Thursday, February 26, 2015

Miscarriage Risk

I wasn’t planning on posting again until I had a heartbeat appointment, but I found a cool / terrifying website that collects medical journal articles on miscarriage risks / factors.  Right up my alley!
The website summarizes the medical journal articles, and I’ll summarize the website’s summaries. (Although here's a nice summary from the website:
Things you can (theoretically) control that have been shown to help fertility/decrease miscarriage risk:
·        Eat chocolate.  :)
·        Eat good fats (olive oil).  
·        Eat whole milk, yogurt, ice cream, and cheese.
·        Eat eggs.
·        Eat fiber (whole grains, veggies, certain fruits).
·        Eat fruit.  (“Eating 2+ servings of fruit per day lowers risk of miscarriage by 70%.”) 
·        Eat veggies.
·        Eat fish.
·        Moderate exercise is okay/good.
·        Multivitamins are good.  (Pretty much all vitamins are good, including DHEA.)
·        Gluten free is good… if you have celiac disease.

·        Don’t drink when TTC.  (This one made me sad because l love my booze.)  Drinking makes it more likely you’ll have a short luteal phase (luteal phase defect!), and decreases pregnancy and live birth rate.   :(
·        Don’t eat a lot of butter or oil.  
·        Don’t eat bad fats (cake).
·        Don’t be fat.
·        Strenuous exercise is bad.
Things your hubby/boyfriend/sperm donor can do that have been shown to help fertility/decrease miscarriage risk:
·        Eat cereal, fruit, folate, fish.
·        Don’t drink.
·        Don’t be fat.  And also don’t diet.  (Damned if you do, damned if you don’t.)
·        Don’t eat (too much?) red meat.
·        Don’t smoke.
It also provides general miscarriage statistics:
Miscarriage risk
Gestational sac
Heartbeat 6 wks
Heartbeat 7 wks
Heartbeat 8 wks
Heartbeat 9 wks
Heartbeat 10 wks
Second trimester

Other factors relating to miscarriage risk:
·        Miscarriage risk increases 12% after (mom) age 30; goes up 39% after age 35; doubles after age 40
·        Miscarriage risk increases after (mom) age 35; increases 5 fold after age 40
·        Miscarriage risk doubles after (mom) age 40 and triples after age 45
·        Having a partner (dad) over 40 years old increases risk of miscarriage by 60%
·        Risk of miscarriage increases by 43% when partner (dad) is age 35, by 90% at age 50
·        Miscarriage risk increases 88% if the father is over 50 years old
·        Miscarriage risk doubles for those who need more than a year to successfully conceive (boo!)
·        Induced abortion increases the risk of miscarriage 128% for up to 2 years
We already knew this one:
·        Morning sickness associated with 70% reduction in miscarriage risk, with a marked increasing trend of reducing odds with increasing severity of nausea.
And here are a few real bummers for those of us with recurrent miscarriages:
·        Recurrent miscarriage increases risk of stillbirth 1300%, preterm birth 60%, ectopic pregnancy 160%
·        Miscarriage risk is normally 2% after a heartbeat is seen; but 18% in women with recurrent miscarriage
·        Risk of miscarriage only increases by 7% after one loss; nearly doubles after three or more
·        After two miscarriages, one still has a 91.2% chance of successful pregnancy; drops to 20% after 7.  In other words, the most miscarriages you’ve had, the more likely you are to have another one:

Previous number of miscarriages
Live birth rate for 1stpregnancy after exam
Cumulative success rate (birth of at least 1 child)

·        Each miscarriage raises risk of future heart attack by 40%
I have not read any of the underlying studies.  Like, for the last one, did it account for obesity?  I mean, is it possible that being obese was a risk factor for infertility (it is) and heart attack (it is), but that infertility alone has no connection to heart attack?  I hope so!
Okay, here a few more:
·        Supplemental progesterone decreases miscarriage risk after unexplained recurrent miscarriages.
Anyway, after I read this I ate a bowl of strawberries, and was happy I had some chocolate today, but regretted the pizza I had for dinner… and breakfast.

