Wednesday, November 6, 2013

Reproductive Immunology Follow-Up: Eh, Not Sold

I wanted to give a follow-up to my previous blog about RI (reproductive immunology). After speaking to a doctor who practices it, some preliminary testing and extensive consideration, we've reached a verdict on whether or not it's worth pursuing in our situation. However, let me be clear that I'm only speaking to OUR personal situation and no one else's. I know there are some other ladies curious about this stuff as well. I'll share my results here so you can see what they look like.
Re-Cap: We are currently in a Femara/IUI cycle. Before this, after our 3rd IVF transfer and subsequent chemical pregnancy (our 3rd pregnancy loss) we asked our RE, Dr. Vaughn, about need for further testing and/or second opinions. He gave us his blessing to do so.

We spoke with Dr. Sher (Sher Institute for Reproductive Medicine) who felt it was worth looking into possibilities related to implantation dysfunction. He ran a couple tests through Reprosource Labs in Boston, MA.

Results: 

Expanded APA Panel-
Nothing new here really. We already knew I had +APA’s (Anti-Phospholipid Antibodies). This just uncovered some additional ones I wasn’t tested for previously with my hematologist...just further confirmation of a blood clotting disorder.


Expanded APA Panel


NK Cell Activation Assay- Test showed NK (Natural Killer) cells were normal in their native state (as they are for most people) but when stimulated with Interleukin 2 (IL-2) they became abnormally elevated. (See IL-2 stim values of 11 on p.1 & 11.7 on p.2.) 

NK Cell Assay: Page 1 of 2

NK Cell Assay: Page 2 of 2

Dr. Sher’s perspective:
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Suggests using Lovenox 40 mg for entire cycle of conception, in addition to entire pregnancy. I’m already doing this anyway. I started Lovenox on CD6 this cycle. I take baby aspirin in the AM and Lovenox in PM.

-Says NK results show heightened NK cell activation with introduction of IL-2. This mimics the same reaction that will occur in my body when an embryo presents in the uterus....My overactive immune system will see any embryo as a “foreign invader” and will then attack it. This can result in infertility (by not allowing successful implantation) or early pregnancy loss (by attacking embryos once implanted).

-Says my suspected ectopic could have even occurred due to heightened NK cells in the uterus, because NK cells do not live in the fallopian tubes...Embryos may seek refuge in the tube in some cases.

-Suggests using low dose steroid such as dexamethasone or prednisone for entire cycle of conception (actually from 2 weeks before cycle begins) to lower immune response. He keeps patients on this until 10 weeks into pregnancy, weaning them off around week 8.

-Suggests doing two intralipid infusions to lower immune response; Once before conception cycle & once upon + pregnancy test. (IVIg is not being used much anymore. Intralipid is just as effective, much cheaper, safer).

-Suggests a combination of Lovenox + low dose steroid + intralipid MUST be used if I am ever to have a successful pregnancy carried to term.


My perspective:
- We have no interest in leaving our current RE at the moment. We just don’t want to spin our wheels with more losses and failures if something other than “bad embryos” or a random “tubal malfunction” is causing our issues.

-I made up my mind ahead of time that if these results came back as merely "borderline high" that I would not take too much stock in them. Conversely, if results came back with multiple values off-the- charts high, we might be more compelled to pursue further testing or a more intensive immunology based protocol for our last FET (if needed after this IUI). However, out of all NK values tested, only two (@ 11 & 11.7) came back just over the cut-off considered high (>10).

- Due to the above, I am NOT sold on the need for a protocol based heavily on experimental immunological treatments. There isn't enough evidence here to warrant my own personal need for intralipid infusions or other controversial immunological treatments such as IVIg and LIT.


-I will admit, there seem to be a few signs pointing to something autoimmune in nature amiss in my body. My hematologist told me previously “Clearly you have autoimmune activity in your body, even if it’s not full blow lupus yet.”

-Because of this, I’ve always wondered if it wouldn’t hurt to at least add a low dose steroid to our protocol. There is some medical literature showing effectiveness of steroids to lower NK cells, as well as to reduce pregnancy loss rates. My RE and I have tossed the idea of adding a low dose steroid around for a while without actually moving on it. At minimum, this is a low risk option I feel comfortable trying.

