Your AFC, your age and your basal FSH all suggest to me that the AMH value might  not br accurate. I would definitely repeat it!~

Good luck!

Geoff Sher

______________________________________________________________________________________

ADDITIONAL INFORMATION:

I am attaching online links to two E-books which I recently  co-authored with  my partner at SFS-NY  (Drew Tortoriello MD)……. for your reading pleasure:

1.From In Vitro Fertilization to Family: A Journey with Sher Fertility Solutions (SFS) “

https://sherfertilitysolutions.com/sher-fertility-solutions-ebook.pdf

1. “Recurrent Pregnancy Loss and Unexplained IVF Failure: The Immunologic Link

https://drive.google.com/file/d/1iYKz-EkAjMqwMa1ZcufIloRdxnAfDH8L/view

………………………………………………………………..

Regrettably! , this does not sound like a viable pregnancy! I hope I am wrong!

Geoff Sher

_____________________________________________________________

Measuring and interpreting Blood hCG to Assess Pregnancy Viability Following ART Treatments.

Geoffrey Sher MD

I know of no medical announcement associated with the degree of emotional anticipation and anguish as that associated with a pending diagnosis/confirmation of pregnancy following infertility treatment. In fact, hardly a day goes by where I am not confronted by a patient anxiously seeking interpretation of a pregnancy test result.

Testing urine or blood for the presence of human chorionic gonadotropin (hCG) is the most effective and reliable way to confirm conception. The former, is far less expensive than the latter and is the most common method used. It is also more convenient because it can be performed in the convenience of the home setting. However, urine hCG testing for pregnancy is not nearly as reliable or as sensitive e as is blood hCG testing. Blood testing can detect implantation several days earlier than can a urine test. Modern pregnancy urine test kits can detect hCG about 16-18 days following ovulation (or 2-3 days after having missed a menstrual period), while blood tests can detect hCG, 12-13 days post-ovulation (i.e. even prior to menstruation).

The ability to detect hCG in the blood as early as possible and thereupon to track its increase, is particularly valuable in women undergoing controlled ovarian stimulation (COS) with or without intrauterine insemination (IUI) or after IVF. The earlier hCG can be detected in the blood and its concentration measured, the sooner levels can be tracked serially over time and so provide valuable information about the effectiveness of implantation, and the potential viability of the developing conceptus.

There are a few important points that should be considered when it comes to measuring interpreting blood hCG levels. These include the following:

• All modern day blood (and urine) hCG tests are highly specific in that they measure exclusively for hCG. There is in fact no cross-reactivity with other hormones such as estrogen, progesterone or LH.
• Post conception hCG levels, measured 10 days post ovulation or egg retrieval can vary widely (ranging from 5mIU/ml to above 400mIU/ml. The level will double every 48–72 hours up to the 6th week of gestation whereupon the doubling rate starts to slow down to about 96 hours. An hCG level of 13,000-290, 0000 mIU/ml is reached by the end of the 1st trimester (12 weeks) whereupon it slowly declines to approximately 26,000– 300,000 mIU/ml by full term. Below are the average hCG levels during the first trimester:

• • 3 weeks LMP: 5 – 50 mIU/ml
  • 4 weeks LMP: 5 – 426 mIU/ml
  • 5 weeks LMP: 18 – 7,340 mIU/ml
  • 6 weeks LMP: 1,080 – 56,500 mIU/ml
  • 7 – 8 weeks LMP: 7, 650 – 229,000 mIU/ml
  • 9 – 12 weeks LMP: 25,700 – 288,000 mIU/ml

