No follicle left behind

Last weekend, C & I went out with some local infertility survivor friends. (They conceived their daughter on their second IVF attempt). I was so excited to see them and ask for their advice and provider recommendations. They’ve been understandably busy with their little bundle of joy, and we hadn’t seen them since deciding to undergo IVF.

Early in our dinner, I was reminded of how different this journey is for each of us, when I started explaining my protocol to this friend and she interrupted me to offer some well-meaning advice,

“You just need to forget about all those stats and research and just believe that this is going to work!”

Um. Yeah.

C suppressed a laugh, and I quickly explained that, in fact, the only way I was going to make it through this was to read and research everything I could, because I like learning about stuff (especially stuff that, you know, matters this much…), because it gives me something I can do, and because by doing it I can regain some feeling of control.

To her credit, she quickly relented, “I forget. You’re such a scientist!” Yes, yes I am.

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So, after asking for your book suggestions and reading your comments (Thank you SO MUCH for those by the way!), I got inspired to make the leap from nonfiction books on infertility (which were too general to answer specific questions about my IVF protocol or my diminished ovarian reserve) to the primary medical literature. It’s a far cry from my area of expertise, but I’m doing my best to find answers to some of my most pressing questions… But before I continue with what I think I know, let me offer an important disclaimer:

I am NOT an endocrinologist, or any kind of medical professional! This blog does NOT purport to offer medical advice, medical opinions, or recommendations. Please take this for what it is – the ramblings of an infertile woman trying to make sense of her complicated treatment protocol!

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Now that I’ve got that out of the way, let’s talk about Estrace! I’m currently on day 16 of Estrace supplements. I take two tabs (4 mg total) each evening (and thanks to you bloggy friends, I make sure to silently thank Dr. Y each time for instructing me to take them orally. No smurf sex for me, thank you!)

As I’ve mentioned several times by now, Estrace is just estradiol (E2) – the most potent of the female sex hormones. So, why take estradiol?

Here’s what I think I know about E2:

1) Estradiol serves a similar purpose to that of birth control pills in traditional IVF cycles. That is, it suppresses pituitary signaling to keep levels of follicle stimulating hormone (FSH) and luteinizing hormone (LH) low. The idea here is to shut down ‘business as usual’, so that Dr. Y can take control of my hormones with the stims when he is ready.

I was confused by this at first, since in a lot of the hormone signaling diagrams that I got from Dr. Google, estrogens (including estradiol) are shown stimulating the pathway leading to FSH and LH (a so-called positive feedback effect). But upon further study, I learned that moderate levels of estrogens inhibit production of FSH and LH (a negative feedback effect), while high levels of estrogens (such as occur when there are a couple of big lead follicles spitting out estradiol) stimulate FSH and LH production. Endocrinology is weird (and cool…and confusing, but mostly weird).

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Here’s some data I collected with a fertility monitor stick that corroborates this claim:

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To fully appreciate the significance of this blank stick, you might check out this post about how the CBFM works. In brief, the absence of an LH line (left) shows that no LH is being detected, while the faint E2 line (right) shows the presence of ‘moderate’ circulating E2 levels… (In case you’re wondering, the monitor read ‘high’ fertility due to the estradiol; it doesn’t realize that I’m in the middle of an IVF cycle and won’t be ovulating normally this month…)

But why not just use BCPs like everybody else?

Apparently, it is thought that in some people,  the classic ‘long Lupron’ protocol with BCPs might lead to less responsive ovaries, suppressed ovarian function, and/or decreased egg yields. From what I can tell, this may be a particular concern for members of the DOR club (like me), who need all the ovarian function we can muster…

2) Estradiol helps make lots of EWCM. I can vouch for this side effect of the Estrace pills. However, this is irrelevant to my cycle, since we’re doing IVF. No sperm needs to travel through my cervix this month (via my sperm-friendly EWCM).

3) Estradiol helps to prep the uterine lining for implantation. (Progesterone plays a major role in this, but apparently E2 can help out.) This is also irrelevant for me right now, since we’ll be freezing any embryos and doing a frozen embryo transfer in August. (I’m interested to see if Estrace is part of my protocol for getting ready for the embryo transfer, though. If so, I’ll assume this is the reason.)

4) The most interesting – and from what I can tell, least certain – effect of estradiol is that it in theory (C does a great impression of Dr. Y gesturing with both hands as he tilts his head to the side and says “in theory,…”)

Anyway, in theory, estradiol promotes the gradual, coordinated growth of follicles, which hopefully will yield more, high quality embryos. We don’t want one or two show-off follicles running ahead of the pack. It’s sort of a “No follicle left behind” situation.

Here’s hoping it works!

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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:

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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.

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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.

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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.