Antagonistic

The ultrasound today seemed to go fine. Lefty is at 17 mm, with Righty lagging behind… still measuring 11 mm. (Dr. Y also measured a third at 8 mm, but didn’t say anything about it.) C and I think that Dr. Y was disappointed with Righty’s slow growth, but felt sorry for us and refrained from saying anything… He recommended continuing stims + Antagon for a couple more days to give them more time to grow. He’d like Lefty to be at 20 mm for retrieval.

The next ultrasound will be Wednesday, with tentative retrieval on Friday – possibly later. Back when we started the cycle, Dr. Y said that it will be good if we can get a couple extra stim days prior to retrieval, so I’m going to stick with that and say this is a good thing…

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So, Antagon

I’m on day 3 of Antagon (aka ganirelix), which I inject into my belly every morning by way of a prefilled syringe with an annoyingly dull needle. (It doesn’t hurt that much, but it actually bounces off of my skin if I don’t shove it hard enough!) Aside from looking like a human pincushion, I haven’t observed any side-effects.

Despite my disappointing Saturday, I didn’t want to put off writing about Antagon for too much longer, since it is actually the drug that I find the most interesting, but first:

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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Before explaining what Antagon does, it’s probably worth reviewing how this whole sex hormone signaling cascade is supposed to go normally.

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First, my brain sends a signal to my pituitary, which in turn sends a signal to my ovaries, which in turn make estrogen, grow eggs, and ovulate.

The ‘signal’ that my brain sends to my pituitary is carried by a peptide hormone called gonadotropin-releasing hormone (GnRH; also known as luteinizing hormone-releasing hormone or LHRH).

The ‘signal’ that my pituitary sends to my ovaries is carried by two proteins – our old friends FSH and LH. Normally, FSH stimulates one or two of the follicles to grow and develop into a single mature egg. LH (released in a surge) signals the ovaries to ‘drop’ the mature egg.

Of course, in the case of IVF, we don’t want to just have one mature egg, and we don’t want to have it get released before we are good and ready for it.

Here’s where Antagon comes in.

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As its name suggests, Antagon (aka ganirelix) is a GnRH antagonist, which means that it looks a lot like GnRH, but it doesn’t act like GnRH. You can see this if you look at the chemical structures of the two (below). Antagon is about the same size and shape as GnRH; it has similar atoms and functional groups (I highlighted the differences in red for your convenience). As a result, it can fit into the same tight spaces that GnRH can fit into – like the inside of the receptor protein ‘switch’ that GnRH normally turns on to make the pituitary send its signal…

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While Antagon looks like GnRH, it doesn’t act like GnRH. So when Antagon fits into the GnRH receptor protein, it doesn’t actually flip the switch ‘on’.

To pick another analogy, GnRH is the key that opens a lock on the pituitary gland. Antagon is like another key that fits into the same keyhole…but doesn’t open the lock. Having lots of Antagon around filling up keyholes makes it really hard for GnRH to actually turn any locks. (In biochemistry-speak, Antagon is a competitive inhibitor.) The effect is the same as if we had somehow removed all the GnRH from the system.

Without GnRH stimulating the pituitary gland, the pituitary gland doesn’t produce LH (or FSH, but we’re more concerned with LH at the moment), and we don’t get the surge, and ovulation is prevented (left panel, below).

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What about Lupron?

Interestingly, using a GnRH antagonist isn’t the only (or even the most popular) option for preventing ovulation.

The other, more common, method involves using a GnRH agonist (such as Lupron, aka leuprolide). A GnRH agonist both looks and acts like GnRH.

Lupron has a chemical structure that is even closer to that of GnRH. In fact, they differ by only one amino acid (in blue on the previous chemical structure drawing). Lupron also flips the GnRH receptor protein ‘on’…and keeps it on for longer than GnRH does.

But I thought we were trying to prevent GnRH from sending its signal?

The initial response of the agonist is to increase the GnRH signal – the opposite of what we want. But we’re counting on what happens next. All this signaling is very carefully regulated, so after a few days of having its GnRH switch frozen in the ‘on’ position, the pituitary figures out that something is wrong. It absorbs the GnRH receptors (the keyholes) from the cell surface, and all further signaling in the pathway gets shut down (above right).

It’s like the sirens go off, red lights start flashing, and the pituitary says “TERMINAL ERROR DETECTED. COMMENCE SYSTEM SHUTDOWN.

With the signal shut down, the pituitary doesn’t continue to make LH, and ovulation can be prevented until we’re ready for it.

