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PGS IN IVF: Some embryos that test PGS- chromosomally abnormal can self- correct in the uterus: Are we wrongly discarding embryos that are capable of developing into healthy babies?

by Dr. Geoffrey Sher on January 11, 2016

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  an 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.” 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 practical 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 aneuploid embryos to the uterus.

Certain meiotic aneuploid trisomy embryos (e.g. trisomies 13, 18, & 21) can and sometimes do, result in aneuploid concepti. Thus, in my opinion, 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 such embryos . Other autosomal trisomy embryos will hardly ever produce viable euploid concepti and can thus, in my opinion be transferred in the hope that auto correction will occur in-utero. However, in all cases, and amniocentesis or CVS should be performed to make certain that the baby is euploid.  Conversely, no autosomal monosomy embryos are believed to be capable of resulting in viable pregnancies, thereby making the transfer of autosomal monosomy embryos, in the hope that they are “mosaic”, a far less risky proposition. Needless to say, if such action is being contemplated 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.

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119 comments

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  • Anna F - May 24, 2018 reply

    Dear Dr Sher
    Thank you so much for you wonderful article – it makes such a complex subject easier to understand. I am 35 yrs old and had 22 eggs collected however only 3 made it to day 6 testing. Of these 3 they are all reported as abnormal:
    1. Monosomy 13, 16
    2. Trisomy 6
    3. Monosomy 8
    I cannot believe they are all abnormal. Would you recommend I transfer any of these or shall I just dig deeper and find the money for more egg retrievals? Many thanks for your wonderful blog, I have read every word!

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - May 25, 2018 reply

    It is in my opinion worth transferring #2 & 3 in the hope that one or both are mosaic.

    Geoff Sher

  • Katy Morn - May 21, 2018 reply

    Dr. Sher, I have just turned 41 and have done three back to back egg retrieval cycles for banking. We got 18 embryos total and just found out that only 1 came back normal from PGS testing. We have 6 abnormal complex, 1 trisomy 22, 1 trisomy 9, 1 monosomy 10, 1 monosomy 22, 1 monosomy 20, and 6 more with both a monosomy and trisonomy defect. My doctor won’t transfer abnormal embryos so I’m going to try to find someone who will but want to see if any of these would be viable in your opinion. We have spent over $45,000 so far out of pocket and can’t go any further in debt with more cycles. Thank you.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - May 21, 2018 reply

    I would transfer those embryos that have single autosomal chromosomal aneuploidies (monosomy or Trisomy). However, in the event of a pregnancy, I would strongly advise either chorionic villus sampling and/or amniocentesis to rule out an aneuploidy-affected conceptus.

    Geoff Sher

  • Vanessa - May 16, 2018 reply

    I read your post and am in full support of patients having the option to transfer mosaics. What appalled me was your suggestion that couples be required to consent to testing of a pregnancy or agreement to terminate if the baby has issues.

    Your statement was: “Certain meiotic aneuploid trisomy embryos (e.g. trisomies 13, 18, & 21) can and sometimes do, result in aneuploid concepti. Thus, in my opinion, 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 such embryos.”

    I find it appalling that you find it acceptable to have a couple terminate these pregnancies. I think my friends with Down Syndrome would find your statement equally appalling.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - May 16, 2018 reply

    Sorry you feel that I “demand” that affected pregnancies be terminated and that our transfer of embryos that are deemed to be potentially “mosaic” is contingent upoin such an agreement. I did not say we would refuse to do a transfer such embryos f the patient objected to termination in the event that a pregnancy is associated with an aneuploid conceptus. Rather, what I said was that I advise termination in such cases. If any patient refuses to terminate an affected pregnancies…that is their choice. My position is that I feel duty bound to present options and advise how my conscience dictates.

    It is never my intention to offend anyone. My role is to provide information and advice, leaving the final decision up to the patient.

    Geoff Sher
    Geoff Sher

    Katy Morn - May 21, 2018 reply

    Thank you for the info Sir.:)

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - May 22, 2018 reply

    You are welcome Katy!

    Geoff Sher

  • Esther - May 12, 2018 reply

    Dear Dr Shear,

    I followed your advise regards PGS, results came back with 1 normal rated B.B. emerito what else should we be doing to improve implantation?

    Intralipids has been advised, steroids for natural killer cells would you advise anything else?

    My other 4 day 5 embryos had multiple missing chromosomes, none were mosaic are these alright to discard? Being 41 going onto 42.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - May 12, 2018 reply

    You need to discuss your treatment plan with your RE.

    In my opinion the embryos with complex abnormalities could be discarded but please 1st discuss with your RE.

    Geoff Sher

  • Ann - March 7, 2018 reply

    Dr. Sher, I am 32, my husband is 32. We had genetic testing done prior to starting IVF and the test came back fine. We were each a carrier of 1 disease individually, but it was not the same disease. I just went through my first round of IVF and received my PGS results. We have two embryo’s with the 46 chromosomes, but they are both showing a duplication in chromosome 7. The results read as follows: 46 XX (dup) 7 (q21)(q21) – the boy embryo read exactly the same. We are both going tomorrow to speak with a genetic counselor and to get tested to see if this is present in our chromosomes, but my question is this: whether this is or is not present, would this be safe (in your opinion) to transfer?

    Thank you!
    Ann

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - March 8, 2018 reply

    In my opinion, it could be a mosaic.

    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.

    Geoff Sher

    Louiza - May 7, 2018 reply

    Dear Dr Sher, my husband and I have been going through IVF for the last five years with recurring failures, firstly using my own eggs and then with a donor. Last year we managed to get two normal embryos from a donor cycle with my husband’s sperm and both pregnancies failed – one just before 10 weeks (the sack was too small for the baby) and the second at 6.5 weeks where the heart stopped beating or no reason. We have 2 embryos left, one complex abnormal (cell 6 M3) and one Mosaic Monosomy 18 (M1). We are considering transferring the latter but are scared of either miscarrying again (since it didn’t work with 2 normal embryos already) or risking a genetically harmed baby. We do not understand what mosaic monosomy 18 (m1) could mean and wanted to ask for your help – what would you advise?

    Thank you for your time.

    Warmly,
    Louiza

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - May 8, 2018 reply

    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

    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

  • Danielle - January 10, 2018 reply

    Dr Sher– thank you so much for your help. I have severe DOR and 3 miscarriages (one CP with euploid; others day 3). I am now 45 and have the following abnormals frozen from the past few years(NGS testing)– (I would really like to try these before moving to donor egg). My other ones are more complex abnormalities and not listed.
    –Known mosaic 4AA (5 day) monosomy 9, monosomy 21
    –Trisomy 7 4AA (5 day)– reportedly not mosaic on testing
    –4AA (5 day) monosomy 15, trisomy 2– reportedly not mosaic on testing
    –4AA (5 day) trisomy 14, trisomy 19– reportedly not mosaic on testing
    What do you think about transferring all/some of these? Thank you!

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - January 10, 2018 reply

    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.

    Geoff Sher

    Erika - January 17, 2018 reply

    Hello Dr. Sher, I am 37 and just learned that out of five day-5 embryos tested with NGS, four are aneuploid, and one is a high-level mosaic. Regarding the mosaic, the report says: del(2)(p 16.3-pter). What does this mean? Is there any hope for transferring this embryo? We cannot afford another round and are grasping at straws. Thank you in advance!

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - January 18, 2018 reply

    Hi Erika,

    I would need much more information to comment authoritatively. Please call 800-780-7437 and set up a Skype consultation with me to discuss in detail.

    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 an 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.” 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 practical 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 aneuploid embryos to the uterus.
    Certain meiotic aneuploid trisomy embryos (e.g. trisomies 13, 18, & 21) can and sometimes do, result in aneuploid concepti. Thus, in my opinion, 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 such embryos. Other autosomal trisomy embryos will hardly ever produce viable euploid concepti and can thus, in my opinion be transferred in the hope that auto correction will occur in-utero. However, in all cases, and amniocentesis or CVS should be performed to make certain that the baby is euploid. Conversely, no autosomal monosomy embryos are believed to be capable of resulting in viable pregnancies, thereby making the transfer of autosomal monosomy embryos, in the hope that they are “mosaic”, a far less risky proposition. Needless to say, if such action is being contemplated 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.

