Loading ...
Welcome to IVF Authority - World Renowned Resource for IVF Information
DQ-alpha Matching in IVF: The Controversy, How It Affects Outcome, & How to Treat!
Dr. Geoffrey Sher Recommends- Blastocyst Transfer: The Preferred Approach!
- Egg Quality and Ovarian Reserve: The Effect of FSH and Inhibin Blood Levels
Loading ...
Phone:
702-892-9696
Fax:
702-892-9666
702-892-9696
Fax:
702-892-9666
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 offer no other alternative plausible explanation. It is largely through the initiative and insistence and persistence of such vocal patients that the veil over the entire issue of immunologic implantation dysfunction has started to lift and has resulted in rapidly growing scientific interest in and attention being paid to the role of selective immunotherapy in IVF.
There are two (2) forms of immunologic implantation dysfunction. The first and by far the most common is autoimmune implantation dysfunction. This variety is usually easily and successfully remedied through treatment with heparinoids (e.g., Lovenox, Clexane), Intralipid (IL), and corticosteroids. The second variety which is often ignored or overlooked is alloimmune implantation dysfunction.
Autoimmune implantation dysfunction is by far the most common variety. It is believed to be implicated in >90% of cases of immunologic implantation dysfunction and occurs when an immunologic reaction is produced by the individual, to his/her body’s own cellular components. Aloimmune implantation dysfunction on the other hand, arises through the reaction of the uterus to an embryo that shares certain genetic (genotypic) similarities (DQa and other HLA genes)with the recipient’s uterus causing immune cells known as natural killer (NK) cells that populate the uterine lining, to start over-producing “ toxins” known as TH-1 cytokines (TNFa and Interferon gamma). Such activated NK cells (NKa+) attack the cells of the embryo’s “root system” (the trophoblast) damaging it and so compromising implantation. Alloimmune implantation dysfunction, while far less common than the autoimmune variety is considerably more complex, much more poorly understood (even by most RE’s) and far more difficult to treat successfully. It involves a reaction by an otherwise normal uterus to the intrusion of one or more embryos that through the contribution of sperm DNA share certain immunogenetic (genotypic) similarities with the recipient.
For some reason, there is a tendency to consider all couples with alloimmune implantation dysfunction (who share DQa similarities) to be incapable of achieving a viable full term pregnancy. Nothing could be further from the truth.
Let me explain: Each individual has two (DQa’s), one is derived from their mother and the other from their father. The fact that many individuals carry identical DQa’s (i.e. both are the same), of necessity means their parents must of necessity have had “matching” DQa’s and yet they were born healthy and normal. The reason is that it is not the “matching” DQa that matters. It is whether upon arriving in the uterus, a DQa “matching” embryo encounters activated uterine natural killer cells (NKa+). These NKa+ release large amounts of TH-1 cytokines that attack and damage the cells of the embryo’s “root system” (trophoblast).It is the extent of such trophoblastic damage that will determine whether such an embryo will immediately “die on the vine” (implantation failure) or “limp along” for some time only to be aborted a few weeks later.
It is important to recognize that NK cell activation only occurs after repeated exposures to DQa-”matching” embryos. This explains why a DQa “matching” embryo that reaches the uterus prior to NK cell activation can and often does implant successfully and then go on to propagate a healthy pregnancy. However, with repeated exposures to DQa “matching” embryos, uterine NK cells will ultimately and inevitably become activated. Such NK cell activity will initially often be limited and accordingly TH-cytokine production will wax and wane (in between exposures), allowing .early implantation (albeit with a damaged embryo) to proceed and even proceed for a limited period of time, only to abort in the first trimester. Ultimately, over time following repeated and successive exposures to DQa-“matching” embryos, NK cell activation will become a permanent feature. Once this happens uterine NK cell activation (as measured by the K-562 target cell test) will exacerbate to the point that as soon as the embryo reaches the uterus implantation will be thwarted and the woman will be considered as being “infertile” when in reality she is experiencing a very early, preclinical miscarriage. .
