Very strongly pregnant

Okay, ummmm, it worked.  It REALLY worked.  I got the call from my doc’s office this afternoon.  He said I was “very strongly pregnant.”  My HCG at 16dpo was 519.  519.  That’s high.  Higher than my son was, which, as I said just yesterday, I would be thrilled to have.  Much higher than the median self-reported for continuing to heartbeat (which is 282).  Based on studies on HCG measurements, it’s >95% likely for a continuing pregnancy.  That’s like TWINS high.  (Okay, okay, not really.  Let’s not get hysterical here!)  And I thought my crappy little thawed day 6 was going to be a dud!  I threw a multi-day tantrum last week!  Goes to show you never can tell.

Of course, we know that my diagnosis is “unexplained, likely high number of genetically abnormal embryos.”  Yuck.  If that’s true, this could be a ticking time bomb.  For a normal person, an HCG of 519 at 16dpo with a chromosomally normal embryo would be a fantastic sign.  For me… well, we will just take it one day at a time.  But, it implanted.  It stuck.  And it’s still going (or at least was).  And that number is high enough that I am HOPING it’s not ectopic.  I have another blood test on Wednesday to confirm that HCG is doubling.  That should rule out an early miscarriage or ectopic.  Then we just have to make it to neural tube closure.  And heartbeat….  But today, things are as good as they could be.

Predictions

Okay, my blood test is tomorrow—16dpo.  (It should have been 14dpo—2 days ago—but no blood testing at my clinic on the weekend.)  I know I had enough HCG in my blood test to get a positive pregnancy result on a pregnancy test 13dpo.  But, that’s just the first of many steps.  I’ve had enough HCG in my blood to have a positive pregnancy result at least six times—my ectopic pregnancy, my first (pre-IVF) miscarriage, my son, my blighted ovum, my post-IVF miscarriage (chemical pregnancy), and my anencephaly pregnancy.  And only one of those resulted in a healthy child.  Sooooo, yea, getting a positive pregnancy test is just the first step for me.

NOW, if I get a good HCG number tomorrow, we’re on to something.  I’ve only had 2-3 strong HCG numbers—my son, my blighted ovum (and it was not that strong of a number), and my anencephaly pregnancy.  My pregnancy losses have tended to be very early, with low HCG numbers, so if we pass THAT hurdle we’ll be cooking.  I already have in my mind a number I’d like to see (my son was 480 on 16dpo—I’d be THRILLED to see that number), although because I had a slow-developing frozen embryo I recognize that its numbers could be a little lower and it could still be viable.  

I know I did not have measureable HCG in my urine on 11dpo… or do I?  I’ve proven I’m incapable of following the directions for HPTs.  After my 13dpo debacle, I fished the 11dpo pregnancy test out of the garbage.  There were two lines.  (The second one was faint, but there.)  Since you’re not supposed to read the results after 10 minutes…. I suspect that means you’re REALLY not supposed to read the lines after 5 days.  So who knows.  (I’ve read that “Some kits improve in detection when read after a wait of 10 minutes, but waiting longer than that may produce a negative result that looks faintly, misleadingly positive” http://www.cbsnews.com/news/the-best-pregnancy-tests/)

I still don’t FEEL pregnant, regardless of whether I have some measurable amount of HCG.  (Still no sore boobs, dammit!)  But, on the evening of 13dpo, I did have some spotting.  At first I freaked out until I remembered—implantation bleeding!  So that was a good sign.  

A friend said something very kind recently.  After I told her that my doc thinks we produce a large number of genetically abnormal (though chromosomally normal) embryos, she suggested that meant that my lower quality embryos might have the same chance of success as my better quality ones.  That was a good point.  And, indeed, now it appears that my lower quality one is doing better than the better quality ones.  (Although maybe that’s because of my thicker lining or Medrol?)  BUT, I have to keep reminding myself, if it’s true that we produce a large number of genetically abnormal embryos, the fact that we have a chromosomally normal embryo that is implanting does not insulate us from failure.  In other words, I might still be fucked.

