Dr. Sher Blog

Official blog of Dr. Geoffrey Sher

Ask Dr. Sher- Open Forum

by Dr. Geoffrey Sher on December 1, 2015

You are not alone. Dr. Sher is here to answer your questions and support you.

If you would like to schedule a one on one Skype, telephone, or in person consultation with Dr. Sher, please fill out the form on the right and our team will get you scheduled right away.

Dear Patients,

I created this forum to welcome any questions you have on the topic of infertility, IVF, conception, testing, evaluation, or any related topics. I do my best to answer all questions in less than 24 hours. I know your question is important and, in many cases, I will answer within just a few hours. Thank you for taking the time to trust me with your concern.

– Geoffrey Sher, MD

Share this post:

12,878 comments

Leave A Reply
  • Evan - September 17, 2017 reply

    development must advance to the expanded blastocyst stage. As of this morning, 1 embryo has developed into an expanded blastocyst and was frozen.

    Dr. Sher: my wife and I love your website; thank you for being such an incredible resource. Was hoping you could help with a couple questions. We are on day 5 post ET and have 1 frozen blastocyst as of today. Should they be providing us “the grade”?
    Also, the clinic says, “there are 5 additional embryos which are early blastocysts today and another 9 embryos which are developing but are very slow and have not reached the blastocyst stage”. They are watching them to see what happens tomorrow, apparently. What are the success rates of non-expanded embroys, or ones that expand on Day 6? Any advise would be much appreciated!

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - September 18, 2017 reply

    There are a variety of classifications for blastocysts. In summary a day 5 or day 6 expanded blastocyst with a cellular inner cell mass is good.

    Good luck!

    Geoff Sher

  • Tamy - September 17, 2017 reply

    Hi Dr. Sher,
    After 5 miscarriages, through testing, we found that I have elevated nk’s and hashimotos disease and my husband has very low morphology. We are also a full DQ alpha match. So we decided to use a sperm donor with Ivf and we were successful and had a full term son. I was also on prednisone, lovenox and intralipids. My question is, we’d like to have another baby and have frozen embryos. However, will I need to use a different sperm donor since I had a son? Did that trigger my immune system to fight off other embryos made with that same sperm donor or will it not have mattered? Thank you so much!

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - September 17, 2017 reply

    No! You would again have the same chance with your frozen embryos but would also again require the same immunotherapy with Steroids and IL.

    Good luck!

    Geoff Sher

  • Heather Shuffield - September 17, 2017 reply

    I was wondering your thoughts on if you think an antagonist cycle without BCP and Lupron priming would be worth a try. I have low very low AMH 0.69, 38 years old and unsure of AFC but did have ovarian wedge resection to both ovaries due to PCOS last year. I am at the end of my first IVF cycle now. I was on BCP for 5 weeks and added Lupron 5 days before discontinuing. I am not sure the name of this protocol but I have done Follistim 225 then added Menopur 75 and eventually this dose was increased to 225 after 7 days of stims. I initially had 5 good size follicles at day 7 of monitoring, then decreased to 4 on day 10 and now day 12 only have 3 but all are good size. We are triggering at day 13 and continuing with the cycle. I have had several chemicals, a 10 week miscarriage, a 7 month fetal demise and 1 live birth. My NK cells is negative but my APA was positive so Lovenox was added to protocol. My question is do you feel it is worth a try to do a cycle without priming so long with BCP to see if we get a better response. I am already a SIRM patient currently in Dallas.

    Heather Shuffield - September 17, 2017 reply

    Let me add I love Dr. Saleh and completely trust him and the staff but just wondering your thoughts and thinking ahead incase this cycle is not successful.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - September 18, 2017 reply

    Copy!

    Geoff Sher

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - September 18, 2017 reply

    In my opinion, the protocol used for ovarian stimulation, against the backdrop of age, and ovarian reserve are the drivers of egg quality and egg quality is the most important factor affecting embryo “competency”.
    Older women as well as those who (regardless of age) have diminished ovarian reserve (DOR) tend to produce fewer and less “competent” eggs, the main reason for reduced IVF success in such cases. The compromised outcome is largely due to the fact that such women tend to have increased LH biological activity which often results in excessive LH-induced ovarian testosterone production which in turn can have a deleterious effect on egg/embryo “competency”.
    Certain ovarian stimulation regimes either promote excessive LH production (e.g. short agonist/Lupron- “flare” protocols, clomiphene and Letrozole), augment LH/hCG delivered through additional administration (e.g. high dosage menotropins such as Menopur), or fail to protect against body’s own/self-produced LH (e.g. late antagonist protocols where drugs such as Ganirelix/Cetrotide/Orgalutron that are first administered 6-7 days after ovarian stimulation has commenced).
    I try to avoid using such protocols/regimes (especially) in older women and those with DOR, favoring instead the use of a modified, long pituitary down-regulation protocol (the agonist/antagonist conversion protocol-A/ACP) augmented by adding supplementary human growth hormone (HGH). I further recommend Staggered IVF with embryo banking of PGS (next generation gene sequencing/NGS)-normal blastocysts in such cases. This type of approach will in my opinion, optimize the chance of a viable pregnancy per embryo transfer procedure and provide an opportunity to capitalize on whatever residual ovarian reserve and egg quality still exists, allowing the chance to “make hay while the sun still shines”.
    I strongly recommend that you visit http://www.DrGeoffreySherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.

    • Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
    • IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation(COS)
    • The Fundamental Requirements For Achieving Optimal IVF Success
    • Ovarian Stimulation for IVF using GnRH Antagonists: Comparing the Agonist/Antagonist Conversion Protocol.(A/ACP) With the“Conventional” Antagonist Aproach
    • Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
    • The “Biological Clock” and how it should Influence the Selection and Design of Ovarian Stimulation Protocols for IVF.
    • Diagnosing and Treating Infertility due to Diminished Ovarian Reserve (DOR)
    • Controlled Ovarian Stimulation (COS) in Older women and Women who have Diminished Ovarian Reserve (DOR): A Rational Basis for Selecting a Stimulation Protocol
    • Human Growth Hormone Administration in IVF: Does it Enhances Egg/Embryo Quality and Outcome?
    • The BCP: Does Launching a Cycle of Controlled Ovarian Stimulation (COS). Coming off the BCP Compromise Response?
    • Staggered IVF: An Excellent Option When. Advancing Age and Diminished Ovarian Reserve (DOR) Reduces IVF Success Rate
    • Embryo Banking/Stockpiling: Slows the “Biological Clock” and offers a Selective Alternative to IVF-Egg Donation.
    • Preimplantation Genetic Testing (PGS) in IVF: It Should be Used Selectively and NOT be Routine.
    • Preimplantation Genetic Sampling (PGS) Using: Next Generation Gene Sequencing (NGS): Method of Choice.
    • PGS in IVF: Are Some Chromosomally abnormal Embryos Capable of Resulting in Normal Babies and Being Wrongly Discarded?
    • PGS and Assessment of Egg/Embryo “competency”: How Method, Timing and Methodology Could Affect Reliability
    • Implications of “Empty Follicle Syndrome and “Premature Luteinization”
    • Premature Luteinization (“the premature LH surge): Why it happens and how it can be prevented.

    If you are interested in seeking my advice or services, I urge you to contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com You can also apply online at http://www.SherIVF.com .

    *FYI
    The 4th edition of my book,”In Vitro Fertilization, the ART of Making Babies” is now available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.

    Geoffrey Sher MD

  • Nafeesa - September 16, 2017 reply

    I’m 25,last year April I got pregnant but after 6 week I got miscarriage..and doctor checked but nothing is problem…all reports came normal and after that 3 months I didn’t get my periods… Then from October I started bleeding continuesly and never stopped for one day also….and I checked with doctors and again all test are normal but she told me to get D&C done because bleeding continued for 3 months(all day spotting) not heavy periods but on normal period days it’s heavy for 4 days. On 29 January I got D&C. For 1 month I didn’t get periods after March till now I’m spotting. Again all test are normal.i dnt know what to do.( 5days spotting and 4 days not ). Please prefer me doctor

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - September 16, 2017 reply

    It is not possible to provide an authoritative opinion without access to much more information.

    Geoff Sher

  • Jyoti - September 16, 2017 reply

    Dr. Sher, We are planning IUI#2 with Gonal F. Do you recommend double insemination over single insemination if cost is not a major concern. Also, what should the timings look like in both the cases post trigger? For double insemination, does it make sense to use a frozen sperm sample to ensure the 3 day abstinence for better sample for the second insemination? Do you suggest natural intercourse before and after insemination? Thanks a lot for your advice.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - September 16, 2017 reply

    Some claim that a double insemination is preferable. In my opinion a single well-timed insemination done immediately prior to ovulation is qui]te adequate.

    Geoff Sher

    Jyoti - September 17, 2017 reply

    Dr. Sure, Thanks for the advice. Your support is invaluable on this journey. Really cant thank you enough. Would you mind answering few more queries please:
    1. After how much time should single insemination be done after the trigger
    2. Do you suggest natural intercourse before and after the insemination
    3. In case of double insemination does it make more sense to use frozen sample for the first insemination so that the second one can be done with a sample of 3 day abstinence.

    Thanks a lot

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - September 17, 2017 reply

    1. After how much time should single insemination be done after the trigger
    A: 25-35 h after trigger.

    2. Do you suggest natural intercourse before and after the insemination
    A: Not necessarily

    3. In case of double insemination does it make more sense to use frozen sample for the first insemination so that the second one can be done with a sample of 3 day abstinence.

    A: No difference.

    Good luck!

    Geoff Sher

  • Darcy Hensley - September 15, 2017 reply

    I have recently suffered a chemical pregnancy with a PGS normal embryo. I do have Type 1 diabetes with an A1c of 5.7 and Hashimoto’s thyroiditis. Current TSH is 1.9.
    I suffered an early miscarriage earlier this year using IUI to conceive as well at 6.5 weeks. I’m not sure my current diagnosis would indicate immune infertility or not. I also have a diagnosis of PCOS, which is why we move forward with IVF. I am interested in getting immune testing, but am not sure what kind of testing I should ask for.
    If you’ve seen success with women who have 2 autoimmune disorders, what kind of protocol would you use or suggest? Thank you!

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - September 16, 2017 reply

    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.

    You should be tested for thyroid antibodies and for natural killer cell activity using the K-562 target cell test. Please call Julie (see below) in my office for directions as to when where and how to have these tests done.

    I strongly recommend that you visit http://www.DrGeoffreySherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.
    • The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
    • Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
    • IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation(COS)
    • The Fundamental Requirements For Achieving Optimal IVF Success
    • Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
    • Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
    • IVF Failure and Implantation Dysfunction:
    • The Role of Immunologic Implantation Dysfunction (IID) & Infertility (IID):PART 1-Background
    • Immunologic Implantation Dysfunction (IID) & Infertility (IID):PART 2- Making a Diagnosis
    • Immunologic Dysfunction (IID) & Infertility (IID):PART 3-Treatment
    • Immunologic Implantation Dysfunction: Importance of Meticulous Evaluation and Strategic Management:(Case Report
    • Intralipid and IVIG therapy: Understanding the Basis for its use in the Treatment of Immunologic Implantation Dysfunction (IID)
    • Intralipid (IL) Administration in IVF: It’s Composition; How it Works; Administration; Side-effects; Reactions and Precautions
    • Natural Killer Cell Activation (NKa) and Immunologic Implantation Dysfunction in IVF: The Controversy!
    • : How can it Affect IUI/IVF Outcome?
    • Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas
    • Should IVF Treatment Cycles be provided uninterrupted or be Conducted in 7-12 Pre-scheduled “Batches” per Year
    • A personalized, stepwise approach to IVF

    If you are interested in seeking my advice or services, I urge you to contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com You can also apply online at http://www.SherIVF.com .
    *FYI
    The 4th edition of my newest book ,”In Vitro Fertilization, the ART of Making Babies” is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.

    Geoff Sher

  • Abby - September 15, 2017 reply

    I started progesterone today, my lining yesterday was 8.2 (they want it above 8) and my estradiol was 712. Today I got a message saying to cut my estradiol Valerate injection dose from 5 mg to 2.5 mg. Is this normal protocol??

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - September 16, 2017 reply

    Sorry Abby,

    It is impossible for me to advise authoritatively without much more information!

    Geoff Sher

  • El McGrath - September 15, 2017 reply

    Dr Sher, with regard to your agonist-antagonist conversion protocol – must the antagonist be started with stimulation medication immediately following cessation of the agonist? My doctor has suggested stopping agonist, starting stims and then waiting a few days before introducing an antagonist. From my reading, this seems a deviation from the norm. Do you have any advice please? Thank you so much

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - September 15, 2017 reply

    In the A/ACP it starts immediately after the agonist is stopped and the gonadotropin stimulation begins.

    Geoff Sher

    El - September 16, 2017 reply

    Thank you very much Dr Sher. So will a break between finishing with the agonist and starting the antagonist be detrimental? Or could there be some value to it? Thank you once again

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - September 17, 2017 reply

    I cannot tell you what to do, only that I have no gap between agonist and antagonist!

    Geoff Sher

  • Ella - September 15, 2017 reply

    Hi Dr Sher,

    I’m 35, FSH 17.5 and 0.2 AMH, planning to have embryo freezing procedure asap with the possibility of surrogacy at later stage. Medical issues with fibroids. 6 follicles in the right ovary detected in the recent day 3 scan. Left ovary can’t be seen due to bulky uterus. What do you think our chance are? Many clinics turned us away.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - September 15, 2017 reply

    You have age in your favor but unless a very individualize approach to ovarian stimulation is used, you could have egg quality issues emerge, because of your DOR. In my opinion, the protocol used for ovarian stimulation, against the backdrop of age, and ovarian reserve are the drivers of egg quality and egg quality is the most important factor affecting embryo “competency”.
    Women who (regardless of age) have DOR have a reduced potential for IVF success. Much of this is due to the fact that such women tend to have increased production of LH biological activity which can result in excessive LH-induced ovarian male hormone (predominantly testosterone) production which in turn can have a deleterious effect on egg/embryo “competency”.

    While it is presently not possible by any means, to reverse the effect of DOR, certain ovarian stimulation regimes, by promoting excessive LH production (e.g. short agonist/Lupron- “flare” protocols, clomiphene and Letrozole), can in my opinion, make matters worse. Similarly, the amount/dosage of certain fertility drugs that contain LH/hCG (e.g. Menopur) can have a negative effect on the development of the eggs of older women and those who have DOR and should be limited.I try to avoid using such protocols/regimes (especially) in women with DOR, favoring instead the use of the agonist/antagonist conversion protocol (A/ACP), a modified, long pituitary down-regulation regime, augmented by adding supplementary human growth hormone (HGH). I further recommend that such women be offered access to embryo banking of PGS (next generation gene sequencing/NGS)-selected normal blastocysts, the subsequent selective transfer of which by allowing them to capitalize on whatever residual ovarian reserve and egg quality might still exist and thereby “make hay while the sun still shines” could significantly enhance the opportunity to achieve a viable pregnancy

    Please visit my new Blog on this very site, http://www.DrGeoffreySherIVF.com, find the “search bar” and type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.

    • Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
    • IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation(COS)
    • The Fundamental Requirements For Achieving Optimal IVF Success
    • Ovarian Stimulation for IVF using GnRH Antagonists: Comparing the Agonist/Antagonist Conversion Protocol.(A/ACP) With the “Conventional” Antagonist Approach
    • Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
    • The “Biological Clock” and how it should Influence the Selection and Design of Ovarian Stimulation Protocols for IVF.
    • A Rational Basis for selecting Controlled Ovarian Stimulation (COS) protocols in women with Diminished Ovarian Reserve (DOR)
    • Diagnosing and Treating Infertility due to Diminished Ovarian Reserve (DOR)
    • Controlled Ovarian Stimulation (COS) in Older women and Women who have Diminished Ovarian Reserve (DOR): A Rational Basis for Selecting a Stimulation Protocol
    • Human Growth Hormone Administration in IVF: Does it Enhances Egg/Embryo Quality and Outcome?
    • The BCP: Does Launching a Cycle of Controlled Ovarian Stimulation (COS). Coming off the BCP Compromise Response?
    • Blastocyst Embryo Transfers should be the Standard of Care in IVF
    • Frozen Embryo Transfer (FET) versus “Fresh” ET: How to Make the Decision
    • Frozen Embryo Transfer (FET): A Rational Approach to Hormonal Preparation and How new Methodology is Impacting IVF.
    • Staggered IVF: An Excellent Option When. Advancing Age and Diminished Ovarian Reserve (DOR) Reduces IVF Success Rate
    • Embryo Banking/Stockpiling: Slows the “Biological Clock” and offers a Selective Alternative to IVF-Egg Donation.
    • Preimplantation Genetic Testing (PGS) in IVF: It should be Used Selectively and NOT be Routine.
    • Preimplantation Genetic Sampling (PGS) Using: Next Generation Gene Sequencing (NGS): Method of Choice.
    • PGS in IVF: Are Some Chromosomally Abnormal Embryos Capable of Resulting in Normal Babies and Being Wrongly Discarded?
    • PGS and Assessment of Egg/Embryo “competency”: How Method, Timing and Methodology Could Affect Reliability
    • Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas:
    • Traveling for IVF from Out of State/Country–
    • A personalized, stepwise approach to IVF
    • How Many Embryos should be transferred: A Critical Decision in IVF.
    • The Role of Nutritional Supplements in Preparing for IVF
    • Premature Luteinization (“the premature LH surge): Why it happens and how it can be prevented.
    • IVF Egg Donation: A Comprehensive Overview

    If you are interested in seeking my advice or services, I urge you to contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com You can also apply online at http://www.SherIVF.com .

    *FYI
    The 4th edition of my newest book ,”In Vitro Fertilization, the ART of Making Babies” is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.

    Geoffrey Sher MD

  • Anna - September 14, 2017 reply

    Hi Dr. Sher,

    Would you please explain your preference for Dexamethasone versus Prednisone or Prednisolone in cases of autoimmune IID? Is there a significant difference in the way that each affects the body or is it simply the preference of the doctor/clinic?

    Thanks for your time!

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - September 15, 2017 reply

    Prednisolone is bound to albumin in the blood and is less bio-available. As for Dexamethaone and Prednisone, they are both dissolved in the serum and it is really a toss-up which to use.

    Geoff Sher

  • Sana - September 14, 2017 reply

    I’m 39 have had three boys normally, tried 4 IVF with PGD and sperm spinning for a girl and have been unsuccessful. Do you offer any methods for gender selection?

    I have also had one fetal loss with normal pregnancy at 19 weeks and two FET not taking. Would you test for anything, or add to the normal transfer protocol?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - September 15, 2017 reply

    I think we should talk Sana,

    Please contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com You can also apply online at http://www.SherIVF.com .

    *FYI
    The 4th edition of my newest book ,”In Vitro Fertilization, the ART of Making Babies” is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.

    Geoffrey Sher MD

  • Megan Colon - September 14, 2017 reply

    Hello I have a question about which protocol I should use. I had one failed IVF procedure. I didn’t respond well to the meds. I was on the maximum dosage. I barely got 6 eggs from the retrieval. Sadly I wasn’t able to do the transfer part. Afterwards I had my AMH level tested and it was a 0.72. I’m 31 and never had a pregnancy. I am going to do one more round of IVF. What protocol would you recommend?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - September 15, 2017 reply

    In my opinion, the protocol used for ovarian stimulation, against the backdrop of age, and ovarian reserve are the drivers of egg quality and egg quality is the most important factor affecting embryo “competency”.
    Women who (regardless of age) have DOR have a reduced potential for IVF success. Much of this is due to the fact that such women tend to have increased production of LH biological activity which can result in excessive LH-induced ovarian male hormone (predominantly testosterone) production which in turn can have a deleterious effect on egg/embryo “competency”.

    While it is presently not possible by any means, to reverse the effect of DOR, certain ovarian stimulation regimes, by promoting excessive LH production (e.g. short agonist/Lupron- “flare” protocols, clomiphene and Letrozole), can in my opinion, make matters worse. Similarly, the amount/dosage of certain fertility drugs that contain LH/hCG (e.g. Menopur) can have a negative effect on the development of the eggs of older women and those who have DOR and should be limited.I try to avoid using such protocols/regimes (especially) in women with DOR, favoring instead the use of the agonist/antagonist conversion protocol (A/ACP), a modified, long pituitary down-regulation regime, augmented by adding supplementary human growth hormone (HGH). I further recommend that such women be offered access to embryo banking of PGS (next generation gene sequencing/NGS)-selected normal blastocysts, the subsequent selective transfer of which by allowing them to capitalize on whatever residual ovarian reserve and egg quality might still exist and thereby “make hay while the sun still shines” could significantly enhance the opportunity to achieve a viable pregnancy

    Please visit my new Blog on this very site, http://www.DrGeoffreySherIVF.com, find the “search bar” and type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.

    • Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
    • IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation(COS)
    • The Fundamental Requirements For Achieving Optimal IVF Success
    • Ovarian Stimulation for IVF using GnRH Antagonists: Comparing the Agonist/Antagonist Conversion Protocol.(A/ACP) With the “Conventional” Antagonist Approach
    • Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
    • The “Biological Clock” and how it should Influence the Selection and Design of Ovarian Stimulation Protocols for IVF.
    • A Rational Basis for selecting Controlled Ovarian Stimulation (COS) protocols in women with Diminished Ovarian Reserve (DOR)
    • Diagnosing and Treating Infertility due to Diminished Ovarian Reserve (DOR)
    • Controlled Ovarian Stimulation (COS) in Older women and Women who have Diminished Ovarian Reserve (DOR): A Rational Basis for Selecting a Stimulation Protocol
    • Human Growth Hormone Administration in IVF: Does it Enhances Egg/Embryo Quality and Outcome?
    • The BCP: Does Launching a Cycle of Controlled Ovarian Stimulation (COS). Coming off the BCP Compromise Response?
    • Blastocyst Embryo Transfers should be the Standard of Care in IVF
    • Frozen Embryo Transfer (FET) versus “Fresh” ET: How to Make the Decision
    • Frozen Embryo Transfer (FET): A Rational Approach to Hormonal Preparation and How new Methodology is Impacting IVF.
    • Staggered IVF: An Excellent Option When. Advancing Age and Diminished Ovarian Reserve (DOR) Reduces IVF Success Rate
    • Embryo Banking/Stockpiling: Slows the “Biological Clock” and offers a Selective Alternative to IVF-Egg Donation.
    • Preimplantation Genetic Testing (PGS) in IVF: It should be Used Selectively and NOT be Routine.
    • Preimplantation Genetic Sampling (PGS) Using: Next Generation Gene Sequencing (NGS): Method of Choice.
    • PGS in IVF: Are Some Chromosomally Abnormal Embryos Capable of Resulting in Normal Babies and Being Wrongly Discarded?
    • PGS and Assessment of Egg/Embryo “competency”: How Method, Timing and Methodology Could Affect Reliability
    • Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas:
    • Traveling for IVF from Out of State/Country–
    • A personalized, stepwise approach to IVF
    • How Many Embryos should be transferred: A Critical Decision in IVF.
    • The Role of Nutritional Supplements in Preparing for IVF
    • Premature Luteinization (“the premature LH surge): Why it happens and how it can be prevented.
    • IVF Egg Donation: A Comprehensive Overview

    If you are interested in seeking my advice or services, I urge you to contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com You can also apply online at http://www.SherIVF.com .

    *FYI
    The 4th edition of my newest book ,”In Vitro Fertilization, the ART of Making Babies” is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.

    Geoffrey Sher MD

  • Evan - September 14, 2017 reply

    Hi Dr. Sher. Your website has been an invaluable source of information. In regards to IVF, what factors do you think play a role in monozygotic twinning (where the blastocyst splits)? I’ve heard that 5 day-old blasts and ICSI assisted-hatching increases these odds. We retrieved 38 mature eggs and are doing a frozen eSET next month (with AH). Curious what chances we have for monozygotic twinning?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - September 14, 2017 reply

    The chances are slightly increased by creating an hiatus in the envelopment of the embryo though assisted hatching and/or embryo biopsy for PGS. However the chances are still <1:100.

    Good luck!

    Geoff Sher

  • Caryn Presti - September 14, 2017 reply

    What is your opinion regarding ovarian rejuvenation using PRP injections as well as other methods to restore ovarian function in menopausal women?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - September 14, 2017 reply

    I do not believe it to have merit.

    Geoff Sher

  • Jen - September 14, 2017 reply

    Hi Dr. Sher. With our blastocysts already being frozen, would performing PGS testing at a later date (and then re-freezing) result in compromising the blastocysts or negatively impact them? Thank you so much.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - September 14, 2017 reply

    Secondary thawing for PGS does produce pregnancies but it also in my opinion compromises tghe embryos to some extent. I do not advocate it!

    Geoff Sher

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - September 14, 2017 reply

    It could well have a detrimental effect although pregnancies are reported following such secondary testing.

    Geoff Sher

  • Rachel M - September 13, 2017 reply

    Would you test someone with PCOS to determine what type of PCOS they have prior to proceeding with a cycle? Does it have any impact on how you would proceed with FET?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - September 13, 2017 reply

    THE ANSWER IS YES ON BOTH COUNTS:

    Polycystic ovary syndrome (PCOS) is a common hormonal system disorder among women affecting between 5% and 10% of women of reproductive age worldwide. Women with PCOS may have enlarged ovaries that contain small collections of fluid — called follicles — located in each ovary as seen during an ultrasound. The condition is characterized by abnormal ovarian function (irregular or absent periods, abnormal or absent ovulation and infertility), androgenicity (increased body hair or hirsutism, acne) and increased body weight –body mass index or BMI. The ovaries of women with PCOS characteristically contain multiple micro-cysts often arranged like a “string of pearls” immediately below the ovarian surface (capsule).interspersed by an overgrowth of ovarian connective tissue (stroma).

    PCOS is one of the most common causes of menstrual irregularities, infertility, and hirsutism, Despite an enormous effort to define its cause, the etiology of PCOS remains unclear, and there is no definite cure at this time. PCOS is clearly a heterogeneous disorder which often has a familial (genetic) basis. Infertility associated with PCOS has been attributed to numerous factors, including dysfunctional gonadotropin pituitary secretion, peripheral insulin resistance, elevated adrenal and/or ovarian androgen (male hormone) levels, and dysfunction of several growth factors. Women with this condition are often obese and insulin resistant. The compensatory hyperinsulinemia further stimulates ovarian androgen production which may be detrimental to egg maturation and there is a clear link between the degree of insulin resistance and anovulation. PCOS is also a significant long-term health risk for women, thus necessitating vigilance through regular annual examinations (non-insulin dependent diabetes mellitus, hypertension, hypercholesterolemia, cardiovascular disease and endometrial cancer). Whereas PCOS-related infertility is usually manageable through the use of fertility drugs, lifestyle changes (diet and exercise) remain a mainstay of long-term therapy. More recently, ovulation rates, circulating androgens, pregnancy rates and perhaps even first-trimester miscarriage rates have been shown to improve when insulin sensitizers like metformin are used to correct the underlying insulin resistance.

    Most patients with PCOS are young and have excellent pregnancy rates with oral clomiphene. Those that require more aggressive treatments with injectable medications probably represent a subgroup of PCOS patients with severe ovarian dysfunction. These women often have explosive response to gonadotropins which can result in serious complications like Severe Ovarian Hyperstimulation Syndrome (OHSS…see below) and high order multiple births. In those women, the ability to perform “prolonged coasting” (see below) and selectively transfer fewer embryos during IVF offers a clear advantage over standard gonadotropin injections.

    Egg quality in PCOS

    The potential for a woman’s eggs to undergo orderly maturation, successful fertilization and subsequent progression to “good quality embryos” is in large part genetically determined. However, the expression of such potential is profoundly susceptible to numerous influences, especially intra-ovarian hormonal changes during the pre-ovulatory phase of the cycle. Proper follicular stimulation as well as precise timing of egg maturation with LH (Luteinizing Hormone) or hCG (human chorionic gonadotropin) is crucial to optimal egg maturation, fertilization and ultimately embryo quality. Both pituitary gonadotropins, LH and FSH (follicle stimulating hormone) play a pivotal but different role in follicular development. The action of FSH is mainly directed toward granulosa cell (cells lining the inside of the follicle) proliferation and estrogen production (E2). LH, on the other hand, acts primarily on the ovarian stroma (the connective tissue that surrounds the follicle) to produce androgens. While small amounts of ovarian androgens, such as testosterone, enhance egg and follicle development, over-exposure to them can have a deleterious effect. Furthermore, excessive ovarian androgens can also compromise estrogen-induced endometrial growth and development.

    Suppressing pituitary secretion of LH with gonadotropin releasing hormone (GnRH) agonists such as Lupron®, is particularly useful in PCOS. In that condition, serum LH levels are elevated, leading to stromal overgrowth, follicular arrests (so-called cysts) and high levels of androgens synthesis. It is therefore not surprising that these follicles often yield poorly developed (“immature”) eggs” at the time of egg retrieval (ET) and that “poor egg/embryo quality”, inadequate endometrial development and high miscarriage rates are common features of this condition. However, contrary to popular belief, this is not due to an intrinsic deficit in “egg quality”. Stimulation protocols geared toward optimizing follicle and egg development and avoiding over exposure to androgens correct these problems ad result in pregnancy rates similar to those of non-PCOS women. Whereas the overuse of LH-containing preparations such as Menopur® and Luveris® further aggravates this effect. In conclusion, to maximize ultimate oocyte maturation, we strongly recommend against the exclusive use of such products in PCOS patients, preferring FSH-dominant products such as Folistim®, Gonal F® or Bravelle® over a period of at least 9 days following pituitary suppression with Lupron®.
    PCOS women often have a family history of diabetes and demonstrable insulin resistance (evidenced by high blood insulin levels and an abnormal 2-hour glucose tolerance test).This underlying Diabetes mellitus tendency could play a role in the development of PCOS and contribute to the development of obesity, an abnormal blood lipid profile, and a predisposition to coronary vascular disease. Women with PCOS are slightly more at risk of developing uterine, ovarian and possibly also breast cancer in later life and accordingly should be evaluated for these conditions on a more frequent basis than would ordinarily be recommended to non-PCOS women.

    Most women with PCOS either do not ovulate at all or they ovulate irregularly. As a consequence thereof they in addition usually experience delayed, absent or irregular menstruation. In addition, an inordinate percentage of the eggs produced by PCOS women following ovulation induction, tend to be chromosomally abnormal (aneuploid). Rather than being due to an intrinsic egg defect being inherent in PCOS women, the poor egg quality more than likely the result of over-exposure to male hormones (predominantly, testosterone) produced by the ovarian stroma. These two factors (ovulation dysfunction and poor egg quality) are the main reasons for the poor reproductive performance (infertility and an increased miscarriage rate) in PCOS women.

    PCOS patients are at an inordinate risk of severely over-responding fertility drugs, both oral varieties (e.g. Clomiphene, Serophene & Femara) and especially the injectables (e.g. Follistim, Puregon, Gonal F, Menopur and Bravelle) by forming large numbers ovarian follicles. This can lead to life endangering complications associated with sever ovarian hyperstimulation (OHSS). In addition PCOS women receiving fertility drugs often experience multiple ovulations putting them at severe risk (40%+) of high order multiple pregnancy (i.e. triplets or greater) with often devastating consequences.

    VARIETIES OF POLYCYSTIC OVARIAN SYNDROME:

    1) Hypothalamic-pituitary-PCOS: This is the commonest form of PCOS and is often genetically transmitted and is characteristically associated with a blood concentration of Luteinizing Hormone (LH) that is uncharacteristically much higher than the Follicle Stimulating Hormone (FSH) level (FSH is normally higher than the LH concentration) as well as high-normal or blood androgen ( male) hormone concentrations (e.g. androstenedione, testosterone and dehydroepiandrosterone -DHEA).Hypothalamic-pituitary-ovarian PCOS is also often associated with insulin resistance and in about 40%-50% of the cases.

    2) Adrenal PCOS: Here the excess of male hormones are derived from overactive adrenal glands rather than from the ovaries. Blood levels of testosterone and/or androstenedione raised but here, but here, the blood level of dehydroepiandrosterone (DHEAS) is also raised, clinching the diagnosis.

    3) Severe pelvic adhesive disease secondary to severe endometriosis, chronic pelvic inflammatory disease and/or extensive pelvic surgery: Women who have this type of PCOS tend to less likely to hyperstimulate in response to ovulation induction . Their. DHEAS is also is not raised.

    TREATMENT OF INFERTILITY DUE TO ASSOCIATED OVULATION DYSFUNCTION:

    Hypothalamic-pituitary-/ovarian PCOS: Ovulation induction with fertility drugs such as clomiphene citrate, Letrozole (Femara) or gonadotropins, with or without intrauterine insemination (IUI) is often highly successful in establishing pregnancies in PCOS women. However, IVF is fast becoming a treatment of choice (see below).

    In about 40% of cases, 3-6 months of oral Metformin (Glucophage) treatment results in a significant reduction of insulin resistance, lowering of blood androgen levels, an improvement in ovulatory function, and/or some amelioration of androgenous symptoms and signs.

    Surgical treatment by “ovarian drilling” of the many small ovarian cysts lying immediately below the envelopment (capsule) of the ovaries, is often used, but is less successful than alternative non-surgical treatment and is only temporarily effective. The older form of surgical treatment, using ovarian wedge resection is rarely used any longer as it can produce severe pelvic adhesion formation.

    Adrenal PCOS is treated with steroids such as prednisone or dexamethasone which over a period of several weeks will suppress adrenal androgen production, allowing regular ovulation to take place spontaneously. This is often combined with clomiphene, Letrozole and/or gonadotropin therapy to initiate ovulation.

    PCOS attributable to Pelvic Adhesive Disease is one variety which often is associated with compromised ovarian reserve, a raised FSH blood level and ovarian resistance to fertility drugs. In many such cases, high dosage of gonadotropins (FSH-dominant) with “estrogen priming” will often elicit an ovarian response necessary for successful ovulation induction and/or IVF. Neither steroids nor Metformin are helpful in the vast majority of such cases.

    PCOS women undergoing ovulation induction usually release multiple eggs following the hCG trigger and are thus at inordinate risk of twin or higher order multiple pregnancies. They are also at risk of developing OHSS. Many now believe that IVF should be regarded as a primary and preferential treatment for PCOS. The reason is that it is only through this approach that the number of embryos reaching the uterus can be controlled and in this manner the risk of high-order multiples can be minimized and it is only in the course of IVF treatment that a novel treatment method known as “prolonged coasting” ( see below) which prevents OHSS, can be implemented

    SEVERE OVARIAN HYPERSTIMULATION SYNDROME (OHSS):

    As indicated above, there is an inordinate propensity for women with PCOS to hyper-respond to gonadotropin fertility drugs and in the process produce large numbers of ovarian follicles. If left unchecked this can lead to OHSS, a potentially life endangering condition. The onset of OHSS is signaled by the development of a large number of ovarian follicles (usually more than 25 in number). This is accompanied by rapidly rising plasma estradiol (E2) levels, often exceeding 3000pg/ml within 7 or 9 days of stimulation, often rapidly peaking above 6,000 pg/ml prior to hCG administration. When this happens, the risk of OHSS developing is above 80%.

    Symptoms and signs of OHSS include: abdominal distention due to fluid collection (ascites), fluid in the chest cavity (hydrothorax), rapid weight gain (of a pound or more per day) due to tissue fluid retention, abdominal pain, lower back ache, nausea, diarrhea, vomiting, visual disturbances such as blurred vision and spots in front of the eyes (scotomata), a rapidly declining urine output, cardiovascular collapse and failure of blood to clot which sometimes results in severe bruising (echymosis) and frank bleeding. These symptoms and signs may appear before pregnancy can be diagnosed. If pregnancy occurs, the condition is likely to worsen progressively over a period of 3-5 weeks whereupon it rapidly resolves spontaneously over a few days. If no pregnancy occurs, the symptoms and signs all disappear spontaneously within 10-12 days of the hCG injection.

    When increasing fluid collection in the abdominal cavity (ascites) starts to compromise breathing raising the head of the bed rose slightly by placing a 4-6 inch block at the base of each head post and using a few additional pillows, will sometimes help ameliorate the problem. In cases where this does not help or symptoms become severe, all or most of the fluid can readily and safely be drained through t transvaginal sterile needle aspiration (vaginal paracentesis-performed once or sometimes twice a week) can be performed once or twice weekly . The problem will usually self corrects within 10-12 days of the hCG shot if pregnancy does not occur or, by the 8th week of pregnancy.

    Urine output should be monitored daily to see if it drops below about 500ml a day (about two cups and a half). A chest X-ray, to evaluate for fluid collection in the chest and around the heart should be done weekly along with blood tests for hematocrit, BUN, electrolytes, creatinine, platelet count and fibrin split products (FSP). If indicated on the basis of a deteriorating clinical situation, hospitalization might be needed for close observation and if necessary, to provide intensive care.

    In all case of OHSS, the ovaries will invariably be considerably enlarged. This is irrelevant to the final outcome, unless ovarian torsion (twisting of the ovary on its axis), an extremely rare complication occurs. The latter would usually require surgical emergency surgical intervention.

    It is important to know that symptoms and signs of OHSS are severely aggravated by rising hCG levels. Thus such patients should not receive additional hCG injections.

    Does PCOS cause poor egg/embryo quality? It is an undeniable fact that women with PCOS undergoing IVF are commonly found to have poorly developed (“dysmorphic”) eggs, with reduced fertilization potential and yielding “poor quality embryos”. However, in the author’s opinion (which admittedly runs contrary to popular opinion), this is unlikely to be due to an intrinsic deficit in egg quality. Rather, it more likely relates to intra-ovarian hormonal changes brought about by hyperstimulation and which compromise egg development. This effect, in the author’s opinion, can often be significantly reduced through implementation of an individualized or customized ovarian stimulation protocols that minimize exposure of the developing follicles and eggs to excessive LH-induced ovarian androgens. This can be best achieved by limiting the use of LH-containing gonadotropins such as Menopur through selective institution of “prolonged coasting” (see below).

    In the past, the onset of OHSS, heralded by the presence of large numbers of developing ovarian follicles and rapidly rising plasma estradiol levels often led the treating physician to prematurely administer hCG in an attempt to abruptly arrest the process and prevent escalation of risk to the patient. However the premature administration of hCG, while abruptly arresting further proliferation of estrogen producing granulosa cells in the follicles, unfortunately also prematurely arrests egg development. Since the ability of an egg to achieve optimal maturation upon hCG triggering is largely predicated upon it having achieved prior optimal development, the untimely administration of hCG which triggers meiosis, probably increases the risk of numerical chromosomal abnormalities (aneuploidy) of the egg. This in turn would lead to reduced fertilization potential, poor egg/embryo quality and low embryo implantation potential.

    In women with PCOS the connective tissue that surrounding the follicles (ovarian stroma) is often characteristically overgrown (stromal hyperplasia). It is the stroma that produces androgens (mainly testosterone) in response to LH. It is this, coupled with the fact that PCOS women also often have elevated blood LH concentrations (see above) results in the excessive production of androgen hormones, which is so characteristic in PCOS. While excessive exposure of developing eggs to ovarian androgens compromises follicle and egg growth it also impairs endometrial response to estrogen, which could explain the common finding of poor endometrial thickening in many PCOS women undergoing IVF.
    .
    The obvious remedy for these adverse effects on egg and endometrial development is to employ stimulation protocols that limit ovarian over-exposure to LH and allowing the time necessary for the follicles/eggs to develop optimally, prior to administering hCG through the judicious implementation of “Prolonged coasting” (PC).

    “PROLONGED COASTING”:

    In the early 90’s we were the first to report on “prolonged coasting” (PC), a novel approach that protects egg quality while preventing the development of OHSS. PC has since, gained widespread acceptance as a method of choice for preventing OHSS and has established itself as the “standard of care”. It involves withholding gonadotropin therapy while continuing the administration of the GnRHa and waiting until the plasma estradiol concentration drops below 2,500 pg/ml. Thereupon hCG is administered. In such cases, regardless of the number of developed follicles or the number of eggs retrieved, these women rarely, if ever develop OHSS. It has been reported that while PC virtually eliminates the risk of life-endangering complications associated with OHSS, there are reports in the literature that “the price to pay with PC” is often a poorer fertilization rate and reduced embryo implantation potential, compromising the pregnancy”. It is the author’s opinion an experience in the development of PC that egg/embryo quality deficit likely has little to do with the process of PC, itself and can be explained as follows: When PC is initiated too early, follicle growth and development may cease (as evidenced by the estradiol level plateauing or falling immediately, rather than showing an initial continued increase), and when PC is started too late, the follicles will often become cystic, measuring >21mm by the time the estradiol level falls below the safe threshold of 250000pg/ml, and so harbor dysmorphic eggs. Thus precise timing of the initiation of PC is critical. It should in pact be initiated preemptively in all cases when there are more than 25 follicles and the plasma estradiol reaches or exceeds 2,500pg/ml in association, provided that at least 50% of the follicles measuring 14-16mm in mean diameter. Not a day sooner or a day later. If PC is initiated with precise timing, it will usually be followed by a further progressive rise in the estradiol concentration. After a few days, the estradiol level will plateau and then it will start to fall (often rapidly). The temptation to trigger with hCG before the estradiol level falls below 3000picogtrams per milliliter must be resisted …even if the level falls below 1,000pg/ml by the time hCG is given.

    Since when using agonist ( Cetrotide/Ganirelix/Orgalutron) pituitary suppression throughout the stimulation phase with gonadotropins, the plasma estradiol level often under expressed follicle growth, this method of pituitary blockade should not be used in cases ( such as with PCOS) where PC might be required.,

    Prolonged coasting prevents canceled cycles and with it, canceled dreams.

    If you are interested in seeking my advice or services, I urge you to contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com You can also apply online at http://www.SherIVF.com .
    *FYI
    The 4th edition of my newest book ,”In Vitro Fertilization, the ART of Making Babies” is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.

  • Jennifer McCarty - September 13, 2017 reply

    Hi Dr. Sher,

    I have PCOS (age 37) and my husband has male factor. We are in the process of our 1st IVF/ICSI cycle; had our egg retrieval today (42 eggs retrieved!). We are freezing and bypassing the fresh transfer. We will know soon how many fertilized and then frozen at blastocyst stage. I’m starting to feel some symptoms of OHSS. Your site has been SO incredibly helpful, I was hoping you could help me with a few questions:
    1) Is metformin usually prescribed for PCOS? My clinic has an enormous amount of patients and getting questions answered by anyone is very difficult. I suspect my doctor may have failed to read my diagnosis from my OB (or maybe even my chart at their clinic) regarding my PCOS, since my husband has infertility too. I am wondering if metformin would have helped not produce so many eggs and avoided OHSS? Even the anesthesiologist commented today, “you’re on metformin, correct?”.
    2) The 1st question I was ever able to ask my doctor personally (not a nurse) was today at egg retrieval. I asked him if having so many follicles and PCOS was going to impact egg quality. He said that PCOS does not cause poor egg quality. Is this true? I’ve read on your site (and elsewhere) other statistics. Unfortunately, we cannot afford PGD testing.
    3) We prefer to transfer 2 blastocysts. Our doctor has adamantly refused, saying “their office follows the guidelines from the Society for Reproductive Technology for which your age and history are for one”. However, it appears that the SRT chart indicates 2 blasts at my age. We understand the twin risks. I am just curious if those guidelines are correct and if you would have recommend transferring two? With no PGD testing, a lower success rate with 1 blast, added stress/costs… the transfer of 2 is important to us.