It is important to understand that DQa “matching” refers to a (genotypic) “match” between the male and female partners…rather than a “match” between sperm and egg. An immature sperm contains 23 pairs of chromosomes”…for a total of 46. With maturation division (following meiosis), the immature sperm divides into two mature sperm each of which comprises 23 chromosomes [including only one (1) DQa gene]. Upon fertilization of the egg by such a sperm this single DQa gene is incorporated into the embryo’s genotype. .If that DQa gene “matches” either of the mother’s two (2) DQa’s, then the potential for NK call activation will arise. It follows that if only one (1) of the husband’s two (2) DQa’ genes “matches” either one (1) of the mother’s DQa’ genes, the potential for the resulting embryo to propagate an embryo that containing a DQa gene that “matches” the recipient will be 50%. On the other hand, if both the husband’s DQa’ genes are the same as any one of the mother’s two DQa’s, (or if the mother and father both identical DQa’s genotypes), then 100% of the embryos will “match” and the propensity to activate uterine NK cells will be markedly increased.
What does all this mean when it comes influencing IVF outcome? …….Well, if we are dealing with a 50% chance of embryo DQa “matching” (see above), and we can successfully down-regulate NKa+ through the administration of Intralipid (IL) or immunoglobulin-G (IVIG) in combination with corticosteroids (e.g. prednisone or dexamethasone), then the transfer of a non-“matching” embryo would theoretically provide the same chance of a successful IVF outcome as in the absence of any DQa “matching” between the partners. On the other hand, when the chance of embryo DQa “matching” is 100% (see above) the ability to down-regulate NKa+ with IL or IVIG is diminished as is the likelihood of a successful pregnancy.
What emerges from all this is that not all DQa “matches” are equal. Outcome following IVF treatment (inclusive of IL/IVIG/corticosteroids) is very much influenced by: a) the presence and severity of uterine NK cell activation, b) whether the DQa genotype of both male and female partners “match” absolutely (i.e. both their pairs of their DQa genes “match”), in which case 100% of the embryos will “match” and the prognosis will be poor, c) whether both the male’s DQa genes are identical, in which case, the of a DQa “match” will again be 100% and the chance of a successful IVF outcome will likely be severely diminished.
It is presently not possible to reliably identify the paternal DQa contribution to the embryo. Also, the exposure of DQa “matching” embryos to the uterus will usually activate uterine NK cells. For these reasons, in cases of a 50% risk of a DQa “match”, I usually recommend transferring only one (1) embryo at a time. The reason is my concern that in transferring more than one embryo, uterine exposure to a DQa-“matching” embryo could, by causing local NK cell activation, compromise implantation of a non-“matching” embryo and so, in the process, reduce the likelihood of its successful implantation. In cases of 100% DQa “matching”, this hardly matters since all the embryos would cause NK cell activation anyway.
In truth, when there is a 100% risk of an embryo-DQa “match” between partners (see above) in association with uterine NK cell activation as measured by the K-562 target cell test, the chance of successful pregnancy is very small. In such cases, in my view seeking the help of a gestational surrogate or resorting to the use of donor sperm (ensuring they do not share DQa similarities with the embryo recipient) will in the final analysis become the treatment of choice.
The recent introduction of comparative genomic hybridization (CGH) to identify and select “competent” embryos for transfer can markedly improve the efficiency by which we are able to manage both alloimmune and autoimmune implantation dysfunction.
Lastly; much has been written about the use of endometrial sampling (biopsy) to measure NK cells and cytokine activity. While this is interesting in concept, there is no supportive clinical data to indicate its value in the clinical management of immunologic implantation failure. Presently the K-562 target cell test remains the gold standard for measuring uterine NK cell activity.
41 Responses to “DQ-alpha Matching in IVF: The Controversy, How It Affects Outcome, & How to Treat!”
Leave a Reply
Top Search Terms for In Vitro Fertilization
- Embryo Quality & Embryo “Competence” – Part III – Testing the Seed
- Embryo Quality & Embryo “Competence” – Part One: Planting a Good Seed
- The Needle vs. the Dish: Should ICSI Be Used in All IVF?
