Monthly Archives: November 2017

Update and testing cycle

Whew.  A couple of weeks and four doctors later and finally I have a plan that makes sense.

When I say four doctors, that’s not as nutty as it sounds — one doctor saw me right after the ultrasound that told me I was miscarrying, and she’s the one who prescribed medical management.  She’s also the one who told me it was probably just bad luck and I should try again.  Then I had a follow-up appointment with the totally socially inept but otherwise great senior OBGYN in the practice, who told me that it probably made sense to go back to reproductive endocrinology, but that they’d probably just tell me that at least I could get pregnant.  Then, just by chance, I had my annual visit with my primary care doctor the following week.  She asked me how things were going, and when I told her that in the last six months I’d had two miscarriages and my father died, her response was essentially “Wow, that’s awful… have you tried yoga?”   I’m obviously condensing that conversation a bit, but it was just such an inadequate response that it was both bizarre and painful.  Plus, she gave me a mini-lecture about the benefits of yoga last year, so I don’t even think the yoga talk was specifically related to everything I’ve been going through.  I think she just didn’t know what to say and didn’t really want to go there.

After all of that, I was feeling pretty down in the dumps about the medical establishment.  I mean, the best thing my doctors have to offer me after all this crap is “bad luck” or “at least you can get pregnant” or “have you tried yoga”?!  It made me feel awfully alone, as though nobody was going to take me seriously or help or even have a real conversation with me about what was going on.  Even if they don’t have the expertise of an RE, they could at least be sensitive and/or check on my mental health — there’s actually some literature showing that feeling supported and getting mental health care during RPL can increase the chances of a live birth in the next pregnancy.  But “Have you tried yoga?” was as close as those first three doctors got to asking about mental health.

Yesterday was my appointment with the reproductive endocrinologist.  It did not start off auspiciously.  That morning, I got a phone call and an electronic message from the nurse working with my doctor asking me why I hadn’t done the testing the RE had ordered the last time I saw her and whether I wanted to postpone my appointment until I got it done.  It was the middle of a busy day while I was running around dealing with broken equipment and trying to get eight groups of freshmen through labs with TAs who are shaky on their own understanding of the material, so I just replied briefly that no, I didn’t want to cancel my appointment, and no, I hadn’t done the labs, but my local OB had done some of the bloodwork over the summer and here are the results.  A couple more messages back and forth and eventually I figured out that they didn’t know I’d had two miscarriages since the last time I saw the RE, despite the fact that I had a long conversation about it with the front desk when booking the appointment and left two phone messages with the nurses asking questions that my local OB had said I should ask the RE before I passed the pregnancy tissue (mostly asking about whether or not it was worth trying to save the tissue for testing at this point).  Since doctors’ offices are apparently universally horrible at communication, the message never got through, but I drove the half-hour to the appointment fighting off tears thinking that yet another doctor was going to dismiss what I’d been through, when really the doctor just didn’t know about my miscarriages.

The reality was much better than I’d expected.  The RE actually sat and talked to me about the causes of recurrent miscarriage, the testing they can do, the chance that each of the problems was consistent with my history, and what she recommended the next steps should be.  Then, she asked about my mental health, and gave me the card of their social worker / therapist, encouraging me to call and talk to her about options for emotional support.  Finally!  A reasonable response to everything I’ve been through.

The RE ordered a bunch of tests, including an endometrial biopsy that can’t be done during a conception cycle, and so this next cycle will be reserved for testing rather than trying to get pregnant again, but that’s OK with me.  It seems like she basically ordered a full RPL workup, minus the tests I already had after my 2nd trimester loss.  I was a little skeptical about the endometrial biopsy at first, since I’ve read that they can have a lot of false positives and are usually used to check for luteal phase defects, which are kind of controversial in their link to RPL, but she explained to me that there’s some promising research showing that chronic endometritis can play a role in RPL and that a course of treatment with antibiotics can improve the live birth rate in subsequent pregnancies.  I looked it up when I got home, and it seems that there are some legit-looking studies from the past 2-3 years on the role of chronic endometritis in RPL, so I’m going along with it.  Otherwise, there’s also a repeat sonohysterogram to check the uterine cavity for adhesions (since I’ve had those before) or polyps/fibroids, and then a bunch of bloodwork, including karyotypes of both me and my husband to make sure we don’t have any of the rare chromosomal weirdnesses that are associated with RPL (translocations and the like) — she emphasized that this is low probability, but would be important to know if we happen to be in that category.