    Lastly, we’re considering moving our frozen blasts to another clinic where we receive more personalized care (before our frozen transfer next month). Do you know of any negative impact from doing this? Is it better to stay in the same lab since we’ve started here? I believe we need a more compassionate office where we can ask questions and not feel like a burden or left in the dark. Meanwhile have an option for two blasts (and if refused, to receive more of an detailed answer and discussion instead of a hurried “no”).
    I really appreciate you taking the time to help answer my questions, Dr. Sher.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - September 13, 2017 reply

    Hi Jenifer,

    Thank you so much for your kind words. I enjoy this forum and am glad to be of help! Now to your questions:

    1) Is Metformin usually prescribed for PCOS? My clinic has an enormous amount of patients and getting questions answered by anyone is very difficult. I suspect my doctor may have failed to read my diagnosis from my OB (or maybe even my chart at their clinic) regarding my PCOS, since my husband has infertility too. I am wondering if Metformin would have helped not produce so many eggs and avoided OHSS?

    A: No! I reserve Metformin for PCOS women with insulin resistance (elevated fasting blood insulin). I do not think it helps the remainder.

    2) The 1st question I was ever able to ask my doctor personally (not a nurse) was today at egg retrieval. I asked him if having so many follicles and PCOS was going to impact egg quality. He said that PCOS does not cause poor egg quality. Is this true? I’ve read on your site (and elsewhere) other statistics. Unfortunately, we cannot afford PGD testing.

    A: Very respectfully, the answer you received is in my opinion incorrect. Women with PCOS do in fact hve a much higher percentage of “incompetent” eggs. But this can be somewhat mitigated by using an individualized strategic protocol for ovarian stimulation and to use “prolonged coasting” to avoid OHSS.

    3) We prefer to transfer 2 blastocysts. Our doctor has adamantly refused, saying “their office follows the guidelines from the Society for Reproductive Technology for which your age and history are for one”. However, it appears that the SRT chart indicates 2 blasts at my age. We understand the twin risks. I am just curious if those guidelines are correct and if you would have recommend transferring two? With no PGS testing, a lower success rate with 1 blast, added stress/costs… the transfer of 2 is important to us.

    A: Single embryo transfers are recommended by most for younger women to avoid multiple pregnancies that can have a detrimental effect on both mother and baby. However, with notable exceptions, I personally still recommend up to two blastocysts be transferred to increase the chance of success!

    4)Lastly, we’re considering moving our frozen blasts to another clinic where we receive more personalized care (before our frozen transfer next month). Do you know of any negative impact from doing this?

    A: Provided you choose a center of excellence there is no down side to switching to another clinic. Embryos are relocated all the time without significant risk.

    So again…..yes, PCOS can indeed exact a toll on egg quality but egg quality can in part protected through the judicious implementation of an individualized protocol for ovarian stimulation.

    Based on your own experience, you know that women with PCOS are hypersensitive to gonadotropin stimulation and are often at risk of developing serious complications associated with severe ovarian hyperstimulation syndrome (OHSS). Concern for this occurring often leads the treating physician to take precautionary measures aimed at slowing down or stopping hyperstimulation. Such measures include:

    1. Cutting the stimulation short to prevent the E2 from rising too high. Unfortunately this often results in the eggs being underdeveloped at the time of the “trigger” and thus, far more likely to end up being “immature”., “dysmature” and “incompetent”.

    2. Administering a lower “trigger dosage” of hCG , supplanting it (partially or completely) with an Agonist trigger (e.g. Lupron/Buserelin/aminopeptidyl/Superfact). While such measures can certainly reduce the risk/severity of OHSS, it often comes at the expense of egg competency (see below).
    In my opinion, another error of commission during ovarian stimulation of women with PCOS is the indiscriminate use of drugs that either elicit an exaggerated ovarian LH-induced testosterone response (e.g. clomiphene or Letrozole), or provide too much LH (e.g. Menopur/Menogon). Too much ovarian testosterone is harmful to egg development and thus prejudicial to embryo quality/competency.

    In my opinion the best way to approach ovarian stimulation for IVF in women with PCOS, is through the use of a low dosage, FSH-dominant Long ovarian down-regulation protocol, done in readiness for “prolonged coasting” (see below) and “triggering” egg maturation with a full 10,00U dosage of hCG or (no less than) 500mcg of recombinant hCG (Ovidrel)….see below is If this is implemented appropriately, with proper timing, egg/embryo quality can be optimized.
    I strongly recommend that you visit http://www.DrGeoffreySherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.

    • The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
    • Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
    • IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation (COS)
    • The Fundamental Requirements For Achieving Optimal IVF Success
    • Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
    • Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
    • Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas
    • Should IVF Treatment Cycles be provided uninterrupted or be Conducted in 7-12 Pre-scheduled “Batches” per Year
    • A personalized, stepwise approach to IVF
    • Taking A Fresh Look at Ovarian Hyperstimulation Syndrome (OHSS), its Presentation, Prevention and Management
    • Preventing Severe Ovarian Hyperstimulation Syndrome (OHSS) with “Prolonged Coasting”
    • Understanding Polycystic Ovarian Syndrome (PCOS) and the Need to Customize Ovarian Stimulation Protocols.
    • “Triggering” Egg Maturation in IVF: Comparing urine-derived hCG, Recombinant DNA-hCG and GnRH-agonist:
    • The “Lupron Trigger” to Prevent Severe OHSS: What are the Pro’s and Con’s?

    If you are interested in seeking my advice or services, I urge you to contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com You can also apply online at http://www.SherIVF.com .

    *FYI
    The 4th edition of my newest book ,”In Vitro Fertilization, the ART of Making Babies” is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.

    Geoffrey Sher MD

    Jennifer McCarty - September 13, 2017 reply

    Dr. Sher,
    Thank you SO much for these detailed responses. I have so much relief from your message. Of the 42 eggs retrieved, they said that 38 were mature and 17 fertilized (it’s Day 1). Does this mean that these 38 or 17 eggs were in fact ‘competent’?
    To confirm, at my age of 37 (no PGD tests), you would in fact recommend 2 blast transfers?
    Many thanks Dr. Sher, you’ve given me more information today than I received in this whole journey!

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - September 13, 2017 reply

    You are welcome Jennifer!

    No, you cannot determine competency of eggs or embryos with confidence, by their microscopic appearance alone. You need PGS to do that.

    Yes I recommend to my patients that up to 2 blastocysts be transferred in most cases.

    Geoff Sher

  • Roxanne - September 13, 2017 reply

    I am on my second cycle to try and freeze eggs. I have low Amh, first cycle with gonal f stopped after about 11 days of injections as follicles not increasing in size. I am 1o days in again, scan on day 8 of injections showed some follicles but small again. This time on 450 of merional and did 5 days of clomid at start. I just wondered if there is anything else I can do?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - September 13, 2017 reply

    No Roxanne. The most important factor in my opinion is for an optimal protocol for ovarian reserve to be used so as not to compromise your eggs during stimulation.

    In my opinion, the protocol used for ovarian stimulation, against the backdrop of age, and ovarian reserve are the drivers of egg quality and egg quality is the most important factor affecting egg/embryo “competency”.
    Women who (regardless of age) have DOR have a reduced potential for IVF success. Much of this is due to the fact that such women tend to have increased production of LH biological activity which can result in excessive LH-induced ovarian male hormone (predominantly testosterone) production which in turn can have a deleterious effect on egg/embryo “competency”.

    While it is presently not possible by any means, to reverse the effect of DOR, certain ovarian stimulation regimes, by promoting excessive LH production (e.g. short agonist/Lupron- “flare” protocols, clomiphene and Letrozole), can in my opinion, make matters worse. Similarly, the amount/dosage of certain fertility drugs that contain LH/hCG (e.g. Menopur) can have a negative effect on the development of the eggs of older women and those who have DOR and should be limited.I try to avoid using such protocols/regimes (especially) in women with DOR, favoring instead the use of the agonist/antagonist conversion protocol (A/ACP), a modified, long pituitary down-regulation regime, augmented by adding supplementary human growth hormone (HGH).
    to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com You can also apply online at http://www.SherIVF.com .

    *FYI
    The 4th edition of my newest book ,”In Vitro Fertilization, the ART of Making Babies” is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.

    Geoffrey Sher MD

  • Jyoti - September 13, 2017 reply

    Dr. Sher
    I am my husband are both 34 years of age. My hormone levels are:
    Day 2 results: FSH: 4.41 mIU/ml, LH: 3.53 mIU/ml, Prolactin: 14.24 ng/ml, E2: 40.67 pg/ml
    Day 6: AMH: 1.86 ng/ml

    Do you suggest taking any supplements to improve chances of natural conception or success through IUI/IVF?

    Thanks

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - September 13, 2017 reply

    I do not think any supplements will alter your fertility. I would not try without keeping a watchful eye on your AMH. If it drops below 1.5 you should start being proactive.

    Geoff Sher

  • Michelle - September 12, 2017 reply

    Hi Dr. Sher,
    How many PGS-tested normal, Day 5 blastocysts would you recommend transferring for a 40 year old with 4 first trimester miscarriages? This is my first transfer.
    Would your recommendation change knowing I am very petite (4’8″) but have a normal size uterus? Is it true that smaller women tend to have earlier term pregnancies?
    Thanks for your professional opinion!

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - September 12, 2017 reply

    Hi Michelle,

    I personally would transfer two (2).

    Geoff Sher

  • Sue - September 11, 2017 reply

    Hello Dr. Sher
    Am 34yrs old and I was diagnosed with PCOS about 10yrs ago. I convinced my boy with clomid 2yrs ago after 3yrs of trying. I will like to have a second child and I have been trying for 14months now with 2 failed iui. I was given Letrozole 7.5mg from 3-7 with all the cycle and Ovidrel shot. With all the cycle, I always end up with three mature follicles with the size ranging from 19-21mm and I always end in BFN.I took a break for a month and now I like will to start trying again but am confused if I should try another iui or keeping trying naturally or think of doing ivf. My husband sperm analysis is excellent. Please I need your advice.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - September 11, 2017 reply

    Sue,

    Thanks for the inquiry but alas, I need MUCH more information to be able to respond authoritatively.

    I strongly recommend that you visit http://www.DrGeoffreySherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.
    • The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
    • Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
    • IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation(COS)
    • The Fundamental Requirements For Achieving Optimal IVF Success
    • Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
    • Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
    • IVF Failure and Implantation Dysfunction:
    • The Role of Immunologic Implantation Dysfunction (IID) & Infertility (IID):PART 1-Background
    • Immunologic Implantation Dysfunction (IID) & Infertility (IID):PART 2- Making a Diagnosis
    • Immunologic Dysfunction (IID) & Infertility (IID):PART 3-Treatment
    • Thyroid autoantibodies and Immunologic Implantation Dysfunction (IID)
    • Immunologic Implantation Dysfunction: Importance of Meticulous Evaluation and Strategic Management:(Case Report
    • Intralipid and IVIG therapy: Understanding the Basis for its use in the Treatment of Immunologic Implantation Dysfunction (IID)
    • Intralipid (IL) Administration in IVF: It’s Composition; How it Works; Administration; Side-effects; Reactions and Precautions
    • Natural Killer Cell Activation (NKa) and Immunologic Implantation Dysfunction in IVF: The Controversy!
    • Endometrial Thickness, Uterine Pathology and Immunologic Factors
    • Vaginally Administered Viagra is Often a Highly Effective Treatment to Help Thicken a Thin Uterine Lining
    • Understanding Polycystic Ovarian Syndrome (PCOS) and the Need to Customize Ovarian Stimulation Protocols.
    • Intrauterine Insemination (IUI): Who Needs it & who Does Not: Pro’s & Con’s!
    • IUI-Reflecting upon its Use and Misuse: Time for a Serious “Reality Check”.
    • Micro-IVF: Often Preferable to Ovarian Stimulation with or Without IUI
    • The Role of Gender Selection in IVF.
    • Induction of Ovulation With Clomiphene Citrate: Mode of Action, Indications, Benefits, Limitations and Contraindications for its ue
    • Clomiphene Induction of Ovulation: Its Use and Misuse!
    • My Retirement in the Year Ahead: A letter of Thanks From me to You!

    If you are interested in seeking my advice or services, I urge you to contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com You can also apply online at http://www.SherIVF.com .
    *FYI
    The 4th edition of my newest book ,”In Vitro Fertilization, the ART of Making Babies” is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.

  • Randi - September 11, 2017 reply

    Dear Dr. Sher,

    I am 5.5 weeks pregnant today. I did a lipid infusion before the retrieval and then another lipid infusion at 4 weeks (when I got the positive pregnancy test). Should I be getting a lipid infusion once every 2 weeks (at 6 weeks, 8 weeks, 10 weeks, etc…) or once every 3 weeks, or once every 4 weeks?

    Also, how many weeks along should I be before I stop the lipid infusions?

    Thank you,
    Randi

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - September 11, 2017 reply

    Unless you have an alloimmune implantation dysfunction causing NK cell activation, it is my opinion that 2 ifusions are sufficient with the 2nd one due with the +VE beta hCG test!

    Geoff Sher

    Randi - September 12, 2017 reply

    I don’t know if I have alloimmune implantation dysfunction, my RE didn’t do a DQ Alpha genotyping test. I do have stage IV Endometriosis (had a laparoscopy to remove the endo in April and did Depot Lupron and Letrozole for about 4 months before this IVF), so after 3 miscarriages they added lipid infusions to my protocol. Any suggestions on whether or not I should continue to do the lipid infusions, and if so how often and for how long? I really appreciate your advice.

    Thank you,
    Randi

    Randi - September 12, 2017 reply

    … to give you a little extra info on my history Dr. Sher, my 1st miscarriage was a chromosomal abnormality (conceived the pregnancy naturally), 1st IVF I got pregnant but had a miscarriage at about 7 weeks (no chromosomal abnormality found when the tissue was tested), 2nd IVF failed, 3rd IVF I got pregnant but I had miscarriage very early (the betas were up and down and up, really no gestational sac formed and not enough tissue to test), 4th IVF failed, 5th IVF failed. Now I am pregnant having done a 6th IVF.

    Thank you again for your time,
    Randi

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - September 12, 2017

    Thank you for that!

    Geoff Sher

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - September 12, 2017 reply

    Randi,

    It certainly sounds as if yours is an autoimmune, rather than alloimmune issue, but that is not certain. It could be either or both and in my opinion it is important to make that determination. Thus I am not in a position to coldly advise you until I have much more information.

    I think we need to talk!

    I strongly recommend that you visit http://www.DrGeoffreySherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.
    • The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
    • Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
    • IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation(COS)
    • The Fundamental Requirements For Achieving Optimal IVF Success
    • Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
    • Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
    • The Role of Immunologic Implantation Dysfunction (IID) & Infertility (IID):PART 1-Background
    • Immunologic Implantation Dysfunction (IID) & Infertility (IID):PART 2- Making a Diagnosis
    • Immunologic Dysfunction (IID) & Infertility (IID):PART 3-Treatment
    • Thyroid autoantibodies and Immunologic Implantation Dysfunction (IID)
    • Immunologic Implantation Dysfunction: Importance of Meticulous Evaluation and Strategic Management:(Case Report
    • Intralipid and IVIG therapy: Understanding the Basis for its use in the Treatment of Immunologic Implantation Dysfunction (IID)
    • Intralipid (IL) Administration in IVF: It’s Composition; How it Works; Administration; Side-effects; Reactions and Precautions
    • Natural Killer Cell Activation (NKa) and Immunologic Implantation Dysfunction in IVF: The Controversy!
    • Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas
    • Should IVF Treatment Cycles be provided uninterrupted or be Conducted in 7-12 Pre-scheduled “Batches” per Year
    • A personalized, stepwise approach to IVF
    • The Role of Nutritional Supplements in Preparing for IVF
    • Endometriosis and Infertily
    • Endometriosis and Immunologic Implantation Dysfunction (IID) and IVF
    • Endometriosis and Infertility: Why IVF Rather than IUI or Surgery Should be the Treatment of Choice.
    • Endometriosis and Infertility: The Influence of Age and Severity on Treatment Options
    • Early -Endometriosis-related Infertility: Ovulation Induction (with or without Intrauterine Insemination) and Reproductive Surgery Versus IVF
    • Treating Ovarian Endometriomas with Sclerotherapy.

    If you are interested in seeking my advice or services, I urge you to contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com You can also apply online at http://www.SherIVF.com .
    *FYI
    The 4th edition of my newest book ,”In Vitro Fertilization, the ART of Making Babies” is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.

    Randi - September 13, 2017

    Dear Dr, Sher,

    Thank you so much for all of this information, I have been reading this morning many of these links above that you suggested. I will be contacting Julie asap to set up a consultation! I really appreciate your knowledge and time!

    Sincerely,
    Randi

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - September 13, 2017

    You are very welcome, Randi!

    Geoff Sher

  • Anita - September 10, 2017 reply

    Hello,
    I just did a frozen transfer aug 30 and my first beta at 9 days (post 5 day blastocyst) was 57. 48 hours later it was 78. My RN seems to think it’s over and to continue progesterone until I do a third HCG. I am 46 years old and have a healthy child. Is this bad luck or maybe a slow start? Everyone says 48-72 hours but I’m not hopeful anymore. Thank you.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - September 11, 2017 reply

    Hi Anita,

    I hope I am wrong but this slow rise in the beta, in my mind does not auger well for a successful outcome!

    Sorry!

    G-d bless!

    Geoff Sher

  • Mandy - September 10, 2017 reply

    Im 44 and am on the tww. If this fails i have one not so great 3 day embryo left. If that fails i asked my specialist if i could do another round to try for more eggs (i was a poor responder with diminished ovarian reserve at 40. Most rounds got cancelled except one which i managed 5 follicles of which i got two embros to freeze at day 3. I had a large fibroid that needed to be removed and then i had my sisters children living with us for 2 years as she was addicted to meth hence i have just had my first FET) and he said with sincerity he has enough money and that he wouldn’t want to take money for nothing. What are your thoughts on DHEA? Do you think it can help older women? We have no children and we are desperate for a child. Thank you

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - September 10, 2017 reply

    Whenever a patient fails to achieve a viable pregnancy following embryo transfer (ET), the first question asked is why! Was it simply due to, bad luck?, How likely is the failure to recur in future attempts and what can be done differently, to avoid it happening next time?.
    It is an indisputable fact that any IVF procedure is at least as likely to fail as it is to succeed. Thus when it comes to outcome, luck is an undeniable factor. Notwithstanding, it is incumbent upon the treating physician to carefully consider and address the causes of IVF failure before proceeding to another attempt:
    1. Age: The chance of a woman under 35Y of age having a baby per embryo transfer is about 35-40%. From there it declines progressively to under 5% by the time she reaches her mid-forties. This is largely due to declining chromosomal integrity of the eggs with advancing age…”a wear and tear effect” on eggs that are in the ovaries from birth.
    2. Embryo Quality/”competency (capable of propagating a viable pregnancy)”. As stated, the woman’s age plays a big role in determining egg/embryo quality/”competency”. This having been said, aside from age the protocol used for controlled ovarian stimulation (COS) is the next most important factor. It is especially important when it comes to older women, and women with diminished ovarian reserve (DOR) where it becomes essential to be aggressive, and to customize and individualize the ovarian stimulation protocol.
    We used to believe that the uterine environment is more beneficial to embryo development than is the incubator/petri dish and that accordingly, the earlier on in development that embryos are transferred to the uterus, the better. To achieve this goal, we used to select embryos for transfer based upon their day two or microscopic appearance (“grade”). But we have since learned that the further an embryo has advanced in its development, the more likely it is to be “competent” and that embryos failing to reach the expanded blastocyst stage within 5-6 days of being fertilized are almost invariably “incompetent” and are unworthy of being transferred. Moreover, the introduction into clinical practice about a decade ago, (by Levent Keskintepe PhD and myself) of Preimplantation Genetic Sampling (PGS), which assesses for the presence of all the embryos chromosomes (complete chromosomal karyotyping), provides another tool by which to select the most “competent” embryos for transfer. This methodology has selective benefit when it comes to older women, women with DOR, cases of unexplained repeated IVF failure and women who experience recurrent pregnancy loss (RPL).
    3. The number of the embryos transferred: Most patients believe that the more embryos transferred the greater the chance of success. To some extent this might be true, but if the problem lies with the use of a suboptimal COS protocol, transferring more embryos at a time won’t improve the chance of success. Nor will the transfer of a greater number of embryos solve an underlying embryo implantation dysfunction (anatomical molecular or immunologic).Moreover, the transfer of multiple embryos, should they implant, can and all too often does result in triplets or greater (high order multiples) which increases the incidence of maternal pregnancy-induced complications and of premature delivery with its serious risks to the newborn. It is for this reason that I rarely recommend the transfer of more than 2 embryos at a time and am moving in the direction of advising single embryo transfers …especially when it comes to transferring embryos derived through the fertilization of eggs from young women.
    4. Implantation Dysfunction (ID): Implantation dysfunction is a very common (often overlooked) cause of “unexplained” IVF failure. This is especially the case in young ovulating women who have normal ovarian reserve and have fertile partners. Failure to identify, typify, and address such issues is, in my opinion, an unfortunate and relatively common cause of repeated IVF failure in such women. Common sense dictates that if ultrasound guided embryo transfer is performed competently and yet repeated IVF attempts fail to propagate a viable pregnancy, implantation dysfunction must be seriously considered. Yet ID is probably the most overlooked factor. The most common causes of implantation dysfunction are:
    a. A“ thin uterine lining”
    b. A uterus with surface lesions in the cavity (polyps, fibroids, scar tissue)
    c. Immunologic implantation dysfunction (IID)
    d. Endocrine/molecular endometrial receptivity issues
    Certain causes of infertility are repetitive and thus cannot readily be reversed. Examples include advanced age of the woman; severe male infertility; immunologic infertility associated with alloimmune implantation dysfunction (especially if it is a “complete DQ alpha genetic match between partners plus uterine natural killer cell activation (NKa).
    I strongly recommend that you visit http://www.DrGeoffreySherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.

