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.
Good morning,
Doctor Sher, I need your advice. I have a question about my infertility treatment. I have positive ANA, deep Endometriosis, which was removed during Laparo’s previous year. Ovulation is every month but without pregnancy. I am 36 years old and my husband 37 years old. I have never had a pregnancy ( I had a problem with a tube, but after Laparo the doctor said to get pregnant).
Can I have an immune factor of infertility? My doctor tried to use intralipid 20% but another scheme 3-4 days before ovulation (ovulation is usually 10-11 day of the cycle)100 ml intalipid to 100 ml sodium chloride during 1-3 hours and 5 mg prednisolone in the second phase of the menstrual cycle but without result ( we used it for 7 cycles). We want to get pregnant ourselves without IVF.
I will be very grateful for your answer.
Thanks
1/3 of women with endometriosis, regardless of its severity will have an immunologic implantation dysfunction. If you are shoqwn to, have this, the combination of endometriosis, your age and the immunologic implantation dysfunction, would in my opinion be an indication to do IVF.
More than half of women who have endometriosis harbor antiphospholipid antibodies (APA) that can compromise development of the embryo’s root system (trophoblast). In addition and far more serious, is the fact that in about one third of cases endometriosis, regardless of its severity is associated with NKa and cytotoxic uterine lymphocytes (CTL) which can seriously jeopardize implantation. This immunologic implantation dysfunction (IID) is diagnosed by testing the woman’s blood for APA, for NKa (using the K-562 target cell test or by endometrial biopsy for cytokine activity) and, for CTL (by a blood immunophenotype). Activated NK cells attack the invading trophoblast cells (developing “root system” of the embryo/early conceptus) as soon as it tries to gain attachment to the uterine wall. In most cases, this results in rejection of the embryo even before the pregnancy is diagnosed and sometimes, in a chemical pregnancy or an early miscarriage. As such, many women with endometriosis, rather than being infertile, in the strict sense of the word, often actually experience repeated undetected “mini-miscarriages”.
Women who harbor APA’s often experience improved IVF birth rates when heparinoids (Clexane/Lovenox) are administered from the onset of ovarian stimulation with gonadotropins until the 10th week of pregnancy. NKa is treated with a combination of Intralipid (IL) and steroid therapy: Intralipid (IL) is a solution of small lipid droplets suspended in water. When administered intravenously, IL provides essential fatty acids, linoleic acid (LA), an omega-6 fatty acid, alpha-linolenic acid (ALA), an omega-3 fatty acid.IL is made up of 20% soybean oil/fatty acids (comprising linoleic acid, oleic acid, palmitic acid, linolenic acid and stearic acid) , 1.2% egg yolk phospholipids (1.2%), glycerin (2.25%) and water (76.5%).IL exerts a modulating effect on certain immune cellular mechanisms largely by down-regulating NKa.
The therapeutic effect of IL/steroid therapy is likely due to an ability to suppress pro-inflammatory cellular (Type-1) cytokines such as interferon gamma and TNF-alpha. IL/steroids down-regulates NKa within 2-3 weeks of treatment the vast majority of women experiencing immunologic implantation dysfunction. In this regard IL is just as effective as Intravenous Gamma globulin (IVIg) but at a fraction of the cost and with a far lower incidence of side-effects. Its effect lasts for 4-9 weeks when administered in early pregnancy.
The toxic pelvic environment caused by endometriosis, profoundly reduces natural fertilization potential. As a result normally ovulating infertile women with endometriosis and patent Fallopian tubes are much less likely to conceive naturally, or by using fertility agents alone (with or without intrauterine (IUI) insemination. The only effective way to bypass this adverse pelvic environment is through IVF. I am not suggesting here that all women who have endometriosis require IVF! Rather, I am saying that in cases where the condition is further compromised by an IID associated with NKa and/or for older women(over 35y) who have diminished ovarian reserve (DOR) where time is of the essence, it is my opinion that IVF is the treatment of choice.
I strongly recommend that you visit http://www.SherIVF.com . Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.
•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
•How Many Embryos should be transferred: A Critical Decision in IVF?
•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-IUI) and Reproductive Surgery Versus IVF
•Treating Ovarian Endometriomas with Sclerotherapy.
•Effect of Advanced Endometriosis with Endometriotic cysts (Endometriomas) on IVF Outcome & Treatment Options.
•Deciding Between Intrauterine Insemination (IUI) and In Vitro Fertilization (IVF).
•Intrauterine Insemination (IUI): Who Needs it & who Does Not: Pro’s &
•Induction of Ovulation with Clomiphene Citrate: Mode of Action, Indications, Benefits, Limitations and Contraindications for its use
•Clomiphene Induction of Ovulation: Its Use and Misuse!
