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,
My husband and I have a complete DQ alpha match (and I have auto-immune issues). After several losses, we are now planning to use a gestational surrogate but wanted to get her DQ alpha profile checked first. My husband is homozygous 1.2; 1.2 (I am 3.1; 1.2). Our surrogate’s profile has come back as 0201 and 0302, so that’s 2.1 and 3.2. Is the 2.1 a match to my husband’s 1.2? (I’m not sure if a match can be caused where the numbers are reversed, if you see what I mean). And if so, would this be an issue? I think we can assume she doesn’t have activated NK cells given that she has had 2 of her own children in the last 3 years, the youngest being 18 months old. I would be so grateful to know your view on this. With many thanks for your help and kindest regards.
No Match with GS. However, if you do not have NKa, then at this time the match between you and your husband is not relevant.
Geoff Sher
Dear Dr. Sher,
first of all thanks for all the support you give to so many people all over the world. I enjoy your articles very much.
My wife and me have 2 naturally conceived boys which are now 11 and 14. Since 2 years we tried for another baby and since once year through IVF. We used PGS and transferred only one embryo per time, as my wife is quite small and we wanted to minimize the risk of multiples.
All 3 FET though came back negative.
The last embryo transfer was 3 weeks ago. As it came again negative, my wife was tested for Killerzells etc, 1 week ago, the results below;
how would you interprete those results by a lab in Chicago (we live in Panama) ?
am i an candidate for Intralipid ?
NK %CD56 14,6(H) 2,0-12,0
NK %CD19+cells,CD5+ 3,0(L) 5,0-10,0
TH1/TH2 Intercellular Cytokine Ratios
TNF-a:IL-10(CD3+CD4+) 43,0 (H) 13,2-30,6
IFN-g:IL-10(CD3+CD4+) 24,8(H) 5,8-20,5
ANA w/Reflex if Positiv
ANA Screen POSITIV
ANA Pattern NUCLEOLAR
ANA Titer 1:80
best regards
Diana & Pino
Based on your endometrial cytokines alone, you clearly have activated NK cells. The NK assay done is in my opinion not the correct test and can not be considered here! You would require the K-562 target cell test (not measurement of NK cell concentration in the blood).
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.
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)
•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!
If you are interested in seeking my advice or services, I urge you to contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com You can also apply online at http://www.SherIVF.com .
*FYI
The 4th edition of my newest book ,”In Vitro Fertilization, the ART of Making Babies” is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.
Geoffrey Sher MD
Hello Dr Sher,
We have decided on surrogacy as we both share a 100% DQ alpha gene. I have found a surrogate and have had her DQ alpha tested and her results have come back with a 100% match to us! Do I start looking for a new surrogate? I don’t want to waste my precious embryos.
Firstly, bear in mind that the negative effect of NK cell activity is only relevant if in addition you have NK cell activation as measured by the K-562 target cell blood test. If there is no NKa, then you can conceive as easily as if you did not have a match and thus would NOT require a GS.
Good luck!
Geoff Sher
I did my ivf egg transfer (5day frozen) 5/14/18, we transferred 2 eggs. 5/24/18 my hcg was 107. 5/29/18 my hcg was 801. What does this mean?
This bodes well for a successful IVF and possibly even a twin pregnancy.
Good luck!
Geoff Sher
I was on Estrace for 3 weeks then my FET got canceled. I never started the Progesterone shots. Approximately how long does it take for withdrawal bleeding and period to begin after Estrace only?
It has been 5 days and no sign of withdrawal bleeding.
Is it best to wait until you bleed on your own or take Progesterone or something else to force it? My doctor wants me to have the withdrawal bleed naturally then wait until my next period to start a new FET.
I am worried my cycle is stuck in limbo since my follicles were shut down by the Estrace. I don’t want to wait too long for my natural withdrawal bleed but also want my cycle to be optimal for the FET when my period starts.
Thank you for your help!
You should blewed within 10-14 days of stopping the Estrace.
Good luck!
Geoff Sher