Advanced Maternal Age

One week ago I turned 35. In pregnancy terms, this makes me officially old.

Visit with the genetic counselor

On Thursday, to celebrate, I got to meet with a genetic counselor through Kaiser (a meeting recommended for AMA women like me). Here’s what I learned:

At 35, my risk for chromosomal abnormalities is much higher than it was at 25. (Okay, so I already knew that!) The counselor was kind enough to point out that – despite the medical community’s black-and-white labeling method – there is nothing magic about the age 35. My risk increased slightly every year, so that now my risk of conceiving a baby with:

  • Down Syndrome (aka Trisomy 21) is 1 in 296
  • Edwards Syndrome (aka Trisomy 18) is 1 in 1152
  • Any chromosomal disorder is 1 in 134

(When you think about the fact that a few months ago, I was looking at odds of successful IVF with my eggs as about 1 in 4, 133 in 134 odds of having a chromosomally-normal baby really don’t look all that bad…)

I also learned a bit about the different disorders. Down syndrome (a disorder arising from three copies of chromosome 21, hence the name trisomy 21) is the most common, but is actually somewhere in the middle of the spectrum in terms of severity and prognosis.

Trisomies 13 (Patau syndrome) and 18 (Edwards syndrome) are more serious. The vast majority of babies with these disorders don’t survive a year. Those that do have severe disabilities.

Then there are the ‘milder’ sex chromosome disorders, like Klinefelter syndrome (in which baby boy gets an extra X chromosome, to get XXY) and Turner syndrome (in which baby girl gets an extra X, to get XXX). These may lead to slight reductions in cognitive function, health problems (e.g. diabetes in the case of Turner syndrome), abnormal physical characteristics (e.g. webbed neck in the case of Turner syndrome, small testicles and man boobs in the case of Klinefelter syndrome) and infertility. (I have to admit to finding it perversely amusing to think about infertility as the most minor of possible birth defects.)

(In case you’re wondering, XYY is also a possibility, but one that apparently doesn’t lead to any noticeable difference in cognitive or other abilities…)

 

Prenatal Screening Tests

To find out my likelihood of having a baby with one of these disorders, I was offered a variety of screening options.

I. California Prenatal Screening Program (PNS)

The first was the California Prenatal Screening Program. The charge for this test is $160 (fully covered by my insurance), and I found it interesting that that the money from all the women who get screened gets thrown into a communal pot. Uninsured women who get a positive screening test are eligible to use funds from the pot to pay for follow-up tests (like amniocentesis), and further prenatal care. Kind of cool.

Anyway, the California Prenatal Screening includes up to three different elements:

A.  A first-trimester blood test that measures levels of two molecules:

  1. human chorionic gonadotropin (hCG) – the protein hormone that’s used to confirm pregnancy in both home pregnancy tests and blood pregnancy tests, and
  2. pregnancy-associated plasma protein A (PAPP-A) an enzyme that chops up other proteins

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First trimester hCG levels tend to be a bit higher in Down syndrome pregnancies than in normal pregnancies, while PAPP-A levels tend to be a bit lower in Down syndrome pregnancies than in normal ones. Here are some figures I found on the interwebs showing the rough trends. In one-dimension:

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In two-dimensions (hCG is on the x-axis; PAPP-A is on the y-axis):

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Notice that there is a large overlap between Down syndrome and normal pregnancies in each plot. The genetic counselor also assured me that the levels change significantly over the course of the pregnancy, so a correct pregnancy date is crucial for an accurate result. Ultimately, this one blood test alone is insufficient to reliably predict Down syndrome risk, which is why the CA screening folks won’t give a result until they have at least one other piece of data, such as the following:

B.  A high-resolution ultrasound called nuchal translucency (NT) ultrasound is used to measure the thickness of a fluid-filled ‘translucent’ layer in the baby’s neck. More fluid in the neck is correlated with higher risk of congenital heart defects, which in turn is correlated with Down syndrome.

