human genome) comprising a combination of the genetic material from both partners. For the embryo to have exactly 46 chromosomes (the euploid number), both the mature egg and mature spermatozoon must contain exactly 23 chromosomes. Only such euploid embryos are “competent” (capable of developing into healthy babies). Those with an irregular number of chromosomes (aneuploid embryos) are “incompetent” and are incapable of propagating healthy babies. While embryo “incompetence” can result from either egg or sperm aneuploidy, it usually stems from egg aneuploidy. However, in cases of moderate or severe male factor infertility, the sperm’s contribution to aneuploidy of the embryo can be significantly greater.
While embryo ploidy (numerical chromosomal integrity) is not the only determinant of its “competency, it is by far the most important and in fact is a rate-limiting factor in human reproduction. It is causal in the vast majority of cases of “failed nidation which in turn is responsible for most cases of a failed pregnancy (natural or assisted) and causes most sporadic early pregnancy losses (both chemical gestations and miscarriages) as well as many chromosomal birth defects such as Turner syndrome (X-monosomy ) Down syndrome (trisomy 21) and Edward syndrome (trisomy 18) .
In most cases, embryos that develop too slowly as well as those that grow too fast (i.e. ones that by day 3 post-fertilization comprise fewer than 6 cells or more than 9 cells) and/or embryos that contain cell debris or “fragments” are usually aneuploid and are thus unable to propagate a healthy pregnancy (“incompetent”). Additionally, embryos that fail to survive in culture to the blastocyst stage are also almost always aneuploid/”incompetent”.
At a certain point in the later stage of a woman’s reproductive career, the number of remaining eggs in her ovaries falls below a certain threshold, upon which she is unable to respond optimally to fertility drugs. Often times this is signaled by a rising day 3 basal blood follicle stimulating hormone (FSH) level (>9.0MIU/ml) and a falling blood anti-Mullerian hormone (AMH) level (<2.0ng/ml or <15nmol/L). Such women who have diminished ovarian reserve (DOR) produce fewer eggs in response to ovarian stimulation. While DOR is most commonly encountered in women over 40 years of age it can and indeed also can occur in much younger women.
A few important (but often overlooked concepts should be considered in this regard:
•Age: It is advancing chronologic age and NOT declining ovarian reserve (as evidenced by abnormal blood AMH or FSH that results in an increased incidence of egg/embryo "incompetence" due to aneuploidy
•The ovaries and developing eggs of women with DOR (regardless of age) are highly susceptible to the adverse effect of excessive Luteinizing Hormone (LH)-induced, ovarian overproduction of male hormones (e,g. testosterone and androstenedione). While a little testosterone produced by the ovary promotes normal follicle growth and orderly egg development excessive testosterone has a converse effect. That is why in older women and those who regardless of their age have DOR (and thus excessive LH bioavailability and increased ovarian testosterone production), the use of ovarian stimulation protocols that fail to down-regulate LH activity prior to initiating ovarian stimulation with gonadotropins, often prejudices egg/embryo quality and IVF outcome.
•Simply stated, while age is certainly the most important factor in determining the incidence of egg/embryo aneuploidy, women with DOR (regardless of their age), are less likely to propagate euploid (competent) eggs/embryos. While virtually nothing can be done to lower the incidence of age related aneuploidy, it is indeed possible to avoid a further decrease in egg/embryo “competency” by individualizing the protocols of ovarian stimulation used.
