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      • Understanding Immunologic Implantation Dysfunction Part 1: Setting the Stage for Selective Immunotherapy with Intralipid and IVIg

      Dr. Geoffrey Sher Recommends

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      It is an unfortunate reality that many IVF programs attach little importance to factors that affect embryo implantation in general, and immunologic implantation dysfunction (IID) in specific (see below). Perhaps the lack of attention given to evaluating IVF patients for factors that adversely affect the receptivity of the uterine lining (endometrium/decidua) is due to the fact that in humans, IVF failure and miscarriage are both four times more likely to be due to embryo “incompetence” than to dysfunctional implantation.Thus, a high measure of IVF success can still be achieved in spite of ignoring less common (and more complex) factors such as IID.

      But for the 20% of IVF patients with problems relating to lack of endometrial receptivity, it becomes a different matter altogether. For them, the emotional, physical and financial roller coaster ride goes on and on. Often after “spinning their wheels” and enduring repeated IVF failures, many of them will be advised to move on to egg donation…only to fail there as well. Optimal implantation is not only important for embryo survival; it is also a major factor in determining normal intrauterine growth and development. As such, it is a major determinant of the very quality of life after birth.

      Immunologic acceptance of the implanting embryo by the uterus of the mother is both highly complex and magnificent. Not only is it essential for pregnancy to occur, but it also sets the scene for our body’s own cells, tissues and organs to be shielded from attack by our own immune systems. For a moment, consider how, when confrontedby foreign proteins (bacteria, viruses, foreign tissue grafts/transplantation), the body’s immune system goes on the attack, but yet an embryo that is derived from proteins that come from another individual (the sperm or paternal antigen), usually safely implants in the pre-pregnancy uterine lining and then grows into a healthy baby.This phenomenon has come to be referred to as the “immunologic riddle” of pregnancy.

      For such a complex arrangement to be foolproof would be without precedent in human biology. To argue that this system can never fail is in my opinion, an absurdity, bordering on arrogance. It can and does go wrong in about 15-20% of women with reproductive failure.When it does, it presents either as failed implantation (presumed by the patient to be infertility), as miscarriage, or (much less frequently) as placental failure and compromised fetal development or intrauterine death. It all depends on the timing, nature and severity of the immune assault.

      It is well known that the reason the implanting normal embryo thrives in the womb is that unique immunologic adjustments convert the pre-pregnancy uterine lining (decidua) into a “privileged site” where the embryo and the fetus come to be regarded as the “body’s own” and as such are protected from immune attack. This initial acceptance of the embryo as “self” or “friend” rather than “non-self” or “foe” (in spite of it being composed partially of the father’s “foreign” cells), is one of the miraculous adaptations of nature, and is in large part responsible for our survival as a species.

      As soon as implantation begins, the paternal genetic contribution to the embryo (so called DQ alpha genes) initiates asignal to the pre-pregnancy decidual immune system which thereupon determines whether the embryonic “allograft” should be welcomed as “friend” or be rejected as “foe” through immune attack. The process is referred to as “alloimmune recognition.”Given that with the exception of monozygotic twins, interpersonal differences in genotype are inevitable, it follows that maternal and paternal DQ alpha gene combinations will usually also differ in the vast majority of cases. Thus, preservation of the human species required that in spite of such immunogenetic dissimilarities, the immune system of the pre-pregnancy endometrium (decidua) evolutionarily adapt and recognize the embryo as friend rather than foe.

      Upon reaching the uterine environment, the genetically “competent” embryo hatches and within 12-24 hours starts sending its root system (trophoblast) into the decidua. The trophoblast has both a villous (root-like) and an extravilous (diffuse) component. The extravilous trophoblast which diffusely permeates the decidua, expresses several so-called “major histocompatibility complex” (MHC) class-1 genes (e.g. histocompatibility leukocyte antigen [HLA]-C, E & G)].These HLA genes, (mainly HLA-G) regulate primarily two types of lymphocytes present in the decidua.These are: a) uterine natural killer cells (NK) and b) cytotoxic lymphocytes (CTL). NK cells comprise approximately 75% of decidual lymphocytes and CTL comprise about 10%. They both play a vital role in regulating the normal implantation process by controlling the penetration and functioning of the trophoblast.