Here’s a figure showing normal (right) and Down syndrome (left) NT scans:

ImageSource

As with the blood test, this is all based on correlations, and just gives probabilities. (We infertiles just love probabilities…) Anyway, it is far from diagnostic.

These first two tests are sometimes referred to as the first trimester screen.

C.  The final data point that can be used as part of the California screen is a blood test in the second trimester. This test is sometimes called the quadruple test or quad screen, as it measures the levels of four molecules:

  1. human chorionic gonadotropin (hCG, see above)
  2. α-fetoprotein (AFP) – the most abundant plasma protein in human fetuses; its function in humans is unknown; AFP levels are elevated in pregnancies of babies with certain birth defects, including Down syndrome and neural tube defects like spina bifida.
  3. unconjugated estriol (UE3) – a  steroid hormone produced in pregnancy; low levels of UE3 may indicate chromosomal abnormalities
  4. inhibin A – a protein that inhibits follicle-stimulating hormone (FSH) production; inhibin levels are especially high in cases of Down syndrome, and especially low in cases of Edwards syndrome

 

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Like with the first trimester screen, the specific levels of these molecules can either more closely resemble a ‘normal’ or a ‘Down syndrome’ (or other chromosomal abnormality) pregnancy.

Even with all three data points, the best the CA screen can do is give probabilities of an abnormality. A probability of 0.5% (1 in 200) or greater is considered a positive test. In other words, the vast majority of women who get a ‘positive’ screening result will go on to have normal babies.

 

II. Non-Invasive Prenatal Test (NIPT)

The genetic counselor informed me that I’m also eligible for a very new blood test called the Non-Invasive Prenatal Test (or NIPT). This test is so new that Kaiser just began routinely offering it to women over 35 in June (which may explain why my OB failed to mention it in our first prenatal visit…even after C and I had made it clear that we wanted every non-invasive test available…)

This test is also a blood test, but instead of measuring the levels of proteins and small molecules in my blood, the NIPT looks at fragments of DNA in my blood. This post is getting rather long, but I’ll try to give the basic gist.

Apparently if you looked at all the DNA in my blood right now, about 10% of it would actually be pieces of DNA from my baby’s blood. Unfortunately, there’s no easy way to recognize which DNA is from me and which is from baby.

It is, however, possible to extract the DNA soup (including mine and baby’s) from my blood, and then make copies of certain portions of DNA from certain chromosomes. (For any biology types, they use quantitative PCR for this.) To detect Down syndrome, they make copies of a piece of DNA that only appears on chromosome 21, along with copies specific to several other chromosomes. Then they compare the amount of chromosome 21-specific copied DNA to the amount of other chromosome-specific copied DNA.

  • If the amounts are the same, it suggests that there weren’t ‘extra’ copies of chromosome 21 floating around to begin with, and that my baby probably does not have Down syndrome.
  • If there is an excess of chromosome 21-specific DNA, it suggests there were extra copies of chromosome 21 in our combined blood. Since we are pretty sure I don’t have Down syndrome, the most likely explanation is that my baby does.

This test catches a higher percentage of Down syndrome cases than the California screen (99% versus 90-95% for the combined CA screen), and has a much lower false-positive rate. (The detection rate is a bit lower for some of the other chromosomal disorders, for reasons that I haven’t taken the time to investigate.) It doesn’t, however, give any information about neural tube defects (which the California screen does), and it still does not give a definitive yes or no answer. For that, one would have to do chorionic villus sampling (CVS) or amniocentesis, both of which actually look at the full set of chromosomes in baby’s cells.

 

What I did

So, if you’ve been reading this blog for long, you know that I’m a sucker for data, so perhaps it comes as little surprise that I requested both tests. I gave blood for part A of the California Prenatal Screening right after my first OB visit three weeks ago. No doubt my results are sitting on a computer somewhere, but they won’t release them until I’ve completed my nuchal translucency ultrasound (part B)…which I’ll do bright and early tomorrow morning.