•My preferred protocols for women who have relatively normal ovarian reserve:
•The conventional long pituitary down regulation protocol: BCP are commenced early in the cycle and continued for at least 10 days. Starting 3 days before the BCP is to be discontinued, it is overlapped with an agonist such as Lupron 10U daily for three (3) days and continued until menstruation begins (which should ensue within 5-7 days of stopping the BCP). At that point an US examination is done along with a baseline measurement of blood estradiol to exclude a functional ovarian cyst. Daily Lupron (10U) is continued and an FSH-dominant gonadotropin such as Follistim, Puregon or Gonal-f daily is administered daily falong with 37.5U of Menopur (an FSH/LH combination) for 2 days. On the 3rd day the gonadotropin dosage is reduced by about one half and the dosage of Menopur is increased to 75U daily. Daily ultrasound and blood estradiol measurements are conducted starting on the 7th or 8th day of gonadotropin administration and continued until daily ultrasound follicle assessments indicate that most follicles have fully developed. At this point egg maturation is “triggered” using an intramuscular injection of a recombinant hCGr (Ovidrel) 500mcg or urinary derived hCGu (Pregnyl/Profasi/Novarel) 10,000U. And an egg retrieval is scheduled for 36h later.
•The agonist/antagonist conversion protocol (A/ACP): This is essentially the same as the conventional long down regulation protocol (see “a”-as above), except that with the onset of post-BCP menstruation, the agonist is supplanted by daily administration of a GnRH antagonist (e.g. Ganirelix, Cetrotide or Orgalutron) at a dosage of 125-250mcg daily until the day of the “trigger”. When it comes to women who have DOR I favor the use of the A/ACP, adding supplementary human growth hormone (HGH). In cases where the DOR is regarded as severe (AMH=<0.2), I often augment the AACP protocol by using estrogen priming for 7-9 days prior to or with the commencement of gonadotropin therapy; For this I prescribe E2 skin patches or intramuscular estradiol valerate (Delestrogen), prior to or sometimes concurrent with, the commencement of the GnRH antagonist administration.
•The following Ovarian stimulation protocols are in my opinion best avoided in stimulating olderf women and /or thosed who regardless of age , have DOR :
a)Microdose agonist (e.g. Lupron) “flare” protocols which result in an out-pouring of pituitary-LH at the critical time that ovarian follicles and eggs start developing/growing.
b)High dosages of LH -containing fertility drugs (e.g. Menopur).
c)Supplementation with preparations that are testosterone-based
d)Supplementation with DHEA (which is converted to testosterone in the ovaries.
e)Clomiphene citrate or Letrozole which cause increased release of LH and thus increase ovarian male hormone (testosterone and androstenedione output.
f)“Triggering” egg maturation using too low a dosage of hCG (e.g. 5,000U rather than 10,000U) or Ovidrel (e.g. 250mcg of Ovidrel rather than 500mcg)
g)“Triggering” women who have DOR, with an agonist (alone)such as Lupron Superfact/ Buserelin/Aminopeptidyl/Decapeptyl.
•Preimplantation Genetic Screening (PGS):
The introduction of preimplantation genetic testing/screening (PGT/PGS) for e permits identification of all the chromosomes in the egg and embryo (full karyotyping) allowing for the identification of the most "competent" (euploid) embryos for selective transfer to the uterus. This vastly improves the efficiency and success of the IVF process and renders us fare better equipped us to manage older women and those who regardless of their age, have DOR.
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)
Founded in April 2019, Sher Fertility Solutions (SFS) offers online (Skype/FaceTime) consultations to patients from > 40 different countries. All consultations are followed by a detailed written report presenting my personal recommendations for treatment of what often constitute complex Reproductive Issues.
If you wish to schedule an online consultation with me, please contact my assistant (Patti Converse) by phone (800-780-7437/702-533-2691), email (concierge@SherIVF.com) or, enroll online on then home-page of my website (www.SherIVF.com).
PLEASE SPREAD THE WORD ABOUT SFS!
