Ask Our Doctors – Archive
Our Medical Directors are outstanding physicians that you will find to be very personable and compassionate, who take care to ensure that you have the most cutting-edge fertility treatments at your disposal. This is your outlet to ask your questions to the doctors.
Dear Dr. Geoffrey Sher,
I’m a 38 year old woman and my male partner is 36 years and we have undergone 4x IVF treatments (during the years 2015/2016 and 2018). Despite a low AMH 0.29 µg/L we had in total 9 transfers with fresh and frozen good quality embryos/blastocysts. We also had the chance to participate in a study and check two embryos in a PGS-studies in which one was ok and transferred. We have so far had no success with any of the IVF treatments.
At the age 27 dermoid cysts (8-9 cm) one on each side of the ovaries was removed with laparotomy. My partner’s sperm count and motility values are normal. Before IVF treatment a Hysterosalpingogram (HSG) was done without any remarks.
My period now is around 21/24 days with 4-5 days of period and ovulate during day 11-12. I have always had issues with PMS and I have the same issues before ovulation. I have from my teenage years until now struggled with acne, especially on my back and some on the face. Being originally from Iran I also suffer from hirsutism. I also take extra multivitamin for women and high dosage of D-vitamin since I have olive-skin and live in Sweden. I’m allergic to lactose, grass pollen, leguminous and fur.
We are both normal weighted, non-smokers, exercising 1-2 time a week, working as engineers and trying to live and eat as healthy as possible.
During the fourth IVF treatment I ate DHEA for 1-2 months (50mg/day) and got additional extra medicine and treatments such as Lutinus, Progynon, Prednisolon, Trombyl, LEI and Intralipid to increase the chances. I also was treated with Letrozole before the last embryo transfer since I wanted to make sure that I had a ovulation so we could get back the two remaining embryos.
I have always got the long agonist protocol for all treatments, high dosage of Menopur up to 450 units/day with and without Elonva 150 units/day. My NK-cell levels where tested as well and they were too high.
My outcome from the 4 IVF’s has so far been:
IVF 1
11 eggs.
8 fertilized.
1x day 2 embryo regained.
2x day 5 blastocyst to the freezer, regained in natural cycles.
IVF2:
8 eggs.
6 fertilized.
1x day 2 embryo regained.
1x day 5 blastocyst and 1x day 6 blastocyst to the freezer, regained in natural cycles.
IVF3
8 eggs.
6 fertilized.
2x day 6 checked with PGS. 1 regained in natural cycle.
IVF4
8 eggs.
6 fertilized.
1x day 5 blastocyst regained.
2x day 5 blastocyst to the freezer, regained both of them in the same natural cycle.
Even if the chances are low to achieve a pregnancy, I’m looking for a options to increase our chances during the little time we got by trying at home, hey why not?! My doctor whom prescribed DHEA thinks I can take the medicine during 4 months since he has good experience with it and patients that achieved pregnancy trying at home. I wanted also to add Letrozole as an option. But then I read your statements regarding women suffering from DOR and that was absolutely not a good option, so now I’m a bit lost and need help before taking any decisions.
Kind regards from Sweden,
S
I would need much more information in order to advise authoritatively. I believe that central to your problem lies an implantation dysfunction> I also do not believe that using DHEA is helpful…but that is far less important here.
Whenever a patient fails to achieve a viable pregnancy following embryo transfer (ET), the first question asked is why! Was it simply due to, bad luck?, How likely is the failure to recur in future attempts and what can be done differently, to avoid it happening next time?.
It is an indisputable fact that any IVF procedure is at least as likely to fail as it is to succeed. Thus when it comes to outcome, luck is an undeniable factor. Notwithstanding, it is incumbent upon the treating physician to carefully consider and address the causes of IVF failure before proceeding to another attempt:
1.Age: The chance of a woman under 35Y of age having a baby per embryo transfer is about 35-40%. From there it declines progressively to under 5% by the time she reaches her mid-forties. This is largely due to declining chromosomal integrity of the eggs with advancing age…”a wear and tear effect” on eggs that are in the ovaries from birth.
2.Embryo Quality/”competency (capable of propagating a viable pregnancy)”. As stated, the woman’s age plays a big role in determining egg/embryo quality/”competency”. This having been said, aside from age the protocol used for controlled ovarian stimulation (COS) is the next most important factor. It is especially important when it comes to older women, and women with diminished ovarian reserve (DOR) where it becomes essential to be aggressive, and to customize and individualize the ovarian stimulation protocol.
