Be prepared for a bit of stream of consciousness below….
So, no surprise, I am pregnant. BUT. B.U.T. But my beta HCG is low. Not really low, but pretty concerning-ly low. This time it’s at 131 10dp6dt [10 days post 6 day transfer] (or 16dpo [days post ovulation]). Last time (miscarriage, early blighted ovum) it was 112 at 9dp6dt (or 15dpo). With my first (and only) kid my HCG was 146 at 9dp5dt (or 14dpo). So this embryo is TWO days more developed than my kid was, and its numbers are still not as good. (I’m not sure how much we can hold the extra day of freezing against it hatching, but still.) Its numbers are not as good as my blighted ovum, either. In fact, at 16dpo with my one successful pregnancy I was at 480! Compare that to what I have now—131. So it’s not good.
Late implantation can account for an initial hCG level that's lower than the norm, BUT I had a fully hatched blasty that should have implanted the day of the procedure. So not good at all.
I sensed from the doctor’s voice that he was thinking my HCG was low, but when I asked about it he said the odds were in my favor, and that I should be cautiously optimistic.
{see a later post on this with a chart here: http://3yearwait.blogspot.com/2015/11/beta-hcg-measurements-part-ii.html}
Self-reported beta (all pregnancies, including natural)
Remember that handy chart I showed you all those years ago, showing beta HCG scores? (I’m going to use beta and HCG interchangeably, just to make this even harder to follow.) Well, here it is again:
It says for 16 days post ovulation I’m low (but not out!). The average self-reported HCG for 16dpo was 278. So roughly double where I am—or two days ahead. (Betas are supposed to double every two days.) Again, though, this collects ALL betas, and we know (or will know, when this post is over) that the in vitro process results in lower early betas.
Beta correlation study #1 – 16dpo (infertility treatments including, but not limited to, IVF)
No surprise, there’s a correlation between better beta scores and successful pregnancies:
(Information that makes crazy wanna-be moms like me totally nuts in early pregnancy.) This medical study suggests an early low HGC means the pregnancy is less likely to continue. (Again, no surprise there.) The authors define the result as pregnancy “outcome,” which they define as progression to >20 weeks’ gestation.
It suggests that at 16 days post ovulation (me today!): “Low hCG levels between 25 and 50 IU/L are associated with a low probability of ongoing pregnancy (<35%), whereas levels of >500 IU/L predict a >95% chance of ongoing pregnancy.” The authors include super helpful images of your chances of success based on your HCG measurement. (Seriously, take a look at the article—very interesting.)
And here’s the info by category:
HCG (IU/L)
|
No. of women
|
Ongoing pregnancy rate (%)
|
Miscarriage rate (%)
|
25–50
|
78
|
<35
|
>65
|
50–100
|
95
|
35–64
|
65–36
|
100–200
|
159
|
64–80
|
36–20
|
200–500
|
220
|
80–95
|
20–5
|
500–1,000
|
87
|
95–100
|
0–5
|
>1,000
|
23
|
100
|
0
|
The median HCG level for 16dpo was 193. I’m 131—below average. L If you have an HCG of 131 16dpo (like me) you’re looking at around a 65-70% chance of success. (I’m under 40, but I suspect because of my age—36—fertility issues, and use of FET, I might be on the low end of that range, if not actually a fair bit lower.) Well, that’s certainly not terrible. But it’s not great. Oh how I’d like to be in the 500s!
Beta correlation study #2 – 13dpo and 15dpo (IVF)
Here’s another article about measurements 13 and 15 days after fertilization (ovulation):
Some highlights:
“Serum beta-hCG concentrations determined 13 and 15 days after fertilization in pregnancies established by transferring cleavage-stage embryos on day 3 or blastocysts on day 5.”
“In singleton pregnancies, serum beta-hCG concentrations were 75 +/- 54 (mean +/- SD, n = 203) or 62 +/- 41 (n = 109) IU/mL after day 3 or day 5 transfers, respectively. In twin pregnancies, the beta-hCG concentrations were 162 +/- 105 (n = 52) or 109 +/- 55 (n = 49) after day 3 or day 5 transfers, respectively. The percentage increases in beta-hCG concentrations between the first and second measurements were similar in the two groups (day 3: 144 +/- 109, day 5: 142 +/- 63, not statistically significant).”
“Initial beta-hCG concentrations in pregnancies resulting from day 5 transfers were lower than those from day 3 transfers when assessed at equivalent intervals from fertilization. This suggests that embryo development or implantation may be impaired by the additional 2 days in culture.”