Last Thursday, after my meeting with the genetic counselor, I gave a blood sample for the NIPT. I’m told the results of that test should come back to me within a week. (Oh, and did I mention, the NIPT will also tell us baby’s gender?!)

Given that the NIPT is so much more accurate than the California screen, one might argue (as the genetic counselor sort of did) that the NT ultrasound is a waste of time. For one thing, there’s a decent chance that the CA screen may indicate an abnormality, while the NIPT may come back normal. If that happens, it may indicate that baby has a chromosomal disorder but is in the very small percentage of cases that are missed by the NIPT. Or, it may mean that baby has no chromosomal disorder, but has an unrelated congenital heart defect (giving rise to the thicker-than-usual nuchal translucency). Or (most likely) it may mean that baby is fine and the CA screen gave a false positive.

The uncertainty could easily cause a lot of stress, which is why the genetic counselor was careful to make sure I didn’t choose it blindly. I’m probably being a bit naïve (or arrogant?), but I’d like to believe that I could think logically about the likelihood of each possibility and handle any ambiguity that might arise.

Also, I really want to see my baby in high resolution.

 

What if?

In all this talk about the science behind these screening tests, I’ve conveniently avoided the most important question that all this brings up.

Namely, what will we do if the screening tests (particularly the NIPT) show a chromosomal abnormality?

The short answer is, I don’t know.

After all that we’ve been through, it’s hard to imagine choosing to terminate this pregnancy under any circumstances. In particular, I don’t think I’d terminate if faced with any of the ‘mild’ abnormalities (Turner or Klinefelter Syndrome). I don’t even think I’d terminate in the case of Down syndrome. (The way I see it, this may be my only chance at genetic parenthood, and I’d rather be mom to a child with Down syndrome than to no child at all…)

The decision gets harder for the ‘severe’ chromosomal abnormalities – trisomy 13 or 18. Could I continue with all the emotional and physical pains of pregnancy and childbirth, knowing that my baby would in all likelihood not survive infancy?

On the other hand, could I choose to end a life – my baby’s life – even knowing that it wouldn’t live long anyway?

I just don’t know.

And then there’s the fact that this isn’t just my decision. This decision would affect C too, and we’d need to somehow arrive at a plan together.

It’s enough to make me think that the people who refuse to test are on to something. Perhaps mothers like me – who aren’t prepared to terminate yet do decide to test – are just betting on a negative test result so that we can enjoy rest of our pregnancies with one less thing to worry about…

Well, I’ve already placed my bet, so all I can do now is wait and hope that my big gamble pays off.

I’ll keep you posted.

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Supplements, Part I: DHEA

As I mentioned in my last post, our game plan is to proceed with the “soft science” in an effort to improve my egg quality before trying IVF again. Dr. Y (and I) refer to this as soft science because there is so little evidence that it works. But, since there isn’t any “hard science” to suggest how I might improve my egg quality, the soft stuff is all I have available to me! And the specific weapons in my soft science arsenal include acupuncture and dietary supplements.

Here are the supplements I’m taking (in my fancy new pill organizer – it’s a bit unnatural how fond I am of it…see, you push down the little colored tab, and the compartment pops open with a satisfying ‘click’…)

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By name, here’s what I’m taking:

  • aspirin (81 mg, 1X per day)
  • coenzyme Q10 (400 mg, 3X per day)
  • DHEA, micronized (25 mg, 3X per day)
  • fish oil (1000 mg, 1X per day)
  • L-arginine (1000 mg, 1X per day)
  • melatonin (3 mg, at bedtime)
  • myo-inositol (2 gm, 2X per day)
  • prenatal vitamin (2X per day)
  • pycnogenol (30 mg, 3X per day)
  • vitamin C (500 mg, in the morning)
  • vitamin E (200 IU, 1X per day)

As you can see, it’s a long list, so I’ll break it down into a few posts. Today I’ll start with DHEA, perhaps the most widely-prescribed supplement for DOR-sufferers like me (albeit with scanty scientific evidence to support it…) Here’s what I think I know about DHEA, 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 diagnosis and treatment!