• A single hCG blood level is not sufficient to assess the viability of an implanting embryo. Caution should be used in making too much of an initial hCG level. This is because a normal pregnancy can start with relatively low hCG blood levels. It is the rate of the rise of the blood hCG level that is relevant.
• In some cases the initially hCG level is within the normal range, but then fails to double in the ensuing 48-72hours. In some cases it might even plateau or decline, only to start doubling appropriately thereafter. When this happens, it could be due to:
  • A recovering implantation, destined to develop into a clinical gestation
  • A failing implantation (a chemical pregnancy)
  • A multiple pregnancy which is spontaneously reducing (i.e., one or more of the concepti is being lost) or,
  • An ectopic pregnancy which will either absorb spontaneously (a chemical-tubal gestation), or evolve into a full blown tubal pregnancy continue and declare itself through characteristic symptoms and signs of an intraperitoneal bleed.
• The blood hCG test needs to be repeated at least once after 48h and in some cases it will need to be repeated one or more times (at 48h intervals) thereafter, to confirm that implantation is progressing normally.
• Ultimately the diagnosis of a viable pregnancy requires confirmation of the presence of an intrauterine gestational sac by ultrasound examination. The earliest that this can be achieved is when the beta hCG level exceeds 1,000mIU/ml (i.e., around 5-6 weeks).
• Most physicians prefer to defer the performance of a routine US diagnosis of pregnancy until closer to the 7th week. This is because by that time, cardiac activity should be clearly detectable, allowing for more reliable assessment of pregnancy viability.
• There are cases where the blood beta hCG level is extraordinarily high or the rate of rise is well above the normal doubling rate. The commonest explanation is that more than one pregnancy has implanted. However in some cases it can point to a molar pregnancy
• Finally, there on rare occasions, conditions unrelated to pregnancy can result in detectable hCG levels in blood and urine. They include ovarian tumors that produce hCG, such as certain types of cystic teratomas (dermoid cysts) and some ovarian cancers such as dysgerminomas.

________________________________________________________________________________________________________________________

ADDITIONAL INFORMATION:

I am attaching online links to two E-books which I recently  co-authored with  my partner at SFS-NY  (Drew Tortoriello MD)……. for your reading pleasure:

1.From In Vitro Fertilization to Family: A Journey with Sher Fertility Solutions (SFS) “

https://sherfertilitysolutions.com/sher-fertility-solutions-ebook.pdf

1. “Recurrent Pregnancy Loss and Unexplained IVF Failure: The Immunologic Link

https://drive.google.com/file/d/1iYKz-EkAjMqwMa1ZcufIloRdxnAfDH8L/view

………………………………………………………………..

I

Measuring and interpreting Blood hCG to Assess Pregnancy Viability Following ART Treatments.

Geoffrey Sher MD

I know of no medical announcement associated with the degree of emotional anticipation and anguish as that associated with a pending diagnosis/confirmation of pregnancy following infertility treatment. In fact, hardly a day goes by where I am not confronted by a patient anxiously seeking interpretation of a pregnancy test result.

Testing urine or blood for the presence of human chorionic gonadotropin (hCG) is the most effective and reliable way to confirm conception. The former, is far less expensive than the latter and is the most common method used. It is also more convenient because it can be performed in the convenience of the home setting. However, urine hCG testing for pregnancy is not nearly as reliable or as sensitive e as is blood hCG testing. Blood testing can detect implantation several days earlier than can a urine test. Modern pregnancy urine test kits can detect hCG about 16-18 days following ovulation (or 2-3 days after having missed a menstrual period), while blood tests can detect hCG, 12-13 days post-ovulation (i.e. even prior to menstruation).

The ability to detect hCG in the blood as early as possible and thereupon to track its increase, is particularly valuable in women undergoing controlled ovarian stimulation (COS) with or without intrauterine insemination (IUI) or after IVF. The earlier hCG can be detected in the blood and its concentration measured, the sooner levels can be tracked serially over time and so provide valuable information about the effectiveness of implantation, and the potential viability of the developing conceptus.

There are a few important points that should be considered when it comes to measuring interpreting blood hCG levels. These include the following:

• All modern day blood (and urine) hCG tests are highly specific in that they measure exclusively for hCG. There is in fact no cross-reactivity with other hormones such as estrogen, progesterone or LH.
• Post conception hCG levels, measured 10 days post ovulation or egg retrieval can vary widely (ranging from 5mIU/ml to above 400mIU/ml. The level will double every 48–72 hours up to the 6th week of gestation whereupon the doubling rate starts to slow down to about 96 hours. An hCG level of 13,000-290, 0000 mIU/ml is reached by the end of the 1st trimester (12 weeks) whereupon it slowly declines to approximately 26,000– 300,000 mIU/ml by full term. Below are the average hCG levels during the first trimester:

• • 3 weeks LMP: 5 – 50 mIU/ml
  • 4 weeks LMP: 5 – 426 mIU/ml
  • 5 weeks LMP: 18 – 7,340 mIU/ml
  • 6 weeks LMP: 1,080 – 56,500 mIU/ml
  • 7 – 8 weeks LMP: 7, 650 – 229,000 mIU/ml
  • 9 – 12 weeks LMP: 25,700 – 288,000 mIU/ml