Geoff Sher
Hi Dr. Sher,
I have had two failed FETs (both chemical pregnancies) of euploid embryos. I had an ERA done within the past year prior to transferring any embryos showing I needed 12 hours extra of progesterone. Is the fact that I have had two chemical pregnancies show that the embryos implanted and we did the transfer at the correct window of implantation? Or is there any value in doing a repeat ERA? What is your thought on the value of doing the receptiva test? Thanks so much
I personally am not a big believer in the ERA. In my opinion, your failure to achieve a viable pregnancy with euploid embryos, is highly suggestive of an underlying implantation dysfunction:
Implantation dysfunction is unfortunately often overlooked as an important cause of IVF failure. In the pursuit of optimizing outcome with IVF, the clinician has a profound responsibility to meticulously assess and address this important issue if IVF success is to be optimized. This is especially relevant in cases of “unexplained IVF failure, Recurrent Pregnancy Loss (RPL) and in women suspected of having underlying anatomical and immunologic factors. Doing so will not only maximize the chance of a viable pregnancy but enhancing placentation, will at the same time promote the noble objective of optimizing the quality of life after birth.”
IVF success rates have been improving over the last decade. The average live birth rate per embryo transfer in the U.S.A for women under 40y using their own eggs , is currently better than 1:3 women. However, there is still a wide variation from program to program for IVF live birth rates, ranging from 20% to near 50%. Based upon these statistics, the majority of women undergoing IVF in the United States require two or more attempts to have a baby. IVF practitioners in the United States commonly attribute the wide dichotomy in IVF success rates to variability in expertise of the various embryology laboratories. This is far from accurate. In fact, other factors such as wide variations in patient selection and the failure to develop individualized protocols for ovarian stimulation or to address those infective, anatomical and immunologic factors that influence embryo implantation are at least equally important.
About 80% of IVF failures are due to “embryo incompetency” that is largely due to an irregular quota of chromosomes (aneuploidy) which is usually related to advancing age of the woman and is further influenced by other factors such as the protocol selected for ovarian stimulation, diminished ovarian reserve (DOR)m and severe male factor infertility. However in about 20% of dysfunctional cases embryo implantation is the cause of failure.
This blog article will focus on implantation dysfunction and IVF failure due to:
•Anatomical abnormalities in the uterine cavity (polyps/scarring/internal fibroids)
Several studies performed both in the United States and abroad have confirmed that a dye X-Ray or hysterosalpingogram (HSG) will fail to identify small endouterine surface lesions in >20% of cases. This is significant because even small uterine lesions have the potential to adversely affect implantation. Hysteroscopy is the traditional method for evaluating the integrity of the uterine cavity in preparation for IVF. It also permits resection of most uterine surface lesions, such as submucous uterine fibroids (myomas), intrauterine adhesions and endometrial or placental polyps. All of these can interfere with implantation by producing a local “inflammatory- type” response similar in nature to that which is caused by an intrauterine contraceptive device. Hysterosonography (syn; HSN/ saline ultrasound examination) and hysteroscopy have all but supplanted HSG to assess the uterine cavity in preparation for IVF. HSN which is less invasive and far less expensive than is than hysteroscopy involves a small amount of a sterile saline solution is injected into the uterine cavity, whereupon a vaginal ultrasound examination is performed to assess the contour of the uterine cavity.
•Endometrial Thickness: As far back as in 1989 I first reported on the finding that ultrasound assessment of the late proliferative phase endometrium following ovarian stimulation in preparation for IVF, permits better identification of those candidates who are least likely to conceive. We noted that the ideal thickness of the endometrium at the time of ovulation or egg retrieval is >9 mm and that a thickness of less than 8 mm bodes poorly for a successful outcome following IVF.
Then in 1993, I demonstrated that sildenafil (Viagra) introduced into the vagina prior to hCG administration can improve endometrial growth in many women with poor endometrial development. Viagra’s mechanism of action is improvement in uterine blood flow with improved estrogen delivery…thereby enhancing endometrial development.
