Genetically Testing Embryos for IVF

Preimplantation Genetic Screening (PGS):  PGS is the process whereby the chromosomes in the cells of an embryo (or the polar body of an egg) are examined (karyotyped). Embryo cells that have all 46 chromosomes intact are termed euploid. Those with additional chromosomal material and those with deficient chromosomal material are aneuploid.  In younger women, euploid embryos have better than a 50% chance of propagating a viable pregnancy. The chances in women >39y decreases slowly over time but regardless of the woman’s age is still around 40%. For those that conceive using such embryos, the miscarriage rate is well below 10%.

Embryo aneuploidy and “mosaicism”. While most embryo aneuploidy (>70%) originates from aneuploidy that occurs during reproductive division (meiosis) of either the egg or the sperm, the vast majority of cases are egg related. Such meiotic aneuploidy is irreversible and is responsible for >80% of IVF failures and early miscarriages. In contrast, in some cases where both the egg and sperm are euploid and upon fertilization propagate a euploid fertilized egg (zygote), during subsequent mitosis where the embryos cells multiply, some undergo “mutation” and become aneuploid while the majority maintain euploid division. This is referred to as embryo “mosaicism”. Upon reaching the uterine environment, mosaic embryos have the potential to leach out their aneuploid blastomeres, while allowing the euploid cells to multiply in an orderly fashion. This results in autocorrection and in most cases, in the subsequent development of a normal, euploid conceptus/baby.

Since some mitotically aneuploid (“mosaic”) embryos can, and indeed do “autocorrect’ while meiotically aneuploid embryos cannot, it follows that an ability to reliably differentiate between these two varieties of aneuploidy would potentially be of considerable clinical value. The introduction of a variety of preimplantation genetic screening (PGS) known as next generation gene sequencing (NGS) has vastly improved the ability to reliably and accurately karyotype embryos and thus to diagnose embryo “mosaicism”.

The ability of “mosaic embryos” to autocorrect is influenced by the stage at which the condition is diagnosed as well as the percentage of mosaic cells. Many embryos diagnosed as being mosaic while in the earlier cleaved state of development, subsequently undergo autocorrection to the euploid state (normal numerical chromosomal configuration) during the process of undergoing subsequent mitotic cell to the blastocyst stage. Similarly, mosaic blastocysts can also undergo autocorrection after being transferred to the uterus. The lower the percentage of mosaic cells in the blastocyst the greater the propensity to autocorrect and propagate chromosomally normal (euploid) offspring. By comparison, a blastocyst with 10% mosaicism could yield a 30% healthy baby rate with 10-15% miscarriage rate, while with >50% mosaicism the baby rate is roughly halved and the miscarriage rate double.

I advise all patients who subsequently conceive after undergoing ET using such “potentially mosaic” embryos to undergo prenatal genetic testing to rule out the development of an aneuploid fetus so that they can terminate affected pregnancies if they so choose.

Should PGS be done routinely in IVF? When Levent Keskintepe and I first introduced PGS testing into the clinical IVF arena (2005) initial results were most-encouraging. Embryo implantation rates of >50% and birth rates of 50-60% when up to two euploid blastocysts were transferred, were being  reported. In addition, the reported incidence of miscarriages and chromosomal birth defects was likewise greatly reduced.  In fact, we were so encouraged that most of us predicted that a time would come where full embryo karyotyping through PGS would become a routine part of IVF.  But alas…..we were soon to be disappointed when following the widespread introduction of PGS testing success rates started dropping. This was especially the case when PGS was performed on embryos derived from the eggs of older women and women with severely diminished ovarian reserve (DOR).  With further investigation it began to dawn upon us that:

  • Chromosomal numerical integrity, while being the most important determinant of embryo “competency” was likely not the only factor that impacted embryo “competency”. Indeed advancing age was revealed to increase the incidence of embryo aneuploidy, independent of embryo karyotype and this is probably linked to non-chromosomal, genetic and metabolomic factors that might also be age-related.
  • Independent of embryo competency, there are many variables, that can and also do determine IVF outcome and these are often outside the control of the embryology/genetic laboratory. They include selection and implementation of individualized protocols for controlled ovarian stimulation (COS), endometrial factors that determine embryo implantation (e.g. anatomical an immunologic implantation dysfunction), technical skill of the physician performing embryo transfer etc.
  • Not all PGS-aneuploid embryos are “incompetent”. Some are mosaic (see elsewhere) and these are often capable of “autocorrecting” upon being transferred to the uterus, and propagating healthy babies. In my experience, embryos that have additional or deficient chromosomal material affecting only one of the 23 chromosome pairs, are the ones most likely to be “mosaic”, while those that have absence or addition of chromosomal material involving several chromosome pairs, are almost always meiotically aneuploid