We used to believe that the uterine environment is more beneficial to embryo development than is the incubator/petri dish and that accordingly, the earlier on in development that embryos are transferred to the uterus, the better. To achieve this goal, we used to select embryos for transfer based upon their day two or microscopic appearance (“grade”). But we have since learned that the further an embryo has advanced in its development, the more likely it is to be “competent” and that embryos failing to reach the expanded blastocyst stage within 5-6 days of being fertilized are almost invariably “incompetent” and are unworthy of being transferred. Moreover, the introduction into clinical practice about a decade ago, (by Levent Keskintepe PhD and myself) of Preimplantation Genetic Sampling (PGS), which assesses for the presence of all the embryos chromosomes (complete chromosomal karyotyping), provides another tool by which to select the most “competent” embryos for transfer. This methodology has selective benefit when it comes to older women, women with DOR, cases of unexplained repeated IVF failure and women who experience recurrent pregnancy loss (RPL).
3.The number of the embryos transferred: Most patients believe that the more embryos transferred the greater the chance of success. To some extent this might be true, but if the problem lies with the use of a suboptimal COS protocol, transferring more embryos at a time won’t improve the chance of success. Nor will the transfer of a greater number of embryos solve an underlying embryo implantation dysfunction (anatomical molecular or immunologic).Moreover, the transfer of multiple embryos, should they implant, can and all too often does result in triplets or greater (high order multiples) which increases the incidence of maternal pregnancy-induced complications and of premature delivery with its serious risks to the newborn. It is for this reason that I rarely recommend the transfer of more than 2 embryos at a time and am moving in the direction of advising single embryo transfers …especially when it comes to transferring embryos derived through the fertilization of eggs from young women.
4.Implantation Dysfunction (ID): Implantation dysfunction is a very common (often overlooked) cause of “unexplained” IVF failure. This is especially the case in young ovulating women who have normal ovarian reserve and have fertile partners. Failure to identify, typify, and address such issues is, in my opinion, an unfortunate and relatively common cause of repeated IVF failure in such women. Common sense dictates that if ultrasound guided embryo transfer is performed competently and yet repeated IVF attempts fail to propagate a viable pregnancy, implantation dysfunction must be seriously considered. Yet ID is probably the most overlooked factor. The most common causes of implantation dysfunction are:
a.A“ thin uterine lining”
b.A uterus with surface lesions in the cavity (polyps, fibroids, scar tissue)
c.Immunologic implantation dysfunction (IID)
d.Endocrine/molecular endometrial receptivity issues
e.Ureaplasma Urealyticum (UU) Infection of cervical mucous and the endometrial lining of the uterus, can sometimes present as unexplained early pregnancy loss or unexplained failure following intrauterine insemination or IVF. The infection can also occur in the man, (prostatitis) and thus can go back and forth between partners, with sexual intercourse. This is the reason why both partners must be tested and if positive, should be treated contemporaneously.
Certain causes of infertility are repetitive and thus cannot readily be reversed. Examples include advanced age of the woman; severe male infertility; immunologic infertility associated with alloimmune implantation dysfunction (especially if it is a “complete DQ alpha genetic match between partners plus uterine natural killer cell activation (NKa).
I strongly recommend that you visit http://www.DrGeoffreySherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.
•The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
•Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
•IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation (COS)
•The Fundamental Requirements for Achieving Optimal IVF Success
•Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
•Ovarian Stimulation in Women Who have Diminished Ovarian Reserve (DOR): Introducing the Agonist/Antagonist Conversion protocol
•Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
•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
•IVF: How Many Attempts should be considered before Stopping?
•“Unexplained” Infertility: Often a matter of the Diagnosis Being Overlooked!
•IVF Failure and Implantation Dysfunction:
•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
•Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas:
•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
My final IVF cycle at SIRM-LV commences on March 19th and concludes on April 2nd. If you are interested in undergoing a fresh IVF treatment cycle with me or if you have embryos cryopreserved at SIRM-LV and wish to undergo a Frozen Embryo Transfer (FET) prior to my departure, please contact me immediately….. My March cycle is likely to be very much in demand…….So, time is of the essence!
Following my departure from SIRM in mid-April, 2019, I will continue to provide comprehensive consultations to those of you that wish to have my guidance. Upon scheduling a SKYPE consultation with me, you will promptly receive a detailed questionnaire, along with a request that you submit available medical records for my review prior to our consultation. Additional tests and records can/will be requisitioned later, as needed. Your +/- 1 hour comprehensive SKYPE consultation will be followed by a detailed written report which you can also share with your personal Fertility Physician.
