A rousing game of ‘Guess Dr. Schoolcraft’s Answer’ [updated with results]

Thanks to all of you for your help compiling questions to ask Dr. Schoolcraft during our upcoming CCRM consultation. Per your suggestions, I added some questions and prioritized them to make sure we get to my most pressing questions first. Then, during my run this morning, I got a little cocky and found myself thinking that I probably can guess Dr. Schoolcraft’s answer to most of my questions. Next I thought, why not make it interesting?

So I’m putting my educated guesses in writing, here on the interweb for all to see. [Gulp!] If you have guesses of your own, please share them in the comments! After our phone consultation on Monday, I’ll update I updated this post with Dr. Schoolcraft’s answers – so don’t forget to check back and see how well (or poorly) we all did!

[Insert cheesy game show music]

Deep announcer voice, building: And now it’s time. Let’s play…

Audience shouting in unison: GUESS! DOCTOR! SCHOOLCRAFT’S! ANSWER!

[Applause]

* My answers are shown in black. Dr. Schoolcraft’s answers (as best I can remember them) are in blue.

1. What do you estimate our chances of success with my eggs to be?

Actually, I have no idea what his answer to this one will be, which is why I want to ask it first. My fear is that he “won’t be able to say without the information from my one-day-workup.” (The one-day workup is the full set of tests that CCRM conducts – in one day – for all new out-of-state patients. If he defers to the one-day-workup as an answer to each question, then I’m going to wonder why I went to all the trouble of sending my medical records and completing the detailed medical history. I’ll also be bummed to have spent $250 for what amounts to an elaborate advertisement…)

<<DING!>>

I won’t have enough information to say until we have your results from the one day workup. I can say that between the options of 1) doing IVF again with your eggs, 2) doing nothing, and 3) doing IVF with donor eggs, your best chance of success would be from IVF with donor eggs.

2. If you think it’s worth trying with our eggs, what new information would change your mind? At what point should we seriously consider donor eggs?

Aside from perhaps deferring to the one-day-workup, I imagine that he would recommend trying at least one cycle at CCRM with my own eggs before moving on to donor eggs. Seeing how I respond to a new protocol, after 3 months of supplements, would provide additional data to inform our next steps.

<<DING!>>

I would recommend trying IVF at least once with a conventional [i.e. high-stim] protocol. That would give you the greatest chance of recruiting the maximum possible number of eggs. And then we’d know how many eggs/embryos each subsequent cycle is likely to yield.  Your response to the stimulation, as well as the results of genetic testing on any embryos retrieved, will help us to know whether your problem is with egg quality [in which case egg donation might be a good option] or if there is another issue.

3. What do you think accounts for CCRM’s remarkable success rates?/What can CCRM do to improve my prognosis relative to my local clinic?

I’m guessing he’ll say some combination of the following three things: (a) world-class embryologists (In general, I’m told the embryology lab is the biggest factor in determining IVF success rates.); (b) genetic testing (A procedure called Comprehensive Chromosomal Screening or CCS – which permits selection of only embryos with the correct number of chromosomes – was developed at CCRM. Transfer of selected embryos dramatically increases success rates, as can be seen here.); and/or (c) experience (CCRM did 2464 ART cycles in 2011, about 5 times as many as my local clinic. Such a large number of cycles per year means that the embryologists are constantly honing their skills, while the doctors have more data to draw from in choosing appropriate protocols, etc.)