    • The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
    • Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
    • IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation (COS)
    • The Fundamental Requirements for Achieving Optimal IVF Success
    • Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
    • Ovarian Stimulation in Women Who have Diminished Ovarian Reserve (DOR): Introducing the Agonist/Antagonist Conversion protocol
    • Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
    • Human Growth Hormone Administration in IVF: Does it Enhances Egg/Embryo Quality and Outcome?
    • The BCP: Does Launching a Cycle of Controlled Ovarian Stimulation (COS). Coming off the BCP Compromise Response?
    • Blastocyst Embryo Transfers should be the Standard of Care in IVF
    • IVF: How Many Attempts should be considered before Stopping?
    • “Unexplained” Infertility: Often a matter of the Diagnosis Being Overlooked!
    • IVF Failure and Implantation Dysfunction:
    • The Role of Immunologic Implantation Dysfunction (IID) & Infertility (IID): PART 1-Background
    • Immunologic Implantation Dysfunction (IID) & Infertility (IID): PART 2- Making a Diagnosis
    • Immunologic Dysfunction (IID) & Infertility (IID): PART 3-Treatment
    • Thyroid autoantibodies and Immunologic Implantation Dysfunction (IID)
    • Immunologic Implantation Dysfunction: Importance of Meticulous Evaluation and Strategic Management 🙁 Case Report)
    • Intralipid and IVIG therapy: Understanding the Basis for its use in the Treatment of Immunologic Implantation Dysfunction (IID)
    • Intralipid (IL) Administration in IVF: It’s Composition; how it Works; Administration; Side-effects; Reactions and Precautions
    • Natural Killer Cell Activation (NKa) and Immunologic Implantation Dysfunction in IVF: The Controversy!
    • Endometrial Thickness, Uterine Pathology and Immunologic Factors
    • Vaginally Administered Viagra is Often a Highly Effective Treatment to Help Thicken a Thin Uterine Lining
    • Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas:
    • A personalized, stepwise approach to IVF
    • How Many Embryos should be transferred: A Critical Decision in IVF?
    • The Role of Nutritional Supplements in Preparing for IVF

    If you are interested in seeking my advice or services, I urge you to contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com You can also apply online at http://www.SherIVF.com .

    *FYI
    The 4th edition of my newest book ,”In Vitro Fertilization, the ART of Making Babies” is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.

    Geoffrey Sher MD

    _________________________________________________________________________________________________________________________
    ADDENDUM:

    Potential Downsides of DHEA Supplementation in Preparing for IVF: Why take the Risk?

    Geoffrey Sher MD

    Dehydroepiandrosterone (DHEA), is steroid hormone produced by the adrenal glands and ovary. It is involved in producing the male hormones, androstenedione testosterone and also estrogen. DHEA blood levels tend to decline naturally with age.
    Under the effect if luteinizing hormone (LH), DHEA is metabolized to testosterone in ovarian connective tissue (theca/stroma). Thereupon the testosterone is transported to the granulosa cells that form the innermost layer of the ovarian follicles where, under the influence of follicle stimulating hormone (FSH)-induced desmolase and aromatase enzymatic activity the testosterone is converted to estradiol. As this happens, granulosa cells multiply, follicle fluid volume increases along with estrogen output and egg development is promoted.
    It is recognition of the essential/indispensable role that male hormones (mainly testosterone) play in follicle and egg development that prompted the belief that by giving DHEA and boosting ovarian testosterone production might benefit follicle/egg development. This belief was given some credence by an Israeli study that in 2010 reported on improved fertility when a group of infertile women were given the administration of 75mg of oral DHEA for 5 months. However, this study was seriously flawed by the fact that it did not separate out women who had diminished ovarian reserve, older women and those with PCOS, all of whom have increased LH-induced production of testosterone. In fact, we recently completed a study (currently being processed for publication) where we conclusively showed that when follicular fluid testosterone levels exceeded a certain threshold, egg quality was seriously prejudiced as evidenced by a marked increase in the incidence of egg chromosomal defects (aneuploidy).
    Consider the following: Ovarian testosterone is needed for follicular development. However, the amount required is small. Too much ovarian testosterone spills over into the follicular fluid and has a deleterious effect on egg/follicle development. Some women (women with diminished ovarian reserve –DOR, older women and those with polycystic ovarian syndrome-PCOS) who tend to have increased LH biological activity, already over-produce testosterone. To such women, the administration of DHEA to such women, by “adding fuel to the fire” can be decidedly prejudicial, in my opinion. Young women with normal ovarian reserve do not over produce LH-induced ovarian testosterone, and are thus probably not at significant risk from DHEA supplementation. It is noteworthy that to date, none of the studies that suggest a benefit from DHEA therapy have differentiated between young healthy normal women with normal ovarian reserve on the one hand and older women, those with DOR and women with PCOS on the other hand.

    In Some countries DHEA treatment requires a medical prescription and medical supervision. Not so in the U.S.A where it can be bought over the counter. Since DHEA is involved in sex hormone production, including testosterone and estrogen, individuals with malignant conditions that may be hormone dependent (certain types of breast cancer or testicular cancer) should not receive DHEA supplementation. Also, if overdosed with DHEA some “sensitive women” might so increase their blood concentrations of testosterone that they develop increased aggressive tendencies or male characteristics such as hirsuites (increased hair growth) and a deepening voice. DHEA can also interact other medications, such as barbiturates, corticosteroids, insulin and with other oral diabetic medications.
    BUT the strongest argument against the use of routine DHEA supplementation is the potential risk of compromising egg quality in certain categories of women and since there is presently no convincing evidence of any benefit, why take the risk in using it on anyone.
    Finally, for those who in spite of the above, still feel compelled to take DHEA, the best advice I can give is to consult their health care providers before starting the process.

    Addendum: One potential advantage of DHEA therapy if used appropriately came from a study conducted by Washington University School of Medicine in St. Louis, MI and reported in the November 2004 issue of the “Journal of the American Medical Association” which showed that judicious (selective) administration of 50mg DHEA daily for 6 months resulted in a significant reduction of abdominal fat and blood insulin in elderly women.

    .

  • sapy - September 9, 2017 reply

    Dear Dr Sher,

    I have a rather long and sad infertility journey. I had my first ectopic pregancy (unplanned) when I was 26 and my left tube was damaged (later confirmed by a tubal patency test). After which for 2 yrs we did not try to get pregnant. we tried for 6 months post that and didn’t have any success. So visited a gynecologist, who after investigating told me that I have PCOS and put me on metformin for 2 months and gave me clomid. No luck with 4 cycles of clomid (I was on metformin for those 4 months) and then I stopped all medication. I conceived naturally after 4 months of stopping all medication but it was an ectopic pregnancy of the right tube. Then I had no other choice than to go for an IVF. Two cycles of IVF (2 different centers) and 3 embryo transfers later … I did not conceive. and my gynecologist told me the reason its failing could be because my endometrium is resisting implantation and should go for surrogacy next. which was extremely heart breaking!! But when I did a literature search on this I found that conditions like PCOS can cause high testosterone levels and can prevent implantation. Also, the drugs given for ovarian stimulation could cause hormonal imbalance which could prevent implantation. I have also noticed excessive acne and oiliness of my skin post IVF treatment. could it be possible that my IVF s are failing due to this and I need to get myself treated for this before going ahead? Please suggest what I should do?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - September 9, 2017 reply

    Whenever a patient fails to achieve a viable pregnancy following embryo transfer (ET), the first question asked is why! Was it simply due to, bad luck?, How likely is the failure to recur in future attempts and what can be done differently, to avoid it happening next time?.
    It is an indisputable fact that any IVF procedure is at least as likely to fail as it is to succeed. Thus when it comes to outcome, luck is an undeniable factor. Notwithstanding, it is incumbent upon the treating physician to carefully consider and address the causes of IVF failure before proceeding to another attempt:
    1. Age: The chance of a woman under 35Y of age having a baby per embryo transfer is about 35-40%. From there it declines progressively to under 5% by the time she reaches her mid-forties. This is largely due to declining chromosomal integrity of the eggs with advancing age…”a wear and tear effect” on eggs that are in the ovaries from birth.
    2. Embryo Quality/”competency (capable of propagating a viable pregnancy)”. As stated, the woman’s age plays a big role in determining egg/embryo quality/”competency”. This having been said, aside from age the protocol used for controlled ovarian stimulation (COS) is the next most important factor. It is especially important when it comes to older women, and women with diminished ovarian reserve (DOR) where it becomes essential to be aggressive, and to customize and individualize the ovarian stimulation protocol.
    We used to believe that the uterine environment is more beneficial to embryo development than is the incubator/petri dish and that accordingly, the earlier on in development that embryos are transferred to the uterus, the better. To achieve this goal, we used to select embryos for transfer based upon their day two or microscopic appearance (“grade”). But we have since learned that the further an embryo has advanced in its development, the more likely it is to be “competent” and that embryos failing to reach the expanded blastocyst stage within 5-6 days of being fertilized are almost invariably “incompetent” and are unworthy of being transferred. Moreover, the introduction into clinical practice about a decade ago, (by Levent Keskintepe PhD and myself) of Preimplantation Genetic Sampling (PGS), which assesses for the presence of all the embryos chromosomes (complete chromosomal karyotyping), provides another tool by which to select the most “competent” embryos for transfer. This methodology has selective benefit when it comes to older women, women with DOR, cases of unexplained repeated IVF failure and women who experience recurrent pregnancy loss (RPL).
    3. The number of the embryos transferred: Most patients believe that the more embryos transferred the greater the chance of success. To some extent this might be true, but if the problem lies with the use of a suboptimal COS protocol, transferring more embryos at a time won’t improve the chance of success. Nor will the transfer of a greater number of embryos solve an underlying embryo implantation dysfunction (anatomical molecular or immunologic).Moreover, the transfer of multiple embryos, should they implant, can and all too often does result in triplets or greater (high order multiples) which increases the incidence of maternal pregnancy-induced complications and of premature delivery with its serious risks to the newborn. It is for this reason that I rarely recommend the transfer of more than 2 embryos at a time and am moving in the direction of advising single embryo transfers …especially when it comes to transferring embryos derived through the fertilization of eggs from young women.
    4. Implantation Dysfunction (ID): Implantation dysfunction is a very common (often overlooked) cause of “unexplained” IVF failure. This is especially the case in young ovulating women who have normal ovarian reserve and have fertile partners. Failure to identify, typify, and address such issues is, in my opinion, an unfortunate and relatively common cause of repeated IVF failure in such women. Common sense dictates that if ultrasound guided embryo transfer is performed competently and yet repeated IVF attempts fail to propagate a viable pregnancy, implantation dysfunction must be seriously considered. Yet ID is probably the most overlooked factor. The most common causes of implantation dysfunction are:
    a. A“ thin uterine lining”
    b. A uterus with surface lesions in the cavity (polyps, fibroids, scar tissue)
    c. Immunologic implantation dysfunction (IID)
    d. Endocrine/molecular endometrial receptivity issues
    Certain causes of infertility are repetitive and thus cannot readily be reversed. Examples include advanced age of the woman; severe male infertility; immunologic infertility associated with alloimmune implantation dysfunction (especially if it is a “complete DQ alpha genetic match between partners plus uterine natural killer cell activation (NKa).
    I strongly recommend that you visit http://www.DrGeoffreySherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.

    • The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
    • Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
    • IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation (COS)
    • The Fundamental Requirements for Achieving Optimal IVF Success
    • Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
    • Ovarian Stimulation in Women Who have Diminished Ovarian Reserve (DOR): Introducing the Agonist/Antagonist Conversion protocol
    • Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
    • Human Growth Hormone Administration in IVF: Does it Enhances Egg/Embryo Quality and Outcome?
    • The BCP: Does Launching a Cycle of Controlled Ovarian Stimulation (COS). Coming off the BCP Compromise Response?
    • Blastocyst Embryo Transfers should be the Standard of Care in IVF
    • IVF: How Many Attempts should be considered before Stopping?
    • “Unexplained” Infertility: Often a matter of the Diagnosis Being Overlooked!
    • IVF Failure and Implantation Dysfunction:
    • The Role of Immunologic Implantation Dysfunction (IID) & Infertility (IID): PART 1-Background
    • Immunologic Implantation Dysfunction (IID) & Infertility (IID): PART 2- Making a Diagnosis
    • Immunologic Dysfunction (IID) & Infertility (IID): PART 3-Treatment
    • Thyroid autoantibodies and Immunologic Implantation Dysfunction (IID)
    • Immunologic Implantation Dysfunction: Importance of Meticulous Evaluation and Strategic Management 🙁 Case Report)
    • Intralipid and IVIG therapy: Understanding the Basis for its use in the Treatment of Immunologic Implantation Dysfunction (IID)
    • Intralipid (IL) Administration in IVF: It’s Composition; how it Works; Administration; Side-effects; Reactions and Precautions
    • Natural Killer Cell Activation (NKa) and Immunologic Implantation Dysfunction in IVF: The Controversy!
    • Endometrial Thickness, Uterine Pathology and Immunologic Factors
    • Vaginally Administered Viagra is Often a Highly Effective Treatment to Help Thicken a Thin Uterine Lining
    • Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas:
    • A personalized, stepwise approach to IVF
    • How Many Embryos should be transferred: A Critical Decision in IVF?
    • The Role of Nutritional Supplements in Preparing for IVF

    If you are interested in seeking my advice or services, I urge you to contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com You can also apply online at http://www.SherIVF.com .

    *FYI
    The 4th edition of my newest book ,”In Vitro Fertilization, the ART of Making Babies” is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.

    Geoffrey Sher MD

  • Denise - September 8, 2017 reply

    In my recent hysteroscopy done on CD 8, my uterine cavity was filled with a lot of white fluffy material that was not there in previous hysteroscopies. It was removed and tested to be “benign proliferative endometrium with focal glandular and stroma breakdown.”

    Have you seen this before? If it grows back, do you think it should be removed again before my upcoming FET or is it not an impediment as long as the rest of the uterine wall looks healthy? I am concerned the embryo might get lost in the tissue overgrowth, be crowded out, or can’t easily find a good landing place. There were also some blood clots mixed in the tissue.

    I appreciate your expertise!

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - September 9, 2017 reply

    As long as it is not endometrial pathology and there are no adhesions inside the uterine cavity, it is likely to be insignificant in my opinion.

    Geoff Sher

  • Denise - September 8, 2017 reply

    Hi Dr. Sher,
    Do you think endometrial scratches work?
    If so, what is the best timing before FET?

    I understand the exact placement of the embryos is paramount to implantation success. Where in the endometrium cavity do you like to place the embryos for FET?

    Thanks!

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - September 9, 2017 reply

    I have absolutely no belief in the endometrial scratch porocedure and do not do it.

    The ideal location for embryo placement is about 1cm below the roof of the uterine cavity.

    Good luck and G-d bless!

    Geoff Sher

  • Nicola - September 8, 2017 reply

    Dear Dr. Sher,
    I am a fragile x permutation carrier with amh of 0.36 and amenorrhea. I have a very low BMI. I recently began an ivf cycle after being on birth control pills for 13 days. I have failed to respond to six days of gonal-f and menopur. The gonal-f was increased from 300 units to 450 units for the last three days. My e2 level was under 5 pgmol at baseline and after three days of stimulation. I have an antral follicle count of four (all still unmeasurable).

    Do you believe it is possible that the use of birth control was ill timed? I would like to determine whether it is possible that this apparent lack of response may be overcome in a future cycle with a modified protocol. Any guidance that you may be kind enough to give would be most appreciated.

    Many thanks in advance,
    Nicola.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - September 8, 2017 reply

    In my opinion, the protocol used for ovarian stimulation, against the backdrop of age, and ovarian reserve are the drivers of egg quality and egg quality is the most important factor affecting embryo “competency”.
    Women who (regardless of age) have DOR have a reduced potential for IVF success. Much of this is due to the fact that such women tend to have increased production of LH biological activity which can result in excessive LH-induced ovarian male hormone (predominantly testosterone) production which in turn can have a deleterious effect on egg/embryo “competency”.

    While it is presently not possible by any means, to reverse the effect of DOR, certain ovarian stimulation regimes, by promoting excessive LH production (e.g. short agonist/Lupron- “flare” protocols, clomiphene and Letrozole), can in my opinion, make matters worse. Similarly, the amount/dosage of certain fertility drugs that contain LH/hCG (e.g. Menopur) can have a negative effect on the development of the eggs of older women and those who have DOR and should be limited.I try to avoid using such protocols/regimes (especially) in women with DOR, favoring instead the use of the agonist/antagonist conversion protocol (A/ACP), a modified, long pituitary down-regulation regime, augmented by adding supplementary human growth hormone (HGH). I further recommend that such women be offered access to embryo banking of PGS (next generation gene sequencing/NGS)-selected normal blastocysts, the subsequent selective transfer of which by allowing them to capitalize on whatever residual ovarian reserve and egg quality might still exist and thereby “make hay while the sun still shines” could significantly enhance the opportunity to achieve a viable pregnancy

    Please visit my new Blog on this very site, http://www.DrGeoffreySherIVF.com, find the “search bar” and type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.

    • Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
    • IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation(COS)
    • The Fundamental Requirements For Achieving Optimal IVF Success
    • Ovarian Stimulation for IVF using GnRH Antagonists: Comparing the Agonist/Antagonist Conversion Protocol.(A/ACP) With the “Conventional” Antagonist Approach
    • Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
    • The “Biological Clock” and how it should Influence the Selection and Design of Ovarian Stimulation Protocols for IVF.
    • A Rational Basis for selecting Controlled Ovarian Stimulation (COS) protocols in women with Diminished Ovarian Reserve (DOR)
    • Diagnosing and Treating Infertility due to Diminished Ovarian Reserve (DOR)
    • Controlled Ovarian Stimulation (COS) in Older women and Women who have Diminished Ovarian Reserve (DOR): A Rational Basis for Selecting a Stimulation Protocol
    • Human Growth Hormone Administration in IVF: Does it Enhances Egg/Embryo Quality and Outcome?
    • The BCP: Does Launching a Cycle of Controlled Ovarian Stimulation (COS). Coming off the BCP Compromise Response?
    • Blastocyst Embryo Transfers should be the Standard of Care in IVF
    • Frozen Embryo Transfer (FET) versus “Fresh” ET: How to Make the Decision
    • Frozen Embryo Transfer (FET): A Rational Approach to Hormonal Preparation and How new Methodology is Impacting IVF.
    • Staggered IVF: An Excellent Option When. Advancing Age and Diminished Ovarian Reserve (DOR) Reduces IVF Success Rate
    • Embryo Banking/Stockpiling: Slows the “Biological Clock” and offers a Selective Alternative to IVF-Egg Donation.
    • Preimplantation Genetic Testing (PGS) in IVF: It should be Used Selectively and NOT be Routine.
    • Preimplantation Genetic Sampling (PGS) Using: Next Generation Gene Sequencing (NGS): Method of Choice.
    • PGS in IVF: Are Some Chromosomally Abnormal Embryos Capable of Resulting in Normal Babies and Being Wrongly Discarded?
    • PGS and Assessment of Egg/Embryo “competency”: How Method, Timing and Methodology Could Affect Reliability
    • Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas:
    • Traveling for IVF from Out of State/Country–
    • A personalized, stepwise approach to IVF
    • How Many Embryos should be transferred: A Critical Decision in IVF.
    • The Role of Nutritional Supplements in Preparing for IVF
    • Premature Luteinization (“the premature LH surge): Why it happens and how it can be prevented.
    • IVF Egg Donation: A Comprehensive Overview

    If you are interested in seeking my advice or services, I urge you to contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com You can also apply online at http://www.SherIVF.com .

    *FYI
    The 4th edition of my newest book ,”In Vitro Fertilization, the ART of Making Babies” is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.

    Geoffrey Sher MD

    Addendum:

    Fragile X syndrome: Which IVF Candidates Should be Tested and How Should Results be Interpreted?
    Geoffrey Sher MD
    Fragile X syndrome occurs in individuals who carry the gene, FMR1 on an X-chromosome. This condition is inherited as a dominant X-linked disorder. With a dominant disorder, the condition results when there is only one copy of the altered gene in each cell.
    Fragile syndrome occurs twice as frequently in males (1:1,200) as compared to females (1:2,500) A striking characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons. The Fragile X gene, FMR1, can be passed on in a family by individuals who have no apparent signs of this genetic condition. In some families, a number of members appear to be affected, whereas in other families a newly diagnosed individual may be the first family member to exhibit symptoms.
    By and large, Fragile X syndrome results from a mutation in the FMR1 gene where a segment, known (CGG triplet repeat), is expanded. Under normal circumstances, the CGG triplet is repeated from 5 to approximately 55 times. In contrast, those who have Fragile X syndrome will have more than 200 repeats. CGG segments prevent the FMR from propagating the formation of a specific protein needed to protect against the development of Fragile X syndrome. Thus over-expression of CGG triplet (>200 times) on an X chromosome represents a degree of loss of this “protective protein” as to lead to the development of fragile X syndrome. Since boys have only one X chromosome, Fragile X syndrome tends to manifest much more severely in males than in females, (who have two X chromosomes).
    In a normal population, the number of repeated FMR1 genes varies from 5 to about 55. Those with 55 to 200 repeats of the CGG segment are said to have an FMR1 premutation (carriers”). In women, this is liable to increase to >200 repeats in the developing eggs. Accordingly, such women are at increased risk of having a child with fragile X syndrome. Conversely, when passed by men to the next generation, CGG repeats either remain the same in size or shorten. This is why men with a permutation do not transmit the disease. However they do transmit the permutation which if carried to a subsequent female offspring can result in them transmitting Fragile X syndrome in subsequent generations.
    Both males and females with fragile X pre-mutation are by and large intellectually and physically normal in outward appearance. Some may manifest with mild but often socially harmful intellectual or behavioral symptoms,. They are however usually not infertile.
    Some men with a premutation are at risk of developing a manifestation of fragile X-associated tremor/ataxia syndrome (FXTAS) a condition characterized by loss of balance, tremors and memory loss. It occurs in some older male carriers of the gene. Heart bone and skin problems are also often present. Age distribution is a s follows: Seventeen percent (17%) of males aged 50-59 years, in 38 percent of males aged 60-69 years, in 47 percent of males aged 70-79 years, and in 75 percent or males aged 80 years or older. Some female premutation carriers may have diminished ovarian reserve (DOR), premature ovarian failure and FXTAS.
    It is important to bear in mind that women who have approximately 55 to 200 repeats. There is no clear cut-off between the upper limit of normal and the lower limit of the premutation range. Accordingly, cases with 45-55 repeat copies fall into the so called “gray zone.” In some cases, premutations expand from generation to generation such that over time they ultimately express as full Fragile X syndrome. The larger the premutation in cases that fall in the “gray zone”, the greater is the risk of subsequent expansion to a full mutation in the offspring.
    Boys with full FMR1 mutation (Fragile X syndrome) will almost routinely have moderately severe mental retardation. They will tend to have a characteristic facial appearance with a long face, enlarged cranium, protruding ears and an elongated face with a protuberant chin and forehead. Affected boys after puberty tend also to experience enlargement of the scrotum and laxicity of joints. There will also usually be characteristic behavioral problems such as lack of impulse control, temper tantrums, delay in speech and language development and perseverative speech. Hand biting, hand flapping and attention deficit /hyperactivity are other common manifestations. Fragile X syndrome is also the most common known cause of autism or “autistic-like” behaviors.
    Girls with Fragile X on the other hand, tend to only have mild mental retardation. Women who have fewer repeats of the FMR-1 gene usually do not have mental retardation but often will have prematurely diminishing of ovarian reserve (DOR) with early menopause and infertility. Both men and women may develop FXTAS.
    While most males with full blown clinical fragile X syndrome are mentally retarded and exhibit some or all the physical and behavioral characteristics, only about one third of females are mentally retarded. Another one third are partially mentally impaired, and the remaining third are unaffected.
    Fragile X syndrome is diagnosed through DNA testing of cells using one of two methods:
    1. Polymerase Chain Reaction (PCR) or
    2. Southern blot analysis
    Both methods exhibit a high degree of interpersonal variability and thus when it comes to interpreting results, there are significant limitations. This is especially the case when diagnosing a “carrier state.” Interpretation is further complicated by the presence of other fragile sites in the same region of the X chromosome.
    It is recommended that in the following circumstances, patients undergoing assisted reproduction be tested for Fragile-X:
    • All mentally challenged individuals, those who are autistic, and in cases of developmental delay
    • Women with unexplained premature reduction in ovarian reserve or premature ovarian failure (menopause)
    • Individuals who have physical or behavioral characteristics of fragile X syndrome
    • Those with a family history of fragile X syndrome
    • Those with a family history of mentally challenged male or female relatives where no definitive cause has been ascertained.
    • Offspring of known carrier mothers
    Prenatal diagnosis can be made by 2nd trimester amniocentesis, which yields definitive results. In contrast, results obtained from 1st trimester chorionic villus sampling (CVS) should be interpreted with caution, because the status of the FMR1 gene often will not fully manifest in chorionic villi until the second trimester.
    .

