Dr. Geoffrey Sher on January 11, 2019 at 9:30 pm

1. Hypothyroidism (most of which is autoimmune) and immunologic implantation dysfunction:

Between 2% and 5% of women of the childbearing age have reduced thyroid hormone activity (hypothyroidism). Women with hypothyroidism often manifest with reproductive failure i.e. infertility, unexplained (often repeated) IVF failure, or recurrent pregnancy loss (RPL). The condition is 5-10 times more common in women than in men. In most cases hypothyroidism is caused by damage to the thyroid gland resulting from of thyroid autoimmunity (Hashimoto’s disease) caused by damage done to the thyroid gland by antithyroglobulin and antimicrosomal auto-antibodies.
The increased prevalence of hypothyroidism and thyroid autoimmunity (TAI) in women is likely the result of a combination of genetic factors, estrogen-related effects and chromosome X abnormalities. This having been said, there is significantly increased incidence of thyroid antibodies in non-pregnant women with a history of infertility and recurrent pregnancy loss and thyroid antibodies can be present asymptomatically in women without them manifesting with overt clinical or endocrinologic evidence of thyroid disease. In addition, these antibodies may persist in women who have suffered from hyper- or hypothyroidism even after normalization of their thyroid function by appropriate pharmacological treatment. The manifestations of reproductive dysfunction thus seem to be linked more to the presence of thyroid autoimmunity (TAI) than to clinical existence of hypothyroidism and treatment of the latter does not routinely result in a subsequent improvement in reproductive performance.
It follows, that if antithyroid autoantibodies are associated with reproductive dysfunction they may serve as useful markers for predicting poor outcome in patients undergoing assisted reproductive technologies.
Some years back, I reported on the fact that 47% of women who harbor thyroid autoantibodies, regardless of the absence or presence of clinical hypothyroidism, have activated uterine natural killer cells (NKa) cells and cytotoxic lymphocytes (CTL) and that such women often present with reproductive dysfunction. We demonstrated that appropriate immunotherapy with IVIG or intralipid (IL) and steroids, subsequently often results in a significant improvement in reproductive performance in such cases.
The fact that almost 50% of women who harbor antithyroid antibodies do not have activated CTL/NK cells suggests that it is NOT the antithyroid antibodies themselves that cause reproductive dysfunction. The activation of CTL and NK cells that occurs in half of the cases with TAI is probably an epiphenomenon with the associated reproductive dysfunction being due to CTL/NK cell activation that damages the early “root system” (trophoblast) of the implanting embryo. We have shown that treatment of those women who have thyroid antibodies + NKa/CTL using IL/steroids, improves subsequent reproductive performance while women with thyroid antibodies who do not harbor NKa/CTL do not require or benefit from such treatment.

