Ask Our Doctors – Archive
Our Medical Directors are outstanding physicians that you will find to be very personable and compassionate, who take care to ensure that you have the most cutting-edge fertility treatments at your disposal. This is your outlet to ask your questions to the doctors.
Dear Dr. Sher,
I am 30 years old . My husband and I trying to conceive for almost 3 years. I was diagnosed with damage to both of my fallopian tubes .After having 2 failed IUI’s, we decided to try IVF. My first IVF was BFN. My second FET ( Frozen Embryo Transfer) with a PGD embryo failed as well and ended up in early miscarriage. However, during my second transfer, my husband and I decided to try and transfer 2 embryos. So we transferred 1 PGD and 1 unknown embryo. My current clinic ran tests on me after the miscarriage and everything looked normal. After reading about (IID) on your blog, I spoke to my dr. about immunological implementation dysfunction, however, he does not believe that it can be tested or treated. I have 2 questions:
1. Could an untested embryo , which might be abnormal have any negative affect on the PGD embryo?
2. Since I know that my immune system is not very strong and I tend to get sick very often. Do you think that it may have a reason for my repeated failed IVF? what can I do to test and make sure that my next IVF is not going to end up negative?
Thank you,
Yana
1. Could an untested embryo , which might be abnormal have any negative affect on the PGD embryo?
A: I do not believe so!
2. Since I know that my immune system is not very strong and I tend to get sick very often. Do you think that it may have a reason for my repeated failed IVF? what can I do to test and make sure that my next IVF is not going to end up
A: This would need further evaluation.
Whenever a patient fails to achieve a viable pregnancy following embryo transfer (ET), the first question asked is why! Was it simply due to, bad luck?, How likely is the failure to recur in future attempts and what can be done differently, to avoid it happening next time?.
It is an indisputable fact that any IVF procedure is at least as likely to fail as it is to succeed. Thus when it comes to outcome, luck is an undeniable factor. Notwithstanding, it is incumbent upon the treating physician to carefully consider and address the causes of IVF failure before proceeding to another attempt:
1.Age: The chance of a woman under 35Y of age having a baby per embryo transfer is about 35-40%. From there it declines progressively to under 5% by the time she reaches her mid-forties. This is largely due to declining chromosomal integrity of the eggs with advancing age…”a wear and tear effect” on eggs that are in the ovaries from birth.
2.Embryo Quality/”competency (capable of propagating a viable pregnancy)”. As stated, the woman’s age plays a big role in determining egg/embryo quality/”competency”. This having been said, aside from age the protocol used for controlled ovarian stimulation (COS) is the next most important factor. It is especially important when it comes to older women, and women with diminished ovarian reserve (DOR) where it becomes essential to be aggressive, and to customize and individualize the ovarian stimulation protocol.
We used to believe that the uterine environment is more beneficial to embryo development than is the incubator/petri dish and that accordingly, the earlier on in development that embryos are transferred to the uterus, the better. To achieve this goal, we used to select embryos for transfer based upon their day two or microscopic appearance (“grade”). But we have since learned that the further an embryo has advanced in its development, the more likely it is to be “competent” and that embryos failing to reach the expanded blastocyst stage within 5-6 days of being fertilized are almost invariably “incompetent” and are unworthy of being transferred. Moreover, the introduction into clinical practice about a decade ago, (by Levent Keskintepe PhD and myself) of Preimplantation Genetic Sampling (PGS), which assesses for the presence of all the embryos chromosomes (complete chromosomal karyotyping), provides another tool by which to select the most “competent” embryos for transfer. This methodology has selective benefit when it comes to older women, women with DOR, cases of unexplained repeated IVF failure and women who experience recurrent pregnancy loss (RPL).
