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.