These are 1999-2001 numbers, so a little older. They measured HCG 13 and 15 days after egg retrieval and fertilization (ovulation) of day 3 and day 5 fresh (never tastes frozen!) embryos. So the numbers for the day 3 and day 5 embryos should in theory be similar because the embryos are exactly the same ages, just transferred at different times, but as we see the ones that sat around in the lab a little longer are a little behind:
|
Day 3 embryo transfer
|
Day 5 embryo transfer
|
First test (13dpo)
|
75 ± 54
|
62 ± 41
|
Second test (15dpo)
|
173 ± 101
|
138 ± 105
|
[This is an excerpt from Table 2]
The authors explain, “Our data indicate that, at equivalent time intervals subsequent to fertilization, serum β-hCG concentrations are about 50% higher in pregnancies resulting from day 3 transfers in contrast to those resulting from day 5 transfers. . . . Serum β-hCG concentrations in early pregnancy roughly double every 2 days, corresponding to a 40% rise per day. The observed discrepancy therefore corresponds to slightly more than 1 day.” The potential theories about why: “First, the observed discrepancy might result from a difference in the rate of very early, subclinical losses. Second, delaying transfer to day 5 might result in a gender bias, which in turn has been suggested to be related to the rate at which early embryos develop. Third, the additional 2 days of in vitro culture might directly, and adversely, affect the normal development of the embryo, resulting in subtle delay or reduction in hCG production.”
The authors then go on to reject the first argument, reject the second, and accept the third, but with the caveat that it does not seem to impact pregnancy rates. In other words, my slow-grower might do just fine, even though my numbers are low right now.
Interestingly, the authors note that “although our data did not reach statistical significance, they reflect a nearly 2:1 male to female bias after day 5 transfer.” Uh, oh, we had a day 6 transfer, so we’re having another boy! They suggest, “Delaying transfer to day 5 could potentially result in a gender bias that may contribute to the difference in β-hCG concentrations. However, our findings are inconsistent with this hypothesis. When β-hCG concentrations were compared by gender (combining singleton pregnancies with twin pregnancies with both newborns of the same gender), we found that male gestations were associated with significantly higher β-hCG concentrationsthan female gestations (data not shown). Because day 5 transfers appear to lead to the birth of more males, higher β-hCG concentrations would be expected in pregnancies after day 5 transfers, which is opposite our findings. Male embryos appear to develop faster than female embryos during the preimplantation period in mice and cattle. Therefore, male embryos are more likely to be selected for transfer when the cleavage rate or blastocyst formation on a fixed day after fertilization is used as the primary selection criterion, which is consistent with our observations.
If we treat my little 6 day embryo like a 5 day embryo (and we know culture impairs development, the authors tell us as much!) and thus treat me like 15dpo instead of 16dpo, maybe, just maybe it’s doing okay. (Again, my 16dpo measurement was 131, and the averages measured in this study at 15dpo were 138.) How do you like that optimism?!
Beta correlation study #3 – 14dpt (IVF)
Another study (using data from 2007-12) talks about correlations between HCG on day 14 after embryo transfer and ongoing pregnancy:
Some tidbits: “Pregnancies achieved by in vitro fertilization (IVF) are at increased risk of adverse outcome as compared with natural pregnancies.” Super. Thanks for reminding me.
This study considered fresh day 3 and day 5 embys. (And I have to keep reminding myself that frozen cycles have more adverse outcomes than fresh… so I don’t know how much stock I can put in the fresh HCG numbers.) In their study, of 139 pregnancies 39 did not make it to 12 weeks. (So miscarriage/chemical pregnancy/ectopic rate of just under 30%.) The average HCG rate for the 100 pregnancies that continued to 12 weeks was 600 14 days after embryo transfer. The average HCG rate for the 100 pregnancies that did not continue was 178 on day 14 after embryo transfer. It postulates, “initial serum β-HCG can be taken as the single best predictor of pregnancy outcome in patients undergoing IVF.” It concludes: “The β-HCG level on day 14 of more than 347 mIU/ml has a sensitivity of 72.2% and specificity of 73.6% in prediction of pregnancy beyond 12 weeks period of gestation. Positive likelihood ratio (LR) is 2.74 and negative LR is 0.37, (receiver operating characteristic area = 0.79).”
Okay, well this one is hard to do anything with, as I am not yet 14dpt. BUT, I’m having my beta retaken in two days. (12dpt, 18dpo.) It needs to double. (So we’re looking for something over 260.) If it doubles again 2 days later, it would be 520. That’s still below the median 600 in this study, but it’s over the “more than 347 mIU/ml” threshold for pregnancies likely to go 12 weeks.
