Ask Our Doctors – Archive
Our Medical Directors are outstanding physicians that you will find to be very personable and compassionate, who take care to ensure that you have the most cutting-edge fertility treatments at your disposal. This is your outlet to ask your questions to the doctors.
Hello Dr. Sher,
I am getting ready for FET and my acupuncturist recommended to stop eating dairy and red meat, since he thinks it causes inflammation and overactive immune system, which in turn can make my body reject the embryo. Do you shy with that? Is there a certain diet you would recommend during FET?
Thank you,
Sophia
Sorry, one more question. My doctor put me on Metformin for insulin resistance, claiming that it helps with egg quality and implantation. I don’t have PCOS. What is your point of view on using Metformin for infertility?
Very respectfully, I see no rational justification or basis for such advice.
Geoff Sher
Hello Dr. Sher,
I hope you’re having a happy holiday season!
My question is about lead follicle triggering and PGS results.
I have had 3 IVF cycles. 39 years old, good ovarian reserve, no problems with uterus, I’ve had all the tests and do have MTHFR gene and Factor II (not Factor V). I can to seek IVF because I had two miscarriages back to back. My husband is 43 and has no issues with sperm.
My first cycle was with a doctor who triggered me at the standard protocol of 18-20mm. They retrieved 11 eggs and most arrested immediately. We had two that survived to blastocyst, but were later pronounced abnormal.
We then changed doctors and upon reviewing the protocol of the first doctor, our new doctor mentioned that by observing the attretic rate of the eggs that my cycle was “over cooked” and I needed to be triggered earlier and at a smaller size.
Our second IVF cycle (with our new doctor) produced 34 retrieved eggs, 15 fertilized, and four went to blastocyst stage and PGS testing. Those were still all abnormal.
Our doctor observed the rate of attrition and said that we would go down in size again, another millimeter, of triggering the lead follicle at 15-16. This resulted in 44 eggs retrieved, 27 were mature, 22 fertilized, and 6 survived to blastocyst and were tested for PGS. Having read your comments on abnormal embryos we wanted to proceed with caution but not automatically reject embryos that might self correct. Our IVF doctor believes there were yet again signs of post maturity and that I may need to be triggered at an unusually small size (I think we are getting to 14-15mm now) if I were rock do another cycle. We have emptied our savings as it is -this is all out of pocket. I don’t know if I can afford to do another cycle and am wondering if we have some embryos with potential.
December 2017 cycle:
#1 complex abnormal
#2 normal
#3 monosomy 18
#4 monosomy 17, monosomy 21
#5 Mosaic monosomy 9 (low percentage of mosaicism: 20-40%), Trisomy 13
#6 Partial Trisomy 16pter-p12.2, Mosaic Trisomy 19
Apparently our October 2017 cycle mosaic embryos were high level mosaics (40-80%) so I am asuming those are no good.
My October cycle resulted in:
#1 complex abnormal
#2 Trisomy 9
#3 Mosaic monosomy 6, Mosaic monosomy 18 (high level Mosaic, 40-80%)
#4 Mosaic Trisomy 19 (high level Mosaic, 40-80%)
So Dr Sher, are any of these embryos worth saving? Thank you very much for your respected opinion.
Those with single chromosome monosomies such as those three with monosomy 18, 2 with trisomy 9, 3 with trisomy 19 could be “mosaic”. But there is in my opinion no reliable, clinically applicable method by which to diagnose mosaicism.
Human embryo development occurs through a process that encompasses reprogramming, sequential cleavage divisions and mitotic chromosome segregation and embryonic genome activation. Chromosomal abnormalities may arise during germ cell and/or pre-implantation embryo development, and represents a major cause of early pregnancy loss. About a decade ago, I and an associate, Levent Keskintepe Ph.D were the first to introduce full embryo karyotyping (identification of all 46 chromosomes) through preimplantation genetic sampling (PGS) as a method by which to selectively transfer only euploid embryos (i.e. those that have a full component of chromosomes) to the uterus. We subsequently reported on a 2-3 fold improvement in implantation and birth rates as well as a significant reduction in early pregnancy loss, following IVF. Since then PGS has grown dramatically in popularity such that it is now widely used throughout the world.
Most IVF programs that offer PGS services, require that all participating patients consent to all their aneuploid embryos (i.e. those with an irregular quota of chromosomes) be disposed of. However, there is now growing evidence to suggest that following embryo transfer, some aneuploid embryos will in the process of ongoing development, convert to the euploid state (i.e. “autocorrection”) and then go on to develop into chromosomally normal offspring. In fact, I am personally aware of several such cases occurring within our IVF network. So clearly , summarily discarding all aneuploid embryos as a matter of routine we are sometimes destroying some embryos that might otherwise have “autocorrected” and gone on to develop into normal offspring.