Wednesday, February 25, 2015

Infertility when you have a kid

I do not want to minimize how stressful/upsetting it is for someone else to be unable to have a second (or third, or fourth) kid, but for me there is something very different about infertility now that I have a child.  I really want a second child.  (I’ve done FOUR IVF cycles, for goodness sakes!)  But if it does not work out, we will be okay, and incredibly, immensely grateful that we were able to have our (amazing, wonderful, perfect) one. 
That said, I’m feeling optimistic about this!  I’ll give an update in a couple weeks after the heartbeat appointment.

Tuesday, February 24, 2015

IVF risks

Another question many potential IVF parents ask is, what are the risks to the health of my kids?  My IVF doctor was quick to reply to this question that there has been nothing proven to be related to the IVF process, and any potentially increased adverse consequences could be related to the fact that many IVF pregnancies are multiples (hence our stubborn refusal to implant more than one embryo) and/or that the IVF population (ie. the old, unhealthy, infertile parents) is more likely to produce unhealthy kids.  (Have I mentioned that getting old is a bitch?)
So I’ve looked around to see what I can find.  Like my doc said, I can’t find anything that demonstrates the IVF process is potentially harmful to the health of the resulting children…. But there are certainly a number of studies drawing concern. - listing a series of studies showing increased risks with IVF/ICSI; focuses on a study, in mice, that IVF babies are smaller, placentas larger, and embryo development delayed – has tons of interesting statistics to help a couple predict likelihood of success.  Another one relates to chance of a low birthweight baby, depending on factors like age of mom and cause of infertility. - IVF has an impact on gene expression in mouse studies.  Unclear if this persists / matter, but the authors suggest there could be a “long lasting predisposition to disease”.  Grrreeeat. - summary suggesting more data needed - no clear difference between frozen embryo babies and fresh embryo babies.  Also notes again that “The risks [to the health of children born from IVF] identified to date do not seem to be associated with the techniques per se, but rather as being attributable to parental characteristics and from clinical policies of transferring more than one embryo at the time, causing highly increased proportions of multiple pregnancies and deliveries.”

While I think there is no doubt that IVF is not better for the health of the humans born from it, I also think all things being equal it’s still worth the risk, especially for singletons, and especially when you consider what great parents IVF parents are. :)

Monday, February 23, 2015

Holy shit! We’re going to have a second kid (knock on wood)… and maybe a third, and a fourth, and a fifth, and a sixth….!

Well, I got TWO results back from the RE’s office today, each of which alone would have been enough for me to say “wow, that’s amazing news!”
First, I had my 21dpo HCG measurement today – 4167.  I’m still pregnant!  And 4167…. Well, I have no idea if that’s a fine, good, or great measurement, but I know for sure it’s not a bad one, and that’s all that matters!  My next doc’s appt. will be in two weeks when I have my confirmation of heartbeat appointment.  (Which has been a disappointment before, so my optimism will remain tempered for at least a while.)  But I’m 5 weeks pregnant today!  Yay! 
Second, and even more shocking…. We got the results of our genetic testing back today.  Of our five little blastys, FOUR are genetically normal.  Knock me over with a feather!  I was sure that most of them were going to be total crap based on our last disastrous cycle.  I guess this goes to show, it never hurts to give it a second try.  (And here, I should say, there is a question that has been gnawing at me for the better part of a year.  The last time we did a stim cycle, it was right after I had an insane work thing going on, and I was working upwards of 20 hour days [seriously] for weeks, super stressed out, and working out of a hotel [okay, it was a casino] where they allowed smoking.  I can’t help but wonder if that was not the greatest environment for me to be growing my poor little eggs, any maybe had something to do with our dramatic failure?  This time I was much more relaxed and rested.  Could that make all the difference?)
AAAND, boy bias be damned, my little frosties are almost all girls!  Here are their stats:
Day 5 B2
??? (not tested – currently pregnant)
Day 6 B2
Day 6 B2
Day 6 B3
Day 6 B3
Day 6 B3
Genetically abnormal

Ummm, are you thinking what I’m thinking?  We’re going to have another kid!  Okay, it’s not a foregone conclusion, but as soon as an embryo is genetically normal the “rating” (B2, B3, whatever) falls out the window.  That sucker has like a 70% chance of success.  So, the fact that I have managed to get to at least 5 weeks pregnant, and the fact that I have FOUR genetically normal embryos (and a fifth crap one from the last cycle) stored means… We’re going to have another kid!  (Hopefully!)  My god, we could potentially have two more kids, or even three!  (My husband has always dreamed of driving a minivan.  Not really.)
I had intended to ask in what way any of the embryos were genetically abnormal, but it totally slipped my mind.  I’ll get that info later if I can.
But, are you kidding me, wow!