Anyway, what are my predictions?  It’s VERY hard to be optimistic in this situation, but the fact that I have gotten a positive HPT result and had some implantation bleeding is encouraging.  Right now I give this a 50/50 shot at best.  If I get a good number tomorrow… well depending on how good… I’ll revise my prediction.  If I get a bad number, well, depending on how bad that might answer the question.

There IS a silver lining, whether this fails or succeeds.  I was fretting last week that maybe something happened to the frozen embryos and that it was a lab issue—what are the chances that I would have so many failures??  But now that this seems to be at least progressing a little bit, it’s hard to believe it’s been caused by my lab.  It’s just my shit embryos.  I won’t have to look back and worry that I should have done something else.

The steroid of choice: methylprednisolone

Did I mention that (for the first time) I am on a steroid this time around?  After our conversation about “Hail Mary” protocols, my doctor agreed to use a steroid.  Initially he wanted to proscribe dexamethasone, but I’d read a lot more good things about prednisone. 

http://3yearwait.blogspot.com/2015/10/switching-horse-mid-race.html

http://3yearwait.blogspot.com/2015/10/cheating-on-my-fertility-doctor.html

http://3yearwait.blogspot.com/2016/01/the-other-corticosteroid-dexamethasone.html

http://3yearwait.blogspot.com/2016/02/its-not-meits-you-embryos.html

We split the difference (?) and went with methylprednisolone (Medrol).  I’m on a 16mg oral tablet once a day at night, right before bed.  I started on day 10 of my cycle (so before my transfer) and will be on it… well, we’ll see.  If this does not work I’ll go off of it right away.  Otherwise I think he was thinking I’d be on it sometime through the first trimester.

Via blogs, I’ve read about a lot of IVF clinics putting patients on Medtrol around their transfer, especially in situations where the patients used ICSI/assisted hatching.  It seems that many patients only go on it for a handful of days before transfer. 

The side effects sound similar to other corticosteroids, although I’ve read some may be more minor.  A friend who was on a similar dosage (during her egg retrieval) said she had insomnia, so started taking it during the day.  I have not had any problems falling asleep, but I have been waking up a little early recently…. Maybe just a coincidence. 

Other than it’s a corticosteroid (like prednisone/prednisolone/dexamethasone), I don’t know much about methylprednisolone.  I just don’t have the energy to read about methylprednisolone versus prednisone (or prednisolone) versus dexamethasone right now.  If this does not work, I’ll look into it some more.

In which a husband tells his wife she's pregnant

There was a story--maybe a year ago?--where a husband allegedly put a pregnancy test in the toilet and was the one who broke the news to his wife that they were pregnant.

What a bunch of hippy dippy baloney. (I won't post a link to the story because I'm sure it's fake and also the people seem horrible.)

But I can imagine a scenario where a husband tells his wife she's pregnant. Maybe it's a situation where they've been trying to get pregnant for years. Maybe after 6 (or 5, depending on how you count) failed IVF attempts, she's not feeling very optimistic. Maybe this was the worst embryo they've ever used (or tied for last). Maybe she has no symptoms--no sore boobs, no implantation bleeding, absolutely nothing. Maybe she took an early pregnancy test and it was negative. Maybe she cried all day for two days and called her clinic to see if she could come in early just to get the inevitable bad news. (They probably said no.) Maybe she took one last pregnancy test the day before her missed period, just to be sure. Maybe she read it after two minutes and got back into bed, dejected. Only one line, as expected. Maybe when her husband went to brush his teeth half an hour later, the test was still on the floor, but this time there were two lines instead of one. Maybe he walked back into their room, holding the test, confused. Maybe she told him tests were not accurate after ten minutes... But decided to take a second test and wait the full three minutes like the instructions say, this time. Maybe after three minutes there were two lines--the second one was faint, but it was there. Maybe she knows that a measurable amount of HCG the day before her missed period is in no way a guarantee of a viable pregnancy, but she's excited that there's still a chance. 