I will soon be posting a list of internationally regarded Fertility Specialists whom I endorse and who will have expressed a willingness to implement my suggested approaches, at their discretion. It is to one of these doctors that I would selectively refer you…upon request.
CONTACT INFORMATION:
•Online: Go to sherivf.com and Schedule a Skype Consultation. Upon doing so, you will be able to download a free copy of my new eBook ” Recurrent Pregnancy Loss (RPL) and Unexplained IVF Failure: The Immunologic Link”
•Phone
oIf you live in the USA or Canada: Please call 1-800-780-7437 or 702-533-2691
oIf you reside elsewhere Abroad: Please call 702-533-2691
oEmail: concierge@SherIVF.com
Please monitor this website for future announcements on further developments.
Geoff Sher
I cant see my wife crying for a baby writing to you for help.
tbpcr with endmoetrial tissue negative
endometriosis,polycystic ovaries.
trying for 6 years
2 iui failure
1 self cycle ivf + one FET failure
1 donor egg cycle FET (ERA guided zoladex given a month before planning the transfer ,ecosprin 75 mg,aquajest 100ml ,progynova ,duphaston) (detected hcg 30 mIU/mL 2 weeks after transfer then droped to 13 mIU/mL after 2 days).
We are unable to diagonise the root cause of the problem. with so many failures we are begining to loose hope.
please suggest what to do.
I am nearly 41 years old. I had a TFMR due to Trisomy 18 last year. I am undergoing IVF with PGS to avoid the same outcome as I terminated at 4 months and it was another 3 months before my period returned. I am doing several cycles to bank embryos as I would like to have more than one child. Since April of last year I have done 5 cycles.
4/2018- no 5 day embryos
6/2018- 6, 5 day Embryos tested, one euploid, one inconclusive
9/2018 – 1, 5 day Embryo tested, aneuploid
11/2018 – 3, 5 day Embryos, one euploid, one inconclusive
1/2019 – no 5 day embryos
prior to this in Sept 2017 there was my first IVF attempt at the age of 39 which resulted in the termination. I have 2 untested embryos frozen from this cycle.
My clinic says I should transfer as I have 2 euploid embryos and they think my ovaries need a break from stimulation. I feel that if I do get pregnant now and it is successful, when I can try again, it will be far more challenging to produce viable embryos than it is now. As I have been producing a euploid embryos atleast every other cycle and I am still responding to the medications, I would like to try a few more cycles. Looking at the statistics I was hoping to bank 3-5 euploid embryos in order to have 2 viable pregnancies. I am aware of the limitations of PGS, but still I do not want to transfer any untested embryos at the moment as if I have a miscarriage or termination, I feel I will lose too much time when I am at the cusp of when fertility drastically declines for women. Is it inadvisable for me to try a few more cycles over the coming months? What would you advise to a patient like me?
My FSH is 9,68mUI/ml; LH 2.76 mUI/mL; prolactin 26,8 ng/ml 562,8 uUI/ml, AMH 1,91 ng/ml 13,64 pmol/L, T4L 12, 30 pg/ml, TSH 1,53 uUI/ml
I personally, completely agree with your position. At this time with what appears to be normal ovarian reserve, you have the best existing chance to bank more euploid embryos and I would urge to do so before transferring. I also suggest that your ovarian protocol for stimulation be carefully reviewed and possibly revised.
The potential for a woman’s eggs to undergo orderly development and maturation, while in large part being genetically determined can be profoundly influenced by the woman’s age, her “ovarian reserve” and proximity to menopause. It is also influenced by the protocol used for controlled ovarian stimulation (COH) which by fashioning the intra-ovarian hormonal environment, profoundly impacts egg development and maturation.
After the menarche (age at which menstruation starts) a monthly process of repeatedly processing eggs continues until the menopause, by which time most eggs will have been used up, and ovulation and menstruation cease. When the number of eggs remaining in the ovaries falls below a certain threshold, ovarian function starts to wane over a 5 to10-years. This time period is referred to as the climacteric. With the onset of the climacteric, blood Follicle Stimulating Hormone (FSH) and later also Luteinizing Hormone (LH) levels begin to rise…. at first slowly and then more rapidly, ultimately culminating in the complete cessation of ovulation and menstruation (i.e. menopause).
One of the early indications that the woman has entered the climacteric and that ovarian reserve is diminishing DOR) , is the detection of a basal blood FSH level above 9.0 MIU/ml and/ or an AMH level og <2.0ng/ml.
