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 dr sher how are you
thak you aswering all our question.
i recently change my ivf doctor. allways puregon and orgalutron were my medicines.. amd i strated 2nd or 3th of my period. this doctor said after ovulation this month around cd15 he is going to check my uterus and ovary and start estrofem to ensure me eggs to be same size.. is it ok? and after ngs test i am going to have FET. he suggested natural cycles no estrofem etc.. because he said abortus ratio is low by this way (i had 2 abortions beace heartbeat stoped) but despite of my uterin lining and all other stuff ate normal i rejected this natural thing because i am 43 years old.. what do you think?
Hi
I had frozen transfer done 01/10. My first beta today was 52. Any reason to panic? My next is in 2 days.
We need to wait to see if it doubles. That is what it will take.
Good luck!
Geoff Sher
Hello Dr Sher.
We just completed an IVF cycle: Five eggs were retrieved, two were mature, and zero fertilized.
I’m 41 w/ day-three AFC of 12, AMH of 1.5, and FSH of 7.7. I eat right and exercise regularly. I do not drink coffee or alcohol, and have never smoked. My thyroid levels are normal range. I take CoQ10, omegas, zinc, D, E, folic acid, etc. (I do not take DHEA supplements or maca, however.)
The protocol used consisted of estradiol, beginning one-week after LH surge, through menses. Then, on cycle day 3, beginning GonalF 450IU in the evening, adding Cetrotide 0.25 mg and Novarel 4IU, beginning on cycle day 7, through hCG trigger. The follicle sizes the day before trigger were 19.0, 15.5, 14.5, 13.0, 11.5, 10.0, and 9.0 on the right and 21.5 and 21.0 on the left. Trigger was with Novarel 10000IU intramuscular, 35 hours prior to scheduled retrieval time.
During the two previous IUI cycles, with letrozole 7.5 mg, I easily produced four follicles of good size, though the cycles did not result in pregnancy. (We found out, later, during the mock transfer, that I have uterine polyps. This was thought to be the reason for the failed IUIs. They will be removed, after banking embryos, and a later FET will take place in the spring.)
My husband is 51 w/ normal SA, although his morphology scores are on the low end. We have not had a DNA fragmentation test done on his sperm. He did practice recurrent ejaculation every 24 hours the week of retrieval, and ejaculated 24 hours prior to collection. Fertilization was performed by ICSI.
We are disheartened by the failed first retrieval cycle, and are preparing to begin a second retrieval cycle. Do you have any advice to offer?
Thanks so very much for your time.
Sincerely,
Marie Ziegfeld
Dr Sher
I am preparing to transfer an abnormal (non mosaic embryo) that is a trisomy 7, hoping that it is an “undiagnosed mosaic”. It is a 4AA. I know you have encouraged this approach in patients who have few other options. My question is– could you share any data you know about, or even just your own personal experience, about specific healthy live births from PGS NGS “abnormal” biopsies. How come there is nothing published on this?!
There is not enough data out there to use in order to answer your question authoritatively. Moreover, Complete trisomy 7 has never been reported in a liveborn child.
So here is my opinion, for what it is worth……for what it is worth. Since it is not possible to say with certainty that such an embryo that only has one additional chromosome on position #7 is not mosaic. Thus I personally would transfer. A trisomy 7 embryo, even if it implants , will only do so temporarily and then likely be lost through miscarriage. So what do you have to lose. Notwithstanding this, I would encourage you that if a viable pregnancy occurs,m to have an amniocentesis done for safety sake.
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 preimplantation embryo development and represents a major cause of early pregnancy loss. About a decade ago, I and my associate, Levent Keskintepe PhD 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.”
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 normal (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 likely 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 reliably differentiate between these two varieties of aneuploidy would potentially be of considerable clinical value. The recent introduction of a variety of preimplantation genetic screening (PGS) known as next generation gene sequencing (NGS) has vastly improved the ability to reliably and accurately karyotype embryos and thus to diagnose embryo “mosaicism”.
The ability of mosaic embryos to autocorrect is influenced by the stage at which the condition is diagnosed as well as the percentage of mosaic cells. Many embryos diagnosed as being mosaic while in the earlier cleaved state of development, subsequently undergo autocorrection to the euploid state (normal numerical chromosomal configuration) during the process of undergoing subsequent mitotic cell to the blastocyst stage. Similarly, mosaic blastocysts can also undergo autocorrection after being transferred to the uterus. The lower the percentage of mosaic cells in the blastocyst the greater the propensity to autocorrect and propagate chromosomally normal (euploid) offspring. By comparison, a blastocyst with 10% mosaicism could yield a 30% healthy baby rate with 10-15% miscarriage rate, while with >50% mosaicism the baby rate is roughly halved and the miscarriage rate double.
Aneuploidy involves the addition (trisomy) or subtraction (monosomy) of one or part of one chromosome in any 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 several pairs (i.e. complex aneuploidy). Aside from monosomy involving the absence of the y-sex chromosome (i.e. XO) which can result in a live birth (Turner syndrome) of a compromised baby, virtually all monosomies involving autosomes (non-sex chromosomes) are likely to be lethal and will rarely result in viable offspring. Some autosomal meiotic aneuploidies, especially trisomies 13, 18, 21, can propagate viable and severely chromosomally defective babies. 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 as stated, mitotic aneuploidy (“mosaicism) can autocorrect, yielding healthy offspring. Most complex aneuploidies are meiotic in origin and will thus almost invariably fail to propagate viable pregnancies.