    Geoff Sher

  • Danielle - January 9, 2018 reply

    Hi Dr Sher. I recently completed my first round of IVF at 40. I conceived 3 children naturally in my 20’s but had a tubal at 28. I’m remarried now and would like a child with new husband. He has one from previous marriage as well. First round I had 14 retrieved, 11 fertilized, 8 tested blasts but 1 came back normal, 3 mosaic trisomy 16, a trisomy 17 and 3 with multiple abnormalities. The dr refuses to consider transferring the mosaics if the normal embryo transfer doesn’t work. He recommends another cycle since I produce an adequate amount of eggs but that’s not an option for me. Is there anything I can do or should I just leave it alone?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - January 9, 2018 reply

    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 an 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.” 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 practical 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 aneuploid embryos to the uterus.
    Certain meiotic aneuploid trisomy embryos (e.g. trisomies 13, 18, & 21) can and sometimes do, result in aneuploid concepti. Thus, in my opinion, 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 such embryos. Other autosomal trisomy embryos will hardly ever produce viable euploid concepti and can thus, in my opinion be transferred in the hope that auto correction will occur in-utero. However, in all cases, and amniocentesis or CVS should be performed to make certain that the baby is euploid. Conversely, no autosomal monosomy embryos are believed to be capable of resulting in viable pregnancies, thereby making the transfer of autosomal monosomy embryos, in the hope that they are “mosaic”, a far less risky proposition. Needless to say, if such action is being contemplated 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.

    Hope this helps!

    Geoff Sher

  • Esther - January 4, 2018 reply

    I recently had two round sessions of batching IVF resulting in 9 good quality embryos, 5, 8-9 cell and 2, 8-9 cell, 2 pre morula day 3 and frozen. I have had 2 failed ivf attempts with Day 3 transfers. Clinic offering PGS and PGD, have read your article shall I do these tests after thawing and growing to day 5? Or transfer those that make it to day 5?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - January 5, 2018 reply

    I would thaw..take to day 5 and then do PGS-biopsy.

    Geoff Sher

  • Dr. Geoffrey Sher

    Dr. Geoffrey Sher - December 23, 2017 reply

    I think this was a wise call on the part of your RE.

    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.

    Geoff Sher

  • Saravanan - December 20, 2017 reply

    we gone for 2 IVf cycle and got 3 blactocyst, after PGS 1 girl and 2 boy but all anuepliod…and we need a boy…the boy Emrayos results shows only one chromosome abnormality below,
    Embrayo no 6 (Chromosome no 12 shows PG(Partial gain)) and Embrayo no 8 (Chromosome no 15 shows G(Gain).
    Whether we can transfer these empryaos? if so which is best one? what are the risks involved?
    Your kind advise would a great help for me to take decison…please help me..

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - December 20, 2017 reply

    They could be “mosaic” and if so propagate a baby. Either or both could be tried!

    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 an 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.” 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 practical 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 aneuploid embryos to the uterus.
    Certain meiotic aneuploid trisomy embryos (e.g. trisomies 13, 18, & 21) can and sometimes do, result in aneuploid concepti. Thus, in my opinion, 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 such embryos. Other autosomal trisomy embryos will hardly ever produce viable euploid concepti and can thus, in my opinion be transferred in the hope that auto correction will occur in-utero. However, in all cases, and amniocentesis or CVS should be performed to make certain that the baby is euploid. Conversely, no autosomal monosomy embryos are believed to be capable of resulting in viable pregnancies, thereby making the transfer of autosomal monosomy embryos, in the hope that they are “mosaic”, a far less risky proposition. Needless to say, if such action is being contemplated 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.

    Geoff Sher

    Saravanan - December 22, 2017 reply

    Dear Doctor,
    Thanks for your detail reply. Actually bymistake i mentioned PGS in my previous message but actually done NGG(Next generation Genomic), Further, again i asked the lab for more details about aneuploid contribution and they replied that No. 6 Gain Chrromosome 70% , No. 8 Gain Chromosome for 100%.
    I am not sure this range under mosaic or beyond that..please advise more would be a great guidance for me..
    Thank you.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - December 23, 2017 reply

    NGS is a form of PGS testing so my comments apply as stated.

    About 12 years ago, Levent Keskintepe PhD and I introduced Comparative Genomic Hybridization (CGH) into the clinical IVF arena, as a preimplantation genetic sampling (PGS) method that enables full karyotyping (numerically chromosomal analysis) of all 23 pairs of an embryo’s chromosomes so mas to determine its subsequent ability to propagate a viable pregnancy (i.e. its “competence”). Since then we have, over a period of a 12 years, authored many articles on the clinical utility and advantages associated with the selective performance of embryo PGS and with it have witnessed embryo karyotyping emerge as a valuable efficiency tool in the IVF arena. Several alternatives to CGH have since emerged and while none are perfect, they have all enhanced our ability to better select the most “competent embryos for transfer to the uterus, thereby improving the efficiency of IVF, and reducing the risk of chromosomal miscarriages and birth defects.
    One recently introduced method known as “Next Generation Gene Sequencing (NGS)” bears special mention since its improved accuracy and reliability over previously used methodologies, has established it as a method of choice when it comes to embryo karyotyping..
    Gene Sequencing is a method that determines the precise order of nucleotides within a DNA molecule. The method/ technology determines the order of the four bases—adenine, guanine, cytosine, and thymine—in a strand of DNA. A new generation of sequencing technologies known as NGS now provides unprecedented opportunities for high-throughput functional genomic research. NGS is currently being applied to identify the karyotype of the human embryo and in my opinion is more reliable than other available PGS methodologies.
    NGS can be conducted reliably on blastomeres (derived from day 5-6, cleaved embryos) d from a blastocyst. .
    Based upon available data, it is my opinion that the time has arrived to recommend that blastocyst NGS be used as the preferred method for PGS in IVF.

    Geoff Sher

  • Kellie - December 11, 2017 reply

    Dear Dr. Sher,
    Thank you for your great article! My IVF cycle resulted in only three embryos that made to the 5 day blastocyst and PGS tested them one abnormal and two mosaics (one partially monos0my 9 and one partially monosomy 11). The partially monos0my 9 did not survive the thawing, so we transferred the partially monos0my 11. I just found out that I am pregnant. My question is that how big the risk of a miscarriage and how big the risk of a baby born with chromosome 11 deleted will be? Thanks!

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - December 11, 2017 reply

    Usually autosomal monosomy is incompatible with a viable pregnancy. So, while it is always advisable in such cases to do amniocentesis or CVS to confirm the chromosomal integrity of the conceptus, it is in my opinion very unlikely to result in a baby with a chromosomal birth defect. Simply stated, if the pregnancy survives beyond 12 weeks, it is likely to be unaffected.

    Good luck!

    Geoff Sher

    Kellie - December 11, 2017 reply

    Thank you so much for your super fast response! You are the best!

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - December 11, 2017 reply

    Thank you and G-d bless!

    Geoff Sher

    Kellie - February 9, 2018

    I am writing to share my story so it might provide useful information for some one going through the same thing. Sadly I lost the baby at 8.5 weeks after seeing a healthy strong heartbeat and perfect measurement at 8 weeks. We tested the tissue and it came back normal, so it did self-correct. We don’t know what caused the miscarriage but we are going to do another IVF cycle and hope the next baby will stick!

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - February 9, 2018

    Good luck Kellie,

    But keep the following in mind:

    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

    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

    Kellie - February 12, 2018

    Thank you so much for your detailed comment! You’re incredible! I just ordered your book and will read all the articles in your response. I conceived my first child through IUI a few years ago and carried him full-term, so I know I am capable of a successful pregnancy. However, I understand that I am older now (just turned 35). This is my first miscarriage (my fertility doctor could not find the reason why a seemingly good pregnancy suddenly ended) and I hope it’s my last one. Off to read your articles now. I will come back and report how everything is going. Pray for good news soon!

