My acupuncturist's advice

I’ve been doing acupuncture with someone who specializes in infertility for a long time.  (I started when we cycled with our son.)  She has A LOT of opinions about fertility based both on her training as an acupuncturist and her experience with all of her many, many patients going through infertility / IVF.  Up until this point, I’ve really only relied on her for acupuncture.  But after my most recent failure, she wanted to sit down and talk about a two-month plan to build up my lining before the next cycle starts, and to discuss some ideas for what we should do now that we’re looking at our last two embryos. 

Basically, she thinks my lining is crap and we should be working on building it.  She knows that we’ve met the bare minimum threshold for my clinic, but definitely thinks a thicker lining is better (and science supports her: http://3yearwait.blogspot.com/2015/11/unlucky-77mm-aka-another-crap-lining.html).  I have to say, my period after our last failed cycle was SUPER light.  (Like, I definitely could have gotten away with just using panty liners.)  Again, a light period is nice from a lifestyle perspective, but not great for getting pregnant.

Here’s her thinking / advice both to build my lining and to use any hail Mary strategies:

Diet (build lining)

·        Red meat once a week (I basically do not eat red meat now)

·        Eat egg yolks a couple times a week

·        A glass of red wine 3-4 times a week until starting birth control is fine, but more alcohol than that is undesirable

Exercise (build lining)

·        Moderate exercise is fine, but no heavy sweating (hot yoga is out, running more than 2 miles is out)

Supplements (build lining)

·        Prenatal vitamin

·        Fish oil

·        Baby aspirin

·        She also suggested two kinds of herbs (stop when go in birth control)

o   Green dragon – 2 pills 2 times a day (http://shop.americanhealing.net/index.php?main_page=product_info&products_id=45)

o   Wen Jing Pian – 6 pills 2 times a day (http://www.activeherb.com/wenjing/?Screen=CTGY&Category_code=wenjing)

·        And I’m going to stay on my CoQ10 and super doses of folic acid

[As a side-note, following these protocols means I am taking THIRTY pills a day, some of them quite large in size: 1 prenatal, 1 fish oil, 1 CoQ10, 1 baby aspirin, 10 folic acid, 4 green dragon, and 12 wen jing pian.  To avoid having my liver poop out, I’ve cut my inositol for now.  I’ll start it when I start on birth control and drop the supplements.  I’m also thinking about taking Wobenzym N, but that’s a post for another day.]

Acupuncture (build lining)

·        Weekly until birth control starts

·        2x/wk acupuncture during cycle

Embryo 

We talked about how we know our last three fails were all female embryos, and now we have a decent quality boy and a poor quality girl remaining.  She suggested using the boy next time, as maybe there was something with the female embryos that was not right / my body did not like, and obviously we have a better chance of success with the better embryo.  She also suggested that, even at this point, she still would just put one in, because we know they are chromosomally normal. 

Meds

·        Heparin 

·        Prednisone 

We talked a fair bit about the last two bullets.  She’s not a medical doctor, but she said that in her 15 years of doing fertility acupuncture she’s had maybe five patients that met the standard of having a “clotting disorder,” but many more of her patients’ doctors chose to put them on heparin after multiple unexplained failures.  Same with prednisone—she actually knew A LOT about the drug (I happen to know a fair bit about it from my job, and her knowledge was dead-on) and acknowledged that it’s a dangerous and powerful drug, but said that at this point if it were her, she’d be having serious conversations with her doctor about it.  She also noted that a number of her repeat failure patients are on it.

Sooo, we have an appointment with our RE in January.  I’m going to generally follow her diet, exercise, supplement, and acupuncture recommendations.  I will talk more with my doctor (again) about the meds.  I need to read more about them first….

With respect to which embryo to use next, my husband and I are going to discuss, but I think she might be right.  As much as I would love to have a daughter, I’m not sure I’m meant to be the mom of a girl…. Or the mom of a second child.  (My heart broke a little the other night when my son asked me “when am I going to get a baby sister?”)

Predicting success part 3: SART’s predictions of success

The Society for Assisted Reproductive Technology also has a simple chart for predicting success:

https://www.sartcorsonline.com/Predictor/Patient

Based on my age, weight, height, prior pregnancies, full term birth, and diagnosis [unexplained], it suggests the following ism my chances of success for a live birth:

Probability of live birth after one cycle is 37%

Probability of live birth after two cycles is 56%

Probability of live birth after three cycles is 70%

One Cycle with One embryo:

Probability of live birth is 34%

Risk of multiple pregnancy is 1%

Two Cycles with One embryo:

Probability of live birth is 51%

Risk of multiple pregnancy is 2%

One Cycle with Two embryos:

Probability of live birth is 46%

Risk of multiple pregnancy is 31%

If I change my diagnosis from unexplained to tubal problem, my chances of success fall slightly.

Note that SART predictions are a little more optimistic than some of the other ones. http://3yearwait.blogspot.com/2015/11/predicting-success-part-1-cumulative.html

Predicting success part 2: blastocyst quality

No big surprise, the SART grading categories are highly correlated to success:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3644132/

Good is considered AA or AB.  Fair is considered BA, BB, or BC.  Poor is considered CB or CC. 

In this article, over 60% of “good” embryos implanted, and over 50% resulted in a live birth.  Just under 50% of “fair” embryos implanted, with over 35% resulting in live birth.  They had few data points for the “poor,” but none of them worked.  (I’ve read some clinics will not freeze poor quality embryos because of their low chance of success.)  Now I’m re-thinking my guesses at what my embryos were rated.  My lab says it has at least an 18% pregnancy rates with B3s, which suggests B3s are better quality than CC.  Maybe BC.  (http://3yearwait.blogspot.com/2015/11/blastocyst-grading-no-students-here.html)

Here’s another one that breaks it down further:

“From the results, the pregnancy rates of AA, BA, AB, and BB for patients <30 years of age were similar and there were no significant differences. The pregnancy rates of AA, BA, and AB tended to be higher than that of BB for patients 30-34 years of age, and this tendency was observed for the patients 35-39 years of age.”

“The pregnancy rates of blastocyst grading AA, BA, AB, and BB for the patients who were more than 40 years of age were 61.9, 54.5, 38.7, and 17.6%, respectively.”

http://humrep.oxfordjournals.org/content/28/suppl_1/i104.abstract?_sm_au_=iVV3t8VMPNtsjRfP

So if you’re young, anything with an A or a B will do.  If you’re old, you definitely want As, and all Bs are bad news.

Okay, and here’s an article that suggests, unsurprisingly, that better-quality embryos were more likely to be chromosomally normal:

Blastocyst grade	AA	AB	BA	BB
Chromosomally normal	62%	41%	62%	33%

http://www.aclr.com.es/clinical-research/euploidy-predictability-of-human-blastocyst-inner-cell-mass-and-trophectoderm-grading.pdf

They also give you a chart regarding which one you should choose.  Basically AA = BA > AB > BB

I would be interested in knowing what my embryos would be considered rated using these standards.

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.