What does DOR have to do with it?

Despite sounding more complicated, the agonist protocol is the more commonly-used option, or ‘plain Vanilla IVF’ if you prefer, and works well for the majority of IVF patients. However, some recent studies seem to suggest that using an antagonist might be better for poor responders (like people with diminished ovarian reserve). I think this is still pretty controversial, though.

I think the theory is that for DOR patients, the traditional agonist long protocol suppresses signaling for too long and gets in the way of recruiting the already-poorly-responsive eggs. For the agonist protocol to work, the agonist has to begin to be administered relatively early – before there are any follicles ready to drop (otherwise the initial burst of LH & FSH might trigger ovulation before the desired ‘System Shutdown’), so things are shut down for a relatively long period. By contrast, the antagonist can be administered later in the cycle, for just a few days.

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Whatever the reason, I’m gambling on the short, antagonist protocol. Odds are that I’m going to lose this poker hand, but dammit, I am not folding!

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Poor turnout

The ultrasound today did not go well. You may recall that when we saw 7 antral follicles at the baseline u/s, Dr. Y was careful to point out that

“There’s no guarantee that everyone on the guest list will show up to the party.”

Well, at this point we’ve got two RSVPs – “Lefty,” the 14 mm lead follicle, and “Righty,” who is 11 mm. The other follicles are in there, but it seems they have other plans for Wednesday. So much for the virtues of estrogen- and androgen-priming…

Dr. Y said the chances of party crashers at this point is very very small. He said that he might be able to retrieve both big follicles…and that both might fertilize…and that both might grow into blasts.

He also said that there’s a good chance we could get nothing out in the end.

Our options, then, are to quit, convert to an IUI cycle (“so that at least you get something out of it”), or continue with IVF. It definitely seemed like Dr. Y thought the sensible thing would be to convert to an IUI. In that case, we would be refunded most of the $10K we paid last time, and could return the leftover meds for a restocking fee.

Ugh.

Since this was my first IVF appointment without C, I was trying to ask enough questions to be able to anticipate what C would want to know. Although I kept myself together, tears kept ‘leaking’ out of my eyes, and the poor nurse kept trying to pass me tissues.

I called C on my way out the door (he was on the way back from dropping friends at the airport) and we met a few minutes later at the beach. We sat on a bench and stared at the ocean and talked through the options. And we decided to move forward.

It’s probably stupid, but we thought we’d feel better knowing that we tried.

Will we feel ten thousand dollars better? I don’t know. But we both felt better knowing that we were moving ahead with the plan. We walked back to my car and I injected myself with my first dose of ganirelix. (No alcohol wipe or anything. Fuck it!) C also called Dr. Y and talked through our reasoning with him. He sounded good with it, once he was sufficiently convinced that we were informed and were comfortable with the cost.

So that’s where we are. The chances of success at this point are very slim. In the likely event that it doesn’t work out, we’ll probably pursue a second opinion and/or starting alternative therapy (acupuncture + supplements) to see if it helps with my responsiveness.

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I hope you’ll forgive me, but I’m feeling a bit deflated at the moment and not really in the mood to write a chemistry post about ganirelix. I may feel like it Monday, or maybe not.

Stims

Yesterday at 7:45 am I had my first IVF monitoring appointment. Since Kaiser doesn’t cover IVF, Dr. Y does all his IVF appointments in the early morning, across town from his main office. Lucky for me, this is only about 10 minutes from my house. (The Kaiser office is about 10 minutes from my work, so it’s been pretty convenient all-around.) I liked my new clinic. The waiting room looked much nicer than the Kaiser facility: lots of good magazines, friendly staff, and a beautiful aquarium. I sat and watched the fish eating their breakfast while C studied his iPhone.

And… my follies are growing, but slowly (which Dr. Y insisted isn’t necessarily a bad thing). The biggest one measured 8 mm. Estradiol level was 83. Dr. Y said to keep taking the same dose of Clomid & Menopur (and dexamethasone, although he didn’t mention that), and to come back on Saturday.

Oh, and we paid the first big bill: $10,115 “Global Fee” for IVF + ICSI. This amount covers all the monitoring appointments and labs, the egg retrieval, and the embryology part. The Global Fee does NOT cover meds, “Embryo Banking” (freezing and storing the embryos), or frozen embryo transfer, so a complete account of the full cost will have to wait.

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Given where I’m at in my cycle, it seems like my stims would be a good science topic for today, but first the usual:

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!