I could imagine that kind of a scenario, in which a husband tells his wife she's pregnant. 

Do you (I) have a good fertility clinic?

It can be hard to know if you have a good fertility clinic.  So, where does one begin if they want to figure that out?

Take a look at this chart showing the national averages:

http://nccd.cdc.gov/DRH_ART/Apps/NationalSummaryReport.aspx

If your clinic has stats below the national averages (check here: http://www.sart.org/Find_A_Clinic/), find a new clinic.

(My clinic has stats that are way above the national average, and I still have some regret that we did not just pull the trigger and go to CCRM.)

Also, here’s some guidance on what the “best” labs do.  

http://fertilitylabinsider.com/2010/09/common-practices-of-the-best-ivf-programs/ 

From what I know, my lab does almost all of these things.  

When to take a home pregnancy test

For most of my cycles, I’ve “cheated” and taken home pregnancy tests.  They’ve always been accurate.

The first question is whether it matters—the fact that you have HCG is less important than what the number is and whether it’s doubling.  (Which is why fertility clinics want clients to wait for the blood tests.)  But assuming you just want to know something as early as possible, well, you can use home pregnancy tests.  

As I’ve written in the past, HCG rises during the pregnancy, but people can definitely have different measurements and still have successful pregnancies:

http://3yearwait.blogspot.com/2015/11/beta-hcg-measurements-part-ii.html

An embryo that implants later would be expected to have lower HCG than one that implanted earlier, and twins have higher HCG than singletons.  Also, not all pregnancy tests are created equally.  (I like the Clearblue Easy Earliest Result Pregnancy Test and First Response Early Result Pregnancy Test, both of which allegedly measure at 25 mIU/ml.)

http://3yearwait.blogspot.com/2015/10/to-pee-on-hpt-or-not-to-pee-that-is.html

I found an interesting article on the question of when to test…. 

http://www.ivfconnections.com/forums/content.php/673-The-IVF-Two-Week-Wait-%282WW%29-If-and-When-to-Do-a-Home-Pregnancy-Test

So here are my thoughts on HPT testing:

Cycle day	Event / Thoughts on HPT
12	HCG trigger (for fresh cycle)
13
14	Retrieval (“ovulation”)
15 (1dpo)
16 (2dpo)
17 (3dpo)	3-day transfer
18 (4dpo)
19 (5dpo)	5-day transfer (embryo could start to implant today)
20 (1dp5dt)      (6dpo)	(embryo could implant today)
21 (2dp5dt)      (7dpo)	(embryo could implant today)
22 (3dp5dt)      (8dpo)	Some women allegedly get a positive HPT on this day (early implantation, twins?)
23 (4dp5dt)      (9dpo)	The earliest high quality home pregnancy tests claim to start to be accurate (“5 days before missed period”)
24 (5dp5dt)      (10dpo)
25 (6dp5dt)     (11dpo)	Generally the first day I would feel comfortable testing to get a reliable result
26 (7dp5dt)      (12dpo)	Would expect a sensitive HPT to work for most viable pregnancies
27 (8dp5dt)      (13dpo)
28 (9dp5dt)      (14dpo)	Official blood test at doc’s office (“missed period”)

I guess this would be a good time to mention that I took a home pregnancy test this morning and it was negative.

Day 5 versus day 6 blastocysts

My doctor’s office has suggested it sees similar success rates with frozen day 5 and day 6 embryos, so I never really worried about the fact that many of our embryos were day 6. 

(http://3yearwait.blogspot.com/2014/08/my-snow-babies.html)

I’m reconsidering.  I have used three day 5 embryos.  They have all “worked.”  (My son, blighted ovum at 6 weeks, and anencephaly pregnancy.)  Of course they were also B2s, so good quality.  And they were also all fresh.  So they were the best of the bunch—they should have been the best ones.  I’ve also used four day 6 embryos.  None of them have worked.  (Chemical pregnancy, no pregnancy, and my last two with HCG of 2 and 1.)  Of course 3 of the 4 were poor quality B3s.  And all were frozen.