Against this background,  it is my considered opinion that PGS-embryo selection only be considered in the following circumstances:

  • Women over the age of 39Y and those who, regardless of age have significant DOR, are running out of eggs and time, and need to “make hay while the sun shines”!
  • Unexplained IVF failure.
  • Certain cases of recurrent pregnancy loss (RPL).
  • Family gender balancing cases
  • Women who have alloimmune implantation dysfunction (IID) with activation of uterine natural killer cells (NKa)…see elsewhere.
  • Where karyotyping reveals one or other partner to have a balanced chromosomal translocation
  • Known or anticipated specific genetic abnormalities

PGS for Gender Selection and Family balancing. Nevertheless, It is an inescapable reality that the very idea of medical sex selection challenges moral and ethical beliefs at their very foundation. Many hold that the growing popularity of gender selection solely for the convenience of altering a family’s gender balance represents an unwanted example of how assisted reproductive technology is subject to abuse…and thus it should be outlawed. They also see it as an example of a disturbing trend towards “designer babies” where genetic engineering could be used to manipulate the intellect, body configuration, build, height, and the talents of future offspring. This assertion is commonly followed by the tantalizing question as to where all this would end and whether we as a society “would really want to live in such a world.” There is, however, one clear exception to the apparent across-the-board opposition to sex selection that is well worthy of mention. This applies in cases where sex selection is used to avoid the occurrence of a serious medical disorder that selectively affects one gender or the other (e.g., Hemophilia, a life threatening bleeding disorder that selectively affects male offspring).PGD using comparative genomic hybridization (CGH) next generation gene sequencing (NGS) which assesse all the embryo’s chromosomes can be used for both detecting all the embryo’s chromosomes and thus can determine embryo “competency” reliably. It also reliably identifies gender.

Sex selection done purely for family balancing is somewhat controversial, raising concern that if widely accessible and freely available, such practice could distort the natural sex ratio, leading to a population gender imbalance. However, for this to happen, there would have to be a significant population preference for sex selection. In reality, the contrary seems to apply, since studies conducted in western societies discount these concerns. In fact, the relatively high cost of IVF with the added cost of gender selection in the United States makes it unlikely that the demand would ever become large enough to impact overall population gender balance. In addition, several studies done in Western countries have shown that the majority of people do not seem to be concerned about the gender of their offspring, and that with a few notable exceptions, gender preference does not appear to be slanted in the direction of either male or female. Thus, from a practical standpoint, such concerns are overstated.

Given that in the United States most couples do not care about the gender of their offspring, and only a minority are interested in selecting the sex of their children there is currently no risk that IVF sex-selection will impact the population gender balance. Thus, in my opinion by and large, freedom of choice should prevail and a service for sex selection should be freely available

So, I absolutely do offer gender selection in the following circumstances.

  • Medical Indications for Gender Selection:
    • For cases associated with
      • Sex-linked genetic disorders or,
      • Serious genetic disorders that are more likely to occur in one gender or the other.
    • Family balancing
      • For couples who have at least one child of the opposite gender to that which they choose for their IVF embryo transfer and,
      • For those women who do not have any children at all but prefer to have a child of one or the other gender.

 

6 Comments

Caroline

I am 43 years old and recently had my embryos tested through PGS testing (had frozen eggs when I was 38). I had my child naturally at the age of 41 (pregnant at 40) on our first try but now trying for a second child. One came back normal, 4 abnormal (multiple chromosomal issues), and 3 that had single monosomies. These are the notes
Abnormal mono 11 (grading 2-3BB-)
Abnormal mono 22 (grading 3BB?, contr)
Abnormal mono 22 (grading Cav-M, +F)

would you recommend transferring any of these if the normal one doesn’t work out? If so in which order.
Thank you!