Prior to the changes that immediately precede ovulation, virtually all human eggs have 23 pairs (i.e. 46) of chromosomes. Thirty six to forty hours prior to ovulation, a surge occurs in the release of LH by the pituitary gland. One of the main e purposes of this LH surge is to cause the chromosomes in the egg to divide n half (to 23 in number) in order that once fertilized by a mature sperm ends up having 23 chromosomes) the resulting embryo will be back to having 46 chromosomes. A “competent” mature egg is one that has precisely 23 chromosomes, not any more or any less. It is largely the egg, rather than the sperm that determines the chromosomal integrity of the embryo and only an embryo that has a normal component of 46 chromosomes (i.e. euploid) is “competent” to develop into a healthy baby. If for any reason the final number of chromosomes in the egg is less or more than 23 (aneuploid), it will be incapable of propagating a euploid, “competent” embryo. Thus egg/embryo aneuploidy (“incompetence”) is the leading cause of human reproductive dysfunction which can manifest as: arrested embryo development and/or failed implantation (which often presents as infertility), early miscarriage or chromosomal birth defects (e.g. Down’s syndrome). While most aneuploid (“incompetent”) embryos often fail to produce a pregnancy, some do. However, most such pregnancies miscarry early on. On relatively rare occasions, depending on the chromosome pair involved, aneuploid embryos can develop into chromosomally defective babies (e.g. Down’s syndrome).
Up until a woman reaches her mid- thirties, at best, 1:2 of her eggs will likely be chromosomally normal. As she ages beyond her mid-thirties there will be a a progressive decline in egg quality such that by age 40 years only about 15%-20% of eggs are euploid and, by the time the woman reaches her mid-forties, less than 10% of her eggs are likely to be chromosomally normal. While most aneuploid embryos do appear to be microscopically abnormal under the light microscope, this is not invariably so. In fact, many aneuploid embryos a have a perfectly normal appearance under the microscope. This is why it is not possible to reliably differentiate between competent and incompetent embryos on the basis of their microscopic appearance (morphologic grade) alone.
The process of natural selection usually precludes most aneuploid embryos from attaching to the uterine lining. Those that do attach usually do so for such only a brief period of time. In such cases the woman often will not even experience a postponement of menstruation. There will be a transient rise in blood hCG levels but in most cases the woman will be unaware of even having conceived (i.e. a “chemical pregnancy”). Alternatively, an aneuploid embryo might attach for a period of a few weeks before being expelled (i.e. a “miscarriage”). Sometimes (fortunately rarely) an aneuploid embryo will develop into a viable baby that is born with a chromosomal birth defect (e.g. Down’s syndrome).
The fact that the incidence of embryo aneuploidy invariably increases with advancing age serves to explain why reproductive failure (“infertility”, miscarriages and birth defects), also increases as women get older.
It is an over-simplification to represent that diminishing ovarian reserve as evidenced by raised FSH blood levels (and other tests) and reduced response to stimulation with fertility drugs is a direct cause of “poor egg/ embryo quality”. This common misconception stems from the fact that poor embryo quality (“incompetence”) often occurs in women who at the same time, because of the advent of the climacteric also have elevated basal blood FSH/LH levels and reduced AMH. But it is not the elevation in FSH or the low AMH that causes embryo “incompetence”. Rather it is the effect of advancing age (the “biological clock”) resulting a progressive increase in the incidence of egg aneuploidy, which is responsible for declining egg quality. Simply stated, as women get older “wear and tear” on their eggs increases the likelihood of egg and thus embryo aneuploidy. It just so happens that the two precipitating factors often go hand in hand.
The importance of the IVF stimulation protocol on egg/embryo quality cannot be overstated. This factor seems often to be overlooked or discounted by those IVF practitioners who use a “one-size-fits-all” approach to ovarian stimulation. My experience is that the use of individualized/customized COS protocols can greatly improve IVF outcome in patients at risk – particularly those with diminished ovarian reserve (“poor responders”) and those who are “high responders” (women with PCOS , those with dysfunctional or absent ovulation, and young women under 25 years of age).
While no one can influence underlying genetics or turn back the clock on a woman’s age, any competent IVF specialist should be able to tailor the protocol for COS to meet the individual needs of the patient.
During the normal ovulation cycle, ovarian hormonal changes are regulated to avoid irregularities in production and interaction that could adversely influence follicle development and egg quality. As an example, small amounts of androgens (male hormones such as testosterone) that are produced by the ovarian stroma (the tissue surrounding ovarian follicles) during the pre-ovulatory phase of the cycle enhance late follicle development, estrogen production by the granulosa cells (cells that line the inner walls of follicles), and egg maturation.