Sunday, February 22, 2015

The Boy Bias

There are some studies that suggest that IVF favors the birth of boys (potentially because it favors the selection of the furthest along blasty, and male embryos tend to develop faster):
BUT, there are others that suggest when ICSI or frozen embryos are involved, that is not true and that girls are actually favored:
Who knows?!  We’d be happy with anything.

Saturday, February 21, 2015

Younger (sperm) is not always better

Many women going through infertility have secretly (or openly!) wished for younger eggs. Because even though financially, emotionally, etc. many of us were not ready to start trying to have kids until our 30s (or later), biology thinks we should have been doing it right after graduating from high school, when our eggs were as good as they were going to get.

Well, maybe that's true of eggs, but apparently sperm, like cheese and fine wine, do better with some aging. A new study found teenage fathers have an increased risk of having children with birth defects--their sperm have more mutations than fathers in their 20s and 30s:

Good to know.

Friday, February 20, 2015

Mom blogs

As anyone who has read more than a few of my posts knows, I spend a lot of time writing about things I read in medical journal articles.  While I do love to read medical journal articles, I spend more of my time reading mom blogs about infertility / IVF.  I say “mom” blogs because they are ALL written by moms (or women who really, really want to be moms).  I can only imagine what my husband would write if he had a similar blog….  “DW insisted on peeing on a $10 HPT tonight even though she has her blood test tomorrow AM.  It was positive.  We are excited.  I reminded her to ask the doctor tomorrow when we can start having sex again.”
Anyway, I read a lot of blogs.  A LOT.  I find them the same way people might find this—searching a topic and running across someone’s story.  I often cheat and read the first entry followed by the last entry.  I want to know, “how did this person get here” and “where did they end up?”  Sometimes I catch someone right in the midst of their story (like I am now).  But sometimes, happier times, I read the “this will be my last entry for a while” posting… because they’ve reached the end of their journey, wherever they ended up.  Some had (via natural conception, help from a doctor, help from a doctor and an egg/sperm/embryo donor, or help through adoption or other means) a kid.  Others (and I’ve found this to be the minority, so hold out hope!) did not.  Either way, the journey was over.  And for most of them, the painful path they followed was a vague memory, something they acknowledged that they learned and grew from, but not something that continued to cause them the kind of pain they may have suffered while they were in the worst part of the process, whenever that might have been.
Over the years, I have peeked into a number of these women’s lives, and shared their joy/heartbreak/surprises/setbacks/perseverance/acceptance.  I have not written any of the blogs down (of course) but recently I found a really cool site that collects blogs on a variety of topics, including infertility/IVF:
I have never really looked for blogs on other topics (do people get really excited about photography or irritable bowel syndrome?), but I think there is a special passion that drives many women to blog about infertility.  It’s something that, on one hand, is all many of us want to talk/think about while we’re in the midst of it, and on the other hand is intensely personal and private.  And that combination is a great fit for the internet.  I’m not going to talk to my co-workers about ovulation predictor kits, stimulation protocols, or pregnancy symptoms, but I’ll anonymously dissect every little aspect of my chunky discharge (implantation bleeding or BFN?) with other like-minded women who might be doing the exact same thing.  I guess it’s the combination of infertility being so isolating and, at the same time, something so many women experience and want to talk about.
I, like many of these blog-happy women, have found great comfort in detailing my own thoughts/feelings.  So if you’re reading this because you’re a fellow I-want-to-be-a-mom-so-bad-er-but-it’s-just-not-working!—if you’re in the worst part of it—know that you’re not alone, there are others like you, and you will get through it.  And maybe you should start a blog.

Wednesday, February 18, 2015

Yes—we’re still talking about this…. How many embryos to transfer?