      The recognition of proteins as self (“friend”) or non-self (“foe”) is propagated by highly specialized immune lymphocytes known as Regulatory T-cells. These so called Treg cells can “turn-off” immune reactions even once they have been started by conventional immune cells. They play a pivotal role in the immune system’s ability to prevent rejection of an embryo whether due to an autoimmune or alloimmune response. Other immune cells known as “dendritic cells” introduce antigenic proteins to these Treg cells, whose concentration increases when the antigen is recognized as “friend” and decreases when recognized as “foe.” MHC (primarily HLA-G) signaling, through the Treg lymphocyte mechanism working in combination with other regulatory proteins, influences the production and release of so-called cytokines by the NK and CTL cells.

      There are 3 varieties of cytokines, two of which play defining roles in the maintenance of implantation:The first is TH-2 cytokines, which encourage growth and expansion of the trophoblast and promote proliferation of blood vessels (angiogenesis). TH-1 cytokines promote destruction (cytolysis) of trophoblastic cells and also cause blood to clot (procoagulant effect).A balance between TH-1 and TH-2 cytokines is essential for normal implantation and development of the placenta (placentation). Over-activity (dominance) of TH-1, the hallmark of NK cell and CTL activation, leads to damage of the trophoblast, implantation dysfunction and reproductive failure.

      Part 2 of this post will discuss the diagnosis and treatment of immunologic implantation dysfunction.

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      17 Responses to “Understanding Immunologic Implantation Dysfunction Part 1: Setting the Stage for Selective Immunotherapy with Intralipid and IVIg”

      1. Tippy says:
        May 11, 2011 at 4:27 pm

        I have a related question. I recently had a very early miscarriage, or chemical pregnancy with an IVF cycle. Does the fact that I had a positive pregnancy hcg beta with a level of 25 at 16dpo indicate that implantation did occur and therefore, I don't have immunological implantation dysfunction and instead it was a chromosomal issue?

        Reply
      2. Geoffrey Sher, MD says:
        May 11, 2011 at 9:47 pm

        No it does not,

        You could have dysfunctional implantation that starts with a =ve beta and then fizzles out sometime later. My next and final blog on this topic (next Tuesday) should explain this.

        Geoff Sher

        Reply
      3. Horserider says:
        September 12, 2012 at 5:49 pm

        Dr. Sher, (Question from Orlando, FL)

        My new IVF doctor, Dr. Milton McNichol, asked that I contact you with my immune results from Kwak and Braverman. Dr. McNichol would like to know if you agree with what has been prescribed.

        In the last five years, I’ve had over 7 miscarriages, from natural and IUI conceptions. One failed IVF, and one fresh donor cycle failed recently while on 100 mg. of Intralipids every 9 days, 20 mg Prednisone daily, and 30 mg of Lovenox daily with Baby Aspirin, Calcium, and other vitamins. (My blood work showed abnormally low NKs, but elevated Cytokines during transfer). There was a 10 cell and one 8 cell from an 18 year old donor (I am 43). My results from Dr. Braverman’s findings were normal except for the following: CD4=53.9; CD56=12.1; TNF=35.9; IFN=20.9 (all tested from Rosalind Lab). Anti-DNA=28; PAI-1: Heterozygous for the 4G/5G. T4=1.26; TSH=1.56. My husband and I do not have matches, and his Fragmentation was <20%.

        I'm sure you are aware of all of the extensive testing that goes on in these clinics, especially since we've been with Dr. David in NYC, Kwak, Braverman, Beer, and still no family.

        Dr. McNichol wanted to specifically know if I need Prednisone and Lovenox. If my PAI-1 is Heterozygous Mutated, and the beta-Fibrinogen 455/G/A Gene Polymorphism is Heterozygous Mutated; and my MTHFR gene was homozygous positive (2 copies) A1298C; do I required Lovenox? Also, because my cytokines are usually (I should say ALWAYS) elevated, do I required Prednisone 20 mg daily during a cycle? I've never been pregnant while on any of these meds. The last cycle with a fresh donor did not have implantation. Dr. Braverman and Kwak suggest Prednisone and Lovenox. Kwak wanted me to do IVIG, but I can't afford it. Dr. B said it was not necessary, and nor was Intralipids necessary. Per Dr. B, I started a Gluten Free diet and 3 months later tested and had normal NKs, but slightly elevated cytokines. I've had numerous uterine biopsies, all normal, including testing for NK Cell activity, and infections… all normal. No STDs. Diagnosed with Hashimotos, so I take 100 mcg Synthroid brand daily. Dr. B said I could try Neupogen with Prednison and Lovenox. Your thoughts? I have one more shot with my FET and then we're done. Purely tapped out.