I mean, it makes sense that the more advanced the embryo, the more likely it is to work.  Fully hatched > hatching > nothing.  No surprise that the fastest embryo out of the gate is the most likely to work.

This article suggests that similarly developed frozen day 5 versus day 6 embryos have similar success rates (like my clinic suggests):

http://humrep.oxfordjournals.org/content/early/2010/06/11/humrep.deq143.full

“[A]nalysis of those studies where the Day 5 and Day 6 blastocysts had the same morphological quality at the time of freezing showed no difference in clinical pregnancy and ongoing pregnancy/live birth rates.”

This article agrees:

http://link.springer.com/article/10.1111%2Fj.1447-0578.2008.00203.x

However, the fresh results are not the same:

http://www.ncbi.nlm.nih.gov/pubmed/11384637

“Embryos that develop to the expanded blastocyst stage and are transferred on day 5 after retrieval are approximately twice as likely to implant compared to those for which expansion and transfer are delayed until day 6.”

Although, interestingly, day 5 embryos are more likely to survive the thaw than day 6 (maybe because they tend to be higher quality?):

http://fertstertforum.com/kovalevskyg-blastocyst-frozen-embryo-transfer/

“A total of 1,406 embryos were thawed with a survival of 90.7% for day 5, 83.7% for day 6, and 78.7% for day 7. Implantation rates were 43.3%, 28.9%, and 28.9%, respectively. Ongoing PRs were 43.9%, 32.9%, and 26.7%, respectively.”

This article makes no distinction between quality.  I’m guessing that the day 5 embryos tended to be better quality than the day 6s (as has been our experience).

So I guess I should not fret over the day 5 v. day 6 issue… and just continue fretting over their poor quality.

Miscarriages... More likely with girls?

I can’t help but observe that I know the gender of 5 of my pregnancies.  My son and the last four transfers we have done, which are all girls.

And only the boy made it.  (So far, we’re still waiting on the last girl.)

I’ve been wondering—is that a sign?  Am I not meant to be the mom of a daughter?  Or is it possible there’s an unknown reason—like something genetic related only to girls?  Or is it just dumb luck?

Maybe it’s because females are more likely to miscarry.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3150206/

This article suggests that for women with recurrent miscarriages, 64% of the embryos were female:

“In total, 313 specimens were successfully karyotyped, with a median gestational age of 10 weeks at miscarriage (interquartile range 8–13); 199 (64%) were females and 114 (36%) were males. In total, 121 (39%) had abnormal karyotypes, the most prevalent of which were chromosome 21 and 16 trisomies, triploidy, and monosomy X.”

Because the minority of the miscarriages were related to chromosomal abnormalities… something else was going on.  This article suggests that “In our opinion, during the first trimester of pregnancy, miscarried female POC may be partially due to imprinted paternal genes.”

I’m sorry—what now?  

I had to go to Wikipedia.  (https://en.wikipedia.org/wiki/Genomic_imprinting) It’s complicated, but from what I can gather from the article, some women’s bodies may just prefer male embryos.  (We’ve all known that couple that decided for a third… or fourth… because they wanted a daughter, only to end up with yet another boy.)

This article also recognizes the fact that miscarriages are more likely to be female:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4130929/

And here’s another article noting the same thing:

https://www.theguardian.com/science/2015/mar/30/female-embryos-more-likely-to-die-in-pregnancy-than-males-study-claims

It suggests, “Female embryos could be at greater risk due to the way X chromosomes are inactivated in cells, scientists said. Females have two X chromosomes, but one is randomly switched off in each cell, leaving just one with active genes. However, sometimes this process becomes unbalanced and one X chromosome begins to dominate all the body’s cells. If there are genetic flaws on the dominant chromosome, it can lead to fatal health problems.”

Maybe my uterus wants boys.  We’ll see if this girl makes it (I’m not feeling optimistic).

Bootie shots

As I mentioned, we decided to change things up last time and use progesterone shots.

http://3yearwait.blogspot.com/2015/11/getting-into-butt-shots.html

Boy, those suck.

