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!

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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!

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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:

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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!

Hypothetical of a hypothetical

So we’re moving along with Plan D – completing our IVF homework. Here’s what I’ve accomplished in the last week:

  1. Repeated my day 3 bloodwork. This revealed virtually the same bad numbers as before. Actually, to be fair, they were a smidge better…but probably not statistically significant; FSH went from 13.7 to 13.5, E2 went from 24.6 to 27.2; AMH went from 0.17 to 0.22. More importantly, they didn’t get worse in the past 4 months, which I’ll take as good news. (Funny story about the blood draw: after so many IF-related blood draws, I decided that I was now a needle badass and would therefore watch as the phlebotomist drew my blood…naturally, that was the first time ever that someone missed the vein and had to stick me a second time! I did NOT watch the second stick. So much for being a badass.)
  2. Took blood pregnancy test. No surprises here. This test was a liability necessity before they’d do #4.
  3. Start Zithromax with C. Apparently they want to make sure neither of us has any infections prior to IVF (not sure why this isn’t required for IUI…) I’ll write about the chemistry of Zithromax below…
  4. Saline sonogram & mock transfer. Dr. Y filled my uterus with saltwater and observed it by ultrasound to make sure there were no obstructions that might pose a problem for an embryo. (Kind of like the HSG, except with saltwater in place of the dye and ultrasound instead of x-rays.) He also practiced inserting a catheter to get the ‘lay of the land’ for the real transfer. The whole thing was very anticlimactic. The most uncomfortable part was that I had to do it with a full bladder. (I have a very small bladder and practically live in the bathroom…) I would have asked C to take a picture of this, but it didn’t really look like anything. My HSG photo was much cooler.
  5. Sign & initial 9-page informed consent document. The first 6 1/2 pages of the thing discussed various aspects of the medical interventions involved. Yes, I understand that there may be side-effects of drugs, complications of surgery, that I may have multiples, and that the whole procedure may fail miserably…The unsettling part was the other 2 1/2 pages, which consisted of depressing hypothetical scenarios and our decisions about what we would want to do with our hypothetical embryos. For example, what should happen to our hypothetical embryos…
  • if we fail to pay our embryo storage bill?
  • if one of us dies?
  • if both of us dies?
  • if we are legally separated or get a divorce?
  • after I exceed my “normal reproductive life”? (defined as age 50; phew!)

C was no help at all, and I struggled with how seriously to take the whole thing. On the one hand, I was making a decision about what would happen to our precious embryos – C’s and my potential children (and the only that I might ever have). On the other hand, we were planning for a doomsday hypothetical of a hypothetical. Given my antral follicle count, we’ll be lucky to get one or two ‘good’ embryos to transfer. What are the chances that we’ll have ‘extras’ to store and worry about in the event of further hypothetical catastrophes? In the end, I tried my best to take the questions seriously…If we stop paying our bill or don’t use the hypothetical embryos by the time I’m 50, we’ll donate them to research; if one of us dies or we get divorced, they’ll be made available to the partner who wants them (probably only pertains to me, since if I die or we get divorced, C can make cheaper babies with his new wife!), and if we both die, they can be donated to another couple. Gosh I hope this post is the last time I have to think about such bummer scenarios!

 Still on our ‘To Do before IVF’ list:

  1. Submit C’s semen culture (after we finish the Zithromax course) to confirm no infection.
  2. Attend a ‘teach class’ with the nurse to learn how to do our new injections.
  3. Call the finance lady at the IVF clinic to work out arrangements for payment.
  4. Start taking estrogen (estrace) and testosterone gel.
  5. Do a blood draw (including a progesterone test, and others?) to confirm that my hormones are ‘turned off’ before officially beginning our cycle.