2. DOR:

The older a woman becomes, the more likely it is that her eggs will be chromosomally/genetically “incompetent” (not have the potential upon being fertilized and transferred, to result in a viable pregnancy). That is why, the likelihood of failure to conceive, miscarrying and of giving birth to a chromosomally defective child (e.g. with Down Syndrome) increases with the woman’s advancing age. In addition, as women age beyond 35Y there is commonly a progressive diminution in the number of eggs left in the ovaries, i.e. diminished ovarian reserve (DOR). So it is that older women as well as those who (regardless of age) have DOR have a reduced potential for IVF success. Much of this is due to the fact that such women tend to have increased production, and/or biological activity, of LH. This can result in excessive ovarian male hormone (predominantly testosterone) production. This in turn can have a deleterious effect on egg/embryo “competency”.
While it is presently not possible by any means, to reverse the age-related effect on the woman’s “biological clock, certain ovarian stimulation regimes, by promoting excessive LH production (e.g. short agonist/Lupron- “flare” protocols, clomiphene and Letrozole), can make matters worse. Similarly, the amount/dosage of certain fertility drugs that contain LH/hCG (e.g. Menopur) can have a negative effect on the development of the eggs of older women and those who have DOR and should be limited.
I try to avoid using such protocols/regimes (especially) in older women and those with DOR, favoring instead the use of the agonist/antagonist conversion protocol (A/ACP), a modified, long pituitary down-regulation regime, augmented by adding supplementary human growth hormone (HGH). I further recommend that such women be offered access to embryo banking of PGS (next generation gene sequencing/NGS)-selected normal blastocysts, the subsequent selective transfer of which by allowing them to to capitalize on whatever residual ovarian reserve and egg quality might still exist and thereby “make hay while the sun still shines” could significantly enhance the opportunity to achieve a viable pregnancy
Please visit my new Blog on this very site, http://www.DrGeoffreySherIVF.com, find the “search bar” and type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly
•Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
•IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation(COS)
•The Fundamental Requirements For Achieving Optimal IVF Success
•Ovarian Stimulation for IVF using GnRH Antagonists: Comparing the Agonist/Antagonist Conversion Protocol.(A/ACP) With the “Conventional” Antagonist Approach
•Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
•The “Biological Clock” and how it should Influence the Selection and Design of Ovarian Stimulation Protocols for IVF.
• A Rational Basis for selecting Controlled Ovarian Stimulation (COS) protocols in women with Diminished Ovarian Reserve (DOR)
•Diagnosing and Treating Infertility due to Diminished Ovarian Reserve (DOR)
•Controlled Ovarian Stimulation (COS) in Older women and Women who have Diminished Ovarian Reserve (DOR): A Rational Basis for Selecting a Stimulation Protocol
•Human Growth Hormone Administration in IVF: Does it Enhances Egg/Embryo Quality and Outcome?
•The BCP: Does Launching a Cycle of Controlled Ovarian Stimulation (COS). Coming off the BCP Compromise Response?
•Blastocyst Embryo Transfers Should be the Standard of Care in IVF
•Frozen Embryo Transfer (FET) versus “Fresh” ET: How to Make the Decision
•Frozen Embryo Transfer (FET): A Rational Approach to Hormonal Preparation and How new Methodology is Impacting IVF.
•Staggered IVF: An Excellent Option When. Advancing Age and Diminished Ovarian Reserve (DOR) Reduces IVF Success Rate
•Embryo Banking/Stockpiling: Slows the “Biological Clock” and offers a Selective Alternative to IVF-Egg Donation.
•Preimplantation Genetic Testing (PGS) in IVF: It Should be Used Selectively and NOT be Routine.
•Preimplantation Genetic Sampling (PGS) Using: Next Generation Gene Sequencing (NGS): Method of Choice.
•PGS in IVF: Are Some Chromosomally Abnormal Embryos Capable of Resulting in Normal Babies and Being Wrongly Discarded?
•PGS and Assessment of Egg/Embryo “competency”: How Method, Timing and Methodology Could Affect Reliability
•Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas:
•Traveling for IVF from Out of State/Country–
•A personalized, stepwise approach to IVF
•How Many Embryos should be transferred: A Critical Decision in IVF.
•The Role of Nutritional Supplements in Preparing for IVF
•Premature Luteinization (“the premature LH surge): Why it happens and how it can be prevented.
•IVF Egg Donation: A Comprehensive Overview

I urge you to set up a Skype or an in-person consultation with me. To do so, simply call 1-800-780-7437 (if you reside in the U.S.A or Canada) or 702-533-2691 (if you reside elsewhere). Alternatively you can enroll online by going to the home page of the Sher-IVF website, http://www.SherIVF.com where, upon completing an enrollment form), you will immediately be eligible to download my new book, “Recurrent Pregnancy Loss (RPL) and unexplained IVF Failure: The Immunologic Link”, free of charge.

Geoffrey Sher MD

19,771 Comments

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Sophia on January 11, 2019 at 9:12 pm

Hi Dr. Sher,

I need to take Depro-Lupon prior to transfer (treating of Endometriosis, since I don’t have an operation before).
How bad are side effects?
- Dr. Geoffrey Sher on January 11, 2019 at 9:23 pm
  
  I do not think the side effects are an issue. I am not a strong advocate of long acting antagonists prior to IVF. I think that >2 weeks of antagonist prior to stimulation can have a supposing effect on response.
  
  Geoff Sher
Lori on January 11, 2019 at 7:49 pm

Hi Dr. Sher,
On your other site I was reading where you said that only follicles measuring more than 15 will likely become mature eggs when triggered. This might seem like a dumb question, but, do you mean if they measure 15 early in the morning when monitoring is done that a trigger late that night will work OR, if a follicle measured 14 in the morning, could it grow to 15 or 16 by the evening when the trigger is taken and still work out? Or were you meaning the follicle is measured at the same time that the trigger is happening?

Also — I have a BMI of 35 and my RE just agreed to move my dose of HCG to 10000 because I was getting a lot of immature eggs with the standard protocol they had me on of 5000. She said that my blood levels were showing that the 5000 was appropriate so she is not sure that 10000 will do anything differently. Do the blood levels pretty much tell the story or is it still good to up the dosage?
What about the lupron trigger given with the HCG at 40mg, does this ever get adjusted for body weight/age? It seems the same amount is given to everyone.
Thanks!
- Dr. Geoffrey Sher on January 11, 2019 at 9:26 pm
  
  As long leading follicles are >18mm and 50% of the remainder are >15mm by the time of the trigger, the eggs have a reasonable shot at being mature.
  