<<DING!>>

The lab. The embryology lab makes the biggest difference for IVF outcomes, and we have the best lab. This is especially true in your case, where you can only afford a low margin of error. For example, if you had 17 eggs retrieved, and six make it to blast, and you get pregnant, it looks like a success, even though more than half of the eggs didn’t make it. But you’re not going to have that many; you may only have one or two eggs. You want the best embryology lab to maximize the odds that those eggs make it to blast. At CCRM, we’ve also developed several specific techniques that improve outcomes, like embryo glue [and others that I didn’t hear because C was whispering that my typing was too loud…]

4. What other kinds of tests will CCRM do? Do you recommend genetic testing in our case?

I’m not sure what all the tests they do are, but I’m pretty confident that it is more than I’ve had so far (namely Day 3 FSH, AMH, and E2 testing; antral follicle count; HSG; and saline sonogram). I’m guessing that he will recommend CCS (since I turn 35 in November), but probably not PGD/PGS (since C and I are different races and have no family history of genetic disorders).

<<DING!>>

I would definitely recommend that you do chromosomal screening [CCS]. If the cycle doesn’t work, you want to know whether it’s because of a genetic issue [which would be resolved by using a donor] or if there is some other factor – a lining issue, etc. [which would not be]. The goal is to “get a baby or get an answer.”

5. How would we go about scheduling a cycle with CCRM, given my & C’s work schedules? (I can’t exactly take off for 10 consecutive days in the middle of the semester!)

I’m not sure what he’ll say about this. Assuming he recommends a fresh cycle, I’m guessing that he’ll say I should schedule retrieval & transfer between semesters (in December/January). Alternatively, if he recommends a freeze-all cycle (as would be the case if we do CCS), maybe it wouldn’t require so much time off and I might be able to time something around Fall Break?

<<DING!>>

C would only need to be here for one day, and assuming you did most of your monitoring appointments at home, you would only need to be here for 4-5 days [since I recommend freezing all for CCS]. One possibility is that we might time it so you could come over Thanksgiving break.

6. If, due to scheduling constraints, we opt to do another cycle locally before cycling with CCRM, do you have any recommendations for our local cycle? (With regard to stims? freeze day? other?)

No idea what he’ll say to this… I’m guessing he’ll push for going straight to CCRM, but I’d love to be surprised here.

<<<BUZZ!!!>>>

Not really. Our lab is here. There’s no way to take it with you.

7. How much variability do you expect from cycle to cycle? In other words, is it worth trying a particular protocol again if the first cycle yielded nothing?

I think he’ll say that there can be variability from cycle to cycle even with the same protocol, although I’m guessing that he will also suggest a protocol change…

<<<BUZZ!!!>>>

The outcome is not likely to change much if you use the same protocol. But I would recommend changing the protocol.

8. Do you recommend trying low stim (like last time) vs. high stim? What do you think about ‘natural cycle IVF’?

Based on what I’ve heard from other CCRM patients, I think he’ll say, “There are no scientific studies to suggest that high levels of stimulation drugs damage eggs, nor any that show better outcomes for low-stim or natural cycle IVF (whether for DOR sufferers or others).” He might also add that IVF is a numbers game, and that the goal is to get as many mature eggs as we can, and that high doses of stims are our best bet to get them.

<<DING!>>

Natural cycle IVF is “a total waste of time.” You’re not taking anything to prevent ovulation, and there’s a 40% chance of ovulating prematurely. With mini-IVF [low-stim], you’ve basically decided, “I’m gonna be happy with 2 or 3 eggs.” I suggest that you give this “one really good try” [meaning with high-stims]. If you try the “Bazooka” protocol and only get 2 or 3 eggs anyway, then you’ll know that mini-IVF is just as good in your case…plus it’s a lot cheaper.

9. What particular stims would you recommend in my case? What sort of suppression drugs would you use? (Ganirelix? microdose Lupron (agonist)? Other?)

I have no idea what he’ll say. Since my cycle with Clomid/Menopur + Ganirelix yielded just three eggs and no embryos, I might expect that he would suggest trying something different, but who knows.

<<<BUZZ!!!>>>

Your particular protocol will be determined using the results of your one-day-workup.