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - February 12, 2018

    Thanks, good luck and G-d bless!

    Geoff Sher

  • Tina - November 29, 2017 reply

    Hi Dr. Geoff,

    We have one embryo that is monosomy 16… what are the risks outside of increased chance for miscarriage with implanting that embryo?

    Thank you,
    Tina

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - November 30, 2017 reply

    Traditionally egg retrievals are timed for about 36 hours after a 10,000U hCG “trigger”. The hCG hormone thereupon remains in the system for up to a week. When patients who overstimulate following ovarian stimulation experience prolonged exposure to hCG the risk of developing severe ovarian hyperstimulation syndrome with its incumbent life-endangering complications escalates. Attempts to mitigate this risk have included:
    a) withholding the hCG trigger altogether thereby preventing luteinization of follicle granulosa cells and preventing the production of vasoactive substances (e.g. VEGF) which when overproduced escalate the risk/severity of OHSS,
    b) prematurely administering the hCG trigger to arrest further follicular growth and escalation in blood estradiol levels,
    c) reducing the dosage of hCG by half, to 5,000U in the hope of limiting/restricting the luteinization process and,
    d) supplanting the “hCG trigger’ by an “Agonist (e.g. Lupron) trigger” that causes promotes meiotic egg maturation buy causing a surge in the release of pituitary LH.
    All of the options above do indeed reduce the risk of developing OHSS. “a)” completely prevents egg maturation from occurring and thus virtually precludes the harvesting of “competent” eggs, while “b), c), and d)”all adversely affect egg “competency” to a lesser or greater degree, thereby compromising both embryo quality and IVF outcome.
    Use of the “Lupron trigger” bears further mention: Since its recent introduction, this approach has really gained popularity and caught on in a big way. In truth, there can be little argument that it markedly reduces the incidence, severity and risk of complications associated with severe ovarian hyperstimulation. However use of the “Lupron trigger” often comes at the expense of egg/embryo quality as well as IVF outcome. Thus, the question arises as to whether this approach is advisable, and if not, what the best alternative to its use would be. The reason why the “Lupron trigger” is in my opinion ill-advised, is that in cases of ovarian hyperstimulation, where there are numerous follicles with eggs that need to undergo meiosis following the “trigger”, the magnitude of the LH surge, induced by a “Lupron GnRHa trigger” is often insufficient. This can result in suboptimal egg maturation (meiosis), leading to the generation of an inordinate number of immature/dysmature eggs as well as in an increase in the number of large follicles that fail to yield eggs at all (“so called “empty follicles). This is why I do not employ the “Lupron trigger” approach in my practice, preferring instead to use the long pituitary down-regulation, along with “prolonged coasting” in women who are deemed to be at risk for developing OHSS. My position is further supported by a recent publication showing that for this very reason, the use of a GnRHa-induced “trigger is not helpful.
    Prolonged Coasting, my preferred choice!: My approach is consistently to have my patients who are at risk of developing OHSS, launch their ovarian stimulation, coming off a monophasic birth control pill (BCP). The last few days on the BCP is accompanied by the addition of Lupron. Thereupon the BCP is stopped and Lupron therapy is continued. After 3-7 days menstruation usually ensues, at which point the dosage of Lupron is reduced and low dosage FSHr (Follistim/Gonal-F/Puregon) -dominant ovarian stimulation is commenced. Lupron and gonadotropins are then continued together. This approach is referred to as the “Long Pituitary Down-regulation protocol” Use of the BCP is intended to lower LH and thereby reduce stromal activation (hyperthecosis) in the hope of controlling ovarian androgen (mainly testosterone) release (too much ovarian testosterone is harmful to egg development). Seventy five (75) units of LH/hCG (Luveris/Menopur) is added from the 3rd day of gonadotropin stimulation. Starting on the 7th day of ovarian stimulation with gonadotropins, I start watching daily for the # and size of follicles developing and for the rise in blood [E2]. If there are > 25 follicles, the patient becomes a candidate for “prolonged coasting” I keep stimulating with gonadotropins (regardless of the [E2]) until: a) 50% of all follicles reach 14mm and b) the [E2] reaches 2500pg/ml. At that point, gonadotropin stimulation is discontinued abruptly while daily Lupron injections continue. Thereupon I follow the daily blood [E2] without doing further US examinations. The [E2] will almost invariably continue to rise. I carefully plot the rise in [E2] (regardless of how high it goes). Usually, within 1-3 days it will plateau and then start to decline. As soon as the [E2] drops below 2500pg/ml (and not before then), I administer the 10,000U hCGu (Novarel/Pregnyl/Profasi) “trigger” or 500mcg of hCGr (Ovidrel) and then schedule an egg retrieval for 36h later. ICSI is a MUST because “coasted” eggs usually have few or no surrounding cumulus cells and eggs without a cumulus layer will not readily fertilize on their own. All fertilized eggs are cultured to the blastocyst (up to 6 days) whereupon I transfer up to two into the uterus, or vitrify all expanded blastocysts for subsequent dispensation at the directive of the patient. In some cases the embryos are biopsied for PGS testing prior to being cryostored. Subsequent frozen embryo transfers are conducted as per the wishes of the patients.

    It is important to point out that the success of this “prolonged coasting” approach depends on precise timing of the initiation and the conclusion of “prolonged coasting”. If you start too early, follicle growth will stop and the cycle will be lost. If you start too late, you will encounter too many post-mature/cystic follicles (>22mm) that usually harbor abnormally developed eggs.

    Use of the above approach avoids unnecessary cycle cancellation, severe OHSS, and optimizes egg/embryo quality. The worst you will encounter is mild to moderate OHSS and this too is uncommon.

    The use of an agonist or GNRH trigger while reducing the risk of severe OHSS developing comes at the expense of egg/embryo quality and could compromise IVF outcome.

    Geoff Sher

  • Kelly Jones - November 29, 2017 reply

    Dr. Sher, I am 39 years old and after several miscarriages trying on our own, we turned to IVF and completed three cycles. AMH 0.169. My first cycle was cancelled due to poor response, second cycle none of the seven eggs retrieved made it to day 7. Third cycle, five retrieved and only one made it to blast and after biopsy was determined 47XY +16 (full trisomy 16). My reluctant yet supportive RE, understanding this was our last hope, allowed me to transfer the abnormal embryo yesterday. Quality was however graded “Good”. I have not found any reliable information of a Full Trisomy 16 transfer with success and was hoping for your opinion. I know the genetic testing company we used has a 95-98% accuracy guarantee so we are praying for the 2-5% error or for a miracle in the uterus. To your knowledge, has any full trisomy 16 made it to live birth? My second questions is, I actually ovulated a leftover egg last week through the estrogen protocol in which we tried to fertilize naturally, what is the likelihood of both sticking and twins or if our trisomy 16 embryo miscarries will it affect our other embryo (if we were able to fertilize? Thank you for your time!

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - November 29, 2017 reply

    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 an 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.” 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 practical 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 aneuploid embryos to the uterus.
    Certain meiotic aneuploid trisomy embryos (e.g. trisomies 13, 18, & 21) can and sometimes do, result in aneuploid concepti. Thus, in my opinion, 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 such embryos. Other autosomal trisomy embryos will hardly ever produce viable euploid concepti and can thus, in my opinion be transferred in the hope that auto correction will occur in-utero. However, in all cases, and amniocentesis or CVS should be performed to make certain that the baby is euploid. Conversely, no autosomal monosomy embryos are believed to be capable of resulting in viable pregnancies, thereby making the transfer of autosomal monosomy embryos, in the hope that they are “mosaic”, a far less risky proposition. Needless to say, if such action is being contemplated 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.

    Good luck!

