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:
-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.