Also, this one is a little questionable because it lumps day 3 and day 5 transfers together for testing 14 days post transfer, even though the day 5s are “older” and should be more mature and have higher numbers. (See more on this below.)
Beta correlation study #4 – 14dpt [IVF]
Here’s another one dealing with the same issue, with some different details:
Most interesting, the authors say that HCG levels for boys are lower than girls. The authors state: “Although the mean beta-hCG value was higher in women who had female fetuses compared to males, it was not statistically significant in our study. Various other studies had quoted a higher value in woman with female fetus. Fetal gender has been shown to have a significant influence on maternal serum levels of hCG.” (Remember the earlier study said more boys came out of 5 day transfers, and the authors suggested that was because boys developed faster and had higher earlier HCGs. So maybe this one needs more thought.) Also, the authors show mean HCG compared to outcome, 14 days after embryo transfer. (Again, very interesting, read the article.) The authors also suggest, again unsurprisingly, that a 6 day embryo should be much more developed 14 days after transfer than a 2, 3, 4, or 5 day transfer. There is no way I’m going to be at close to 5000 (mean 6-day measurement) at 14 days post transfer. (I was 131 10 days post transfer, so I’m very likely looking at under 1000.) I’m just chalking that one up to small sample size. One last chart that shows status of pregnancy at 6 weeks based on beta measurement 14 days post transfer.
This is a little silly to me, because it’s considering 14 days post-transfer whether a baby 2 day old embryo is used or a geriatric 6 day old embryo is used. Especially because the authors just told us that the 6 day-ers should be a lot more developed than the 2 day-ers at the same time 14dpt. So the “mean” doesn’t seem to have much value to me. (I guess if you transfer a relatively sprite 2 or 3 day embryo and 14dpt you’re above 500, you can be feeling pretty good about things.) But the numbers appear consistent with the study above. If 14dpt you’re at 178 (the average bad number cited above), you seem pretty screwed here too.
Okay, I may have totally hacked my summaries of these articles (have I mentioned I’m not a doctor?), but I hope some of the charts and data provided (and links to the full articles) are interesting to you in case you’re fretting over your first beta. (Who in the world would spend hours and hours researching initial beta results? That’s crazy.)
As this all relates to me, I feel like I’ve got about a 50-50 shot. Downside, we did FET, which has lower success rates. Downside, we used a very poor quality embryo, which should have a lower success rate. Downside, low HCG numbers. Downside, we know that it was fully hatched, which means it should have implanted early. (Low HCG numbers may be from late implanters.) Downside, I’m 36, which is older than the averages of most of these patents and leads to more adverse outcomes. Upside, we used a 6-day embryo, which may start with lower numbers because sitting in solution may arrest development. Upside, using my HCG numbers alone, I have at least some chance. We just have to wait until Thursday.
Final thoughts
What do I want? Well, I want a healthy pregnancy that results in a healthy kid. So, for a start, I want to see an HCG that is at least doubling. (Preferably doing much more than that.) But if this pregnancy is not going to work out, I want a super low level. I want an early miscarriage. I do not want to spend more time plodding along with a pointless pregnancy. I do not want a late miscarriage, after I get my hopes up. I do not want a D&C. I don’t want to see a heartbeat, only to have it all taken away. And I really, really, really do not want an ectopic pregnancy. So, if I can’t have high numbers, I want low numbers. If I can’t have high numbers, I want to mourn with a nice glass of wine.
Okay, one last (dark) thought. Is anyone else wondering if pregnancies that continue from low HCG numbers are more likely to result in children with health issues?
Well, this study is pretty hard to follow (there’s a lot of math and statistics!), but I like at least this sentence: “Low levels of PAPP-A had a stronger association with adverse pregnancy outcomes than a low level of free β-hCG…. Studies investigating free β-hCG and adverse pregnancy outcomes have had mixed results.”
Another one says the same thing:
Low PAPP-A I no good, looks like not as much for low HCG. What the hell is PAPP-A? The last one says: “Low pregnancy-associated plasma protein A levels in the first trimester were associated strongly with a number of adverse pregnancy outcomes. Low free-beta subunit human chorionic gonadotropin levels and large nuchal translucency were both associated with early fetal loss.” In other words, if you have early low HCG, you’re more likely to miscarry (see above, no surprise) but it does not appear to be linked to health issues if the kid makes it. Whooh!