3.The number of the embryos transferred: Most patients believe that the more embryos transferred the greater the chance of success. To some extent this might be true, but if the problem lies with the use of a suboptimal COS protocol, transferring more embryos at a time won’t improve the chance of success. Nor will the transfer of a greater number of embryos solve an underlying embryo implantation dysfunction (anatomical molecular or immunologic).Moreover, the transfer of multiple embryos, should they implant, can and all too often does result in triplets or greater (high order multiples) which increases the incidence of maternal pregnancy-induced complications and of premature delivery with its serious risks to the newborn. It is for this reason that I rarely recommend the transfer of more than 2 embryos at a time and am moving in the direction of advising single embryo transfers …especially when it comes to transferring embryos derived through the fertilization of eggs from young women.
4.Implantation Dysfunction (ID): Implantation dysfunction is a very common (often overlooked) cause of “unexplained” IVF failure. This is especially the case in young ovulating women who have normal ovarian reserve and have fertile partners. Failure to identify, typify, and address such issues is, in my opinion, an unfortunate and relatively common cause of repeated IVF failure in such women. Common sense dictates that if ultrasound guided embryo transfer is performed competently and yet repeated IVF attempts fail to propagate a viable pregnancy, implantation dysfunction must be seriously considered. Yet ID is probably the most overlooked factor. The most common causes of implantation dysfunction are:
a.A“ thin uterine lining”
b.A uterus with surface lesions in the cavity (polyps, fibroids, scar tissue)
c.Immunologic implantation dysfunction (IID)
d.Endocrine/molecular endometrial receptivity issues
Certain causes of infertility are repetitive and thus cannot readily be reversed. Examples include advanced age of the woman; severe male infertility; immunologic infertility associated with alloimmune implantation dysfunction (especially if it is a “complete DQ alpha genetic match between partners plus uterine natural killer cell activation (NKa).
My answer to patients who ask me when is the time to stop undergoing IVF is ….Aside from the weight of the financial burden, the time to stop is when in spite of thorough and comprehensive evaluation, there is no remediable and treatable explanation for repeated failure.
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.
•Blastocyst Embryo Transfers Done 5-6 Days Following Fertilization are Fast Replacing Earlier day 2-3 Transfers of Cleaved Embryos.
•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.
•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)
•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:
•Traveling for IVF from Out of State/Country–
•A personalized, stepwise approach to IVF
Please call or email Julie Dahan, my patient concierge. She will guide you on how to set up an in-person or Skype consultation with me. You can reach Julie at on her cell phone or via email at any time:
Julie Dahan
•Email: Julied@sherivf.com
•Phone: 702-533-2691
?800-780-7437
Geoff Sher
I also suggest that you access the 4th edition of my book ,”In Vitro Fertilization, the ART of Making Babies”. It is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.
Dear Dr. Sher.
I wrote to you previously and your answer was very much appreciated. I am 40 years, healthy, my husband 65, diabetic.. My BW results from January: AMH 3.76, FSH 5.97, LH 5.47, Prolactin 29.37.
In preparation for IVF: BCP start on a first day of April’s AF, taking them for 26 days. I did not tolerate them well (rash all over the body, worsen eczema, spotting and lot of cramping). Baseline U/S with following AF that was suppose to be a start of IVF showed a cyst, that was still producing estrogen even on a CD4 (E2 128). This IVF cycle was cancelled. I went thru a lot of IUI cycles before, never happened to me, that estrogen would not go down, so I think it could be BCP, that made me react like this. So as a preparation for next IVF I started Provera on CD18 for 7 days. AF started on the 4th day after stopping Provera. Cyst still there, but CD3 E2 was 62 (still much higher, than my usual E2 on CD3, but I was able to start IVF cycle).
Medications:
CD3 – CD5: Follistim 300, Menopur 150
CD6 – CD7: Follistim 225, Menopur 150
CD8 – CD11: Cetrotide, Follistim 225, Menopur 150
CD12: Cetrotide and in the evening the trigger with I believe 2500 IU Pregnyl (I had specific instruction how to mix and how much to use out of mix) and 40 units (or 0.4) of Lupron.