My RE's perspective (via my nurse):
-Dr. Vaughn has reviewed your questions. He is good with you taking the Lovenox and baby Aspirin.

-Dr. Vaughn and the other doctors at TFC do not do NK cell testing due to the fact the testing is not very conclusive and not enough studies to show NK cells play a role in infertility. Dr. Vaughn is not convinced this is an issue.

-Dr. Vaughn said you were on Dexamethasone for your IVF retrieval in the past and is OK with you adding a low dose steroid to your regime. He wants you to take Dexamethasone 0.5 mg 2 pills each evening.



So, there you have it. We will not be putting all of our eggs in the RI basket so to speak. We'll add a low dose steroid, but that's it. I will continue eating an anti-inflammatory diet as usual, as well as continuing to eat gluten-free & dairy-free to assist in dampening any autoimmune type of activity internally.

Am I glad I had this testing done? Yes, because there is no longer a giant ? looming over my head. Do I think some borderline high NK cells have been THE THING that have kept us from having a successful pregnancy? Not necessarily. I have to agree with my own RE on this one....not convinced. While there is some research showing a correlation between NK cells and infertility/pregnancy loss, it's just that...limited amount of correlation and not causation. If a low dose steroid could potentially squash some risks associated with an overactive immune system or pregnancy loss I'll do it, but I'm not going further than that. I have read up on this as much as humanly possible, and there isn't enough evidence in my humble opinion...and actually the opinion of most RE's out there.


Additionally, I'd like to be frank on my own limited experience. Dr. Sher himself was fairly easy to discredit in my opinion. On one hand, Dr. Sher admits that at least 70%+ of early pregnancy losses are likely due to chromosomal abnormalities. This is something that typically increases with egg age...no RE or RI refutes this. However, he then made the blanket statement... "It's clear that NK cells are THE REASON for your issues" and stated, "You will never be able to become pregnant and carry to term without intralipid, steroids, and Lovenox ALL combined." (insert eye roll here) That is just very far reaching to me, and I don't buy it. I don't think I'm in denial either. There's simply not enough proof to make that sort of claim to me or anyone else for that matter.

Do I think that some women have benefited from immunology protocols and have achieved motherhood this way? Sure. However, I am inclined to believe the number of women out there with TRUE immunological issues affecting their ability to reproduce is fairly small and that there are quite a few women pursuing RI who don't really need it. I have suspicion there are doctors capitalizing on this as a business, and that some of these doctors may care more about a dollar than the Hippocratic Oath.

Could it be that many women with infertility are in search of an "answer" and when they don't get one they turn to the only thing left they haven't tried (like RI)? In some cases, it's possible. After all, it was my own quest to find more answers which led me to Dr. Sher. Unfortunately, infertility is much like a dart game. When one thing doesn't work, we try another. It's one big ole crapshoot basically.


It's worth noting the firsthand accounts I've read through blogs; Women who have had pregnancy losses, IVF failures, years of infertility, and have pursued RI as their last resort in having their own biological child. Some of these women were told the same thing, "You will never have a baby without immunological treatment." How then, have some of them gone on to have their own biological children AFTER immunological treatments have failed?

Other women have pursued donor eggs AFTER immunological treatments have failed, and have gone on to have successful pregnancies without immunological treatment. To me, this is further evidence that it was more likely a case of poor egg quality/embryos for these women.

Vice versa, there are cases where donor eggs have failed, yet the same couples went on to have their own biological child with the addition of immunological treatments. I don't doubt this is true. However, even in cases where some claim "xyz immunological treatment finally got me my baby!" you may read further into it and see that they also did IVF or an injectables cycles with IUI...Well, if there are 6 eggs waiting to be fertilized & upping your chances so exponentially, how can you possibly say with 100% certainty it WAS the immunological treatment and not that you just finally found a good egg or embryo?