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DHEA is short for dehydroepiandrosterone, a “male” steroid sex hormone (or androgen) that serves as a precursor to testosterone (and estradiol for that matter). I wrote previously about the theory behind using androgens to treat female infertility. In brief, DHEA produced in the adrenal glands and ovaries gets converted to testosterone in the ovarian theca cells. This testosterone travels to the ovarian granulosa cells, where it is converted to estradiol. In addition to making estradiol, the granulosa cells surround the egg and are responsible for producing additional hormones to stimulate egg growth. Androgen levels (including DHEA and testosterone) tend to decline with age, and some researchers think that diminished ovarian reserve is a condition characterized by low androgen levels. In theory, adding extra DHEA through supplementation will stimulate the granulosa cells, leading to an increase in follicle growth and responsiveness.

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In the US, DHEA is easily available over the counter, and a large number of DOR women are currently taking DHEA with the hopes of improving their ovarian responsiveness. However, the verdict is still out on whether this works at all. From what I can tell, DHEA’s biggest proponents are Drs. Norbert Gleicher and David Barad of the Center for Human Reproduction. Here’s a summary of their research articles and a snazzy video. At the other end of the spectrum, Dr. Geoffrey Sher of the Sher Institutes for Reproductive Medicine is convinced that DHEA supplementation for DOR patients is a bad idea, a stance which he articulates in his popular blog.

To try and get to the bottom of the DHEA debate, I once again enlisted the help of PubMed, a database of citations from the biomedical literature.

First, I searched for “diminished ovarian reserve DHEA”. This search yielded 20 hits, of which 13 concluded that DHEA improves pregnancy rates in DOR patients, and 7 articles concluded there is not enough evidence to indicate a beneficial effect of DHEA supplementation.

At a first glance, this would seem to strongly support using DHEA – 13:7 in favor of DHEA, and the 7 detractors are saying there is no effect, not that there was an adverse effect of DHEA supplementation. But on closer inspection, I noticed that 11 of the 13 pro-DHEA articles came out of a single research team. Many of these articles were case studies. None were the sort of double-blind placebo-controlled studies that satisfy me as a scientist. (Although, in their defense, I found hardly any infertility studies that would qualify as double-blind placebo-controlled studies…Reproductive endocrinology in practice just doesn’t seem to be very evidence-based…)

So, who is this prolific, pro-DHEA research team? They are none other than Norbert Gleicher and David Barad of the Center for Human Reproduction. Now, the fact that they publish a lot about DHEA is certainly not a reason in itself to be suspicious of their conclusions. However, I did find the following disclosure (included in the text of one of their articles) worth considering:

“N.G. and D.H.B. are listed as co-inventors on two, already granted US user patents, which claim therapeutic benefits from DHEA supplementation in women with DFOR and DOR: both authors are also listed on additional pending patents in regard to DHEA supplementation and on pending patents.”

So they clearly have a financial interest in the efficacy of DHEA. I also think it’s worth mentioning that the SART stats for the clinic Dr. Gleicher heads (listed as American Infertility of New York PC on the SART database), are underwhelming…even when I sort the data to view only the stats for couples diagnosed with diminished ovarian reserve. Of course, stats aren’t everything; there are a number of reasons why their clinic might have lower stats (for example, if they take the cases that everybody else won’t, etc.) Still, I’m inclined to take their research conclusions with a grain of salt.