*****

So, stims…

My ovarian stimulation regimen is low-dose menopausal gonadotropins (Menopur, 150 IU), and clomiphene (Clomid, 100 mg). The goal is to get my ovaries to produce not one but several large, mature, healthy eggs. To understand how these drugs are supposed to accomplish this goal, it would probably help to provide some background. And I feel the need to point out, once again, that I am not an expert. (This blog is not called ‘the infertile endocrinologist’! But if you find a blog with that title, please let me know. I’d love to read it.) So anyway, here’s how I think it works:

Sex hormone signaling 101

Normally, when my body wants to produce estradiol (the most important of the estrogens), my brain sends a signal to my pituitary gland. The pituitary responds by sending a signal to my ovaries, which respond by doing a bunch of things, including making estradiol. The estradiol itself acts as a signal that travels around and tells various body parts to do things.

The carrier pigeons transmitting all these signals are hormones. So, more precisely, my brain produces a hormone called luteinizing hormone releasing hormone (LHRH, also known as gonadotropin-releasing hormone or GnRH), which travels to my pituitary and tells it to produce two more hormones: luteinizing hormone (LH) and follicle stimulating hormone (FSH). These hormones travel to my ovaries and stimulate them to do a bunch of things – like grow eggs and make estradiol…which itself helps to prep the uterine lining, and so on.

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Feedback

As the level of estradiol increases, it circulates through the bloodstream and some of it reaches my brain. Once there, the estradiol tells my brain to stop sending the signal to make more estradiol (in other words, to stop making LHRH). This is a natural “negative-feedback loop”.

Estrogen signaling under the influence

While I’m on my stims, the goal is to get lots of follicles to grow at once. This takes high levels of FSH in there, for an extended period of time. There are two main ways of doing this:

  1. Make more of my own FSH. This is what Clomid aims to accomplish. Clomid blocks estradiol from telling the brain to STOP making LHRH. In this case, two wrongs do make a right, and blocking a stop signal is effectively the same as telling the brain to GO! The brain makes LHRH, which stimulates the pituitary to make LH and FSH, which stimulates the ovaries to grow follicles. Nice.
  2. Add in FSH from the outside. This is what I’m doing when I inject Menopur into my belly each night. Technically, Menopur is a mixture of both FSH and LH, but I think FSH plays the bigger role in follicle development (at least, that’s what its name would lead me to believe…)

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The downside of Clomid is that it doesn’t just block estradiol from talking to my brain. It blocks estradiol from talking to anyone…including my ovaries and uterus (who it’s supposed to tell to start prepping the uterine lining for implantation and making lots of sperm-friendly eggwhite cervical mucus). Clomid steals the entire message from the estradiol carrier pigeon.

Enter my weird protocol. Since the Clomid will prevent my uterine lining from being ‘embie-proofed’ in time for transfer this month, we’ll flash freeze those little guys (hopefully lots of them!) and let them chill for a month. This should give me time to do some nesting and get everything nice and ready to welcome the little tykes!

Why such a low dose of Menopur?

It seems counterintuitive that I would be using a low dose of Menopur, since the conventional wisdom is that patients with diminished ovarian reserve are generally less responsive to stims, and should therefore need more stims… For reference, I used 300 – 375 IU (4 or 5 vials) per day for my IUI cycle…more than twice as much as I’m using for IVF. From what I can tell from my limited reading of the literature, it sounds like for DOR patients with few eggs that are available for stimulation, adding more stims doesn’t increase the number of eggs recruited…and might harm egg quality.

Why Clomid?

I haven’t been able to find a clear reason why Clomid is a good choice in my case. The best I can think is that maybe in poor responders using two strategies for increasing FSH levels will work better than just one? Obviously, the fact that we aren’t doing a fresh transfer is a large part of why Clomid becomes a viable option.

What I know for sure

Clomid plus low-dose Menopur is much cheaper than the high-stims alternative.

Aside from a small crop of pimples on my forehead (which I’m guessing is due to the dexamethasone), I haven’t noticed any side-effects so far. I’m grateful for this!

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That’s where we are for now! We’ll see how the follies are doing bright and early Saturday morning!

Inspiration…and testosterone

Since starting this little blog, I’ve enjoyed finding other bloggers to commiserate with. But in finding bloggy friends, I’ve done my best to avoid blogs of people who were already pregnant. (Exceptions include Vanessa at Yeah Science! – the name of her blog was just too tempting,  and JoJo at An Infertile Road, my very first follower, who got pregnant – on her first IUI! – while I was following her.) I avoided pregnant bloggers because I wanted to shield myself from having to think about pregnant women, a sentiment that Jenny at Dogs Aren’t Kids expressed so well in a recent post.