- Embryo Implantation: What Farmers Can Teach us About Growing Healthy Babies
- Acupuncture and IVF: Does it Improve Success?
Dr. Geoffrey Sher Recommends
Loading ...
Loading ...
Loading ...
Loading ...
Loading ...
Loading ...
Loading ...
Loading ...
Loading ...
Loading ...
Dr. Geoffrey Sher Recommends
Loading ...
Loading ...
Loading ...
Loading ...
Loading ...
Loading ...
Loading ...
Loading ...
Loading ...
Loading ...
Loading ...
Loading ...
Loading ...
Loading ...
Loading ...
Loading ...
Loading ...
Loading ...
Loading ...
Loading ...
Loading ...
Loading ...
Loading ...
Loading ...
Loading ...
Loading ...
Loading ...
Loading ...
Loading ...
Ask Our DoctorsA Question
I am in the difficult situation of recurrent pregnancy loss (four miscarriages in one year, all arresting by six weeks, no previous pregnancies/children). We have had many tests, including karotyping, and so far there are no answers.
We are now undergoing IVF to have CGH (four blasts are currently being tested, by array-CGH, for a possible future frozen transfer). But I am worried that even if they find a chromosomally "normal" embryo, if we have an undiagnosed underlying immunological issue we will be wasting our time transferring that embryo.
I haven't yet had a NK cell biopsy but my specialist has mentioned it. However having read your website, you recommend the K-562 test rather than endometrial biopsy. I am in Australia and I realise that testing and research varies by country. Could you please you point me to any more information about this test so I can see if it is available here?
I can tell you that it is not available in Australia since I see many patients here iun the U.S from your country.
I suggest you have your blood tested for NKa and that your and your husband's blood be matched for both DQ alpha and HLA similarities. The bloods can be sent to Reproductive Immunology Associates (RIA) in the U.S.A. Call them at 818-648-3551 and they will provide details.
Geoff Sher
Thank you so much for your response, I am getting my doctor to contact the lab and try to arrange tests asap.
Since my previous comment we had a fifth miscarriage after IVF, this time even earlier (failure began before four weeks) so the urgency to sort this out is even greater.
We should talk. Call 702-699-7437 to set it up.
Geoff Sher
My husband and I got pregnant in March 2006 on the first try and had a perfect pregnancy, resulting in our son who is now 3 1/2. We began trying to conceive again in August 2008. We have been through a series of failed IUIs. After taking a break, we became pregnant naturally in March 2010, only to result in a miscarriage at 5 1/2 weeks. We then got pregnant again naturally in May 2010, ending in a miscarriage at 7 weeks. We have been working with the Sher Institute in Bedminster, NJ. We had the immune blood testing done on both my husband and myself, and out of the 3 tests on me, found out that I have elevated natural killer cells (12.3). After reading your blog, I am very unclear as to why I have these elevated NKcells if all of our other blood tests came out normal. From what it sounds like, the NK cells are activated only if the DQalphas are similar, which is not our case. Is it possible to have elevated natural killer cells with nothing else going on? Could I have had these when I got pregnant with my son and, if so, how did I carry that pregancy to term? Thank you for any input you can give us…
Were you and your husband tested for both DQa and HLA similarities. If so what where were the tests done ande what were the exact results?
Since no one is born with NK activation…it is possible that you developed NKa activity over time.
Geoff Sher
Hi there
I just changed clinics and went through immunological testing (NK assay, APA, Th1/Th2 cytokine ratio). All was negative. I had one prior IVF failure, and a canceled cycle prior to that. Despite all being negative, and having no history of anything autoimmune, my RE is recommending that I still have the intralipid treatment. I'm confused. I already paid out of pocket for all these tests as I have no insurance and now I'll have to pay for a treatment that these tests say I don't need. Is there another reason for using intralipids?
