Predicting success part 1: cumulative chances of success (or failure)

I’ve previously posted about my clinic’s success rates, depending on the quality of embryo used: http://3yearwait.blogspot.com/2014/04/get-out-your-calculator-its-time-for.html

Success statistics are amazing—in theory, they should tell you how many embryos to implant, and whether it’s worth your time and money to continue with further cycles.

Unfortunately, my experience has been that my clinic, at least, treats every cycle like it’s my first cycle—that is, they quote me success statistics based solely on the quality of the embryo and my age, not taking into account the obvious fact that each failure decreases the chances of success in the next round.  I also think they are wrong not to worry more about the lining thickness. 

Also, clinics often treat “pregnancy” as a success, but I think of success as a live birth of a child.  So those high pregnancy rates are not necessarily so wonderful, because the live birth rates are always lower.  (I’ve been pregnant 7 ¾* times, and I’ve had one live birth.  Pregnancy is not a success to me.)

A woman has created a blog that includes a “success rate calculator”:

http://www.smartfertilitychoices.com/ivf/

Now, an ideal success rates calculator would use all of your information – exact age, fertility diagnosis, embryo quality, number of embryos retrieved, whether the embryo is day 5, 6 or 7, whether the embryos are chromosomally normal, lining thickness and quality, body weight, results of previous transfers, etc etc etc. and give you a scientific chance of success based on all of your “data.”  This calculator asks for just a few of those data points (age range [35-39], diagnosis [unexplained], single or double embryo transfer [single], 3 or 5 day transfer [5], freezing method [vitrification]) to give you a chance of success per cycle.  She does not say exactly how she figures out her results, but here are hers for me:

	Chance of live birth
	fresh	frozen
Per cycle:	18.9%	23.1%
Per single embryo transfer:	25.2%	24.9%
Per year:	27.4%	37.4%

“Per cycle” means how likely are you to get pregnant if you start a cycle.  Per embryo transfer is how likely are you to get pregnant after you’ve actually transferred an embryo.  (She also gives a “per embryo” statistic separate from a per transfer statistic for people who are thinking about doing a two-embryo transfer.)  The last one is cumulative success rates for a woman who continues to try for one year.

This is somewhat interesting, but like I said it lacks input for other relevant data.  The most interesting outputs are the first two.  The third one (trying for a year) is nebulous.  Some women might get 6 frozen cycles in a year, others one or two.

Nonetheless, she paints a bleak picture for me—only a 25% chance of success per transfer, and my chances of having a child never go above even 40% if I try for a year.

Even without the robustness that would come with more data, I think she’s spot-on.  I’m screwed.

She also gives predictions for multiple cycle success rates.  For me, with a per embryo success rate of “25%” I have the following cumulative success rate (she does them in intervals of 2, so I’m optimistically using the 26% chance of success instead of rounding down to the 24% chance of success):

Cycle     Cumulative chance for a live birth

1             26%

2             45%

3             59%

4             70%

5             78%

6             84%

7             88%

8             91%

9             93%

10           95%

Wow, 95% looks amazing!  Again, though, that assumes 10 embryos to transfer.  Most women do not. 

Let’s frame this another way to demonstrate the real diminishing returns with more cycles:

Cycle     Chances cycle will work

1             26%

2             19%

3             14%

4             11%

5             8%

6             6%

7             4%

8             3%

9             2%

10           2%

That’s right.  You have a 26% shot with your first cycle.  If that one fails, there’s only a 19% chance the next one will work.  And so on until you only have a 2% chance of success.

That’s what I’ve been saying all along!  It’s not just simple math that you have the exact same chance with your first embryo as you do with your last embryo.  Presumably you used your better—and thus more likely to work—embryos first.  Thus, your chances are not the same at the end as they are at the beginning.  Even if your embryos are literally the exact same quality, your chances of success still decrease because whatever made the last embryo fail might doom the next one as well.

Her chart has cumulative odds from 2% per embryo (sucks to be at 2%) all the way up to 60% (young women, perfect eggs still can’t get above a 60% chance of success).  For those 60%ers, by cycle 5 99% of them will have a kid.  For the 2%, well there’s not a lot of hope. 