    Geoff Sher

  • Patricia - November 22, 2017 reply

    Hi Dr. Sher,
    I am in my mid forties and have done many IVF cycles with PGD. All of my embryos were abnormal except 1 which I miscarried. I am planning to move to donor egg after I transfer any abnormals that might have a chance of being mosaic after NGS testing. Here are the embryos I am considering transferring:
    1- Day 5 Blast grade 323 with Trisomy 11
    2-Day 6 Blast grade 233 with Monosomy 16
    3-Day 6 Blast grade 533 with Monosomy 7, 19, and 20
    4-Day 5 Blast grade 523 with Trisomy 1, Mosaic Trisomy 7, and Trisomy 16
    5-Day 6 Blast grade 532 with Trisomy 9, and Mosaic Monosomy 19

    Please let me know which embryos you think I should transfer in hopes they are mosaic. I understand I may need to terminate a pregnancy under the circumstances. Thank you for your advice. Patricia

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - November 22, 2017 reply

    I personally would only transfer the monosomy 16 and the trisomy 11.

    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 an 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.” 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 practical 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 aneuploid embryos to the uterus.
    Certain meiotic aneuploid trisomy embryos (e.g. trisomies 13, 18, & 21) can and sometimes do, result in aneuploid concepti. Thus, in my opinion, 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 such embryos. Other autosomal trisomy embryos will hardly ever produce viable euploid concepti and can thus, in my opinion be transferred in the hope that auto correction will occur in-utero. However, in all cases, and amniocentesis or CVS should be performed to make certain that the baby is euploid. Conversely, no autosomal monosomy embryos are believed to be capable of resulting in viable pregnancies, thereby making the transfer of autosomal monosomy embryos, in the hope that they are “mosaic”, a far less risky proposition. Needless to say, if such action is being contemplated 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.

    Good luck!

    Geoff Sher

    Patricia - November 23, 2017 reply

    Ok thank you for your opinion. I am assuming the other embryos are probably too risky to transfer in your opinion. I am just wondering if you think it might make sense to rebiopsy them instead to see if there was a mistake or if I get a different result before I just discard them. Thanks

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - November 24, 2017 reply

    I would not re-biopsy them.

    Geoff Sher

  • Christine - November 3, 2017 reply

    Hi Dr. Sher! Thanks for posting this article I found it really helpful. I am currently 10 weeks pregnant resulting from the transfer of 2 mosaic embryo (32mb del of chr 7 and 77mb del of chr 3) from donor eggs and my husband’s sperm. We have 1 daughter from the first IVF cycle of the same batch of embryo, we only did PGS for this second IVF to maximize our results, however all 3 remaining embryo tested abnormal, two of which were mosaic. I miscarried one at 8w5d, however so far remaining pregenacy seems ok. I am incredibly worried about the risk of the remaining pregnancy ending in miscarriage or a chromosomally abnormal live birth, but I am hesitant to submit to further genetic testing due to the risk of harm to the baby. I know normally once a pregnancy enters the 2nd trimester, the miscarriage risk drops considerably, but is this still the case with a mosaic embryo? Is a live birth with chromosomal abnormalities likely? At what point in my pregnancy will I be “out of the woods”. This has all been so incredibly stressful, and an emotional rollercoaster. I am thankful to have a doctor who, like you, sees that there could be a chance of delivering a normal, healthy baby and agreed to transfer.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - November 3, 2017 reply

    Yes! It is the same but I would do an amniocentesis either way!

    Geoff Sher

  • Judy - October 26, 2017 reply

    Hello Dr.
    I just finished two cycles and have 1 normal girl. one 45 monosmy-4 xy, one 47 trisomy 20 xy and one 47 trisomy 17 xx; Do you think there is any chance if I transfer these abnormal ones? Which one have more chance? Thank you very much!

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - October 27, 2017 reply

    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.

    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

  • Becky - October 20, 2017 reply

    Good evening Dr. Sher,
    I truly enjoyed reading this article and thank you for sharing so much valuable information. My husband and I currently have two frozen embryos. The first was both our egg and sperm. PGS testing at day 5 concluded trisomy on chromosome 2 and a monosomy on chromosome 8. Our next cycle we used donor eggs which yielded one day 5 embryo. PGS testing concluded trisomy chromosome 2. It was recommended that my husband be karyotyped, not sure if that is the correct terminology. The results were normal. So we are facing a decision regarding what to do next. The recommendation has been to go through a fresh donor egg transfer rather than frozen donor eggs in the hopes of yielding a higher egg number to work with. Before going through an additional cycle I am wondering if we should go ahead and implant the most current embryo with trisomy 2 and see what happens? I have an appointment with the genetic counselor in the next few weeks and am just trying to gather as much information as possible. Thank you so much for your time and for what you do!

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - October 21, 2017 reply

    Frankly Becky,

    In my opinion both the trisomy and monosomy embryos could be mosaic so I would transfer these. Firstly, in my opinion if they are indeed mosaic they could produce viable pregnancies and if not, they would be highly unlikely to propagate viable pregnancies. Ultimately if you did conceive it would be advisable to do either chorionic villus sampling or amniocentesis to confirm the normalcy of the pregnancy and in the highly unlikely even that an aneuploid embryo does prevail it could then be terminated.

    Geoff Sher

  • Ali - October 10, 2017 reply

    My wife and I are 35, and 36. We had 13 eggs, 8 mature, 5 fertilized with ICSI, 4 made it to day 6. The PGS results shows one normal, one is 45,XY,-14, one is 47,XY,+19, and the final one is 46,XY,del(3)(q13.1). In case that normal one does not work what do you recommend?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - October 10, 2017 reply

    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.

    Geoff Sher

  • Anne - September 23, 2017 reply

    I have three abnormal embryos
    -5, 18
    -11p
    -7, -9, -18

    My comic will not transfer them. If I have them sent to you will you try and transfer them?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - September 23, 2017 reply

    Only the -11p one.

    Geoff Sher

  • maggie - September 18, 2017 reply

    Dr. Sher,
    I am sorry I posted question twice by accident. Would you please delete the last one? there is no way to let me to delete it. I don’t want to mess up your blog. Thanks !

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - September 18, 2017 reply

    No problem!

    Geoff Sher

  • maggie - September 17, 2017 reply

    Dr. Sher,
    I am 42 yr old. I did 3 cycles in one year and got 29 eggs and 11 blast. But all are abnormal and I have no embryos to be implanted. 5 embryos from my last cycle are still frozen. The CCS results are: ( 45, -11), (45.-15),(46, -17),(44,-20,-21), (47,+3). Is there any possibility to transfer any of the above 5 blast embryos to have a living birth? I have no kid and love to have one kid with my own egg. Thanks.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - September 17, 2017 reply

    Some of these blastocysts could be “mosaics capable of propagating a viable normal pregnancy.
    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.

    Geoff Sher

    maggie - September 18, 2017 reply

    Dr. Sher,
    Thank you for your prompt reply and your kindness. Among these five, which are the top 2 embryos I could pick to implant if I want to try. ( 45, -11), (45.-15),(46, -17),(44,-20,-21), (47,+3).

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - September 18, 2017 reply

    45-11; 45-15; 46-17; 47+3…in that order!

    Geoff Sher

  • MD - May 22, 2017 reply

    Hello Dr. Sher,

    At the age of 41, I completed 2 IVF cycles which yielded 6 aneuploid blastocysts that are currently frozen in storage. Would you consider transferring the following embryos: monosony 8, monosony 22, and trisomy 22 ? I’m happy to report that I have a healthy son now, but we would like to have another child (a girl if possible). However, the only female embryo is the trisomy 22 . I had a genetic consultation and the geneticist expressed concern about transferring the trisomy 22 embryo in particular.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - May 23, 2017 reply

    All could be mosaics. I would transfer the T-22 provided that you are willing to for CVS or amniocentesis in any pregnancy that advances and are prepared to terminate the pregnancy in the event that the conceptus is found to be chromosomally aneuploid.

    Geoff Sher

    maggie - September 18, 2017 reply

    Dr. Sher,
    Sincerely thank you for your prompt reply. I have read your article carefully and totally understand what you say. Would you please give a suggestion which one or two of my 5 blast have a higher probability of “mosaics capable of propagating a viable normal pregnancy” than the others. I mean, the top 2 to be transferred if I want to have a try. ( 45, -11), (45.-15),(46, -17),(44,-20,-21), (47,+3). Thank you very much for your help !