The problem with this strategy – at least for me – is that it didn’t leave much room for optimism. I loved that there was/is no shortage of support and excellent company in my misery…but I also found myself doubtful that treatment could work for me. I mean, it didn’t seem to have worked for any of my other bloggy friends, so who was I to expect that it would work for me?! (Another problem with this strategy is that it makes me a little bit afraid of actually getting pregnant – like this amazing support system will suddenly vaporize as all my new friends go running for the hills!)

Since my last post, I took advice from Kimberly at No Good Eggs and joined my local Resolve support group. I haven’t been to a meeting yet (the next one is November 19th), but I joined their online forum. On this forum I found inspiration in the form of a Protocol Buddy – someone who followed my weird IVF protocoland had the same baseline AFCand got pregnant! And she writes a blog! I am so encouraged!

Furthermore, this experience gave me the courage to face my fear of pregnant infertility bloggers, and I started reading Jen’s blog, Overworked Ovaries. (Jen’s name and cute avatar kept popping up in the comments section on all my favorite blogs, with hints that her infertility issues might be similar to mine.) I’m about halfway through reading her posts (oldest first), and I find it so exciting to read a story that I know has a happy ending! It’s also great to see that so many of her awesome bloggy friends haven’t abandoned her, but are following along and cheering her on through her pregnancy. And I can’t help but think this is what it’s about! This is what I want!

And I feel hopeful.

*****

Now, let’s talk about testosterone. But first, the 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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Last night I applied my final Androderm patch. The night I applied my first patch, I noted first that it is weird looking. C calls it my third nipple.

ImageI wasn’t exactly sure how to apply it, so I checked the website. Clearly they are not marketing to women trying to get pregnant:

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I couldn’t help myself, and decided to check out the website for Estrace cream for comparison:

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I’ll leave it to cleverer folks than me to comment…

Anyway, I waited to write about the testosterone-priming until now, partly because I was hoping dreading expecting to observe some side effects. I observed none. This fact makes me a bit skeptical that this low-dose patch would actually do anything for a 200+ lb man with low sex drive. Then again, that’s not why I am taking it.

And why am I taking it?

From what I can tell, the use of androgens (broad term for male sex hormones including testosterone and DHEA) to treat infertility patients is pretty new, and pretty controversial. Most of the papers I read were written by physicians at the same few clinics. But I think the gist goes like this:

  • Recent studies suggest that Diminished Ovarian Reserve is a condition characterized by the reduced ability to make androgens (including testosterone). This correlation seems to be especially strong in younger DOR patients. (Interestingly, several of the papers contrast DOR with PCOS, a condition characterized by overproduction of androgens…)
  • Testosterone is produced in the ovaries, in ‘theca cells’. Testosterone from the theca cells enters the ‘granulosa cells’, where it is converted to estradiol. (You can read more about estradiol in this post.)Image
  • Granulosa cells are the cells that surround the developing follicles and help prep and develop the eggs for ovulation.

The thought is that in theory [insert head tilt and two-handed gesture] since DOR patients can’t make as much testosterone, supplementation (through a gel or patch, or indirectly by taking DHEA – a testosterone precursor), will stimulate the granulosa cells to do their thing and prep those eggs. This is supposed to “enhance follicle recruitment” (more eggs) and “promote follicle growth and development” (better eggs).

At least a few studies seem to support this theory, showing a greater number of large follicles and better overall pregnancy outcomes for DOR patients treated with androgens (versus untreated DOR patients).

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I start stims (Clomid 100 mg + Menopur 150 IU) tonight, so I guess we’ll see!

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!

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.

Green light

Today we had our baseline sonogram for IVF#1. As you may recall, our goal for today was:

  • lots of antral follicles (‘lots’ is relative; the most I’d ever had was 6, the fewest was 3…; more follicles ≈ better IVF outcomes)
  • no ovarian cysts (I had a cyst visible on my last sonogram, and if it hadn’t resolved by now, we would have to delay IVF; small cyst + stims = really big cyst)

And [drumroll please…] I’m happy to announce that Dr. Y observed 7 follicles, and no cyst! We have been given the green light to proceed with our IVF protocol for this month.