        Thanks much.

        Reply
        • Geoffrey Sher says:
          September 14, 2012 at 12:57 pm

          Your TH-1 cytokines are elevated so T gather the K-562 targewt cell test for NK cell actiavtion on your blood showed +ve as well. If this was not done…it should be.

          Provided that you do not have have matching DQa’s or HLA with husband, you should do fine with pre-ER, IL/dexamethosone. Daily Lovenox should be initiated once a +ve pregnancxy is indicated. IVIG is likely redundant in such a setting.

          If you wish to discuss your case with me call 800-7870-7437 for a free video consultation. In the meanwhile, go to http://www.IVFauthority.com and when you get to the home-page type in the following topics into the search bar: 1. Recurrent pregnancy loss and IVF;2. Staggered IVF; 3.Immunologic Implantation dysfunction.

          Geoff Sher

          Reply
      4. savitha says:
        January 20, 2013 at 3:04 am

        Dear Doctor,

        I need an urgent guidance from you regarding Intralipid Infusion.

        My doctor has wholeheartedly agreed to go for Intralipid Infusion 7-10 days before my ET to treat the Immune Issues. But we have today come across an article which says that Intralipids are not to me mixed with Saline, where as you had suggested that Intralipid 20%-100ML is to be mixed with 400ML saline and administered Intravenously in around 2-3 Hrs.

        Grateful if you could confirm urgently if you still stand by the way it is to be administered as we are required to do the Infusion tomorrow, so that it falls between 7-10days before FET.

        Thankyou very much.

        Reply
        • Geoffrey Sher says:
          January 20, 2013 at 7:33 pm

          I think I responded to this previously by email. But let me do so again.

          Intralipid is an isotonic solution as is normal saline. There are no additional electrolytes added. So there is no problem using it as we do. Infusion of 500ml over 3-5 hours poses no risk. There are a few minor contraindications to its usage and none of these apply to you or to almost all other IVF candidates.

          I estimate that we have done >1000 infusions by now and have never encountered a problem.

          Go ahead with the infusion as recommended because you have activated NK cells and in my opinion, without this treatment the chances of success would be small.

          ail

          Reply
      5. CJ says:
        January 29, 2013 at 1:36 pm

        Hi Dr Sher,
        I am in australia and have come across some of your information lately, including an excellent webinar on implantation dysfunction. I have both hashimotos and endometriosis and was fascinated to find that there is such a high incidence of activated natural killer cells in both of these conditions. I have high thyroid antibodies and ANAs. I was tested negative for lupus and antioagulant antibodies but have not yet been tested for APAs or antiovarian antibodies.
        I am currently 31, have been trying (with only one chemical pregnancy early on) for 2.5 years and have had 3 cycles of clomid. I seem to ovulate on my own (progesterone around 20). My first 2 rounds of clomid actually caused me to not ovulate at all which surprised me and then with my 3rd round i had a positive OPK test however a blood test to confirm shows LH of only 15 so i received a trigger injection and that month my progesterone was 47.4 but i was still not pregnant. This month my FS wants to try another clomid/trigger cycle but wants to add prednisone from the day of ovulation.
        After listening to your webinar however, i wish he would have considered the use of intralipids too but i am also concerned as you have recommended that these medications only be used in IVF cycles.
        I personally would like to go straignt to IVF and not do any IUI cycles. But my FS feels IUI is less intrusive and we should try as the next step if this clomid round fails.
        I came across Dr Gammal Matthias yesterday who is the only reproductive endocrinologist in Australia and he sends bloodwork to Chicargo to be tested. Have you heard of him? I am not sure whether we have the ability to test for active natural killer cells in any Australian labs??
        Do you have any advice for me?
        We are not in a position to travel to the US at this stage, I do think however, that if all else fails and i start to move closer to 40 we would try to come to see you.
        Thanks very much
        Cindy

        Reply
        • Geoffrey Sher says:
          January 29, 2013 at 3:22 pm

          I strongly recommend IVF with selective immunotherapy if you have an autoimmune NK cell-cytokinopathy. There are 2 labs in Chicago that can test for NKa. The one is Milenova and the other (preferred) is Finch University. I personally use neither. I refer to Reprosource in Boston, MA or Reproductive Immunology Associates in Van Nuys, CA. Both are superb labs. While being tested for NKa have your and your husband matched for alloimmune implantation issues by having your respective bloods tested for DQ alpha and HLA matching.