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - September 18, 2017 reply

    45-11 and 45-15 and 47+3.

    Good luck!

    Geoff Sher

    maggie - September 18, 2017

    Thank you very much !! My Day 3 data in Sep 2016 :FSH is 8.4 ; E2 is 22, LH is 5.6 AMH is 2.8. AFC is 9 . I know you are the father of IVF and an outstanding expert. If I go to your clinic to have one more cycle, what kind of protocol will you use on me ? My Doctors tried (425 unit follistim+75 menupour) for 15 days , (3oo unit Gonal-f +2 vial of Menupour+100mg clomid)for 11 days; (225 unit Gonal-F + 50 mg clomid )for 11 days in my last 3 cycles. 11 blasts with Chromosome abnormal . none is normal. will you suggest lower dosage or higher dosage for me to improve the chance of passing pgs? Thank you !!

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - September 18, 2017

    We need to talk. I suggest you call Julie at 800-780-7437 and set up a Skype consultation with me please.

    Geoff Sher

  • Sarah - April 19, 2017 reply

    Dr. Sher,
    Would you consider transferring the following types of embryos:
    1) Monosomy 8
    2) Monosomy 16
    3) Monosomy 14

    Thank you,

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - April 20, 2017 reply

    Yes I would…but only after a long discussion/disclosure regarding the need for prenatal genetic testing in early pregnancy and the need to be ready in advance to terminate an abnormal, aneuploid pregnancy. Also the full implications of mosaicism.

    Geoff Sher

  • AB - April 13, 2017 reply

    Hello Dr,

    I am 36 years old and my husband is 37 . My husband has low sperm conc, motility and low morphology at 1%. I already have a 9 year old healthy son – normal pregnancy. However we have been stuck for our second one. We just did our first round of ivf, got 8 eggs retried, ICSI, 3 made to Day 3 and we had two day 5 blasts .. We planted one but lost that at 7 wks 5 days. The other was sent for PGS testing, as my doc advised, and came back as 46 dup(8) q24.1 q24.3 . Now we are thinking to start the next cycle, although financially we are stretched.

    Do you think partial aneuploidy is mosaic? I am planning to talk to my RE about this, but wanted to take your opinion in-case you think there is any chances after implanting this embryo.
    I am concerned that even next cycle can turn out the same, where we may have a fewer eggs with abnormal embryos….

    Thanks Again!

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - April 13, 2017 reply

    Yes! It could be a mosaic!

    Geoff Sher

    AB - April 18, 2017 reply

    thanks Doctor. Do you think I should take a chance of implanting this embryo specially because of the partial aneuploidy?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - April 18, 2017 reply

    that is something you need to discuss with your RE.

    Geoff Sher

  • Melanie - March 30, 2017 reply

    Dr. Sher:

    I’m currently 38 years old. I have had two miscarriages and one live birth. First MC (first trimester loss) was in 2013, then naturally conceived my son, delivered healthy in 2014. When trying for a second I miscarried again in 2015, also a first trimester loss. Neither losses were tested as I miscarried naturally.

    We started IVF in November 2016. My AMH is 0.95. Everything else tested normal. Our RE recommended PGS due to the miscarriages. My protocol for IVF #1 was Estrogen priming, Gonal F/Menopur, and Cetrotide. I ended up with 12 eggs retrieved, 8 mature, and 6 fertilized. Only 1 made it to Blast on day 6 and tested PGS abnormal.

    My 2nd cycle was a very similar protocol, HGH was added. I had 15 eggs retrieved, 11 mature and all fertilized. However, only 2 made it to Blast on day 6. Only 1 blast was good enough quality to send for testing and that also tested PGS abnormal.

    My question is: should we stick with the same strategy with PGS and hope to get that proverbial golden egg? Or consider a fresh transfer and forgo PGS testing? Or try to different protocol? Or something else???

    Thanks so much!

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - March 30, 2017 reply

    In my opinion, your stimulation protocol needs to be critically reviewed and possibly revised and given your diminished ovarian reservbe, you should consider Staggered IVF with Embryo banking and PGS (see below) using a very strategic protocol for ovarian stimulation.

    Again, in my opinion, the protocol used for ovarian stimulation, against the backdrop of age, and ovarian reserve are the drivers of egg quality and egg quality is the most important factor affecting embryo “competency”.
    Women 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 effect of DOR, certain ovarian stimulation regimes, by promoting excessive LH production (e.g. short agonist/Lupron- “flare” protocols, clomiphene and Letrozole), can in my opinion, 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 women 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 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 invite you to arrange to have a Skype or an in-person consultation with me to discuss your case in detail. If you are interested, please contact Julie Dahan, at:
    Email: Julied@sherivf.com
    OR
    Phone: 702-533-2691
    800-780-7437
    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.

  • Ali - February 8, 2017 reply

    I’ve went through one successful round of ICSI, with PGS. Four 6 day blastocysts were screened. Two had multiple abnormalities, one was our current 1 year old, and the fourth is a girl with trisomy 21. Our clinic automatically discarded the two with multiple abnormalities, but kept the girl with trisomy 21. Due to our beliefs my husband and I feel it is only right to try our hardest to find a clinic that will transfer our embryo. Can you help us in any way?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - February 8, 2017 reply

    I can understand your issue, but to be frank, I would have great difficulty transferring an embryo hat could propagate a baby with Down syndrome.The Hippocratic oath says “do no harm”, and I believe that knowingly could bring a baby into the world with Down’s syndrome, violates that oath. This having been said, it is true that the embryo aneuploidy could be mosaic and might autocorrect in-utero, but that would pose a risk that would not be ethically acceptable to me.

    Good luck!

    Geoff Sher

  • Kelley - January 29, 2017 reply

    Dr. sher,

    I find this post very interesting, my RE has suggested me not doing PGS if I do another cycle after 6 failed single FETs of PGS embryos. We currently have a monosomy 16, on with deletion of arm on chromosome 4; trisomy 14 + trisomy 21; and trisomy 14+ trisomy 22. My RE wasn’t excited at the idea of transferring abnormal embryos, but I was curious on your thoughts of transferring the monosomy or deletion on chromosome 4 embryos versus doing another retrieval cycle. Thank you so much for your time.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - January 29, 2017 reply

    Since in my opinion it is not possible to reliably differentiate between mosaicism and meoitic (irreversible) aneuploidy, there is a place for transferring embryos with single chromosomal aneuploidies, provided you are willing to do CVS or amniocentesis if you conceive and would be willing to terminate an aneuploid pregnancy.

    Geoff Sher

  • Trish - January 21, 2017 reply

    Hi Dr Sher,
    I wrote to you a few months ago explaining that I am 46 and can no longer retrieve eggs. I have many abnormal embryos on ice tested with both acgh and Ngs. I had one embryo which originally tested normal per acgh that retested mosaic trisomy 3, trisomy 9, and trisomy 18. I transferred that embryo last month (you agreed that was an option) and I unfortunately am miscarrying. I am glad I transferred it as I could never live with the fact that it originally tested normal. I am now left with many complex abnormal embryos and one aneuploid monosomy 16 and one aneuploid trisomy 11 embryo. These embryos did not test mosaic when retested with NGS, they are just aneuploid. I am considering transferring them anyway as I think you have stated that they could possibly still be mosaic. Do you think I should rebiopsy them with a new sample or just transfer them and hope for the best. I am considering also transferring a donor embryo at the same time. Thanks in advance for your thoughts.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - January 21, 2017 reply

    Given your set decision not to disregard these embryos, why not transfer them without re-testing. And I say again that in my opinion, there is from a practical standpoint, no reliable method by which to diagnose mosaicism in an embryo/blastocysts.

    Geoff Sher

    trish - January 21, 2017 reply

    Ok I understand. I will likely transfer the 2 that had single errors, the monosomy 16 embryo and the trisomy 11 embryo. The rest of the embryos have complex abnormalities, and one other has trisomy 9, and mosaic trisomy 19 abnormalities. Are any of these worth transferring as well? I have a total of 9 embryos with complex abnormalities. Thanks so much.

    trish - January 21, 2017 reply

    I just wanted to add that I just went over the report and most of the complex abnormal embryos had 4 or more abnormalities. The two that seem the most like options are :
    1. Complex abnormal Monosomy 4, Monosomy 13, and Monosomy 22
    2. Complex abnormal Monosomy 7, Monosomy 19, Monosomy 20
    Thanks again.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - January 21, 2017

    In my opinion, it would be best not to transferring embryos with complex aneuploidies.