However, over-production of testosterone can adversely influence the same processes. It follows that protocols for controlled ovarian stimulation (COS should be geared toward optimizing follicle growth and development (without placing the woman at risk from overstimulation), while at the same time avoiding excessive ovarian androgen production. Achievement of such objectives requires a very individualized approach to choosing the protocol for COS with fertility drugs as well as the precise timing of the “trigger shot” of hCG.
It is important to recognize that the pituitary gonadotropins, LH and FSH, while both playing a pivotal role in follicle development, have different primary sites of action in the ovary. The action of FSH is mainly directed towards the cells lining the inside of the follicle that are responsible for estrogen production. LH, on the other hand, acts primarily on the ovarian stroma to produce male hormones/ androgens (e.g. androstenedione and testosterone). A small amount of testosterone is necessary for optimal estrogen production. Over-production of such androgens can have a deleterious effect on granulosa cell activity, follicle growth/development, egg maturation, fertilization potential and subsequent embryo quality. Furthermore, excessive ovarian androgens can also compromise estrogen-induced endometrial growth and development.
In conditions such as polycystic ovarian syndrome (PCOS), which is characterized by increased blood LH levels, there is also increased ovarian androgen production. It is therefore not surprising that “poor egg/embryo quality” is often a feature of this condition. The use of LH-containing preparations such as Menopur further aggravates this effect. Thus we recommend using FSH-dominant products such as Follistim, Puregon, and Gonal-F in such cases. While it would seem prudent to limit LH exposure in all cases of COS, this appears to be more vital in older women, who tend to be more sensitive to LH
It is common practice to administer gonadotropin releasing hormone agonists (GnRHa) agonists such as Lupron, and, GnRH-antagonists such as Ganirelix and Orgalutron to prevent the release of LH during COS. GnRH agonists exert their LH-lowering effect over a number of days. They act by causing an initial outpouring followed by a depletion of pituitary gonadotropins. This results in the LH level falling to low concentrations, within 4-7 days, thereby establishing a relatively “LH-free environment”. GnRH Antagonists, on the other hand, act very rapidly (within a few hours) to block pituitary LH release, so as achieve the same effect.
Long Agonist (Lupron/Buserelin) Protocols: The most commonly prescribed protocol for Lupron/gonadotropin administration is the so-called “long protocol”. Here, Lupron is given, starting a week or so prior to menstruation. This results in an initial rise in FSH and LH level, which is rapidly followed by a precipitous fall to near zero. It is followed by uterine withdrawal bleeding (menstruation), whereupon gonadotropin treatment is initiated while daily Lupron injections continue, to ensure a “low LH” environment. A modification to the long protocol which I prefer using in cases of DOR, is the Agonist/Antagonist Conversion Protocol (A/ACP) where, upon the onset of a Lupron-induced bleed , this agonist is supplanted by an antagonist (Ganirelix/Cetrotide/Orgalutron) and this is continued until the hCG trigger. In many such cases I supplement with human growth hormone (HGH) to try and further enhance response and egg development.
Lupron Flare/Micro-Flare Protocol: Another approach to COS is by way of so-called “(micro) flare protocols”. This involves initiating gonadotropin therapy simultaneous with the administration of GnRH agonist (e.g. Lupron/Buserelin). The intent here is to deliberately allow Lupron to elicit an initial surge (“flare”) in pituitary FSH release in order to augment FSH administration by increased FSH production. Unfortunately, this “spring board effect” represents “a double edged sword” because while it indeed increases the release of FSH, it at the same time causes a surge in LH release. The latter can evoke excessive ovarian stromal androgen production which could potentially compromise egg quality, especially in older women and women with PCOS, whose ovaries have increased sensitivity to LH. I am of the opinion that by evoking an exaggerated ovarian androgen response, such “(micro) flare protocols” can harm egg/embryo quality and reduce IVF success rates, especially in older women, and in women with diminished ovarian reserve. Accordingly, I do not prescribe them at all.
Estrogen Priming – My approach for “Poor Responders” Our patients who have demonstrated reduced ovarian response to COS as well as those who by way of significantly raised FSH blood levels are likely to be “poor responders”, are treated using a “modified” long protocol. The approach involves the initial administration of GnRH agonist for a number of days to cause pituitary down-regulation. Upon menstruation and confirmation by ultrasound and measurement of blood estradiol levels that adequate ovarian suppression has been achieved, the dosage of GnRH agonist is drastically lowered and the woman is given twice-weekly injections of estradiol for a period of 8. COS is thereupon initiated using a relatively high dosage of FSH-(Follistim, Bravelle, Puregon or Gonal F) which is continued along with daily administration of GnRH agonist until the “hCG trigger.” By this approach we have been able to significantly improve ovarian response to gonadotropins in many of hitherto “resistant patients”.