          Please go to http://www.IVFauthority.com . When you get to home page, look for a “search bar” in the upper right hand corner. Type the following subjects into the bar, click on it and it will take you to all the relevant articles posted there.

          1. “”Immunologic Implantation Dysfunction” (posted on May, 10th and on May 16th respectively.

          2. “Embryo Implantation………” (Part-1 and Part- 2—-Posted August 2012)

          3. “IVF success: Factors that influence outcome”

          Good luck!

          Geoff Sher

          Reply
      6. CJ says:
        January 30, 2013 at 3:17 pm

        Thankyou so much for taking the time to respond to me. I have read the articles that you recommended and will hopefully be able to send my blood sample to a preferred lab in the states and will try to have both myself and my husband tested for DQ alpha and HLA matching – will bring it up with the reproductive immunologist i see next month. He does not do IVF himself but works with a willing FS…
        If there any possibility to consult with you over the phone even though I live in Australia – If my FS or reproductive immunologist was happy to work with you?
        Thanks
        Cindy

        Reply
      7. ELENA says:
        March 15, 2013 at 11:28 am

        I live in Spain where I do not get the same information from my doctors, in comparison to medical web pages. I´m 40 years old and my partner and I have been diagnosed with male infertility. I have had three fresh cycles and 1 frozen cycle, all ICSI. One was done with 2 3day embryos, another with 2 blastocysts, another with 2 4day morulas and the frozen cycle was 1 6day hatching blastocyst. All were considered good quality. I only had 1 chemical pregnancy. All other tries resulted in negative betas. My question is related to the fact that I have Rheumatoid Arhtritis, In Spain my rheumatologist, gynocologist and fertility specialists all tell me this illness should not affect my fertility, but after reading posts like yours I wonder if I might have an autoimmune response. Could this be the cause of my problems? What should I ask my doctors to look for?

        Reply
        • Geoffrey Sher says:
          March 15, 2013 at 7:24 pm

          You could easily have an immunologic implantation problem. Also at age 40, egg/embryo competency is another issue.

          Please go to the home page of this blog, (www.IVFauthority.com). When you get there look for a “search bar” in the upper right hand column. Then type in the following subjects into the bar, click and this will take you to all the relevant articles I posted there.

          1. “An Individualized Approach to Ovarian stimulation” (posted on November 22nd, 2010)

          2. “Ovarian Stimulation in IVF: Why is it important to down-regulate LH?”

          3. “Agonist/Antagonist Conversion Protocol”

          4. “Immunologic Implantation Dysfunction” (posted on May, 10th and on May 16th respectively.

          5. “Embryo Implantation………” (Part-1 and Part- 2—-Posted August 2012)

          6. “Traveling for IVF from Out of State/Country– The Process at SIRM-Las Vegas” (posted on March, 21st 2012)

          7.“A personalized, stepwise approach to IVF at SIRM”; Parts 1 & 2 (posted March, 2012)

          8. “IVF success: Factors that influence outcome”

          9. “Staggered IVF”

          10.“Embryo Banking”

          Consider calling 702-699-7437 to arrange a Skype consultation (\with me so we can discuss your case in detail.

          Geoff Sher

          Reply
      8. Abul Salauddin says:
        April 4, 2013 at 7:44 pm

        Dear Dr. Sher,

        My wife and I have been struggling with infertility and recurrent pregnancy losses for the last 7 years; we have had 8 of them now; all terminating between 6-8 weeks (heartbeats in some, blighted ovums, lifeless embryos in others, including 2 ivf failures). We have had every test under the sun from the Beer center, dr. kwak, RFU, etc. My wife is 40 and I am 41. We are at our wits end as to what to do, perhaps biological parenthood is not meant for us. As our last ditch effort, we would like to consult you and see if you could offer any help. A response would be greatly appreciated. Thanks.

        Abul

        Reply
        • Geoffrey Sher says:
          April 4, 2013 at 8:19 pm

          I absolutely look forward to talking to you. Please call 800-780-7437 or 702-699-7437 to arrange a Skype consultation (free of charge to those who reside in the United States or Canada) with me so we can discuss your case in detail

          In the interim, please go to the home page of this blog, http://www.IVFauthority.com . When you get there, look for a “search bar” in the upper right hand corner. Type the following subjects into the bar, click on it and it will take you to all the relevant articles posted there.