Have you had DQa/HLA matching done with your hubby. AND was the NK assay that was done the K-562 target cell test? Remember that the concentration of NK cells is not important here…uit is the K-562 test that matters.
If you have no DQa/HLA matching and the NKa 9K-5620was <10% in all dilutions, then I personally, would not have recommended IL.
Geoff Sher
Dear Dr. Sher-
I am a healthy 33 year old woman who has been trying to conceive for close to a year. In that time, I have had 3 early losses, all before 7 weeks. Two of these losses were on natural cycles, and the last one was on my first round of Clomid. Prior to Clomid I went to an RE and had a recurrent m/c panel, endometrial biopsy, hysteroscopy, and sonohystogram. My husband and I were both karyotyped as well. Everything came back normal and my RE recommended Clomid because my cycles average more than 5 weeks with a shorter luteal phase (10 days). I am meeting with him next week to discuss next steps. Should I request more immunological testing be completed? I do know APA was done but I am not sure what else.
I appreciate your input….Heather
You should have a full alloimmune and autoimmune assessment with hubby. The tests needed can be obtained by calling Linda Danner RN at 800-780-7437. Tell her I asked for her to asist.
Good luck!
Geoff Sher
Hi Dr Sher
I am in New Zealand and don't think many of these tests are available here. I had a child 5 years ago followed by a blighted ovum, another child born at 33.5 weeks, 3 blighted ovums, a 17 week loss due to a subchorionic hematoma, 4 blighted ovums and have just had a 12 week miscarriage, appearing normal except for a gestational sac measuring a week behind the fetus. Can this happen with alloimmune disorders? As far as I'm aware IVIg is not available here, what are my chances to have another child with heparin and steroid treatment? Thanks.
Indeed aloimmune implantation dysfunction can be the cause of this. You do not have to live in the U.S A to get the tests done here. You could (as so many do), send your blood here for testing.
Geoff Sher
Thank you for your reply. If I did send my blood over for testing and it turns out to be a match (1 gene in common I would assume) what would my next step be? Would I have any chance of having another child?
e would need to talk. Please call 800-780-7437 and set up a consultation by phone (free).
Geoff Sher
Dr. Sher, I'm wondering if this situation applies to me. I had 2 miscarriages, followed by a successful pregnancy, and then 6 more miscarriages.
Then we switched to DE, and I lost the pregnancy from the fresh cycle. I'm now in a FET cycle, pregnant again, but betas are very low.
Which tests should my RE do?
Indeed! This is totally compatable with an allimmune problem. I suggest you call 800-78700-780-7437 and set up a free medical telephone consultation with me to discuss.
Geoff Sher
Hi Dr. Sher,
I'm curious as well if this could be our issue. My husband and I are both 33. We have never been pregnant naturally and have been trying for over 4 years. 5 failed IUI's with clomid/hcg.
IVF#1 long lupron; transfered 1-8cell top grade and 1 6-cell good grade, failed.
IVF#2 long lupron; transfered 1-8cell top grade and 1-8cell good grade, blighted ovum.
IVF#3 cancelled (microdose lupron poor response) and converted to IUI; chemical pregnancy.
IVF#4 long lupron; transferred 1-10cell top grade and 2-8cell top grade with assisted hatching; chemical pregnancy detected between 6dp3dt-8dp3dt.
Could this issue of transferring perfect 3day embroys be related to an alloimmune problem? We have never had enough embryos to make it to a 5d transfer as I have not stimmed well even though I have excellent FSH (4-5) and low normal antral follicle counts.
I agree!. Might I suggest that you call 800-780-7437 to set up a free medical telephone consultation with me to discuss in detail.
Geoff Sher
Hello Dr Sher,
I am as well in this unfortunate situation of recurrent miscarriages.
We had two natural achieved pregnancies in 2008 and 2009, first one – miscarried at 5 and 1/2 weeks and second one – ectopic pregnancy misdiagnosed at 6 weeks and ruptured at 8 weeks so I have lost my right Fallopian tube.