    Geoff Sher

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - January 21, 2017 reply

    I personally would stick to embryos with monosomy.

    Geoff Sher

    Trish - January 21, 2017

    Ok So just to clarify, are you saying you would transfer the complex abnormals if they are only have monosomy abnormalities, or are you saying you would only transfer abnormals with a single monosomic abnormality? Thanks

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - January 22, 2017

    The latter!

    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.

    Geoff Sher

    cs - October 26, 2017 reply

    Hi. I just got a report back on trisomy 11 and was curious if you had any luck on implanting the abnormals? Best of luck!

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - October 26, 2017

    It could be a mosaic and is worth transferring.

    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 an 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.” 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 practical 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 aneuploid embryos to the uterus.
    Certain meiotic aneuploid trisomy embryos (e.g. trisomies 13, 18, & 21) can and sometimes do, result in aneuploid concepti. Thus, in my opinion, 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 such embryos. Other autosomal trisomy embryos will hardly ever produce viable euploid concepti and can thus, in my opinion be transferred in the hope that auto correction will occur in-utero. However, in all cases, and amniocentesis or CVS should be performed to make certain that the baby is euploid. Conversely, no autosomal monosomy embryos are believed to be capable of resulting in viable pregnancies, thereby making the transfer of autosomal monosomy embryos, in the hope that they are “mosaic”, a far less risky proposition. Needless to say, if such action is being contemplated 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.

    Geoff Sher

  • Ann - January 7, 2017 reply

    Hi Dr Sher – we just received the results of pgs testing from Reprogenetics on 5 day 5 embryos and 3 day 6 embryos (so 7 total). We had one euploid day 5, one mosaic day 5 (this had additional chromosomes & was a boy) and one mosaic day 6 (was missing chromosomes and was a girl). We plan on transferring the normal embryo first but are having a tricky time understanding if we should keep the two mosaics and/or keep all of them frozen just in case. Currently our RE would recommend discarding all but was supportive of keeping the 2 mosaics on ice if that’s what we wanted to do. thank you in advance for your advice/opinion. best, Ann

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - January 7, 2017 reply

    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.

    Hope this helps!

    Geoff Sher

    Ann - January 7, 2017 reply

    I guess where I’m confused is between the two that have been labeled mosaic and the 4 that have been labeled aneuploid. If they can correctly identify mosaic embryos as the report indicated, then in terms of ranking the embryos to use am I correct in assuming that the two labeled mosaic would be next in line (though would have a decreased chance of viability) and then the 4 labeled aneuploid are not likely to be viable but could still have a very slight chance of self correcting? Thank you in advance for your advice. Also, just as an FYI I went to the foundation link on this page to donate since you’ve been so kind but there’s no donation information.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - January 7, 2017 reply

    Very respectfully Ann, in my opinion it is not possible to accurately diagnose mosaicism without examining multiple cells in the embryo, individually and comparatively. I know that some labs do claim to have this ability, but klet’s just say that I am very skeptical of this assertion.

    Geoff Sher

    Ann - January 8, 2017

    Got it, understood. Thank you again for your reply. I think we will have to do a lot more investigating before we make any decisions regarding the remaining 6.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - January 8, 2017

    Good luck Ann!

    Geoff Sher

  • yx - December 12, 2016 reply

    Dear Dr. Sher, I am 44 years old, for the last one and half year, only 3 embryos were able to be collected. We just recently had those 3 embryos sent to PGS, and all of them came back abnormal. I carefully read your blog, and thinking about transfer hoping for the autocorrection. two of the embroys have trisomy 21, or trisomy 13, so those two may not be the candidate. The only one left still has monosomy 8, monosomy 9, and trisomy 22. with such -8,-9,+22, can we try and transfer this one? worse case could be chemical, miscarriage as I know of. Or Dr. Sher you may think even this one can not be a candidate? We are so desperate, please help. Thanks!

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - December 12, 2016 reply

    In my opinion, the monosomy embryos and even the one with Trisomy 13 are worthy of consideration for FET because they could be mosaic.

    Geoff Sher

  • CindyShirl - December 6, 2016 reply

    Hello Dr. Sher,
    I am 43 years old and just recently got the results from my PGS by Next Generation Sequencing. My results were that all 3 of the blastocycts were abnormal with:
    Embryo 1: Trisomy 15
    Embryo 2: Monosomy 8 & 16
    Embroyo 3: Turner syndrome

    This is my first round of IVF and I don’t know whether to try again or do embryo banking. Do you think my results are age related? Turner syndrome is said to not be age related but could in fact be due to the father’s sperm. Is it possible that the trisomy 15 could auto correct?

    18 eggs were retrieved but only 10 were mature and 7 fertilized with ICSI. 4 arrested between days 3-5 and only 3 made it to blast with none being normal as set out above.

    I don’t know whether to change clinics. Your thoughts?

    Thank you.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - December 6, 2016 reply

    Both age and the protocol used for ovarian stimulation can impact egg “competency” (chromosomal integrity). And yes, in my opinion, your protocol for ovarian stimulation needs to be reviewed and probably revised…followed by Embryo banking of PGS-normal blastocysts.

    Older women as well as those who (regardless of age) have diminished ovarian reserve (DOR) tend to produce fewer and less “competent” eggs, the main reason for reduced IVF success in such cases. The compromised outcome is largely due to the fact that such women tend to have increased LH biological activity which often results in excessive LH-induced ovarian testosterone production which in turn can have a deleterious effect on egg/embryo “competency”.
    Certain ovarian stimulation regimes either promote excessive LH production (e.g. short agonist/Lupron- “flare” protocols, clomiphene and Letrozole), augment LH/hCG delivered through additional administration (e.g. high dosage menotropins such as Menopur), or fail to protect against body’s own/self-produced LH (e.g. late antagonist protocols where drugs such as Ganirelix/Cetrotide/Orgalutron that are first administered 6-7 days after ovarian stimulation has commenced).
    I try to avoid using such protocols/regimes (especially) in older women and those with DOR, favoring instead the use of a modified, long pituitary down-regulation protocol (the agonist/antagonist conversion protocol-A/ACP) augmented by adding supplementary human growth hormone (HGH). I further recommend Staggered IVF with embryo banking of PGS (next generation gene sequencing/NGS)-normal blastocysts in such cases. This type of approach will in my opinion, optimize the chance of a viable pregnancy per embryo transfer procedure and provide an opportunity to capitalize on whatever residual ovarian reserve and egg quality still exists, allowing the chance to “make hay while the sun still shines”.
    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.

    • 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 Aproach
    • 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.
    • 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?
    • 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
    • Implications of “Empty Follicle Syndrome and “Premature Luteinization”
    • Premature Luteinization (“the premature LH surge): Why it happens and how it can be prevented.

