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.
Hi – I’ve had 2 children via IVF, and after both deliveries, I had a hysteroscopy for adhesions before attempting to try again. We are now trying for baby #3, and my endometrium shows calcifications on the ultrasound. I had this before baby #2, and I had 1 chemical pregnancy before I conceived her. I think it’s from the scar tissue? My saline sono is normal, and the hysteroscopies have been successful, but I have these calcifications on the ultrasound – like lots of white spots. my RE says it COULD be affecting implantation, but hard to know? In your experience, what do you make of calcifications, given my history? I am now trying for #3, after a successful hysteroscopy but I have these. Thanks.
I should add I just had 2 chemical pregnancies while trying for #3. I am starting an immune protocol with the next attempt including prednisone and intralipids, but I am wondering about the calcifications
Provided you produce an endometrium that thickens to >8mm on estrogen, I would not be concerned about the calcifications. In my opinion, these are not uncommon after endometrial inflammation causing intrauterine adhesions.
•IVF Failure and Implantation Dysfunction:
•Endometrial Thickness, Uterine Pathology and Immunologic Factors
•Vaginally Administered Viagra is Often a Highly Effective Treatment to Help Thicken a Thin Uterine Lining
Geoff Sher
Dr Sher,
My RE is really stumped by me and I’m beginning to lose hope. Please let me know what you think.
I’m 34, AMH 4.6, AFC 27
IVF 1: bcp,antagonist with 225 Gonal F, 150 Menopur, E2 2400 at trigger, ovidrelle used. At ER 18 follicles retrieved, 5 mature, 3 fertilized with ICSI and one made it to freeze. 3 follicles had ovulated already and I had bad pain at hour 35.
IVF #2: bcp, long Lupron, 300 Gonal F, 75 Menopur, trigger 10,000 HCG, E2 at trigger was 1400. LH check during the whole cycle was always less than 0.6. At ER 17 follicles, 9 mature, 7 fertilized with ICSI. Only one made it to freeze. 2 follicles had ovulated at ER with pain again noted at hour 34.5-35.
Questions 1. Why do I have such a low egg maturity rate?
2. If my LH stays low it doesn’t seem like premature luteinization, do you think I just ovulate earlier than hour 36?
3. What can we do differently?
4. With an AFC of 27, why do so few follicles grow? The non-mature ones are still at the germinal vesicle stage per the embryologist.
Thank you so much! This has been distressing and can’t seem to get any resolution.
You need a thorough reassessment of your pituitary, ovarian thyroid and adrenal endocrinology….. as a prelude to re-strategizing your ovarian stimulation protocol.In my opinion, this likely is where the problem lies.
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
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
Please call or email Julie Dahan, my patient concierge. She will guide you on how to set up an in-person or Skype consultation with me. You can reach Julie at on her cell phone or via email at any time:
Julie Dahan
•Email: Julied@sherivf.com
•Phone: 702-533-2691
?800-780-7437
Geoff Sher
I also suggest that you access the 4th edition of my book ,”In Vitro Fertilization, the ART of Making Babies”. It is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.
Hey Dr! My wife’s first IVF was a little quirky. She was a slow responder. Her CD3 estradiol was 22 and day 5 110 and started to go from there. She ended up at 2500 estradiol with about 14 follicles ranging in size from 13-17 mm at 14 days stimming. They were going to have her keep stimming for a few days but her estradiol slightly dropped to 2300 so they triggered her with 5000 cc’s HCG. She ended up with 17 eggs, 15 matured, with ICSI 9 fertilized. On Day 3 we had all 9 still growing with Grade 1 (4 cell, 6 cell, 7 cell), Grade 2 (4 ranging from 6-9 cells) and 1 grade 3 (8 cell). All looked good but we ended up on Day 5 with one 4BA blast and 1 EC2. We transferred the one blast and are in 2WW and one day 6, the EC2 turned into a 4BB which we froze.
My question is – do you think the conversion of nine day 3 embryos to two blastocysts seems low or is it a normal attrition? I’m concerned this protocol (antagonist with BCP but no Lupron) may have over-suppressed her, hence the slow start. I was surprised that on day 5 only 2 out of 9 ended up at blast. Do yo think this could be a result of a suboptimal protocol leading to not the best eggs/embryos? My wife is 34, and our diagnosis is MFI. She has Day 3 AMh 3.3, 10.7 LSH, and 60 estradiol. Thanks!
In my opinion, the protocol used for ovarian stimulation needs to be reviewed and probably revised.
GnRH antagonists (e.g. Ganirelix, Cetrotide, and Orgalutron) are currently used with many controlled ovarian stimulation (COS) protocols. The conventional approach is to administer 250mcg antagonist, daily starting from the 6th-8th day after commencing ovarian stimulation with gonadotropins. This traditional approach is in my opinion, best suited to younger patients who have normal ovarian reserve (AMH>2.0ng/ml or 15pmol/L) and are “good responders” to COS, provided that the stimulation cycle is launched with a spontaneous menstrual cycle and is not launched coming off a birth control pill (BCP) or following prolonged premenstrual hormonal suppression (see Use of BCP in IVF”, elsewhere on this blog). However, this approach can in my opinion be decidedly disadvantageous when used in older women (>39y), women with diminished ovarian reserve (DOR) or women with polycystic ovarian syndrome (PCOS) who all tend to have increased LH bioactivity.
