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.
I have a mosaic segmental gain on chromosome x xq25-q28 5cb
And an abnormal monosomy 2 5cc
Woukd you suggest transferring both of these together they are frozen in same straw or what are your thoughts on transferring the abnormal monosomy 2?
Thank you
In my opinion, the monosomy-2 embryo is the one that should be preferentially transfered.
Geoff Sher
Dear Dr. Sher,
I’ve been reading some of your articles and I was wondering, if I could ask you about a protocol I’m about to start, please. I’m 46 years old and still have a good ovarian reserve. The protocol suggests 150 IU Bemfola combined with 0.25mg Cetrotide and triggering with 250mcg Ovitrelle.
I’ve done this protocol 3 times in the last 5 years and always had between 6-21 eggs to freeze per cycle. Unfortunately, when I came to use the eggs recently only 3 embryos developed into blastocysts. 2 of them were multiply anapleud and one was anapleud, monosomy 21. I’m aware of decreasing egg quality with age but to increase my chances for the upcoming cycle, would you recommend increasing the amount of the trigger?
Many thanks
Stefanje
Hi Stefanji,
Very respectfully, at 46y of age, regardless of your ovarian reserve, your chance of successful IVF with own eggs is VERY small. I would suggest egg donation. However, of in spite of this, you insist upon trying with own eggs, I would recommend a different approach to stimulation.
consider the following: 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, and/or biological activity, of LH. This can result in excessive ovarian male hormone (predominantly testosterone) production. This 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 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
I urge you to set up a Skype or an in-person consultation with me. To do so, simply call 1-800-780-7437 (if you reside in the U.S.A or Canada) or 702-533-2691 (if you reside elsewhere). Alternatively you can enroll online by going to the home page of the Sher-IVF website, http://www.SherIVF.com where, upon completing an enrollment form), you will immediately be eligible to download my new book, “Recurrent Pregnancy Loss (RPL) and unexplained IVF Failure: The Immunologic Link”, free of charge.
Geoffrey Sher MD
Hi Dr. Sher,
How much does egg freezing reduce the changes of good embryos being created in some years instead of embryo freezing?
Since the birth of the 1st “frozen egg baby” in the mid 1980’s, fewer than 3,000 births resulting from the fertilization of thawed eggs have been reported, worldwide. Compare this to > 4.5 million IVF babies born worldwide in the same time period, and > 2,000,000 babies resulting from the transfer of frozen embryos. Harvesting eggs for freezing typically involves giving a woman fertility drugs to stimulate her ovaries to produce multiple eggs, and then harvesting those eggs from her ovaries using ultrasound guided needle aspiration. In average cases (where the mean age of the woman is <36y), it takes about one cycle of fertility drug administration to harvest 10 to 15 eggs.
Presently, in cases where embryos derived from the eggs of women under 35years are frozen, survive the thaw and are transferred to the uterus, the birth rate per embryo transfer is about 35%. In those cases where the eggs were derived from women between 35y and 40y of age, the birth rate is about 25-30% per embryo transfer (ET) procedure. For women of >40y the comparable birth rate per ET is about 10-15%.
While on the face of it, this sounds like a reasonable outcome (especially when it comes to younger women), it should be borne in mind that many eggs do not survive the freeze/thaw and a significant number of those that survive, fail to fertilize. Moreover, of those that do fertilize, a significant percentage fail to progress to progress to the expanded blastocyst stage of development (regarded as being the ideal stage for ET). That is why depending on their age, women who elect to bank their eggs for fertility preservation (FP) are encouraged to undergo as many egg retrieval procedures as needed in to bank 12-20 eggs before having some degree of confidence, of ultimately being rewarded with a live birth. Since the percentage of eggs that are chromosomally normal (euploid) and “competent”) declines with advancing age, the older the woman becomes, the greater will be the number of eggs (and egg retrieval procedures) needed. .
The ability to accurately identify eggs that are numerically chromosomally normal (“euploid”) and are thus the ones most likely, upon being fertilized and transferred to the uterus, to propagate a live birth is of particularly relevance. Given that in young women, less 50% of eggs are euploid and by the mid-forties, that percentage drops to below <10%, it follows that potential for a successful outcome using frozen eggs largely hinges on their chromosomal integrity (“competency”).
In October 2008, my associate, Levent Keskintepe PhD and I became the first to report (Journal, “Reproductive Biomedicine Online”) on a process that allows for a several fold improvement in the baby-rate per (frozen) egg. It relies upon the selective storage and dispensation of chromosomally (karyotypically) normal (euploid-“competent”) eggs. The process we described and reported on, relied upon removing the 1st polar body from mature (MII) eggs for the performance of preimplantation genetic sampling (PGS) using metaphase- Comparative Genomic Hybridization (mCGH), followed by the selective storage of only those found to have all 23 chromosomes (i.e. euploid) intact. This resulted in a baby rate of 27% per frozen egg (a 3-fold improvement), an 85%+ , freeze/thaw survival rate, an 80% successful fertilization rate and > 60% birth rate following the transfer of 1-2 two blastocysts. While highly effective, this complex process is currently not cost-effective and as such, unfortunately did not gain mainstream acceptance.
Geoff Sher
Very respectfully….In my opinion , to use clomiphene (in any arrangement) in older women, especially in women (like you) who, regardless age have diminished ovarian reserve (DOR)is suboptimal and potentially harful to egg development and thus to embryo “competency”. It markedly increases pituitary LH output resulting in increased stromal ovarian testosterone production which if in excess, compromises egg/embryo quality. Using Ovidrel for the trigger is OK as long as you receive a high enough dosage. One vial (250mcg) is in my opinion too little to evoke optimal egg maturational division (meiosis) and as a result the percentage of chromosomally abnormal eggs (aneuploid) increases. You need double that dosage (i.e. 500mcg).
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, and/or biological activity, of LH. This can result in excessive ovarian male hormone (predominantly testosterone) production. This 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
I urge you to set up a Skype or an in-person consultation with me. To do so, simply call 1-800-780-7437 (if you reside in the U.S.A or Canada) or 702-533-2691 (if you reside elsewhere). Alternatively you can enroll online by going to the home page of the Sher-IVF website, http://www.SherIVF.com where, upon completing an enrollment form), you will immediately be eligible to download my new book, “Recurrent Pregnancy Loss (RPL) and unexplained IVF Failure: The Immunologic Link”, free of charge.
Geoffrey Sher MD
37 yr old, retroverted uterus, one copy of mthfr gene. 5 day blastocyst used….all from 2 back to back cycles that were frozen. 2/14 3 embryos used for fet after 3 months of Lipton depot resulted in healthy single pregnancy. 12/16 2 embryos used for fet from when I was 32 yrs old with Intralipids and one heartbeat detected but by second ultrasound there was no heartbeat. Sent remains for testing which reveal normal chromosomes. 12/17 2 more embryos used for fet with baby aspirin, lovenox, and intralipids and negative. 8/18 Pregnancy using letrozole resulted in blighted ovum. Upcoming laparoscopy is scheduled. Not sure how to proceed with next fet.
It is important to re-evaluate all the factors that contribute to IVF success before going any further.
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
I urge you to set up a Skype or an in-person consultation with me. To do so, simply call 1-800-780-7437 (if you reside in the U.S.A or Canada) or 702-533-2691 (if you reside elsewhere). Alternatively you can enroll online by going to the home page of the Sher-IVF website, http://www.SherIVF.com where, upon completing an enrollment form), you will immediately be eligible to download my new book, “Recurrent Pregnancy Loss (RPL) and unexplained IVF Failure: The Immunologic Link”, free of charge.
Geoffrey Sher MD