          1. “Recurrent pregnancy loss (RPL)”

          2. “Immunologic Implantation Dysfunction” (posted on May, 10th and on May 16th respectively.

          5. “Embryo Implantation………” (Part-1 and Part- 2—-Posted August 2012)

          6. Sincerely,

          Geoff Sher

          Reply
      9. amruta says:
        April 23, 2013 at 7:50 pm

        Dear Dr. Sher,

        me and my husband have been trying to get pregnant for 3 years now.
        we have had in total 3 ivf’s in last 2 years. primary reason MFI ( sperm count varied between 2mil to 2o mill with 5% morphology)
        first attempt resulted in OHSS and i was hospitalized for almost 2 weeeks with negative outcome we had 30 eggs out of which 22 were mature and only 6 fertilized after performing IMSI out of which 3 were transfered on day 3. PGD was performed on remaining 3 embryos and the result was normal.
        second attemt was FET using PGD embryos two went on to blastocyst level one was hatching blast but outcome was negative.
        our latest attemt we changed the specialist and this time we were able to retrieve 10 eggs
        ( doctor said i had already ovulated 5 naturally just before the ER) only 2 were fertilised and went on to blastocyst level with less than 5% fragmentation rest eggs disintegrated after performing icsi. i had a 5 day transfer which went smoothly.. and my beta HCG came back positive at 9DP5DT at 35 then 87 and 270 but within a week i started spotting and beta came down to 200.. doctor performed transvaginal ultrasound and said that my endometrium looks undisturbed and very healthy.. but suspected chemical pregnancy..
        this cycle i was on short protocol triggered without HCG to avoid OHSS..sustain 400 twice, baby asprin and progyanova 2 mg twice and folic acid with mecobalamin and DHA..
        im really worried that i might be suffering from immunological implantation dysfunction..or poor egg quality as eggs didnt survive the ICSI process..all other genetic tests are normal..
        can you please share your thoughts and opinion .. we honestly dont know what to do..

        Amruta

        Reply
        • Geoffrey Sher says:
          April 24, 2013 at 9:48 am

          Hi Amruta,

          You are very intuitive and appropriate in your assumptions.

          specially, if (as I suspect is the case) you are still relatively young, then unexplained repeated IVF failures must take into an account an implantation dysfunction. Obviously immunologic implantation dysfunction is one very important cause of this.

          Please go to the home page of this blog, http://www.IVFauthority.com . When you get there, look for a “search bar” in the upper right hand corner. Type the following subjects into the bar, click on it and it will take you to all the relevant articles posted there.

          1. “An Individualized Approach to Ovarian stimulation” (posted on November 22nd, 2010)

          2. “Ovarian Stimulation in IVF: Why is it important to down-regulate LH?”

          3. “Agonist/Antagonist Conversion Protocol”

          4. “Immunologic Implantation Dysfunction” (posted on May, 10th and on May 16th respectively.

          5. “Embryo Implantation………” (Part-1 and Part- 2—-Posted August 2012)

          6. “Traveling for IVF from Out of State/Country– The Process at SIRM-Las Vegas” (posted on March, 21st 2012)

          7.“A personalized, stepwise approach to IVF at SIRM”; Parts 1 & 2 (posted March, 2012)

          8. “IVF success: Factors that influence outcome”

          You might want to call 800-780-7437 or 702-699-7437 to arrange a Skype consultation (free of charge to those who reside in the United States or Canada) with me so we can discuss your case in detail

          Geoff Sher

          Reply
      10. Gammongirl says:
        May 10, 2013 at 12:41 pm

        Dear Dr Sher,

        I have been diagnosed with MTHFR homozygous for C677T and PAI-1 Antigen 4G/5G (my NK Cell Activation was 9.6 – but I was told this likely isn’t affecting anything. CD56+/16+ NK was a 4.0. I have other similar testing results, but am not sure what is relevant). I have had recurrent miscarriages- 2 chemical pregnancies at less than 5 wks and 2 miscarriages at 5.5 wks with chromosomal abnormalities -trisomy 22 and the second mis was trisomy 2. I’ve completed 3 IVF cycles with PGS – all together 23 embryos were fertilized with ICSI and only 5 made it to blast stage for PGS biopsy. All showed abnormalities, most had multiple monosomies and trisommies. Could the MTHFR or PAI-1 have contributed to the chromosomal abnormalities? (I just turned 41, and the current theory is that all of the abnormalities, starting when I was 38 are due to advanced maternal age.)
        Thank you. I appreciate your feedback!