Even in cases where successful pregnancy is achieved through timed intercourse in conjunction with RI, in all fairness, there is no way to prove with certainty what caused the success on either end of the spectrum.  Maybe it was the treatment. Maybe it was God. Maybe it was finally the perfect match of a healthy sperm and healthy egg.


Another red flag for me is that Dr. Sher, along with the handful of other RI's practicing in the U.S., do not publish their success rates via SART. When I asked Dr. Sher about this, he became defensive, citing multiple reasons why he's "taking a stand against non-uniform reporting standards." He gets very heated easily, and it's almost comical. I pressed him saying, "I totally respect your decision. Is there somewhere on your website that I can find your own method of success rate reporting, in whatever fashion you've chosen to do so?" His time then became very short, and he directed me to the discussion board of his blog. He is literally updating his success rates via random threads on his discussion board, boasting 70-80% pregnancy rates, with the caveat that 15-20% of these will be lost due to miscarriage most likely.

Is this a joke? He can't even make a well-organized chart or something? He obviously does not track live birth rates (one of the most important criteria to consider when looking at clinics) or he just doesn't want to disclose them. If he supposedly specializes in treating women with IVF failure and higher rate of miscarriage, wouldn't he want to publish live birth rates? Nor does he distinguish between age in his "reporting." Huh? How can you not include that info?

Consider this... If his practice is so outstanding and he is soooo passionate about the need for immunological treatments, why not report these fabulous success rates the same way all other clinics nationwide do (way more exposure and credibility) and find alternative ways to be an outspoken advocate of more stringent oversight of SART reporting. I mean, surely if other RE's saw that his immunological protocols were producing 80% pregnancy rates, they would finally LISTEN to what he's recommending as a "pioneer" in his field, right? Believe me, Dr. Sher seems egotistical enough that recognition at this level would surely be beneficial for him. I just see the whole "I'm taking a stand" thing as a cop-out.

Outside of this, Dr. Sher is not a good listener. He's a bit pushy and salesman like. I had only a few well thought out questions to ask him, but it was hard to get a word in edgewise. It's like he was talking from a script (perhaps the same one he uses for everyone) and basically bulldozed the entire conversation. Every time I asked him politely to justify a remark, he became audibly agitated and was quick to refer me to his ever expansive blog full of his own personal articles, none of which are taken from peer reviewed research journals by the way. It seems his modus operandi is to bombard you with information so that you will think it's all legit.

To his credit, I think it's generous he consulted with me twice and ordered tests for me without charging me a dime for his services. However, ultimately I think it's just a way for him to grow his business. Let's just say, I don't get a "mother Theresa" vibe from him. In fact, both times I've talked with him, I've had an invisible angel firmly planted on my shoulder saying, "RUN the other way!" That is the only way I can describe my first impression and intuitive feelings toward him.

Still, I will say that Dr. Sher must care about his line of work to do it as long as he has. He has 30+ years of experience and has clearly been around a while. I found his book very informative as an IVF newbie not knowing what to expect when we began IVF. I do think though, that his focus as a doctor has perhaps changed over the years. Before RI was ever on the map, Dr. Sher was practicing what we'd consider a more traditional approach to RE. Now, he's focused on working mostly with a specific population of women. I just can't help but wonder if he's reaching a little too far with his recommendations to some women.


So, sorry this is long, but I wanted to give a detailed run down of what my personal thoughts were with my minimal exposure to RI. I realize I did not have all of the possible RI tests run, and that there are many more things like DQ Alpha matching, etc. that exist out there. I am also not in the same boat as a woman with 10+ pregnancy losses or failed IVF's and who might have more reason to accept immunology as THE THING keeping them from motherhood.

By no means do I think women pursuing RI are doing the wrong thing either. I admire any woman who will go to great lengths to create the family that she so desperately desires. Each of us has to weigh our own quest for answers, our own history/risk factors, and our own timeline to achieving motherhood with the recommendations given by any doctor
. For now, I feel we are on the right path for us, and that's where we intend to stay as we continue working towards and believing for a family.