Thus by discarding aneuploid embryos the possibility exists that we could be denying some women the opportunity of having a baby. This creates a major ethical and moral dilemma for those of us that provide the option of PGS to our patients. On the one hand, we strive “to avoid knowingly doing harm” (the Hippocratic Oath) and as such would prefer to avoid or minimize the risk of miscarriage and/or chromosomal birth defects and on the other hand we would not wish to deny patients with aneuploid embryos, the opportunity to have a baby.
The basis for such embryo “autocorrection” lies in the fact that some embryos found through PGS-karyotyping to harbor one or more aneuploid cells (blastomeres) will often also harbor chromosomally normal (euploid) cells (blastomeres). The coexistence of both aneuploid and euploid cells coexisting in the same embryo is referred to as “mosaicism.” As stated, some mosaic embryos will In the process of subsequent cell replication convert to the normal euploid state (i.e. autocorrect)
It is against this background, that an ever increasing number of IVF practitioners, rather than summarily discard PGS-identified aneuploid embryos are now choosing to cryobanking (freeze-store) certain of them, to leave open the possibility of ultimately transferring them to the uterus. In order to best understand the complexity of the factors involved in such decision making, it is essential to understand the causes of embryo aneuploidy of which there are two varieties:
1.Meiotic aneuploidy” results from aberrations in chromosomal numerical configuration that originate in either the egg (most commonly) and/or in sperm, during preconceptual maturational division (meiosis). Since meiosis occurs in the pre-fertilized egg or in and sperm, it follows that when aneuploidy occurs due to defective meiosis, all subsequent cells in the developing embryo/blastocyst/conceptus inevitably will be aneuploid, precluding subsequent “autocorrection”. Meiotic aneuploidy will thus invariably be perpetuated in all the cells of the embryo as they replicate. It is a permanent phenomenon and is irreversible. All embryos so affected are thus fatally damaged. Most will fail to implant and those that do implant will either be lost in early pregnancy or develop into chromosomally defective offspring (e.g. Down syndrome, Edward syndrome, Turner syndrome).
2.“Mitotic aneuploidy” occurs when following fertilization and subsequent cell replication (cleavage), some cells (blastomeres) of a meiotically euploid early embryo mutate and become aneuploid. This is referred to as mosaicism. Thereupon, with continued subsequent cell replication (mitosis) the chromosomal make-up (karyotype) of the embryo might either comprise of predominantly aneuploid cells or euploid cells. The subsequent viability or competency of the conceptus will thereupon depend on whether euploid or aneuploid cells predominate. If in such mosaic embryos aneuploid cells predominate, the embryo will be “incompetent”). If (as is frequently the case) euploid cells prevail, the mosaic embryo will be “competent” and capable of propagating a normal conceptus.
Since some mitotically aneuploid (“mosaic”) embryos can, and indeed do “autocorrect’ while meiotically aneuploid embryos cannot, it follows that an ability to differentiate between these two varieties of aneuploidy would be of considerable clinical value. And would provide a strong argument in favor of preserving certain aneuploid embryos for future dispensation.
Aneuploidy, involves the addition (trisomy) or subtraction (monosomy) of one chromosome in a given pair. As previously stated, some aneuploidies are meiotic in origin while others are mitotic “mosaics”. Certain aneuploidies involve only a single, chromosome pair (simple aneuploidy) while others involve more than a single pair (i.e. complex aneuploidy). Aside from monosomy involving absence of the y-sex chromosome (i.e. XO) which can resulting in a live birth (Turner syndrome) all monosomies involving autosomes (non-sex chromosomes) are lethal and will not result in viable offspring). Some autosomal meiotic aneuploidies, especially trisomies 13, 18, 21, can progress to viable, but severely chromosomally defective babies. All other meiotic autosomal trisomies will almost invariably, either not attach to the uterine lining or upon attachment, will soon be rejected. All forms of meiotic aneuploidy are irreversible while mitotic aneuploidy (“mosaicism) often autocorrects in the uterus. Most complex aneuploidies are meiotic in origin and will almost invariably fail to propagate viable pregnancies.
There is presently no microscopic or genetic test that can reliable differentiate between meiotic and mitotic aneuploidy. Notwithstanding this, the fact that some “mosaic” embryos can autocorrect in the uterus, makes a strong argument in favor of transferring aneuploid of embryos in the hope that the one(s) transferred might be “mosaic” and might propagate viable healthy pregnancies. On the other hand, it is the fear that embryo aneuploidy might result in a chromosomally abnormal baby that has led many IVF physicians to strongly oppose the transfer of any aneuploid embryos to the uterus.
