A farewell to Lefty, politics, & acupuncture

Thanks again for all your well-wishes. I just got the call from Dr. Y, and he told me that Lefty stopped growing. 😦 In the words of IVFfervescent gal, I hope he enjoyed his few days on earth.

We have our WTF appointment scheduled for Friday at 9am.

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The news of the end of Lefty’s fight was somewhat softened by this morning’s Supreme Court rulings. I don’t mean to get political on y’all, but as an infertile heterosexual Californian, I’m grateful that SCOTUS rejected the argument that the ability to procreate was a prerequisite to a valid marriage… (No really, that was “the essential thrust of” the defendants’ position!) 

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In other news, I did something very unscientific yesterday. I went to see an acupuncturist who specializes in infertility, let’s call her J. I learned about her on the forum of my local Resolve support group, where she has rave reviews. She is also conveniently located 7 minutes from my house, and had an evening appointment available for the next day.

C and I arrived at J’s office at 5:30 and went in. She read over my forms (9 pages of them!) and asked some questions about me and my future treatment plans. The stuff she said sounded reasonable. She didn’t promise to cure my diminished ovarian reserve or improve egg quality. She said that our goal would be to increase blood flow to my lady organs, and hopefully achieve subtle improvement in my antral follicle count. She expressed interest in hearing what Dr. Y says to us at our upcoming appointment so she can adjust our treatment plan accordingly. We also discussed coffee and alcohol and supplements (more on those in a future post). C asked her whether she could do anything for his rib and back pain from the accident. She said she would be glad to once she got me set up.

The mood of the office was very spa-like: dim lighting, relaxing New Age music, faint smell of incense and massage oil. J had me strip except for bra & underwear and lay on my back on the table (which resembled a massage table), covered by towels. She directed a heat lamp at my feet; put needles in my tummy, arms, hands and feet; and covered my eyes with an eye pillow. I didn’t feel much as the needles went in. Then she did moxibustion (burning a cigar-like stick of mugwort to warm the regions where the acupuncture needles were). Lastly, J started a CD of ‘Meditations for the Fertile Soul’ by Randine Lewis and placed a bell in my hand, in case I needed anything. Then she left and took C to another room.

I’m not a very good meditator. I tried, but my mind would wander after a few minutes each time. But I was pretty relaxed, and the heat lamp felt good.

J came back (30 minutes later? 45 minutes?), removed the needles, put a heat pad on my belly, and massaged my back, shoulders, and feet with a peppermint-scented massage oil. And that was it!

With the support group discount ($10 off), she charged me $115 for this visit, with future visits costing $75. She didn’t charge at all for C’s treatment, which included acupuncture and cupping therapy. (C is Vietnamese, and despite usually being pretty skeptical, he seems to have inherited a belief in the efficacy of Eastern medicine from his parents.)

Overall, we were both pleased and plan to go back once a week for the time being.

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So, why do I say acupuncture is unscientific?

Here’s what I learned about acupuncture from a few hours of PubMed searching and reading abstracts. (As I mentioned before, I am not an expert. Specifically, I have no idea whether certain journals or researchers are more or less credible, though I speculate below about their possible biases…)

First, I looked for PubMed articles about acupuncture and diminished ovarian reserve:

Well…There aren’t many. A PubMed search of “acupuncture diminished ovarian reserve” turned up no hits; modifying the search to “acupuncture ovarian reserve” returned a whopping three hits. “Acupuncture AMH” returns a single article about treating PCOS. “Acupuncture FSH” turned up more, but most were about PCOS or treating menopausal symptoms…

In conclusion, I don’t think a lot of people have studied the effect of acupuncture on egg quality or quantity, but here are promising quotes from the abstracts of a few of the articles I found:

  • “Electroacupuncture therapy has a good clinical effect for IVF patients with poor ovarian reserve, and can improve oocyte quality and pregnancy outcome.”
  • There was “no statistical difference in the number of retrieved oocytes and the fertilization rate…Acupuncture combined CM-MTSSG [Chinese materia medica for tonifying shen and soothing gan] could obviously alleviate unfavorable emotions as anxiety and depression in patients with IVF-ET, effectively improve the treatment outcomes. Its effects might be correlated with lowering the excitability of the sympathetic nervous system, elevating the quality of oocytes, and improving the endometrial receptivity.” [my emphasis]
  • “The results suggest that electroacupuncture could decrease serum FSH and LH levels and increase serum E2 level in women with primary ovarian insufficiency with little or no side effects; however, further randomized control trials are needed.”