One of the hardest decisions many hopeful IVF parents make is how many embryos to implant.  Well, in 2013 some fancy committees proposed some criteria for number of embryos to transfer:
Helpful!  Here’s their suggestion:

Day 2/3 embys - favorable
Day 2/3 embys - other
Day 5/6 blasys - favorable
Day 5/6 blasys - other

“Favorable” is defined as first cycle of IVF OR good quality embryo OR excess embryos available to freeze OR previous successful IVF attempt.  For patients with two or more failed fresh IVF cycles, or a “less favorable prognosis,” one additional embryo may be transferred.  For women >43, there is insufficient data to recommend the number of embryos to transfer.  For donors under 35, a single embryo should be used.  The recommendations for frozen are the same for fresh.
So this would have suggested one embryo transfer with my first kid, which is what we did and what obviously worked.  But for my second round, it would have suggested two each time, which would have been the right result since none of those blastys (except the crappy still-frozen one, maybe) were viable.  We (stubbornly?) decided to do continue to do a SET (single embryo transfer) for our FIFTH round.  Obviously if this does not work and we have any “genetically normal” ones from our genetic testing, we will continue to implant single embryos.  We just have to wait and see!

Tuesday, February 17, 2015

The cold never bothered me anyway

I continue to worry about damage to a potentially viable blastocyst during the freeze/thaw process. At very high quality labs, about 90% of frozen blastys will survive the thaw.  (See article below, which shows just a hair under that.)  But what about that last 10%?  
A doctor at my office suggested that high quality embryos survive the thaw at a higher rate than poor quality ones, so maybe the freezing process is just another method of weeding out embryos that are unlikely to work.  (My lab has about an 85% survival rate, but he suggested it might be as high as 90% with good quality embryos, which means there is still some loss of potentially viable embryos.)
At high quality labs, the implantation rate using frozen is the same as fresh.  Blastys have to be of a higher quality to be frozen than to be transferred fresh, so that’s not a surprise.  While the implantation rate is similar between fresh and frozen, my lab suggests that frozen have a higher miscarriage rate.
At the end of the day, there is no question that freezing causes some damage to cells in the freezing process.  The only question is whether it is catastrophic.
Like anything, there are good things about freezing and bad things about freezing.  We know the bad, but what about the good?  Among other things, I’ve read that the stim process is hard on your body and, theoretically, you should be able to grow a better lining if you have a chance to do that without a harsh stim cycle right on top of it.  Here’s a non-medical journal article that suggests frozen cycles result in better outcomes for babies than fresh cycles:
Of course in our case, we still decided to transfer a fresh one because we were not sure we would have more than one embryo (we were wrong) and we did not want to risk anything in the freeze/thaw process.
And, no surprise, the better a fresh embryo looks, the better it’s likely to look when it’s thawed.  This article goes through prediction of success in a frozen cycle based on pre- and post-freeze ratings:
Don’t skip the tables—they’re the most interesting part!  Unsurprisingly, the best quality fresh blastys make the best quality thawed blastys.  Better blastys resulted in better outcomes.  Faster expanding frozen blastys are better (double the pregnancy rate!).  Having a failed cycle (or more) did not appear to have a significant impact on success.  As we’ve already discussed, doing a freeze of a blasty that hits at day 5 versus day 6 made no difference on outcome.  Unsurprisingly, there is much greater success for women under 37.  It also notes that their clients that used ICSI had more success.  (I’ve read elsewhere that is not necessarily true.)  Also interestingly, people with MORE than 16 follicles or more than 11 eggs had LOWER outcomes.  (More is not better!)  Everyone knows that being “overweight” is not good for fertility.  But this article says BMI of less than 22.8 is best.  (I calculated mine—I’m in the 21s.  I do not consider myself to be overweight at all, but I’m around five pounds away from the bad BMI.  A BMI of 22.8 isn’t even considered overweight!!)  So forget being “not fat”—you have to be downright skinny.
Here’s another interesting article on freezing:
Anyway, it seems like there is some risk to the freezing process, but that for most people it may be worth the risk.