  • Sofy - September 8, 2017 reply

    Hi Dr. Sher.
    I am 37. Have AMH 5.7. Had four follicles at collection, three eggs collected, two have fertilised. Tomorrow I will find out how they are and if I should have a two day transfer or wait and try to grow them to blastocyte. I could have them both put back but I’m not sure about that. I have to decide if I should go tomorrow for a two day transfer or wait till day 5. (If they are still ok that is by the morning) What would you advise?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - September 8, 2017 reply

    Embryo transfer (ET) is undoubtedly a rate limiting factor when it comes to IVF outcome. In fact, in my opinion, it is the single most important procedural step in IVF. Optimal performance of ET takes practice, confidence, dexterity, timing, gentility and skill. Of all the hands-on procedures involved in the IVF process, embryo transfer is by far the most difficult to teach. In fact, any women fail to conceive simply because the practicing physician did (could) not perform this procedure optimally.

    The issue of whether it is better to transfer early (day 2-3,post fertilization) cleaved embryos rather than (day 5-6) blastocysts continues to rage. Here I wish to focus on the reasons why I favor transferring blastocysts.

    Not too long ago, it was believed that the sooner an embryo was transferred into the “natural environment” of the uterus, the greater would be the chance of it implanting and propagating a viable pregnancy. Thus most IVF physicians advocated day 2 or day 3 embryo transfers preferentially. About 20 years ago, we began to realize that there was no validity to the belief that an embryo would develop better and have a greater chance of propagating a baby by being inside the uterus earlier than it would by being allowed to first develop into a blastocyst in an incubator. About a decade later, it was realized that cleaved embryos that fail to develop into blastocysts are with few exceptions numerically chromosomally “incompetent” (aneuploid) such that had they been transferred earlier, they almost certainly would not have developed into blastocysts and would not have propagated a pregnancy anyway. Now most of us practicing in this field believe it to be preferential to selectively transfer blastocysts rather than earlier cleaved embryos. Don’t get me wrong! I am not saying that there is never a place for doing earlier pre-blastocyst transfers. Patients that only have one or two cleaved embryos available might as well transfer them early.

    The recent popularization of full preimplantation genetic sampling (PGS) using methods such as comparative genomic hybridization (CGH), next generation gene sequencing (NGS) and SNP array, now allow us to identify those blastocysts that are the most “competent”. Selective transfer of such embryos improves the implantation rate per embryo by a factor of 2-3.

    It is important to bear in mind that morphologically good looking day 3 embryos/blastocysts that are determined microscopically to be of a “high grade” , are by no means always numerically chromosomally “competent” euploid , and the likelihood of such embryos being “competent” diminishes progressively with advancing age of the woman. Only through the performance of full PGS can his age-related discrepancy be reduced.

    While it would be acceptable to me to transfer 2 PGS-untested blastocysts to women under 39 years, and to transfer 3 to older women, I would not recommend transferring more than 2 PGS-normal embryos at any age.

    The following are arguments in favor of performing blastocysts transfers:
    • By waiting to day 5-6 many unworthy, many aneuploid and “incompetent” embryos can be culled out, thereby allowing for the transfer of fewer embryos and minimizing the risk of high order multiple pregnancies.
    • Diagnostic Advantages:
    o Failure of the expected number of cleaved embryos to advance to the blastocyst stage of development in culture, raises the suspicion of underlying inherent embryo “incompetence”, which is usually (but not exclusively) egg-related rather than due to a sperm factor. While age of the woman is the most important factor involved, it can also be due to the wrong protocol of ovarian stimulation being used).
    o It facilitates the performance of PGS to identify and then selectively transfer only most “competent” (euploid) blastocysts. In such cases, provided there is no underlying uterine implantation dysfunction implantation and pregnancy rate is enhanced significantly.

    Of course, for the treating physician it is far less stressful not have to have to confront a patient with her having no surviving embryos to transfer. The avoidance of this has in my opinion, in the past, been one of the main reasons why IVF practitioners have elected to transfer cleaved embryos rather than blastocysts. But such a policy is usually not in the in the patients’ best interest. In my opinion, it is far better to advise the patient to do a blastocyst transfer since that is almost always in their best interest.

    Hope this helps!

    Geoff Sher
    PH: 800-780-7437

  • Annie Royena - September 7, 2017 reply

    Dr. I just wanted to ask my last menstrual period is august 1,2017-so im expecting my next period on the 26th. I got my period but only for one day..after a few days i use hpt….and it came out with a very blurred lines but showing positive…i test again after two days and its really positive….i got docs appt…and the urine test shows negative…and the doc says my hcg level is too low at about 25000….so i took blood test and its positive.but when i went to a maternty hospital the urine test is negative….pls advice me do you think im pregnant?thank you in advance

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - September 7, 2017 reply

    It clearly suggests that you conceived. Howsoever, the viability of the pregnancy needs still to be established. i suggest you orange for an ultrasound, sooner rather than later.

    Good luck!

    Geoff Sher

  • Jyoti - September 7, 2017 reply

    Dr. Sher, I had one failed cycle of IUI with 50mg Clomid. On the day of trigger(Day-11), my lining was found to be 6.6mm which my RE mentioned was thin potentially as a side effect from clomid. We are planning to start another cycle of IUI and would like your advice on whether to replace clomid with femara or Gonadotropin? Which of these has a better success rates with lesser side-effects that might affect success?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - September 7, 2017 reply

    Absolutely I would do so. Clomiphene is an anti-estrogen and makes it harder for endorgans (such as the endometrium) to respond optimally to estrogen. It is more likely for this to happen with a build up of clompihene after several back to back cycles .

    Geoff Sher

    Jyoti - September 8, 2017 reply

    Thanks for your advice. Dr. Sher. Would you recommend using Femara or Gonad F? Is one preferred over another? Thanks

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - September 8, 2017 reply

    Gonal-F.

    Geoff Sher

    Jyoti - September 20, 2017

    Thanks for your advice Dr. When on Clomid 50mg, I developed 2 follicles 18mm and 17mm and another smaller one 11.7mm. What dose of Gonal F would you recommend to avoid over stimulation and a potentially cancelled cycle? Thanks a lot.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - September 20, 2017

    Sorry Jyoti…Not enough information for me to advise
    e.

    Geoff Sher

  • Susan - September 7, 2017 reply

    Hi Dr. Sher,
    I am 37 with severe DOR and have been pursuing donor egg IVF. My first eSET worked, but I had a missed miscarriage at 9 weeks; the tissue from the D and E tested as chromosomally normal. Since then we have done 4 more eSETs, each failing to implant. I also have a bicornuate uterus which seems to be complicating implantation. This past cycle I was on metformin and baby aspirin (I was not taking either when I became pregnant on that first eSET). We have one more embryo left; if that doesn’t work, we can choose a new donor. We did not do PGS testing on this batch of embryos; the donor was 21, and all embryos were 5AA or 5AB blasts that thawed beautifully.

    Should we be investigating immunology at this point? Should we do PGS testing on our embryos if we have to choose a new donor? Thanks!

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - September 7, 2017 reply

    Him Susan,

    A bicornuate uterus does NOT lead to infertility or deven early miscarriages. It is associated with late miscarriages and premature birth however. Also, in my opinion, it is not usually necessary to do PGS in cases of egg donation with IVF since about 50% of embryos derived the eggs of young women should be chromosomally intact (euploid and “competent”).

    Whenever a patient fails to achieve a viable pregnancy following embryo transfer (ET), the first question asked is why! Was it simply due to, bad luck?, How likely is the failure to recur in future attempts and what can be done differently, to avoid it happening next time?.
    It is an indisputable fact that any IVF procedure is at least as likely to fail as it is to succeed. Thus when it comes to outcome, luck is an undeniable factor. Notwithstanding, it is incumbent upon the treating physician to carefully consider and address the causes of IVF failure before proceeding to another attempt:
    1. Age: The chance of a woman under 35Y of age having a baby per embryo transfer is about 35-40%. From there it declines progressively to under 5% by the time she reaches her mid-forties. This is largely due to declining chromosomal integrity of the eggs with advancing age…”a wear and tear effect” on eggs that are in the ovaries from birth.
    2. Embryo Quality/”competency (capable of propagating a viable pregnancy)”. As stated, the woman’s age plays a big role in determining egg/embryo quality/”competency”. This having been said, aside from age the protocol used for controlled ovarian stimulation (COS) is the next most important factor. It is especially important when it comes to older women, and women with diminished ovarian reserve (DOR) where it becomes essential to be aggressive, and to customize and individualize the ovarian stimulation protocol.
    We used to believe that the uterine environment is more beneficial to embryo development than is the incubator/petri dish and that accordingly, the earlier on in development that embryos are transferred to the uterus, the better. To achieve this goal, we used to select embryos for transfer based upon their day two or microscopic appearance (“grade”). But we have since learned that the further an embryo has advanced in its development, the more likely it is to be “competent” and that embryos failing to reach the expanded blastocyst stage within 5-6 days of being fertilized are almost invariably “incompetent” and are unworthy of being transferred. Moreover, the introduction into clinical practice about a decade ago, (by Levent Keskintepe PhD and myself) of Preimplantation Genetic Sampling (PGS), which assesses for the presence of all the embryos chromosomes (complete chromosomal karyotyping), provides another tool by which to select the most “competent” embryos for transfer. This methodology has selective benefit when it comes to older women, women with DOR, cases of unexplained repeated IVF failure and women who experience recurrent pregnancy loss (RPL).
    3. The number of the embryos transferred: Most patients believe that the more embryos transferred the greater the chance of success. To some extent this might be true, but if the problem lies with the use of a suboptimal COS protocol, transferring more embryos at a time won’t improve the chance of success. Nor will the transfer of a greater number of embryos solve an underlying embryo implantation dysfunction (anatomical molecular or immunologic).Moreover, the transfer of multiple embryos, should they implant, can and all too often does result in triplets or greater (high order multiples) which increases the incidence of maternal pregnancy-induced complications and of premature delivery with its serious risks to the newborn. It is for this reason that I rarely recommend the transfer of more than 2 embryos at a time and am moving in the direction of advising single embryo transfers …especially when it comes to transferring embryos derived through the fertilization of eggs from young women.
    4. Implantation Dysfunction (ID): Implantation dysfunction is a very common (often overlooked) cause of “unexplained” IVF failure. This is especially the case in young ovulating women who have normal ovarian reserve and have fertile partners. Failure to identify, typify, and address such issues is, in my opinion, an unfortunate and relatively common cause of repeated IVF failure in such women. Common sense dictates that if ultrasound guided embryo transfer is performed competently and yet repeated IVF attempts fail to propagate a viable pregnancy, implantation dysfunction must be seriously considered. Yet ID is probably the most overlooked factor. The most common causes of implantation dysfunction are:
    a. A“ thin uterine lining”
    b. A uterus with surface lesions in the cavity (polyps, fibroids, scar tissue)
    c. Immunologic implantation dysfunction (IID)
    d. Endocrine/molecular endometrial receptivity issues
    Certain causes of infertility are repetitive and thus cannot readily be reversed. Examples include advanced age of the woman; severe male infertility; immunologic infertility associated with alloimmune implantation dysfunction (especially if it is a “complete DQ alpha genetic match between partners plus uterine natural killer cell activation (NKa).
    I strongly recommend that you visit http://www.DrGeoffreySherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.

    • The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
    • Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
    • IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation (COS)
    • The Fundamental Requirements for Achieving Optimal IVF Success
    • Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
    • Ovarian Stimulation in Women Who have Diminished Ovarian Reserve (DOR): Introducing the Agonist/Antagonist Conversion protocol
    • Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
    • Human Growth Hormone Administration in IVF: Does it Enhances Egg/Embryo Quality and Outcome?
    • The BCP: Does Launching a Cycle of Controlled Ovarian Stimulation (COS). Coming off the BCP Compromise Response?
    • Blastocyst Embryo Transfers should be the Standard of Care in IVF
    • IVF: How Many Attempts should be considered before Stopping?
    • “Unexplained” Infertility: Often a matter of the Diagnosis Being Overlooked!
    • IVF Failure and Implantation Dysfunction:
    • The Role of Immunologic Implantation Dysfunction (IID) & Infertility (IID): PART 1-Background
    • Immunologic Implantation Dysfunction (IID) & Infertility (IID): PART 2- Making a Diagnosis
    • Immunologic Dysfunction (IID) & Infertility (IID): PART 3-Treatment
    • Thyroid autoantibodies and Immunologic Implantation Dysfunction (IID)
    • Immunologic Implantation Dysfunction: Importance of Meticulous Evaluation and Strategic Management 🙁 Case Report)
    • Intralipid and IVIG therapy: Understanding the Basis for its use in the Treatment of Immunologic Implantation Dysfunction (IID)
    • Intralipid (IL) Administration in IVF: It’s Composition; how it Works; Administration; Side-effects; Reactions and Precautions
    • Natural Killer Cell Activation (NKa) and Immunologic Implantation Dysfunction in IVF: The Controversy!
    • Endometrial Thickness, Uterine Pathology and Immunologic Factors
    • Vaginally Administered Viagra is Often a Highly Effective Treatment to Help Thicken a Thin Uterine Lining
    • Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas:
    • A personalized, stepwise approach to IVF
    • How Many Embryos should be transferred: A Critical Decision in IVF?
    • The Role of Nutritional Supplements in Preparing for IVF

    If you are interested in seeking my advice or services, I urge you to contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com You can also apply online at http://www.SherIVF.com .

    *FYI
    The 4th edition of my newest book ,”In Vitro Fertilization, the ART of Making Babies” is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.

    Geoffrey Sher MD

  • Stefanie Z. - September 7, 2017 reply

    I have now had 2 failed frozen cycles, with PGS tested, normal 5-day blasts. I did eSET each round. After the first round failed we found out I had immunological issues (very elevated APA levels, active NK cells and borderline positive ANA). On the second round of IVF, I did IViG one week prior to the ET, took prednisone, and lovenox. My HSG was perfect and so were all my hormone levels, lining (9+), etc.). After reading your blogs the only undiscovered issue at hand seems to be the DQ Alpha topic. However, my husband and I already have one son that was conceived through IVF a few years ago. SO, the question is: Does having a child already eliminate the fact that there could be a ‘complete’ match issue between my husband and I… and if so, am I correct to assume that there could be a partial match issue causing the failure this last time, meaning that each transfer is a 50/50 chance of success? Thank you!!!

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - September 7, 2017 reply

    Hi Stefanie,

    It is a misconception that having had a child in the past precludes an immunologic implantation dysfunction, especially in cases of alloimmune dysfunction (see below) where having had a child in the past is not uncommon.

    Whenever a patient fails to achieve a viable pregnancy following embryo transfer (ET), the first question asked is why! Was it simply due to, bad luck?, How likely is the failure to recur in future attempts and what can be done differently, to avoid it happening next time?.
    It is an indisputable fact that any IVF procedure is at least as likely to fail as it is to succeed. Thus when it comes to outcome, luck is an undeniable factor. Notwithstanding, it is incumbent upon the treating physician to carefully consider and address the causes of IVF failure before proceeding to another attempt:
    1. Age: The chance of a woman under 35Y of age having a baby per embryo transfer is about 35-40%. From there it declines progressively to under 5% by the time she reaches her mid-forties. This is largely due to declining chromosomal integrity of the eggs with advancing age…”a wear and tear effect” on eggs that are in the ovaries from birth.
    2. Embryo Quality/”competency (capable of propagating a viable pregnancy)”. As stated, the woman’s age plays a big role in determining egg/embryo quality/”competency”. This having been said, aside from age the protocol used for controlled ovarian stimulation (COS) is the next most important factor. It is especially important when it comes to older women, and women with diminished ovarian reserve (DOR) where it becomes essential to be aggressive, and to customize and individualize the ovarian stimulation protocol.
    We used to believe that the uterine environment is more beneficial to embryo development than is the incubator/petri dish and that accordingly, the earlier on in development that embryos are transferred to the uterus, the better. To achieve this goal, we used to select embryos for transfer based upon their day two or microscopic appearance (“grade”). But we have since learned that the further an embryo has advanced in its development, the more likely it is to be “competent” and that embryos failing to reach the expanded blastocyst stage within 5-6 days of being fertilized are almost invariably “incompetent” and are unworthy of being transferred. Moreover, the introduction into clinical practice about a decade ago, (by Levent Keskintepe PhD and myself) of Preimplantation Genetic Sampling (PGS), which assesses for the presence of all the embryos chromosomes (complete chromosomal karyotyping), provides another tool by which to select the most “competent” embryos for transfer. This methodology has selective benefit when it comes to older women, women with DOR, cases of unexplained repeated IVF failure and women who experience recurrent pregnancy loss (RPL).
    3. The number of the embryos transferred: Most patients believe that the more embryos transferred the greater the chance of success. To some extent this might be true, but if the problem lies with the use of a suboptimal COS protocol, transferring more embryos at a time won’t improve the chance of success. Nor will the transfer of a greater number of embryos solve an underlying embryo implantation dysfunction (anatomical molecular or immunologic).Moreover, the transfer of multiple embryos, should they implant, can and all too often does result in triplets or greater (high order multiples) which increases the incidence of maternal pregnancy-induced complications and of premature delivery with its serious risks to the newborn. It is for this reason that I rarely recommend the transfer of more than 2 embryos at a time and am moving in the direction of advising single embryo transfers …especially when it comes to transferring embryos derived through the fertilization of eggs from young women.
    4. Implantation Dysfunction (ID): Implantation dysfunction is a very common (often overlooked) cause of “unexplained” IVF failure. This is especially the case in young ovulating women who have normal ovarian reserve and have fertile partners. Failure to identify, typify, and address such issues is, in my opinion, an unfortunate and relatively common cause of repeated IVF failure in such women. Common sense dictates that if ultrasound guided embryo transfer is performed competently and yet repeated IVF attempts fail to propagate a viable pregnancy, implantation dysfunction must be seriously considered. Yet ID is probably the most overlooked factor. The most common causes of implantation dysfunction are:
    a. A“ thin uterine lining”
    b. A uterus with surface lesions in the cavity (polyps, fibroids, scar tissue)
    c. Immunologic implantation dysfunction (IID)
    d. Endocrine/molecular endometrial receptivity issues
    Certain causes of infertility are repetitive and thus cannot readily be reversed. Examples include advanced age of the woman; severe male infertility; immunologic infertility associated with alloimmune implantation dysfunction (especially if it is a “complete DQ alpha genetic match between partners plus uterine natural killer cell activation (NKa).
    I strongly recommend that you visit http://www.DrGeoffreySherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.

    • The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
    • Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
    • IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation (COS)
    • The Fundamental Requirements for Achieving Optimal IVF Success
    • Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
    • Ovarian Stimulation in Women Who have Diminished Ovarian Reserve (DOR): Introducing the Agonist/Antagonist Conversion protocol
    • Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
    • Human Growth Hormone Administration in IVF: Does it Enhances Egg/Embryo Quality and Outcome?
    • The BCP: Does Launching a Cycle of Controlled Ovarian Stimulation (COS). Coming off the BCP Compromise Response?
    • Blastocyst Embryo Transfers should be the Standard of Care in IVF
    • IVF: How Many Attempts should be considered before Stopping?
    • “Unexplained” Infertility: Often a matter of the Diagnosis Being Overlooked!
    • IVF Failure and Implantation Dysfunction:
    • The Role of Immunologic Implantation Dysfunction (IID) & Infertility (IID): PART 1-Background
    • Immunologic Implantation Dysfunction (IID) & Infertility (IID): PART 2- Making a Diagnosis
    • Immunologic Dysfunction (IID) & Infertility (IID): PART 3-Treatment
    • Thyroid autoantibodies and Immunologic Implantation Dysfunction (IID)
    • Immunologic Implantation Dysfunction: Importance of Meticulous Evaluation and Strategic Management 🙁 Case Report)
    • Intralipid and IVIG therapy: Understanding the Basis for its use in the Treatment of Immunologic Implantation Dysfunction (IID)
    • Intralipid (IL) Administration in IVF: It’s Composition; how it Works; Administration; Side-effects; Reactions and Precautions
    • Natural Killer Cell Activation (NKa) and Immunologic Implantation Dysfunction in IVF: The Controversy!
    • Endometrial Thickness, Uterine Pathology and Immunologic Factors
    • Vaginally Administered Viagra is Often a Highly Effective Treatment to Help Thicken a Thin Uterine Lining
    • Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas:
    • A personalized, stepwise approach to IVF
    • How Many Embryos should be transferred: A Critical Decision in IVF?
    • The Role of Nutritional Supplements in Preparing for IVF

    If you are interested in seeking my advice or services, I urge you to contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com You can also apply online at http://www.SherIVF.com .