        Reply
        • Geoffrey Sher says:
          May 10, 2013 at 3:07 pm

          There is no relationship between MTHFR thrombophilia and egg/embryo chromosomal issues. With regard to the NK assay being normal, please go to the home page of this blog, http://www.IVFauthority.com. When you get there, look for a “search bar” in the upper right hand corner. Type the following subjects into the bar, click on it and it will take you to all the relevant articles posted there.

          1. “Immunologic Implantation Dysfunction” (posted on May, 10th and on May 16th respectively.

          2. “Embryo Implantation………” (Part-1 and Part- 2—-Posted August 2012)

          3. “Traveling for IVF from Out of State/Country– The Process at SIRM-Las Vegas” (posted on March, 21st 2012)

          4.“A personalized, stepwise approach to IVF at SIRM”; Parts 1 & 2 (posted March, 2012)

          Consider calling 800-780-7437 or 702-699-7437 to arrange a Skype consultation (free of charge to those who reside in the United States or Canada) with me so we can discuss your case in detail

          Geoff Sher

          Reply

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      Understanding Immunologic Implantation Dysfunction Part 2: A Rational Basis for Selective Intralipid & IVIg Immunotherapy in IVF
      ALLOIMMUNE VS. AUTOIMMUNE DYSFUNCTION Alloimmune Implantation Dysfunction Every human being has two DQ-alpha genes. One is contributed by the father and the other by the mother. In a small percentage of patients undergoing IVF, paternal-maternal DQ-a... more
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      DQ-alpha Matching in IVF: The Controversy, How It Affects Outcome, & How to Treat!
      IVF patients, especially those who find themselves inexplicably repeatedly failing treatment after treatment are no longer willing to blindly accept platitudes from those who would ignore the role of immunologic causes of IVF failure while unable to ... more
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      Unexplained Infertility: True Diagnosis or Cop Out?
      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 su... more
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      Egg Banking of Genetically (CGH)-Tested Eggs Could Change The Face Of IVF-Ovum Donation
      For more than a quarter century, medical scientists have attempted to defy the biological clock by freezing a woman’s eggs to preserve her fertility. Most of these efforts have failed. Consider the fact that since the birth of the world’s 1st “... more
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      Case Study: Hydrosalpinx (Blocked/Fluid Filled Fallopian Tubes) and IVF Failure
      RL, a 31-year-old woman, presented with a 7 year history of inability to conceive, in spite of 2 prior fresh and 1 frozen IVF attempts, where a total of six good quality blastocysts had been transferred to her uterus.  Her husband PL, had normal spe... more
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      Recurrent Unexplained IVF Failure with “Good Quality” Embryos
      The following is a case study of a recent patient that came to me for treatment.  CJ, a 34 year old, and her husband RJ (age 35) presented to me with a six-year history of infertility. Based on semen analysis, RJ, who had initiated two pregnancies i... more
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      Karmann and Ryan’s Journey – My Approach to Their Treatment
       Please refer to last week’s blog post, where Karmann tells in her own words her struggles with recurrent miscarriage – nine miscarriages to be exact – and her long journey  of heartbreak, disappointment, and finally – hope.... more
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      Karmann and Ryan – Nine Miscarriages, Then Hope!
      In observation of National Infertility Awareness Week (NIAW), I wanted to share the touching story of a couple that I first met last year – after they had already experienced 8 years of heartbreak and frustration.  Their story is representativ... more
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      IVF in a Same-Sex Male Couple: A Case Study
      Background: About two years ago, I received a call from a gentleman that I will call “John”. John was a movie producer who stated that he and his partner “Brian” had been in a monogamous same-sex relationship for 7 years and each wanted to si... more
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      Recurrent Molar Pregnancy Treated By “IVF Genetic Chess”
      Background: Maria (fictitious name), a childless 34-year-old Hispanic lady, presented with a history of having had five (5) successive spontaneous pregnancy losses at 7 weeks gestation, all due to hydatidiform moles. Four (4) of these losses were ... more
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      Case Study: Donor Egg IVF in a Post Menopausal Woman
      Mary (fictitious name), a 54 year menopausal woman, presented at SIRM-Las Vegas for IVF using an egg donor. She had been menopausal for 7-plus years and had NOT been on any hormone replacement therapy. Mary gave a history of having undergone IVF with... more
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      Case Study: Endometriosis Presenting as “Unexplained Infertility”