•Immunologic factors: These also play a role in IVF failure. Some women develop antibodies to components of their own cells. This “autoimmune” process involves the production of antiphospholipid, antithyroid, and/or anti-ovarian antibodies – all of which may be associated with activation of Natural Killer (NK) cells in the uterine lining. Activated NK cells (NKa) release certain cytokines (TH-I) that if present in excess, often damage the trophoblast (the embryo’s root system) resulting in immunologic implantation dysfunction (IID). This can manifest as “infertility” or as early miscarriages). In other cases (though less common), the problem is due to “alloimmune” dysfunction. Here the genetic contribution by the male partner renders the embryo “too similar” to the mother. This in turn activates NK cells leading to implantation dysfunction. These IID’s are treated using combinations of medications such as heparin, Clexane, Lovenox, corticosteroids and intralipid (IL).
I strongly recommend that you visit http://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.
•A Fresh Look at the Indications for IVF
•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.
•Human Growth Hormone Administration in IVF: Does it Enhances Egg/Embryo Quality and Outcome?
•IVF and the use of Supplementary Human Growth Hormone (HGH) : Is it Worth Trying and who needs it?
•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
•Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
•IVF: Approach to Selecting the Best Embryos for Transfer to the Uterus.
•Fresh versus Frozen Embryo Transfers (FET) Enhance IVF Outcome
•Frozen Embryo Transfer (FET): A Rational Approach to Hormonal Preparation and How new Methodology is Impacting IVF.
•Genetically Testing Embryos for IVF
•Staggered IVF
•Staggered IVF with PGS- Selection of “Competent” Embryos Greatly Enhances the Utility & Efficiency of IVF.
•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
•Endometrial Receptivity Array (ERA): Is There an actual “There, There”?
•IVF Failure and Implantation Dysfunction:
•Diagnosing and Treating Immunologic Implantation Dysfunction (IID)
•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!
•Endometrial Thickness, Uterine Pathology and Immunologic Factors
•Vaginally Administered Viagra is Often a Highly Effective Treatment to Help Thicken a Thin Uterine Lining
•A Thin Uterine Lining: Vaginal Viagra is Often the Answer (update)
•Cervical Ureaplasma Urealyticum Infection: How can it Affect IUI/IVF Outcome?
•The Role of Nutritional Supplements in Preparing for IVF
•The Basic Infertility Work-Up
•Defining and Addressing an Abnormal Luteal Phase
•Male Factor Infertility
•Routine Fertilization by Intracytoplasmic Sperm Injection (ICSI): An Argument in Favor
•Hormonal Treatment of Male Infertility
•Hormonal Treatment of Male Infertility
•Antisperm Antibodies, Infertility and the Role of IVF with Intracytoplasmic Sperm Injection (ICSI)
•Endometriosis and Infertily
•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
•Deciding Between Intrauterine Insemination (IUI) and In Vitro Fertilization (IVF).
•Intrauterine Insemination (IUI): Who Needs it & who Does Not: Pro’s & Con’s!IUI-Reflecting upon its Use and Misuse: Time for a Serious “Reality Check
•Mode of Action, Indications, Benefits, Limitations and Contraindications for its ue
•Clomiphene Induction of Ovulation: Its Use and Misuse!
ADDENDUM: PLEASE READ!!
INTRODUCING SHER FERTILITY SOLUTIONS (SFS)
Founded in April 2019, Sher Fertility Solutions (SFS) offers online (Skype/FaceTime) consultations to patients from > 40 different countries. All consultations are followed by a detailed written report presenting my personal recommendations for treatment of what often constitute complex Reproductive Issues.
If you wish to schedule an online consultation with me, please contact my assistant (Patti Converse) by phone (800-780-7437/702-533-2691), email (concierge@SherIVF.com) or, enroll online on then home-page of my website (www.SherIVF.com).
PLEASE SPREAD THE WORD ABOUT SFS!
Geoff Sher
Hi I was just wondering if I’m on the right meds?
I’ve done 3 EPUs (3rd being 3 days ago) with all being different doses/meds.
Round 1: 300iu gonal f-increased to 325iu second week, orgalutran and ovidrel for trigger.
11 follicles, only 7 eggs, lost all but 1x blastocyst.