38 comments:

  1. Wow. So much information to take in. I absolutely agree with your determination of the test results. This doctor reminds me so much of Dr. Asshat (remember him?), my first RE. Major God complex.

    I truly believe that you are on the road to success. You are one of the most savvy women I "know" on these blogs/boards/forums, and I have no doubt that you are in complete control of your care.

    You're gonna be a mama, no doubt about it. I hope it's very, very soon. xoxo

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    1. Yep, you nailed it. Total God complex!

      My current RE, on the other hand, is openly Christian and has a statue on his desk that reads "Babies are a gift from God." What a stark contrast between practitioners I must say.

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  2. Wherever you have peace is the place or direction to be. That's a whole lot of information and honestly sometimes too much info gives us undo worry. I agree with the comment about your baby is on his/her way. Praying for you.

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    1. Couldn't agree more. I rely heavily on how I feel, and peace was not the feeling I got in speaking with this doctor. I'm not worried about these test results one bit either. If anything, I now feel more confident it's not a road I am meant to travel...which does bring me more peace in place of question marks that were there before.

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  3. Holy moly loads of information there! I think you are on the right path too! Praying xo

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    1. Ha! Sorry if it's information overload. I only posted so many details because I know there are a couple other women who read that are looking into this RI route as well. Thanks for the prayers Kasey!

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  4. I'm totally with Charity on this. If you're at peace with the low-dose steroid and that's it, then that's the right choice for you! Hope this is the missing puzzle piece.

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  5. Thank you SO much for sharing all of this information! I have a feeling that I will re read this a bunch more times for it all to sink in :)

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    1. No problem! Was thinking of you when writing this. Definitely some interesting things to consider, but with eyes open very wide!

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  6. Wow! I admire how knowledgeable you are. Whenever you want answer you seek in depth for them and don't take beating around bush type of answer and that my friend is truly amazing. You are on the right path and I'm glad you are consulting with your RE as far as opinion wise am not keeping him out of the loop. There's no doubt you are going to be an exceptional mother.

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    1. Well, thank you for saying that. I don't know any other way to be though. I guess you could call me an "open skeptic" if that's possible. ;) And yes, I've been very open with my RE on every little thing. Even though we haven't reached more permanent success yet with him, I have a tremendous amount of respect for him...He's helped us get pregnant twice. We just need one to stick now!

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  7. I am proud of you for going with your gut on this one. I think we often feel the pressure to do "more" when what we're doing isn't working as quickly as we'd like it to, and the thought of "answers" and "a new plan" can be so enticing. But like you said, infertility can be such a crapshoot, and most of us will probably never know exactly what is causing our problems no matter how many tests we do or treatments we do. Going through all this, it is so important to be working with someone that you can trust and respect, because all the rest is really out of our hands. I'm glad that you had a chance to explore your options, though!

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    1. Couldn't have said it better myself Farra. All so true!

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  8. THANK YOU for this post! I can't help but feel like I'm "cheating" myself by not pursuing RI solutions, but I've now made it further with this pregnancy (#3) than I did with the other two. Honestly, I think for me it was cutting out gluten that did it. That's what my gut is telling me (literally). Yes, I'm taking my Lovenox and my steroid (Prednisone) just in case. And maybe that's helping. But the Prednisone didn't do crap last time, so I have some serious doubts.

    All in all, I do think Reproductive Immunology is on to something, but it's not the be-all, end-all solution in every single case. Sometimes something as simple as diet change can make all the difference. I do think that battery of tests is excessive, and the fact that most people don't have coverage is a real head-scratcher. Plus, the non-publishing of results thing? That's shady.

    But I was already pissed at Dr. Sher for not giving me my free consult, so maybe I'm biased. Then again, seems like maybe it was a blessing in disguise. He probably would have scared me into taking out huge loans to pay for the treatments or something.

    Sounds like you're doing everything right. Women's intuition is an amazing thing. You know you better than anyone. I'm wishing you the best of luck with everything!

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    1. I agree....something to RI, but not necessarily the solution in all cases. I do think nutrition itself is a very powerful thing. Been doing the gluten-free/mostly dairy free thing for many many months now, so hopefully it just puts the environment internally in my favor. Wishing you all the best as well with your pregnancy. Sounds like this is THE ONE! :)

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  9. Fascinating! Thank you so much for sharing your experience!

