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.

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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!

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.

My colorful protocol

Today, C and I went in for our IVF medications “teach class”. I’m not sure why they need to add the word ‘teach’ in there. Are there classes that don’t involve any teaching that they need to distinguish this one from? Are they distinguishing this class from a “learn class”? (Our legal counsel informs us that we can’t promise that you’ll learn anything, but by God, we’ll teach you!) Actually, maybe I can use this…I think I’m going to rename all my courses “teach classes” to spare myself any responsibility for my students actually learning anything…

Anywho, it turns out IVF is a hell of a lot more work than medicated IUI. (Once again, I can hear all the seasoned IFers in unison…No shit!) The list of medications that I have to take is long and expensive, and I can see why my insurance drew the line after IUI…

It also seems like my protocol is a little unusual, so I thought I’d share the details of it here:

First, my calendar for May:

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And my calendar for June:

calendar a

Here’s my limited understanding of what everything is for:

  • Zithromax – to ensure that C & I are infection-free prior to beginning the cycle
  • Estradiol – to help me recruit more eggs and to prevent any new cysts from forming (which would force me to delay the cycle)
  • Testosterone (gel & patch) – to try and recruit a few more eggs (In explaining this one Dr. Y was careful to say “in theory” several times, leading me to think that this claim has not been proven…)
  • Aspirin – to improve blood flow to my uterus
  • Menopur – to stimulate multiple follicles to grow
  • Clomid – to stimulate multiple follicles to grow
  • Dexamethasone – to help with implantation
  • Growth hormone – to help the eggs develop/mature fully (to achieve better egg quality)
  • Ganirelix – to prevent premature ovulation (We don’t want those eggs to drop; we want Dr. Y to suction them out with a needle instead…)
  • Follistim (FSH) – same general idea as (and one of the ingredients of) Menopur; I think this serves as a little boost to get the eggs ready to go for retrieval the next day
  • hCG – stimulates ovulation; I’m guessing this finishes getting the eggs ready to drop, but that we’ll time it so that I go in for retrieval before they actually drop
  • Doxycycline – antibiotic prophylactic to prevent infection from the retrieval
  • Prednisone – not sure what the purpose of this steroid is…maybe prevent inflammation?

Has anybody else used testosterone in their cycles? From the mysterious way that Dr. Y talked about it, I get the idea that it’s not part of the typical IVF protocol.

I think another unusual (weird?) thing is that I’m using pretty low doses of stims (especially considering the fact that I’ve got diminished ovarian reserve): 100 mg of Clomid and 150 IU of Menopur per day…that’s less than half the daily dose of Menopur that I used for IUI. Dr. Y says that they’ve found that success rates with the low stim protocol are comparable to those with high stim, but at much lower cost.

Lastly, you may have noticed that the calendar above doesn’t include an embryo transfer. Dr. Y insisted that an important feature of this protocol – and one that he recommends for old lady patients (and patients with old lady ovaries, like me) is that it does NOT involve a fresh embryo transfer following retrieval. Instead, the plan is to flash freeze (vitrify) my embryos and store them for a full cycle while my body purges itself of the colorful drug cocktail listed above. In particular, the Clomid is supposed to make for a somewhat hostile uterine environment. According to Dr. Y, for older women, postponing the transfer for a month actually gives higher pregnancy rates.

My read of the clinic stats seems to validate Dr. Y’s claim: In 2011, the % of FETs resulting in clinical pregnancy was 58.3% for 38-40 year-olds, compared to 56.3% for fresh transfers for the same age group – despite transferring more embryos on average for the fresh transfers (2.1 per transfer versus 1.8). For younger women, the fresh transfer is definitely better, so the only question is whether this 34-year-old with diminished ovarian reserve will behave more like the average infertile 38-40 year-old, or like the average infertile <37 year-old…

I guess we’ll see! Anyway, I trust Dr. Y and am perfectly happy to go with his professional judgment. (Of course, my trust for Dr. Y’s judgment didn’t prevent me from trying to mine the SART data to answer this question, but it turns out that my clinic didn’t treat enough <37 year-olds with DOR to give meaningful data…)

The punch line of this is that assuming my sonogram in two weeks looks good (crossing my fingers for lots of follicles and no more cyst!), I’ll be moving ahead with the egg retrieval in mid-June, and assuming we get any good embryos (fingers crossed yet again), I’ll take a uterus-cleansing drug holiday in July followed by a frozen embryo transfer in August!