Switching horse mid-race

After a number of failed cycles, many women (smartly) switch fertility clinics.  If we had nothing but failures at my clinic, it would be a no-brainer.  We would have switched for our last fresh cycle.  BUT my clinic has gotten me pregnant in all of our cycles but one (5/6) and has actually gotten us pregnant with “viable” pregnancies twice (2/6).  So I would not say I have no confidence in them.

Still, I did cheat and get a second opinion with CCRM.  I was impressed, but I wanted to see what my doctor had to say after our most recent failure.  It was interesting and reassuring.

First, he reiterated the fertility doctor mantra—for recurrent pregnancy loss, the biggest reason (70%?) is due to genetic causes.  Those losses tend to be earlier in pregnancy (first trimester).  The second biggest reason for recurrent pregnancy loss is due to uterine abnormalities (ie polyps, fibroids, scar tissue, etc.).  Those losses tend to be later in the first trimester.  The third biggest reason relates to “systemic” causes—basically, are you sickly (ie diabetes, thyroid conditions, infections, autoimmune disorders like lupus or rheumatoid arthritis)?  These losses also tend be later (10-12 weeks).  In this bucket he also placed immune issues.  He basically said what the docs at CCRM said—nobody knows if immune issues play a part in recurrent loss, there’s debate but nothing has been proven.  The theory is, much like the way the body can reject a transplanted organ, the body can reject a pregnancy as invasive.  He said some doctors will treat patients with steroids (such as prednisone) or blood thinners (heparin, aspirin.  

With respect to the “systemic” causes—I have none of the known things that would cause concern.  Also, all of my losses have been very early, so they are likely not systemic.  With respect to the uterine abnormalities—they have been repeatedly ruled out after the doctor has done saline sonograms.  (I just had another one that confirmed—my uterus has no issues.)  Plus, they also tend to be later losses, not earlier losses.

Which leaves us with genetic issues.  This one is confusing, too, as we have now failed with chromosomally normal embryos (ie. the right number of chromosomes).  But it might be our genes (ie. the question of whether the chromosomally normal embryo develops normally) that are the issue.

I had three pregnancy losses before I even saw a fertility doctor.  One was definitely ectopic, and at least one of the other two was also likely ectopic (we saw further scarring of my tube).  SO, we have to put those in a different bucket because they may have been caused by my tubal issue.  (Which itself may have been caused by hernia surgery I had as a baby.  My whole life my mom worried I would be infertile because the doctor told her, just after operating on a month old baby, that my ovaries were “swollen” and I might have trouble conceiving children.  Fast forward 30 odd years later, and it turns out that abdominal surgeries are thought to potentially increase the likelihood of tubal pregnancies.)  Anyway, we can’t really say for sure, but we won’t “count” those in the recurrent pregnancy loss bucket we’re trying to solve for now because they may have been related to a tubal issue that IVF all but solves.

Okay, my second “bucket” of losses are the two failed pregnancies I had with chromosomally untested embryos after my second IVF cycle.  One was a blighted ovum, so it was likely a genetic issue.  The other one was a chemical pregnancy, and those are also generally due to genetic issues. 

My third “bucket” of losses was with chromosomally normal embryos after my third IVF cycle.  As it related to the anencephaly pregnancy, that embryo turned out to be chromosomally normal.  (We did not know that when we put it in, but we had it tested at 12 weeks.)  While the “chromosomes” were normal, there was a genetic issue, as anencephaly is, as we have previously discussed, some mixture of genetic and environmental.  So there was a genetic issue.  My FET after that was with a chromosomally normal embryo, but that also ended in a chemical pregnancy.  It too was likely related to genetic issue, even though the chromosomes were normal.

In other words, our genes might be a problem.

And how do you solve for a “genes” issue when all you can do is test the embryos for chromosomes?  Well, you just keep putting chromosomally normal embryos back in and hope that one of them is genetically normal as well.

FUN.

