A funny thing happened on the way to Colorado…

But first, I want to apologize for the radio silence. It started because I was so busy with the start of the school year…

  • We traveled to Chicago Labor Day weekend (8/31-9/2) for a good friend’s wedding. (I got my positive OPK there, so, once again, our plans for natural cycle IUI were foiled…)
  • Fall classes started that Wednesday (9/4).
  • My promotion portfolio was due Friday (9/6).
  • Then on Saturday (9/7), I flew to Indianapolis for a whirlwind trip the American Chemical Society meeting.
  • Then back Monday (9/9) to teach the second week of classes…

And then on Friday (9/13), I found myself…

a little bit.

pregnant.

 

 

As most of you know, I’ve been diagnosed with diminished ovarian reserve (AMH 0.19, FSH 13). I was a poor responder in both menopur + IUI and low-stim + IVF cycles. We were told by three different doctors that our chances of success with my eggs were slim.

We spent the last couple months doing (well, intending to do…) natural cycle IUI and taking a laundry list of supplements in the hope that they might improve egg quality, in preparation for a ‘last ditch’ high-stim IVF cycle at CCRM.

We had our CCRM phone consult a couple weeks ago, and scheduled our one day workup for this coming Tuesday (9/24).

As most of you also know, I’m a religious BBT charter. As a result, I know that I have a short luteal phase (usually only 10 days or so). When I got to 11, 12, 13dpo without a temperature drop (and noticed that my boobs were almost filling the cups of my bra…), I started to hope. Then a week ago Friday, I caved and used an old home pregnancy test I had lying around.

It was positive.

I called Dr. Y’s office and the advice nurse ordered a blood test.

  • Beta #1 (at 13dpo) was 110.

Then on Saturday, the spotting started. Red at first, then brown. On Sunday my BBT dropped half a degree and we just knew that we were miscarrying again. That morning I also realized that I had somehow FORGOTTEN to use the progesterone suppositories that the nurse told me to use when I called on Friday!! (You have no idea how completely out of character it is for me to ‘forget’ instructions from my healthcare provider…especially about something this important!!!) So I cried in bed for over an hour on Sunday, reading and rereading supportive comments on the online forum for my local Resolve support group, sure that I had killed our miracle baby with my thoughtlessness.

 

But I went in on Monday for Beta#2.

  • Beta #2 (at 16dpo) was 380.

I continued spotting for six days, but I kept going in for blood tests.

  • Beta #3 (at 18dpo) was 980.
  • Beta #4 (at 21dpo) was 3512.

Thankfully, the spotting seems to have stopped for now.

 

 

So now I’m feeling a bunch of things:

1) Elated. This is what we’ve been praying for the past 19 months. What we paid about $12K for so far, with nothing to show for it. What we were prepared to shell out another $25-30K more for at CCRM… And somehow we hit the jackpot ‘the old-fashioned way’?!

2) Terrified. Last time we got a BFP (nearly a year and a half ago), we miscarried at 9 weeks after seeing no heartbeat at our 8 week ultrasound. We were sad, but that was just the start of our infertility journey. At the time we were so sure that we would be pregnant again in a month or two. We’ve had a roller coaster year of infertility, a DOR diagnosis, a life-threatening injury, and two failed ART cycles since then. I can only imagine what a miscarriage would be like now that we know what is at stake… We are so far from out of the woods, and I’m really scared.

3) Embarrassed. I know it sounds really stupid, but I feel like a big fat infertility fraud. Like all the wonderful people I’ve met through this journey will resent me. (I could hardly blame them, as I’ve resented my share of pregnant women.) I feel bad for even saying that I feel this way. I’m sure you’re all like “Boo hoo for the poor pregnant girl.” But it’s weird. Infertility has become a part of my identity somehow. If this pregnancy sticks, does that part of me just die?

 

 

So we canceled the trip to Colorado. (Well, for fear of jinxing it, I waited until Beta #2, and used the word “postpone” rather than “cancel” when I called CCRM…)

Our first ultrasound is on Friday.

We are cautiously hopeful…

*******

To our friends IRL, I’m sorry that you’re hearing our news for the first time like this. Given our history and how early it is in the pregnancy (just 5 weeks today), we’re not ready to share far and wide yet… But I didn’t want to leave you hanging! C & I would appreciate your discretion for now.