ER 36 hours after trigger. They retrieved 30 eggs from which 16 were matured. For all 16 used ICSI. 11 fertalized next morning. Three biopsied on day 5 and frozen (3AB, 3BB, 4BB), four biopsied on day 6 and frozen (6BA, 5AA, 4BA, 3BB). PGS NGS results were: 4 abnormal, 2 mosaic (one had some problem on chromosome 13 and the other I think had a missing chromosome 1), 1 normal (5AA)
I am aware of my age, but considering my hormonal levels from January, I was hoping for better outcome. Could you please give me you opinion on the cycle I described? Is it possible, that the outcome would be better with different protocol, or I have to just accept the fact, that in my age this outcome was the best I can get? From comunication with my RE I feel, that this is it, my eggs are not good anymore and that’s why I was not getting pregnant with IUIs (actually I got pregnant with 2nd IUI in 2014, but miscarried in 2nd trimester due to incompetent cervix, but after that no luck anymore in 2015). I read most of your blogs, so I know how imprtant the protocol is and I know you prefere to use the agonist/antagonist conversion protocol-A/ACP. What would you suggest if I don’t tolerate BCP well? What protocol would you choose if the BCP would not be used? Do you think the cetrotide can compromise the quality of the egg in IVF cycle? (most of my IUIs I did without it and E2 was growing nicely and then I used it in some cycles and growth of E2 was slower and in one IUI cycle actually decreased after I used it). I understand the importance of HCG 10000 now.
I am glad, that there is at least one normal embryo, but your blog ‘PGS and Assessment of Egg/Embryo “competency”: How Timing, Process, and Methodology Can Affect Reliability’ makes me think, how reliable this results are. I’m currently on Lupron, preparing myself for FET, where according PGS the normal One is going to be transfered. But I believe, they still keep the mosaic two frozen and I just keep wondering, what is going to happen to them. I read about some small study in Italy, where even from these embryos healthy babies were born. Do you have some experience with transfering mosaic embryo and with outcome after that? Thank you for your blogs and answers…
Indeed, I do think that protocol selection is one of the most important decisions to be made in IVF. It litterally can make the difference between success and failure (see below).Your thyroid condition also needs careful evaluation.
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 https://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.
• 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
• Why did my IVF Fail
• 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
• 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)
• 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:
• 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
Please call or email Julie Dahan, my patient concierge. She will guide you on how to set up an in-person or Skype consultation with me. You can reach Julie at on her cell phone or via email at any time:
Julie Dahan
• Email: Julied@sherivf.com
• Phone: 702-533-2691
? 800-780-7437
Geoff Sher
I also suggest that you access the 4th edition of my book ,”In Vitro Fertilization, the ART of Making Babies”. It is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.
All of my husbands SA have shown sperm agglutination. My gynecologist said that our only option is IVF with ICSI. Is this true? Is there anything that can be done for agglutination? They did check his semen for WBC’s and it was not an abnormal level I believe because nothing was mentioned about there being an infection.
Your gynecologist is almost certainly correct.
Antisperm antibodies (ASA) are immunoglobulins that attach to sperm. They are most commonly encountered in semen, blood, cervical mucous and follicular fluid. Not all ASA bind to sperm. However, those that do so can inhibiting fertilization. Methods used to detect for the presence of SAs in blood, in the seminal plasma of the ejaculate or in the cervical mucus only measure those immunoglobulins that bind to sperm components.
ASAs are related to the stimulation of sperm antigen. Detection of ASA requires access to standard sperm antigens that are associated with fertilization. An ideal sperm antigen should be sperm specific, accessible to the antibody and play a key role in fertilization..
In about 1-4% of infertility cases the presence of antisperm antibodies (ASA) in the male or female appear to be the cause. While the presence of ASA reduces both male and fertility significantly, it does not necessarily always prevent conception altogether. Rather, the effects are graduated; i.e., the larger the immunologic response (concentration of antibodies), the less likely it is that a pregnancy will occur and when the blood level rises above 40%, natural conception is highly unlikely to occur.