Here’s an article that recognizes, generally, that IVF has certain cumulative success rates depending on age:

“Among 6164 patients undergoing 14,248 cycles, the cumulative live-birth rate after 6 cycles was 72% … with the optimistic analysis and 51% … with the conservative analysis. Among patients who were younger than 35 years of age, the corresponding rates after six cycles were 86% … and 65% … Among patients who were 40 years of age or older, the corresponding rates were 42% … and 23% …. The cumulative live-birth rate decreased with increasing age….”

http://www.nejm.org/doi/full/10.1056/NEJMoa0803072?viewType=Print&viewClass=Print&_sm_au_=iVV3t8VMPNtsjRfP

As one article recognizes, “Contrary to the perception of many, IVF does not guarantee success; almost 38–49% of couples that start IVF will remain childless, even if they undergo six IVF cycles.”

http://en.journals.sid.ir/ViewPaper.aspx?ID=266706

That’s me.  Six cycles and no kid.  

The article recognizes many of the different factors that play into chances of success:

·        female age (younger is much better)

·        duration of subfertility (shorter is better)

·        type of subfertility (that a previous pregnancy or live birth substantially increases chances of success)

·        indication for IVF (male vs female, but it’s unclear which is worse)

·        basal follicle stimulating hormone (bFSH) (estimate of ovarian reserve, higher value is worse)

·        fertilization method (ICSI increases pregnancy rates)

·        number of oocytes (perfect number to retrieve is 15, and lower is worse)

·        number of embryos transferred (obviously more embryos transferred increases success rates)

·        embryo quality (obviously higher embryo quality is better)

It also cites 21 other articles that tried to model chances of success, defined as either pregnancy, ongoing pregnancy, or live birth.  Unfortunately, it does not propose a model, and the ones it says are good are not freely available.

Now, if my doctor’s off-the-cuff stats are to be believed (and I have complained already that they treat all cycles as easily likely to result in a pregnancy, which is just not true), here are my theoretical chances of pregnancy and live birth per embryo we have used:

	untested B2	untested B3	untested B3	normal B2	tested B2	tested B3
Approximate chances of pregnancy	51%	18%	18%	55%	55%	40%
Approximate chances of miscarriage	15%	15%	15%	8%	8%	8%
Approximate chances of live birth	43%	15%	15%	51%	51%	37%

If those statistics are true (which they are not) we have only a 6% chance that at this point all of those cycles would have ended in failure.  Which sounds low but that’s more than 1 in 20 women.

So, what are my chances of success for my last two embryos?  You got it.  NOT GOOD.

Here’s an article proposing a model for success, but it uses measurements that I either don’t know or don’t have:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3551786/

*Yea, this cycle did not work.  HCG of 1, which means it implanted and stopped growing.  This is the second time in a row that this has happened.  I will now refer to this as my ¼ pregnancy.  Who says you can’t be a little bit pregnant?

Update on linings

I threw a fit when I found out my lining was only 7.7mm for this transfer.  I’d read enough to know that with linings, more is generally better, and that’s on the thin side. (http://3yearwait.blogspot.com/2015/11/unlucky-77mm-aka-another-crap-lining.html;http://3yearwait.blogspot.com/2015/11/damn-thin-linings.html) 

I ended up calling my doctor’s office before transfer to see if I should take more estrogen or do anything else to bulk up my lining.  The nurse was super confused about why I was concerned (“An 8B is good!”) but did ask the doctor.  He got back to me that he was “happy” with where my lining was.  

I was still fretting on transfer day—I asked if they re-measure the lining.  (The answer is no.)  But I was told, again, that an 8B is good.  7.7! I responded.  She said they even do transfers with a 6. 

Well, whatever, I had what I had.  (I will note my husband trusts doctors more than I do, and took the fact that the doctor was not worried as proof that I worry about things that do not matter.  Whatever. I know my truth.)

Here’s an interesting blog entry on endometrial lining, improving the lining quality and thickness, and again noting that above 9mm is better:

http://fertilitylabinsider.com/2013/10/q-from-u-causes-of-thin-uterine-lining-and-treatments-to-improve-receptivity/

Assuming this cycle does not work (not much of a stretch now), we are going to take a long break and work with my acupuncturist to develop a plan to try to build that lining back up.