Catching up

Today’s ultrasound went better than Monday’s. Dr. Y seemed much more upbeat. Lefty is at 22 mm, with Righty catching up at 17 mm. The third follicle has also been growing, and is now at 12 mm. Dr. Y said it could grow enough before retrieval to be good, but the chance of this is definitely less than for the other two. My estradiol was at 781 (whatever that means…)

The net result is that we’ll trigger tonight at 9:30, with egg retrieval scheduled for 7:30 on Friday morning!

Given the fact that we have only two good-looking follicles, Dr. Y explained a few special precautions he’s taking with the retrieval.

First, he added another drug called indomethacin.

ImageIndomethacin is a non-steroidal anti inflammatory drug (NSAID) that apparently is also useful for preventing ovulation. Dr. Y said this would be extra insurance (in addition to the ganirelix) to make sure that Lefty waits around until Saturday.

Second, he said he’ll use a double lumen needle in place of the usual single lumen one. Dr. Google informs me that the double lumen needle looks like a needle within a needle:

ImageI think the inner (bigger) hole is used to aspirate up the egg (like with a single lumen needle), but the double lumen needle has the added functionality of being able to squirt water from the outer hole into the follicle and ‘rinse’ it out. The rinse can be aspirated out again to catch the egg if it wasn’t sucked up the first time.

Dr. Y seemed to think we have a good chance of retrieving the two big eggs. Either way, he said he will be able to tell us how many he got immediately after surgery. (C is not looking forward to the responsibility of being first to know the news…) If we get something on Friday, then we’ll find out on Saturday whether it/they fertilized. And if something fertilizes, then we’ll find out on Monday whether it survived to Day 3 for freezing. Given the small number of follicles, Dr. Y doubts that we would risk letting them grow to Day 5, but he didn’t rule it out completely.

So today is my last day of stims, ganirelix, dexamethasone, aspirin and prenatals. I’m also supposed to do a Follistim ‘boost’ tonight right after C gives me my hCG trigger shot at 9:30 tonight. That makes a total of 5 shots today! Tomorrow I continue the indomethacin and growth hormone (which I haven’t written anything about yet…sorry!)

Here’s an updated version of my protocol that reflects the adjustments:

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One-woman pharmacy, Redux

Now that we have the green light for IVF, I finally trekked over to the pharmacy and picked up the rest of the drugs for my protocol. Here’s the loot this time:

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Between Dr. Y’s sketchy (in my favor) billing and two hefty manufacturer coupons, I got quite a discount. Even with the discount, though, the grand total was quite a bit more than for my IUI drugs:

 

List price

Covered by Kaiser?

Coupon?

My cost

Androgel ~$380

Yes

$20

Androderm ~$390

Yes

$20

Estrace ~$100

Yes

$10

Aspirin ~$5

No

$5

Menopur $750 for 10 vials

Yes

$20

Clomid ~$50

Yes

$20

Decadron ~$7

Yes

$10

Prednisone ~$5

Yes

$10

Vibra-Tabs ~$120

Yes

$10

Pregnyl $89

No

$89

Follistim $299

No

$300

$0

Antagon $354 for 3 syringes

No

$100

$254

Omnitrope $867

No

$867

Total $3416

I actually paid:

$1335

From a chemical standpoint, this list includes 8 small molecule drugs, 4 protein drugs, and one peptide (ganirelix) that is pushing the upper limit of what I’d usually call a small molecule. (I usually give 1000 atomic mass units as the cutoff; ganirelix has a molecular weight of 1570 amu…)

Here are the structures and modes of administration for my drugs:

Image

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Notice anything?

The small molecules tend to have more appealing modes of entry (often pills). Protein and peptide drugs tend to involve needles, for reasons I explained in a previous post.

*****

I also found the biological source of many of these drugs interesting. (Note: If you’re using any of these drugs and are easily grossed out, or are philosophically opposed to Genetically Modified Organisms, you may not want to keep reading!)

Testosterone was originally discovered by painstaking isolation from bull testicles. The yield was paltry, though – just 20 milligrams from 40 pounds of testicles. (I’m trying not to think about how many bulls had to be emasculated to get 40 pounds of testicles…) Thankfully, nowadays testosterone – along with most other steroid drugs – is made semisynthetically from steroids isolated from plants (often soybeans or Mexican yams). In other words, chemists isolate a similar plant steroid and perform chemical reactions in a laboratory to convert it to the desired human hormone. Drug companies sometimes use the term ‘bioidentical’ to emphasize to non-chemists that hormones that are made semisynthetically are exactly the same – chemically and biologically – as the ones produced in your ovaries (or testicles…)

Menopur is a mixture of FSH and LH purified from the urine of postmenopausal women (hence its name; think Menopausal urine…) Historically this urine came from nuns living in convents in Italy, though I’m not sure if that’s still the case.