Monday, February 16, 2015

Let’s talk about something we haven’t talked about yet—endometrial thickness

There are a number of studies that talk about endometrial thickness.  In a nutshell, the thicker the better: - “Endometrial thickness was greater in cycles resulting in pregnancy than in cycles not resulting in pregnancy (11.9 vs. 11.3 mm, respectively). Clinical pregnancy rates increased gradually from 53% among patients with a lining of <9 mm, to 77% among patients with a lining of > or =16 mm”
That article we discussed the other day (on measurements) also opined that bigger, fluffier lining is better: - “Grade I was characterized by homogenous echogenicity of the endometrium, while grade II was characterized by an outer peripheral layer of dense echogenicity surrounding a central sonolucent area (halo pattern). Grades I and II were subclassified into group A (>9 mm thick) and group B (<9 mm). Grade IIA was optimal, as it was associated with a clinical pregnancy rate per embryo transfer of 33% while the other three groups were poor as they were associated with a rate of 7% only. Women aged 41-45 years experienced a 25% incidence of poor sonographic grades compared to only 5% incidence in women <40 years.” 
Yikes, that lining really matters!  This cycle they said I had an 11B.  Reading those two articles makes me think I would hesitate to do a transfer with a bad lining… although I’d have to trust my doctor’s recommendation on that front.  And boy-o-boy getting old is a bitch.  Bad eggs.  Bad lining.  Geez!

Sunday, February 15, 2015

What do all of those measurements really mean?

I’m obsessed with numbers.  So I liked this article, which had a lot of good information about the numbers people see during the monitoring process:
Some of my take-aways from this article (and take with a grain of salt) follow.
Measurement of E2 is based on follicle size
My doctors certainly seemed to think that my E2 measurement had some relationship to the number of follicles, and this article proves that.  These authors actually have an E2 formula depending on the sizes of the follicles!  Here it is:
Thus the serum E2 level on the day of hCG injection is:
E2 = 291 pg/ml + 180 (x) + 64 (y) + 18.7 (z)
where x, y and z represent follicles measuring >17 mm, 15 to 16 mm and <14 mm respectively.
Okay, that’s a little complicated, but they do give a rule of thumb (much more helpful for most of us):
“E2 level is approximately 400 pg/ml per large follicle.” 
Also, as we all know, the authors indicate that there is a risk of OHHS with “extremely high levels of E2 (over 3000 pg/ml).”
It’s not good if E2 is rising too fast or two slow, or falling
The article suggests, “It is inadvisable to give hCG to patients in whom the serum estradiol level is seen to increase rapidly (i.e. doubling in 24 hours).”  The article suggests that a “linear” E2 growth is best.  It says “very slow or very rapid estrogen growth rates (EGRs), calculated from the 4 days preceding oocyte aspiration in CC/hMG stimulated cycles, were associated with a reduced pregnancy rate. EGRs of 0.31 to 0.41 were associated with optimal pregnancy rates. EGR is calculated by the formula: EGR = e-B -1 where B is the slope of the least square line corresponding to the semilogarithmic plot of E2 values versus time and e = 2.718.”
Whaaaaa?  I get that you don’t want your E2 to double, but I’m not sure what the optimal amount of increase is. 
I charted my E2 measurements.  My E2 growth (as opposed to the E2 measurement itself) was not doubling every day—it was rising about 64% per day (and was always rising in the 60%s).  So I *think* that’s “linear growth” (and thus optimal) as the authors define it.  
Here’s my E2 measurements for this cycle:
Stim day 
E2 Growth
[not stimming yet]



~9 follicles
ave 61.35% [over 2 days]
~3 mature, ~11 follicles total
~8 mature, ~11 follicles total
[trigger shot]

I put my data on a graph (with the “x” or horizontal axis being my “stim” day and the “y” or vertical axis being my E2 measurement) but, unfortunately, I don’t know how to make it visible on this blog.  It looks something like this:
2500                                                                         x (2376)
1500                                                                  x (1449)
1000                                                        x (853)
500                                           x (328)
0                                  x (108)
               0             2             4             6             8             10
                                             Stim Day
It’s hard to tell from the little mini-chart above, but my E2 measurements were growing exponentially.  (My E2 “growth” [or increase] in measurements was linear, while my E2 measurements themselves were growing exponentially.  If it’s been a while since you had… whatever level math this kind of stuff was taught in… think about it like this.  If you gain 10% of your body weight a year, you will actually gain MORE weight year after year.  So if you start at 100lbs, the next year you’ll be at 110 (gained 10 lbs or 10% of 100lbs), and the next year you’ll be at 121 lbs (gained 11 lbs, or 10% of 110 lbs), and the next year you’ll be 133.1lbs (gained 12.1lbs), and so on.  So your weight gain GROWTH is linear (always 10%) but your weight GAIN is exponential (you gain more pounds each year).)  Anyway, the formula showing my E2 measurements (y) as compared to my stim day (x) is: 24.024e0.5119x
Aaaand if we put in on a log scale (so that the axis showing E2 is on a logarithmic scale—ie. Increases in increments of 10x).  It looks approximately like this:      
10000                                                                               x (2376)
       x (1449)
1000                                                                  x (853)
                                                  x (328)
100                             x (108)                                                             