      I consulted with a 36 year old lady (whom I will refer to as “Sandra”) and her partner, about 18 months ago. She and her husband of 5 years had been having regular unprotected intercourse throughout this time and had been unable to conceive. Sand... more
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      Case Study: Pelvic Tuberculosis, Hypothyroidism, and Immune Implantation Dysfunction
      About 18 months ago I saw an Asian Indian couple who presented with a very interesting history. The female partner (whom I will refer to as DB) had regular menstrual cycles and normal ovarian reserve, was ovulating regularly and had a fertile male pa... more
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      Dear Dr. Sher: A Healthy Baby Followed by Multiple Miscarriages
      This is the second in a series of posts taken from questions that have been submitted to me via email, website, or discussion boards.  This question is from a patient who had a healthy baby from her first pregnancy, but then went through a period of... more
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      Karmann and Ryan’s Journey – My Approach to Their Treatment
       Please refer to last week’s blog post, where Karmann tells in her own words her struggles with recurrent miscarriage – nine miscarriages to be exact – and her long journey  of heartbreak, disappointment, and finally – hope.... more
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      Why Did My IVF Fail? Part 2 – Uterine Receptivity and Transfer Technique
      This is the second part of a two-part post on IVF failure. In my January 22nd post, I discussed what I often refer to as the “seed” variable in the “seed/soil” relationship – the embryo. This week’s post will address the “soil” variab... more
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      My IVF Cycle Failed – What Went Wrong? Question #19: Why Do I Keep Having Chemical Pregnancies and Miscarrying?
      This is the 19th in a series of answers to common questions about failed IVF. Early pregnancy loss – whether due to miscarriage or chemical pregnancy – is due to two major factors. In more than 70-80% of cases the cause is attributable to... more
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      My IVF Cycle Failed – What Went Wrong? Question #18: My Fertility Clinic Reports a High Success Rate – How Could I Have 2 Failed Cycles In A Row?
      This is no. 18 in a series of answers to common questions about failed IVF. While it is true that IVF failure can be due to preventable factors, it is as important to understand that optimal medical care does not always equate with an optimal outcome... more
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      My IVF Cycle Failed – What Went Wrong? Question #17: Why Didn’t I Get Pregnant When I Used a Young Egg Donor and Had Good Quality Embryos?
      This is #17 in a series of answers to common questions about failed IVF. For women whose advancing age and/or ovarian resistance make having a baby with their own eggs unfeasible or unlikely, IVF using donated eggs from a young donor (under 35 years)... more
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      My IVF Cycle Failed – What Went Wrong? Question #16: Why did my hCG levels stop rising properly?
      This is the 16th in a series of answers to common questions about failed IVF. Immediately following implantation, the root system (trophoblast) of the embryo begins to release the pregnancyhormone, human chorionic gonadotropin (hCG) into the surround... more
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      My IVF Cycle Failed – What Went Wrong? Question #15: Might My Mental State Have Played a Role?
      This is the 15th in a series of responses to common questions about failed IVF There is little doubt that stress and emotional lability plays a role in the normal physiological/hormonal regulation of the menstrual cycle.After all, Eskimos often stopp... more
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      My IVF Cycle Failed – What Went Wrong? Question #14: Could it Have Been Due to Inadequate Hormonal Support After the Egg Retrieval & Embryo Transfer?
      This is the 14th in a series of answers to common questions about failed IVF. In vitro fertilization establishes an abnormal hormonal environment in the uterus.In some cases (especially older women and those with a diminished ovarian reserve), high o... more
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      My IVF Cycle Failed – What Went Wrong? Question #13: Did the Number of Embryos I Had Transferred Play a Role?
      This is the 13th in a series of answers to common questions about failed IVF. Virtually everyone recognizes that pregnancy with multiples (especially triplets or greater) is associated with a high incidence of premature delivery that has serious cons... more
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      My IVF Cycle Failed – What Went Wrong? Question #12: Might the Timing of Embryo Transfer – Day 2-3 (Cleaved) vs. Day 5-6 (Blastocyst) Play a Role?
      This is the 12th in a series of answers to common questions about failed IVF. (Note: I’ll be hosting a live video chat on Aug. 2 on the topic of Failed IVF where I’ll discuss the issues addressed in this series of posts and take your ques... more
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