Pregnyl is also urine-derived, but presumably not from nuns… Pregnyl is purified hCG from the urine of pregnant women.

Follistim, on the other hand, is made from recombinant FSH (Follicle stimulating hormone) produced in Chinese hamster ovary (CHO) cells. This means that scientists copied a piece of human DNA – the blueprint that tells our cells how to make the FSH protein – and put it into the hamster cells. In effect, they hijacked the hamster cell’s protein factory and programmed it to produce large amounts of human FSH protein. (Don’t worry, the hamster cells now grow in Petri dishes; nobody is manufacturing protein in live hamsters…)

Omnitrope is also made from recombinant DNA technology, but in E. coli bacterial cells instead of hamster ovary cells. Unlike FSH (which is a challenging-to-make glycoprotein requiring sophisticated mammalian cell machinery), growth hormone is relatively easy to make. The human DNA ‘blueprint’ for growth hormone can be put into Escherichia coli cells and the bacteria cells produce the hormone for us.

*****

I think I’ll stop there. If you want to know more about the chemistry of these drugs, you might check out my previous posts about the structures of FSH, LH, hCG and Clomid; doxycycline; aspirin; testosterone and estradiol (in the context of my current IVF cycle, or of what makes them steroids); the role of estradiol in predicting ovulation with the Clearblue fertility monitor; how hCG is detected in home pregnancy tests; or the significance of FSH and estradiol for diagnosing infertility.

Rookie mistake

I made a rookie mistake this week. Since I was feeling so optimistic about this cycle, I decided to test early – at 8 dpo (that’s 8 days past ovulation, for the non IFers). I saw the faintest second line, and woke C. to tell him that we were pregnant. I tried not to get TOO excited (after all, C. and I know all too well that a BFP is a far cry from a live baby…), but in my head, I had calculated the due date, lamented the end of my blog (okay, not much of a lament, but I thought about it nonetheless), and imagined how quickly all this ‘infertility stuff’ would be a distant memory. Not wanting to burst my bubble, C. gently asked “What’s the chance that it could still be due to the trigger shot?” to which I replied, “It’s been 10 days. There is no way that protein could still be detectable in my pee after 10 days!!!) I fantasized about our rainbow baby all the way to work, and then decided to Google it. And guess what?

hCG can totally remain at detectable levels…for up to 14 days following a trigger shot!

Ugh. I’m sure all the seasoned IFers out there are like “Duh!”

So what did I do? I tested again at 9dpo, 10dpo, and 11dpo. And the second line was like faint, fainter, gone. 😦

So today C. and I went to meet with Dr. Y. to plan our our next step. (One ‘perk’ from the accident: C. is available to go with me to all my appointments!) I found this meeting super depressing, which is to say, it was exactly like every other meeting at that office… “Yadda yadda yadda, diminished ovarian reserve, yadda yadda, born with all the eggs you’ll ever have, yadda, let’s do another day 3 blood test and antral follicle count, yadda yadda, we can try IVF but you’ll be lucky to get 5 eggs out, yadda yadda yadda…” You get the idea.

Rather than rehash the rest of the conversation, or the tear-filled ride home, I’d prefer to learn and then write about the biochemistry behind how home pregnancy tests work.

Here’s a nifty image I found online. I’ll attempt to caption it in my own words.

Image

(A) So the purple blobs are hCG, which is present in the urine of pregnant women (and of wannabe pregnant women who had a trigger shot 10 days ago…)

Capillary action carries hCG along the stick (or down in this particular figure; nevermind that HPT instructions definitely do not say to hold the test with pee end up like that…) Anyway, capillary action carries hCG toward where the action is.

(B) The reddish things that look kind of like lobsters holding a blue balloon are the anti-α-hCG antibodies which were pre-deposited on the stick (between the pee end and the viewing end). The antibodies have a pigment attached (in the case of the test I used – FRER – the pigment is pink, not blue). They will grab the hCG (specifically the alpha subunit of hCG – for more about the structure of hCG, see this post) and hold on tight…and be pink.