Here are some selected quotes from articles about DHEA:

from articles in favor of DHEA supplementation for poor responders from articles showing no benefit to DHEA supplementation
  • “several studies have suggested an improvement in pregnancy rates…While the role of DHEA is intriguing, evidence-based recommendations are lacking…large randomized prospective trials are sorely needed. Until (and if) such trials are conducted, DHEA may be of benefit in suitable, well informed, and consented women with diminished ovarian reserve.”
  • “DHEA supplementation is an effective option for patients with DOR.”
  • “Although more data on the dehydroepiandrosterone effect on assisted reproduction are needed, results obtained over the last few years confirm the improvement of oocyte production and pregnancy rates. No significant side effects are reported, and those include mainly hirsutism and acne.”
  • “DHEA does not appear to exert influence via recruitment of pre-antral or very small antral follicles (no change in AMH and inhibin B) but rather by rescue from atresia of small antral follicles (increased AFC).”
  • “The improvement of reproductive parameters after DHEA supplementation in poor responders may be explained through the effect that this pro-hormone exerts on follicular microenvironment.”
  • “Dehydroepiandrosterone supplementation can have a beneficial effect on ovarian reserves for poor-responder patients on IVF treatment.”
  • “no significant difference in the clinical pregnancy rate and miscarriage rates…insufficient data to support a beneficial role of DHEA”
  • “low DHEA levels do not suggest that supplementation with DHEA would improve response or pregnancy rate.”
  • “Although androgens may be biologically plausible, current evidence is not sufficient to prove their effectiveness…patients should be counseled regarding the experimental nature of such a treatment.”
  • “We believe that large-scale, well-designed confirmatory studies are necessary to prove the efficacy of DHEA before it can be recommended for routine use.”
  • “Based on the limited available evidence, transdermal testosterone pretreatment seems to increase clinical pregnancy and live birth rates in poor responders undergoing ovarian stimulation for IVF. There is insufficient data to support a beneficial role of rLH, hCG, DHEA or letrozole administration in the probability of pregnancy in poor responders undergoing ovarian stimulation for IVF.”
  • “There is currently insufficient evidence from the few randomized controlled trials to support the use of androgen supplementation or modulation to improve live birth outcome in poor responders undergoing IVF/ICSI treatment.”

What did I conclude from all this?

  • Dr. Y was right not to prescribe DHEA off the bat. Now I’m not a physician, but if I were, the amount of evidence out there about DHEA and DOR is insufficient for me to justify encouraging patients to pump themselves full of expensive performance-enhancing steroids. (Yes, DHEA is on the WADA List of Prohibited Substances. I’ll write more on the overlap between this list and most IF treatments in a future post…)
  • Aside from acne and hair growth, DHEA probably won’t hurt me. Dr. Sher’s objections notwithstanding, I can’t find any evidence to show that DHEA supplementation (at a dose of 50-75 mg/day) is likely to be harmful. Even Dr. Sher’s blog didn’t give any particular reason why he thinks DHEA is harmful, or any published studies showing that it is. Publishing an opinion on a blog is just that – an opinion. I certainly don’t lend it the same level of credibility as an article published in a peer-reviewed scientific journal. (Unless it’s my opinion on my blog; in that case, you should take it as Gospel!)
  • I’m ready to try DHEA. While I think it was the right decision not to take DHEA prior to my first IVF cycle, now we have more information. From my failed cycle, we know that I’m a poor responder (even on the protocol specifically designed for poor responders), and that my egg quality is crap. The properly randomized and placebo-controlled “good science” has failed me, and all that’s left is this “soft science”.

I think it’s significant that several of the studies I found specifically suggested that physicians should only prescribe DHEA to “well-informed” and consenting women who fully appreciate its experimental nature. I think now I can safely say that I fall into that group…

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.

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

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

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

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

Here’s where Antagon comes in.

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

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

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

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

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What about Lupron?

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

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

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

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

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

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

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

What does DOR have to do with it?

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

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

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

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!

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!

No follicle left behind

Last weekend, C & I went out with some local infertility survivor friends. (They conceived their daughter on their second IVF attempt). I was so excited to see them and ask for their advice and provider recommendations. They’ve been understandably busy with their little bundle of joy, and we hadn’t seen them since deciding to undergo IVF.

Early in our dinner, I was reminded of how different this journey is for each of us, when I started explaining my protocol to this friend and she interrupted me to offer some well-meaning advice,

“You just need to forget about all those stats and research and just believe that this is going to work!”

Um. Yeah.