While certain meiotic aneuploid trisomies (e.g. trisomies 13, 18, & 21) can and sometimes do result in chromosomally defective babies, no other meiotic autosomal trisomies can do so. Thus the transfer of trisomic embryos in the hope that one or more might be mosaic, should exclude the use of embryos with trisomies 13, 18 or 21. Conversely, no autosomal monosomic embryos are believed to be capable of resulting in viable pregnancies, thereby making the transfer of autosomally monosomic embryos, in the hope that they are “mosaic”, a far less risky proposition. Needless to say, if such action is being contemplated, it is absolutely essential to make full disclosure to the patient (s) , and to insure the completion of a detailed informed consent agreement which would include a commitment by the patient (s) to undergo prenatal genetic testing aimed at excluding a chromosomal defect in the developing baby and/or a willingness to terminate the pregnancy should a serious birth defect be diagnosed.
My advice is to use a long pituitary down regulation protocol starting on a BCP, and overlapping it with Lupron 10U daily for three (3) days and then stopping the BCP but continuing on Lupron 10u daily (in my opinion 20U daily is too much) and await a period (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 and simultaneously, the Lupron dosage is reduced to 5U daily to be continued until the hCG (10,000u) trigger. An FSH-dominant gonadotropin such as Follistim, Puregon or Gonal-f daily is started with the period for 2 days and then the gonadotropin dosage is reduced and a small amount of menotropin (Menopur—no more than 75U daily) is added. This is continued until US and blood estradiol levels indicate that the hCG trigger be given, whereupon an ER is done 36h later. I personally would advise against using Lupron in “flare protocol” arrangement (where the Lupron commences with the onset of gonadotropin administration.
I strongly recommend that you visit https://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.
• Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas
• Should IVF Treatment Cycles be provided uninterrupted or be Conducted in 7-12 Pre-scheduled “Batches” per Year
• A personalized, stepwise approach to IVF
• “Triggering” Egg Maturation in IVF: Comparing urine-derived hCG, Recombinant DNA-hCG and GnRH-agonist:
. Staggered IVF
•Staggered IVF with PGS- Selection of “Competent” Embryos Greatly Enhances the Utility & Efficiency of IVF.
If you are interested in seeking my advice or services, I urge you to contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com You can also apply online at http://www.SherIVF.com .
*FYI
The 4th edition of my newest book ,”In Vitro Fertilization, the ART of Making Babies” is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.
Geoffrey Sher MD
Is it ok to do back to back ivf cycles? I just had a failed long protocol. So could I try the short protocol on my next period? Do doctors advise a 3 month wait for physical or emotional reasons. Emotionally I am fine but wouldn’t do it if physically it would be a bad idea.
In my opinion, it is advisable to rest your ovaries for at least 1 cycle before another attempt!
Geoff Sher
Hi Dr Sher, why do you routinely prescribe dexamethasone to IVF patients on the day they start their IVF cycles? Is it in preparation for implantation or is it to help reduce cytokine levels in follicular fluid?
In your opinion, is there a difference between dexamethasone and prednisone? is one better than the other? I was prescribed them but was not keen, but i notice you use them so now i am keen, but is it too late to start at the time you start stims? or must it be started weeks before?
It is an immune modulator which in my opinion, enhances implantation.
Geoff Sher
Dear Dr. Sher,
Thank you so much for generously sharing your expertise! I purchased your book and I am currently almost halfway done reading. I am so excited about everything that I’m learning, but it’s bringing up so many new questions for me as well! 🙂
I had previously posted a question about BCP and potential concern regarding suppressing ovarian response. My doctor no longer prescribes Lupron. She is open to starting a cycle without BCP, per my request (as my first cycle with BCP resulted in poor and uneven follicle growth). Would you advise against starting a cycle without first doing a suppression of some type (e.g., BCP & Lupron or estrogen priming)? I also have several fibroids (my largest recently doubled in size, likely due to the hormones with an unsuccessful pregnancy that ended in a first trimester miscarriage)- so, I’m guessing that estrogen priming would not be recommended?
Is there a way to tell if there is already uneven recruitment of follicles at a baseline ultrasound? Thereby providing a method to determine if it is OK to move forward with the cycle or if it would be problematic to move on to stims?
I look forward to hearing your thoughts! 🙂
You can start the cycle without a BCP launch. However, in my opinion, if you do so it is advisable to start the Lupron about 1 week after ovulation (usually starting 1 week prior to anticipated menstruation in regularly ovulating women or roughly on day 21 of the cycle. Then continuing until the period stats at which time you either continue on Lupron until the hCG trigger or switch to an antagonist (Ganirelix/Cetrotide or Orgalutron). It is not possible to recognize uneven follicle recruitment.
Geoff Sher