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…


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!


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


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.


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…


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).


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.


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!


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.


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.


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.

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:


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?


My cost

Androgel ~$380



Androderm ~$390



Estrace ~$100



Aspirin ~$5



Menopur $750 for 10 vials



Clomid ~$50



Decadron ~$7



Prednisone ~$5



Vibra-Tabs ~$120



Pregnyl $89



Follistim $299




Antagon $354 for 3 syringes




Omnitrope $867



Total $3416

I actually paid:


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:



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.