    *FYI
    The 4th edition of my newest book ,”In Vitro Fertilization, the ART of Making Babies” is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.

    Geoffrey Sher MD

  • Caitlin M - September 6, 2017 reply

    Hi Dr Sher,
    what are yout thoughts on natural FETs? I have two children after many many transfers (8 total of which 1/2 fresh were successful and 1/6 FET were successful). Until recently I thought perhaps embryo quality was my issue but we just received word that 6/7 blasts tested on our recent fresh cycle (with no transfer) were euploid. I am 32 and we are doing IVF because of antibodies post vasectomy reversal). We always have an amazing lining at FET of 10+ and have always had good quality blasts…and yet, so many failures. We have tested for natural killer cells and other such immune issues and all has been normal.
    One thing that is off is that my estrogen has been on the lower end prior to transfer (around 200) even though my lining has been perfect. My Dr. is comfortable increasing my estrogen if that is what I want (I had switched clinics because of a move this year), but he says that if the lining is good the estrogen level has proven to be insignificant.
    I am strongly considering a natural cycle FET (I do have regular 30 days cycles) in hopes that this will be our answer.
    What would you do? Increase estrogen on a medicated cycle, or try for a natural cycle with an hcg trigger shot and progesterone support?

    Caitlin M - September 6, 2017 reply

    PS – all of my prior FETs have been medicated, with various methods of estrogen including patches/creams/oral (the last one was just oral and my estrogen was 190) though my lining was 12.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - September 6, 2017 reply

    If you wish, I would be happy to review your immune test results. Remember, the NK cell blood concentration is irrelevant. It is the toxicity as measured by the K-562 target cell test that matters most.

    Good luck!

    Geoff Sher

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - September 6, 2017 reply

    Catlin!

    I almost always do HRT for FET’s. It far easier to reliably predict the optimal implantation window that way. In fact, in my opinion the results are superior.

    This having been said, I target a blood estradiol level of >500pg/ml for my HRT-FET’s.

    Geoff Sher

  • nicole - September 6, 2017 reply

    Hi Dr. Sher,
    I had an Eset a few weeks ago.
    My beta at 15dpo was 99 and today at 5 weeks is 1320. We saw a small sack today via ultrasound.
    My issue is spotting. I’m continuously spotting. I’m on endometrin 3 times a day and prometrium twice a day orally. My progesterone has been 12.3 consistently. Shouldn’t it be going up? Is this a cause of concern for you, to be on so much supplementation and have a low number? What are your thoughts?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - September 6, 2017 reply

    I do not think there is anything more to do but wait. I would not add more progesterone. In my opinion, all that is needed is for you to do a repeat US in a week and see!

    Good luck!

    Geoff Sher

    Nicole - September 6, 2017 reply

    Is low progesterone a sign of an abnormal embryo?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - September 6, 2017 reply

    No! Not necessarily…

    Geoff Sher

    Nicole - September 6, 2017 reply

    Also, I should mention this FET was a natural fet. I did a trigger to time ovulation and progesterone suppositories after ovulation. So shouldn’t my body be making more progesterone? It just doesn’t seem right to me.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - September 6, 2017 reply

    In fact to the contrary…I would expect the progesterone to be on the lower side!

    Geoff Sher

  • Sheena - September 6, 2017 reply

    Hi Dr Sher, is it safe to do vaginal ultrasound scans if you could be pregnant? Are the IVF ultrasound scans the same scans that are done during pregnancy?

    Sheena - September 6, 2017 reply

    Hi Dr Sher … to clarify the above … I mean at very early stages of pregnancy (first few days or week). We are trying to conceive naturally and I ovulated about 5 days ago but I have a scan tomorrow to check my endometrium lining (as it was very thin at the last month’s IVF cycle). I just wanted to make sure it’s ok to do a scan if I happen to be pregnant.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - September 6, 2017 reply

    Sure it is OK!

    Geoff sher

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - September 6, 2017 reply

    Perfectly OK in my opinion.

    Geoff Sher

    Sheena - September 6, 2017 reply

    Thanks so much for the reassurance Dr Sher!! So there isn’t a specific time period to wait after pregnancy before it is safe to scan then is there? Any time from day one of pregnancy is fine to scan?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - September 6, 2017 reply

    No Sheena, there is not!

    Geoff Sher

    Sheena - September 7, 2017

    Thank you so much Dr Sher. I really appreciate your advice and value your opinion!!

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - September 7, 2017

    You are very welcome Sheena!

    Geoff Sher

  • Lucinda Smith - September 6, 2017 reply

    Dear Dr Sher, I am aged 43 and am about to go into my final IVF round after several failed attempts. I am from Australia and have interest in your articles about the A/ACP protocol etc. I was wondering if you could advise me your thoughts on this protocol prescribed from my IVF dr here?:
    – Commence 7 days before period Synarel morning and night
    – Day 2 onwards take FSH 450mg concurrently with 250mg Orgulatran also day 2 until egg collection.
    – take progynova (estrogen) daily one week before period due also
    – melatonin 5mg daily from 1 week before period.
    Could you advise your thoughts on the above and whether it sounds reasonable??
    Kind regards,
    Lucinda

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - September 6, 2017 reply

    This is not the way I personally do it but by starting off in the mid luteal phase with an antagonist (albeit a nasally administered product) and ching to an antagonist with the onset of stimulation is an acceptable variation. I start with a BCP, then overlap with Lupron (an injectable medication), supplanted with half the dosage of antagonist (125mcg) + FSH with the onset of bleeding.You are priming with oral estradiol valerate (Progynova) starting 1 week before stimulation. I usually do not prime with estrogen unless there is very severe DOR and I use injectable estradiol valerate (Delestrogen) every 3 days. IO also do not prescribe Melatonin but I do not see it having a harmful effect. I t7hen trigger with 10,000U hCGu (Novarel/Pregnyl/Profasi).

    I must hasten to say that I have no concrete evidence that my approach is better than the variation that you will be on. There are probably several acceptable variations on the agonist/antagonist protocol approach.

    Good luck!

    Geoff Sher

    Lucinda Smith - September 8, 2017 reply

    Hi Dr Sher, thank you for your reply. I just wanted to clarify – Synarel is an agonist – I believe the equivalent to Lupon in the States and not an antagonist as you have written? Also, what is the benefit of doing 125mg of antagonist Orgulatran instead of 250mg as my dr has suggested – is there any difference?? Thank you again!!

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - September 8, 2017 reply

    Oops…sorry if I mistyped. It is an agonist taken nasally. My problem is that nasal absorption is erratic and not as reliable as injections with Lupron or Superfact.

    Geoff Sher

    Lucinda Smith - September 12, 2017

    Dear Dr Sher, May I ask is there any difference doing 125mg of Orgulatran instead of 250mg? Also would there be any benefit of me adding Luveris in there at any stage. I have read where you advise against it in older women additional LH but then I have also read in your a/acp protocol that you would add a small dose. Which would you recommend? Thank you 🙂

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - September 12, 2017

    Only 125mcg is needed in my opinion. However, I doubt that the use of 250mcg would be harmful and yes, a small amount of LH-like activity is needed . Up to 75U Luveris or 75U menotropin (e.g. Menopur) is fine.

    Geoff Sher

  • Sheena - September 6, 2017 reply

    Hi Dr Sher, I notice you previously mentioned you prefer medicated over natural ETs. What is the reason for this? I was told they both have the same success rates. Is this true? Many thanks in advance.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - September 6, 2017 reply

    In my nopinion, natural cycle FET’s yield significantly lower success because it is more difficult to pinpoint the optimal implantation time in natural cycles than with hormone regulated cycles.

    Geoff Sher

  • marla carroll - September 5, 2017 reply

    My daughter had a 5 day frozen genetically tested embryo transfer 7 weeks 5 day ago, her ultra sound showed a strong heart beat but the fetal pole measured 1 week behind, is there a chance for a healthy pregnancy?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - September 6, 2017 reply

    It can catch up and recover!

    Good luck!

    Geoff Sher

  • Sheena - September 5, 2017 reply

    Hi Dr Sher, have you had much experience with ERA tests? What kind of success rates have you seen doing the ERA tests? Does the ERA biopsy cause damage to the lining?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - September 5, 2017 reply

    I personally have no confidence in the value of ERA testing and unless patients insist on having it done, I do not use it at all!

    Geoff Sher

    Sheena - September 5, 2017 reply

    Thank you Dr Sher. Is there any particular reason why you are of this opinion? With your patients where you have used ERA has there been any success?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - September 5, 2017 reply

    It does not make physiological sense testing the endometrial lining in one cycle and using that as a predictive measaure for a subsequent cycle.

    Geoff Sher

    Sheena - September 6, 2017

    Hi Dr Sher, if that is the case (that endometrial lining in one cycle isn’t predictive of future cycles) is it possible that ERA can in fact have a detrimental impact and worsen success rates? Eg if ERA results say to transfer on day 4 when it fact it turns out day 5 is more optimal?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - September 6, 2017

    I cannot answer that question authoritatively, although it is a possibility in my opinion.

    Geoff Sher

  • Kerrie - September 4, 2017 reply

    Hi doctor,

    I am currently 7w3d pregnant after a fresh transfer. I started endometrin suppositories at 6w3d after hearing our babies heartbeat. Last night I had a little bit of brown spotting that seems to have subsided now. Is this expected? I don’t have any cramping, just normal symptoms.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - September 5, 2017 reply

    In most cases this will subside and all will be well. Only if fresh bleeding increases and is associated with worsening cramping would it become of concern. More importantly, there is probably nothing that you can do about this anyway.

    Repeat the US to see if there is subchorionic bleeding and to be able to trace its evolution.

    Good luck!

    Geoff Sher

  • Janeen - September 4, 2017 reply

    Hi Dr. Sher- I’m a patient at your facility in St. Louis, MO. I have a three year history of secondary infertility. I just experienced my third failed embryo transfer with fresh donor egg. I had a failure in December 2016 with frozen donor egg, and a failure in March 2016 with my own egg. My husband and I can conceive easily. Our son wad a first time first try baby. He is a healthy 4 year old. Our problem is genetics. My husband carries a 1q21.1 deletion on the first chromosome, with no known symptoms (but literature seems to support a baby could be very symptomatic). I am a fragile x carrier, with related low ovarian reserve. Due to not wanting to pass on our genetic problems, we went the route of IVF with PGD. Unfortunately 4 egg retrievas only yielded 5 wmbryos, almost all with my husband’s deletion, a trisomy, and/or the full mutation of fragile x. Most all were males, too. Last year in between treatments we became pregnant on our own (I was 39.9 years old then) We had a medical termination of pregnancy last year when our baby boy was 19 weeks, due to full mutation fragile x and the deletion. It still haunts me. This is the reason we went the route of donor. We thought it would be a slam dunk and we wouldn’t lose any more babies. And here we are, still struggling. My lining is good, the ERA in March revealed we are implanting at the right time, my thyroid was normal (in July it was undertreated so I had to wait for August to do embryo transfer). I’ve had intralipid infusion before the transfer. The only thing I wonder about is thrombophilia. I was found to have one mutation of MTHFR and a protrombin mutation. Should I have been on baby aspirin and/or lovenox before my transfer? But, when I’ve gotten pregnant on my own I haven’t been on these until after the pregnancy and things were okay.
    I am really hoping you can help me figure out what’s causing these repeat transfer failures and what I can do to stop them. I find it odd I can get pregnant quickly on my own but this isn’t working for me. If the risk of loss or serious genetic disease weren’t ao high, we’d consider trying on our own again. But, my carrier number for fragile x is 89 or 91, with an almost 80% chance of it turning into the full mutation if I pass it on. It is a miracle our four year old son has none of oue genetic problems!

    We are heartbroken and broke from the recent failed embryo transfer. I am so sad for my son; I desperately want him to have a sibling and he talks of having a little sister. I am 41 years old and just really wanted this to happen yesterday. We’ve been doing this for three years with no success. Please please help! Thank you so much! Janeen

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - September 4, 2017 reply

    Hi Janseen,

    I can only imagine your distress and my heart goes out to you. Frankly, I am not knowledgeable on the specific implications of your husband carrying a 1q21.1 deletion act of the first chromosome. However, this should be detectable in the embryo through PGS. I am also not a believer in the utility and benefit of ERA testing either. I believe that with selective transfer of a PGS-normal blastocyst, you should be successful if you can address what is clearly an anatomical or immunologic implantation dysfunction. Any MTHFR mutation depending on whether it is heterozygous or homozygous in nature is also amenable to folate/heparinoid therapy. I do not advocate aspirin here either.

    So this leaves you with the need to clearly identify and typify any implantation issue. Given your Uterine lining could have been impacted on by post-partum or post-termination endometritis and this needs careful assessment. Idealy you want a trilaminar uterine lining that measures >9mm. You also should have a hysteroscopic evaluation of the contour of your uterine cavity to exclude local lesions that could thwart implantation. Finally, it is important to know that the fact that you have had a child and terminated another pregnancy does NOT absolutely exclude an immunologic implantation dysfunction (IID), especially not an alloimmune IID (which might not be reversible through IL/steroid therapy alone—see below).

    Whenever a patient fails to achieve a viable pregnancy following embryo transfer (ET), the first question asked is why! Was it simply due to, bad luck?, How likely is the failure to recur in future attempts and what can be done differently, to avoid it happening next time?.
    It is an indisputable fact that any IVF procedure is at least as likely to fail as it is to succeed. Thus when it comes to outcome, luck is an undeniable factor. Notwithstanding, it is incumbent upon the treating physician to carefully consider and address the causes of IVF failure before proceeding to another attempt:
    1. Age: The chance of a woman under 35Y of age having a baby per embryo transfer is about 35-40%. From there it declines progressively to under 5% by the time she reaches her mid-forties. This is largely due to declining chromosomal integrity of the eggs with advancing age…”a wear and tear effect” on eggs that are in the ovaries from birth.
    2. Embryo Quality/”competency (capable of propagating a viable pregnancy)”. As stated, the woman’s age plays a big role in determining egg/embryo quality/”competency”. This having been said, aside from age the protocol used for controlled ovarian stimulation (COS) is the next most important factor. It is especially important when it comes to older women, and women with diminished ovarian reserve (DOR) where it becomes essential to be aggressive, and to customize and individualize the ovarian stimulation protocol.
    We used to believe that the uterine environment is more beneficial to embryo development than is the incubator/petri dish and that accordingly, the earlier on in development that embryos are transferred to the uterus, the better. To achieve this goal, we used to select embryos for transfer based upon their day two or microscopic appearance (“grade”). But we have since learned that the further an embryo has advanced in its development, the more likely it is to be “competent” and that embryos failing to reach the expanded blastocyst stage within 5-6 days of being fertilized are almost invariably “incompetent” and are unworthy of being transferred. Moreover, the introduction into clinical practice about a decade ago, (by Levent Keskintepe PhD and myself) of Preimplantation Genetic Sampling (PGS), which assesses for the presence of all the embryos chromosomes (complete chromosomal karyotyping), provides another tool by which to select the most “competent” embryos for transfer. This methodology has selective benefit when it comes to older women, women with DOR, cases of unexplained repeated IVF failure and women who experience recurrent pregnancy loss (RPL).
    3. The number of the embryos transferred: Most patients believe that the more embryos transferred the greater the chance of success. To some extent this might be true, but if the problem lies with the use of a suboptimal COS protocol, transferring more embryos at a time won’t improve the chance of success. Nor will the transfer of a greater number of embryos solve an underlying embryo implantation dysfunction (anatomical molecular or immunologic).Moreover, the transfer of multiple embryos, should they implant, can and all too often does result in triplets or greater (high order multiples) which increases the incidence of maternal pregnancy-induced complications and of premature delivery with its serious risks to the newborn. It is for this reason that I rarely recommend the transfer of more than 2 embryos at a time and am moving in the direction of advising single embryo transfers …especially when it comes to transferring embryos derived through the fertilization of eggs from young women.
    4. Implantation Dysfunction (ID): Implantation dysfunction is a very common (often overlooked) cause of “unexplained” IVF failure. This is especially the case in young ovulating women who have normal ovarian reserve and have fertile partners. Failure to identify, typify, and address such issues is, in my opinion, an unfortunate and relatively common cause of repeated IVF failure in such women. Common sense dictates that if ultrasound guided embryo transfer is performed competently and yet repeated IVF attempts fail to propagate a viable pregnancy, implantation dysfunction must be seriously considered. Yet ID is probably the most overlooked factor. The most common causes of implantation dysfunction are:
    a. A“ thin uterine lining”
    b. A uterus with surface lesions in the cavity (polyps, fibroids, scar tissue)
    c. Immunologic implantation dysfunction (IID)
    d. Endocrine/molecular endometrial receptivity issues
    Certain causes of infertility are repetitive and thus cannot readily be reversed. Examples include advanced age of the woman; severe male infertility; immunologic infertility associated with alloimmune implantation dysfunction (especially if it is a “complete DQ alpha genetic match between partners plus uterine natural killer cell activation (NKa).
    I strongly recommend that you visit http://www.DrGeoffreySherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.

    • The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
    • Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
    • IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation (COS)
    • The Fundamental Requirements for Achieving Optimal IVF Success
    • Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
    • Ovarian Stimulation in Women Who have Diminished Ovarian Reserve (DOR): Introducing the Agonist/Antagonist Conversion protocol
    • Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
    • Human Growth Hormone Administration in IVF: Does it Enhances Egg/Embryo Quality and Outcome?
    • The BCP: Does Launching a Cycle of Controlled Ovarian Stimulation (COS). Coming off the BCP Compromise Response?
    • Blastocyst Embryo Transfers should be the Standard of Care in IVF
    • IVF: How Many Attempts should be considered before Stopping?
    • “Unexplained” Infertility: Often a matter of the Diagnosis Being Overlooked!
    • IVF Failure and Implantation Dysfunction:
    • The Role of Immunologic Implantation Dysfunction (IID) & Infertility (IID): PART 1-Background
    • Immunologic Implantation Dysfunction (IID) & Infertility (IID): PART 2- Making a Diagnosis
    • Immunologic Dysfunction (IID) & Infertility (IID): PART 3-Treatment
    • Thyroid autoantibodies and Immunologic Implantation Dysfunction (IID)
    • Immunologic Implantation Dysfunction: Importance of Meticulous Evaluation and Strategic Management 🙁 Case Report)
    • Intralipid and IVIG therapy: Understanding the Basis for its use in the Treatment of Immunologic Implantation Dysfunction (IID)
    • Intralipid (IL) Administration in IVF: It’s Composition; how it Works; Administration; Side-effects; Reactions and Precautions
    • Natural Killer Cell Activation (NKa) and Immunologic Implantation Dysfunction in IVF: The Controversy!
    • Endometrial Thickness, Uterine Pathology and Immunologic Factors
    • Vaginally Administered Viagra is Often a Highly Effective Treatment to Help Thicken a Thin Uterine Lining
    • Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas:
    • A personalized, stepwise approach to IVF
    • How Many Embryos should be transferred: A Critical Decision in IVF?
    • The Role of Nutritional Supplements in Preparing for IVF

    If you are interested in seeking my advice or services, I urge you to contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com You can also apply online at http://www.SherIVF.com .

    *FYI
    The 4th edition of my newest book ,”In Vitro Fertilization, the ART of Making Babies” is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.

    Geoffrey Sher MD

    Janeen - September 4, 2017 reply

    Hi Dr. Sher– thanks so much for your response. It sounds like in my situation you think it was an implantation issue and not an embryo issue, correct? The embryo was grade B with some fragmentation. The donor was 30 years old. She has been successful in getting six other women pregnant. I’m the first unsuccessful one. I think I’d like to use her again. Do you think this is a good idea? Thanks

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - September 4, 2017 reply

    I do not see why not…As long as the optimal stimulation protocol is used.

    Geoff Sher

  • Eleanore - September 4, 2017 reply

    Hello dr. Sher.

    Do you perhaps have experience with patients whose body won’t ‘absorb’ the Pregynl/ HCG?
    Because I triggered 28 august with 10.00 IU Pregynl and did on 31 aug. a pregnancy test which was negative and this morning another one which also was negative. Does this mean that my body doesn’t absorb the HCG? Could this be te cause of my immature eggs in the previous 3 ICSI cycles?
    Do you perhaps have an idea of how to manage this?

    Kinds regards.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - September 4, 2017 reply

    This clearly was in all likelihood a defective product that was administered.

    Geoff Sher

  • Kika - September 4, 2017 reply

    Hi Dr. Sher! I’m approaching my 38th birtbday and my husband is 35 years old. We have been trying to conceive naturally for the last 9 years and no luck whatsoever. Three years ago we adopted our daughter because we lost hope in conceiving so we stopped trying. We thought we might be one of those couples that would conceive after adopting but no luck again. At this point, where do we start to find out what the issue is and what steps we need to take to conceive? Thank you!