reply
Dr. Geoffrey Sher

I would definitely recommend transferring any/all of thewe monosomic embryos. One or more could be “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 preimplantation embryo development and represents a major cause of early pregnancy loss. About a decade ago, I and my associate, Levent Keskintepe PhD were the first to introduce full embryo karyotyping (identification of all 46 chromosomes) through preimplantation genetic sampling (PGS) as a method by which to selectively transfer only euploid embryos (i.e. those that have a full component of chromosomes) to the uterus. We subsequently reported on a 2-3-fold improvement in implantation and birth rates as well as a significant reduction in early pregnancy loss, following IVF. Since then PGS has grown dramatically in popularity such that it is now widely used throughout the world.
Most IVF programs that offer PGS services, require that all participating patients consent to all their aneuploid embryos (i.e. those with an irregular quota of chromosomes) be disposed of. However, there is now growing evidence to suggest that following embryo transfer, some aneuploid embryos will in the process of ongoing development, convert to the euploid state (i.e. “autocorrection”) and then go on to develop into chromosomally normal offspring. In fact, I am personally aware of several such cases occurring within our IVF network. So clearly, summarily discarding all aneuploid embryos as a matter of routine we are sometimes destroying some embryos that might otherwise have “autocorrected” and gone on to develop into normal offspring.
Thus, by discarding aneuploid embryos the possibility exists that we could be denying some women the opportunity of having a baby. This creates a major ethical and moral dilemma for those of us that provide the option of PGS to our patients. On the one hand, we strive “to avoid knowingly doing harm” (the Hippocratic Oath) and as such would prefer to avoid or minimize the risk of miscarriage and/or chromosomal birth defects and on the other hand we would not wish to deny patients with aneuploid embryos, the opportunity to have a baby.
The basis for such embryo “autocorrection” lies in the fact that some embryos found through PGS-karyotyping to harbor one or more aneuploid cells (blastomeres) will often also harbor chromosomally normal (euploid) cells (blastomeres). The coexistence of both aneuploid and euploid cells coexisting in the same embryo is referred to as “mosaicism.”
It is against this background, that an ever-increasing number of IVF practitioners, rather than summarily discard PGS-identified aneuploid embryos are now choosing to cryobanking (freeze-store) certain of them, to leave open the possibility of ultimately transferring them to the uterus. In order to best understand the complexity of the factors involved in such decision making, it is essential to understand the causes of embryo aneuploidy of which there are two varieties:
1. Meiotic aneuploidy” results from aberrations in chromosomal numerical configuration that originate in either the egg (most commonly) and/or in sperm, during preconceptual maturational division (meiosis). Since meiosis occurs in the pre-fertilized egg or in and sperm, it follows that when aneuploidy occurs due to defective meiosis, all subsequent cells in the developing embryo/blastocyst/conceptus inevitably will be aneuploid, precluding subsequent “autocorrection”. Meiotic aneuploidy will thus invariably be perpetuated in all the cells of the embryo as they replicate. It is a permanent phenomenon and is irreversible. All embryos so affected are thus fatally damaged. Most will fail to implant and those that do implant will either be lost in early pregnancy or develop into chromosomally defective offspring (e.g. Down syndrome, Edward syndrome, Turner syndrome).
2. “Mitotic aneuploidy” occurs when following fertilization and subsequent cell replication (cleavage), some cells (blastomeres) of a meiotically normal (euploid) early embryo mutate and become aneuploid. This is referred to as “mosaicism”. Thereupon, with continued subsequent cell replication (mitosis) the chromosomal make-up (karyotype) of the embryo might either comprise of predominantly aneuploid cells or euploid cells. The subsequent viability or competency of the conceptus will thereupon depend on whether euploid or aneuploid cells predominate. If in such mosaic embryos aneuploid cells predominate, the embryo will be “incompetent”). If (as is frequently the case) euploid cells prevail, the mosaic embryo will likely be “competent” and capable of propagating a normal conceptus.
Since some mitotically aneuploid (“mosaic”) embryos can, and indeed do “autocorrect’ while meiotically aneuploid embryos cannot, it follows that an ability to reliably differentiate between these two varieties of aneuploidy would potentially be of considerable clinical value. The recent introduction of a variety of preimplantation genetic screening (PGS) known as next generation gene sequencing (NGS) has vastly improved the ability to reliably and accurately karyotype embryos and thus to diagnose embryo “mosaicism”.
The ability of mosaic embryos to autocorrect is influenced by the stage at which the condition is diagnosed as well as the percentage of mosaic cells. Many embryos diagnosed as being mosaic while in the earlier cleaved state of development, subsequently undergo autocorrection to the euploid state (normal numerical chromosomal configuration) during the process of undergoing subsequent mitotic cell to the blastocyst stage. Similarly, mosaic blastocysts can also undergo autocorrection after being transferred to the uterus. The lower the percentage of mosaic cells in the blastocyst the greater the propensity to autocorrect and propagate chromosomally normal (euploid) offspring. By comparison, a blastocyst with 10% mosaicism could yield a 30% healthy baby rate with 10-15% miscarriage rate, while with >50% mosaicism the baby rate is roughly halved and the miscarriage rate double.
Aneuploidy involves the addition (trisomy) or subtraction (monosomy) of one or part of one chromosome in any given pair. As previously stated, some aneuploidies are meiotic in origin while others are mitotic “mosaics”. Certain aneuploidies involve only a single, chromosome pair (simple aneuploidy) while others involve several pairs (i.e. complex aneuploidy). Aside from monosomy involving the absence of the y-sex chromosome (i.e. XO) which can result in a live birth (Turner syndrome) of a compromised baby, virtually all monosomies involving autosomes (non-sex chromosomes) are likely to be lethal and will rarely result in viable offspring. Some autosomal meiotic aneuploidies, especially trisomies 13, 18, 21, can propagate viable and severely chromosomally defective babies. Other meiotic autosomal trisomies will almost invariably, either not attach to the uterine lining or upon attachment, will soon be rejected. All forms of meiotic aneuploidy are irreversible while as stated, mitotic aneuploidy (“mosaicism) can autocorrect, yielding healthy offspring. Most complex aneuploidies are meiotic in origin and will thus almost invariably fail to propagate viable pregnancies.
Since certain “mosaic” meiotic aneuploid trisomy embryos (e.g. trisomies 13, 18, & 21) can potentially result in aneuploid concepti. For this reason, it is my opinion that unless the woman/couple receiving such embryos is willing to commit to terminating a resulting pregnancy found through amniocentesis or chorionic villus sampling (CVS) to be so affected, she/they are probably best advised not to transfer have them transferred to the uterus. Embryos harboring other autosomal mosaic trisomic embryos, should they not autocorrect in-utero will hardly ever produce a baby and as such there is hardly any risk at all…in transferring such embryos. However, it is my opinion that in the event of an ongoing pregnancy, amniocentesis or CVS should be performed to make certain that the baby is euploid. Conversely, when it comes to mosaic autosomal monosomy, given that virtually no autosomal monosomy embryos are likely to propagate viable pregnancies, the transfer of such mosaic embryos is virtually risk free. Needless to say, in any such cases , it is absolutely essential to make full disclosure to the patient (s) , and to insure the completion of a detailed informed consent agreement which would include a commitment by the patient (s) to undergo prenatal genetic testing (amniocentesis/CVS) aimed at excluding a chromosomal defect in the developing baby and/or a willingness to terminate the pregnancy should a serious birth defect be diagnosed.