And finally, here’s your IF chemistry lesson for the day:

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Azithromycin (aka Zithromax) is a macrolide antibiotic. That just means that it contains a large (15-member, in the case of azithromycin) lactone ring (shown in blue). Actually, a lactone is defined as a cyclic ester, so “lactone ring” is redundant…kind of like “ATM machine”. Anyway, azithromycin is a synthetic analog of the natural product 🙂 erythromycin, produced by the soil bacterium Saccharopolyspora erythraea. Like erythromycin and other macrolide antibiotics, azithromycin has a sugar part (technically, two sugar parts, shown in green) that dangle off of the lactone ring.

On being Catholic and infertile

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I’m a practicing Roman Catholic. And so, when first faced with our infertility troubles, I made an effort to better understand the church’s stance. (I knew that the church does not approve of IVF, but why exactly? What about IUI? Hormone injections?) Fortunately, while exiting church one day, I spotted the above pamphlet for $0.50. I bought it, and here’s what I learned:

Catholic church-approved infertility treatments:

  • charting (also the only approved form of birth control; we Catholics call it Natural Family Planning or NFP)
  • ovulation test strips/monitors (POAS = not a sin)
  • most testing/evaluation procedures (see exception below)
  • drugs, hormones, suppositories (whether taken for the purpose of encouraging ovulation or supporting implantation or pregnancy)
  • corrective surgery

Unapproved infertility treatments:

  • Testing sperm obtained by masturbation (Yep, jerking off = still a no-no. As an intriguing side note, there are apparently Catholic church-approved ‘perforated condoms’ that can be used to collect semen samples during sex – the perforations are necessary to avoid violating church teaching about contraception. And, suddenly my mind jumps to a wildly inappropriate prank idea…Then, that thought is replaced by a mental image of showing up at Dr. Y’s office and handing him a dripping condom…)
  • IUI or any other form of artificial insemination
  • IVF (or ZIFT or GIFT…do people still do these?)

So, what are the underlying moral objections to these forms of treatment? What I learned in this little booklet didn’t come as much of a surprise. I’ll paraphrase:

  1. The purpose of sex is procreation, so any act that divorces the two is a sin.
  2. Life begins at conception, and any act that destroys life [even an embryo] is a sin.

Now I have to acknowledge that Catholic Church teaching is consistent. That first statement is the single reason why the church forbids masturbation, anal/oral/etc. sex, contraception, and gay sex – all of which represent sex without the possibility of procreation. Assisted reproductive technologies (including IUI, IVF, etc.) on the other hand represent procreation without sex.

It wasn’t hard for me to reject the first argument. In fact, I rejected that argument a long time ago. (Judging by the size of the average Catholic family these days, I think it’s safe to say most American and European Catholics reject that argument, whether consciously or not.) Specifically, I don’t believe that God would make gay people only to present them the unappealing choice between being celibate or a sinner. I also don’t believe that God would limit heterosexual couples to a contraceptive choice that forces one partner to choose between ignoring her hormonal urges each month or getting pregnant with her 12th child… (Incidentally, I was especially surprised a few years back to learn that my favorite Dominican priest, Fr. D. shares this concern!)

The second argument is more difficult for me, and I’ve managed to avoid it during the IUI process, but not if we move forward with IVF. This is the same argument for why the Catholic Church opposes abortion, an issue which I also struggle with – perhaps more so now that we are experiencing infertility. I’ll set aside abortion for now, but what do I think about the destruction of embryos as a result of IVF? If you had asked me a year ago, I would have given a totally lame answer:

“I think it’s great that many suffering from infertility will get to achieve their dream of pregnancy by IVF, but I wouldn’t go to those lengths.”

If pressed, I might have continued that it would seem like “such an extravagant use of resources just for the luxury of my own biological child.” That “there are so many unwanted children in need of homes,” and that “maybe it was God’s way of saying he had another plan for me.” Yup, I was one of those people. I can’t believe my good friend N. (who went through 3 or 4 fresh IVF cycles – I lost count – ultimately resulting in a gorgeous little boy) didn’t slap me across the face when I told her I’d never do IVF. I’ve since apologized for being such a hypocritical idiot!

So my feelings about IVF have changed. Did they change because now it’s me? Because now IVF is my best chance at a genetic child? Certainly that has something to do with it. But something else has changed too.