10. Should I be avoiding alcohol? Caffeine? Exercise? For three months prior to cycling? During my cycle? During stims?

I’m guessing – okay, I’m hoping – that he’ll say something along the lines of, “As long as you’re practicing moderation (defined as 1 alcoholic beverage, 1 cup of coffee, and 1 hour of exercise per day), and assuming that you’re at a healthy weight, there’s no reason to believe that these things would hurt fertility. However, to be safe, we recommend abstaining from all three during your IVF cycle, starting at Day 1 of stims.”

<<DING! DING! Hallelujah! DINGGG!!!>>

Moderate consumption of caffeine and alcohol (up to 1 cup per day of a caffeinated beverage, and up to 3 glasses per week of wine) shouldn’t be a problem. [I volunteered that I would stop when we start stims, so he didn’t say anything about that.]

11. Is limited exposure to organic solvents (in the context of teaching lab courses) a problem?

Again, here’s what I desperately hope he will say: “In the spectrum of organic solvent exposure, working as a lab chemist or chemistry teacher (where you are educated about safety and working in rooms designed with appropriate ventilation and fume hoods) is actually quite safe. Workers at hair and nail salons, dry cleaners, janitors, exterminators, and (non-organic) farmers all have much more dangerous levels of chemical exposure, yet no link has been discovered between these professions and infertility.” I don’t actually think he’ll say this, but I’m confident that it’s true, and it would be so nice to hear (and have C hear) it coming from a world-renowned infertility expert… Sigh!

<<DING!>>

I don’t think that your exposure to chemicals caused your diminished ovarian reserve. [Boo ya!] It’s mainly a concern when we get to the point of embryo transfer. At that point, you will want to avoid chemical exposure, as you would when you’re pregnant.

12. Am I taking the right set & doses of supplements?

I think he’ll say ‘yes’, since my list is essentially the same as the CCRM-recommended list. (The exceptions are that I’m taking a higher dose of CoQ10, along with aspirin, and a high antioxidant drink powder called Nanogreens.)

<<DING!>>

Probably. When you schedule your one-day workup, we’ll give you our list of recommended supplements.

13. Should I be taking PQQ (recommended by my acupuncturist) to promote mitochondria generation?

I’m guessing he’ll say something along the lines of, “There is no evidence to suggest that PQQ improves pregnancy outcomes for patients undergoing IVF.”

<<DING!>>

There are no human studies on PQQ.

14. In your experience, does taking the aforementioned supplements actually make a difference? In AMH and/or FSH levels? In number of eggs retrieved? In embryos that make it to blast? In ultimate pregnancy outcomes?

I’m not sure what he’ll say. I haven’t found any good scientific studies that say these supplements help, but the fact that CCRM recommends them suggests that they at least believe it may help. Dr. Schoolcraft has seen enough patients that he may have an opinion about what the supplements do, even if he hasn’t gotten around to conducting and publishing a study to that effect.

<<DING!>>

Nobody knows. There isn’t good data to support it, but it probably won’t hurt. The groups of common supplements including the antioxidants (of which you have many choices, including pycnogenol, vitamin C, vitamin, E, melatonin, etc.) These decrease reactive oxygen species, which are thought to cause a deterioration in egg quality. Another supplement is CoQ10, which is thought to affect mitochondrial function. However, this has not been shown in human studies, only in a mouse study. Based on the results of the mouse study, the corresponding effective dose in humans would be 600 mg/day.

In the case of DHEA, there is retrospective data, but no good prospective data. There is good prospective data showing that testosterone priming (for at least 21 days) improves outcomes, so we will likely put you on testosterone for 21 days prior to starting stims. Based on the results with testosterone, it looks like androgens are good; it may be that DHEA is just too weak an androgen to show the same result…

15. What do you think about estrogen- and/or testosterone-priming?

Again, no idea.

<<<BUZZ!!!>>>

[See answer to #14, above.]

16. Assuming we were able to get any embryos, would you go for a fresh vs. frozen transfer?

I’m guessing that he’ll suggest we do CCS (see #s 3 and 4, above). In that case, they have to freeze the embryos while performing the testing.