At this point, I’m totally fine with spending one cycle on testing before moving forward.  I’m not wild about the idea of more painful and invasive testing (the SGH I had before was much worse than either the HSGs or the hysteroscopy, but it was also the only test that I had done at my local OB, and they seemed kind of inept at it, so maybe RE will be better?).   But it seems worth it just to make sure that there’s no treatable cause lurking undiagnosed before we move forward with pregnancy #5.

That’s where we are now.  The timing could be worse, since there’s only one week left in the semester, which means that all of this testing will take place between semesters — much easier to schedule inconvenient and inflexible medical procedures when I’m not teaching, thank goodness.  But after yesterday’s appointment I feel a little bit more hopeful and supported than I felt before, which is probably the best possible outcome.

Bad Luck Math

Because I’m me, I’ve been doing the math on my bad luck.  And because this is my blog, I figured I’d share it with you.  If you hate math, this might be one to skip, but I find it to be a helpful perspective.

My question: Among all women who have been pregnant four times before, what is a typical outcome, and how common is my type of outcome?

Assumptions: I’ll assume that first-trimester miscarriage has a ~20% probability, since that seems to be in the middle of the 15-25% estimates.  It depends a bit on week of gestation, but mine have been in the 6-8 week range, and I think 20% is probably about right for that gestational age; I also think first-trimester miscarriages at that gestational age are pretty typical. As for 2nd trimester losses, it depends a little bit.  The overall risk is something like 1%, but the risk of losing a chromosomally normal fetus like I did is about half that, or ~0.5%.  If I were being totally self-consistent, I’d make the probability of live birth ~79% and first-trimester loss ~19% to account for the ~2% of pregnancies that are lost in the 2nd and 3rd trimesters, but it won’t change my answer much so I’ll keep using round numbers for at least these initial back-of-the-envelope calculations.

What is a typical outcome for a woman with four pregnancies? 

The highest-probability event in any pregnancy (other than mine, that is) is a live birth, with a probability of ~80%.  The probability of having four live births in a row is (0.8)^4, or about 41%.  So, fewer than half of women with four pregnancies will have all live births.  That jives with my experience — most women I know with three kids had one miscarriage along the way.  So let’s explore the probability of three live births and one miscarriage.

There are four ways to have one miscarriage in four pregnancies: either your first pregnancy can result in a miscarriage, or your second, or your third, or your fourth.  So the overall probability of having one miscarriage among four live births is 4*(0.8)^3*0.2 = 41%.  That means that just according to the typical probabilities, 80% of women who have been pregnant four times will have either one or no miscarriages, and it’s more or less a coin toss between those groups.

What about the other 20%?

The other 20% are women who are less lucky.  They might have had two or three or even four miscarriages, typically in the first trimester.  But which fraction is which?  The easiest to calculate is having four miscarriages in a row: (0.2)^4 = 1.6%.  So, how unlucky do you have to be to have four miscarriages in a row, just by chance?  Unluckier than 98.4% of other women.  If you somehow manage to collect 100 women who have been pregnant four times in a room, you would expect about 2 of them to have had this outcome by chance.

But what about the other 18 women who had more than one miscarriage?  Most of them will have had two miscarriages.  There are six ways to do that (1st and 2nd pregnancy, or 1st and 3rd, or 1st and 4th, or 2nd and 3rd, or 2nd and 4th, or 3rd and 4th), so the probability is 6*(0.8)^2*(0.2)^2 = 15%  So a whopping 3/4 of the 20% of women who had more than one miscarriage had two miscarriages, and there are only 5 women in our hypothetical room of 100 G4 women who had three or four miscarriages out of four pregnancies, just by chance.

That’s actually more than I might have expected.  I mean, I don’t know very many women who have had four pregnancies, but of the ones I know, they mostly had one or two first trimester miscarriages along the way.  I think the largest total number of pregnancies I know of in my normal everyday life (not counting blogland, which is a very biased sample), is a grad school mentor of mine who once shared that it took her six pregnancies to have her three kids.  (I was appalled at the time, but now I’m 2/3 of the way to her total number of pregnancies and I only have one kid to show for it, so there’s that.)  But the point is that if you somehow collect 20 G4 women in a room — this is the size of a typical seminar course that I might teach at my college — you would expect only one of them to have had more than two miscarriages just by chance.