• A single hCG blood level is not sufficient to assess the viability of an implanting embryo. Caution should be used in making too much of an initial hCG level. This is because a normal pregnancy can start with relatively low hCG blood levels. It is the rate of the rise of the blood hCG level that is relevant.
• In some cases the initially hCG level is within the normal range, but then fails to double in the ensuing 48-72hours. In some cases it might even plateau or decline, only to start doubling appropriately thereafter. When this happens, it could be due to:
  • A recovering implantation, destined to develop into a clinical gestation
  • A failing implantation (a chemical pregnancy)
  • A multiple pregnancy which is spontaneously reducing (i.e., one or more of the concepti is being lost) or,
  • An ectopic pregnancy which will either absorb spontaneously (a chemical-tubal gestation), or evolve into a full blown tubal pregnancy continue and declare itself through characteristic symptoms and signs of an intraperitoneal bleed.
• The blood hCG test needs to be repeated at least once after 48h and in some cases it will need to be repeated one or more times (at 48h intervals) thereafter, to confirm that implantation is progressing normally.
• Ultimately the diagnosis of a viable pregnancy requires confirmation of the presence of an intrauterine gestational sac by ultrasound examination. The earliest that this can be achieved is when the beta hCG level exceeds 1,000mIU/ml (i.e., around 5-6 weeks).
• Most physicians prefer to defer the performance of a routine US diagnosis of pregnancy until closer to the 7th week. This is because by that time, cardiac activity should be clearly detectable, allowing for more reliable assessment of pregnancy viability.
• There are cases where the blood beta hCG level is extraordinarily high or the rate of rise is well above the normal doubling rate. The commonest explanation is that more than one pregnancy has implanted. However in some cases it can point to a molar pregnancy
• Finally, there on rare occasions, conditions unrelated to pregnancy can result in detectable hCG levels in blood and urine. They include ovarian tumors that produce hCG, such as certain types of cystic teratomas (dermoid cysts) and some ovarian cancers such as dysgerminomas.

______________________________________________________________________________________________

ADDITIONAL INFORMATION:

I am attaching online links to two E-books which I recently  co-authored with  my partner at SFS-NY  (Drew Tortoriello MD)……. for your reading pleasure:

1.From In Vitro Fertilization to Family: A Journey with Sher Fertility Solutions (SFS) “

https://sherfertilitysolutions.com/sher-fertility-solutions-ebook.pdf

1. “Recurrent Pregnancy Loss and Unexplained IVF Failure: The Immunologic Link

https://drive.google.com/file/d/1iYKz-EkAjMqwMa1ZcufIloRdxnAfDH8L/view

………………………………………………………………..

It is primarily the egg (rather than the sperm) that determines the chromosomal integrity (karyotype) of the embryo, the most important determinant of egg/embryo competency”. A “competent” egg is therefore one that has a normal karyotype and has the best potential to propagate a “competent” embryo. In turn, a “competent embryo is one that possesses the highest potential to implant and develop into a normal, healthy, baby.

When it comes to reproductive performance, humans are the least efficient of all mammals. Even in young women under 35y, at best only 2 out of 3 eggs are chromosomally numerically normal (euploid). The remainder will have an irregular number of chromosomes (aneuploid) and are thus “incompetent”. The incidence of egg aneuploidy increases with age such by age 39 years, 3 in 4 are “competent”, and by the mid-forties, at best one in 10 are likely to be aneuploid. The fertilization of an aneuploid egg will inevitably lead to embryo aneuploidy (“incompetence”). As previously stated,   an aneuploid embryo cannot propagate a normal pregnancy