Round 2: 350iu gonal f, orgalutran and ovidrel for trigger. 21 follicles (all different sizes- big and small eg 11mm-24mm), with only 1 egg. I also ovulated early. 5pm Friday ovulation test positive (testing every 4-6hrs), but trigger was 9pm Saturday for EPU Monday 8:30am.
Round 3: 337.5iu menopur, orgalutran and ovidrel for trigger.
13-15 follicles last Wednesday all @ 14-15mm… come Friday lost half/stopped growing.
EPU 6 eggs, 3 fertilised and as day 3s, I’m down to 2 top quality. They’re hopeful they will both be blastocysts.
I am doing a 4th round next month. It was suggested maybe 337.5iu menopur with low dose gonal f.
All doses start CD2.
I have PCOS/diabetes and also over active endometrial lining. I had 2 endometrial polyps removed 17th August, and another removed 3wks ago. One grew back within 2 months.
I’ve been on 850mg metformin twice a day for over 17yrs.
Normally I ovulate on day 14, but with immature follicles (at around 13mm).
I have done a few letrozole rounds in between.
1x 5mg and 2x 7.5mg.
We transferred my only embryo on 4th Nov and found out on 15th Nov (my birthday) that it was negative.
I got what I thought was implantation pains… but I was checking my temp, and when it dropped a few days later I knew it was unsuccessful.
Should round 4 be 337.5iu menopur alone…. or should we try with gonal f also???
Im 38, my AMH is 19…. but I just seem to have poor quality eggs, or immature.
Im in Victoria, Australia.
Im very good with knowing all the sizing, timing, dates of surgery before being told, finding polyps before the sonographer suggests they are there, etc.
A lady from the egg donor line told me with PCOS, I should be on low dose 150iu gonal f as a longer stims cycle…. but with that I worry I would ovulate early- even being on orgalutran.
I’ve found menopur to be the best cycle so far…. because they looked the best normal shape follicles (ie, not polycystic odd shape), best controlled constant size (all within mms of each other- no too small, too large scale) and the best levels/lining.
The only problem with the menopur cycle, is we can’t do a fresh transfer as my progesterone levels are too high…. every other time they’ve been too low, and I take crinone gel morning and night (besides a letrozole round with endometrial polyps that gave high progesterone level).
My Dr and I didn’t think it would be this hard, even with PCOS.
I plan to be at 6000iu vitamin d3 by start of 4th stim cycle. I read that high dose can help.
Im on 4000iu- through other stims. I use to get kidney stones all the time, but since increasing my d3, I haven’t, so it must be good for me.
I have dermatographia/MCAS, diabetes, PCOS, cobblestone throat, post nasal drip, reoccurring kidney stones, over-active endometrial lining, tilted cervix, right ovary has scar tissue and big vain (so has to access through uterus and down through tubes), had tonsillectomy, asthma, (can’t wear masks- chest infections and sinus infections, and sick from covid tests).
It would be interesting to know ur opinion being overseas.
If you are ever interested in knowing Australian ivf treatment plans, your welcome to ask me anything about my cycles. I also know some treatment plans for iui and for natural at home with little help- ie clomid, letrozole, combined 50iu-100gonal f with letrozole etc.
Thank you for your time
Oh, they also do ICSI as standard for all my cycles
All I can say is that the protocol used for ovarian stimulation must be carefully reviewed and revised. The need for individualizing the cycle for ovarian stimulation is particularly important for women with PCOS.
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 “normal” amount of testosterone. Over-exposure of the follicle to testosterone can in my opinion, 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.
A significant percentage of 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.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 estrogen skin patches applied every 2nd day (or with the BCP) for 10 days or longer, overlap it for 3 days with a GnRHa whereupon the estrogen priming 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 patient is given twice-weekly injections of estradiol valerate (Delestrogen) for a period of 7-8 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)
Founded in April 2019, Sher Fertility Solutions (SFS) offers online (Skype/FaceTime) consultations to patients from > 40 different countries. All consultations are followed by a detailed written report presenting my personal recommendations for treatment of what often constitute complex Reproductive Issues.