Next, I tried to find PubMed articles about acupuncture and IVF:

A PubMed search of “acupuncture IVF” returned 63 hits. Most of these were about the effect of acupuncture on embryo transfer, some were about acupuncture analgesia during egg-retrieval, and others were about acupuncture and male factor infertility.

The articles fell into four major categories:

  1. Articles that said acupuncture is effective
  2. Articles that said acupuncture is ineffective
  3. Articles that said acupuncture is effective, but that its effectiveness can be attributed to the placebo effect
  4. Articles that said there is not enough evidence to say

The majority of articles in Category 1 appear in journals with titles like Acupuncture in Medicine, Journal of Alternative and Complementary Medicine, Complementary Therapies in Clinical Practice, Zhonguo Zhen Jiu [translation: Chinese Acupuncture & Moxibustion], Zhongguo Zhong Xi Yi Jie He Za Zhi [translation: Chinese Journal of Integrated Traditional and Western Medicine], Evidence-Based Complementary and Alternative Medicine, and Clinical Journal of Integrated Medicine.

Now, I don’t want to say that these journals are suspect, but I think it’s fair to say that their titles at least suggest a belief in the efficacy of acupuncture…

Some quotes from abstracts that supported acupuncture:

  •  “The results mainly indicate that acupuncture, especially around the time of the controlled ovarian hyperstimulation, improves pregnancy outcomes in women undergoing IVF.”
  • “Transcutaneous electrical acupoint stimulation, especially double transcutaneous electrical acupoint stimulation, significantly improved the clinical outcome of embryo transfer.” (I think it’s worth noting that this was an article in Fertility and Sterility.)
  • “acupuncture can improve the outcome of IVF-ET, and the mechanisms may be related to the increased uterine blood flow, inhibited uterine motility, and the anesis of depression, anxiety and stress. Its effect on modulating immune function also suggests helpfulness in improving the outcome of IVF-ET. Even though a positive effect of acupuncture in infertility has been found, well-designed multi-center, prospective randomized controlled studies are still needed to provide more reliable and valid scientific evidence.”
  • “In this study, there appears to be a beneficial regulation of cortisol and prolactin in the acupuncture group during the medication phase of the IVF treatment with a trend toward more normal fertile cycle dynamics.” (Another article in Fertility and Sterility.)
  • “Limited but supportive evidence from clinical trials and case series suggests that acupuncture may improve the success rate of IVF and the quality of life of patients undergoing IVF and that it is a safe adjunct therapy. However, this conclusion should be interpreted with caution because most studies reviewed had design limitations, and the acupuncture interventions employed often were not consistent with traditional Chinese medical principles. The reviewed literature suggests 4 possible mechanisms by which acupuncture could improve the outcome of IVF: modulating neuroendocrinological factors; increasing blood flow to the uterus and ovaries; modulating cytokines; and reducing stress, anxiety, and depression.”
  • “Luteal-phase acupuncture has a positive effect on the outcome of IVF/ICSI.”

The majority of articles in Categories 2-4 appear in journals with names like Fertility and Sterility, Human Reproduction, BJOG – An International Journal of Obstetrics and Gynaecology, and Clinical and Experimental Obstetrics & Gynecology.

One might argue that these journals – which focus on Western medical interventions – might be biased against acupuncture and other alternative therapies.