During the surgery for ectopic pregnancy I have been diagnosed with endometriosis and we moved directly to IVF treatment.
natural IVF #1 – a grade one embryo transferred but chemical pregnancy
natural IVF #2 – another grade one transferred, no pregnancy.
We live in The Netherlands and clinics in Europe are not very willing to check immune issues.
What would you recommand to us?
Thank you,
AdaByron
Dear Dr.Sher,
I have experienced recurrent pregnancy loss from 2009. I have lupus ,cytokines ,NK cells and some blood clotting disorders. I have gone through many IVF cycles. Firt IVF – 1 embryo transferred, it split into 2 embies in 6 weeks, lost both of them in 9 weeks after seeing the heartbeats ( due to allergic reaction caused by high cytokines/NK cells). Second cycle FET( frozen embryo transfer) 1 embryo transferred , failed due to thin lining. Third cycle simulated FET, 2 embryos transferred lost both of them in 6 weeks( hcg tend to rise for first few weeks and then declined). All this time I was not aware of having cytokines and NK cells. Then mid last year I met a reproductive immunologists, she identified all my autoimmune issues, we charted out a plan with IVIG and prednisone,went ahead with
fourth cycle -fresh IVF 2 embryos transferred ,1st HCG borderline positive, then increased during the second test from third HCG test, it started to decline and ended up in a chemical pregnancy. We went ahead with DQAlpha HLA test. My gene combination is 0102 0105 and my husband's 0102 0103. My immunologist was not too concerned with the DQAlpha test since its not 0501 gene type which is mainly responsible for miscarriage, the explanation she provided for chemical pregnancy would have been due to my sudden drop in estrogen levels inspite of being on estrogen patches. Also, I am taking plaquenil for lupus. She said that could have made my follicles shrink and stop producing estrogen. For the next cycle, she asked me to stop the med before embryo transfer until she ask me to start it back. (Note : All embryos transferred until now in each cycle were graded as the best quality embryos. Also, I got allergic reaction from the brand of estraderm patches that I used my cycle. Rashes in the spot where I applied the patches…not sure if that has do anything with estrogen levels dropping). Does the gene match I mentioned above reveal 50% match between me and my husband? what do they mean by DQALPHA 4.1 match? Do we have to transfer only one embryo then? Please let me know.
Thanks.
Dear Dr. Sher,
I am 39 years old went through 1 IVF cycle and transfered three ovums. 2 implanted but resulted in blighted ovums. Is there any testing that you recommend for my RE to do before moving on to the next IVF Cycle?
I have an autoimmune disease called inner ear auto immune disease that attached my right ear in 2006. I also have had elevated prolactin levels previously.
What can be done to prevent the blighted ovums from reoccuring? Do you recommend the Progesterone in Oil (PIO) versus the Crinone?
i must first bless you for you are not one of these ivf docs which behaves as if there is nothing like reccurent failure but only hard luck. i am a md myself and have put my diagnosis myself after 13 misses (with your help)and have done my Hla dq alpha myself. i have 50 percent share with my husband. my question is; i am planning a last ivf next month (as i cannot make hla dq test to a blastocyst) i found a center to make endometrial coculture. i am planing to have transferred only one blastocyst which have succeced to survive in my endometrial cells. i know 5 days is very short but may this make a sense in your opinion?
My wife and I have 7 matches on the DQ Alpha Test. We have had 3 miscarrigages, all at 7 weeks. Should we maybe consider a suurrogate or using someone elses egg or sperm. We have not been able to get pregnant for 3 years as my wifes system is killing my sperm before it gets to her egg.
You are needless to say referring to HLA matches because there can only be 2 DQa matches.
Please do not rush into any decision without us first talking.
Please go to http://www.IVFauthority.com and when you get to the home page find the “search bar” in the right hand column. Type in the following subjects into the bar and it will take you to all the relevant articles I posted there.
1. “Recurrent Pregnancy loss”
2. “Gestational Surrogacy ”
3. “Immunologic Implantation Dysfunction” (posted on May, 10th and on May 16th respectively.