If you wish to schedule an online consultation with me, please contact my assistant (Patti Converse) by phone (800-780-7437/702-533-2691), email (concierge@SherIVF.com) or, enroll online on then home-page of my website (www.SherIVF.com).
PLEASE SPREAD THE WORD ABOUT SFS!
Geoff Sher
I have 5 PGS tested embryos and a potential surrogate. I am looking to do IVF with these embryos and surrogate. Does your practice practice such IVF Treatments? If so, what are the overall costs through discharge to obstetrician upon pregnancy confirmation?
Hi Maria,
Indeed we do offer such services. I suggest you call my assistant, Patti Converse and set up an online consultation with me to discuss in detail!
Geoff Sher
Dear Dr. Sher,
I would really appreciate your insight and second opinion. If you cannot answer my question for your blog, please provide me a quote for a private consult for my question. I will plan to discuss your recommendations with my RE for protocol changes.
I am a 37yo with 1 ovary, low AMH (0.52), AFC 4-10 and normal FSH. I have had 2 pregnancy and 2 live births. My husband had 2 vials of TESE sperm and we have been advised that our upcoming cycle will likely finish the 2 vials (so our last IVF attempt). I have done 4 oocyte retrieval cycles using Gonal-F doses between 300-450iu and Menopur 75mg. We have had similar outcomes from all of our cycles with regards to # of oocytes retrieved (7-8), fertilization (4-5) and quality of day 3 embryos (mostly equal amounts of good and fair day 3 embryos).
Our last cycle was different, and this is were my question will come into play. My meds were changed to Gonal 225mg-300mg and Menopur was doubled to 150mg. I retrieved 12 oocytes (highest number for me), fertilization was similar to past cycles (5), but quality was significantly worse– all poor and fair quality embryos. Is there some way to maintain the Menopur at 150mg (in the hopes of retrieving a higher number of oocytes) while also increasing the quality of embryos? OR do you think one of my prior protocols with Menopur 75mg, aiming for quality over quantity would be most advantageous? Appreciate your insights.
This is all about the protocol used in a woman with diminished ovarian reserve. Please see below.
It is primarily the egg (rather than the sperm) that determines the chromosomal integrity (karyotype) of the embryo, the most important determinant of egg/embryo competency”. A “competent” egg is therefore one that has a normal karyotype and has the best potential to propagate a “competent” embryo. In turn, a “competent embryo is one that possesses the highest potential to implant and develop into a normal, healthy, baby.
When it comes to reproductive performance, humans are the least efficient of all mammals. Even in young women under 35y, at best only 2 out of 3 eggs are chromosomally numerically normal (euploid). The remainder will have an irregular number of chromosomes (aneuploid) and are thus “incompetent”. The incidence of egg aneuploidy increases with age such by age 39 years, 3 in 4 are “competent”, and by the mid-forties, at best one in 10 are likely to be aneuploid. The fertilization of an aneuploid egg will inevitably lead to embryo aneuploidy (“incompetence”). As previously stated, an aneuploid embryo cannot propagate a normal pregnancy
Within 38-42 hours of the initiation of the spontaneous pre-ovulatory luteinizing hormone (LH) surge (and also following administration of the human chorionic gonadotropin (hCG) “trigger” shot, given to induce egg maturation after ovarian stimulation with fertility drugs), the egg embarks on a rapid maturational process that involves halving of its 46 chromosomes to 23. During this process, (known as meiosis) 23 chromosomes are retained within the nucleus of the egg while the remaining 23 chromosomes are expelled in a membrane envelopment, from the egg nucleus. This small structure known as the polar body, comes to lie immediately below the “shell” of the egg (the zona pellucida) and is known as the 1st polar body or PB-1. The sperm, in the process of its maturation also undergoes meiosis divides into two separate functional gametes, each containing 23 chromosomes (half its original number of 46 chromosomes). With subsequent fertilization, the 23 chromosomes of the egg now fuse with the 23 chromosomes of the mature sperm resulting in the development of an embryo with 46 chromosomes (the normal human genome) comprising a combination of the genetic material from both partners. For the embryo to have exactly 46 chromosomes (the euploid number), both the mature egg and mature spermatozoon must contain exactly 23 chromosomes. Only such euploid embryos are “competent” (capable of developing into healthy babies). Those with an irregular number of chromosomes (aneuploid embryos) are “incompetent” and are incapable of propagating healthy babies. While embryo “incompetence” can result from either egg or sperm aneuploidy, it usually stems from egg aneuploidy. However, in cases of moderate or severe male factor infertility, the sperm’s contribution to aneuploidy of the embryo can be significantly greater.