The “Trigger”: hCG (Profasi/Pregnyl/Novarel) versus Lupron: With ovulation induction using fertility drugs, the administration of 10,000U hCGu (the hCG “trigger”) mimics the LH surge, sending the eggs (which up to that point are immature (M1) and have 46 chromosomes) into maturational division (meiosis) This process is designed to halve the chromosome number , resulting in mature eggs (M2) that will have 23 chromosomes rather that the 46 chromosomes it had prior to the “trigger”. Such a chromosomally normal, M2 egg, upon being fertilized by mature sperm (that following maturational division also has 23 chromosomes) will hopefully propagate embryos that have 46 chromosomes and will be “:competent” to propagate viable pregnancies. The key is to trigger with no less than 10,000U of hCGu (Profasi/Novarel/Pregnyl) and if hCGr (Ovidrel) is used, to make sure that 500mcg (rather than 250mcg) is administered. In my opinion, any lesser dosage will reduce the efficiency of meiosis, and increase the risk of the eggs being chromosomally abnormal. . I also do not use the agonist (Lupron) “trigger”. This approach which is often recommended for women at risk of overstimulation, is intended to reduce the risk of OHSS. The reason for using the Lupron trigger is that by inducing a surge in the release of LH by the pituitary gland it reduces the risk of OHSS. This is true, but this comes at the expense of egg quality because the extent of the induced LH surge varies and if too little LH is released, meiosis can be compromised, thereby increasing the percentage of chromosomally abnormal and of immature (M1) eggs. The use of “coasting” in such cases) can obviate this effect
.I strongly recommend that you visit 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.
•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.
My final IVF cycle at SIRM-LV commences on March 19th and concludes on April 2nd. If you are interested in undergoing a fresh IVF treatment cycle with me or if you have embryos cryopreserved at SIRM-LV and wish to undergo a Frozen Embryo Transfer (FET) prior to my departure, please contact me immediately….. My March cycle is likely to be very much in demand…….So, time is of the essence!
Following my departure from SIRM in mid-April, 2019, I will continue to provide comprehensive consultations to those of you that wish to have my guidance. Upon scheduling a SKYPE consultation with me, you will promptly receive a detailed questionnaire, along with a request that you submit available medical records for my review prior to our consultation. Additional tests and records can/will be requisitioned later, as needed. Your +/- 1 hour comprehensive SKYPE consultation will be followed by a detailed written report which you can also share with your personal Fertility Physician.
I will soon be posting a list of internationally regarded Fertility Specialists whom I endorse and who will have expressed a willingness to implement my suggested approaches, at their discretion. It is to one of these doctors that I would selectively refer you…upon request.
CONTACT INFORMATION:
•Online: Go to sherivf.com and Schedule a Skype Consultation. Upon doing so, you will be able to download a free copy of my new eBook ” Recurrent Pregnancy Loss (RPL) and Unexplained IVF Failure: The Immunologic Link”
•Phone
oIf you live in the USA or Canada: Please call 1-800-780-7437 or 702-533-2691
oIf you reside elsewhere Abroad: Please call 702-533-2691
oEmail: concierge@SherIVF.com
Please monitor this website for future announcements on further developments.
Geoff Sher
Hi Dr Sher
I’m currently undergoing my second IVF cycle and am in the UK. My first cycle produced low number of eggs so this time my stimulation dose is menopur 300iu I took this for 7 days and had a tracking scan on tuesday this week which showed 14 follicles, some measuring up to 20mm, estradiol level was around 14,000pmol/L. My dosage was reduced to 150iu menopur. I took this for 2 days and another scan today showed 16-20 follicles all 15-22mm roughly. Blood levels today showed estradiol at around 22,000pmol/L. I have been advised to take another 150iu menopur injection now and a trigger injection this evening for collection on saturday morning. I have read your information on this site about OHSS and coasting and am worried my estradiol level is too high. Do you think this is the right course of action for me, or are my estradiol levels too high to be triggering? Many thanks for your advice, K
This is a very high E2 and probably suggests that in actuality there are MANY more than 20 follicles. My calculation based upon you E2 level is that the number of overall follicles is likely >double that number. In my opinion you are are significant risk of OHSS BUT it is probably too late to “coast” at this stage as that would severely prejudice egg/embryo quality. I would definitely discuss this risk with your RE. Without much more detail I really cannot comment further ..authoritatively.