I strongly recommend that you visit http://www.SherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.
• A Fresh Look at the Indications for IVF
• The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
• Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
• IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation(COS)
• The Fundamental Requirements For Achieving Optimal IVF Success
• Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
• Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
• Controlled Ovarian Stimulation (COS) in Older women and Women who have Diminished Ovarian Reserve (DOR): A Rational Basis for Selecting a Stimulation Protocol
• Optimizing Response to Ovarian Stimulation in Women with Compromised Ovarian Response to Ovarian Stimulation: A Personal Approach.
• Hereditary Clotting Defects (Thrombophilia)
• Blastocyst Embryo Transfers done 5-6 Days Following Fertilization are Fast Replacing Earlier day 2-3 Transfers of Cleaved Embryos.
• Embryo Transfer Procedure: The “Holy Grail in IVF.
• Timing of ET: Transferring Blastocysts on Day 5-6 Post-Fertilization, Rather Than on Day 2-3 as Cleaved Embryos.
• IVF: Approach to Selecting the Best Embryos for Transfer to the Uterus.
• Fresh versus Frozen Embryo Transfers (FET) Enhance IVF Outcome
• Frozen Embryo Transfer (FET): A Rational Approach to Hormonal Preparation and How new Methodology is Impacting IVF.
• Staggered IVF
• Staggered IVF with PGS- Selection of “Competent” Embryos Greatly Enhances the Utility & Efficiency of IVF.
• Staggered IVF: An Excellent Option When. Advancing Age and Diminished Ovarian Reserve (DOR) Reduces IVF Success Rate
• Embryo Banking/Stockpiling: Slows the “Biological Clock” and offers a Selective Alternative to IVF-Egg Donation
• Preimplantation Genetic Testing (PGS) in IVF: It should be Used Selectively and NOT be Routine.
• IVF: Selecting the Best Quality Embryos to Transfer
• Preimplantation Genetic Sampling (PGS) Using: Next Generation Gene Sequencing (NGS): Method of Choice.
• PGS and Assessment of Egg/Embryo “competency”: How Method, Timing and Methodology Could Affect Reliability
• IVF outcome: How Does Advancing Age and Diminished Ovarian Reserve (DOR) Affect Egg/Embryo “Competency” and How Should the Problem be addressed.