Here are two decent overviews of causes of recurrent pregnancy loss: 

http://emedicine.medscape.com/article/260495-overview

http://www.glowm.com/section_view/heading/Genetic%20and%20Nongenetic%20Causes%20of%20Pregnancy%20Loss/item/318

And here’s one that says that for women with recurrent pregnancy loss, they are losing chromosomally normal pregnancies at a higher rate:

http://www.ncbi.nlm.nih.gov/pubmed/15298979

We talked about whether, with our history, we should just bite the bullet and put in two embryos in our next cycle. This process is just NOT FUN.  But our doctor (like the CCRM docs) is anti-twin.  As he said, even the best twin pregnancy has more risk than a singleton pregnancy.  Twin pregnancies are hard on moms (higher blood pressure, more likely to go on bed rest, more likely to get gestational diabetes, more likely to need a C-section) and hard on the babies too (more likely to be preemies, more likely to suffer from health issues).  He was like, if you want one healthy baby, but not twins, put one embryo in at a time. 

We also discussed whether it was ethically appropriate to use a B3 girl instead of a B2 boy.  He said their rating system (B1-B2-B3) was not strongly correlated with success (it’s as much art as science to rate those little suckers) and once they are tested to be chromosomally normal, the ratings of the embryos matter even less.  So he was like, go ahead and use your B3s if you’d like to have a daughter. 

I had a whole list of questions for him, so I’ll just run through them now.

First I asked, is it possible we have a translocation?  He said no, both my husband’s blood and my blood had been tested for translocations, and we were both normal (I was 46xx, hubby was 46xy).  He said that he did not do a “skit test” to look for DNA damage because we had good luck getting embryos to the blastocyst stage.  (If there is DNA damage, the hubby can go on folic acid in an attempt to improve sperm quality.)  So, it’s not a translocation.  We’ve ruled that out.

Second, I asked, is it possible it’s thrombophilia (clotting issue).  He said probably not, as those tend to cause late first trimester / early second trimester losses.  But, just to be sure, we had my blood tested to confirm.  (Factor 5 test, factor 2 test, protein C test, and protein S test.)  If that was an issue, I would go on baby aspirin / lovenox or heparin (blood thinners).  But the tests came back normal.  We’ve ruled that out.

Third, I asked if it was possible I had structure abnormalities.  He said unlikely—we’ve had saline sonograms that have said things are normal, and confirmed after each of our losses.  He assured me that if there was a structural abnormality, the saline sonogram would catch it.  We did another saline sonogram.  Normal.  We’ve ruled that out.

Fourth, we discussed the “immune response” issue.  He basically said nothing was proven and he has never treated a patient with steroids (such as prednisone) and / or antihistamines just for the hell of it.  (In other words, he poo-poo’s CCRM’s hail Mary approach.)  My husband was very uncomfortable with us doing any protocol that had no scientific support—especially with a drug as potentially dangerous as prednisone.  So, we decided that we were comfortable not using a “hail Mary” approach… for now.

(The theory behind the use of a steroid such as prednisone is that embryos might be exposed to bacteria or leukocyte infiltration if the protective coating of the zona pellucida is breached and that immunosuppression via steroids would help combat that. But a study by did not find any beneficial effect of adding low dose progesterone during the luteal phase:

http://www.ncbi.nlm.nih.gov/pubmed/12042275)

Fifth, I asked if we should use inter-muscular progesterone next time.  (Keep in mind I’m the one that’s been pushing NOT to use IM P4 in oil this whole time.)  He said, yes, let’s do it.  Again, there’s no scientific proof the shots are better than the suppositories, but he said they might be so let’s do it.  Big needles, here I come.

So, where does this leave us?  CCRM was very impressive, but our doctor said basically all the same things.  The big difference in protocol is the “hail Mary” approach that would include the use of prednisone.  My doc is against it, CCRM is for it.  At the end of the day, my husband is against anything that has not been shown to improve our chances of success, so he’s against the unproven “hail Mary.”  From what I’ve read, I’m comfortable with that approach… for now.

I was not convinced that transferring our embryos would be a good decision.  If we were considering doing another fresh cycle, I think we would switch.  But there did not appear to be much of a benefit to us to transfer the frozen embryos to a new lab.  Another consideration is the fact that (a) we would have to use our boy first and (b) CCRM might not even accept our girls.  Neither of those things make us want to switch.

Finally, I DO still have confidence in my doctor.  He gave us our son.  He got us pregnant a bunch of times, twice legitimately, and it’s probably true that those generally failed due to genetic causes or other causes outside of their control.  So let’s just blow through the rest of these embryos and see if we’re lucky enough to stumble onto a good one.

We’re staying with our current horse.