What about later losses?

So far I’ve ignored 2nd and 3rd trimester losses, because they are so improbable that they make up a pretty tiny fraction of all pregnancy outcomes.  For example, the chance of having one late loss out of four pregnancies is 4*(0.98)^3*0.02 = 7%.  That’s not nothing, unfortunately, but it’s also fairly small — it’s about the same as the chance of having 3 or 4 first trimester miscarriages out of four total pregnancies.  The more times you get pregnant, the more likely you are to have an improbable outcome like a late loss, alas.  The good news is that for a typical woman, even if she gets pregnant four times, she has a 93% chance of never experiencing a late loss — and probably it’s actually significantly better than that, since I’m assuming that all pregnancies are equal, whereas the research shows that women who have had one late loss are more likely to have another, so in reality it’s almost certainly skewed so that women with generally poor reproductive outcomes account for a larger-than-chance share of the late pregnancy losses, and a truly typical woman is less likely to ever have a late pregnancy loss.

So, how unlucky am I?

Let’s explore the probability of my particular reproductive outcome: four pregnancies, one late loss, two early losses.  We’ll assume that the order is random, although it might not be — for example, the adhesions from my first pregnancy could conceivably have contributed to my early losses in later pregnancies, or I could have some sort of weird immune-mediated thing that got worse after a live birth.  But those are fairly speculative possibilities, so I’ll just assume that the order is random.  In that case, the probability of having an outcome like mine (one late loss + two early losses, random order) is something like 12*0.02*(0.2)^2*0.8 = 0.8%.  So, if you got 100 G4 women in a room, maybe one of them would have a history like mine, but maybe not.  You’d need a thousand to get me some buddies for sure.

And I’ve also been generous in defining what “like mine” means.  If you narrow the definition to the loss of a chromosomally normal fetus in the 2nd trimester (plus two early losses), that brings the numbers down by a factor of 4 to 0.2%, which means that I’d need a room full of 1000 G4 women to maybe have one friend who’d been through something similar.  This thought experiment is also interesting because it brings the probability of having an outcome like mine below the threshold of 0.3%, which means that my outcome is 3-sigma bad, or that there’s a 3-sigma probability that my obstetrical history is not just due to bad luck, but rather to some other contributing factor that predisposes me to poor pregnancy outcomes.  That’s significant enough to get you publication in a journal in my field (though not in all fields).

Now, of course, when you get down into the weeds of these small-number probabilities, there are a lot of outcomes that look similar.  Another outcome that has a probability of 1-2 women in a group of 1000 G4 women is having two late losses and two full-term births, and you can add a bunch of different permutations that also give you similar answers.  But the point is, by the time we get into the land of both late losses and multiple losses, we’re down in the tenths digits of the percentages, which is a fairly lonely land to be in.  It’s also increasingly absurd to be told that your problems are due to “bad luck” and told that you should just try again — when you’re out in 3-sigma land, while it’s certainly true that your outcomes could be due to bad luck, the probability is low enough that it seems like any reasonable person with at least a slight grasp of statistics would want to do more investigation.  It’s easy to say that investigation is a waste of resources when you’re talking about two first-trimester losses out of four pregnancies (roughly a 1 in 5 chance), but not when you’re talking about an outcome that only a few in 1000 or even 10,000 women will experience (since most women don’t get pregnant four times and therefore aren’t even represented in the above numbers — you actually expect overrepresentation of poor pregnancy outcomes in G4 women for exactly this reason).

So there you have it.  I am so statistically significantly unlucky that it seems unlikely that my issues are due to random chance (i.e., they are probably more than just “bad luck”).  However, I’m not as dramatically unlucky as I guessed going into this exercise (I guessed that I’d be 4-sigma unlucky, but I’m not that unlucky).  So, that’s good news, I guess?  The other good news is that I live in a time when the internet exists to connect me to all the other women having a tough time out in 3-sigma land, so it doesn’t feel as lonely as if I’d been a prairie mama trying to deal with this all in isolation, never knowing another woman who had been through something similar (waving at you, blog friends!).  Though in that case I’d probably already be dead and/or completely infertile from the infection I contracted after my 2nd-trimester loss, or from hemorrhaging due to retained products of conception before the infection — huzzah for 21st century medicine!  It’s keeping me alive, even if it’s not telling me how to keep my babies alive.