Women like yourself are at risk that ovarian stimulation with gonadotropins will result in the, of development of severe ovarian hyperstimulation syndrome (OHSS), a life-endangering condition that is often accompanied by a profound reduction in egg “competency” and on fertilization often yield an inordinately high percentage of “incompetent” embryos which have a reduced potential to propagate viable pregnancies.
Concern that a patient will develop of OHSS often leads the treating RE to take measures aimed at reducing the risk of this life-endangering condition. One such measures is to “trigger” egg maturation prematurely in the hope of arresting further follicular growth and the other, is to initiate the “trigger” with a reduced dosage of hCG (i.ed. 5,000U rather than the usual 10,000U of of Pregnyl/Profasi/Novarel, to use or 250mcg rather than 500mcg of Ovidrel or to supplant the hCG “trigger” with a Lupron “trigger” which causes a prompt LH surge from the woman’s pituitary gland to take place. While such measures do indeed reduce the risk of OHSS to the mother, this often comes at the expense of egg quantity and “competency”. Fewer than the anticipated number of eggs are harvested and those that are retrieved are far more likely to be “immature” and chromosomally abnormal (aneuploid”), or “immature” , thereby significantly compromising IVF outcome.
Against this background, It is my considered opinion that when it comes to performing IVF in women at risk of developing OHSS, the most important consideration must be the selection and proper implementation of an individualized or customized ovarian stimulation protocol. Thereupon, rather than prematurely initiating the “trigger” to arrest further follicle growth, administering a reduced dosage of hCG or “triggering with a GnRH agonist (e.g. Lupron/Buserelin) that can compromise egg “competency”….. use of one of the following techniques will often markedly reduce the risk of OHSS while at the same time protecting egg quality:
1. PROLONGED COASTING…my preferred approach: My preferred approach is to use a long pituitary down-regulation protocol coming off the BCP which during the last 3 days is overlapped with the agonist, Lupron/Buserelin/Superfact. The BCP is intended to lower LH and thereby reduce stromal activation (hyperthecosis) in the hope of controlling LH-induced ovarian androgen (predominantly, testosterone) production and release. I then stimulate my PCOS patients using a low dosage of recombinant FSH-(FSHr) such as Follistim/Gonal-F/Puregon. On the 3rd day of such stimulation a smidgeon of LH/hCG (Luveris/Menopur) is added. Thereupon, starting on day 7 of ovarian stimulation, I perform serial blood estradiol (E2) and ultrasound follicle assessments, watching for the number and size of the follicles and the blood estradiol concentration [E2]. I keep stimulating (regardless of the [E2] until 50% of all follicles reach 14mm. At this point, provided the [E2] reaches at least >2,500pg/ml, I stop the agonist as well as gonadotropin stimulation and track the blood E2 concentration daily. The [E2] will almost invariably increase for a few days. I closely monitor the [E2] as it rises, plateaus and then begins to decline. As soon as the [E2] drops below 2500pg/ml (and not before then), I administer a “trigger” shot of 10,000U Profasi/ Novarel/Pregnyl or 500mcg Ovidrel/Ovitrel. This is followed by an egg retrieval, performed 36 hours later. Fertilization is accomplished using intracytoplasmic sperm injection (ICSI) because “coasted” eggs usually have little or no cumulus oophoris enveloping them and eggs without a cumulus will not readily fertilize naturally. Moreover, they also tend to have a “hardened” envelopment (zona pellucida), making spontaneous fertilization problematic in many cases. All fertilized eggs are cultured to the blastocyst stage (up to day 5- 6 days) and thereupon are either vitrified and preserved for subsequent transfer in later hormone replacement cycles or (up to 2) blastocysts are transferred to the uterus, transvaginally under transabdominal ultrasound guidance. The success of this approach depends on precise timing of the initiation and conclusion of “prolonged coasting”. If started too early, follicle growth will arrest and the cycle will be lost. If commenced too late, too many follicles will be post-mature/cystic (>22mm) and as such will usually harbor abnormal or dysmature eggs. Use of “Coasting” almost always prevents the development of severe OHSS, optimizes egg/embryo quality and avoids unnecessary cycle cancellation. If correctly implemented, the worst you will encounter is moderate OHSS and this too is relatively uncommon.