Some quotes from abstracts that did not support acupuncture:

  • “When studies with and without placebo controls were analyzed separately, a placebo effect was suggested.”
  • “No significant benefits of acupuncture are found to improve the outcomes of IVF or ICSI.” (Perhaps also worth noting that this was an article in the Journal of Alternative and Complementary Medicine.)
  • “New emerging evidence from clinical trials demonstrates that acupuncture performed at the time of embryo transfer does not improve the pregnancy or live birth outcome after treatment.”
  • “There was no statistically significant difference in the clinical or chemical pregnancy rates between both groups [true acupuncture vs. sham acupuncture]… There were no significant adverse effects observed during the study, suggesting that acupuncture is safe for women undergoing ET.”
  • “Currently available literature does not provide sufficient evidence that adjuvant acupuncture improves IVF clinical pregnancy rate.”
  • “The use of acupuncture in patients undergoing IVF was not associated with an increase in pregnancy rates but they were more relaxed and more optimistic.”
  • “Acupuncture performed twice weekly during the follicular and luteal phase does not seem to improve pregnancy rates following IVF-ET.”

Particularly interesting were the articles that explored the possible placebo effect of acupuncture. Many of these studies used “sham” acupuncture needles that don’t actually penetrate the skin (in one case referred to as the Streitberger control). What they generally found is that patients who did sham acupuncture got the same benefit as (or in one case greater than) those receiving real acupuncture. Here are some quotes from abstracts that addressed the placebo effect of acupuncture:

  • “Placebo acupuncture was associated with a significantly higher overall pregnancy rate when compared with real acupuncture. Placebo acupuncture may not be inert.”
  •  “Acupuncture improves clinical pregnancy rate and live birth rate among women undergoing IVF based on the results of studies that do not include the Streitberger control. The Streitberger control may not be an inactive control.” (In Fertility and Sterility.)
  • “Even if adjuvant acupuncture were to increase IVF success rates only through a psychosomatic effect mechanism, such as by reducing stress, this stress-reduction effect would be integral to the working mechanism by which adjuvant acupuncture increases IVF pregnancy rates; therefore, it seems inappropriate to control for and separate out any such stress-reduction effect by using a sham control.” (In Reproductive Medicine Online.)

So why am I doing acupuncture?

Not one of the studies I saw in my search showed a negative impact of acupuncture on pregnancy rates. And very few said there was no improvement relative to no acupuncture. Rather, they said that there was no improvement relative to sham acupuncture. They also seemed to agree that patients enjoyed acupuncture, and that there was likely a psychological benefit. The fact also remains that the Chinese have been performing acupuncture for thousands of years, which in my mind affords it a level of credibility beyond that of other ‘unproven’ treatments.

So, I think that acupuncture might help – either by “correcting my flow of qi” and thereby increasing blood flow to my lady organs (as J tells me), or by simply forcing me to lie still and relax for an hour or so each week, or via the placebo effect. The scientist in me thinks the latter two mechanisms are more likely, even as the romantic in me (and the 20-year-old who studied abroad in the People’s Republic of China) would love to think that it might work via the former.

But frankly, I don’t really care why it might work; I’m just looking for it to work. Worst case scenario, I spend $75 per week for an hour of quiet relaxation.

 

p.s. If you want to read a different take on gay marriage and acupuncture, check out Stupid Stork’s latest post.

Slowly growing

Thanks everyone for your well-wishes and words of encouragement. You all make infertility suck a little bit less…

Well, at 6:15 pm today the embryologist finally called to give us the status update on Lefty. He did fertilize, but is growing verrryyyy sloooooooooooowwlyyyyyyyyyyyyyyyyy. He is currently two cells, when he should be at least six cells by now…

Here’s a random photo I found online of what a two-cell embryo looks like:

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Here’s what Lefty should look like by now:

ImageThe embryologist was not very encouraging; she said, “most likely it will go nowhere”, but they are going to check again in two more days to see.

Dr. Y was also on the phone for the call (which is probably why they waited until 6:15 to do it), and so I asked him if we should make an appointment to sit down with him and plan the next step.

I also made an appointment with an acupuncturist, and spent a couple hours at work searching PubMed for articles about supplements to treat diminished ovarian reserve. (I’ll write a post about what I learned sometime soon.)

I figure if we’re going to throw away another $12K+, I’d like to have some reason (however improbable) for expecting a different result…

Bust

Got the call from the embryologist today. The two “intermediate” eggs didn’t mature, so they only ICSI-ed the one. And they “can’t confirm that it fertilized”. They’ll know for sure on Monday, but at this point it looks like IVF#1 is a bust.