My inner skeptic: To be fair, 7 is still a pretty terrible number for IVF and Dr. Y really really had to hunt to find the last one… Dr. Y also made a point of saying,

“There’s no guarantee that everyone on the guest list will show up to the party.”

Translation: Not all the follicles that we see today will be successfully harvested as mature eggs (and not all those eggs will successfully fertilize to embryos)…

My inner Pollyanna: It’s still the best AFC I’ve ever had and I’ll take it! My usually lazy right ovary doubled its production from last month (from 1 follicle to 2). Maybe it’s all the CoQ10 I’ve been taking. Maybe Dr. Y is being more liberal in his interpretation of what a ‘follicle’ is (Hell if I can see what he’s pointing to!) Maybe all your well-wishes/prayers/baby dust found their way through the ether to motivate my ovaries… Whatever it is, I’ll take it!

So now the plan is to continue my estrace and testosterone-priming for now, and start stims (injections and other goodies) at the end of next week. This also means that I no longer have an excuse to postpone forking over $1K for my non-Kaiser-covered drugs. You can expect upcoming posts on the chemistry of these new (to me) drugs, the biology behind my unconventional protocol (I’ve been doing some more research into this lately), and the finances of all this (I finally talked to the clinic financial administrator)…

 

But before I go, I’ve been thinking about this lovely post from Rain Before Rainbow. In it, redbluebird explains why she has chosen to keep her blog anonymous and not to share it with her IRL (in real life) friends and family.

By contrast, I’d say that this blog is semi-anonymous. I’ve avoided using any real names or photos of my face and have tried to be vague enough to minimize the temptation to find me out. But to be fair, anyone who knows me even a little bit who happens to come across this blog will easily figure out it’s me (my dogs and wedding photo are easy giveaways). Academics or chemistry-types who don’t already know me but who have even a slight detective bent could also find me using information on this blog. And if that weren’t enough, I’ve shared the blog with select friends and family members who want to follow along with our journey. (Judging by our IRL conversations, I’m pretty sure that only a small fraction of them actually read it.)

The downside of having some IRL acquaintances reading this blog is well articulated by redbluebird. For one thing, I can’t go into ‘angry infertile rant mode’, however much I might want to. (Not that I’d ever rant about anybody I’ve shared this blog with, but I’m afraid to rant about other people, lest someone I love even think that I might be ranting about them…) I also find myself watching my language (a bit) and being careful about TMI (a tiny bit).

But there are also clear advantages to sharing my blog with my IRL friends and family. The first is a major reason I started this blog – to avoid having to tell the same bad news, and explain the same sad lessons in reproductive biology over and over. In this regard, the blog has already served me quite well.

One unforeseen – and amazing – benefit is that a few especially empathetic IRL friends have used information from my blog to anticipate my moods and do exactly the right thing to make me feel awesome (or less awful, depending on the situation). Such was the case a few weeks ago, after a particularly demoralizing RE appointment. My friend A invited us over for dinner and had a bottle of good red wine waiting for me. 🙂

Or last night, when I arrived home from work to find a beautiful bouquet of flowers and a card from S & Q, wishing us Good Luck for our appointment this morning. I didn’t even know that they knew we had an appointment today!

ImageThank you S & Q for the amazing flowers! I hope at the end of all this we have some gorgeous hapa babies just like yours! And thank you to everyone (IRL and cyber friends alike) who are reading this and wishing us well. I firmly believe that it makes a difference!

Seeking book recommendations

While it’s still ICLW, I’m hoping to get your input!

I love to read. When I got my first teaching job, I spent the next year reading every book I could get my hands on about teaching, mentoring students, navigating academic politics, setting up a research program, and so on. Not surprisingly, I took the same approach when we started trying to conceive.

Here’s a list of the books I read in the last year or so (in the order I read them), and what I thought of them:

  1. Taking Charge of Your Fertility by Toni Weschler. This book is the charting bible. My only suggestion is to excise the chapter on choosing the sex of your baby, since it is pretty much nonsense. The rest is fantastic. We got pregnant the first month we charted according to the instructions in this book…(We miscarried a few weeks later, but I don’t blame Weschler or this book for that!)
  2. The Mayo Clinic Guide to a Healthy Pregnancy. After successfully getting pregnant, I was interested in a book other than the ubiquitous, alarmist What to Expect When You’re Expecting. For a fabulously concise rationale for not trusting Heidi Murkoff, see this post by Yeah Science!
  3. Belly Laughs: The Naked Truth About Pregnancy and Childbirth by Jenny McCarthy. I had heard this one was funny, and bought it for my Kindle before learning that Jenny McCarthy was an anti-science wack-job. (As much as I hate to offend any readers, as a card-carrying scientist, I have to call it how I see it: Jenny McCarthy and her anti-vaccine buddies are anti-science, and I can’t help but feel anti-Jenny McCarthy.) I did read her book, though, which I think pre-dated her anti-vaccine stance, and was amusing.
  4. The Impatient Woman’s Guide to Getting Pregnant by Jean Twenge. I bought this book after learning that we were about to miscarry. This book is awesome. It is a brilliantly written, funny, thoroughly researched (Twenge is a psychology professor at San Diego State), and concise guide. I especially appreciated her thoughts on age and fertility, and her discussion of antral follicle count (she got pregnant naturally…twice, after having the same crappy AFC as me). This book – along with TCOYF – impressed upon me the importance of visiting a specialist soon, especially if you know you’re timing things right. The one thing Dr. Twenge’s book doesn’t include is a detailed discussion of ART, as she didn’t end up needing it.
  5. Preventing Miscarriage: The Good News by Jonathan Scher. I expected more from the founder of one of the world’s top ART clinics. This book was dreadful. It is anecdotal with no citations or scientific support for Dr. Scher’s claims. Worse, Dr. Scher seems to imply that women who don’t quit their jobs and submit to 9-month bedrest are at fault for their miscarriages! This book also had the feel of an advertisement for the Scher clinic. Blech!
  6. The Infertility Survival Handbook: Everything You Never Thought You’d Need to Know by Elizabeth Swire-Falker. Another excellent book, well-written and researched, and yet personal and touching. (Swire-Falker is a former attorney, and, like Twenge, knows how to do proper research.) The one downside of this book is that I found it a little depressing that despite years of attempts at ART, she was ultimately unsuccessful in carrying a pregnancy to term. She did however successfully adopt (and breastfeed!) In this book, Swire-Falker convinced me not to save IVF as a ‘last resort’ treatment, and also suggested making and stashing little self-care baskets to pull out as a pick-me-up on the inevitable rough days of an ART cycle…
  7. Conquering Infertility: Dr. Alice Domar’s Mind/Body Guide to Enhancing Fertility and Coping with Infertility by Alice Domar. I liked this book a lot. There were parts that felt like an advertisement for her program, but it wasn’t nearly as bad as Scher’s book. Dr. Domar was honest about acknowledging which of her recommendations are controversial (like giving up exercise). I especially appreciated her treatment of the emotional difficulty of IF and miscarriage.
  8. What to Do When You Can’t Get Pregnant: The Complete Guide to All the Technologies for Couples Facing Fertility Problems by Daniel Potter & Jennifer Hanin. This book was fine. Not great (it had type-os and some slightly misleading information), but fine.
  9. If at First You Don’t Conceive by William Schoolcraft. This book has some of the same shortcomings as Dr. Scher’s book (weird organization, shameless plug for Dr. Schoolcraft’s clinic – The Colorado Center for Reproductive Medicine, and not a single reference for any study or literature support for his claims – apparently having a medical degree means you don’t have to bother with proper use of sources?!), but I liked it a million times better than Dr. Scher’s book. Unlike Scher’s book, Schoolcraft’s contains lots of interesting and useful information, including cool figures like these:Image    It also contains a section on Traditional Chinese Medicine.

And that’s it! I’m almost through with Dr. Schoolcraft’s book, and I want to know what to read next. I have a slight preference for TTC-related (particularly IVF-related) nonfiction at the moment, but I’ll entertain all suggestions (fiction? websites? movies?).

So…what do you recommend?

Roid Monkey

So, on Monday I started rubbing Androgel on my upper arm each morning…and taking two Estrace (orally…phew!) each night. This is the hormone priming step of my IVF protocol. Add these to the Pulmicort inhaler that I use to keep my asthma under control and the progesterone that my corpus luteum is dutifully excreting, and you’ve got quite a steroid soup warming in my innards… I keep checking in the mirror for facial hair, bacne, or increased muscle mass. Aside from my pesky chin hair (excuse me while I find my tweezers…erm…got it!) I haven’t noticed anything.

ImageA sampling of roids in my system. You can read about progesterone, and what makes a steroid a steroid, here.

 

Speaking of progesterone, I’ve relapsed into another of my pre-IUI TTC habits, namely, charting. I keep track of each morning’s BBT (basal body temp) measurement, my CBFM (ClearBlue Fertilility Monitor) reading, any eggwhite sightings, and sexual encounters on a little paper chart on my nightstand. Recording it on the paper chart has a certain old-school charm about it, but can be a bit tricky to analyze and doesn’t quite satisfy my appetite for data.