______________________________________________________
ADDENDUM: PLEASE READ!!
INTRODUCING SHER FERTILITY SOLUTIONS (SFS)
Founded in April 2019, Sher Fertility Solutions (SFS) offers online (Skype/FaceTime) consultations to patients from > 40 different countries. All consultations are followed by a detailed written report presenting my personal recommendations for treatment of what often constitute complex Reproductive Issues.
Patients are encouraged to share the information I provide, with their treating Physicians and/or to avail themselves of my personal hands-on services, provided through batched IVF cycles that I conduct every 3 months at Los Angeles IVF (LAIVF) Clinic, Century City, Los Angeles, CA.
If you wish to schedule an online consultation with me, please contact my assistant (Patti Converse) by phone (800-780-7437/702-533-2691), email (concierge@SherIVF.com) or, enroll online on then home-page of my website (www.SherIVF.com).
PLEASE SPREAD THE WORD ABOUT SFS!
Geoff Sher
Good evening Doctor,
I am 40 years old with 3 health boys. I was pregnant at the beginning of the year and lost the baby at 20weeks. I went in for ultrasound and their was no heart beat. I had the blood test done at 10 weeks that checks for the trisomy defects and the test came back “extra X chromosome indeterminate” . The baby was take out. I am now approximately 6 weeks pregnant. Hcg and progesterone levels are good. What’s the chance of that happening agin with this pregnancy?
Of course it could happen again but it is unlikely!
Good luck!
Geoff Sher
Can you explain why you feel PGS screening should be used in cases have alloimmune implantation dysfunction (IID) with activation of uterine natural killer cells is an issue? I am 38, with high nk cells found in endometrial biopsy and considering options for my upcoming ivf cycle.
The presence of alloimmune implantation dysfunction partial DQ alpha match + NKa+)reduces the chance of one embryo propagating a viable pregnancy, by about one half. When it comes to a woman without an alloimmune, immunologic implantation dysfunction (IID), the chance of a single embryo transfered propagating a viable pregnancy would be about about 25% while for women with a partial DQ alpha match + NK cell activation, the comparable chance of a baby would have been about 12.5%. These rates are dependent upon appropriate treatment using selective immunotherapy with Intralipid and steroids.
Using these same two examples, had the embryos been found through PGS testing to euplolid, the the chance of a baby would have been double (50% and 25% respectively).
Natural conception rates are significantly lower, with or without the use of fertility drugs and/or IUI.
Given that at 38y of age the chance of an untested blastocyst being euploid is at best 30%, it follows that the performance of IVF (provided it is combined with PGS testing) significantly enhances overall pregnancy potential. And given the inevitability of a natural decline in egg/embryo “competency” with advancing age and declining ovarian reserve, you might not have the luxury of safely considering non-IVF alternatives.
Central to making a diagnosis of an immunologic implantation dysfunction (IID) is a need for the appropriate interpretation of Natural Killer Cell Activity (NKa). In this regard, one of the commonest and most serious errors, is interpret the blood concentration of natural killer cells as being relevant. Rather it is the activity (toxicity) of NK cells that matters as mentioned. This activity can best be measured using the blood, K-562 target cell test (the gold standard). and/ or endometrial biopsy for cytokine activity.
With the K-562 test, the most important consideration is the percentage of target cells “killed” in the “native state”. In most cases a level of >10% killing should be regarded with suspicion and >12% overtly abnormal. In addition to reporting the result of the K-562 test, in the “native state” (without adding, Immunoglobulin-G (IVIG) or Intralipid (IL) which many Laboratories erroneously do to try and determine whether either or both of these immune therapies would have a therapeutic benefit or is/are unlikely to be of clinical value. The entire premise upon which this assertion is based, is in my opinion flawed. Clinically such NK cell deactivation can only be significantly affected in vivo as it takes more than a week following infusion to occur. Thus, what happens to the percentage of target cells killed with the K-562 test, by adding IVIG or IL is in my opinion irrelevant
Another way to assess endometrial NKa is by measuring TH-1 and TH-2 cytokines in endometrial tissue derived through biopsy.TH-1 cytokines kill the trophoblast (the root system of the embryo). Thus if is an excess of TH-1 cytokine activity is found with/without a disruption in the TH-1: TH-2 ratio, this points to NK cell activation.
There are basically two causes of immunologic implantation dysfunction (IID), a) Autoimmune (85%) & , b) Alloimmune (15%). The former occurs when the body reacts to its own tissue and the latter (far less common) when the male and female partners share certain genotypic similarities involving DQ alpha and HLA genes. In both cases IID results in rejection of the pregnancy due to uterine Natural Killer (NK) Cell and T-cell activation leading to the release of an excessive amount of TH-1 cytokines. These, “toxins” attack the embryo’s root system (trophoblast), killing the cells and causing implantation to fail.