Within 38-42 hours of the initiation of the spontaneous pre-ovulatory luteinizing hormone (LH) surge (and also following administration of the human chorionic gonadotropin (hCG) “trigger” shot, given to induce egg maturation after ovarian stimulation with fertility drugs), the egg embarks on a rapid maturational process that involves halving of its 46 chromosomes to 23. During this process, (known as meiosis) 23 chromosomes are retained within the nucleus of the egg while the remaining 23 chromosomes are expelled in a membrane envelopment, from the egg nucleus. This small structure known as the polar body, comes to lie immediately below the “shell” of the egg (the zona pellucida) and is known as the 1st polar body or PB-1. The sperm, in the process of its maturation also undergoes meiosis divides into two separate functional gametes, each containing 23 chromosomes (half its original number of 46 chromosomes).  With subsequent fertilization, the 23 chromosomes of the egg now fuse with the 23 chromosomes of the mature sperm resulting in the development of an embryo with  46 chromosomes (the normal human genome) comprising a combination of the genetic material from both partners. For the embryo to have exactly 46 chromosomes (the euploid number), both the mature egg and mature spermatozoon must contain exactly 23 chromosomes. Only such euploid embryos are “competent” (capable of developing into healthy babies). Those with an irregular number of chromosomes (aneuploid embryos) are “incompetent” and are incapable of propagating healthy babies. While embryo “incompetence” can result from either egg or sperm aneuploidy, it usually stems from egg aneuploidy. However, in cases of moderate or severe male factor infertility, the sperm’s contribution to aneuploidy of the embryo can be significantly greater.

While embryo ploidy (numerical chromosomal integrity) is not the only determinant of its “competency, it is by far the most important and in fact is a rate-limiting factor in human reproduction. It is causal in the vast majority of cases of “failed nidation which in turn is responsible for most cases of a failed pregnancy (natural or assisted) and causes most sporadic early pregnancy losses (both chemical gestations and miscarriages) as well as  many chromosomal birth defects such as Turner syndrome (X-monosomy ) Down syndrome (trisomy 21) and Edward syndrome (trisomy 18) .

In most cases, embryos that develop too slowly as well as those that grow too fast (i.e. ones that by day 3 post-fertilization comprise fewer than 6 cells or more than 9 cells) and/or embryos that contain cell debris or “fragments” are usually aneuploid and are thus unable to propagate a healthy pregnancy (“incompetent”). Additionally, embryos that fail to survive in culture to the blastocyst stage are also almost always aneuploid/”incompetent”.

At a certain point in the later stage of a woman’s reproductive career, the number of remaining eggs in her ovaries falls below a certain threshold, upon which she is unable to respond optimally to fertility drugs. Often times this is signaled by a rising day 3 basal blood follicle stimulating hormone (FSH) level (>9.0MIU/ml) and a falling blood anti-Mullerian hormone (AMH) level (<2.0ng/ml or <15nmol/L). Such women who have  diminished ovarian reserve (DOR) produce fewer eggs in response to ovarian stimulation. While DOR is most commonly encountered in women over 40 years of age it can and indeed also can occur in much younger women.

A few important (but often overlooked concepts should be considered in this regard:

• Age: It is advancing chronologic age and NOT declining ovarian reserve (as evidenced by abnormal blood AMH or FSH that results in an increased incidence of egg/embryo “incompetence” due to aneuploidy
• The ovaries and developing eggs of women with DOR (regardless of age) are highly susceptible to the adverse effect of excessive Luteinizing Hormone (LH)-induced, ovarian overproduction of male hormones (e,g. testosterone and androstenedione). While a little testosterone produced by the ovary promotes normal follicle growth and orderly egg development excessive testosterone has a converse effect. That is why in older women and those who regardless of their age have DOR (and thus excessive LH bioavailability and increased ovarian testosterone production), the use of ovarian stimulation protocols that fail to down-regulate LH activity prior to initiating ovarian stimulation with gonadotropins, often prejudices egg/embryo quality and IVF outcome.
• Simply stated, while age is certainly the most important factor in determining the incidence of egg/embryo aneuploidy, women with DOR (regardless of their age), are less likely to propagate euploid (competent) eggs/embryos. While virtually nothing can be done to lower the incidence of age related aneuploidy, it is indeed possible to avoid a further decrease in egg/embryo “competency”  by individualizing the protocols of ovarian stimulation used.
• My preferred protocols for women who have relatively normal ovarian reserve:
• The conventional long pituitary down regulation protocol: BCP are commenced early in the cycle and continued for at least 10 days. Starting 3 days before the BCP is to be discontinued, it is overlapped with an agonist such as Lupron 10U daily for three (3) days and continued until menstruation begins (which should ensue within 5-7 days of stopping the BCP). At that point an US examination is done along with a baseline measurement of blood estradiol to exclude a functional ovarian cyst. Daily Lupron (10U) is continued and an FSH-dominant gonadotropin such as Follistim, Puregon or Gonal-f daily is administered daily falong with 37.5U of Menopur (an FSH/LH combination) for 2 days. On the 3^rd day the gonadotropin dosage is reduced by about one half and the dosage of Menopur is increased to 75U daily. Daily ultrasound and blood estradiol measurements are conducted starting on the 7^th or 8^th day of gonadotropin administration and continued until daily ultrasound follicle assessments indicate that most follicles have fully developed. At this point egg maturation is “triggered” using an intramuscular injection of a recombinant hCGr (Ovidrel) 500mcg or urinary derived hCGu (Pregnyl/Profasi/Novarel) 10,000U. And an egg retrieval is scheduled for 36h later.
• The agonist/antagonist conversion protocol (A/ACP): This is essentially the same as the conventional long down regulation protocol (see “a”-as above), except that with the onset of post-BCP menstruation, the agonist is supplanted by daily administration of a GnRH antagonist (e.g. Ganirelix, Cetrotide or Orgalutron) at a dosage of 125-250mcg daily until the day of the “trigger”. When it comes to women who have DOR I favor the use of the A/ACP, adding supplementary human growth hormone (HGH). In cases where the DOR is regarded as severe (AMH=<0.2), I often augment  the AACP protocol by using estrogen priming for 7-9 days prior to or with the commencement of gonadotropin therapy; For this I prescribe E2 skin patches  or intramuscular  estradiol valerate (Delestrogen), prior to or sometimes concurrent with, the  commencement of the GnRH antagonist administration.
• The following Ovarian stimulation protocols are in my opinion best avoided in stimulating olderf women and /or thosed who regardless of age , have  DOR :

1. Microdose agonist (e.g. Lupron) “flare” protocols which result in an out-pouring of pituitary-LH at the critical time that ovarian follicles and eggs start developing/growing.
2. High dosages of LH -containing fertility drugs (e.g. Menopur).
3. Supplementation with preparations that are testosterone-based
4. Supplementation with DHEA (which is converted to testosterone in the ovaries.
5. Clomiphene citrate or Letrozole which cause increased release of LH and thus increase ovarian male hormone (testosterone and androstenedione output.
6. “Triggering” egg maturation using too low a dosage of hCG (e.g. 5,000U rather than 10,000U) or Ovidrel (e.g. 250mcg of Ovidrel rather than 500mcg)
7. “Triggering” women who have DOR, with an agonist (alone)such as Lupron Superfact/ Buserelin/Aminopeptidyl/Decapeptyl.

• Preimplantation Genetic Screening (PGS):

The introduction of preimplantation genetic testing/screening (PGT/PGS) for e permits identification of all the chromosomes in the egg and embryo (full karyotyping) allowing for the  identification of the most “competent” (euploid) embryos for selective transfer to the uterus. This vastly improves the efficiency and success of the IVF process and renders us fare better equipped us to manage older women and those who regardless of their age, have DOR.

Please visit my new Blog on this very site, www. SherIVF.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

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ADDENDUM: PLEASE READ!!

INTRODUCING SHER FERTILITY SOLUTIONS (SFS)

Founded in April 2019, Sher Fertility Solutions (SFS) offers online (Skype/FaceTime) consultations to patients from > 40 different countries. All consultations are followed by a detailed written report presenting my personal recommendations for treatment of what often constitute complex Reproductive Issues.

________________________________________________________________________________

ADDITIONAL INFORMATION:

I am attaching online links to two E-books which I recently  co-authored with  my partner at SFS-NY  (Drew Tortoriello MD)……. for your reading pleasure:

1.From In Vitro Fertilization to Family: A Journey with Sher Fertility Solutions (SFS) “

https://sherfertilitysolutions.com/sher-fertility-solutions-ebook.pdf

1. “Recurrent Pregnancy Loss and Unexplained IVF Failure: The Immunologic Link

https://drive.google.com/file/d/1iYKz-EkAjMqwMa1ZcufIloRdxnAfDH8L/view

………………………………………………………………..

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.