<<DING!>>

I recommend doing CCS, which requires that you freeze all embryos for testing.

17. Do you recommend trying to do multiple retrievals to try and ‘bank’ embryos? How many embryos is ‘enough’?

Given my poor response on my first cycle, I think he will recommend banking embryos. Also, since the cost for CCS is ‘per test’ rather than ‘per embryo’, the most economical option is to bank a bunch of embryos and then test them all at once. The question of ‘how many is enough’ is tough to know up front. If all my embryos test normal, then I may not need that many. On the other hand, odds are good that half or more might not be. The limiting factors for determining ‘how many embryos are enough’ will probably be time and money…

<<<BUZZ!!!>>>

It depends how your first cycle goes. If you only get 1 or 2 embryos, I would probably suggest banking them to have more for CCS; if you get more, it may be worth testing them immediately.

18. What causes DOR? In other words, what could I have done differently (besides have babies in my twenties…)? Could my career choice (organic chemistry) have contributed?

I think he’ll say that he has no idea. It may be a combination of genetic and/or environmental factors, but the only environmental factor that is known to cause a decrease in egg quantity and quality is smoking (which I don’t). On the topic of chemistry and DOR, see my wishful answer to #11.

[I didn’t technically ask this question, but see his answer to #11…]

19. What would be the cost per cycle with CCRM?

I don’t need to ask this one anymore, as I found the answer here.

————————————————————————————————————-

Deep announcer voice: Well done, knalani! You correctly guessed 12 answers out of 17! Bambi, show her what her prize is…

Sultry assistant voice: It’s…a no-expense-paid trip to the lovely city of Denver!

Audience: Ooh! Aah!

Deep announcer voice: Thank you for playing, and we’ll see you next time on…

Audience shouting in unison: GUESS! DOCTOR! SCHOOLCRAFT’S! ANSWER!

[Cheesy game show music]

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I need your help!

My phone consultation with CCRM is fast approaching. Faster, since I got a call from Dr. Schoolcraft’s assistant last week, asking to move up my appointment from September 16 to August 26. It may even happen sooner, as I added my name to the cancellation list. (I got one call last Friday asking me if I would do the consultation ‘right now’. I declined, since I want to have C on the phone with me!)

I also recently learned that I need to be thorough about preparing my questions prior to the phone consultation. A friend from my Resolve support group is a patient of Dr. Schoolcraft’s, and she said that he basically calls and says, “So, what questions do you have for me?” She said if I’m not ready to drive the conversation, it could be a very short one… Not exactly what I’m looking to pay $250 for!

So I’m asking for your help in compiling questions for Dr. Schoolcraft. Here’s what I have so far:

Regarding the protocol:

* Do you recommend trying low stim (like last time) vs. high stim?

*Would you use Ganirelix (antagonist) vs. microdose Lupron (agonist)? Or another drug?

*What do you think about estrogen- and/or testosterone-priming?

*Assuming we were able to get any embryos, would you go for a fresh vs. frozen transfer?

Regarding my lifestyle:

*Am I taking the right set & doses of supplements?

* Should I be taking PQQ (recommended by my acupuncturist) to promote mitochondria generation?

*Should I be avoiding alcohol? Caffeine? Exercise? For three months prior to cycling? During my cycle? During stims?

* Is limited exposure to organic solvents (in the context of teaching lab courses) a problem?

Regarding our prognosis:

* In your experience, does taking the aforementioned supplements actually make a difference? In AMH and/or FSH levels? In number of eggs retrieved? In embryos that make it to blast? In ultimate pregnancy outcomes?

*How much variability do you expect from cycle to cycle? In other words, is it worth trying a particular protocol again if the first cycle yielded nothing?

* Do you recommend trying to do multiple retrievals to try and ‘bank’ embryos? How many embryos is ‘enough’?