If you are interested in my advice or medical services, I urge you to contact my patient concierge, ASAP to set up a Skype or an in-person consultation with me. You can also set this up by emailing concierge@sherivf.com or by calling 702-533-2691 and/or 800-780-743. You can also enroll for a consultation with me, online at http://www.SherIVF.com.
Also, my book, “In Vitro Fertilization, the ART of Making Babies” is available as a down-load through http://www.Amazon.com .

Geoffrey Sher MD

reply
C Cox

Thank you very much Dr Sher, your information has been most helpful. I have also contacted concierge to try and organize a Skype call. This will be our last attempt due to my age and would ideally prefer to transfer the remaining 2 embryos (as per our 5 previous attempts) which have come back from PGS – 1 x mosaic 20 and 1 x normal. Rather than dealing with moral and emotional dilemma of leaving one in storage or having to decide its fate. I understand transferring both is not without risk but this is our first PGS so previously we’ve not known the genetic make up either nor does the normal embryo come with guarantee of being genetically normal. I am 43 years and good egg reserve with 16 retrieved last month, 9 fertilized and 4 PGS tested. No reason for PGS, apart from advanced maternal age.

Thank you again

reply
Dr. Geoffrey Sher

I agree with your reasoning and wish you al the good fortune possible.

Geoff Sher

reply
C Cox

I have a embryo with Trisomy 20 Mosaic and I have read many articles and case studies, all indicate that I have a 90% chance of a healthy child. My clinic doesn’t class it as abnormal so I am left with the decision. Would you transfer?

reply
Dr. Geoffrey Sher

I do not buy the 90% bit. However, I would definitely transfer the blastocyst with trisomy 20.