Blastocyst grading - no A students here

A very common criteria for evaluating blastocysts is the Gardner blastocyst grading system.  It assigns 3 separate quality scores to each blastocyst embryo:

·        Blastocyst development stage - expansion and hatching status

1 - Blastocoel cavity less than half the volume of the embryo

2 - Blastocoel cavity more than half the volume of the embryo

3 - Full blastocyst, cavity completely filling the embryo

4 - Expanded blastocyst, cavity larger than the embryo, with thinning of the shell

5 - Hatching out of the shell

6 - Hatched out of the shell

·        Inner cell mass (ICM) score, or quality

A - Many cells, tightly packed

B - Several cells, loosely grouped

C - Very few cells

·        Trophectoderm (TE) score, or quality

A - Many cells, forming a cohesive layer

B - Few cells, forming a loose epithelium

C - Very few large cells

More info available here:

http://fertilitylabinsider.com/2011/12/understanding-the-gardner-blastocyst-grading-scale/

http://www.advancedfertility.com/blastocystimages.htm (includes pictures!)

My lab does not use the Gardner blastocyst grading system.  It just rates the blastocysts 1, 2, or 3, with 1 good (around 10% of what they use), 2 fair (around 50% of what they use) and 3 poor (less than 15% of what they use).  Those numbers don’t add up to 100 because they also use embryos that have not made it to blastocyst stage.  [Note that they retrieve more low quality embryos than they use because, hopefully, they only have to use good quality ones for those to stick.]  I think 1 very, very roughly correlates closest to AA, 2 to BB, and 3 to CC.

The lab will tell you if you have a hatching blastocyst.  So I know for some of my cycles that the blastocyst was hatching or hatched.  I don’t know if any of my day 5 embryos were hatching, so I’m going to assume they were not.  Instead, I think they were close, so I’m going to give them a rating of “4” – “Expanded blastocyst, cavity larger than the embryo, with thinning of the shell” – but they might be less.  I know that all of my day 6s were hatching or hatched. 

Emby	My lab rating	~Gardner rating	Result
1	Day 5 B2 (fresh)	4BB	Baby!
2	Day 5 B2 (fresh)	4BB	Blighted ovum
3	Day 6 B3 – hatching (frozen)	5CC	No pregnancy
4	Day 6 B3 – hatched (frozen)	6CC	Chemical pregnancy
5	Day 6 B3 (frozen)	?CC	Still on ice (lab said it looked very rough when they froze it, unlikely to survive thaw?)
6	Day 5 B2 (fresh) [chromo normal]	4BB	Anencephaly
7	Day 6 B2 – hatched (frozen) [chromo normal]	6BB	No pregnancy (implanted but failed immediately – ½ pregnant?)
8	Day 6 B3 – hatching (frozen) [chromo normal]	5CC	Two-week wait
9	Day 6 B2 (frozen) [chromo normal]	?BB	Still on ice
10	Day 6 B3 (frozen) [chromo normal]	?CC	Still on ice
11	Day 6 un-ratable [chromo abnormal]

When I look at the sample pictures of blastocysts, though, I think my ratings might be a little bit too high.  A number of the ones we have transferred look like a hot mess.  So they may not even be as good as what I have suggested above.  Or they might be better.  So far all of my frozen ones have survived the thaw.   We did not use our fifth embryo (and might never use it) because apparently it looked really bad.  So it’s possible that it’s chromosomally abnormal/will not survive the thaw.  And even if it did, it would have a super low chance of success.

Pregnancy symptoms, or lack thereof

I’m feeling better today.  Thanks for the indulgence in listening to me throw my “I don’t think it worked” tantrum. 

Yup.  I don’t think it worked.  I’m five days post-transfer and I don’t have any pregnancy symptoms. 

But I have to keep reminding myself, I usually feel like it did not work at the beginning.  Initially I did not think it worked with my son, although then I was pretty sure it did a few days before my blood test.  (Late implantation bleeding and sore boobs.)  I did not think it worked with my anencephaly pregnancy because I had no symptoms before my positive pregnancy test at 7dp5dt. 

I’ve learned a lot after having been pregnant 7 ½ times.  (I’m not sure what to make of my last one, where my HCG measured at a 2—“not pregnant”—and yet my doctor suggested the embryo did implant.  I’m going with a little bit pregnant.)  Most of my pregnancies were very early losses, but a few lasted for a month or more.  I’ve learned that sometimes I have implantation bleeding and sometimes I don’t.  I’ve learned that sometimes I have nausea; most of the time I don’t.  Sometimes I have insomnia.  Most of the time none.  Sometimes my breasts are super sore, other times not so much.