Now, capillary action will carry the bound-to-hCG anti-α-hCG antibodies, and the free anti-α-hCG antibodies (there are extras that don’t get any hCG) along the stick.

(C) At the ‘test line’, there is a line of anti-β-hCG antibodies (blue lobsters in the figure, although they are actually colorless) that are fixed to the stick. These antibodies also grab onto hCG (specifically, the beta-subunit) and hold tight…and don’t go anywhere. Everybody holds on tight, and the resulting group of anti-β-hCG—hCG—anti-α-hCG sandwiches appear as a pink line on the stick.

Meanwhile, the free anti-α-hCG antibodies (that is, the ones that didn’t get any hCG) continue to be carried by capillary action along the stick.

(D) Finally, the free anti-α-hCG antibodies reach the ‘control’ line, where there is a line of antibodies that specifically bind to the anti-α-hCG antibodies (no hCG needed). These antibodies are the green turtle-heads in the figure, and are themselves fixed to the stick. The resulting antibody—anti-α-hCG complex appears as the pink control line.

I go in for a blood pregnancy test (which works a bit differently; but I’m too lazy to figure out how right now…) on Saturday, but with a negative HPT at 11dpo, I’m decidedly not optimistic about it. I’m also not optimistic about moving forward with IVF, but I’m sure that will pass. In the mean time, I think I’ll console myself with a glass of wine tonight.

Trigger shot

I had my estradiol and follicles checked today. Two looked like they could drop any minute, so the nurse practitioner – D. – administered the hCG trigger shot while I was there. (Poor C. didn’t get to “stick me” after all!)

For all the data monkeys (like me) out there, here’s a summary of my test results:

Estradiol (E2):

  • baseline estradiol (taken during infertility workup 1/26) = 25 pg/mL
  • estradiol on 4/17 (after 4 days of injections) = 281 pg/mL
  • estradiol today (4/19, after 6 days of injections) = 572 pg/mL

According to this FAQ (http://www.fertilityplus.com/faq/iui.html), the target is 200-600 pg/mL per big follicle; since I only have two big follicles, I think this means I’m good.

Follicle size & count:

  • On Wednesday (4/17) I had three visible follicles, measuring 14.5 mm, 13 mm, and 11 mm.
  • Today (4/19) the same follicles measured 18.5 mm, 16.6 mm, and 11.5 mm. Below is a picture of my biggest follicle, viewed on ultrasound. (The follicle is the black oval just left of center with the dotted cross through it). 18.5 millimeters sounded huge to me, so I posed a penny (also 18.5 mm in diameter) in the photo for reference!

Image

According to that same FAQ above, it looks like 16-18 mm is a good range for Menopur-stimulated follicles, which is consistent with what nurse D. said. She expects that the smaller one will probably not release, so we’re looking at two follicles this cycle.

Things are slightly less than ideal. For our best chances of pregnancy, our target would have been 3-4 big follicles (to increase the odds of at least one ‘good’ egg taking). But 2 is better than 1, and better than 5+ (in which case we would’ve had to cancel the cycle or risk a multiple pregnancy). In addition, it would have been better to inseminate 36 hours after the trigger shot, but since the clinic is closed on Sunday, 24 hours will have to do! Nurse D. pointed out that it’s better to inseminate early than late, since the sperm can “wait for the egg”, while the egg can’t do the same. (I’m sure there’s a sexist joke to be made there…) She also suggested BDing on Sunday to be sure…

So I’ll be back tomorrow for the insemination. Wish me luck!

Injections

After three days of injections, I can honestly say that they’re not that bad. C. seems genuinely impressed at how comfortable I’ve become with it. He also seems to enjoy making references to “sticking me” whenever he can…

So, what is it that I’m sticking myself with each evening?

So far, it’s been Menopur, a combination of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) purified from the urine of postmenopausal women. (Since menopause may not be that far off for me, I’ve got it on my ‘to do’ list to find out how to donate my pee to the cause!) Anyway, the idea here is that both LH and FSH work together to stimulate my ovaries to develop pre-eggs (“follicles”). At the right dose, we can hopefully get my ovaries to prep 2 or 3 eggs. They’ll be monitoring me closely by ultrasound to see if that’s what is happening.