Human embryo development occurs through a process that encompasses reprogramming, sequential cleavage divisions and mitotic chromosome segregation and embryonic genome activation. Chromosomal abnormalities may arise during germ cell and/or preimplantation embryo development and represents a major cause of early pregnancy loss. About a decade ago, I and my associate, Levent Keskintepe PhD were the first to introduce full embryo karyotyping (identification of all 46 chromosomes) through preimplantation genetic sampling (PGS) as a method by which to selectively transfer only euploid embryos (i.e. those that have a full component of chromosomes) to the uterus. We subsequently reported on a 2-3-fold improvement in implantation and birth rates as well as a significant reduction in early pregnancy loss, following IVF. Since then PGS has grown dramatically in popularity such that it is now widely used throughout the world.
Most IVF programs that offer PGS services, require that all participating patients consent to all their aneuploid embryos (i.e. those with an irregular quota of chromosomes) be disposed of. However, there is now growing evidence to suggest that following embryo transfer, some aneuploid embryos will in the process of ongoing development, convert to the euploid state (i.e. “autocorrection”) and then go on to develop into chromosomally normal offspring. In fact, I am personally aware of several such cases occurring within our IVF network. So clearly, summarily discarding all aneuploid embryos as a matter of routine we are sometimes destroying some embryos that might otherwise have “autocorrected” and gone on to develop into normal offspring.
Thus, by discarding aneuploid embryos the possibility exists that we could be denying some women the opportunity of having a baby. This creates a major ethical and moral dilemma for those of us that provide the option of PGS to our patients. On the one hand, we strive “to avoid knowingly doing harm” (the Hippocratic Oath) and as such would prefer to avoid or minimize the risk of miscarriage and/or chromosomal birth defects and on the other hand we would not wish to deny patients with aneuploid embryos, the opportunity to have a baby.
The basis for such embryo “autocorrection” lies in the fact that some embryos found through PGS-karyotyping to harbor one or more aneuploid cells (blastomeres) will often also harbor chromosomally normal (euploid) cells (blastomeres). The coexistence of both aneuploid and euploid cells coexisting in the same embryo is referred to as “mosaicism.”
It is against this background, that an ever-increasing number of IVF practitioners, rather than summarily discard PGS-identified aneuploid embryos are now choosing to cryobanking (freeze-store) certain of them, to leave open the possibility of ultimately transferring them to the uterus. In order to best understand the complexity of the factors involved in such decision making, it is essential to understand the causes of embryo aneuploidy of which there are two varieties:
1. Meiotic aneuploidy” results from aberrations in chromosomal numerical configuration that originate in either the egg (most commonly) and/or in sperm, during preconceptual maturational division (meiosis). Since meiosis occurs in the pre-fertilized egg or in and sperm, it follows that when aneuploidy occurs due to defective meiosis, all subsequent cells in the developing embryo/blastocyst/conceptus inevitably will be aneuploid, precluding subsequent “autocorrection”. Meiotic aneuploidy will thus invariably be perpetuated in all the cells of the embryo as they replicate. It is a permanent phenomenon and is irreversible. All embryos so affected are thus fatally damaged. Most will fail to implant and those that do implant will either be lost in early pregnancy or develop into chromosomally defective offspring (e.g. Down syndrome, Edward syndrome, Turner syndrome).
2. “Mitotic aneuploidy” occurs when following fertilization and subsequent cell replication (cleavage), some cells (blastomeres) of a meiotically normal (euploid) early embryo mutate and become aneuploid. This is referred to as “mosaicism”. Thereupon, with continued subsequent cell replication (mitosis) the chromosomal make-up (karyotype) of the embryo might either comprise of predominantly aneuploid cells or euploid cells. The subsequent viability or competency of the conceptus will thereupon depend on whether euploid or aneuploid cells predominate. If in such mosaic embryos aneuploid cells predominate, the embryo will be “incompetent”). If (as is frequently the case) euploid cells prevail, the mosaic embryo will likely be “competent” and capable of propagating a normal conceptus.
Since some mitotically aneuploid (“mosaic”) embryos can, and indeed do “autocorrect’ while meiotically aneuploid embryos cannot, it follows that an ability to reliably differentiate between these two varieties of aneuploidy would potentially be of considerable clinical value. The recent introduction of a variety of preimplantation genetic screening (PGS) known as next generation gene sequencing (NGS) has vastly improved the ability to reliably and accurately karyotype embryos and thus to diagnose embryo “mosaicism”.
The ability of mosaic embryos to autocorrect is influenced by the stage at which the condition is diagnosed as well as the percentage of mosaic cells. Many embryos diagnosed as being mosaic while in the earlier cleaved state of development, subsequently undergo autocorrection to the euploid state (normal numerical chromosomal configuration) during the process of undergoing subsequent mitotic cell to the blastocyst stage. Similarly, mosaic blastocysts can also undergo autocorrection after being transferred to the uterus. The lower the percentage of mosaic cells in the blastocyst the greater the propensity to autocorrect and propagate chromosomally normal (euploid) offspring. By comparison, a blastocyst with 10% mosaicism could yield a 30% healthy baby rate with 10-15% miscarriage rate, while with >50% mosaicism the baby rate is roughly halved and the miscarriage rate double.
Aneuploidy involves the addition (trisomy) or subtraction (monosomy) of one or part of one chromosome in any given pair. As previously stated, some aneuploidies are meiotic in origin while others are mitotic “mosaics”. Certain aneuploidies involve only a single, chromosome pair (simple aneuploidy) while others involve several pairs (i.e. complex aneuploidy). Aside from monosomy involving the absence of the y-sex chromosome (i.e. XO) which can result in a live birth (Turner syndrome) of a compromised baby, virtually all monosomies involving autosomes (non-sex chromosomes) are likely to be lethal and will rarely result in viable offspring. Some autosomal meiotic aneuploidies, especially trisomies 13, 18, 21, can propagate viable and severely chromosomally defective babies. Other meiotic autosomal trisomies will almost invariably, either not attach to the uterine lining or upon attachment, will soon be rejected. All forms of meiotic aneuploidy are irreversible while as stated, mitotic aneuploidy (“mosaicism) can autocorrect, yielding healthy offspring. Most complex aneuploidies are meiotic in origin and will thus almost invariably fail to propagate viable pregnancies.
Since certain “mosaic” meiotic aneuploid trisomy embryos (e.g. trisomies 13, 18, & 21) can potentially result in aneuploid concepti. For this reason, it is my opinion that unless the woman/couple receiving such embryos is willing to commit to terminating a resulting pregnancy found through amniocentesis or chorionic villus sampling (CVS) to be so affected, she/they are probably best advised not to transfer have them transferred to the uterus. Embryos harboring other autosomal mosaic trisomic embryos, should they not autocorrect in-utero will hardly ever produce a baby and as such there is hardly any risk at all…in transferring such embryos. However, it is my opinion that in the event of an ongoing pregnancy, amniocentesis or CVS should be performed to make certain that the baby is euploid. Conversely, when it comes to mosaic autosomal monosomy, given that virtually no autosomal monosomy embryos are likely to propagate viable pregnancies, the transfer of such mosaic embryos is virtually risk free. Needless to say, in any such cases , it is absolutely essential to make full disclosure to the patient (s) , and to insure the completion of a detailed informed consent agreement which would include a commitment by the patient (s) to undergo prenatal genetic testing (amniocentesis/CVS) aimed at excluding a chromosomal defect in the developing baby and/or a willingness to terminate the pregnancy should a serious birth defect be diagnosed.