I don’t think I’ve had sore boobs every time.  And when I have, I started getting them at different times.  With my blighted ovum, they were sore even before transfer, and stayed sore until my positive pregnancy test.  With my early miscarriage in 2014, they were sore just 2 days after transfer.  I did not have any sore boobs last time (my ½ pregnancy).  I think, generally, early sore breasts has been the most reliable sign of pregnany.  I just keep saying to my boobs, please be sore, please be sore.  Nothing.  I’m probably going to make them sore by checking so often!

When I have had implantation bleeding, it has been a couple days before the clinic blood test.  (So around 7 days after transfer.  Remember that handy implantation bleeding calendar?  It says the average is more like 4 days after transfer:http://www.countdowntopregnancy.com/tools/implantation_calculator.php)  So far nada.

Nausea usually comes after the blood test, so not much good it will do me now in my search for early pregnancy symptoms.

Soooo, of course I’m LOOKING for those symptoms as I wait.  Sore boobs, implantation bleeding, nausea, I’ll even take insomnia!  Bring them all on. But I know just because I don’t have them does not mean it didn’t work.  (That’s a lot of negatives!) 

It’s easy to feel negative because the odds are WAAAY against us at this point—with a low-quality day 6 blastocyst (even a chromosomally normal one) after FIVE failed transfers.

Other pregnancy symptoms… oh yea, peeing on a home pregnancy test and getting a positive pregnancy result.  That’s generally been a good sign.  I should, in theory, be able to get a positive result as early as today (5 days after transfer).  If I thought it worked (sore boobs, implantation bleeding) I would take a HPT then.  But with the error ranges being what they are (Sunday would be the EARLIEST I could get a positive) and me being pretty sure it was not successful, Monday (6dp6dt) or Tuesday (7dp6dt) are better bets.  By Wednesday (8dp6dt) if I’m not getting a positive result, we’ll know for sure it was negative.  (And yes, I know pregnancy tests can be wrong, they just never have been for me.)  [Note that HCG measurements will be higher for twins, so women pregnant with twins should get results sooner.  No risk of that with us… unless they’re identical….]

Until then, I’ll just be feeling my boobs every few hours.

Wanting to be pregnant before my due date and other emotional baggage

After my anencephaly pregnancy, I was a mess.  (And still am, but doing better.)  One of my motivations to terminate instead of just carrying until the baby passed or delivering and then having her die was I really do want a second kid, and I did not want to push that off for a year+, which, with my age being what it is, could mean never.  (Other motivators included not wanting to put myself through the physical and emotional challenges of pregnancy just to have the child die, or to have to explain/confront that level of death to my son, or to take on the additional risks of such a pregnancy, etc. etc. etc.)

Anyway, after our termination was complete (end of May), one of my first questions to my doctors was—when can we try again?  They all said we had to wait a minimum of three months, so we could start again in September.  I thought that was good because my due date was in October, so if we did a cycle in September and I got pregnant, I’d be pregnant before my due date.  Then, my reasoning went, I’d at least have something happy on my due date.  Maybe I’d even think, it all had to work out this way….

No dice.  On my due date, all I had was another failed IVF cycle.

I’ve reflected on my borderline irrational desire to be pregnant on my due date quite a few times since then.  What I find most interesting is that I think A LOT of women feel the same way after a much-wanted pregnancy loss, especially if it was a little further along (but not so far along that it would not be an option).  A woman I know who lost a pregnancy at 13 weeks expressed the same desire to me.  (She also did not end up pregnant before her due date.)  And I’ve read a number of blogs where women express the same desire after loss.  (Just google “pregnant before my due date”.)  

I think it’s understandable to want to look for a silver lining when something terrible happens, and the desire for a child does not necessarily decrease just because of a pregnancy loss.  (I think we’ll all agree that for most women it has the opposite effect.)

Anyway, I wanted to be pregnant before my due date.   I rushed into my next cycle as fast as I could.  That cycle did not work and so I rushed into the next one, taking no break in between.  (My current cycle.)  If this cycle does not work, I will take some time off.  I need to get my head together.  Of course, while my frozen embryos might not be aging anymore, my lining and hormones are.   Plus, my little guy will be starting kindergarten before he has a sibling at this rate.  No reason to make it middle school…. 