Autoimmune Implantation Dysfunction: Autoimmune implantation dysfunction, most commonly presents with presumed “infertility” due to such early pregnancy losses that the woman did not even know she was pregnant in the first place. Sometimes there as an early miscarriage. Tests required are: a) blood levels of all IgA, IgG and IgM-related antiphospholipid antibodies (APA’s) directed against six or seven specific phospholipids, b) both antithyroid antibodies (antithyroid and antimicrosomal antibodies), c) a comprehensive reproductive immunophenotype (RIP) and, c) most importantly, assessment of Natural Killer (NK) cell activity (rather than concentration) by measuring by their killing, using the K-562 target cell test and/or endometrial cytokine activity tests.
It is important to recognize that currently there are only about 3 or 4 Reproductive Immunology Reference Laboratories in the U.S.A that, are capable of reliably analyzing the required elements with a sufficient degree of sensitivity and specificity. I use a Reprosource, a laboratory located in Boston,MA.
Patients with Alloimmune implantation Dysfunction usually present with a history of unexplained (usually repeated) miscarriages or secondary infertility (where the woman conceived initially and thereupon was either unable to conceive again or started having repeated early miscarriages. However, it can also present as “presumed” primary infertility. Alloimmune dysfunction is diagnosed by testing the blood of both the male and female partners for matching DQ alpha genes and NK/CTL activation. It is important to note that any DQ alpha match (partial or complete) will only result in an IID when there both a DQa/HLA match exists along with NK cell activation. With the exception of cases where both partners have a total (absolute DQa match and treatment requires the use of sperm from a non-matching sperm donor, about 90% of cases alloimmune implantation will have a partial match where 1: 2 embryos will match the woman’s DQa genotype and half will not. In cases of an alloimmune dysfunction (with associated NKa), treatment with IL or IVIG will in my opinion, will not protect against a matching embryo being rejected. It can only clear the NK environment for an embryo that does not match the woman’s DQa genotype. For this reason, it is my opinion that only 1 embryo should be transferred at a time because, given the fact that i:2 embryos will match, transferring >1 embryo at a time creates a risk that the matching embryo will evoke a local NKa/’cytokine response that will “muddy the water” for both. Thus, in cases of a “partial” DQa match I recommend against transferring more than a single embryo at a time.
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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.
•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) Why did my IVF Fail
•Recurrent Pregnancy Loss (RPL): Why do I keep losing my Pregnancies
•Genetically Testing Embryos for IVF
•Staggered IVF
•Staggered IVF with PGS- Selection of “Competent” Embryos Greatly Enhances the Utility & Efficiency of IVF.
•Embryo Banking/Stockpiling: Slows the “Biological Clock” and offers a Selective Alternative to IVF-Egg Donation
•Preimplantation Genetic Testing (PGS) in IVF: It should be Used Selectively and NOT be Routine.
•IVF: Selecting the Best Quality Embryos to Transfer
•Preimplantation Genetic Sampling (PGS) Using: Next Generation Gene Sequencing (NGS): Method of Choice.
•PGS in IVF: Are Some Chromosomally abnormal Embryos Capable of Resulting in Normal Babies and Being Wrongly Discarded?
•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!
•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
______________________________________________________
ADDENDUM: PLEASE READ!!
INTRODUCING SHER FERTILITY SOLUTIONS (SFS)
Founded in April 2019, Sher Fertility Solutions (SFS) offers online (Skype/FaceTime) consultations to patients from > 40 different countries. All consultations are followed by a detailed written report presenting my personal recommendations for treatment of what often constitute complex Reproductive Issues.
If you wish to schedule an online consultation with me, please contact my assistant (Patti Converse) by phone (800-780-7437/702-533-2691), email (concierge@SherIVF.com) or, enroll online on then home-page of my website (www.SherIVF.com).
PLEASE SPREAD THE WORD ABOUT SFS!
Geoff Sher
.
I hope this helps.
If you are still unclea
What is the best kind of needle to use for flushing each follicle when doing a retrieval? I have done several ivf cycles and at this clinic I am at now two different doctors have had problems during the retrieval. I know it’s not empty follicles syndrome because I am using the a/acp and that doesn’t happen on this protocol for me and no other doctor have had this issue. I have read that a double lumen needle is best. Is true?
I do not use double lumen needles!
Good luck!
Geoff Sher
My hcg was 8,800 at 5+3 days. My only symptom so far is a missed period and sore breasts. I have had some mild cramping. Does this appear to be a healthy viable pregnancy?
Very promising!
Geoff Sher