C suppressed a laugh, and I quickly explained that, in fact, the only way I was going to make it through this was to read and research everything I could, because I like learning about stuff (especially stuff that, you know, matters this much…), because it gives me something I can do, and because by doing it I can regain some feeling of control.

To her credit, she quickly relented, “I forget. You’re such a scientist!” Yes, yes I am.

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So, after asking for your book suggestions and reading your comments (Thank you SO MUCH for those by the way!), I got inspired to make the leap from nonfiction books on infertility (which were too general to answer specific questions about my IVF protocol or my diminished ovarian reserve) to the primary medical literature. It’s a far cry from my area of expertise, but I’m doing my best to find answers to some of my most pressing questions… But before I continue with what I think I know, let me offer an important disclaimer:

I am NOT an endocrinologist, or any kind of medical professional! This blog does NOT purport to offer medical advice, medical opinions, or recommendations. Please take this for what it is – the ramblings of an infertile woman trying to make sense of her complicated treatment protocol!

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Now that I’ve got that out of the way, let’s talk about Estrace! I’m currently on day 16 of Estrace supplements. I take two tabs (4 mg total) each evening (and thanks to you bloggy friends, I make sure to silently thank Dr. Y each time for instructing me to take them orally. No smurf sex for me, thank you!)

As I’ve mentioned several times by now, Estrace is just estradiol (E2) – the most potent of the female sex hormones. So, why take estradiol?

Here’s what I think I know about E2:

1) Estradiol serves a similar purpose to that of birth control pills in traditional IVF cycles. That is, it suppresses pituitary signaling to keep levels of follicle stimulating hormone (FSH) and luteinizing hormone (LH) low. The idea here is to shut down ‘business as usual’, so that Dr. Y can take control of my hormones with the stims when he is ready.

I was confused by this at first, since in a lot of the hormone signaling diagrams that I got from Dr. Google, estrogens (including estradiol) are shown stimulating the pathway leading to FSH and LH (a so-called positive feedback effect). But upon further study, I learned that moderate levels of estrogens inhibit production of FSH and LH (a negative feedback effect), while high levels of estrogens (such as occur when there are a couple of big lead follicles spitting out estradiol) stimulate FSH and LH production. Endocrinology is weird (and cool…and confusing, but mostly weird).

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Here’s some data I collected with a fertility monitor stick that corroborates this claim:

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To fully appreciate the significance of this blank stick, you might check out this post about how the CBFM works. In brief, the absence of an LH line (left) shows that no LH is being detected, while the faint E2 line (right) shows the presence of ‘moderate’ circulating E2 levels… (In case you’re wondering, the monitor read ‘high’ fertility due to the estradiol; it doesn’t realize that I’m in the middle of an IVF cycle and won’t be ovulating normally this month…)

But why not just use BCPs like everybody else?

Apparently, it is thought that in some people,  the classic ‘long Lupron’ protocol with BCPs might lead to less responsive ovaries, suppressed ovarian function, and/or decreased egg yields. From what I can tell, this may be a particular concern for members of the DOR club (like me), who need all the ovarian function we can muster…

2) Estradiol helps make lots of EWCM. I can vouch for this side effect of the Estrace pills. However, this is irrelevant to my cycle, since we’re doing IVF. No sperm needs to travel through my cervix this month (via my sperm-friendly EWCM).

3) Estradiol helps to prep the uterine lining for implantation. (Progesterone plays a major role in this, but apparently E2 can help out.) This is also irrelevant for me right now, since we’ll be freezing any embryos and doing a frozen embryo transfer in August. (I’m interested to see if Estrace is part of my protocol for getting ready for the embryo transfer, though. If so, I’ll assume this is the reason.)

4) The most interesting – and from what I can tell, least certain – effect of estradiol is that it in theory (C does a great impression of Dr. Y gesturing with both hands as he tilts his head to the side and says “in theory,…”)

Anyway, in theory, estradiol promotes the gradual, coordinated growth of follicles, which hopefully will yield more, high quality embryos. We don’t want one or two show-off follicles running ahead of the pack. It’s sort of a “No follicle left behind” situation.