If this does not work, my original plan was to do another cycle in February (giving myself a full month break before starting anything).  And if that cycle did not work, and I had anything left to thaw, I’ll do my last cycle in May.  And if that did not work, we’d be done.  

But my husband and I have been talking recently, because it looks like this cycle did not work either (that’s a post for another day), and we’re re-thinking that plan.  My emotional state has become more and more fragile, and during this cycle in particular I have been really, really fraying. 

Part of it is that I reached my limit a while ago, so pushing on has been hard.  Part has been, obviously, the termination, which will be something I struggle with for a long time.  Part of it is because it looks like this really is not going to work.  After six failed cycles, well, the odds are really not good.  And after having gone through so much—the drugs and the hormones and the time and the stress and the sacrifice and the cost and the loss—it’s just hard to accept that it was for absolutely nothing.  As I told my husband, if someone could have told me two years ago, it’s not going to work, I would have been sad but fine not having a second child.  And I would have been happy the last two years.  As it is now, it has been all-consuming, and it has made me a bad mom and a bad wife and a bad daughter and a bad friend and a bad employee.  Of course, my husband says, don’t let it do that.  But it’s impossible.  I’ve LITERALLY been doing fertility treatments or recovering from miscarriages or terminations for two years of my life SOLID.  The entire fertility nightmare has lasted seven years.  I spent my thirties in this insane vortex, and while the light’s at the end of the tunnel one way or the other, I’m worn out.  I’m fucking tired.

Of course I have my wonderful little boy, and I am so so so lucky and I know many women go through as much or more than I do and have no biological child at the end.  I know that.  But it still really sucks.  And I hate it.  And I hate what it’s done to me—what I’ve let it do to me.  I don’t like myself right now.  Up until this point, I always was able to separate myself and my unhappiness from what others experienced.  I was never jealous.  I always loved on my friends’ babies, happily threw them baby showers and knitted them little hats.  But I feel that creeping sensation—jealousy, anger, frustration.  Why them?  Why not me?  Friends who got pregnant so easily they didn’t even know for months.  Friends who have had three children in the time we’ve been trying.  I cannot STAND to hear women talk about pregnancy.  The site of a pregnant woman is physically painful to me.

All of this makes me hate myself.   I’m not that person.  I don’t want to be that person.  And yet, that’s who I am.  That’s who I have become.  A really shitty and jealous infertile asshole.  It does not have a great ring to it.

Getting into the butt shots

So, this is the first cycle (out ouf 7!) where I’ve done the progesterone shots.  There’s no scientific evidence that I could find that suggests the butt shots are better than the suppositories, and many labs are moving away from the shots because they’re so painful—and hard to do without a partner!  (http://3yearwait.blogspot.com/2015/02/to-ass-shot-or-not-to-ass-shot.html)  My doctor still generally prefers the shots, especially for older patients and especially for frozen cycles, so this time we agreed to do them.  (Just to switch things up, since we’re not having a great deal of success.)  Well, as the countdown to shots loomed closer, I regretted my decision to do them, especially because my husband does travel and I REALLY don’t want to give them to myself.

I called the doc’s office again to see if I could at least alternate shots and suppositories (that’s what CCRM suggested they would do).  He came back to me and said let’s do shots for the first 10 days.  I said SOUNDS GOOD!  Then, on my transfer day, the doctor (a different one) suggested that she would prefer progesterone shots until the pregnancy test.  Since that only meant I had to do shots for 15 days (it would be 14, but no blood tests on Thanksgiving), I said okay. 

So far the shots are going okay.  I’m following my technique to the letter (http://3yearwait.blogspot.com/2015/11/the-best-way-to-stick-toothpick-into.html) and have had very little pain, no knots, and no bruising.  So that’s good, right??  The downside is that it’s a major process that takes about an hour total, the shot does hurt a bit, and the next day the spot where the shot was feels pretty sore.  I can do this for a few more days.  As the nurse noted, eventually people run out of “good space” to do the shots (unless they have a really, really big butt) and it starts to really hurt to put a new shot in the same place where an old one was.  So I’m glad I’ll be done with shots before that point, one way or the other.