While embryo ploidy (numerical chromosomal integrity) is not the only determinant of its “competency, it is by far the most important and in fact is a rate-limiting factor in human reproduction. It is causal in the vast majority of cases of “failed nidation which in turn is responsible for most cases of a failed pregnancy (natural or assisted) and causes most sporadic early pregnancy losses (both chemical gestations and miscarriages) as well as many chromosomal birth defects such as Turner syndrome (X-monosomy ) Down syndrome (trisomy 21) and Edward syndrome (trisomy 18) .
In most cases, embryos that develop too slowly as well as those that grow too fast (i.e. ones that by day 3 post-fertilization comprise fewer than 6 cells or more than 9 cells) and/or embryos that contain cell debris or “fragments” are usually aneuploid and are thus unable to propagate a healthy pregnancy (“incompetent”). Additionally, embryos that fail to survive in culture to the blastocyst stage are also almost always aneuploid/”incompetent”.
At a certain point in the later stage of a woman’s reproductive career, the number of remaining eggs in her ovaries falls below a certain threshold, upon which she is unable to respond optimally to fertility drugs. Often times this is signaled by a rising day 3 basal blood follicle stimulating hormone (FSH) level (>9.0MIU/ml) and a falling blood anti-Mullerian hormone (AMH) level (<2.0ng/ml or <15nmol/L). Such women who have diminished ovarian reserve (DOR) produce fewer eggs in response to ovarian stimulation. While DOR is most commonly encountered in women over 40 years of age it can and indeed also can occur in much younger women.
A few important (but often overlooked concepts should be considered in this regard:
•Age: It is advancing chronologic age and NOT declining ovarian reserve (as evidenced by abnormal blood AMH or FSH that results in an increased incidence of egg/embryo "incompetence" due to aneuploidy
•The ovaries and developing eggs of women with DOR (regardless of age) are highly susceptible to the adverse effect of excessive Luteinizing Hormone (LH)-induced, ovarian overproduction of male hormones (e,g. testosterone and androstenedione). While a little testosterone produced by the ovary promotes normal follicle growth and orderly egg development excessive testosterone has a converse effect. That is why in older women and those who regardless of their age have DOR (and thus excessive LH bioavailability and increased ovarian testosterone production), the use of ovarian stimulation protocols that fail to down-regulate LH activity prior to initiating ovarian stimulation with gonadotropins, often prejudices egg/embryo quality and IVF outcome.
•Simply stated, while age is certainly the most important factor in determining the incidence of egg/embryo aneuploidy, women with DOR (regardless of their age), are less likely to propagate euploid (competent) eggs/embryos. While virtually nothing can be done to lower the incidence of age related aneuploidy, it is indeed possible to avoid a further decrease in egg/embryo “competency” by individualizing the protocols of ovarian stimulation used.