Enter FertilityFriend. I type in my data to this website and it uses an algorithm that incorporates the data from my temperature, cervical fluid, fertility monitor, and OPK (when I use it) to determine when I ovulated. Actually, there’s a ridiculous amount of other data I could enter, but even a data junkie like me has to draw the line somewhere…

charts aMy paper chart for this month (left), and the FertilityFriend version, with est. ovulation shown as a red vertical line (right).

If you spring for the VIP membership (or if you are a new member, in which case you get a free ‘teaser’ VIP membership), the website will evaluate how well you timed intercourse. C and I apparently did ‘Good’ this month

ImageAnother feature of the VIP membership is that it will overlay up to 7 charts and show you the average BBT pattern. I’m not sure what this would be useful for, but it looks pretty cool:

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The average line (in blue) eliminates some of the noise of individual monthly charts to reveal a general trend of low temps pre-ovulation, followed by progesterone-elevated temps post-ovulation, which drop off just before the next cycle start (bonus benefit of charting – no surprise visits from AF!)

 

And this brings me to my newest dilemma: when to pick up my meds. Obviously, I already have some of them (including the Androgel and Estrace), but there are still ~$1K-worth of meds that Kaiser pharmacy doesn’t carry, which I have to pick up. If it weren’t for traffic, I would have picked them up the day Dr. Y prescribed them. But now that there is a chance – however miniscule – that I might be pregnant, I can’t bring myself to shell out that $1K until I’m sure I’ll need it…

So it’s one more thing on my ‘to do’ list. If FertilityFriend is right about my ovulation date, and if I follow my usual luteal phase of 11 days, then AF should arrive on Monday, and I can swing by the pharmacy after that, with plenty of time before I need those particular stims… On the other hand, maybe I should wait longer – until my baseline ultrasound (next Thursday) to make sure there are any follicles to stimulate with those drugs…yes, I think that makes more sense.

It’s a plan! And thank you, bloggy friends, for inspiring me to think this through, and patiently reading while I do. 🙂 Yet another perk of blogging…it forces me to think before shelling out C’s hard-earned money!

 

p.s. Welcome ICLW visitors! You can read my TTC resume here, but in brief: I’m a 34-year-old chemistry professor with diminished ovarian reserve, who has been TTC for about 15 months, including one missed miscarriage at 9 weeks. After 1 unsuccessful round of IUI, we are moving ahead with our first IVF next month. I use this blog as a form of therapy, and as a repository for interesting chemistry (and biology) that I learn along the way!

Why my husband rocks!

As we go through this infertility business, it’s easy to focus on myself – after all, I’m the one who has to take my temperature every morning, pee on countless sticks, miss work, strip from the waist down to get violated on a regular basis, check my panties every time I pee, overcome my needle phobia to give myself nightly injections, and on and on. But over the last few months, I’ve come to appreciate C more than ever before. Here are a few reasons why:

C has to put up with constant reminders of our infertility. I’m a college science professor, which means that the vast majority of people I interact with each day are either (a) 18-to-21-year-olds who haven’t started trying to make babies yet (not great for my body image, but an advantage nonetheless when it comes to IF), or (b) 40+ year-old men. Of the colleagues I come in contact with on a regular basis, only one is pregnant (to my knowledge), and two have a very cute children whom I welcome on the rare occasions when they bring them to work. C, on the other hand, is a pediatric dentist. When he’s not recovering at home from senseless injury accidents, he sees kids all day, every day. He gets asked every day whether he has kids and (when he says no) whether and when he plans to. The fact that he doesn’t have any kids yet is somewhat of a professional liability. (What kind of weirdo trains for a job that puts him in constant contact with kids but doesn’t have any of his own?!)

On top of that, C has to put up with his aunts who have no qualms asking about our babymaking plans and sharing their wisdom. (Incidentally, C’s parents have been awesome. C is Vietnamese, and wasn’t surprised when his dad sat him down after our wedding to impress upon him the importance of focusing on having a baby…preferably one born in the Year of the Dragon. Sadly, I miscarried that Dragon Baby while staying at their house; and C’s parents brought me heating pads and ibuprofen and said all the right things. Since then, they haven’t asked once about grandbabies, or given any family-building advice, or commented on my work hours or nightly glass of wine, or…)

C has been present and supportive through all this. He was with me at my first OB appointment last June, where we learned of the missed miscarriage. C held my hand through the appointment, walked me down to the lab for my hCG blood draw where I started crying (to the bewilderment of the phlebotomist), and later told me that he had never loved me more than in that awful moment.