My strategy (heat the butt, heat the oil-filled needle, ice the butt, change the needle, do the shot, rub the butt, heat the butt) generally worked.  I had no knots, little bruising, and just some pain.  EXCEPT ONE TIME.  I think we got the shot just out of the perfect zone and got too close to a nerve.  That spot hurt for MONTHS.  It’s getting better every day, but it’s STILL SORE.  Especially when I would exercise, it would just HURT.  Yuck.

We’re doing the butt shots again this time.  Same protocol as before, but we’re trying to be really careful with the placement of the shots.  Interestingly, the needle gauge is smaller this round than my prior round. And yet, it hurts WORSE this time.  The shot doesn’t hurt, but because the needle is so small it takes like 2 minutes to empty the syringe.  And it’s two minutes of PAIN.  Double yuck.

I feel bad for my poor husband too.  As he confessed the other night, “I really hate this.”  Me too, buddy.

Choosing how many to implant

I’ve been pretty consistent with the opinion that we do not want twins / the health risks that accompany them, and for that reason we’ve done EIGHT single embryo transfers.

http://3yearwait.blogspot.com/2014/04/the-age-old-question-to-implant-two.html

http://3yearwait.blogspot.com/2015/02/yeswere-still-talking-about-this-how.html

Studies suggest that, obviously, putting in more embryos increases the chance of success in any single cycle, but it also dramatically increases the risk of twins.  On the other hand, if you are willing to serially implant embryos (ie. two single embryo transfers back-to-back), you end up with the same overall pregnancy rates, albeit with more cycles:

http://humrep.oxfordjournals.org/content/20/10/2681.full

So that’s what we’ve been doing.  I’m not going to lie, embryo transfers are a major, major drag, emotionally and physically.  (And for people who don’t enjoy burning money like we obviously do, they’re expensive too!)  So doubling the number of transfers one has to do… well, it’s not for the faint of heart.  But, and I still believe this, it would be my biggest regret if we put two embryos in and then ended up with twins and something terrible happened to either me or the babies.  Which is why, as much as I HATE this process, we continue down the SET road. 

Everyone (my doc, the docs we talked to at CCRM, and my acupuncturist) agreed that twin pregnancies are not desirable, and too risky with chromosomally normal embryos.  But, after six failed single embryo transfers in the past two years (or five, if we do not want to count the anencephaly one against us), it can be tempting just to say “fuck it, put two in!”  I told my husband, I am CERTAIN that we are the only people in the world who would have six (or five, depending on how we want to count) failed SETs in a row and choose another SET for our seventh cycle.  His response: “we don’t want twins.”  I like his optimism!

So we stayed the course and implanted only one embryo—a bedraggled looking one, which looked particularly rough when I compared it to pictures of its smooth and hatching (or hatched!) failed siblings.  I don’t think it was the ugliest embryo we ever used (there was a rough untested one in 2014…) but it’s definitely less cute than the other seven we’ve used. 

If this one makes it, it will be like the ugly duckling turning into a swan.  

I’ll admit that less than 12 hours after our transfer I started having regrets about choosing another SET.  (Hell, when I looked at how rough the embryo looked before our transfer I started having regrets!)  But if this one does not work, we’re going to thaw our last two embryos together.  Chances are the chromosomally untested one—which we were told was a very early and rough looking blastocyst when it was frozen—will probably not survive the thaw or work.  Even if it does, after as many failed cycles as we’ve had, many with chromosomally normal embryos, I think our chances of twins are approaching zero.  (Famous last words?)

So, let’s hope this one works.  Otherwise, for our last cycle we’re doing what most people would have done long ago… rolling the dice on two embryos.