4. “IVF success: Factors that influence outcome”
5. “Traveling for IVF from Out of State/Country– The Process at SIRM-Las Vegas” (posted on March, 21st 2012)
6. “A stepwise approach to IVF at SIRM” (posted March,9th, 2012)
7. “Staggered IVF”
8. “Gestational Surrogacy with St-IVF”
Consider calling 800-780-7437 or 702-699-7437 to set up a telephone consultation with me (which is free if you reside in the U.S.A or in Canada) so we might discuss your case in detail.
Geoff Sher
DR Sher my DQ Alpha is 0301,0505 my husbands is 0401,0501. Do we have a match?
Dr. Sher
I’m currently a SIRM patient.
We have 5 frozen embryos (grade 1s and 2s) and are trying to make a difficult decision. We have one more chance at parenthood, either doing another FET (our 3rd IVF attempt) or moving along to a GC, my sister, who volunteered to carry for us.
Our first fresh cycle we transferred 2 (intralipids & dexamethasone) and ended in a chemical pregnancy, and our second cycle was frozen where we again transferred 2 (doubled the intralipids & continued .75 dex), which did not result in a pregnancy.
I came back positive in the k562 target cell test for NKa but negative for APA. We never did CGH testing on our frozen embryos. We also never tested for DQalpha matching. I need your advice, we strongly believe in our hearts GC is the way to go with our frozen embryos that we already have. We’re torn with making a decision, we can’t afford to do another fresh cycle & CGH testing when we already have 5 grade 1 and 2 embryos and a healthy, willing surrogate which we’re comfortable with. What should we do? Another FET but test for DQ? And if it comes back partial or 100% match, then whats the future for our 5 embryos on ice? Thank you, Mary Roberts
Given this information and being your last try, a GC is of course the safest bet. However, I do suggest that you test your and hubby’s DQa/HLA because if there is any match, it makes the decision (in yourpecific case) even easier..
Good luck!
Geoff Sher
are repeated exposures to DQa-”matching” embryos the only cause of NK cell activation???
No! There is a autoimmune causes of NK cell activation. In fact they are X 4 as common. Please go to http://www.IVFauthority.com and when you get to the home page find the “search bar” in the right hand column. Type in “Immunologic Implantation Dysfunction” (posted on May, 10th and on May 16th respectively), click on it and it will take you to all the relevant articles I posted there.
Feel free to call 800-780-7437 or 702-699-7437 to set up a web-based video conference or a telephone consultation with me (which is free if you reside in the U.S.A or in Canada) so we might discuss your case in detail.
Geoff Sher
Dr Sher,
Please help me!
I am 32 and DH is 30. He has low counts/motility/morphology but his dna fragmentation is normal.
I had a pregnancy when i was 20 and at college with the wrong partner and had a termination at 9 weeks (it haunts me every day).
We have been ttc for over 3 years and have had 2 failed iui’s, 2 failed icsi’s, 2 failed fet’s and on our last (3rd) icsi cycle we got pregnant and bhcg numbers doubled every 30 hrs aprox between 4-5 weeks and then i had a miscarriage at 6 weeks.
In all my 3 fresh ivf cycles we had 24,23 & 18 eggs and always had good fertilization rate and excellent quality embryos at day 3 but the embryos never reached blastocyst stage by day 5 but were close and were good quality blast by day 6. Only ever had 2-3 blasts by day 6.
Do u think it could be a sperm issue that is causing the embryos to slow down after day 3 or could i just have slower embryos to reach blasto.
Do u think we could have an immune problem even though i had a pregnancy when i was 20. is it possible to develop immune problems over time or could it just be that my new partner and i are not compatible which is causing NK cells to attach my embryos?
I am getting immune testing done in a few weeks but i am worried that maybe it is the a sperm problem causing aneuploid embryos but i hope this is not the case. Should i take refudge in the fact that we seemed to have good quality embryos, if it was a sperm issue would my embryos make it to blast?