Ugh.

Bring on the margaritas…

Three’s company

I’ll jump to the punchline and let you know that Dr. Y got all three eggs!

Here’s a breakdown of the day:

6:15 am – Woke up & showered…but skipped deodorant, lotion, or anything scented. (Apparently perfume is not good for eggs.)

7:23 am – Checked in at the surgery center with C.

8:00 am – Got IV sedative placed. Lights out.

~9:30 am – Woke up with a slight headache and waited a long time for C’s chance to give his sample. (Apparently the “collection room” got backed up…)

~10:45 am – The embryologist came by and gave us the egg report. She said one egg is “mature” and two are “intermediate”. She said that there’s a “good chance” that one of the two intermediate eggs will mature today in time for intracytoplasmic sperm injection (ICSI). She also told us that they’ll be growing our embryos in coculture with some cumulus cells from my ovaries (a technique called cumulus coculture). This is supposed to “detoxify” the medium that the embies are growing in, and provide some growth factors to help my embryos grow better.

11 am – “Collection room” finally free. C did his part.

11:30 am – Headed home.

In summary, we got pretty much the best result we could hope for at this point, given how things looked going in. Now we just pray that they all fertilize and grow.

Stay tuned for tomorrow’s fertilization report!

Catching up

Today’s ultrasound went better than Monday’s. Dr. Y seemed much more upbeat. Lefty is at 22 mm, with Righty catching up at 17 mm. The third follicle has also been growing, and is now at 12 mm. Dr. Y said it could grow enough before retrieval to be good, but the chance of this is definitely less than for the other two. My estradiol was at 781 (whatever that means…)

The net result is that we’ll trigger tonight at 9:30, with egg retrieval scheduled for 7:30 on Friday morning!

Given the fact that we have only two good-looking follicles, Dr. Y explained a few special precautions he’s taking with the retrieval.

First, he added another drug called indomethacin.

ImageIndomethacin is a non-steroidal anti inflammatory drug (NSAID) that apparently is also useful for preventing ovulation. Dr. Y said this would be extra insurance (in addition to the ganirelix) to make sure that Lefty waits around until Saturday.

Second, he said he’ll use a double lumen needle in place of the usual single lumen one. Dr. Google informs me that the double lumen needle looks like a needle within a needle:

ImageI think the inner (bigger) hole is used to aspirate up the egg (like with a single lumen needle), but the double lumen needle has the added functionality of being able to squirt water from the outer hole into the follicle and ‘rinse’ it out. The rinse can be aspirated out again to catch the egg if it wasn’t sucked up the first time.

Dr. Y seemed to think we have a good chance of retrieving the two big eggs. Either way, he said he will be able to tell us how many he got immediately after surgery. (C is not looking forward to the responsibility of being first to know the news…) If we get something on Friday, then we’ll find out on Saturday whether it/they fertilized. And if something fertilizes, then we’ll find out on Monday whether it survived to Day 3 for freezing. Given the small number of follicles, Dr. Y doubts that we would risk letting them grow to Day 5, but he didn’t rule it out completely.

So today is my last day of stims, ganirelix, dexamethasone, aspirin and prenatals. I’m also supposed to do a Follistim ‘boost’ tonight right after C gives me my hCG trigger shot at 9:30 tonight. That makes a total of 5 shots today! Tomorrow I continue the indomethacin and growth hormone (which I haven’t written anything about yet…sorry!)

Here’s an updated version of my protocol that reflects the adjustments:

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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.

Image

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!

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…)

Image

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!

Super sweet

How sweet! Aislinn at Ms Baby Makin, Ana at In My Garden Grow, My Eggtimer at The Egg Timer is About to Ring, and Lauren at On Fecund Thought (cutest IF blog name ever!) nominated me for a Super Sweet Blogging award. I’m so flattered!

I apologize that it took me so long to accept and pass along the love. (Don’t worry, this chain letter isn’t accompanied by a threat of 7 years of bad luck!)  In any case, I decided to accept this excuse to lavish praise on some great bloggers.