Thickening linings

Anyone who has been following this blog knows that I’ve become a bit obsessed with my “thin” endometrial lining.  (http://3yearwait.blogspot.com/2015/11/unlucky-77mm-aka-another-crap-lining.html; http://3yearwait.blogspot.com/2015/11/damn-thin-linings.html;http://3yearwait.blogspot.com/2015/12/my-acupuncturists-advice.html;http://3yearwait.blogspot.com/2015/02/lets-talk-about-something-we-havent.html;http://3yearwait.blogspot.com/2015/02/lets-talk-about-something-we-havent.html)  Of course, now that I know it’s probably just my shitty embryos and not my lining, I’m a little less worried about it.  (http://3yearwait.blogspot.ca/2016/02/its-not-meits-you-embryos.html)  Nevertheless, I’ve been doing everything in my power to thicken my lining “naturally”—which probably is much less important than the estrace I’m on 3x/day! 

I managed to thicken up my lining for this transfer.  All of my linings have been “B”s, which is good.  With my early fresh cycles I had thin linings (fresh cycle with son 8mm, fresh cycle with blighted ovum, 8mm), but that’s always a risk with a fresh cycle.  (The drugs that make you grow lots of eggs are not necessarily the same ones to grow a great lining.)  I managed to get some thick ones for my later failed frozen transfers (11mm, 10mm).  Then I pulled a really thick one for my fresh anencephaly pregnancy (11mm).  Unfortunately, since my abortion I have gone back to thinner linings for my subsequent frozen cycles (8mm each time)—a risk from having an abortion, unfortunately.  SO, for this cycle I religiously did acupuncture one to two times a week, gagged down supplements (literally), drank ginger tea, put heat packs on my abdomen, started eating red meat again, and begged my clinic to keep me on birth control for the bare minimum 21 days (which they did). 

And what do I have to show for all of my hard work?  I’m at 9mm (8.5, actually).  Well, it’s not amazing but it might be the best I can do.  Everyone knows how worried I’ve been about my lining, so they’re all super positive about it.  (The nurses: “GREAT lining!” My acupuncturist: “Super!”)  It’s good to have cheerleaders.  L-I-N-I-N-G!  Go lining! Go lining!

Lucky number 7?

I cannot believe we are still doing this over two years later…. But here we are.  We’re on the home stretch now.  If this one does not work, we have one more frozen cycle left.  And then we’re done.  I’ll be happy to leave behind the stress and the drugs and the endless doctors’ appointments and the vitamins and the disappointment and the lifestyle restrictions and most of all the uncertainty.  Hopefully we end up with a kid so I can say, “it was all worth it” or “it had to happen this way” or something else with a positive spin.  

So FOR THE EIGHTH TIME (and seventh time since we started our quest for a second kid), we begin the two week wait.

Repeated implantation failure

I generally do not appear to have implantation failure—they implant and then stop working.  Sigh.  But for anyone struggling with this, here is the most robust article I’ve ever read on implantation failure:

http://www.iffs-uit.com/article/S1472-6483(13)00475-6/fulltext

And here’s another article that talks about repeated implantation failure:

http://www.sciencedirect.com/science/article/pii/S1110569014200124

It suggests that “day-3 and day-5 sequential transfer” can be helpful—that is, transfer one on day 3 and then transfer another one on day 5.  I’d never even heard of that!  We’re not doing another fresh cycle, so this is just more of a “good to know” kind of thing.  Obviously putting two in would increase the chances of twins, but for people with repeated implantation failure that might not be such a concern.  The other problem with this method, of course, is that it does not leave room for genetic testing.

Recurrent miscarriages

This article goes through common reasons for miscarriage: chromosomal abnormalities, blood disorders, and endocrine abnormalities (including anatomical abnormalities, luteal phase defect, and LH hypersecretion). 

http://www.medscape.com/viewarticle/722321

Here are some high points:

“Chromosomal anomalies are known to be the single most common cause of spontaneous abortion. . . . In up to 7% of couples with at least 2 spontaneous abortions, one partner carries a balanced chromosome rearrangement.”