Sorry for long post but just wanted to explain my situation.
Really would appreciate ur advice xx
I really think you should first talk with me before going further. I also suggest that you defer t6he immune testing until then. I think I might be able to shed some light and help you in your plight to have a baby.You might consider calling 800-780-7437 or 702-699-7437 to arrange a video conference (or Skype) consultation (free of charge to those who reside in the United States or Canada). If need be, someone from SIRM-Patient Relations can contact you in advance of the consultation and assist you in setting this up through your computer. Such audiovisual interaction it is much more personable than a discussion by telephone. However, if you prefer the latter, this too can be arranged.
Might I recommend that you go to the home page on this site, find a “search bar” in the upper right hand column and type in the following subjects into the bar and it will take you to all the relevant articles I posted there.
“An Individualized Approach to Ovarian stimulation” (posted on November 22nd, 2010)
“Ovarian Stimulation in IVF: Why is it important to down-regulate LH?”
“Agonist/Antagonist Conversion Protocol”
“Immunologic Implantation Dysfunction” (posted on May, 10th and on May 16th respectively.
“Embryo Implantation………” (Part-1 and Part- 2—-Posted August 2012)
“Traveling for IVF from Out of State/Country– The Process at SIRM-Las Vegas” (posted on March, 21st 2012)
“A personalized, stepwise approach to IVF at SIRM”; Parts 1 & 2 (posted March, 2012)
“IVF success: Factors that influence outcome”
“Staggered IVF”
“Male Infertility”Embryo Banking”
“Egg Donation”
“ICSI: Is it for all needing IVF?”
Regards,
Geoff Sher
Hello Dr. Sher.
We had a healthy son through natural conception after 5 miscarriages.–(1 with IVF) Since our son was born, we have had 3 more miscarriages,that we know of.
I thought I had been tested for everything under the sun, with no diagnosable issue other than a protein S deficiency that we treat with lovenox. Finally last month, I was referred to Dr. George Ndukwe in London, and he told us about this kind of immune testing.
We worked with him remotely to do our testing because we live in NYC. He just shared our results via skype, and referred us to you. My NK cells are slightly elevated. I had no blocking antibodies. And we are a HLA DQ alpha match. I am 0102 and 0105. My husband is 0102 and 0102.
I called your office to set up a phone consultation/skype. It would be our desire to do IVF either with you in LV or at your clinic here in NYC, being treated with Intralipid, Pred.,… But the article that you published here in 2010 says that our chances of success through IVF would be severely diminished because we would be labeled a 100% match.
Has anything changed in your opinion about 100% matches since you wrote this article?
Does the option of traveling overseas to treat this issue with the ‘active’ method of immunizing me by an injection of his white blood cells increase our odds of a successful pregnancy through IVF, in your opinion?
Let’s talk ASAP to clear this up. Would you call 702-892-9696 and arrange such. I look forward to discussing your case with you sooner rather than later.