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  10. I am always so amazed at how much research you do and how much you know about all of this! I love that you don't take any flack from these Dr's too :) I think you are on the right path and your baby will come in the perfect timing :) Keeping you in my prayers Emily.

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    1. Aren't you sweet! No flack no sir!

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  11. I'm very happy to read that you are, most importantly, happy and at peace with the path you're on. :) Thank you for sharing this. Emily. I take Prednisolone during my cycles just to cover these bases.

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    1. How long have you been on the steroid? Any side effects? I don't exactly like the idea of it for too long, since our immune system is actually pretty darn important to fight off other things like cancer and whatnot, but I'm willing to give it a go since it's low dose and worth a shot I figure.

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  12. You inspire me! I am so type A and love to see all the information you gather. I frequently have a question and remember that you have posted something about it in the past. It usually takes me awhile to find it, but I almost always do. Your blog is such a great resource for info! I don't know if I've ever told you that, so if I haven't, THANK YOU!! :)

    I'm so glad that you are happy with the current plan, I think it sounds really great. I am shocked with Dr. Sher's outlook on everything. Something just doesn't add up with that guy. In this infertility world, the last thing we need is an egotistical dr trying to sell himself. We need someone intelligent who actually cares about US, not making himself look/sound smarter! Reading your info on him got me all riled up and I know I well NEVER be a patient of his now! :) Thanks again for all the info!

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    1. Type A geeks unite! hehe Yeah, everyone has to judge a doctor for themselves, but I didn't get the warm fuzzies with Sher.

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  13. I don't disagree with you at all and I'm actually participating in them myself! All I can say is although I don't know if any of this will work, I had to try it. Nothing has worked for us in almost 7 years so we are kind of at the end of our rope. I think trying Prednisone, Lovenox, and IVIG is exciting because it's something different but I can see why people aren't sold. I'm not either but since it does work for a lot of people where nothing else has, I just had to try it. Any amount of money is worth my peace of mind to move on to other options when a biological child is no longer an option but that is just what is right for me. I hope we are both wrong and reproductive immunology is the answer we've been searching for all this time. Good luck and prayers for your journey!

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    1. I totally understand and respect that...esp. the part about having peace of mind to know if/when to move onto other options that don't include a bio child. I don't blame you one single bit for going the RI route, and in fact...if we had 7 years under our belts, I'm sure my blog would have been written totally differently. I am excited for you to try IVIg too, and I pray more than anything that it does work for you! It is hard to deny some of the success stories! I really hope you become one of them!

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    2. Thanks! And you're right. 5 years ago I certainly wouldn't be doing all of this crazy stuff! :)

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  14. I agree with you, that MANY RI's out there are good at convincing people they NEED RI treatment when they really don't...There are a few cases, like myself, where there are several contributing immmune/allo immune issues at hand, in which case a RI is probably one of the only ways to go ( still, we ( personally) have decided to stop pursuing RI stuff due to expense / lack of studies on IVIG etc)...IBut I also think MANY RE's are pushing women into IVF without really NEEDING it, because they get more money, and the women get a baby faster (in theory)...All in all, I am appalled at our medical system right now, in almost every single aspect, regardless of IF or not...One MUST be their own advocate when dealing with the medical community at large these days....I am glad you are at peace with your decision, and I am praying so hard you get that sticky little bean!!!!

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    1. So glad you chimed in Megz. You probably know about 10x's more than I do about this topic, and I so appreciate your feedback. Such a good point on the unneeded IVF as well. So many women are told they will never conceive without IVF and yet they do! Advocating for ourselves is work I tell ya, but such a necessity!