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - September 4, 2017 reply

    For about 10% of all infertile couples, the cause of the infertility cannot be readily determined using conventional diagnostic methods. Such cases are often referred to as “unexplained infertility.” The truth however is that in most such cases, the diagnosis of “unexplained infertility is in fact “presumptive because a more in-depth evaluation would have revealed a cause. This having been said, people diagnosed with so called “unexplained infertility” fall into two broad groups: a)those couples who don’t have any biological problems interfering with pregnancy and, b) those who do but the reason cannot be found due to insufficient medical information or technology. It is in this latter group that improved testing techniques have made infertility easier to diagnose and treat.
    In order to make even a presumptive diagnosis of “unexplained infertility” the answers to the following questions must be in the affirmative.
     Is the woman ovulating normally?
     Is the couple having intercourse regularly in the periovulatory phase of the cycle?
     Are the fallopian tubes normal and open?
     Can endometriosis be excluded?
     Does the male partner have normal semen parameters (most specifically with regard to sperm count and motility?
     Is the post coital (Huhner) test (periovulatory examination of cervical mucous, done 6-18 hours after intercourse) normal?
    The definitive diagnosis of “unexplained infertility” has a lot to do with the thoroughness of the health care provider in excluding all possible causes. The fewer tests performed, the more likely a presumptive diagnosis
    For Example:
     Abnormalities of the fallopian tubes (adhesions or developmental defects) of the finger-like “petals” at their outer ends of the tubes that help sweep eggs inside (i.e. fimbriae). can prevent eggs from being collected and transported to the awaiting sperm
     Chromosomal abnormalities of eggs or embryos: Eggs must be euploid (contain the right number of chromosomes) to be successfully fertilized and embryos must also be euploid in order to implant successfully in the uterine lining. Until recently there was no reliable method for determining whether eggs and embryos were euploid. The recent introduction of genetic tests such as comparative genomic hybridization (CGH) now allows for identification of all chromosomes in the egg and embryo. As such CGH represents an important addition to the “infertility” diagnostic armamentarium.
     Luteinized Unruptured Follicle (LUF)Syndrome: Here, the eggs can become trapped in the follicle and not be released (trapped ovulation) In such cases routine tests done to detect ovulation ((temperature charting, Urine LH testing, Blood progesterone levels) may be normal resulting in false interpretation that ovulation is actually occurring.
     Ovulation (hormonal) Dysfunction: Abnormalities in ovarian hormone production in the preovulatory phase of the cycle (follicular phase defect) and/or in the postovulatory phase (luteal phase defect) can negatively affect preparation of the uterine lining (endometrium), thus thwarting normal implantation.
     Immunologic implantation dysfunction (IID): Sometimes, the woman’s or the man’s own immune system can attack sperm cells, killing them or causing them to become immobilized. Also, immunologic dysfunction involving the uterine lining can cause the implanting embryo to be rejected so early that the woman does not even recognize that she in fact had conceived.
     Cervical infection; Ureaplasma urealyticum infection of the cervical glands can prevent sperm from migrating through the cervix and uterus to reach the egg(s) in the fallopian tube(s). Such infection will usually not be detectable through routine examination and/or cervical culturing methods.
     Mild or Moderate Endometriosis: Endometriosis is in 100% of cases associated with the production of “pelvic toxins” that reduce the fertilization potential of otherwise normal eggs by a factor of 3-5. In addition, about 1/3 of woman with endometriosis (regardless of its severity) have immunologic implantation dysfunction (IID). Furthermore mild and often even moderately severe endometriosis can only be accurately diagnosed by direct visualization of the lesions through laparoscopy or laparotomy and, the detection of IID requires highly sophisticated tests that can only be adequately performed by a handful of Reproductive Immunology Reference Laboratories in the United States. Finally, a condition called nonpigmented endometriosis, in which the endometrium may be growing inside the pelvic cavity with many of the same deleterious effects as overt endometriosis, cannot be detected even by direct vision (at laparoscopy/laparotomy). The fertility of these patients may be every bit as compromised as if they had detectable endometriosis.
     Psychological Factors: The entire reproductive process is governed by the brain. Thus it should come as no surprise that stress and negativity can interfere with hormonal balance and decrease the ability to conceive.
     Mild Male Factor
     Antisperm antibodies in the man or woman.
    Management:
    Successful management of “Unexplained Infertility” requires that a very individualized approach be taken. Wherever possible the underlying cause should first be identified. Problems that involve ovulation dysfunction (hormonal imbalance) require ovulation induction with oral or injectible fertility drugs. Cervical mucous hostility due to infection with ureaplasma (which is transferred back and forth sexually to both partners) requires specific and concurrent antibiotic therapy. In other cases involving younger women (under 39 years) where there is a problem with sperm migration via the cervix and uterus to the fallopian tube(s) intrauterine insemination (IUI) with or without ovulation induction, is indicated. When these treatments fail, in cases, women over the age of 39 years, in women with IID, in men or women who harbor antisperm antibodies in significant concentrations and in cases associated with tubal abnormalities, in vitro fertilization (IVF) is needed. All cases of intractable, moderate or severe male infertility call for injecting sperm directly into the egg to achieve forced fertilization (intracytoplasmic sperm injection-ICSI).
    It is an indisputable fact that most causes of infertility can be diagnosed and it is a great pity that the diagnosis of “unexplained infertility” is often used as an excuse for not having performed a full and detailed evaluation of the problem. Couples should not simply accept a diagnosis of “unexplained infertility” at face value since treatment is most likely to be successful when the specific cause of the problem can be fully identified

    strongly recommend that you visit http://www.DrGeoffreySherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.

    • The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
    • Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
    • IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation (COS)
    • The Fundamental Requirements for Achieving Optimal IVF Success
    • Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
    • Ovarian Stimulation in Women Who have Diminished Ovarian Reserve (DOR): Introducing the Agonist/Antagonist Conversion protocol
    • Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
    • Human Growth Hormone Administration in IVF: Does it Enhances Egg/Embryo Quality and Outcome?
    • The BCP: Does Launching a Cycle of Controlled Ovarian Stimulation (COS). Coming off the BCP Compromise Response?
    • Blastocyst Embryo Transfers should be the Standard of Care in IVF
    • IVF: How Many Attempts should be considered before Stopping?
    • “Unexplained” Infertility: Often a matter of the Diagnosis Being Overlooked!
    • IVF Failure and Implantation Dysfunction:
    • The Role of Immunologic Implantation Dysfunction (IID) & Infertility (IID): PART 1-Background
    • Immunologic Implantation Dysfunction (IID) & Infertility (IID): PART 2- Making a Diagnosis
    • Immunologic Dysfunction (IID) & Infertility (IID): PART 3-Treatment
    • Thyroid autoantibodies and Immunologic Implantation Dysfunction (IID)
    • Immunologic Implantation Dysfunction: Importance of Meticulous Evaluation and Strategic Management 🙁 Case Report)
    • Intralipid and IVIG therapy: Understanding the Basis for its use in the Treatment of Immunologic Implantation Dysfunction (IID)
    • Intralipid (IL) Administration in IVF: It’s Composition; how it Works; Administration; Side-effects; Reactions and Precautions
    • Natural Killer Cell Activation (NKa) and Immunologic Implantation Dysfunction in IVF: The Controversy!
    • Endometrial Thickness, Uterine Pathology and Immunologic Factors
    • Vaginally Administered Viagra is Often a Highly Effective Treatment to Help Thicken a Thin Uterine Lining
    • Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas:
    • A personalized, stepwise approach to IVF
    • How Many Embryos should be transferred: A Critical Decision in IVF?
    • The Role of Nutritional Supplements in Preparing for IVF

    If you are interested in seeking my advice or services, I urge you to contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com You can also apply online at http://www.SherIVF.com .

    *FYI
    The 4th edition of my newest book ,”In Vitro Fertilization, the ART of Making Babies” is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.

    Geoffrey Sher MD

  • Stephanie - September 4, 2017 reply

    Hello Dr Scher,
    I have underwent 3 mini Ivf attempts and all three times , my doctor tells me I have empty follicles. I’m in my mid-forties. The first time , I took clomid and follistim, to start, ovidrell to trigger. Estrogen was 1537 fish 39 and LH 116 day before retrieval resulting in 2 cysts 29mm. 26mm and two empty follicles 19 and 16.5mm. Second attempt was unmedicated cycle. Follicle was 16,5 mm . Lh began to surge naturally on day 9 to 20 and attempted retrieval day 10 with LH at 74. Again, an empty follicle. This last time, i stimmed with 75 iu follistim on day 6 increased to 150 day 9and 10 and didn’t come back to office til day 11 which blood work showed lh was 33 fish was 21 estrogen 431 and progesterone .23. One follicle that was 17 mm was empty again and the 13,5 mm was empty . The other two were too small. Do empty follicles always show signs of cells? My first retrieval, the follicles showed cells no egg. But these last two retrievals, the doctor said there were no cells at all so this is how he knew they did not have an egg. Blood work usually shows I ovulate when taken afterwards. Is it possible to ovulate a follicle without an egg??im very confused. Any thoughts on what is happening? Thank you for any input you may provide.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - September 4, 2017 reply

    Frequently, when following vigorous and often repeated flushing of follicles at egg retrieval they fail to yield eggs, it is ascribed to “Empty Follicle Syndrome.” This is a gross misnomer, because all follicles contain eggs. So why were no eggs retrieved from the follicles? Most likely it was because they would/could not yield the eggs they harbored.
    This situation is most commonly seen in older women, women who have severely diminished ovarian reserve, and in women with polycystic ovarian syndrome (PCOS). In my opinion it is often preventable when an optimal, individualized and strategic protocol for controlled ovarian stimulation (COS) is employed and the correct timing and dosage is applied to the “hCG trigger shot.”
    Normally, following optimal ovarian stimulation, the hCG “trigger shot” is given for the purpose of it triggering meiosis (reproductive division) that is intended to halve the number of chromosomes from 46 to 23 within 32-36 hours. The hCG trigger also enables the egg to signal the “cumulus cells” that bind it firmly to the inner wall of the follicle (through enzymatic activity), to loosen or disperse, so that the egg can detach and readily be captured at egg retrieval (ER).
    Ordinarily, normal eggs (and even those with only one or two chromosomal irregularities) will readily detach and be captured with the very first attempt to empty a follicle. Eggs that have several chromosomal numerical abnormalities (i.e., are “complex aneuploid”) are often unable to facilitate this process. This explains why when the egg is complex aneuploid, its follicle will not yield an egg…and why, when it requires repeated flushing of a follicle to harvest an egg, it is highly suggestive of it being aneuploid and thus “incompetent” (i.e., incapable of subsequently propagating a normal embryo).
    Older women, women with diminished ovarian reserve, and those with polycystic ovarian syndrome, tend to have more biologically active LH in circulation. LH causes production of male hormone (androgens, predominantly testosterone), by ovarian connective tissue (stroma/theca). A little testosterone is needed for optimal follicle development and for FSH-induced ovogenesis (egg development). Too much LH activity compromises the latter, and eggs so affected are far more likely to be aneuploid following meiosis.
    Women with the above conditions have increased LH activity and are thus more likely to produce excessive ovarian testosterone. It follows that sustained, premature elevations in LH or premature luteinization (often referred to as a “premature LH surge”) will prejudice egg development. Such compromised eggs are much more likely to end up being complex aneuploid following the administration of the hCG trigger, leading to fruitless attempts at retrieval and the so called “empty follicle syndrome.”
    The developing eggs of women who have increased LH activity (older women, women with diminished ovarian reserve, and those with PCOS) are inordinately vulnerable to the effects of protracted exposure to LH-induced ovarian testosterone. Because of this, the administration of medications that provoke further pituitary LH release (e.g., clomiphene and Letrozole), drugs that contain LH or hCG (e.g., Menopur), or protocols of ovarian stimulation that provoke increased exposure to the woman’s own pituitary LH (e.g., “flare-agonist protocols”) and the use of “late pituitary blockade” (antagonist) protocols can be prejudicial.
    The importance of individualizing COS protocol selection, precision with regard to the dosage and type of hCG trigger used, and the timing of its administration in such cases cannot be overstated. The ideal dosage of urinary-derived hCG (hCG-u) such as Novarel, Pregnyl and Profasi is 10,000U. When recombinant DNA-derived hCG (hCG-r) such as Ovidrel is used, the optimal dosage is 500mcg. A lower dosage of hCG can, by compromising meiosis, increase the risk of egg aneuploidy, and thus of IVF outcome.
    There is in my opinion no such condition as “Empty Follicle Syndrome.” All follicles contain eggs. Failure to access those eggs at ER can often be a result of the protocol used for controlled ovarian stimulation.

    I strongly recommend that you visit http://www.DrGeoffreySherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.

    • The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
    • Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
    • IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation (COS)
    • The Fundamental Requirements for Achieving Optimal IVF Success
    • Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
    • Ovarian Stimulation in Women Who have Diminished Ovarian Reserve (DOR): Introducing the Agonist/Antagonist Conversion protocol
    • Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
    • Human Growth Hormone Administration in IVF: Does it Enhances Egg/Embryo Quality and Outcome?
    • The BCP: Does Launching a Cycle of Controlled Ovarian Stimulation (COS). Coming off the BCP Compromise Response?
    • Blastocyst Embryo Transfers should be the Standard of Care in IVF
    • IVF: How Many Attempts should be considered before Stopping?
    • Vaginally Administered Viagra is Often a Highly Effective Treatment to Help Thicken a Thin Uterine Lining
    • Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas:
    • A personalized, stepwise approach to IVF
    • How Many Embryos should be transferred: A Critical Decision in IVF?
    • The Role of Nutritional Supplements in Preparing for IVF

    If you are interested in seeking my advice or services, I urge you to contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com You can also apply online at http://www.SherIVF.com .

    *FYI
    The 4th edition of my newest book ,”In Vitro Fertilization, the ART of Making Babies” is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.

    Geoffrey Sher MD

  • Rachel M - September 4, 2017 reply

    Hello Dr. Sher, I am a 37 yr old with PCOS. I’ve had 3 fresh cycles this year, none of which progressed/implanted. What would you suggest next? Testing – like endometrial receptivity? PGS? A break? At this stage of the process, I’m looking for answers. Is a “mock cycle” (prepping for frozen) with hormone testing for the mo an option? Obviously with PCOS, cycles are very irregular. How do docs determine the best day/time to transfer with PCOS clients?
    In advance, thank you for your time.
    Kindly,
    Rachel

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - September 4, 2017 reply

    Polycystic ovary syndrome (PCOS) is a common hormonal system disorder among women affecting between 5% and 10% of women of reproductive age worldwide. Women with PCOS may have enlarged ovaries that contain small collections of fluid — called follicles — located in each ovary as seen during an ultrasound. The condition is characterized by abnormal ovarian function (irregular or absent periods, abnormal or absent ovulation and infertility), androgenicity (increased body hair or hirsutism, acne) and increased body weight –body mass index or BMI. The ovaries of women with PCOS characteristically contain multiple micro-cysts often arranged like a “string of pearls” immediately below the ovarian surface (capsule).interspersed by an overgrowth of ovarian connective tissue (stroma).

    PCOS is one of the most common causes of menstrual irregularities, infertility, and hirsutism, Despite an enormous effort to define its cause, the etiology of PCOS remains unclear, and there is no definite cure at this time. PCOS is clearly a heterogeneous disorder which often has a familial (genetic) basis. Infertility associated with PCOS has been attributed to numerous factors, including dysfunctional gonadotropin pituitary secretion, peripheral insulin resistance, elevated adrenal and/or ovarian androgen (male hormone) levels, and dysfunction of several growth factors. Women with this condition are often obese and insulin resistant. The compensatory hyperinsulinemia further stimulates ovarian androgen production which may be detrimental to egg maturation and there is a clear link between the degree of insulin resistance and anovulation. PCOS is also a significant long-term health risk for women, thus necessitating vigilance through regular annual examinations (non-insulin dependent diabetes mellitus, hypertension, hypercholesterolemia, cardiovascular disease and endometrial cancer). Whereas PCOS-related infertility is usually manageable through the use of fertility drugs, lifestyle changes (diet and exercise) remain a mainstay of long-term therapy. More recently, ovulation rates, circulating androgens, pregnancy rates and perhaps even first-trimester miscarriage rates have been shown to improve when insulin sensitizers like metformin are used to correct the underlying insulin resistance.

    Most patients with PCOS are young and have excellent pregnancy rates with oral clomiphene. Those that require more aggressive treatments with injectable medications probably represent a subgroup of PCOS patients with severe ovarian dysfunction. These women often have explosive response to gonadotropins which can result in serious complications like Severe Ovarian Hyperstimulation Syndrome (OHSS…see below) and high order multiple births. In those women, the ability to perform “prolonged coasting” (see below) and selectively transfer fewer embryos during IVF offers a clear advantage over standard gonadotropin injections.

    Egg quality in PCOS

    The potential for a woman’s eggs to undergo orderly maturation, successful fertilization and subsequent progression to “good quality embryos” is in large part genetically determined. However, the expression of such potential is profoundly susceptible to numerous influences, especially intra-ovarian hormonal changes during the pre-ovulatory phase of the cycle. Proper follicular stimulation as well as precise timing of egg maturation with LH (Luteinizing Hormone) or hCG (human chorionic gonadotropin) is crucial to optimal egg maturation, fertilization and ultimately embryo quality. Both pituitary gonadotropins, LH and FSH (follicle stimulating hormone) play a pivotal but different role in follicular development. The action of FSH is mainly directed toward granulosa cell (cells lining the inside of the follicle) proliferation and estrogen production (E2). LH, on the other hand, acts primarily on the ovarian stroma (the connective tissue that surrounds the follicle) to produce androgens. While small amounts of ovarian androgens, such as testosterone, enhance egg and follicle development, over-exposure to them can have a deleterious effect. Furthermore, excessive ovarian androgens can also compromise estrogen-induced endometrial growth and development.

    Suppressing pituitary secretion of LH with gonadotropin releasing hormone (GnRH) agonists such as Lupron®, is particularly useful in PCOS. In that condition, serum LH levels are elevated, leading to stromal overgrowth, follicular arrests (so-called cysts) and high levels of androgens synthesis. It is therefore not surprising that these follicles often yield poorly developed (“immature”) eggs” at the time of egg retrieval (ET) and that “poor egg/embryo quality”, inadequate endometrial development and high miscarriage rates are common features of this condition. However, contrary to popular belief, this is not due to an intrinsic deficit in “egg quality”. Stimulation protocols geared toward optimizing follicle and egg development and avoiding over exposure to androgens correct these problems ad result in pregnancy rates similar to those of non-PCOS women. Whereas the overuse of LH-containing preparations such as Menopur® and Luveris® further aggravates this effect. In conclusion, to maximize ultimate oocyte maturation, we strongly recommend against the exclusive use of such products in PCOS patients, preferring FSH-dominant products such as Folistim®, Gonal F® or Bravelle® over a period of at least 9 days following pituitary suppression with Lupron®.
    PCOS women often have a family history of diabetes and demonstrable insulin resistance (evidenced by high blood insulin levels and an abnormal 2-hour glucose tolerance test).This underlying Diabetes mellitus tendency could play a role in the development of PCOS and contribute to the development of obesity, an abnormal blood lipid profile, and a predisposition to coronary vascular disease. Women with PCOS are slightly more at risk of developing uterine, ovarian and possibly also breast cancer in later life and accordingly should be evaluated for these conditions on a more frequent basis than would ordinarily be recommended to non-PCOS women.

    Most women with PCOS either do not ovulate at all or they ovulate irregularly. As a consequence thereof they in addition usually experience delayed, absent or irregular menstruation. In addition, an inordinate percentage of the eggs produced by PCOS women following ovulation induction, tend to be chromosomally abnormal (aneuploid). Rather than being due to an intrinsic egg defect being inherent in PCOS women, the poor egg quality more than likely the result of over-exposure to male hormones (predominantly, testosterone) produced by the ovarian stroma. These two factors (ovulation dysfunction and poor egg quality) are the main reasons for the poor reproductive performance (infertility and an increased miscarriage rate) in PCOS women.

    PCOS patients are at an inordinate risk of severely over-responding fertility drugs, both oral varieties (e.g. Clomiphene, Serophene & Femara) and especially the injectables (e.g. Follistim, Puregon, Gonal F, Menopur and Bravelle) by forming large numbers ovarian follicles. This can lead to life endangering complications associated with sever ovarian hyperstimulation (OHSS). In addition PCOS women receiving fertility drugs often experience multiple ovulations putting them at severe risk (40%+) of high order multiple pregnancy (i.e. triplets or greater) with often devastating consequences.

    VARIETIES OF POLYCYSTIC OVARIAN SYNDROME:

    1) Hypothalamic-pituitary-PCOS: This is the commonest form of PCOS and is often genetically transmitted and is characteristically associated with a blood concentration of Luteinizing Hormone (LH) that is uncharacteristically much higher than the Follicle Stimulating Hormone (FSH) level (FSH is normally higher than the LH concentration) as well as high-normal or blood androgen ( male) hormone concentrations (e.g. androstenedione, testosterone and dehydroepiandrosterone -DHEA).Hypothalamic-pituitary-ovarian PCOS is also often associated with insulin resistance and in about 40%-50% of the cases.

    2) Adrenal PCOS: Here the excess of male hormones are derived from overactive adrenal glands rather than from the ovaries. Blood levels of testosterone and/or androstenedione raised but here, but here, the blood level of dehydroepiandrosterone (DHEAS) is also raised, clinching the diagnosis.

    3) Severe pelvic adhesive disease secondary to severe endometriosis, chronic pelvic inflammatory disease and/or extensive pelvic surgery: Women who have this type of PCOS tend to less likely to hyperstimulate in response to ovulation induction . Their. DHEAS is also is not raised.

    TREATMENT OF INFERTILITY DUE TO ASSOCIATED OVULATION DYSFUNCTION:

    Hypothalamic-pituitary-/ovarian PCOS: Ovulation induction with fertility drugs such as clomiphene citrate, Letrozole (Femara) or gonadotropins, with or without intrauterine insemination (IUI) is often highly successful in establishing pregnancies in PCOS women. However, IVF is fast becoming a treatment of choice (see below).

    In about 40% of cases, 3-6 months of oral Metformin (Glucophage) treatment results in a significant reduction of insulin resistance, lowering of blood androgen levels, an improvement in ovulatory function, and/or some amelioration of androgenous symptoms and signs.