Here’s hoping it works!

One-woman pharmacy, Redux

Now that we have the green light for IVF, I finally trekked over to the pharmacy and picked up the rest of the drugs for my protocol. Here’s the loot this time:

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Between Dr. Y’s sketchy (in my favor) billing and two hefty manufacturer coupons, I got quite a discount. Even with the discount, though, the grand total was quite a bit more than for my IUI drugs:

 

List price

Covered by Kaiser?

Coupon?

My cost

Androgel ~$380

Yes

$20

Androderm ~$390

Yes

$20

Estrace ~$100

Yes

$10

Aspirin ~$5

No

$5

Menopur $750 for 10 vials

Yes

$20

Clomid ~$50

Yes

$20

Decadron ~$7

Yes

$10

Prednisone ~$5

Yes

$10

Vibra-Tabs ~$120

Yes

$10

Pregnyl $89

No

$89

Follistim $299

No

$300

$0

Antagon $354 for 3 syringes

No

$100

$254

Omnitrope $867

No

$867

Total $3416

I actually paid:

$1335

From a chemical standpoint, this list includes 8 small molecule drugs, 4 protein drugs, and one peptide (ganirelix) that is pushing the upper limit of what I’d usually call a small molecule. (I usually give 1000 atomic mass units as the cutoff; ganirelix has a molecular weight of 1570 amu…)

Here are the structures and modes of administration for my drugs:

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Notice anything?

The small molecules tend to have more appealing modes of entry (often pills). Protein and peptide drugs tend to involve needles, for reasons I explained in a previous post.

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I also found the biological source of many of these drugs interesting. (Note: If you’re using any of these drugs and are easily grossed out, or are philosophically opposed to Genetically Modified Organisms, you may not want to keep reading!)

Testosterone was originally discovered by painstaking isolation from bull testicles. The yield was paltry, though – just 20 milligrams from 40 pounds of testicles. (I’m trying not to think about how many bulls had to be emasculated to get 40 pounds of testicles…) Thankfully, nowadays testosterone – along with most other steroid drugs – is made semisynthetically from steroids isolated from plants (often soybeans or Mexican yams). In other words, chemists isolate a similar plant steroid and perform chemical reactions in a laboratory to convert it to the desired human hormone. Drug companies sometimes use the term ‘bioidentical’ to emphasize to non-chemists that hormones that are made semisynthetically are exactly the same – chemically and biologically – as the ones produced in your ovaries (or testicles…)

Menopur is a mixture of FSH and LH purified from the urine of postmenopausal women (hence its name; think Menopausal urine…) Historically this urine came from nuns living in convents in Italy, though I’m not sure if that’s still the case.

Pregnyl is also urine-derived, but presumably not from nuns… Pregnyl is purified hCG from the urine of pregnant women.

Follistim, on the other hand, is made from recombinant FSH (Follicle stimulating hormone) produced in Chinese hamster ovary (CHO) cells. This means that scientists copied a piece of human DNA – the blueprint that tells our cells how to make the FSH protein – and put it into the hamster cells. In effect, they hijacked the hamster cell’s protein factory and programmed it to produce large amounts of human FSH protein. (Don’t worry, the hamster cells now grow in Petri dishes; nobody is manufacturing protein in live hamsters…)

Omnitrope is also made from recombinant DNA technology, but in E. coli bacterial cells instead of hamster ovary cells. Unlike FSH (which is a challenging-to-make glycoprotein requiring sophisticated mammalian cell machinery), growth hormone is relatively easy to make. The human DNA ‘blueprint’ for growth hormone can be put into Escherichia coli cells and the bacteria cells produce the hormone for us.

*****

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.