After a miscarriage at 9 weeks followed 10 months of infertility (not to mention another six failed pregnancies among close friends in that same time period), I just don’t think of embryos the same way. Before this whole experience, I think I easily could have viewed each sperm cell and each egg as a ‘potential baby’. Under the right conditions, they could fulfill their destiny and grow into a living breathing human being. [insert slight sarcasm here]

What is now apparent is that, even under the best conditions I can muster (cushy uterus, healthy & “relaxed” host, optimum timing, perfect super-sperm), I’ll be lucky to get one of my eggs to reach its so-called ‘potential’. And the best chance of doing so is through IVF.

So how can I view the demise of 3- or 5-day-old embryos (assuming I’m lucky enough to get any) as ‘destroying a life’, when they almost certainly would never have existed without IVF, and when we are actively doing everything in our power to help them develop into a baby?

Frankly, I can’t (or won’t) see IVF that way. At least not now. And as a Roman Catholic, I’m okay with that!

Postscript: To those who would call me a ‘Cafeteria Catholic’

I know you’re out there; people who will accuse me of being a ‘Cafeteria Catholic’ or ‘CINO’ (Catholic-In-Name-Only), or what have you. Aside from trotting out my Catholic credentials (baptized, confirmed, and married in the church; attend mass weekly and on all holy days of obligation – including while traveling; fast and abstain during lent; confirmation sponsor to my sister; selected by the priest to serve on my church’s Pastoral Council; etc.), and getting angry (man that term irritates me!), I like to point out two observations:

  1. Everyone I’ve ever heard accuse someone of being a ‘Cafeteria Catholic’ is, by their own definition, a Cafeteria Catholic. It’s hard not to be. The Catholic Church – more than any other church – has an official opinion on just about everything. To not be a Cafeteria Catholic, someone would first have to take the time to learn everything that the Catholic Church teaches, and then take on the Herculean task of adhering to that teaching. Actually, to spot the hypocrisy involved in this accusation, you typically don’t even have to work that hard. Pick an issue outside of Catholic moral teaching (better yet, just pick something outside of the small subtopic of sexual morality) and ask the accuser how they live that teaching in their own life. Almost invariably, users of the term Cafeteria Catholic totally ignore some or all tenets of Catholic teaching on social justice, stewardship of the environment, capital punishment, just war, and so on. (For some reason, these folks seem to be obsessed with sex. Maybe they are angry that they’re not having enough …and are envious of everyone that is.)
  2. The use of the term ‘Cafeteria Catholic’ betrays an utter misunderstanding of where Church teaching comes from. Catholic Church teaching is not static. In fact, one of the things about it that so many fundamentalist Christians find objectionable is that we don’t believe the bible to be the final and supreme word of God. Instead, we believe that God continues to speak through an ever-growing Church tradition. New issues (moral and otherwise) arise, and the Church responds, typically by enlisting a panel of experts and church leaders, who engage in extensive discussions, and prayer, and ultimately arrive at some kind of consensus that is adopted as the official Church teaching. Thoughtful and prayerful consideration of issues is part of the process. Consistent with that tradition, priests are NOT mindless drones that regurgitate official Church teaching. The majority are highly educated critical thinkers, taught to ask challenging questions and grow in their faith through independent thought and prayer. Why should laypeople behave any differently?

If I disagree with American policy (or even a small subset of American policy), am I a ‘Cafeteria American’? Can I be a ‘Cafeteria Chemist’? The Catholic Church is losing enough believers as it is. Do we really want to be in the business of telling people they don’t belong?

I don’t mean to imply that the Church is ‘wrong’ about infertility treatment, and that my beliefs are ‘right’. I fully recognize that my knowledge and experience is inherently limited, that God’s plan is beyond my comprehension in this life. But I also feel confident that I am thoughtfully and prayerfully considering the consequences of my infertility treatment, and as of today, I am comfortable proceeding with IVF if this IUI cycle fails…