               0             2             4             6             8             10
                                             Stim Day

Okay!  That looks like a pretty straight line!  (It’s better on the real graph—it’s seriously a straight line.)  My “B” value from above (“the slope of the least square line corresponding to the semilogarithmic plot of E2 values versus time”) appears to be 0.5119.  (The number from the formula above.)  Which means that my EGR from above (e-B -1) is 0.40.  Right in the range of optimal above.

About 20 years ago I was pretty good at math (I took a number of advanced engineering math classes in college), but it’s been a looooong time so it’s possible I totally messed this all up.  Since my calculated number appears normal (I didn’t calculate an EGR of 750, when the optimal range is 0.31 to 0.41) and indeed is “optimal,” I’m going to call it a victory and move along.

Back to the article.  Here are a few more of the authors’ observations on E2…  

•     Non responders/low responders: E2 levels did not reach 300 pg/ml by day 8 of stimulation, <800 pg/ml on date of hCG shot.
•     Slow responders: E2 levels were <300 pg/ml by day 5, but >300 pg/ml by day 8 of stimulation, 800-1500 pg/ml on date of hCG shot.
•     Fast responders: E2 levels >300 pg/ml by day 5 of stimulation, >1500 pg/ml on date of hCG shot.

No differences between the three groups in respect to development of mature oocytes and rapidly cleaving embryos, but the pregnancy rate in the low responding group was significantly lower than in the other two groups.  “Thus it seems that the receptivity of the endometrium depends at least partially on adequate E2 levels. It also seems that E2 levels do not directly correlate with oocyte maturity and embryonic growth.”
Here’s another article that suggests it is better when E2 grows slowly:
Finally, as we all know, you always want the E2 to be rising: “in good outcome cycles, E2 continued to rise until hCG was administered, but in nonpregnant cycles, E2 plateaued on the day before hCG administration, which suggests that luteinization or atresia of the more advanced follicles had commenced spontaneously.”  Mine was always rising, so I guess that’s good.  A nurse at my doctor’s office told me, in response to a question, that sometimes they do see a fall in E2, which suggests that the follicles are overripe, and in that situation they immediately trigger.  She said “it’s not ideal.”  Um, yea.
Stimming too long (unclear how long “too long” is) is not good
Another suggestion from the authors—you want the “active phase of E2 rise to be 6±1 days, and >7 days is not as good.” “They attributed the high incidence of early abortion, when the active phase was >7 days, to be an expression of oocyte overexposure to hMG prior to hCG injection. Such overexposure may result in postmature oocytes and end in early abortion.”  (citing Elsewhere the article suggests “Patients who fail to achieve adequate follicular development after 6-8 days of ovarian stimulation do not receive hCG, and the treatment cycle is cancelled.” 
I don’t know what to make of this because I don’t know what the “active phase” is.  (I stimmed for 8 days before my hCG shot on day 9, and I’ve read that a lot of people stim for up to 10 days.  I don’t think that is too long….)  I think I had adequate follicular development with a day 9 trigger shot.  Maybe the “first” day of the active phase is day 3?  (That’s when my first E2 measurement was.)  In which case, my “active phase” was day 3 to day 8, or 6 days?  Or is this one of those things where you don’t count the first day?  I don’t know.  I guess the takeaway is that stimming too long is bad.  Unclear how long is “too long.”
Too many mature follicles prior to trigger shot is not good
The article also suggests “It is advisable that hCG not be administered if there are more than 3-4 follicles of 14 mm or more in diameter.”  I think I had EIGHT follicles larger than this the day before my hCG trigger day.  Hmm.