Since certain “mosaic” meiotic aneuploid trisomy embryos (e.g. trisomies 13, 18, & 21) can potentially result in aneuploid concepti. For this reason, it is my opinion that unless the woman/couple receiving such embryos is willing to commit to terminating a resulting pregnancy found through amniocentesis or chorionic villus sampling (CVS) to be so affected, she/they are probably best advised not to transfer have them transferred to the uterus. Embryos harboring other autosomal mosaic trisomic embryos, should they not autocorrect in-utero will hardly ever produce a baby and as such there is hardly any risk at all…in transferring such embryos. However, it is my opinion that in the event of an ongoing pregnancy, amniocentesis or CVS should be performed to make certain that the baby is euploid. Conversely, when it comes to mosaic autosomal monosomy, given that virtually no autosomal monosomy embryos are likely to propagate viable pregnancies, the transfer of such mosaic embryos is virtually risk free. Needless to say, in any such cases , 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 (amniocentesis/CVS) 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.
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.
•Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
•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.
•Hereditary Clotting Defects (Thrombophilia)
•Blastocyst Embryo Transfers done 5-6 Days Following Fertilization are Fast Replacing Earlier day 2-3 Transfers of Cleaved Embryos.
•Embryo Transfer Procedure: The “Holy Grail in IVF.
•Timing of ET: Transferring Blastocysts on Day 5-6 Post-Fertilization, Rather Than on Day 2-3 as Cleaved Embryos.
•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.
•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 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
Started IVF last Dec at at 42.5 . Married late in life, husband had radical prostatectomy. Using TESE sperm.
BMI is 35. AMH was 2.5.
All cycles had no “priming” — I’m not even sure what that is. Sometimes I was on birth control leading up to a cycle –seemed to have my worst cycles when they had me on the pill first. Every cycle ran about 9 days with 300 Follistim, 150 menopur, and Ganirelex starting a few days in.
First IVF — retrieved 9 eggs, 7 mature, 6 fertilized, 2 embryos still alive on day 5, 1 tested PGS normal frozen
Second IVF — retrieved 15 eggs, 13 mature, 12 fertilized, 4 alive on day 5, 1 PGS tested as a mosaic (others abnormal)
Third IVF — retrieved 12 eggs, 8 mature, 6 fertilized, 1 embryo alive on day 5, it was a PGS normal!
Fourth IVF — retreived 17, 13 mature, 12 fertilized, all of them grew slowly so they grew them out to day 6, two alive, none normal
Transfered the normal one from first cycle, did not take. ERA offered after transfer, showed I was prereceptive on day 5. Wish they had offered me the test before transfer. Decided to keep doing retrievals while I still had ability to do so. DId clomid challenge test because of insurance company — FSH 5.8 on day 3, after clomid was 4.5. So we continued….
Change in protocol — 450 gonal-f, 50 low-dose HCG
Fifth cycle — retrieved 13 (2 days earlier than previous cycles), only 5 were mature, 4 fertilized, 2 alive on day 5, none PGS normal
Same protocol as above (but tried 10000 HCG for trigger for the first time (after always doing 5000)
Sixth cycle — retrieved 9 in typical time frame (they told me I had 13 on ultrasound), 7 were mature, 6 fertilized, all grew super slowly and nothing could be biopsied even by day 6
RE recommending donor egg lined up in case while offering one more retrieval using lower dose meds, also telling me to do calorie deprivation and/or NO carb diet.
I feel like my RE doesn’t really have any ideas of what to do, just giving me basically the same protocol each time and even though I had PGS normals 6 months ago, telling me now I shold do donor eggs.
I’m also wondering since many cycles were slow-growers if I should transfer on day 3 and forget pgs testing.
First, it is important to recognize that at 42Y you are already at a disadvantage with regard to egg “competency”. Second, see the article below on use of BCP in IVF and you will realize that you will only have suppression on the pill if you do not overlap with Lupron. Third, in my opinion. 5,000U hCG is too low. It needs to be 10,000U. Finally, I do not believe in the value of ERA.
The older a woman becomes, the more likely it is that her eggs will be chromosomally/genetically “incompetent” (not have the potential upon being fertilized and transferred, to result in a viable pregnancy). That is why, the likelihood of failure to conceive, miscarrying and of giving birth to a chromosomally defective child (e.g. with Down Syndrome) increases with the woman’s advancing age. In addition, as women age beyond 35Y there is commonly a progressive diminution in the number of eggs left in the ovaries, i.e. diminished ovarian reserve (DOR). So it is that older women as well as those who (regardless of age) have DOR have a reduced potential for IVF success. Much of this is due to the fact that such women tend to have increased production of LH biological activity which can result in excessive LH-induced ovarian male hormone (predominantly testosterone) production which in turn can have a deleterious effect on egg/embryo “competency”.
While it is presently not possible by any means, to reverse the age-related effect on the woman’s “biological clock, certain ovarian stimulation regimes, by promoting excessive LH production (e.g. short agonist/Lupron- “flare” protocols, clomiphene and Letrozole), can make matters worse. Similarly, the amount/dosage of certain fertility drugs that contain LH/hCG (e.g. Menopur) can have a negative effect on the development of the eggs of older women and those who have DOR and should be limited.
I try to avoid using such protocols/regimes (especially) in older women and those with DOR, favoring instead the use of the agonist/antagonist conversion protocol (A/ACP), a modified, long pituitary down-regulation regime, augmented by adding supplementary human growth hormone (HGH). I further recommend that such women be offered access to embryo banking of PGS (next generation gene sequencing/NGS)-selected normal blastocysts, the subsequent selective transfer of which by allowing them to to capitalize on whatever residual ovarian reserve and egg quality might still exist and thereby “make hay while the sun still shines” could significantly enhance the opportunity to achieve a viable pregnancy
Please visit my new Blog on this very site, http://www.DrGeoffreySherIVF.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
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