Many 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,  growing evidence  suggests  that following embryo transfer, some aneuploid embryos will in the process of ongoing development,  convert to the euploid state (i.e. “autocorrect”) and then go on to develop into chromosomally normal offspring. In fact, I am personally aware of several such cases having occurred in my own practice. 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 (“Mosaicism”) 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”.

Most complex aneuploidies are meiotic in origin and will thus almost invariably fail to propagate viable pregnancies. The ability of mosaic embryos to autocorrect is influenced by stage of embryo development in which the diagnosis is made, which chromosomes are affected, whether the aneuploidy involves a single chromosome (simple) or involves 3 or more chromosomes (complex), and the percentage of cells that are aneuploid. Many embryos diagnosed as being mosaic prior to their development into blastocysts (in the cleaved state), subsequently undergo autocorrection to the euploid state (normal numerical chromosomal configuration) as they develop to blastocysts in the Petri dish. This is one reason why “mosaicism” is more commonly detected in early embryos than in blastocysts. Embryos with segmental mosaic aneuploidies, i.e. the addition (duplication) or subtraction (deletion), are also more likely to autocorrect.  Finally, the lower the percentage of mitotically aneuploid (mosaic) cells in the blastocyst the greater the propensity for autocorrection and propagation of chromosomally normal (euploid) offspring. A blastocyst with <30% mosaicism could yield a 30% likelihood of a healthy baby rate with 10-15% miscarriage rate, while with >50% mosaicism the baby rate is roughly halved and the miscarriage rate double.

As stated, the transfer of embryos with autosomal meiotic trisomy, will invariably result in failed implantation, early miscarriage or the birth of a defective child. Those with autosomal mitotic (“mosaic”) trisomies, while having the ability to autocorrect in-utero and result in the birth of a healthy baby can, depending on the percentage of mosaic (mitotically aneuploid) cells present, the number of aneuploid chromosomes and the type of mosaicism (single or segmental) either autocorrect and propagate a normal baby, result in failed implantation, miscarry or cause a birth defect (especially with trisomies 13, 18 or 21). This is why when it comes to giving consideration to transferring trisomic embryos, suspected of being “mosaic”, I advise patients to undergo prenatal genetic testing once pregnant and to be willing to undergo termination of pregnancy in the event of the baby being affected. Conversely, when it comes to meiotic autosomal monosomy, there is almost no chance of a viable pregnancy. in most cases implantation will fail to occur and if it does, the pregnancy will with rare exceptions, miscarry. “Mosaic” (mitotically aneuploid) autosomally monosomic embryos where a chromosome is missing), can and often will “autocorrect” in-utero and propagate a viable pregnancy. It is for this reason that I readily recommend the transfer of such embryos, while still (for safety sake) advising prenatal genetic testing in the event that a pregnancy results.

Given our ability to recognize “mosaicism” through karyotyping of embryos, the question arrases as to which “mosaic” embryos are capable of auto-correcting in-utero and propagating viable pregnancies. Research suggests that that virtually no autosomal monosomy embryos will propagate viable pregnancies. Thus, the transfer of such mosaic embryos is virtually risk free.  Needless to say however, in any such cases, it is 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 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.

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ADDENDUM: PLEASE READ!!

INTRODUCING SHER FERTILITY SOLUTIONS (SFS)

Founded in April 2019, Sher Fertility Solutions (SFS) offers online (Skype/FaceTime) consultations to patients from > 40 different countries. All consultations are followed by a detailed written report presenting my personal recommendations for treatment of what often constitute complex Reproductive Issues.

If you wish to schedule an online consultation with me, please contact my assistant (Patti Converse) by phone (800-780-7437/702-533-2691), email (concierge@SherIVF.com) or,  enroll online on then home-page of my website (www.SherIVF.com). 

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ADDITIONAL INFORMATION:

I am attaching online links to two E-books which I recently  co-authored with  my partner at SFS-NY  (Drew Tortoriello MD)……. for your reading pleasure:

1.From In Vitro Fertilization to Family: A Journey with Sher Fertility Solutions (SFS) “

https://sherfertilitysolutions.com/sher-fertility-solutions-ebook.pdf

1. “Recurrent Pregnancy Loss and Unexplained IVF Failure: The Immunologic Link

https://drive.google.com/file/d/1iYKz-EkAjMqwMa1ZcufIloRdxnAfDH8L/view

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Possibly…but I would need much more information to provide an authoritative opinion.

Geoff Sher