* What do you estimate our chances of success with my eggs to be?

* If you think it’s worth trying with our eggs, what new information would change your mind? At what point should we seriously consider donor eggs?

Regarding CCRM:

*What do you think accounts for CCRM’s remarkable success rates?

*What can CCRM do to improve my prognosis relative to my local clinic?

*How would we go about scheduling a cycle with CCRM, given my & C’s work schedules? (I can’t exactly take off for 10 consecutive days in the middle of the semester!)

*What would be the cost per cycle with CCRM?

*If, due to scheduling constraints, we opt to do another cycle locally before cycling with CCRM, do you have any recommendations for our local cycle? (With regard to stims? freeze day? other?)

Out of curiosity:

* What causes DOR? In other words, what could I have done differently (besides have babies in my twenties…)? Could my career choice (organic chemistry) have contributed?

 

And…what else?

Hit me with your awesome questions!

Infertility math*

This post was primarily inspired by a recent, lovely post by Jane at Mine to Command who confronted the myth that stress causes infertility. She delves into the medical literature on the subject, so I won’t provide my own (undoubtedly less eloquent) rehashing of what she’s said there. Go read it! Then come back, if you like.

The myth that stress causes infertility is a pervasive one. And, its logical consequence – namely, that infertiles should “Just relax, and you’ll get pregnant – has lead to a laundry list of charming little chestnuts of advice including:

  • Just adopt, and you’ll get pregnant.
  • Go on vacation, and you’ll get pregnant.
  • Get drunk, and you’ll get pregnant.
  • Don’t try so hard, and you’ll get pregnant.

and so on…

This myth originated – and continues to be fueled – by the observation that indeed many infertile couples get pregnant when they stop trying.

Although I’m not a medical practitioner and haven’t consulted the scientific literature on this particular topic, my intuition (aided by some basic mathematical understanding) tells me that this observation is probably true: many infertiles do get pregnant when they “aren’t actively trying”.

Before you chase after me with torches and pitchforks, please let me explain…

While I do think that the probability of getting pregnant while not “trying” is significant (in some cases rivaling the probability of getting pregnant through medical intervention), the often-touted “logical consequence” of this observation – that infertiles should stop trying to get pregnant…in order to get pregnant – is complete and total hooey!

I’m a chemist, but I nearly minored in math. I’m particularly grateful that I took statistics (both math stats and biostatistics), which comes in quite handy in situations like this…

So, why do so many couples get pregnant when they aren’t actively trying?

As Jane pointed out, this is kind of a silly question. Anybody who is having sex without birth control is, on some level, trying to get pregnant. So immaculate conception and birth control failures aside, everyone who gets pregnant is technically trying. But any infertile knows that there’s a wide spectrum of “trying”, all the way from “pulling the goalie” (aka unprotected intercourse) to spending tens-of-thousands of dollars for the privilege of being poked with needles, pumped full of hormones, subjected to minor and/or major surgery, and violated on a regular basis by an ultrasound wand, among other things…

Statistics provided by reproductive endocrinologists – the infertility experts – tell us that our odds of conceiving are significantly increased by all these interventions. Consider the following per-cycle odds of conception for several common interventions:

Intervention Per-cycle odds of conceiving** Source
timed intercourse 5% Health.com
natural cycle IUI 5-10% Babycenter.com
medicated IUI Up to 20% Babycenter.com
IVF 46% SART

I couldn’t find any odds for “not trying”, but I think it’s safe to say that they would be less than 5% per cycle.

So, how on earth is it possible that so many infertile couples get pregnant after they’ve stopped trying, even though their odds are so much less – more than 9 times less compared to IVF?

The key words here are per cycle. The odds, per cycle, of success from IVF are nine times that for timed intercourse (and >9 times that for ‘not trying’). But how many cycles of IVF do people actually do? Looking around the blogosphere, I can find lots of examples of people who have done IVF two, three, four times. But at over $10K a pop, few people have the financial means (or an IVF clinic willing to risk hurting its SART stats) to do many more cycles than that.