Background information: An important role of LH is to promote male androgen hormone (testosterone, androstenedione and DHEA) production by ovarian connective tissue (stroma or theca) that surrounds follicles. While androgens (predominantly testosterone) represent the building blocks from which follicle granulosa cells manufacture estrogen and are thus essential for optimal follicular growth and egg development, too much LH activity can lead to over-production/exposure to ovarian androgens which might compromise follicular/egg development. Accordingly, when it comes to older women and those DOR and PCOS who tend to have excessive LH-induced ovarian testosterone, it is (in my opinion) essential to maintain LH activity at a subliminal level. Thus LH suppression needs to be in place from the very start of COS…not much later as when antagonist suppression is commenced 6-8 days into the COS process. Accordingly, I believe that GnRH antagonist treatment should be commenced from the very initiation of ovarian stimulation…and that is the concept upon which the agonist/antagonist conversion protocol (A/ACP) is based….see below.
Bear in mind that the main reason for using antagonist suppression is to avoid the “Premature LH Surge”. This is a condition where high ovarian LH activity propagates androgen-induced “follicular exhaustion” and egg dysmaturity. The term “premature LH surge” is a misnomer since it does not involve a sudden “surge” or sporadic rise in LH. In actuality it occurs as a steady rise in LH activity (a “staircase effect”) which elicits a progressive increase in ovarian stromal androgens that ultimately exhausts follicle development and compromises egg “competency”. A more accurate term might be “premature luteinization.” Such poorly developed eggs will often respond to the hCG trigger by becoming aneuploid (a numerical chromosomal abnormality
Thus, trying to avoid “premature luteinization” by administering GnRH antagonist 6-8 days into the COS cycle, is like” shutting the gate after the horse has already left the stable”.
The long pituitary down-regulation COS protocol:
Here, administration of a GnRH-agonist (Lupron, Superfact, and Buserelin) several days before COS is initiated, expunges all LH from the pituitary gland, exhausting it of reservoired LH. Thereupon, agonist administration is continued until the hCG “trigger”. In this way, developing follicles and eggs are protected throughout COS, from over-exposure to LH-induced androgens…thereby avoiding “premature luteinization”. In my opinion, this approach is ideally suited to younger women who have normal LH, normal or increased ovarian reserve (e.g. those with PCOS) and those who have DOR. The downside of this approach is that the GnRHa (Lupron/Buserelin) can competitively bind with ovarian follicle stimulating hormone (FSH) receptors and suppress ovarian response to gonadotropins, something that is more likely to occur with older women and those who have DOR. I introduced the Agonist/Antagonist Conversion Protocol (A/ACP) more than 15 years ago to try and counter this effect.
The agonist/antagonist conversion protocol (A/ACP):
With the A/ACP, GnRH antagonist (Ganirelix, Cetrotide, and Orgalutron) is administered by daily injection from the onset of COS. The A/ACP COS-cycle is launched with the woman coming off a monophasic birth control pill that was administered starting in the 1st 5 days of the preceding cycle and continued for at least 10 days. The BCP is then overlapped with an agonist (e.g. Lupron/buserelin) for three days, whereupon the BCP is stopped and the agonist (Lupron/buserelin) is continued until the onset of menstruation. At or around this point, the agonist (Lupron/Buserelin) is supplanted by an antagonist (Cetrotide/Ganirelix/Orgalutron) and concurrently COS is initiated using an FSH-dominant bias (mainly Follistim/Gonal-F/ Puregon + a small dosage of a menotropins such as Menopur). The combined antagonist/gonadotropin therapy is continued until the hCG trigger. For the reasons cited above, I prescribe some form of the A/ACP for my older IVF patients and those with DOR. ]
A/ACP with estrogen priming: The A/ACP can be modified for women with very severe DOR through incorporation of “estrogen priming”. We have reported on the fact that the administration of intramuscular estradiol starting about a week prior to commencement of COS. This often markedly enhances ovarian response (presumably by “estrogen priming” enhancing the sensitivity of ovarian FSH-receptors).
There is one draw-back to the use of the A/ACP. This is the fact that prolonged administration of GnRH antagonist throughout the stimulation phase of the COS cycle compromises the predictive use of serial plasma estradiol measurements as an indication of ovarian response to COH. The blood estradiol levels tend to be much lower in comparison with cases where GnRHa alone is used.The reason for the lower blood concentration of estradiol seen with prolonged exposure to GnRH-antagonist might be due to the result of subtle, antagonist-induced alterations in the configuration of the estradiol molecule, such that currently available commercial test used to measure estradiol levels are rendered less sensitive/specific. Accordingly, when the A/ACP protocols are employed, we rely much more heavily on the measurement of follicle growth by ultrasound than on the estradiol levels. Because of this downside, I refrain from using this approach in “high responders” who may be at risk of developing of severe ovarian hyperstimulation syndrome (OHSS) and in whom the accurate measurement of plasma estradiol plays a very important role in the safe management of their COS cycles.
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
•Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
•Why did my IVF Fail?
Please call or email Julie Dahan, my patient concierge. She will guide you on how to set up an in-person or Skype consultation with me. You can reach Julie at on her cell phone or via email at any time:
Julie Dahan
•Email: Julied@sherivf.com
•Phone: 702-533-2691
?800-780-7437
Geoff Sher
What size do you recommend follicles to be at trigger?
Several >18mm and 50% >15mm.
Geoff Sher
Dear Dr Sher,
Do you think it is necessary to increase the dosage of stimulation drugs after introduction of cetrotide (antagonist)?
Will follicles continue to mature after introduction of the antagonist on a short protocol?
Not necessary. I usually reduce the dosage on day 3 of stimulation.
Geoff Sher