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.

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:

Image

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

Image

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.

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…