    Surgical treatment by “ovarian drilling” of the many small ovarian cysts lying immediately below the envelopment (capsule) of the ovaries, is often used, but is less successful than alternative non-surgical treatment and is only temporarily effective. The older form of surgical treatment, using ovarian wedge resection is rarely used any longer as it can produce severe pelvic adhesion formation.

    Adrenal PCOS is treated with steroids such as prednisone or dexamethasone which over a period of several weeks will suppress adrenal androgen production, allowing regular ovulation to take place spontaneously. This is often combined with clomiphene, Letrozole and/or gonadotropin therapy to initiate ovulation.

    PCOS attributable to Pelvic Adhesive Disease is one variety which often is associated with compromised ovarian reserve, a raised FSH blood level and ovarian resistance to fertility drugs. In many such cases, high dosage of gonadotropins (FSH-dominant) with “estrogen priming” will often elicit an ovarian response necessary for successful ovulation induction and/or IVF. Neither steroids nor Metformin are helpful in the vast majority of such cases.

    PCOS women undergoing ovulation induction usually release multiple eggs following the hCG trigger and are thus at inordinate risk of twin or higher order multiple pregnancies. They are also at risk of developing OHSS. Many now believe that IVF should be regarded as a primary and preferential treatment for PCOS. The reason is that it is only through this approach that the number of embryos reaching the uterus can be controlled and in this manner the risk of high-order multiples can be minimized and it is only in the course of IVF treatment that a novel treatment method known as “prolonged coasting” ( see below) which prevents OHSS, can be implemented

    SEVERE OVARIAN HYPERSTIMULATION SYNDROME (OHSS):

    As indicated above, there is an inordinate propensity for women with PCOS to hyper-respond to gonadotropin fertility drugs and in the process produce large numbers of ovarian follicles. If left unchecked this can lead to OHSS, a potentially life endangering condition. The onset of OHSS is signaled by the development of a large number of ovarian follicles (usually more than 25 in number). This is accompanied by rapidly rising plasma estradiol (E2) levels, often exceeding 3000pg/ml within 7 or 9 days of stimulation, often rapidly peaking above 6,000 pg/ml prior to hCG administration. When this happens, the risk of OHSS developing is above 80%.

    Symptoms and signs of OHSS include: abdominal distention due to fluid collection (ascites), fluid in the chest cavity (hydrothorax), rapid weight gain (of a pound or more per day) due to tissue fluid retention, abdominal pain, lower back ache, nausea, diarrhea, vomiting, visual disturbances such as blurred vision and spots in front of the eyes (scotomata), a rapidly declining urine output, cardiovascular collapse and failure of blood to clot which sometimes results in severe bruising (echymosis) and frank bleeding. These symptoms and signs may appear before pregnancy can be diagnosed. If pregnancy occurs, the condition is likely to worsen progressively over a period of 3-5 weeks whereupon it rapidly resolves spontaneously over a few days. If no pregnancy occurs, the symptoms and signs all disappear spontaneously within 10-12 days of the hCG injection.

    When increasing fluid collection in the abdominal cavity (ascites) starts to compromise breathing raising the head of the bed rose slightly by placing a 4-6 inch block at the base of each head post and using a few additional pillows, will sometimes help ameliorate the problem. In cases where this does not help or symptoms become severe, all or most of the fluid can readily and safely be drained through t transvaginal sterile needle aspiration (vaginal paracentesis-performed once or sometimes twice a week) can be performed once or twice weekly . The problem will usually self corrects within 10-12 days of the hCG shot if pregnancy does not occur or, by the 8th week of pregnancy.

    Urine output should be monitored daily to see if it drops below about 500ml a day (about two cups and a half). A chest X-ray, to evaluate for fluid collection in the chest and around the heart should be done weekly along with blood tests for hematocrit, BUN, electrolytes, creatinine, platelet count and fibrin split products (FSP). If indicated on the basis of a deteriorating clinical situation, hospitalization might be needed for close observation and if necessary, to provide intensive care.

    In all case of OHSS, the ovaries will invariably be considerably enlarged. This is irrelevant to the final outcome, unless ovarian torsion (twisting of the ovary on its axis), an extremely rare complication occurs. The latter would usually require surgical emergency surgical intervention.

    It is important to know that symptoms and signs of OHSS are severely aggravated by rising hCG levels. Thus such patients should not receive additional hCG injections.

    Does PCOS cause poor egg/embryo quality? It is an undeniable fact that women with PCOS undergoing IVF are commonly found to have poorly developed (“dysmorphic”) eggs, with reduced fertilization potential and yielding “poor quality embryos”. However, in the author’s opinion (which admittedly runs contrary to popular opinion), this is unlikely to be due to an intrinsic deficit in egg quality. Rather, it more likely relates to intra-ovarian hormonal changes brought about by hyperstimulation and which compromise egg development. This effect, in the author’s opinion, can often be significantly reduced through implementation of an individualized or customized ovarian stimulation protocols that minimize exposure of the developing follicles and eggs to excessive LH-induced ovarian androgens. This can be best achieved by limiting the use of LH-containing gonadotropins such as Menopur through selective institution of “prolonged coasting” (see below).

    In the past, the onset of OHSS, heralded by the presence of large numbers of developing ovarian follicles and rapidly rising plasma estradiol levels often led the treating physician to prematurely administer hCG in an attempt to abruptly arrest the process and prevent escalation of risk to the patient. However the premature administration of hCG, while abruptly arresting further proliferation of estrogen producing granulosa cells in the follicles, unfortunately also prematurely arrests egg development. Since the ability of an egg to achieve optimal maturation upon hCG triggering is largely predicated upon it having achieved prior optimal development, the untimely administration of hCG which triggers meiosis, probably increases the risk of numerical chromosomal abnormalities (aneuploidy) of the egg. This in turn would lead to reduced fertilization potential, poor egg/embryo quality and low embryo implantation potential.

    In women with PCOS the connective tissue that surrounding the follicles (ovarian stroma) is often characteristically overgrown (stromal hyperplasia). It is the stroma that produces androgens (mainly testosterone) in response to LH. It is this, coupled with the fact that PCOS women also often have elevated blood LH concentrations (see above) results in the excessive production of androgen hormones, which is so characteristic in PCOS. While excessive exposure of developing eggs to ovarian androgens compromises follicle and egg growth it also impairs endometrial response to estrogen, which could explain the common finding of poor endometrial thickening in many PCOS women undergoing IVF.
    .
    The obvious remedy for these adverse effects on egg and endometrial development is to employ stimulation protocols that limit ovarian over-exposure to LH and allowing the time necessary for the follicles/eggs to develop optimally, prior to administering hCG through the judicious implementation of “Prolonged coasting” (PC)…see below)

    There is no doubt that PCOS exacts a toll on egg quality. This having been said, the egg quality can in large part protected through the judicious implementation of an individualized protocol for ovarian stimulation.
    Women with PCOS are hypersensitive to gonadotropin stimulation and are often at risk of developing serious complications associated with severe ovarian hyperstimulation syndrome (OHSS). Concern for this occurring often leads the treating physician to take precautionary measures aimed at slowing down or stopping hyperstimulation. Such measures include:
    1. Cutting the stimulation short to prevent the E2 from rising too high. Unfortunately this often results in the eggs being underdeveloped at the time of the “trigger” and thus, far more likely to end up being “immature”., “dysmature” and “incompetent”.
    2. Administering a lower “trigger dosage” of hCG , supplanting it (partially or completely) with an Agonist trigger (e.g. Lupron/Buserelin/aminopeptidyl/Superfact). While such measures can certainly reduce the risk/severity of OHSS, it often comes at the expense of egg competency (see below).
    In my opinion, another error of commission during ovarian stimulation of women with PCOS is the indiscriminate use of drugs that either elicit an exaggerated ovarian LH-induced testosterone response (e.g. clomiphene or Letrozole), or provide too much LH (e.g. Menopur/Menogon). Too much ovarian testosterone is harmful to egg development and thus prejudicial to embryo quality/competency.
    In my opinion the best way to approach ovarian stimulation for IVF in women with PCOS, is through the use of a low dosage, FSH-dominant Long ovarian down-regulation protocol, done in readiness for “prolonged coasting” (see below) and “triggering” egg maturation with a full 10,00U dosage of hCG or (no less than) 500mcg of recombinant hCG (Ovidrel)….see below is If this is implemented appropriately, with proper timing, egg/embryo quality can be optimized.

    I strongly recommend that you visit http://www.DrGeoffreySherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.
    • The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
    • Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
    • IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation(COS)
    • The Fundamental Requirements For Achieving Optimal IVF Success
    • Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
    • Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
    • Egg Maturation in IVF: How Egg “Immaturity”, “Post-maturity” and “Dysmaturity” Influence IVF Outcome:
    • Commonly Asked Question in IVF: “Why Did so Few of my Eggs Fertilize and, so Many Fail to Reach Blastocyst?”
    • 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?
    • Taking A Fresh Look at Ovarian Hyperstimulation Syndrome (OHSS), its Presentation, Prevention and Management
    • Preventing Severe Ovarian Hyperstimulation Syndrome (OHSS) with “Prolonged Coasting”
    • Understanding Polycystic Ovarian Syndrome (PCOS) and the Need to Customize Ovarian Stimulation Protocols.
    • “Triggering” Egg Maturation in IVF: Comparing urine-derived hCG, Recombinant DNA-hCG and GnRH-agonist:
    • The “Lupron Trigger” to Prevent Severe OHSS: What are the Pro’s and Con’s?
    • My Retirement in the Year Ahead: A letter of Thanks From me to You!

    If you are interested in seeking my advice or services, I urge you to contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com You can also apply online at http://www.SherIVF.com .

    *FYI
    The 4th edition of my newest book ,”In Vitro Fertilization, the ART of Making Babies” is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.

    Geoffrey Sher MD

    PS: I do not believe in a benefit through ERA

    Rachel M - September 5, 2017 reply

    Dr. Sher,
    Thank you so much for your time and attention to answer my question. I have requested a phone consult with you as well. Looking forward to connecting personally and gathering more information. Thanks again for your generosity and in depth response.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - September 5, 2017 reply

    You are most welcome Rachel!

    We will talk soon!

    Until then….

    Geoff Sher

  • Muna - September 3, 2017 reply

    Hi, I am 35 years old (husband 37), with a 6-year-old (conceived normally). I have PCOS and have been taking Glucophage for 15 months, with my cycles largely regulated now. I have done two cycles of Clomid recently with no success. I have had a goiter for Atleast 15 years, but am euthyroid (TSH 0.8). However, recently we have found that I have elevated Anti Tg antibodies (result: 329 IU/ml – reference less than 115). My gynaecologist believes this could be resulting in implantation failure as I seem to have “unexplained secondary infertility”. I am now taking 50 mg thyroxine. Could you please provide your opinion on this. Thank you.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - September 4, 2017 reply

    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.

    I strongly recommend that you visit http://www.DrGeoffreySherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.
    • IVF Failure and Implantation Dysfunction:
    • The Role of Immunologic Implantation Dysfunction (IID) & Infertility (IID):PART 1-Background
    • Immunologic Implantation Dysfunction (IID) & Infertility (IID):PART 2- Making a Diagnosis
    • Immunologic Dysfunction (IID) & Infertility (IID):PART 3-Treatment
    • Intralipid and IVIG therapy: Understanding the Basis for its use in the Treatment of Immunologic Implantation Dysfunction (IID)
    • Intralipid (IL) Administration in IVF: It’s Composition; How it Works; Administration; Side-effects; Reactions and Precautions
    • Natural Killer Cell Activation (NKa) and Immunologic Implantation Dysfunction in IVF: The Controversy!
    • Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas
    • Should IVF Treatment Cycles be provided uninterrupted or be Conducted in 7-12 Pre-scheduled “Batches” per Year
    • A personalized, stepwise approach to IVF

    If you are interested in seeking my advice or services, I urge you to contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com You can also apply online at http://www.SherIVF.com .
    *FYI
    The 4th edition of my newest book ,”In Vitro Fertilization, the ART of Making Babies” is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.

  • james - September 3, 2017 reply

    Hi Dr Sher
    thanks for the opportunity to ask a question.

    At which week of pregnancy would you think that immunological/implantation issues stop playing a part.

    E.g. if you reached week 15 of pregnancy then lost the baby, would you say that it’s less likely at that point point there was a immunological issue?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - September 3, 2017 reply

    After 12 weeks, this is much less likely but not impossible.

    Geoff Sher

  • Mira - September 3, 2017 reply

    Hello dr.
    Me 40 DH 47 TTC 2 years. On 3rd ivf with new doc he asked for sperm dna frag test (bec he found my body very normal and productive and have no issues at all) so the fragmentation result was 40%.
    After 2 months of vitamins we tranferred 3dt embryos (fertilized using TESE)
    All was normal until day 9 post 3dt: had brief light pink spotting while wiping at 12noon and another one at 7pm. After that all symptoms vanished: sore breasts became normal. Huge bloated even sore abdomen ceased.
    My blood test is due on 4 sept 2017.
    Any advise or prediction what could possibly happenned or went wrong? Should i be worried?
    Am on fraxiparine 0.6 daily, proluton twice a week, endometrin 3/day, pronatal, prednison and aspi-cor81mg once per day.
    Thanking you in advance

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - September 3, 2017 reply

    Unfortunately, you will need to wait for the results of blood pregnancy tests!

    Geoff Sher

  • Katie - September 2, 2017 reply

    Hi Dr Sher
    I’m 30, husband is 33. Our only known issue is low motility (15-30%). We’ve done 6 IUI’s (5 with femara and ovidrel, 1 natural with ovidrel) resulting in 5 negatives and 1 early miscarriage. We are 2 days post egg retrieval on our 1st IVF which was a short protocol –
    – 75 IU Menopur and 200 IU Puregon (not sure if this is called something different in the US) Day 3 – 9
    – Orgalutran Day 7-9
    – Superfact (buselerin) trigger on Day 10 (used superfact instead of hcg due to risk of ohss – not sure why I was at risk?)
    – egg retrieval 36 hours after trigger (Day 12)

    There were 20 follicles on the baseline U/S (7 in left, 13 in right). Ended up with 13 retrieved, 8 mature, 6 fertilized with ICSI. Now, at 2 days post retrieval we were told the 6 are still growing but they are of fair to poor quality. Our clinic grades them on a scale of 1 to 5 with 1 being the best and we have four eggs at level 3, one at level 4 and one at level 5. This seems like a very disappointing result and the clinic wants to do a day 3 transfer rather than risking losing all of them by day 5.

    Here are my questions:
    1. Is there an egg quality issue?
    2. Would a different protocol be better?
    3. What other testing should we undergo if this cycle does not work out? (DNA frag?, immune testing? etc?)
    Thank you!

    Katie - September 2, 2017 reply

    Forgot to add – they tested my estrogen and progesterone the day before trigger and progesterone was at 2.7 (I think this translates to 0.85 in US measurement terms) which they said was well below the threshold where they would do a freeze all for having too high progesterone. I am also on extra estrogen (2mg x 3/day) and progesterone (75mg) after the retrieval due to triggering with the superfact rather than the hcg.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - September 3, 2017 reply

    Copy!

    Geoff Sher

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - September 3, 2017 reply

    I doubt the problem is an intrinsic egg quality issue. In my opinion, it is more likely a stimulation protocol issue, coupled with the use of an agonist (Buserelin) trigger. Aside from this, you need to be evaluated for an anatomical or immunologic implantation dysfunction.

    Whenever a patient fails to achieve a viable pregnancy following embryo transfer (ET), the first question asked is why! Was it simply due to, bad luck?, How likely is the failure to recur in future attempts and what can be done differently, to avoid it happening next time?.
    It is an indisputable fact that any IVF procedure is at least as likely to fail as it is to succeed. Thus when it comes to outcome, luck is an undeniable factor. Notwithstanding, it is incumbent upon the treating physician to carefully consider and address the causes of IVF failure before proceeding to another attempt:
    1. Age: The chance of a woman under 35Y of age having a baby per embryo transfer is about 35-40%. From there it declines progressively to under 5% by the time she reaches her mid-forties. This is largely due to declining chromosomal integrity of the eggs with advancing age…”a wear and tear effect” on eggs that are in the ovaries from birth.
    2. Embryo Quality/”competency (capable of propagating a viable pregnancy)”. As stated, the woman’s age plays a big role in determining egg/embryo quality/”competency”. This having been said, aside from age the protocol used for controlled ovarian stimulation (COS) is the next most important factor. It is especially important when it comes to older women, and women with diminished ovarian reserve (DOR) where it becomes essential to be aggressive, and to customize and individualize the ovarian stimulation protocol.
    We used to believe that the uterine environment is more beneficial to embryo development than is the incubator/petri dish and that accordingly, the earlier on in development that embryos are transferred to the uterus, the better. To achieve this goal, we used to select embryos for transfer based upon their day two or microscopic appearance (“grade”). But we have since learned that the further an embryo has advanced in its development, the more likely it is to be “competent” and that embryos failing to reach the expanded blastocyst stage within 5-6 days of being fertilized are almost invariably “incompetent” and are unworthy of being transferred. Moreover, the introduction into clinical practice about a decade ago, (by Levent Keskintepe PhD and myself) of Preimplantation Genetic Sampling (PGS), which assesses for the presence of all the embryos chromosomes (complete chromosomal karyotyping), provides another tool by which to select the most “competent” embryos for transfer. This methodology has selective benefit when it comes to older women, women with DOR, cases of unexplained repeated IVF failure and women who experience recurrent pregnancy loss (RPL).
    3. The number of the embryos transferred: Most patients believe that the more embryos transferred the greater the chance of success. To some extent this might be true, but if the problem lies with the use of a suboptimal COS protocol, transferring more embryos at a time won’t improve the chance of success. Nor will the transfer of a greater number of embryos solve an underlying embryo implantation dysfunction (anatomical molecular or immunologic).Moreover, the transfer of multiple embryos, should they implant, can and all too often does result in triplets or greater (high order multiples) which increases the incidence of maternal pregnancy-induced complications and of premature delivery with its serious risks to the newborn. It is for this reason that I rarely recommend the transfer of more than 2 embryos at a time and am moving in the direction of advising single embryo transfers …especially when it comes to transferring embryos derived through the fertilization of eggs from young women.
    4. Implantation Dysfunction (ID): Implantation dysfunction is a very common (often overlooked) cause of “unexplained” IVF failure. This is especially the case in young ovulating women who have normal ovarian reserve and have fertile partners. Failure to identify, typify, and address such issues is, in my opinion, an unfortunate and relatively common cause of repeated IVF failure in such women. Common sense dictates that if ultrasound guided embryo transfer is performed competently and yet repeated IVF attempts fail to propagate a viable pregnancy, implantation dysfunction must be seriously considered. Yet ID is probably the most overlooked factor. The most common causes of implantation dysfunction are:
    a. A“ thin uterine lining”
    b. A uterus with surface lesions in the cavity (polyps, fibroids, scar tissue)
    c. Immunologic implantation dysfunction (IID)
    d. Endocrine/molecular endometrial receptivity issues
    Certain causes of infertility are repetitive and thus cannot readily be reversed. Examples include advanced age of the woman; severe male infertility; immunologic infertility associated with alloimmune implantation dysfunction (especially if it is a “complete DQ alpha genetic match between partners plus uterine natural killer cell activation (NKa).
    I strongly recommend that you visit http://www.DrGeoffreySherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.

    • The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
    • Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
    • IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation (COS)
    • The Fundamental Requirements for Achieving Optimal IVF Success
    • Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
    • Ovarian Stimulation in Women Who have Diminished Ovarian Reserve (DOR): Introducing the Agonist/Antagonist Conversion protocol
    • Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
    • Human Growth Hormone Administration in IVF: Does it Enhances Egg/Embryo Quality and Outcome?
    • The BCP: Does Launching a Cycle of Controlled Ovarian Stimulation (COS). Coming off the BCP Compromise Response?
    • Blastocyst Embryo Transfers should be the Standard of Care in IVF
    • IVF: How Many Attempts should be considered before Stopping?
    • “Unexplained” Infertility: Often a matter of the Diagnosis Being Overlooked!
    • IVF Failure and Implantation Dysfunction:
    • The Role of Immunologic Implantation Dysfunction (IID) & Infertility (IID): PART 1-Background
    • Immunologic Implantation Dysfunction (IID) & Infertility (IID): PART 2- Making a Diagnosis
    • Immunologic Dysfunction (IID) & Infertility (IID): PART 3-Treatment
    • Thyroid autoantibodies and Immunologic Implantation Dysfunction (IID)
    • Immunologic Implantation Dysfunction: Importance of Meticulous Evaluation and Strategic Management 🙁 Case Report)
    • Intralipid and IVIG therapy: Understanding the Basis for its use in the Treatment of Immunologic Implantation Dysfunction (IID)
    • Intralipid (IL) Administration in IVF: It’s Composition; how it Works; Administration; Side-effects; Reactions and Precautions
    • Natural Killer Cell Activation (NKa) and Immunologic Implantation Dysfunction in IVF: The Controversy!
    • Endometrial Thickness, Uterine Pathology and Immunologic Factors
    • Vaginally Administered Viagra is Often a Highly Effective Treatment to Help Thicken a Thin Uterine Lining
    • Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas:
    • A personalized, stepwise approach to IVF
    • How Many Embryos should be transferred: A Critical Decision in IVF?
    • The Role of Nutritional Supplements in Preparing for IVF
    • Implications of “Empty Follicle Syndrome and “Premature Luteinization”
    • Premature Luteinization (“the premature LH surge): Why it happens and how it can be prevented.
    • “Triggering” Egg Maturation in IVF: Comparing urine-derived hCG, Recombinant DNA-hCG and GnRH-agonist:
    • The “Lupron Trigger” to Prevent Severe OHSS: What are the Pro’s and Con’s?

    If you are interested in seeking my advice or services, I urge you to contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com You can also apply online at http://www.SherIVF.com .

    *FYI
    The 4th edition of my newest book ,”In Vitro Fertilization, the ART of Making Babies” is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.

    Geoffrey Sher MD

Ask a question or post a comment