Conditions for accepting the award:

Thank the person who nominated you. Thanks so much Aislinn, Ana, Eggtimer and Lauren!

 •Answer 5 super sweet questions:

  1. Cookies or cake? Is cheese not an option? If not, then cake. Preferably made from a box (with pudding in the mix, yum). My favorite flavors are “yellow” and “cherry chip”…with – you guessed it – cream cheese frosting.
  2. Chocolate or vanilla? Vanilla. I know I’m weird, but I am not a huge chocolate fan. I’ll eat white chocolate or very dark chocolate (70% cacao or higher). In particular, Lindt truffles with the white or black wrappers are great! Milk chocolate is totally gross. Especially Hershey’s milk chocolate. Yuck!
  3. Favorite sweet treat? I’m not a big sweets person. I’d choose potato chips over candy hands down. But if I must choose, my favorite sweet treat is probably the aforementioned Lindt truffles…
  4. When do you crave sweet things the most? Sometimes after church I crave a glazed doughnut.
  5. Sweet nickname?  My mom used to call me Suga Buga. I think she meant it affectionately, but it sounds kind of weird now that I think about it – like I pick my nose and eat it so much, my boogers must have sugar in them? Maybe this is why I’m not such a sweet tooth…

 •Include the Super Sweet Blogging award image in the blog post:

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•Nominate 12 other bloggers. Here goes:

I’ll sort them based on what I like about them. I’ve also marked the blogs that talk about pregnancy or parenting with an asterisk, to avoid any surprises!

Fellow scientist (or pro-science medical professional) bloggers:

1. Ana at In My Garden Grow is an immunologist who illustrates her blog with these awesome colored pencil drawings. Okay, so she nominated me, but the rules didn’t technically say ‘no pingbacks’, and she’s a scientist. I couldn’t help myself. (Tag, you’re it again!)

2. Jenny at A Natural Scientist* is a PhD natural scientist of some sort (the few hints I can find point to biotechnology – which narrows it down NOT. AT. ALL.) Jenny ultimately made the brave choice to step out of the lab to be a full-time mom…and to blog about it.

3. Catwoman73 at Two Adults One Child* is a respiratory therapist who struggled with secondary infertility. Catwoman loves chemistry, ergo I love Catwoman.

4. Jane at Mine to Command is a medical professional (with a chemist husband) who has awesome taste in TV shows and movies, which she cleverly peppers into her blog (pay attention to the fictional names she uses for the characters in her stories!)

Inspirational bloggers:

5. TracySue at Journey to Somewhere*. Okay, so she’s actually not blogging anymore (at least not at this site), but she is an endocrinologist friend of a friend (though we’ve never met) who chronicled her experience with IVF. I read her blog from beginning to end as I was starting this journey. With her cute POAS “experiments” and scientific explanations, TracySue inspired me to start this little blog.

6. Jen at Overworked Ovaries* is a fellow DOR-sufferer, who writes one hilarious blog…and is pregnant with twins! Yay!

7. luvnmysailor at The Road to Minimart* is my first Protocol Buddy. I met her through the online forum for my local Resolve support group. She used my weird protocol to the letter. And got pregnant. Yay!

Sweet bloggers:

8. MrsDJRass at Baby Baby Please! is super sweet and a generous commenter. She had a BFN today and could use some words of encouragement!

9. Fertility Doll is sweet, funny, interesting, open, and – most of all – authentic.

10. elaaisa at Childless in Paris writes a poignant and sweet blog, interspersed with charming anecdotes about life amongst the Frenchies. (She’s Italian.)

Generally hilarious bloggers:

11. Aramis at It Only Takes One is in the DOR club. She also writes a brilliantly funny blog which I read from beginning to end in a day. (I couldn’t stop reading!)

12. Jenny at Stupid Stork! is an alchemist who takes the giant pile of shit that infertility gives her, and transforms it to shining gems of side-splitting humor, week after week.

*****

I was going to add a blurb about dexamethasone at the end here, but the story is turning out to be more complicated than I originally thought, and I barely have enough time to shoot up some nun pee before The Bachelorette starts … So, I’ll save the chemistry lesson for next time. Later!

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!

*****

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).

*****

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