Roid Monkey

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

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

 

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

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

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

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

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

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

 

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

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

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

 

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

Old habits die hard

As you may recall from my last post, the current plan is IVF homework this month; stims and ER next month; detox in July; and FET in August. Not wanting to waste a single egg (what if it’s my only good one left?!), I naturally asked Dr. Y for permission to try ‘the old-fashioned way’ this month. Ever the gentleman, Dr. Y refrained from sharing his thoughts (Why not just enjoy the break? Don’t you realize how low your chance of success is?), and he politely said that would be fine.

So I pulled my BBT thermometer, pen, and a blank chart out of the nightstand drawer, and dug around in the bathroom cupboard for my ClearBlue Fertility Monitor and a stash of test sticks. (Okay, so I may have used the phrase ‘the old-fashioned way’ a tad liberally…) I had skipped all this during our IUI cycle thinking it would be a relief not to have to trouble myself with the morning routine, but I actually ended up regretting it. Throughout the cycle I found myself missing all that precious data! I wanted answers:

  • Would the Menopur injections cause a ‘peak’ reading on the monitor?
  • What about the hCG trigger shot?
  • How long after the trigger shot did my BBT rise?
  • Did the progesterone suppositories cause a higher BBT than usual?

I don’t know! And that bugs me a little bit.

Anyway, I’m back to collecting my precious data this month (and probably will through IVF too, because, why not?!)

And to everyone who wondered how the ClearBlue Fertility Monitor works, the rest of this post is for you. (Wait, nobody is wondering that? In that case, read this hilarious post by Stupid Stork instead…)

Still here?

So, the ClearBlue Fertility Monitor…

Like OPKs, the ClearBlue Fertility Monitor (or CBFM for short) monitors the levels of hormone in my urine. While OPKs detect luteinizing hormone (LH) that surges 24-48 hours prior to ovulation, CBFM detects both LH and estradiol (E2). E2 rises a bit sooner, and a bit more gradually than LH, which means the CBFM can give me more advance warning before ovulation. (This makes it easier to have some semblance of romance in this whole TTC thing. I can say ‘It’s been awhile since we’ve gone out; let’s make Wednesday a date night,” instead of “Wake up! Sexytime! Now! NOW!”)

Each morning starting on CD6, I POAS, cap the little stick, and snap it into the appropriate slot on the monitor. The monitor waits 3 minutes for the stick to develop and then shines a little red light on the stick ‘reading’ the result. For the scientists reading this, I assume the monitor works like a visible absorbance spectrophotometer; I’m looking forward to taking it apart to investigate once I’m sure I don’t need it anymore…

Anyway, after reading the stick, the monitor displays one of three possibilities:

  • Low: low E2 and LH levels. You can have sex today for fun or romance, but you can’t in good conscience use TTC as an excuse.
  • High: high E2 but low LH levels. You can use TTC as a pretty good excuse to have sex today.
  • Peak: LH surge. Ovulation is imminent. Sex today is pretty much required.

The sticks (which you have to purchase separately) look a lot like OPK sticks. But there’s no ‘control’ line – just one line for E2 and one for LH. And the color changes (particularly the E2 color change) are definitely more subtle than for OPKs – hence the need for the monitor to read the result.

I tried, unsuccessfully, to figure out the chemistry (or biochemistry) behind how CBFM works. I imagine that the LH line works using antibodies in a way similar to what I described in this post about how HPTs work, but I don’t know for sure. The mechanism for detecting E2 has to be somewhat different since (a) it’s not a protein hormone, and (b) the E2 line gets lighter as E2 levels increase, instead of darker.

Anyway, here’s a figure showing my monitor & corresponding test sticks for each possible fertility reading:

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Note the cute little egg symbol on the display for ‘peak’ fertility.

I color coded the hormone labels in the figure above to match this diagram I found on the interwebs showing how the menstrual hormones rise and fall at varying stages in a cycle. Note the gradual estradiol rise (blue), peaking a day or two before the LH surge (green):

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Incidentally, while doing a Google image search for LH and estradiol levels, I found the coffee mug above right, which I would want…except that I don’t think I’m gutsy enough to use it in public. They also sell a hat…