Like any other kind of antibody manufactured by the body, sperm antibodies are formed in response to antigens. These antigens are proteins, which appear on the outer sperm membranes as the young sperm cells, develop within the male testes. In the man’s own body, his sperm are regarded as foreign invading proteins and as such would normally be targeted for attack However, under normal conditions, direct contact between the man’s blood and sperm is prevented by a cellular structure in the testes called the blood/testis barrier. This barrier is formed by so-called, Sertoli cells, which abut very closely against each other, forming tight junctions that separate the developing sperm cells from the blood and prevent immunologic stimulation. However, the blood/ testis barrier can be broken by physical or chemical injury or by infection. When this barrier is breached, sperm antigens escape from their immunologically protected environment and come in direct contact with blood elements that launch an immunologic attack.
Once sperm and blood come in contact, whether in the male or female, specific antibodies are produced against them by specialized blood cells call T- and B-lymphocytes. The three main types of sperm antibodies produced are Immunoglobulin G (IgG), Immunoglobulin A (IgA) and Immunoglobulin M (IgM). These antibodies bind to the proteins (antigens) on the sperm head, midpiece or tail. The antibodies formed may be of the circulatory type (in the blood serum) or secretory type (in the tissue). This is important because high levels of antibodies in the blood serum do not invariably mean that the antibodies will find their way to the semen where they can affect the sperm. For example, the concentration of IgG is much lower in secretions of the reproductive tract that it is in the blood. Conversely, the local level of IgA is higher in the reproductive secretions than in the blood. This is an important point, which we will return to later.
Once sperm antibodies have formed, they can affect sperm in several different ways. Some antibodies will cause sperm to stick together or agglutinate. Agglutinated sperm clump together in dense masses and thus are unable to migrate through the cervix into the uterus. Other antibodies mark the sperm for attack by Natural killer (NK) cells of the body’s immune system (ie; opsonizing antibodies). Some antibodies cause reactions between the sperm membrane and the cervical mucus preventing the sperm from swimming through the cervix (ie; immobilizing antibodies). Antibodies can also block the sperm’s ability to bind to the zona pellucida of the egg, a prerequisite for fertilization (ie; blocking antibodies). Finally, there is recent evidence that the fertilized egg shares some of the same antigens that are found on the sperm. It is possible that sperm antibodies present in the mother can react with the early embryo, resulting in its destruction by phagocytic (ie; phagocytic antibodies) cells.
In my opinion, ASA tests are best performed on blood. There are a number of diagnostic tests available to detect the presence of sperm antibodies. There are several methods for the diagnosis These tests are performed by flow cytometry and the ELISA (enzyme-linked immunoabsorbent assay), the Franklin-Dukes sperm agglutination assay or the Immunobead Binding Test (IBT).the indirect immunofluorescence (IIF) assay, to name a few. My preference is the IBT.
In the male, IgA and IgG are found in the semen although there is controversy as to whether they originate locally (secreted by testicular cells) or cross over from the circulation. Antibodies of the IgM class are not found in semen.
Like the source of some antibodies, the question of the critical levels of sperm antibodies is also hotly debated among clinicians. There seems to be general agreement that blood levels above 30% by the IBT are associated with significant fertility problems.
Studiers have shown that pregnancy is highly unlikely following natural intercourse or intrauterine insemination when either the woman or the man harbors significant antisperm antibodies.
Attempts have to try and remove antibodies from sperm by allowing the sperm to swim through a column of beads are by and large unsuccessful. And, while there have been isolated reports that administration of corticosteroids (eg; prednisone) will temporarily suppress antibody production pregnancy rates are poor. Besides, corticosteroid therapy carries with it the risk of significant side, some of which (although infrequent) can be serious. As an example, in the man spontaneous fractures (especially of the neck of the femur) have been reported in 2 % of cases. I do not recommend this treatment.
In Vitro Fertilization (IVF) with intracytoplasmic Sperm injection (ICSI) is the best option. Here each egg is injected with a single sperm and whether there are antibodies attached to the outer surface of the sperm becomes irrelevant.. In fact, pregnancy and birth rates are the same as in cases where IVF is performed for reasons other than male factor infertility. IVF/ICSI success rates are also .not unaffected by the concentration of antisperm antibodies.