On the other hand, an infertile couple might have 5-, 10-, 20-years of “not trying” to get pregnant. For a woman who ovulates regularly every 28-days, that corresponds to as many as 65, 130, or 260 cycles of not actively trying to get pregnant.

So, how do we do the math to figure out the odds of getting pregnant by “not trying” versus using a technology such as IVF?

Let’s take an example of a couple that tried IVF three times unsuccessfully, adopted a child, then had unprotected sex for ten years:

First, let’s calculate their odds of a pregnancy resulting from three rounds of IVF. (In statistics, it’s actually slightly easier to calculate the odds of something not happening, and then to convert that to the odds of that thing happening…)

  • According to SART, the average odds of a pregnancy resulting from one cycle of IVF for a woman under 35 are 46%. We can express this value as the decimal 0.46.
  • That means the odds of not getting pregnant from one IVF cycle are 100-46 = 54% or 0.54.
  • The odds of not getting pregnant after two rounds of IVF are 0.54 x 0.54 = 0.29 or 29%.
  • The odds of not getting pregnant after three rounds of IVF are 0.54 x 0.54 x 0.54 (or 0.54 to the third power, 0.54^3), which equals 0.16 or 16%.
  • Now, to get the probability of a pregnancy resulting from three IVF cycles, we just subtract from 100% the probability of not getting pregnant: 100-16 = 84%. (Not bad odds! It seems our hypothetical couple – like many of us – was on the unlucky side of these stats…)

Now let’s calculate the odds of getting pregnant from ten years of unprotected sex.

  • For the sake of argument, I’m going to estimate that the couple’s per-cycle odds of pregnancy are a mere 1% (0.01). (Given that the per cycle odds for infertile couples practicing timed intercourse is estimated at 5%, I think 1% odds for “not trying” is actually pretty conservative…as long as the couple is having sex…) If the odds of a pregnancy are 1%, that means the odds of not getting pregnant are 99% or 0.99 per cycle.
  • The odds of not being pregnant after two cycles are 0.99 x 0.99 = 0.98, or 98%.
  • The odds of not being pregnant after three cycles are 0.99^3 = 0.97. In other words, there is only a 3% chance of a pregnancy resulting from three cycles of “not trying” – not even close to the 84% odds from three cycles of IVF.

Like interest on a long-held bank account, things start to get interesting as these paltry odds compound over large numbers of cycles…

  • The odds of not being pregnant after 13 cycles (one year) are 0.99 to the thirteenth power (0.99^13) or 88%. That means the odds of a pregnancy resulting from those 13 cycles is 12% (100 – 88 = 12). In other words, more than one tenth of “infertile” couples will be pregnant after a year of “not trying”. (Thereby supplying ample anecdotal “evidence” for annoying fertiles to misinterpret and hold up to their infertile friends…)
  • The odds of not being pregnant after 130 cycles (0.99^130) are 0.27, or 27%.

In other words, after ten years of “not trying”, this “infertile” couple had a 73% chance of achieving at least one pregnancy. (And remember, that pregnancy could occur randomly at any time during the ten years of not trying…)

How do you suppose most people interpret this series of events?

The facts: a couple failed to get pregnant from three rounds of IVF, adopted a child, and then got pregnant after a few years of not actively trying to get pregnant.

I can think of a couple of likely interpretations:

“After becoming parents through adoption, they were finally able to “just relax” and get pregnant!”

“In adopting, they were able to resolve the karmic imbalance that had previously interfered with their attempts at pregnancy!”

Nonsense! The real reason is far less romantic:

Over the course of many years of regular unprotected sex (albeit without officially “trying”), chances are that at least once, healthy sperm would meet with healthy egg at the right time to fertilize, and travel through the fallopian tube to find a uterus in just the right condition for implantation.