“Given that about 50% to 60% of patients with recurrent miscarriages harbor a coagulation defect and that identification of the defect, followed by appropriate therapy, will lead to normal-term delivery in 98%, the cost of evaluation (about $1200) can be justified. . . .  All patients found to have a blood-protein or platelet defect associated with recurrent fetal loss caused by hypercoagulability and thrombosis (thrombosis/vasculitis) of placental vessels are treated preconception with low-dose aspirin at 81mg/day. . . . Several studies have assessed the role of the postconception addition of heparin; however, most have used higher doses than those used in our clinical practice.[16]Rosove and colleagues[31] reported a 93% success rate with dose-adjusted subcutaneous heparin, the mean heparin doses being about 25,000 units/day. Kuttah,[32] in a population of 25 patients, treated with aspirin plus dose-adjusted subcutaneous heparin, noting a success rate of 76% (mean heparin dose of 26,000 units/day). In the study by Many and colleagues,[25] patients treated with prednisone plus aspirin plus heparin at 5000 units twice a day had a better outcome (69%) than those treated with aspirin plus prednisone (43%) or prednisone alone (7%).”

“Thus, well-documented, persistently low levels of progesterone in the luteal phase of the cycle are likely to be the consequence of abnormal folliculogenesis. This condition is more likely to be improved by low doses of clomiphene citrate in the early follicular phase of the cycle than by postovulatory administration of progesterone. A search for subtle ovulatory dysfunction, such as that related to hyperprolactinemia, should be conducted, and treatment should be administered accordingly.”

“This study indicates that midfollicular (cycle day 8) LH hypersecretion (random serum LH of 10 mIU/mL or greater) is associated with a marked increase in the incidence of spontaneous abortion. Those findings, which have since been confirmed by others, suggest that hypersecretion of LH is associated with subfertility and early pregnancy failure. To date, however, prepregnancy treatments to suppress elevated serum concentrations of LH with GnRH agonists have not improved pregnancy outcome when compared with expectant management/supportive care during early pregnancy.”

“However, the percentage of miscarriages in which a chromosome abnormality is detected decreases from 70%-80% for a first miscarriage to 40%-50% after 3 or more miscarriages. Therefore, 50% of recurrent miscarriages may be preventable.”

Well, we know we have “chromosomally normal” embryos (they were tested) and we do not have translocations (we’ve been tested).  We’ve also been tested for clotting disorders—no issues there.  We (I) have also been evaluated for uterine abnormalities—all is good there.  The stuff about luteal phase defect and LH hypersecretion is interesting. 

Unfortunately, for about half of all women with recurrent miscarriages, also known as idiopathic recurrent miscarriage, there is no known cause:

“Idiopathic recurrent miscarriage is defined as 3 consecutive pregnancy losses with no contributing features found on investigations. At present there are no treatments of proven efficacy for idiopathic recurrent miscarriage.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2785777/

Here’s another article on recurrent spontaneous miscarriage (RSM):

http://www.karger.com/Article/PDF/365973

It suggests that RSM (3 or more miscarriages before 20 weeks) affects 1-2% of women.  It notes that there is no known cause for 40-60% of RSMs.  Women who have RSM without a live birth have a 50% chance of giving birth.  Women who have RSM after a live birth have a 70% chance.

Reasons can be (1) genetic (3-5% of RSMs), with balanced translocations being the most common chromosomal issue in RSM; (2) anatomical (between 1.8-37.6% of RSMs), more common for women who have already had a child or second trimester losses; (3) antiphospolipid syndrome—an autoimmune condition (15-20% of RSMs) also discussed with thrombophilias; (4) endocrine disorders; (5) immune-related factors and natural killer cells (controversial) – the article suggests that reducing NK cells may increase pregnancy chances, and increased NK cells may be associated with implantation failure; (6) infection.

The article discusses a bunch of tests that can be run to evaluate the diagnosable causes.

The article suggests that for unexplained RSMs, the reason may be immunological or chromosomal abnormalities.

The authors seem to like heparin, but not steroids, for treatment of antiphospolipid syndrome.  It notes that corticosteroids are associated with “significant fetal and maternal morbidity.” Yuck.

Anyway, it’s a good read for anyone suffering from RSMs to think about what testing and treatment options they might have.