Geoff Sher
I wonder if you can shed any light on my situation. I am based in the UK (I know your tests seem to be different to ours, but the outcome of the results should be about the same I guess) I have been TTC through IUI and IVF since 1998 (trying naturally before that). In that time I have managed only 2 pregnancies – 1st in 1999 which on my 8wk scan showed it was a blighted ovum, I had to have D&C at 11wks, the 2nd pregancny was in 2010 with twins, at 6 wks I had some bleeding but stopped after 48 hrs, at my 8 wk scan there were 2 small sacs but nothing else, at 9 wks I had one blighted ovum (which the sca had grown since the previous scan) and 1 feotal pole but it had an irratic looking sac, at 10 wks I had 1 blighted ovum and 1 irratic looking sac – the feotal pole had disappeared, so I went down for another D&C. I had investiagtion bloods done – including one for NK cells. the results came back saying I was aboce the very high levels of Active Marker NK cells – with a CD69 Absolute count [10^6/l] of 2.21 (in the UK anything above 1.8 is considered very high); NK [bright] absolute count [10^6/l] of 18.44 (28.0%); NK [dim] Absolute count [10^6/l] of 47.51 (72%). Most of the other blood results came back normal with the exception of Liver function test – Bilirubin (normal range 0-17) umol/l, mine was recorded as 21, and Lupus Anticoagulant APTT (normal range 23-31) secs mine came back as 31.7. I then had 2 more IVF cycles with no success, the first of which included having IVIg and steroids, but no successful pregnancy, the final one was cancelled due to no viable egg retrieved. Any suggestion or ideas what this means for me being able to conceive going forward would be much apprecated as I seemed to have tried everything and getting no where. Thanks
It sounds very suspicious of implantation dysfunction but alas, the immune tests you describe are inadequate to make a diagnosis of an immunologic cause. 1st, the concentration of NK cells in your blood id irrelevant. What counts is their activity and only 2 tests can be used. Best is the K-562 target cell test (a test on your blood) and 2nd is an endometrial biopsy for uterine cytokine activity. Only if one or both are increased, can you definitely diagnose an immunologic problem. Also, cardiolipin and Lupus anticoagulant tests while helpful to diagnose primary autoimmune conditions lack sensitivity and should not be used in this setting. You need a full antphospholipid antibody profile to identify all 21 varieties,and man immunophenotype. I am not sure anyone in the UK can do these.
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. “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)
5. “IVF success: Factors that influence outcome”
6. Thrombophilia”
Consider calling 702-699-7437 to arrange a telephone or Skype consultation with me so we can discuss your case in detail.. While an audiovisual (Skype) interaction is much more personable and preferable than a discussion by telephone, either will suffice.
Geoff Sher
Hi doc,
I have had 5 IVF failures and 1 miscarriage in a natural pregnancy at 2 months.
I have tested for APCA, DQ Alpha and DQ Beta, NK cell and TNF alpha.
ATA – >1300
APCA is negative
TNF Alpha- 715.718 pg/ml
CD3- 81.3%
CD19- 12.6%
CD56+CD16+ cell – 10.2%
CD56 cells – 17.8%
DQ Alpha(wife)- 0103, 0501
DQ Beta(wife)- 06, 02
DQ Alpha(Husband)- 0104, 0501
DQ Beta(Husband)- 05, 02
My doc has suggested LIT for APCA.
Can partial DQ match be corrected?
What do u suggest doctor.
Thanks for ur response.
It sounds as if you have a partial DQalpha match with your husband and increased uterine cytokines. There is one test result missing and that is the most important of all…namely the K-562 target cell test on your blood for natural killer cell activity (NKa). Contact Reprosource in Boston, MA and get the test done there.
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 “Immunologic Implantation Dysfunction” (posted on May, 10th and on May 16th respectively) into this space, click on it and it will take you to the articles.he
I suggest you call 800-780-7437 or 702-699-7437 to arrange a telephone or 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.. While an audiovisual (Skype) interaction is much more personable and preferable than a discussion by telephone, either will suffice.
Geoff Sher
Hi doc,
I have had 5 IVF failure n now am 31 yrs of age.
Recently got tested for TNF alpha from 2 labs
1) Quest diagnostics- 6.7 pg/ml (normal 1-12)
sample was sent from India.
2) In Indian lab tnf alpha came- 715.718 pg/ml (> 600 pg/ml is considered very high)
I am confused now as Quest says its normal result.
Can u pls suggest??
The test you need is the K-562 target cell test (I do not believe this can be done in India). This blood test evaluates uterine NK cell activity. Thew blood can be sent to Reprosource in Boston MA, by Fedex.
Good luck!
Geoff Sher
702-699-7437
Dear Dr Sher
I do not have a DqA match with my husband (0301, (0103) but I have matching DqAlpha values of 0501, 0501. Am I right in thinking that my own match should not influence IVF outcome ? Dr Beer’s book states that most infertile women have a 0501 DqA figure.
Thanks
Susan
Good for you Susan,
You are absolutely correct.
Geoff Sher