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 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
•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
•Male Factor Infertility
•Routine Fertilization by Intracytoplasmic Sperm Injection (ICSI): An Argument in FavorHormonal Treatment of Male Infertility
•Hormonal Treatment of Male Infertility
•The Sperm Chromatin Structure Assay (SCSA): A Measure of the Potential of Sperm to Help Propagate a Viable Pregnancy
Please call or email Julie Dahan, my patient concierge. She will guide you on how to set up an in-person or Skype consultation with me. You can reach Julie at on her cell phone or via email at any time:
Julie Dahan
•Email: Julied@sherivf.com
•Phone: 702-533-2691
?800-780-7437
Geoff Sher
I also suggest that you access the 4th edition of my book ,”In Vitro Fertilization, the ART of Making Babies”. It is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.
Dr. Sher, learning so much from this blog! Thanks! Age 35-DOR, possibly 1 tube blocked. 3 failed iuis with Gonal and Ovidrel trigger. Had my first retrieval (gonal/menopur/ganorelix/pregnyl), 7 eggs retrieved (expected 5) and 7 fertilized. Waiting patiently for # that make it to 5 day blast. We opted out of CCS testing due to cost and our Dr said that age 35 still has more normal than abnormal eggs. Do you find this to be true based on CCS testing results you’ve experienced? I’ve been on coq10, dhea, vitamin d and thyroid pill for 5 months. I’ve heard abnormal embryos can possibly ‘fix’ themselves and there is also risk of damage to embryo or failed live birth despite a good CCS embryo transfer. What are your thoughts on this? Am I fool to go this far and not take a loan to do the CCS? I plan to bank and do another retrieval, but if transfer doesn’t take is CCS an option on frozen embryos down the line if we save? Thank!
Hi Jessica,
First off, since you are taking thyoid medication, iyt could be that you have an underactive thyroid which in women is usually due to thyroid autoimmune disease. 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.
Second, it is indeed correct that due to mosaicism (see below), some chromosomally abnormal embryos can and do correct themselves “auto-correction….see below.
Third, at 35Y of age , whether to do PGS at all would be a toss-up. Frankly I probably would simply transfer 2 blastocysts (untested) at a time and forego the PGS testing
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.
•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
•Why did my IVF Fail
•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
•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)
•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:
•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
Please call or email Julie Dahan, my patient concierge. She will guide you on how to set up an in-person or Skype consultation with me. You can reach Julie at on her cell phone or via email at any time:
Julie Dahan
•Email: Julied@sherivf.com
•Phone: 702-533-2691
?800-780-7437
Geoff Sher
I also suggest that you access the 4th edition of my book ,”In Vitro Fertilization, the ART of Making Babies”. It is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.
hi Dr. Sher,
I was diagnose with Heterozygous MTHFR, CD56 nk CELLS 40.5 PERCENT, HLA match with my husband complete match. Had LIT twice, Intralipid infusion. FOlate, b6,b12 claxene, dexthemathesone
3 failed cycle,
2 fet failed.
i am now going to my 4 IVF cycle.
my question is what is the best way to achieve pregnancy of it is even possible to me to become pregnant. I am so down and sad that this wont gonna work as I am not on my 36 yrs of age. We really want to have a baby of our own. Thank you. Sorry for my sadness just feeling so down at the moment
I doubt that your IVF failures are due to the heterozygous MTHFR mutation.
Whenever a patient fails to achieve a viable pregnancy following embryo transfer (ET), the first question asked is why! Was it simply due to, bad luck?, How likely is the failure to recur in future attempts and what can be done differently, to avoid it happening next time?.
It is an indisputable fact that any IVF procedure is at least as likely to fail as it is to succeed. Thus when it comes to outcome, luck is an undeniable factor. Notwithstanding, it is incumbent upon the treating physician to carefully consider and address the causes of IVF failure before proceeding to another attempt:
1.Age: The chance of a woman under 35Y of age having a baby per embryo transfer is about 35-40%. From there it declines progressively to under 5% by the time she reaches her mid-forties. This is largely due to declining chromosomal integrity of the eggs with advancing age…”a wear and tear effect” on eggs that are in the ovaries from birth.