Then, when they give me the go-ahead, C. will inject me with a megadose of (generic) human chorionic gonadotropin (hCG) to trigger my ovaries to drop all the mature eggs at once. That way, when we do IUI (intrauterine insemination, aka the turkey baster), the chances are better of getting at least one “good” egg, and a successful pregnancy. (Of course, this also increases the chance of twins, but at this point, twins sounds a lot better than childlessness, so we’re not going to let that stop us!)

hormones 2

Structurally, FSH, LH, and hCG are all related. They are all dimeric glycoproteins (composed of two separate protein pieces, each with sugars attached). One of the protein pieces (the “alpha subunit”) is the same for all three hormones. What differentiates them from one another is the other protein piece (the “beta subunit”).

The beta subunits of hCG and LH are highly similar, and both proteins bind the same receptor. Here are some fun facts that result from this similarity:

  • I don’t feel too bad about the fact that I couldn’t find an image of LH for the figure above. Just put your nose up to the screen and cross your eyes to see two of the hCG structures – that’s pretty much what LH should look like anyway!
  • When C. gives me the trigger injection of hCG, we’ll be technically using hCG as a stand-in for LH, since LH is what normally triggers ovulation. Unfortunately, I can’t seem to find a good explanation why hCG is preferred for this use…
  • You can use an ovulation predictor kit (OPK, which measures the natural LH surge that triggers ovulation) as a poor-man’s home pregnancy test (HPT). The hCG produced by a fertilized egg is similar enough to LH to get a positive test. Don’t believe me? See: http://tracysue.wordpress.com/2012/04/25/experiments/
  • A corollary of that last fact: after getting my trigger injection of hCG, I would test positive on an HPT. I haven’t decided yet if the thrill of seeing a false positive test is worth the expense of the test, but if I do, I’ll post the test (and freak out any sporadic readers…mua-ha-HA)!

And this brings me to why everyone should prefer OChem over biochem. Small molecule drugs (like aspirin, tetracyline and Clomid – the realm of organic chemists) can often be taken in pill form, while protein drugs (like insulin, Menopur and hCG) pretty much never can. This is because the delicate three-dimensional shape of proteins doesn’t hold up well in the stomach (amid all that hydrochloric acid and digestive enzymes), and because their size (~30,000 amu for FSH, LH, and hCG, versus 405 amu for Clomid) makes it hard for them to get absorbed through the intestine and into the bloodstream. On the other hand, Clomid doesn’t work nearly as well as Menopur and hCG do, so perhaps I should wait to condemn the biochemists…

Anyway, tomorrow I’ve got an estradiol blood test and ultrasound to see whether the injections are working. Stay tuned…

One-woman pharmacy

I went to pick up my drugs for medicated IUI yesterday. Annoyingly, the Kaiser pharmacy at the infertility clinic was out of Menopur – the clinic’s most-prescribed infertility drug – and I had to drive across town to the hospital pharmacy…only to find that they were out of needles?!

On the plus side, my insurance is evidently pretty good, and I got over $2K-worth of prescription drugs, syringes, and needles for $32! I wasn’t as lucky with the supplements Dr. L. recommended (including Coenzyme Q10, omega-3 fatty acids, and baby aspirin). Even with a buy-one-get-one-free sale at CVS, these cost me $134!

Here’s the loot:

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For the chemistry of these, I’ll start with the easy stuff (i.e. the small molecules)… Here are structures of the supplements Dr. L. recommended:

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Aspirin is the acetate of salicylic acid – a natural product from the bark of the willow tree. Coenzyme Q10 is a quinone (hence the Q), and an antioxidant. (The quinone part of CoQ10 is shown in blue above.) Omega-3 fatty acids are a class of fatty acids that contain multiple double bonds with the first double bond starting at carbon-3 (counting from the ‘omega’ end, or the left side on the structures above). Omega-3s are made by plants. People can get them by eating plants (especially the seeds), by eating fish (who in turn get them from eating algae and plankton…), or (in my case), by taking fish oil supplements.

Dr. L didn’t go into detail about the rationale, but said that she recommends these supplements to “maximize the quality” of my remaining eggs. From reading the labels, it looks like all are supposed to promote circulation, which I guess is a good thing for eggs. (Did I mention I’m not a biologist?) There’s also something psychologically satisfying about taking a bunch of pills…feels like I am doing something.

I’ll save the chemical structures of Menopur for another day, since it’s more biochemistry (yawn!); this post is already too long; and I’m hungry!

Wish me luck for my first Menopur injection tonight!