C was with me at the first couple of RE appointments…including the one when Dr. Y informed us that I have diminished ovarian reserve. And since his accident in March, C has accompanied me to every single RE appointment, no matter how minor.

C is bankrolling our IF treatment. Yeah, yeah. I know. It’s ‘our’ money, not ‘his’ money, and infertility is ‘our’ problem, not ‘my’ problem. But that doesn’t change the fact that his choice of career and his success at that career make ART a viable option for us. Consistent with his Vietnamese heritage, C is very price-conscious. He’s willing to spend money when he’s confident of what he’s getting for it, but he hates to waste money. So, it came as somewhat of a surprise when Dr. Y was going over our protocol options and mentioned cost as one advantage of the particular protocol he was recommending. Without hesitating, C said,

“Price is not a factor in our decision.”

It turned out that Dr. Y thought this particular protocol was the best for our situation regardless of cost, but it was awesome to know that we were going with the option that Dr. Y thought had the greatest probability of success, not merely the one that would be easiest on our pocketbook.

Money has also come up a few times in our discussion of how long to try IVF with my (scarce, presumably crap) eggs before considering other options…namely donor eggs. Not surprisingly, C was a fan of the donor egg option; it has a much higher probability of success, allows C to have a biological tie to our child, allows me to carry and give birth to our child, and (perhaps most significantly) leaves open the possibility for siblings, since a donor ought to yield a greater number of viable (or, more precisely, vitrifiable) embies.

But C surprised me in a conversation a few days ago. He started out with his thoughts about donor eggs, then pointed out that he hadn’t been thinking about how I might be feeling. He said something to the effect of:

“I thought about how I would feel if it was my sperm that was the problem and we were considering donor sperm…

If we try IVF enough times, it should eventually work. At about $10K per cycle, if it takes us 10 cycles, that’s $100K. So what?! It’s the cost of a basement. I mean, if we can’t have kids, we don’t need a basement anyway!”

Now I’m not so cavalier about spending $100,000 on IVF – or with the emotional toil of ten cycles…yikes! (In truth, I’m sure he doesn’t feel quite that way either.)  But I knew what an amazing turnaround that was for him. I knew that he was working hard to empathize and understand what this must feel like for me. And I loved him SO MUCH in that moment, and told him so.

I could go on and on with reasons why my husband is awesome – like how he jumped through all the hoops to get married in the Catholic Church (he’s agnostic), and went with me to mass the Sunday after the ill-fated OB appointment; or how he listens to me talk NONSTOP about infertility (I try to come up with other stuff to talk about, but it’s like IF is all I think about right now!); or how he never asks me whether I think my job is the reason for my DOR. (I’ve wondered whether breathing low levels of solvent vapors throughout most of my adult life is a factor, and I’m sure he has too, but he’s kind enough not to say it out loud!)

I have no idea how, after four weeks on Match.com, I met this gorgeous, brilliant, rich, generous, stylish and fun guy, who, inexplicably, has a thing for uber-geeky, clutzy, introverted girls. (On our first date, I used the expression ‘rate-limiting step’ in a conversation.) It’s sort of like when Dermot Mulroney’s character on the New Girl fell for Zooey Deschanel…except that I’m no Zooey Deschanel! In terms of cuteness-to-dorkiness ratio, I’m closer to Alyson Hannigan in the first American Pie movie (not in How I Met Your Mother; she’s adorable on that show), just substitute her sexual worldiness and flute skills for some old-fashioned Catholic guilt and chemistry knowledge…

I was already amazed to have met and married C, and I am even more amazed to see how this man – who up until last summer led a charmed life – reacts with grace and humor in the face of shitty circumstances. C has missed the past 9 weeks of work due to excruciatingly painful injuries caused by a cop’s reckless behavior, and he calls this time his “sabbatical”, and spends it taking online classes to improve the efficiency of his business, practicing on the guitar, and designing our future home (hence the basement comment above)!

As much as IF sucks, I’m grateful to be going through it with an amazing man at my side. And the past year – including a miscarriage, infertility, and a car accident that almost took him from me – has only made me appreciate that fact even more.

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The two of us on our wedding day, bowing to request our ancestors’ blessing during the traditional Vietnamese wedding ceremony.