2.Embryo Quality/”competency (capable of propagating a viable pregnancy)”. As stated, the woman’s age plays a big role in determining egg/embryo quality/”competency”. This having been said, aside from age the protocol used for controlled ovarian stimulation (COS) is the next most important factor. It is especially important when it comes to older women, and women with diminished ovarian reserve (DOR) where it becomes essential to be aggressive, and to customize and individualize the ovarian stimulation protocol.
We used to believe that the uterine environment is more beneficial to embryo development than is the incubator/petri dish and that accordingly, the earlier on in development that embryos are transferred to the uterus, the better. To achieve this goal, we used to select embryos for transfer based upon their day two or microscopic appearance (“grade”). But we have since learned that the further an embryo has advanced in its development, the more likely it is to be “competent” and that embryos failing to reach the expanded blastocyst stage within 5-6 days of being fertilized are almost invariably “incompetent” and are unworthy of being transferred. Moreover, the introduction into clinical practice about a decade ago, (by Levent Keskintepe PhD and myself) of Preimplantation Genetic Sampling (PGS), which assesses for the presence of all the embryos chromosomes (complete chromosomal karyotyping), provides another tool by which to select the most “competent” embryos for transfer. This methodology has selective benefit when it comes to older women, women with DOR, cases of unexplained repeated IVF failure and women who experience recurrent pregnancy loss (RPL).
3.The number of the embryos transferred: Most patients believe that the more embryos transferred the greater the chance of success. To some extent this might be true, but if the problem lies with the use of a suboptimal COS protocol, transferring more embryos at a time won’t improve the chance of success. Nor will the transfer of a greater number of embryos solve an underlying embryo implantation dysfunction (anatomical molecular or immunologic).Moreover, the transfer of multiple embryos, should they implant, can and all too often does result in triplets or greater (high order multiples) which increases the incidence of maternal pregnancy-induced complications and of premature delivery with its serious risks to the newborn. It is for this reason that I rarely recommend the transfer of more than 2 embryos at a time and am moving in the direction of advising single embryo transfers …especially when it comes to transferring embryos derived through the fertilization of eggs from young women.
4.Implantation Dysfunction (ID): Implantation dysfunction is a very common (often overlooked) cause of “unexplained” IVF failure. This is especially the case in young ovulating women who have normal ovarian reserve and have fertile partners. Failure to identify, typify, and address such issues is, in my opinion, an unfortunate and relatively common cause of repeated IVF failure in such women. Common sense dictates that if ultrasound guided embryo transfer is performed competently and yet repeated IVF attempts fail to propagate a viable pregnancy, implantation dysfunction must be seriously considered. Yet ID is probably the most overlooked factor. The most common causes of implantation dysfunction are:
a.A“ thin uterine lining”
b.A uterus with surface lesions in the cavity (polyps, fibroids, scar tissue)
c.Immunologic implantation dysfunction (IID)
d.Endocrine/molecular endometrial receptivity issues
Certain causes of infertility are repetitive and thus cannot readily be reversed. Examples include advanced age of the woman; severe male infertility; immunologic infertility associated with alloimmune implantation dysfunction (especially if it is a “complete DQ alpha genetic match between partners plus uterine natural killer cell activation (NKa).
My answer to patients who ask me when is the time to stop undergoing IVF is ….Aside from the weight of the financial burden, the time to stop is when in spite of thorough and comprehensive evaluation, there is no remediable and treatable explanation for repeated failure.
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.
•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?
•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)
•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:
•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
Please call or email Julie Dahan, my patient concierge. She will guide you on how to set up an in-person or Skype consultation with me. You can reach Julie at on her cell phone or via email at any time:
Julie Dahan
•Email: Julied@sherivf.com
•Phone: 702-533-2691
?800-780-7437
Geoff Sher
I also suggest that you access the 4th edition of my book ,”In Vitro Fertilization, the ART of Making Babies”. It is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.