    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.
    Geoff Sher

  • CL - June 23, 2016 reply

    Hi Dr Sher – I’m 34 yrs old and just found out the PGS results of my recent IVF cycle. My partner has 3% morphology so we did ICSI, we extracted 12 mature eggs and all fertilized. By day 5 we had only 3 blastocysts. According to the genetic testing we have one chromo-normal embryo and one mosaic. My question is about the mosaic. The interpretation is Partial Monosomy 11q14.3-qter & Mosaic Partial Monsony 13q31.1-qter. My doctor advises that this is not a safe embryo to implant because of the Partial Monosomy in addition to the mosaic. I would love your opinion on this. Thank you so much.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - June 23, 2016 reply

    I respectfully do not agree!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. “auto correction”) 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, by 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 all aneuploid embryos we, in so doing, might 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 “auto correction” 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.” Many such 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 “auto correction”. 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 enormous clinical value. Since some mosaic embryos can “autocorrect” and even go on to propagate a viable baby, the ability to confirm that aneuploidy is mitotic (potentially reversible) would provide a strong argument in favor of preserving certain aneuploid embryos for future dispensation. Unfortunately however, there is presently no microscopic or genetic test that can reliable differentiate between meiotic and mitotic aneuploidy.
    Aneuploidy, whether meiotic or mitotic in origin involves the addition of one or more chromosomes to a given pair in human embryos. Certain aneuploidies involve only a single, chromosome pair (simple aneuploidy) while others involve more than a single pair (i.e. complex aneuploidy). Evidence suggests that complex aneuploidy, whether meiotic or mitotic in origin is almost always lethal while all forms of meiotic aneuploidy are permanent. Some aneuploidies, especially those that involve addition of a chromosome to any pair (trisomy) will at times progress to clinical pregnancies (e.g. trisomy 15, 18, 21 or when the sex chromosomes are involve). And as stated previously, most aneuploid embryos, should they attach, will miscarry or result in a chromosomally defective offspring.
    On the other hand, some aneuploid embryos have one chromosome (in a given pair) missing (i.e. monosomy). Aside from monosomy involving absence of the Y-sex chromosome (i.e. XO) which can resulting in a live birth (Turner syndrome) all other monosomies involving autosomes (non-sex chromosomes) are lethal and will not result in viable offspring.
    Since it is presently not possible, without removing more than 1 cell from an embryo (a very traumatic event) to differentiate between meiotic and mitotic aneuploidy, it follows that making a diagnosis of embryo aneuploidy does not allow for identification of mosaic embryos for transfer. This is especially true when it comes to trisomic embryos that can and sometimes do, propagate chromosomal birth defects such as Down syndrome. It is important to bear in mind that the transfer of trisomic embryos (whether due to meiotic or mitotic aneuploidy) can result in miscarriage or a birth defect. This makes any attempt to transfer such embryos to the uterus fraught with risk and in my opinion, ill advised. Conversely, since true meiotic autosomal monosomic embryos cannot propagate viable pregnancies, performing embryo transfer in such cases in the hope that the aneuploidy is mitotic (mosaic) in origin and will spontaneously “ auto correct”, is a rational consideration. Needless to say, such action would require full disclosure, and the execution of a detailed, informed consent agreement which would include an expressed commitment 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.
    Since it is meiotic rather than mitotic aneuploidy that is invariably lethal and given that meiotic aneuploidy originates in the egg, it is my belief that the closer to fertilization that embryo biopsy is done for PGS, the more likely it is that any aneuploidy detected, will be meiotic in origin. The longer you wait thereafter, the greater the likelihood that with repeated mitotic division, mutational changes will result in mitotic aneuploidy (mosaicism). This is why I strongly believe embryo biopsies should be performed on day 2-3 post fertilization rather on day 5-6 days (the blastocyst stage).”

    Good luck!

    Geoff Sher

  • E - April 16, 2016 reply

    Dr. Sher,
    I am curious about the difference between meiotic and mitotic. In August I had day 5/6 blastocyst PGS tested and found out 5 of 8 were euploid. Sadly, we lost the first of the five at 8.5 weeks due to twinning. We decided to have each of the 5 biopsies sent for NGS testing and 3 of the 5 euploid embryos came back mosaic (the one we lost was not mosaic).

    You stated, “there is presently no microscopic or genetic test that can reliable differentiate between meiotic and mitotic aneuploidy.” Would it be fair to assume that the 3 embryos that were tested euploid by PGS and mosaic by NGS would be considered mitotic because there is the presence of euploid cells? Or could something else explain this?

    Thanks, this is all very interesting!

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - April 16, 2016 reply

    There is no way to my knowledge that mosaicism can be diagnosed by a single NGS test. At this stage if the result was aneuploid it could be meiotic or mitotic.

    Discuss with your RE please.

    Geoff Sher

  • Louise - March 23, 2016 reply

    Hello Dr. Sher,
    You are very generous with your feedback and advice so I thought I might see what you think here. I’m 44 years old and finally met my now husband only 3 years ago. We just finished our first round of IVF (husband has ED so the natural route was not happening for us) . This first round seemed promising, I responded well to the protocol and they extracted 23 eggs, 16 were fertilized and we had 9 for PGS testing. We were feeling cautiously optimistic because the numbers seemed so good. However, testing showed all nine of the embyos to be abnormal. We are not seeing the doctor again until next week when i assume she will review the report with us and discuss options. Understandably I am feeling deflated. I have read in your blog about the LH levels and how too high levels can have a negative impact on egg quality. How are the levels tested? The only blood tests done during my stimulation were of estradiol (twice). After speaking next week with our doctor, we will be deciding if we will do another round. I guess I feel that I would go through it again only if I am convinced that we are trying a slightly new tack in hopes of better maintaining whatever integrity my eggs might have. I know I am missing information about the PGS test results but my question for you is, under these circumstances, is there any particular strategy you might suggest discussing with my doctor or any questions I should be asking when we meet with her next week?
    Many many thanks to you!

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - March 23, 2016 reply

    At 44Y, regardless of your ovarian reserve, fewer than 1 out of 10 of your eggs are likely to be “chromosomally normal/ euploid and “competent”. So it does not surprise me that all 9 embryos were aneuploid/”incompetent”.

    If you insist on trying with your own eggs, I would advocate a modified, long pituitary down-regulation protocol. I would use an agonist/antagonist conversion protocol with human growth hormone (HGH) augmentation and would recommend Staggered IVF with embryo banking of PGS (next generation gene sequencing)-normal blastocysts, to make hay while the sun still shines.
    Please visit my new Blog at o to http://goo.gl/4hvjoP , 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
    • Ovarian Stimulation for IVF using GnRH Antagonists: Comparing the Agonist/Antagonist Conversion Protocol.(A/ACP) With the“Conventional” Antagonist Aproach
    • IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation(COS)
    • 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.
    • Diagnosing and Treating Infertility due to Diminished Ovarian Reserve (DOR)
    • 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?
    • 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 Sampling (PGS) Using: Next Generation Gene Sequencing (NGS): Method of Choice.
    • IVF Failure and Implantation Dysfunction: The Role of Endometrial Thickness, Uterine Pathology and Immunologic Factors
    • Why did my IVF Fail
    • 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

    I invite you to call 702-699-7437 or 800-780-7437 or go online on this site and set up a one hour Skype consultation with me to discuss your case in detail.

    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.

    Geoff Sher
    I invite you to call 702-699-7437 or 800-780-7437 or go online on this site and set up a one hour Skype consultation with me to discuss your case in detail.

    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.

    Geoff Sher

    P.S. By the way, it will not necessarily be of benefit to test your in-cycle LH levels because the blood concentration will not necessarily reflect the increased biological activity of the hormone, which is virtually inevitably associated with advanced age.

    Louise - March 23, 2016 reply

    Thanks very very much for your feedback! This will help us to get the most out of our next visit with the doctor and help us make the decision about further IVF. I’m very grateful for your help.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - March 24, 2016 reply

    You are most welcome Louise!

    Geoff Sher

  • CJ - March 21, 2016 reply

    Hello,

    I am 28 years old and my husband is 30 and I have been diagnosed with unexplained infertility (although my husband has low morphology at 2%). We just did our first round of ivf, we had two day 5 blasts tested and both came back as mosaics. One with monosomy 16 and one with trisomy 18. The trisomy 18 had a longer name but in short form chromosome 18 and had an extra piece on it. We are about to start our 2nd cycle and they have doubled my drugs to hope I end up with more day 5 blasts to hopefully increase my chances of having a normal.

    We spoke to a genetic counselor who told us that in the last few months they have started using a new technology that is more sensitive and they have seen a 20% increase in mosaics. They were although surprised that at my age I had 2. They also said that it could be the case that if they used the old technology these 2 embryos could have come back normal. Now as I start my second cycle I really question if its the right thing to do to go ahead and test the next batch. Our doctor said if we get all mosaics again he would like us to consider transferring one. The worry that it would bring to me would be very great and I wonder if I am in a better position to just go in blind and not test.