  In my opinion, no one should receive <10,000U hCG for the trigger or many eggs will be immature or aneuploid.
  
  Geoff Sher
Elena on January 11, 2019 at 6:30 pm

My question is about skin care: when a woman is pregnant or trying to get pregnant (going through IVF/FET), should she stay away from certain products? Where I can find more information on that subject? Thanks!
Elena on January 11, 2019 at 6:27 pm

My question is about skin care, creams, lotions, etc. When a woman is pregnant or trying to get pregnant with IVF/FET or naturally. Should she stay away from certain products? Where I can find more info about that? Thanks!
- Dr. Geoffrey Sher on January 11, 2019 at 9:27 pm
  
  As far as I know, most commercially available products in the U.S.A are safe.
  
  Geoff Sher
KM on January 11, 2019 at 5:34 pm

I am 40.75 years old with DOR (AMH 0.02) with a newly dx subclinical hypothyroidism and medicated with levothyroxine 75mcg. I am taking a ton of Vitamins recommended by 1st RE e.g. co-q 10, dhea, l-arginine, fish oil, vit D, vit E, etc. Hubby has excellent sperm quality and quantity. We got a 2nd opinion as my husband was not happy with previous RE’s office. 2nd RE offered an E2 primed antagonist protocol as the option to try with forgoing PGS due to expected limited number of eggs produced… Is this our best option?
- Dr. Geoffrey Sher on January 11, 2019 at 9:30 pm
  
  1. Hypothyroidism (most of which is autoimmune) and immunologic implantation dysfunction:
  
  Between 2% and 5% of women of the childbearing age have reduced thyroid hormone activity (hypothyroidism). Women with hypothyroidism often manifest with reproductive failure i.e. infertility, unexplained (often repeated) IVF failure, or recurrent pregnancy loss (RPL). The condition is 5-10 times more common in women than in men. In most cases hypothyroidism is caused by damage to the thyroid gland resulting from of thyroid autoimmunity (Hashimoto’s disease) caused by damage done to the thyroid gland by antithyroglobulin and antimicrosomal auto-antibodies.
  The increased prevalence of hypothyroidism and thyroid autoimmunity (TAI) in women is likely the result of a combination of genetic factors, estrogen-related effects and chromosome X abnormalities. This having been said, there is significantly increased incidence of thyroid antibodies in non-pregnant women with a history of infertility and recurrent pregnancy loss and thyroid antibodies can be present asymptomatically in women without them manifesting with overt clinical or endocrinologic evidence of thyroid disease. In addition, these antibodies may persist in women who have suffered from hyper- or hypothyroidism even after normalization of their thyroid function by appropriate pharmacological treatment. The manifestations of reproductive dysfunction thus seem to be linked more to the presence of thyroid autoimmunity (TAI) than to clinical existence of hypothyroidism and treatment of the latter does not routinely result in a subsequent improvement in reproductive performance.
  It follows, that if antithyroid autoantibodies are associated with reproductive dysfunction they may serve as useful markers for predicting poor outcome in patients undergoing assisted reproductive technologies.
  Some years back, I reported on the fact that 47% of women who harbor thyroid autoantibodies, regardless of the absence or presence of clinical hypothyroidism, have activated uterine natural killer cells (NKa) cells and cytotoxic lymphocytes (CTL) and that such women often present with reproductive dysfunction. We demonstrated that appropriate immunotherapy with IVIG or intralipid (IL) and steroids, subsequently often results in a significant improvement in reproductive performance in such cases.
  The fact that almost 50% of women who harbor antithyroid antibodies do not have activated CTL/NK cells suggests that it is NOT the antithyroid antibodies themselves that cause reproductive dysfunction. The activation of CTL and NK cells that occurs in half of the cases with TAI is probably an epiphenomenon with the associated reproductive dysfunction being due to CTL/NK cell activation that damages the early “root system” (trophoblast) of the implanting embryo. We have shown that treatment of those women who have thyroid antibodies + NKa/CTL using IL/steroids, improves subsequent reproductive performance while women with thyroid antibodies who do not harbor NKa/CTL do not require or benefit from such treatment.
  