2. EMBRYO FREEZING AND DEFERMENT OF EMBRYO TRANSFEDR (ET): OHSS is always a self-limiting condition. In the absence of continued exposure to hCG, symptoms and signs as well as the risk of severe complications will ultimately abate. Thus, in the absence of pregnancy, all symptoms, signs and risks associated with OHSS will disappear within about 10-14 days of the hCG trigger. Conversely, since early pregnancy is always accompanied by a rapid and progressive rise in hCG , the severity of OHSS will increase until about the 9th or tenth gestational week whereupon a transition from ovarian to placental hormonal dominance occurs, the severity of OHSS rapidly diminishes and the patient will be out of risk. Accordingly, in cases where in spite of best effort to prevent OHSS, the woman develops symptoms and signs of progressive overstimulation prior to planned ET, all the blastocysts should be vitrified and cryostored for FET in a subsequent hormone replacement cycle. In this way women with OHSS can be spared the risk of the condition spiraling out of control.
I strongly recommend that you visit http://www.DrGeoffreySherIVF.com . Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.
·The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
·Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
·IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation(COS)
·The Fundamental Requirements For Achieving Optimal IVF Success
·Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
·Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
·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?
·Taking A Fresh Look at Ovarian Hyperstimulation Syndrome (OHSS), its Presentation, Prevention and Management
·Preventing Severe Ovarian Hyperstimulation Syndrome (OHSS) with “Prolonged Coasting”
·Understanding Polycystic Ovarian Syndrome (PCOS) and the Need to Customize Ovarian Stimulation Protocols.
·“Triggering” Egg Maturation in IVF: Comparing urine-derived hCG, Recombinant DNA-hCG and GnRH-agonist:
·The “Lupron Trigger” to Prevent Severe OHSS: What are the Pro’s and Con’s?
•.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.
•Implications of “Empty Follicle Syndrome and “Premature Luteinization”
•Premature Luteinization (“the premature LH surge): Why it happens and how it can be prevented.
•Preventing Severe Ovarian Hyperstimulation Syndrome (OHSS) with “Prolonged Coasting”
My final IVF cycle at SIRM-LV commences on March 19th and concludes on April 2nd. If you are interested in undergoing a fresh IVF treatment cycle with me or if you have embryos cryopreserved at SIRM-LV and wish to undergo a Frozen Embryo Transfer (FET) prior to my departure, please contact me immediately….. My March cycle is likely to be very much in demand…….So, time is of the essence!
Following my departure from SIRM in mid-April, 2019, I will continue to provide comprehensive consultations to those of you that wish to have my guidance. Upon scheduling a SKYPE consultation with me, you will promptly receive a detailed questionnaire, along with a request that you submit available medical records for my review prior to our consultation. Additional tests and records can/will be requisitioned later, as needed. Your +/- 1 hour comprehensive SKYPE consultation will be followed by a detailed written report which you can also share with your personal Fertility Physician.
I will soon be posting a list of internationally regarded Fertility Specialists whom I endorse and who will have expressed a willingness to implement my suggested approaches, at their discretion. It is to one of these doctors that I would selectively refer you…upon request.
CONTACT INFORMATION:
•Online: Go to sherivf.com and Schedule a Skype Consultation. Upon doing so, you will be able to download a free copy of my new eBook ” Recurrent Pregnancy Loss (RPL) and Unexplained IVF Failure: The Immunologic Link”
•Phone
oIf you live in the USA or Canada: Please call 1-800-780-7437 or 702-533-2691
oIf you reside elsewhere Abroad: Please call 702-533-2691
oEmail: concierge@SherIVF.com
Please monitor this website for future announcements on further developments.
Geoff Sher
Hi!
I am 10.5 weeks pregnant. I received three IVIG already because I suffer from ovarian failure. I had an IVF on December 1st.Two blastocytes were transferred; at first I was pregnant with twins, but at 8.5 weeks one of the two embryos stopped growing. the other one appeared to be well in the last sonogram, which I had three days ago. My last IVIG was on January 11th (I was almost 9 weeks pregnant at that point). One of my immunologists wants me to get a fourth one, the other doctor says that it is not needed because at this stage there is no immunological risk as the placenta is already working. Are there any guidelines that stipulate until when are IVIG recommended for fertility purposes? Do you have any recommendations to share; I am sort of in the middle of the two opinions?
Regards,
Rosaura
There is in my opinion, no significant benefit in IVIG therapy after the 2nd infusion at the time the blood pregnancy test becomes positive, in cases of autoimmune implantation dysfunction. With alloimmune implantation dysfunction , monthly infusions until the 20th week are advised. The cost of IVIG makes this quite a financial burden. However, today, Intralipid infusions have all but supplanted the use of IVIG.
Geoff Sher