It’s not me—it’s you [embryos]

Okay.  I had an eye-opening conversation with my RE.  (And I thought my eyes were already pretty open.)

I should start by saying my RE is not a bull-shitter, and he does not like to speculate.  (Two things I like about him.)  So when he tells me things, I believe him.  I’m not saying he’s always right, but I think that he tells me what he really thinks.  So, here we go…

He thinks the fact that our last two cycles were quick implants and losses suggests that there is something wrong with the embryos.  Because they were tested, we know they had a normal number of chromosomes.  But that does not tell us about the actual genes.  Combined with the fact that we have had seven pregnancy losses, most of which were early, he thinks that we produce a large number of (while chromosomally normal,) genetically abnormal embryos.  And it might be that there’s something with my genes that is wrong but not fatal (I’m okay) and same with my husband, so we can produce normal embryos (our kid!), but we also produce a lot of bad embryos.  Maybe in 10-20 years doctors will be able to sequence the actual genome (and freak everyone out with the prospect of designer babies), and we will be able to tell at that point which embryos were wonky.  Now, we just have to keep putting embryos in and hoping one is okay.  (He also indicated that this was not a common affliction, and that if his theory is true my husband and I could have gone on to have no issues with other partners.  Crazy!)  We know that our last three chromosomally normal embryos that failed were all female, so maybe it’s something just with girls?  Who knows!

Now, this is just his theory, but it would explain why we’ve had so many early losses.  And it could explain our blighted ovum and even our anencephaly pregnancy. 

That theory made me feel much better.  I’ve been beating myself up over and over again that there was something wrong with my womb (clotting disorder, thin lining, immune issues! – I’ve been calling it the bat cave) or something wrong with my actions (not enough folic acid, too much exercise, etc!).  But maybe it’s not me at all…. it’s the wonky embryos!  And if that’s true—we produce some normal embryos, but a lot of abnormal ones, and it’s nothing we can test for—well, it’s just a numbers game.  How many times are we willing to do this?  And if I’d known that was the score from the beginning, I might’ve come to the same decision we find ourselves having made at this point: put ourselves through two fresh retrievals, and use the embryos from those (9 total embryos) and be done.  BRUTAL, of course, but at least we would know what we were in for. 

He and I talked more about dexamethasone.  He said it was a steroid that lowers white blood cells (inflammation), which could cause implantation issues.  He said that less than 5% of his patients go on dexamethasone, and the ones that do are the ones who have later repeated first trimester losses suggesting potential immune issues.  He puts patients on 0.5mg dexamethasone and then tapers them at 6 weeks.  He said he did not have any concerns about impact on the developing fetus.  He noted that dexamethasone was more frequently used during the egg retrieval cycles, as it could be used to decrease cycle cancellation and increase egg retrieval.  (I have a friend who has done several retrieval cycles at CCRM and she told me she had been on dex for all of those cycles.)

He said that he really does not think we have an immune issue, but at this point he’s willing to try a steroid.  We talked about prednisone as well.  He said his lab has only used dexamethasone, but he would consider other steroids.

We also talked about antihistamines.  He said that theoretically they could have an impact, but he would not want to put a patient on both steroids and antihistamines.

The average patient at my clinic with a chromosomally normal embryo has about a 70% chance of getting pregnant.  Based on our history, and his theory that we have chromosomally normal but genetically abnormal embryos, he gives us a chance of 50% with our B2 boy, 40% with our B3 girl, and 10% with our untested mystery embryo.  Okay, those are not great odds, but we’re not totally out of the game!  Based on his opinion of our chances of success, we’ve decided to stay the course.  Our next transfer we will continue to do a selective single embryo transfer, even though we’ve had SIX failed SETs in the last two years.  Yes, we are thrill seekers.  (If we implanted two embryos, they worked, but then something went wrong—it would be one of my greatest regrets.)  IF the next one does not work, we might transfer two for the last cycle, because the chances of the both the last one and the “wonky” one working, considering our history, is incredibly low.