  2. DOR:
  
  The older a woman becomes, the more likely it is that her eggs will be chromosomally/genetically “incompetent” (not have the potential upon being fertilized and transferred, to result in a viable pregnancy). That is why, the likelihood of failure to conceive, miscarrying and of giving birth to a chromosomally defective child (e.g. with Down Syndrome) increases with the woman’s advancing age. In addition, as women age beyond 35Y there is commonly a progressive diminution in the number of eggs left in the ovaries, i.e. diminished ovarian reserve (DOR). So it is that older women as well as those who (regardless of age) have DOR have a reduced potential for IVF success. Much of this is due to the fact that such women tend to have increased production, and/or biological activity, of LH. This can result in excessive ovarian male hormone (predominantly testosterone) production. This in turn can have a deleterious effect on egg/embryo “competency”.
  While it is presently not possible by any means, to reverse the age-related effect on the woman’s “biological clock, certain ovarian stimulation regimes, by promoting excessive LH production (e.g. short agonist/Lupron- “flare” protocols, clomiphene and Letrozole), can make matters worse. Similarly, the amount/dosage of certain fertility drugs that contain LH/hCG (e.g. Menopur) can have a negative effect on the development of the eggs of older women and those who have DOR and should be limited.
  I try to avoid using such protocols/regimes (especially) in older women and those with DOR, favoring instead the use of the agonist/antagonist conversion protocol (A/ACP), a modified, long pituitary down-regulation regime, augmented by adding supplementary human growth hormone (HGH). I further recommend that such women be offered access to embryo banking of PGS (next generation gene sequencing/NGS)-selected normal blastocysts, the subsequent selective transfer of which by allowing them to to capitalize on whatever residual ovarian reserve and egg quality might still exist and thereby “make hay while the sun still shines” could significantly enhance the opportunity to achieve a viable pregnancy
  Please visit my new Blog on this very site, http://www.DrGeoffreySherIVF.com, find the “search bar” and type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly
  •Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
  •IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation(COS)
  •The Fundamental Requirements For Achieving Optimal IVF Success
  •Ovarian Stimulation for IVF using GnRH Antagonists: Comparing the Agonist/Antagonist Conversion Protocol.(A/ACP) With the “Conventional” Antagonist Approach
  •Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
  •The “Biological Clock” and how it should Influence the Selection and Design of Ovarian Stimulation Protocols for IVF.
  • A Rational Basis for selecting Controlled Ovarian Stimulation (COS) protocols in women with Diminished Ovarian Reserve (DOR)
  •Diagnosing and Treating Infertility due to Diminished Ovarian Reserve (DOR)
  •Controlled Ovarian Stimulation (COS) in Older women and Women who have Diminished Ovarian Reserve (DOR): A Rational Basis for Selecting a Stimulation Protocol
  •Human Growth Hormone Administration in IVF: Does it Enhances Egg/Embryo Quality and Outcome?
  •The BCP: Does Launching a Cycle of Controlled Ovarian Stimulation (COS). Coming off the BCP Compromise Response?
  •Blastocyst Embryo Transfers Should be the Standard of Care in IVF
  •Frozen Embryo Transfer (FET) versus “Fresh” ET: How to Make the Decision
  •Frozen Embryo Transfer (FET): A Rational Approach to Hormonal Preparation and How new Methodology is Impacting IVF.
  •Staggered IVF: An Excellent Option When. Advancing Age and Diminished Ovarian Reserve (DOR) Reduces IVF Success Rate
  •Embryo Banking/Stockpiling: Slows the “Biological Clock” and offers a Selective Alternative to IVF-Egg Donation.
  •Preimplantation Genetic Testing (PGS) in IVF: It Should be Used Selectively and NOT be Routine.
  •Preimplantation Genetic Sampling (PGS) Using: Next Generation Gene Sequencing (NGS): Method of Choice.
  •PGS in IVF: Are Some Chromosomally Abnormal Embryos Capable of Resulting in Normal Babies and Being Wrongly Discarded?
  •PGS and Assessment of Egg/Embryo “competency”: How Method, Timing and Methodology Could Affect Reliability
  •Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas:
  •Traveling for IVF from Out of State/Country–
  •A personalized, stepwise approach to IVF
  •How Many Embryos should be transferred: A Critical Decision in IVF.
  •The Role of Nutritional Supplements in Preparing for IVF
  •Premature Luteinization (“the premature LH surge): Why it happens and how it can be prevented.
  •IVF Egg Donation: A Comprehensive Overview
  
  I urge you to set up a Skype or an in-person consultation with me. To do so, simply call 1-800-780-7437 (if you reside in the U.S.A or Canada) or 702-533-2691 (if you reside elsewhere). Alternatively you can enroll online by going to the home page of the Sher-IVF website, http://www.SherIVF.com where, upon completing an enrollment form), you will immediately be eligible to download my new book, “Recurrent Pregnancy Loss (RPL) and unexplained IVF Failure: The Immunologic Link”, free of charge.
  
  Geoffrey Sher MD

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