I strongly recommend that you visit http://www.SherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.
• A Fresh Look at the Indications for IVF
• The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
• Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
• IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation(COS)
• The Fundamental Requirements For Achieving Optimal IVF Success
• Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
• Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
• Controlled Ovarian Stimulation (COS) in Older women and Women who have Diminished Ovarian Reserve (DOR): A Rational Basis for Selecting a Stimulation Protocol
• Optimizing Response to Ovarian Stimulation in Women with Compromised Ovarian Response to Ovarian Stimulation: A Personal Approach.
• Hereditary Clotting Defects (Thrombophilia)
• Blastocyst Embryo Transfers done 5-6 Days Following Fertilization are Fast Replacing Earlier day 2-3 Transfers of Cleaved Embryos.
• Embryo Transfer Procedure: The “Holy Grail in IVF.
• Timing of ET: Transferring Blastocysts on Day 5-6 Post-Fertilization, Rather Than on Day 2-3 as Cleaved Embryos.
• IVF: Approach to Selecting the Best Embryos for Transfer to the Uterus.
• Fresh versus Frozen Embryo Transfers (FET) Enhance IVF Outcome
• Frozen Embryo Transfer (FET): A Rational Approach to Hormonal Preparation and How new Methodology is Impacting IVF.
• Staggered IVF
• Staggered IVF with PGS- Selection of “Competent” Embryos Greatly Enhances the Utility & Efficiency of IVF.
• Staggered IVF: An Excellent Option When. Advancing Age and Diminished Ovarian Reserve (DOR) Reduces IVF Success Rate
• Embryo Banking/Stockpiling: Slows the “Biological Clock” and offers a Selective Alternative to IVF-Egg Donation
• Preimplantation Genetic Testing (PGS) in IVF: It should be Used Selectively and NOT be Routine.
• IVF: Selecting the Best Quality Embryos to Transfer
• Preimplantation Genetic Sampling (PGS) Using: Next Generation Gene Sequencing (NGS): Method of Choice.
• PGS and Assessment of Egg/Embryo “competency”: How Method, Timing and Methodology Could Affect Reliability
• IVF outcome: How Does Advancing Age and Diminished Ovarian Reserve (DOR) Affect Egg/Embryo “Competency” and How Should the Problem be addressed.

If you are interested in my advice or medical services, I urge you to contact my patient concierge, ASAP to set up a Skype or an in-person consultation with me. You can also set this up by emailing concierge@sherivf.com or by calling 702-533-2691 and/or 800-780-743. You can also enroll for a consultation with me, online at http://www.SherIVF.com.
Also, my book, “In Vitro Fertilization, the ART of Making Babies” is available as a down-load through http://www.Amazon.com .

Geoffrey Sher MD

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