Miscarrying and Hypothesizing

Well, I opted for medical management of this miscarriage, and it’s proceeding slowly.  I took the first round of medication Friday night, and not much happened, so I took another round Sunday morning, and finally things are moving.  I don’t think I’ve passed the main pregnancy tissue yet, but hopefully soon (I was so afraid it was going to happen in the middle of my lecture yesterday!).  I’ve got another week before they’ll start pushing a D&C on me, which I’d like to avoid if possible since I have adhesions from my first pregnancy.

In the meantime, I’ve started to do some research on causes of recurrent pregnancy loss.  I’ve already been tested for clotting factors and some of the immunological stuff, and other than being heterozygous for Factor V Leiden it all came back normal.  But it’s hard for me to believe that FVL is the only culprit, since it’s not associated with an increased risk of 1st trimester loss.  The main thing I haven’t really been evaluated for is heritable chromosomal issues, like a balanced translocation in my husband and me — but I find it hard to believe that that could be the source of our woes, since we know that two of our four pregnancies at least have been chromosomally normal, including the daughter we lost in the 2nd trimester.  It’s also not particularly associated with 2nd trimester loss.

There are actually very few issues that are associated with increased risk of both 1st and 2nd trimester loss.  But one thing that I read about immediately clicked for me, and now I am anxious to talk about it with my doctor on Tuesday.  You’d think that with everyone looking at my uterus in every which way over the past four years someone would have brought it up before now, but I’m about 95% certain that on one of my recent ultrasounds the tech noted a slight septum that she didn’t think was clinically relevant.  But anatomical abnormalities like a uterine septum are one of the most common — and most treatable — causes of recurrent pregnancy loss.  They are also one of the few etiologies that causes both 1st and 2nd trimester loss.  The ASRM guidelines on recurrent pregnancy loss note that the likely mediating factor causing 2nd trimester loss is abnormal placentation, which was the leading hypothesis for our daughter’s death.  It just all makes so much sense!  If I have a slight septum that isn’t bad enough to cause total infertility, but is enough to cause poor blood flow to the embryo/fetus, it would explain why I keep getting pregnant but keep losing the pregnancy, sometimes early and sometimes late, even in the absence of chromosomal issues.  It at least seems worth asking about, since the prognosis for treatment is really, really good — there are some studies where the live birth rate jumps up to like 85% (normal!!!) after surgery to correct a septum.  I would love to have an 85% chance of a live birth, instead of the 75% chance of miscarriage that I seem to have had in my pregnancies so far.  Maybe my doctor will tell me I’m nuts and that this slight septum can’t possibly be causing my problems… but I feel like I have to at least bring it up.  And if my regular OB doesn’t listen, I have an appointment with the RE on the 28th and will bring it up again then. And again and again until someone listens and has a real conversation with me about it.

I’m just ready for someone to take this problem seriously and stop telling me it’s just bad luck — it seems so clear that whatever is going on, it’s more than just bad luck.  One 2nd trimester loss… maybe?  But that’s already really bad luck, since it happens in only ~1% of pregnancies.  Two losses?  OK, fine, a single first-trimester loss out of three pregnancies does seem within the realm of normal.  But three losses out of four pregnancies, including a loss in the middle of the 2nd trimester?  How can people keep attributing this stuff to bad luck?  I mean, I know it’s not always possible to find a cause, but it would be so much more helpful if someone would say, “Look, your history is crappy and indicates a problem.  We don’t always know what the problem is or how to solve it, but here are the things we can check for and here’s why I do or don’t think that each of them might be a problem for you specifically.”  That’s what I want.  Why is it so hard for doctors to talk to patients that way?