As Jane would say, “it was just their time.”

For women with diminished ovarian reserve (like me) the odds of conceiving by IVF are far below the 46% average I used in the example above (see this post for the depressing stats). Yet it’s not known how significantly DOR affects our chances of success through natural conception (which only requires one good egg each month…) In such cases, it’s easy for me to believe that the odds of conceiving from 100+ cycles of “not trying” could exceed the odds of conceiving from a handful of IVF cycles!

Am I saying we should all “just relax” and abandon assisted reproductive technologies?

No way! I can think of several good reasons to take a more aggressive approach:

  1. I don’t want to wait ten years to have a decent chance at a pregnancy! (Since I didn’t start until 33, I don’t even have 10 years of trying left in my old lady ovaries anyway…) I want my child yesterday! I want to change her diapers, not ask her to change mine. ART gives me the best odds of a child soon!
  2. Unlike in my simplified example, our odds of success are not static. My odds of pregnancy with my eggs – whether via ART or natural conception – are decreasing every month. With that fact hanging over me, it’s hard to justify waiting around for years for a natural conception. I can always try (or “not try”) for a natural conception after trying other family-building options (IVF, adoption, etc.) But ten years from now, if natural conception doesn’t work, I can’t go backwards and do IVF (at least not with my own eggs, which will have long dried up by then…)
  3. It’s not an either/or situation. If the odds of a pregnancy in my hypothetical example were 84% for three rounds of IVF, or 73% for 130 cycles of “not trying”, the total probability of a pregnancy – given that this hypothetical couple used both methods – was an almost unbelievable 96%! (1 – 0.16 x 0.27 = 0.96). Carefully timing intercourse instead of “not trying” should increase the odds further. Trying a combination of aggressive treatment (using ART) and regular unprotected intercourse will give me the very best odds of a biological child.
  4. There’s comfort in knowing that I’ve “tried everything”. If things don’t work out, and I end up on the unlucky end of all these statistics, at least I won’t wonder whether I might have been a genetic parent, “if only I’d tried X…” I’d rather go ‘all in’ now, and then move on to the next family-building option (or child-free living) without regrets.

As you’ve probably figured out by now, my plan is to continue with high-tech treatment…and to break out the Marvin Gaye around ovulation time every month in between!

It’s a plan that will mean a lot of two-week waits,…

a lot of peeing on sticks,…

and charting temps,…

and reading signs…

You’ll understand if I get tired of all the effort and decide to “take a break” and skip the meticulous timing for a few months…

And if, by chance, I happen to get pregnant that cycle,…

For heaven’s sake, DON’T use me as an example of how you “know this girl who got pregnant as soon as she stopped trying!”

———————————————————————————————————————-

*I can’t write about Infertility Math without acknowledging this brilliant post by Aramis at It Only Takes One.

**Odds shown are for infertile couples (that is, couples who have been trying unsuccessfully for at least a year) in which the woman is less than 35 years old. Other factors can dramatically change these odds. For example, when fertile couples are included, the per-cycle odds are much higher – as high as 25% per cycle for timed intercourse. For older women, the per-cycle odds are lower in each case. Also, note that these stats show approximate pregnancy rates. The live birth rates are (sadly) lower due to miscarriage…

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’…)

Image

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!

*****

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.

Image

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…

Craptastic diagnosis

Sorry it took me a couple days to write this post. My baby sister is visiting for the summer (yay!), and this weekend her boyfriend came to visit. It was my first time meeting him, so I was pretty busy showing them around town.