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  15. I am so happy to hear you so confident you are on the right path and that you got some answers! This post is full of so much great information! Thanks so much for sharing and wishing you success sooner than you expect :)

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  16. Very, VERY well written my friend! *applause* And you know how I feel about SIRM, so I'm glad you gave your review. As for the steroids, WHY do they say to take them at night?! They stimulate your adrenal glands (I've had to take them in large doses for my UC) and I've always made a point to take them in the,morning so I'm not up all night or having nightmares (steroids also stimulate cortisol, the "stress hormone") so see if you can take them in the morning? XO

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    1. I started taking them at 5 AM a few days ago, because I've only been sleeping about 50% of nights. Wonder why in the heck they say to take them in the evening? I swear they increase urine output and that's what keeps me up even more than any stimulated cortisol...peeing twice a night and then can't get back to sleep with racing mind.

      Thank YOU for your feedback on SIRM too. Glad I'm not the only one who found them shady. Still waiting on "the call" from Reprosource with a bill, so that should be interesting. :P

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  17. Hi Emily, So Dr. Sher will consult with you even if your not under his care? I am currently searching for answers for multiple failed IUIs and IVF cycles with being only 32 and no other diagnosed issues. Did you receive your bill from Reprosource? I'm curious how much the testing will cost. Did you need to travel to Nevada to see Dr. Sher for the testing or can you ship the blood? Thanks!

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    1. It's an initial consult, so that is kind of the point....that that Dr. Sher wants you to be under his care, so that is why he gives out free consults. He does the consults via Skype, so there is no need to travel. He can also order the blood tests through Reprosource and then they have you either go to a blood draw center where you live (they search for one for you) OR you can pay $50 to have someone come to your home to draw the blood and mail it back in for you (which is what I did). I haven't received any bills from Reprosource and I am not even seeing it pending in my insurance claims online. Not sure what's going on with that? I do know that if my insurance covers nothing at all, the total cost for the tests I did will be $458.

      I hope this info. helps! I am sorry to hear you've have a long road as well. I know how very frustrating this can be. You definitely aren't alone!

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    2. Oh and P.S. I just saw in your profile you are in Maitland, FL. I grew up in Orlando (Winter Springs actually) and lived there for 20+ years. Great place! :)

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  18. I read this blog with great interest. I have four failed IVF cycles with donor egg and one miscarriage with donor egg. I did immunology testing through Reprosource and they never sent all of my results to the doctor or to me. I've since found out there are other labs that do this immune testing. Hindsight is 20/20, though. Wish I'd tested with a different lab. I still have no results after months, so don't know if I have immunology problems or not. However, I am beginning to think NK cell theories are tricky at best. Talked to many people who failed in spite of immunity treatments, and others with NK cells who succeeded without the treatments.

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    1. That is so insane and totally unacceptable you haven't received your test results. It took a while to get mine....want to say about one month. I would be livid waiting longer than that.

      Like you, I'm not sold on whether NK cells are conclusive as to the root of the problem, but think there is "something" to the immunological theories. I just think we're a bunch of guinea pigs getting testing and trying stuff at this point in such a new area of science. I will say that because I was found to have heightened NK cells, the results gave me extra ammo to give to my regular RE and basically BEG to at least try adding a steroid. I opted not to do the more invasive IVIG/Intralipid infusions that Dr. Sher and others would have suggested. My NK cells were borderline high so I figured adding a steroid couldn't hurt to just squash some autoimmune activity in the uterus.

      Well, it was the cycle that worked, and I'm now 20 weeks pregnant. No telling if it was adding the steroid, the completely different protocol I used to grow my lining for the FET, the fact I had a laparoscopy/hysteroscopy the month before to remove a septum, or maybe my prayers just paid off finally. Who knows! I did, however, stay on the steroid for entire first semester, because even though we don't know why/how some of this autoimmune stuff works, we do know steroid does "seem to prevent" miscarriage and aid in implantation in some people. My MFM doesn't even disagree with that. I lost a twin with this pregnancy, but think that was totally genetic...have a healthy baby growing in this belly finally! Was it the NK cell testing and steroid that did it? I guess I'll never know for sure.

      I wish you all the luck in the world Jan. It can be so frustrating to try to get answers and to keep trying so many times. I hope that you get your take home baby, even if it's not the way you envisioned it happening. ((HUGS))

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