    In your opinion at my age with no known causes of infertility do you think I have a high likelihood of getting a normal in future cycles?

    What are your thoughts on transferring one of these embryos? I assume they would transfer the monosomy 16 based on what your say above in your article.

    Thank you very much for your time.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - March 22, 2016 reply

    Personally, at 28Y of age and no predisposing clinical factors to embryo “incompetency”, I would not do genetic testing if it were up to me.

    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).
    My answer to patients who ask me when is the time to stop undergoing IVF is ….Aside from the weight of the financial burden, the time to stop is when in spite of thorough and comprehensive evaluation, there is no remediable and treatable explanation for repeated failure.

    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 promptl

    • Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
    • Ovarian Stimulation for IVF using GnRH Antagonists: Comparing the Agonist/Antagonist Conversion Protocol.(A/ACP) With the“Conventional” Antagonist Aproach
    • IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation(COS)
    • 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.
    • Diagnosing and Treating Infertility due to Diminished Ovarian Reserve (DOR)
    • 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?
    • Frozen Embryo Transfer (FET): A Rational Approach to Hormonal Preparation and How new Methodology is Impacting IVF.
    I invite you to call 702-699-7437 or 800-780-7437 or go online on this site and set up a one hour Skype consultation with me to discuss your case in detail.

    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.

    Geoff Sher

    CJ - April 11, 2016 reply

    Thank you very much for your advice. I just went through my 2nd retrieval. My doctor decided to keep me on the same drugs as she felt I just needed a boost to get more eggs. I was on 225 iui Menopur in the morning and 225 iui Puregon at night. I took estrace from 7dpo in the previous cycle to day 1 of the stimm cycle. I went in to the retrieval with 14 follicles over 20mm, biggest being at 26mm. And i had 4 under 16mm. She left them on day longer this time but I still only stimmed for 9 days, same as last time. Last time I got 6 eggs all mature, 4 fertilized and then of course only 2 day 5 embies which were both mosaic. Well I’m in the same situation again. 8 eggs retrieved, 7 mature, 4 fertilized. I find out tomorrow if any make it to day 3. My doctor is still heavily pushing me on CCS testing. I did not mention before I have had one miscarried at 26 years old at 10.5 weeks. I am 28 now. That has been my only pregnancy.

    Do you think I should just make the executive decision for myself and ask for a day 3 transfer tomorrow of 1-2 of those 4 embryos I have growing in the lab right now?

    Do you think I should hold off until Day 5 and transfer any if I have any?

    Should I just take the advice of my doctor wait until Day 5/6, do the ccs testing and go from there?

    Also any idea why I have so little eggs?

    My AMH was 2.8, FSH is usually around 5. My follicle count is anywhere from 18-22.

    Growing follicles never seem to be an issue but I cant seem to get a normal number of eggs at my age. It’s devastating and I debate just giving up on this entirely 🙁

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - April 11, 2016 reply

    There is no point in transferring prior to day 5-6 because embryos that do not make blastocyst, are almost always chromosomally abnormal anyway and not worthy of being transferred.

    Respectfully, I do not use the type of protocol you were on. In my opinion, you might do better on a robust, long pituitary down-regulation protocol. I would use an agonist/antagonist conversion protocol with human growth hormone (HGH) augmentation and would recommend Staggered IVF with embryo banking of PGS (next generation gene sequencing)-normal blastocysts, to make hay while the sun still shines.

    Please visit my new Blog at o to http://goo.gl/4hvjoP , 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
    • Ovarian Stimulation for IVF using GnRH Antagonists: Comparing the Agonist/Antagonist Conversion Protocol.(A/ACP) With the“Conventional” Antagonist Aproach
    • IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation(COS)
    • 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.
    • Diagnosing and Treating Infertility due to Diminished Ovarian Reserve (DOR)
    • 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?
    • 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 Sampling (PGS) Using: Next Generation Gene Sequencing (NGS): Method of Choice.
    • IVF Failure and Implantation Dysfunction: The Role of Endometrial Thickness, Uterine Pathology and Immunologic Factors
    • Why did my IVF Fail
    • 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

    I invite you to call 702-699-7437 or 800-780-7437 or go online on this site and set up a one hour Skype consultation with me to discuss your case in detail.

    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.

    Geoff Sher
    I invite you to call 702-699-7437 or 800-780-7437 or go online on this site and set up a one hour Skype consultation with me to discuss your case in detail.

    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.

    Geoff Sher

    CJ - April 13, 2016

    Thank you again for your input. My doctor convinced me yesterday it was the right thing to go ahead and transfer two of the 4 day 3 embryos I have. One was 8 cell and the other 9. By the time I got there one was compacting. I will see what happens but I am not optimistic.

    We live in Canada and we haven’t been able to find a doctor that is really willing to change up my protocol. Do you have any programs for out of country patients. I am hopeless here and really looking for a doctor that can help me get that take home baby. I am 28 and my doctor said “this is obviously a problem with egg quality as you barely produce any eggs on the highest dose of drugs” well…to me its clear evidence the more of that drug she gives me the worst my egg quality seems to get.

    Hopeless at this point.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - April 13, 2016

    Hi CJ,

    I do not believe that at 28y you have an intractable egg issue. I think the protocol for stimulation needs to be individualized and strategized…See the articles below.

    Unfortunately, I do not know who you could be referred to in Canada. perhaps you wish to talk with me and then consider coming to us for treatment.

    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
    • Ovarian Stimulation for IVF using GnRH Antagonists: Comparing the Agonist/Antagonist Conversion Protocol.(A/ACP) With the“Conventional” Antagonist Aproach
    • IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation(COS)
    • 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.
    • The BCP: Does Launching a Cycle of Controlled Ovarian Stimulation (COS). Coming off the BCP Compromise Response?
    • Implications of “Empty Follicle Syndrome and “Premature Luteinization”
    • Premature Luteinization (“the premature LH surge): Why it happens and how it can be prevented.

    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

    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.

    Geoff Sher

    CJ - January 9, 2017

    Hi Dr. Sher,

    I just wanted to let you know and also anyone else that reads your post and my comments that I ended up transferring that monosomy 16 mosaic embryo. I am currently 20 weeks pregnant with a healthy baby boy. So just as your post had said, sometimes they do correct and in my case, it did. Thank you!

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - January 10, 2017

    I am so happy to hear this and am delighted that you took my advice!

    G-d bless!

    Geoff Sher

    Julia - September 2, 2016 reply

    Dear Dr. Sher,
    I am almost 39, looks like DOR by now (AMH 0.78) and MFI with 2% morphology and borderline sperm DNA fragmentation. We just had a cycle with SIRM NY (300 FSH, HGH) where we got 3 mature eggs and froze 2 picture perfect 5-day expanded blasts, which both tested abnormal with Igenomix NGS (+7 and +22).
    Would you support transferring any of these?
    If so, should we check their Mitoscore?
    SET or both together?

    With having both abnormals, would you recommend trying again or move onto donor eggs?

    Thanks a lot!

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - September 2, 2016

    You could, in the hope that these are mosaic embryos but the likelihood is that they are abnormal. Thus it might be in your interest to try again so as to make hay while the sun still shines.

    Discuss with your RE.

    Geoff Sher

  • Maya - February 5, 2016 reply

    What percentage of the time do you think this occurs? There was an article from a NY practice stating 3/5 monosmy embryos implanted and produced a pregnancy, a very high rate

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - February 5, 2016 reply

    I do not know but please visit my new Blog on this very site, find the “search bar” and type “PGS in IVF: Are Some Chromosomally abnormal Embryos Capable of Resulting in Normal Babies and Being Wrongly Discarded?” 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.

    I invite you to call 702-699-7437 or 800-780-7437 or go online on this site and set up a one hour Skype consultation with me to discuss your case in detail.

    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.

    Geoff Sher

  • BernardRenteria - February 4, 2016 reply

    I think the pregnant women should get all the necessary health care facilities and services during her pregnancy period.

    http://www.cupissima.com

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - February 4, 2016 reply

    I agree!

    Geoff Sher

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