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.
I would like to ask your opinion . I only have 1 chance at being a mom. I had 1 embryo make it to blast. She is a 4AA, and we sent for genetic testing. Unfortunately she came back abnormal -5qter. I’ve seen many come back with several additions or deletions. Again this is my only chance, what do you think about transferring it? It’s day 7 blast, 4AA, could sge autocorrect? Could it be wrong ?
Sadly Ashley,
Day 7 blastocysts are highly unlikely to propagate viable pregnancies, in my opinion.
Geoff Sher
Good afternoon,
I hope you might be able to give me some information. I have had an endometrioma (about 3 cm across in size) for at least the past 2 years. Following a late miscarriage, I was found to have elevated anticardiolipin (tested twice, 3 months apart). I have read that over half of patients with endometriosis also had elevated anti phospholipids. My question is the following: would removing the endometrioma bring back anticardiolipin levels in the normal range or are the anticardiolipin the reason why I might have an endometrioma? I am reluctant to try to conceive again with anticardiolipin in my blood.
Many thanks
You do need the endometrioma removed but doing so would NOT affect your immunologic status one way or the other.
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.
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
This is an edit of my previous question….it was my cd19 cells that were high not cd25.
I had stage 3 endometriosis removed by laparoscopy in October 2020 and did donor egg IVF in December and transferred two grade 1 embryos. I had strong positive hpts the second week after transfer then hcg plateaued at 5 weeks and I miscarried around the 6 week mark. I had Chicago bloods done and they showed normal levels of NKC and cytokines. The only thing that was abnormal was cd25. I am planning to transfer two more grade 2 embryos and I plan to take IVIG and steroids. My question is due to my history of endometriosis would you recommend Humira also even though my cytokines were in the normal range?
You are on the right track and no…I do not prescribe Hmira.
Unless tests for immunologic implantation dysfunction (IID) are performed correctly and conducted by a one of the few reliable reproductive immunology reference laboratory in the United States, treatment will likely be unsuccessful. . In this regard it is most important that the right tests be ordered and that these be performed by a competent laboratory. There are in my opinion only a handful of reliable Reproductive Immunology Laboratories in the world and most are in the U.S.A. Also, it is my opinion that far too often, testing is inappropriate with the many redundant and incorrect tests being requested from and conducted by suboptimal laboratories. Finally for treatment to have the best chance of being successful, it is vital that the underlying type of IID (autoimmune IID versus alloimmune) be identified correctly and that the type, dosage, concentration and timing of treatments be carefully devised and implemented. I recommend that my patients be tested by ReproSource Reproductive Immunology Reference Laboratory, Boston, MA.
WHO SHOULD UNDERGO IID TESTING?
When it comes to who should be evaluated, the following conditions should in always raise a suspicion of an underlying IID, and trigger prompt testing:
•A diagnosis of endometriosis or the existence of symptoms suggestive of endometriosis (heavy/painful menstruation and pain with ovulation or with deep penetration during intercourse) I would however emphasize that a definitive diagnosis of endometriosis requires visualization of the lesions at laparoscopy or laparotomy)
•A personal or family history of autoimmune disease such as hyper/hypothyroidism (as those with elevated or depressed TSH blood levels, regardless of thyroid hormonal dysfunction), Lupus erythematosus, Rheumatoid arthritis, dermatomyositis, scleroderma etc.)
•“Unexplained” infertility
•Recurrent pregnancy loss (RPL)
•A history of having miscarried a conceptus that, upon testing of products of conception, was found to have a normal numerical chromosomal configuration (euploid).
•Unexplained IVF failure
• “Unexplained” intrauterine growth retardation due to placental insufficiency or late pregnancy loss of a chromosomally normal baby
What Parameters should be tested?
In my opinion, too many Reproductive Immunologists unnecessarily unload a barrage of costly IID tests on unsuspecting patients. In most cases the initial test should be for NK cell activation, and only if this is positive, is it necessary to expand the testing.
The parameters that require measurement include:
oFor 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 uterine cytokine measurement. As far as the ideal environment for performing such tests, it is important to recognize that currently there are only about 5 or 6, Reproductive Immunology Reference Laboratories in the U.S capable of reliably analyzing the required elements with a sufficient degree of sensitivity and specificity (in my opinion).
oFor Alloimmune implantation Dysfunction: While alloimmune Implantation usually presents with a history of unexplained (usually repeated) miscarriages or secondary infertility (where the woman conceived initially and thereupon was either unable to conceive started having repeated miscarriages 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 IID when there is concomitant NK/CTL activation (see elsewhere on this blog).
How should results be interpreted?
Central to making a diagnosis of an immunologic implantation dysfunction is the appropriate interpretation of natural killer cell activity (NKa) .In this regard, one of the commonest and most serious errors, is to regard the blood concentration of natural killer cells as being significant. Rather it is the activity (toxicity) of NK cells that matters as mentioned. Then there is the interpretation of reported results. 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 my opinion, trying to interpret the effect of adding IVIG or Intralipid to the sample in order assess whether and to what degree the use of these products would have a therapeutic benefit is seriously flawed and of little benefit. Clinically relevant NK cell deactivation can only be significantly effected in vivo and takes more than a week following infusion to occur. Thus what happens in the laboratory by adding these products to the sample prior to K-562 target cell testing is in my opinion likely irrelevant.
There exists a pervasive but blatant misconception on the part of many, that the addition of Intralipid (IL) /immunoglobulin-G IVIG) can have an immediate down-regulatory effect on NK cell activity. This has established a demand that Reproductive Immunology Reference Laboratories report on NK cell activity before and following exposure to IVIG and/or IL. However, the fact is that activated “functional” NK cells (NKa) cannot be deactivated in the laboratory. Effective down-regulation of activated NK cells can only be adequately accomplished if their activated “progenitor/parental” NK cells are first down-regulated. Thereupon once these down-regulated “precursor” NK cells are exposed to progesterone, they will begin spawning normal and functional NK cells, which takes about 10-14 days. It follows that to assess for a therapeutic response to IVIG/IL therapy would require that the patient first be treated (10-14 days prior to embryo transfer) and thereupon, about 2 weeks later, be retested. While at 1st glance this might seem to be a reasonable approach, in reality it would be of little clinical benefit because even if blood were to be drawn 10 -14 days after IL/IVIG treatment it would require an additional 10 days to receive results from the laboratory, by which time it would be far too late to be of practical advantage.
Neither IVIG nor IL is capable of significantly suppressing already activated “functional NK cells”. For this to happen, the IL/IVIG would have to down-regulate progenitor (parent) NK cell” activity. Thus, it should be infused 10-14 several prior to ovulation or progesterone administration so that the down-regulated “progenitor/precursor” NK cells” can propagate a sufficient number of normally regulated “functional NK cell” to be present at the implantation site 7 days later. In addition, to be effective, IL/IVIG therapy needs to be combined with steroid (dexamethasone/prednisone/prednisolone) therapy to down-regulates (often) concomitantly activated T-cells.
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 PregnanciesGenetically 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
Hello,
I had my IUI procedure on 01/10 so my doctor is certain about my dates. My hcg levels were:
4w1d: 98
4w3d: 212
5w3d: 3,227
6w3d: 13,404
6w5d: I had my first ultrasound and she saw a gestational sac and yolk sac but didn’t hear a heartbeat. She said I was measuring behind and was unable to get an accurate crown to rump length.
She wants me to return for another ultrasound in 12 days but does not seem hopeful this is a viable pregnancy. Is there any chance for this pregnancy?
It might just have been missed. Repeat the US in 1 week!
Good luck!
Geoff Sher