•My preferred protocols for women who have relatively normal ovarian reserve:
•The conventional long pituitary down regulation protocol: BCP are commenced early in the cycle and continued for at least 10 days. Starting 3 days before the BCP is to be discontinued, it is overlapped with an agonist such as Lupron 10U daily for three (3) days and continued until menstruation begins (which should ensue within 5-7 days of stopping the BCP). At that point an US examination is done along with a baseline measurement of blood estradiol to exclude a functional ovarian cyst. Daily Lupron (10U) is continued and an FSH-dominant gonadotropin such as Follistim, Puregon or Gonal-f daily is administered daily falong with 37.5U of Menopur (an FSH/LH combination) for 2 days. On the 3rd day the gonadotropin dosage is reduced by about one half and the dosage of Menopur is increased to 75U daily. Daily ultrasound and blood estradiol measurements are conducted starting on the 7th or 8th day of gonadotropin administration and continued until daily ultrasound follicle assessments indicate that most follicles have fully developed. At this point egg maturation is “triggered” using an intramuscular injection of a recombinant hCGr (Ovidrel) 500mcg or urinary derived hCGu (Pregnyl/Profasi/Novarel) 10,000U. And an egg retrieval is scheduled for 36h later.
•The agonist/antagonist conversion protocol (A/ACP): This is essentially the same as the conventional long down regulation protocol (see “a”-as above), except that with the onset of post-BCP menstruation, the agonist is supplanted by daily administration of a GnRH antagonist (e.g. Ganirelix, Cetrotide or Orgalutron) at a dosage of 125-250mcg daily until the day of the “trigger”. When it comes to women who have DOR I favor the use of the A/ACP, adding supplementary human growth hormone (HGH). In cases where the DOR is regarded as severe (AMH=<0.2), I often augment the AACP protocol by using estrogen priming for 7-9 days prior to or with the commencement of gonadotropin therapy; For this I prescribe E2 skin patches or intramuscular estradiol valerate (Delestrogen), prior to or sometimes concurrent with, the commencement of the GnRH antagonist administration.
•The following Ovarian stimulation protocols are in my opinion best avoided in stimulating olderf women and /or thosed who regardless of age , have DOR :
a)Microdose agonist (e.g. Lupron) “flare” protocols which result in an out-pouring of pituitary-LH at the critical time that ovarian follicles and eggs start developing/growing.
b)High dosages of LH -containing fertility drugs (e.g. Menopur).
c)Supplementation with preparations that are testosterone-based
d)Supplementation with DHEA (which is converted to testosterone in the ovaries.
e)Clomiphene citrate or Letrozole which cause increased release of LH and thus increase ovarian male hormone (testosterone and androstenedione output.
f)“Triggering” egg maturation using too low a dosage of hCG (e.g. 5,000U rather than 10,000U) or Ovidrel (e.g. 250mcg of Ovidrel rather than 500mcg)
g)“Triggering” women who have DOR, with an agonist (alone)such as Lupron Superfact/ Buserelin/Aminopeptidyl/Decapeptyl.
•Preimplantation Genetic Screening (PGS):
The introduction of preimplantation genetic testing/screening (PGT/PGS) for e permits identification of all the chromosomes in the egg and embryo (full karyotyping) allowing for the identification of the most "competent" (euploid) embryos for selective transfer to the uterus. This vastly improves the efficiency and success of the IVF process and renders us fare better equipped us to manage older women and those who regardless of their age, have DOR.
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
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ADDENDUM: PLEASE READ!!
INTRODUCING SHER FERTILITY SOLUTIONS (SFS)
Founded in April 2019, Sher Fertility Solutions (SFS) offers online (Skype/FaceTime) consultations to patients from > 40 different countries. All consultations are followed by a detailed written report presenting my personal recommendations for treatment of what often constitute complex Reproductive Issues.
If you wish to schedule an online consultation with me, please contact my assistant (Patti Converse) by phone (800-780-7437/702-533-2691), email (concierge@SherIVF.com) or, enroll online on then home-page of my website (www.SherIVF.com).
PLEASE SPREAD THE WORD ABOUT SFS!
Geoff Sher