Anyway, that’s where I am now.  Waiting to finish miscarrying this pregnancy, walking around, acting like everything’s normal in the meantime, diving back into the literature on pregnancy loss to try to find some answers about what’s happening to me.  This semester has just been so hard, with my dad dying the first week of the semester and my third miscarriage happening in the middle of the semester.  I’m kind of amazed that I’m still functioning, but at the same time I really don’t think I can take any more, and I’m having to bite back yelling at people or bursting into tears all the time.  I have very little patience for anything even a little bit trivial right now, which is really not the frame of mind I should be in during advising week for our freshmen, who are freaking out about their schedules for next semester.  I also can’t handle any kid-related stress, and when my toddler was clinging to me at daycare dropoff yesterday I actually started crying right in the middle of the toddler room.  I don’t think the teachers noticed, and I got myself out and to the car before I really let loose, but I wanted to cling to my son as much as he wanted to cling to me!  You’d think I’d be used to pregnancy loss by now, but I don’t think you really ever get used to it.  Having a living child makes it easier, for sure, but it’s still awfully hard.

So long, pregnancy #4

We had our 6-week ultrasound today for pregnancy #4.  It did not go well.  There wasn’t much of anything to see — a bunch of irregular lumps that might have been bleeds and might have been products of conception but no gestational sac, yolk sac, or fetal pole.  The OB gave me the option of waiting and coming back in a week for another ultrasound, but admitted that she thought there was basically no chance that it was a viable pregnancy, so she gave me a prescription for misoprostol to take this weekend.

I knew, going in.  I’d had some extremely light spotting on and off, and zero pregnancy symptoms.  Even with the encouraging betas last week, I’ve been pregnant enough times now that I just knew something was off.  I usually get stretchy round-ligament-type feelings, and I’d gotten them the week after the positive HPT, but then they tapered off.  I’d had some tenderness while nursing, and it tapered off too.  But even though I expected it, it’s not much easier to deal with.

I just feel the overwhelming weight of needing to (1) get through this miscarriage, (2) go through the whole long process of trying to conceive again, and (3) going through another anxious pregnancy where I’ll be freaking out at every stage.  It just feels like too much right now.  But there’s no getting around step 1 — my only hope is that it won’t drag out too long (like it has the other two times, says my pessimistic self).  I can’t say I’m really looking forward to step 2 either — I just hope that awful ovulation pain doesn’t come back.  And while step 3 is a necessary mile marker on the way to the goal of having another living child, I’m really not looking forward to it either.  I’m just so tired of everything conception- and pregnancy- and miscarriage-related.  God, I can’t wait for this phase of my life to be over.

The other set of decisions I’m having to make is how aggressive to be with follow-up.  I put in a call to my RE’s office this afternoon, although I haven’t seen them in 8 months so I don’t know if they’ll get back to me quickly or have me come in for an appointment before they’ll talk to me.  I need to decide whether or not I want to ask for testing of the products of conception, for example (probably, since I always think that more data are better).  I had a lot of testing after the 2nd-trimester loss of our daughter, but I will probably make an appointment with the RPL clinic at my RE’s office for a consultation to make sure there’s no other testing they recommend (they encourage consultations after two consecutive losses).  For example, it seems like it wouldn’t hurt to have my thyroid and some other things checked again, since they haven’t been checked in several years.  My guess is that everything will come back normal, and they’ll just tell me to quit breastfeeding and send me on my way, but you never know.  My OB did tell me she’d recommend progesterone next time as a precaution (the RE had me on it for my pregnancy with my son, so I’m no stranger to it).

Breastfeeding is a whole other can of worms.  I know that it probably makes sense to wean before we try again.  While there’s no really good evidence, there’s circumstantial evidence that it can lead to difficulties with implantation, and so it seems like a sensible step to take now that my son is 20 months old.  But… he doesn’t want to wean, and I don’t want to wean, and the whole idea is just making me feel a lot more miserable.  It’s like, on top of dealing with dead baby #3, I now have to face the prospect of making my one living baby miserable and bringing an end to one of the few things that has gone perfectly right during my reproductive years — depriving myself of a beautiful part of my relationship with my son just on the off chance that it might help me not kill another baby.  It’s just not fair, dammit.

Well, as many of the readers of this blog know all too well, even with recurrent losses the odds are still reasonably good (though not great) that next time will be a success, so probably the main thing to do is just move on with getting un-pregnant and then trying to get pregnant again.  I can only hope that it will go quickly and not drag out for another eternity.