Anyway, we had the WTF appointment with Dr. Y on Friday morning. (Thanks to my bloggy friends for this term, which seems like a perfect description for the appointment after a failed cycle…) It was not a cheerful conversation. It basically cemented my assessment that diminished ovarian reserve is a craptastic diagnosis. Some highlights:

  • Dr. Y was careful to point out that I am “not through menopause yet”, and therefore there is always a probability (however miniscule) that I could get pregnant naturally. So one option is to stick with timed intercourse + prayer. (In support of this option, he mentioned a patient like me who got pregnant naturally after quitting treatment…then miscarried. Not exactly a ringing endorsement…)
  • On the other end of the spectrum, Dr. Y pointed out that none of the tests to date has shown any problems with my uterus, so we expect a high probability of success from IVF with donor eggs. In that case, I would have to change care providers, because Kaiser doesn’t do third-party reproduction…
  • He was open to the idea of us doing IVF one more time with my eggs, but wanted to be very clear that he doesn’t expect a dramatic difference in outcome – we would be hoping for one quality embryo, not five. And we would want to go into it with a plan for what we would do in the (likely) event that it fails again. He does not support the idea of doing IVF bunches more times, as he said there would be a point of diminishing returns, and he doesn’t want to subject my body to all those drugs over and over if it’s not likely to yield the end result that we want.
  • Dr. Y did not recommend trying a different protocol. He is convinced that the antagonist protocol (with ganirelix/Antagon) is the best option for me. In particular, I had asked about a microflare Lupron protocol, but he felt that the ganirelix “worked” in the sense that it prevented premature ovulation, and that – as a rule – it suppresses my ovaries the least, making it the best choice for a poor responder like me.
  • Dr. Y was supportive of trying what he called “soft science” approaches to improving egg quality – including eating a high antioxidant diet, taking all the recommended supplements, and doing acupuncture – prior to trying IVF#2. He doesn’t necessarily think it will help, but he thinks it can’t hurt. He suggested doing it “all the way”, not half-heartedly, for 3 months, “living like a monk”. I think his rationale was that if I did absolutely everything I could think of, then I would be at peace with moving on with donor eggs (or adoption, or child-free living) if IVF#2 fails. (He did, however, mention that he had a DOR patient like me, who had a failed cycle, then did all the supplements, etc. for 3 months, got one embryo from IVF #2, which implanted and she is now in her 3rd trimester…)
  • We also learned that the embryologist had judged my three eggs as being of “very poor quality”. I think this is another reason for Dr. Y’s pessimism.

Here are some stats from the SART database to help illustrate why DOR is such a crappy diagnosis. For women up to the age of 40, a DOR diagnosis correlates with the worst odds of success from IVF:

SART Fresh IVF cycles Percentage of cycles resulting in live births

<35

35-37

38-40

41-42

>42

all diagnoses

40.1

31.9

21.6

12.2

4.2

ovulatory dysfunction

43.3

36.9

28.3

14.1

3.2

male factor

43.2

36.7

25.6

16.6

5.2

unknown

42.5

33.4

24.7

14.1

7.1

female & male factor

39.5

30.7

20.4

11

5.1

tubal factor

39.2

31.5

20.7

14.6

3.8

endometriosis

38.9

29.6

24.6

13.2

4.7

other

36.5

30.8

21.9

13.2

4.7

multiple female factors

35.2

27.2

18.9

10.4

2.6

uterine factor

33.6

33.8

19.3

15.4

5.9

DOR

27.5

24.2

17.8

11.1

3.8

On the upside, if we ever happen to get any decent frozen embryos, the stats shift in our favor, at least given my relatively young age:

SART FET cycles Percentage of transfers resulting in live births

<35

35-37

38-40

41-42

>42

all diagnoses

39.3

35.7

30.3

24.5

16.5

ovulatory dysfunction

42.1

38.4

34.5

19.4

33.3

DOR

40.8

32.6

25.9

23.3

13.1

unknown

40.8

37.3

33.1

28.7

21.3

male factor

39.9

35.6

29.3

28.1

16.7

other

39.5

37.3

34.1

31.8

16

female & male factor

38.6

35.7

29.3

21.7

17

endometriosis

37.7

33.6

32.7

28.9

3 of 12

tubal factor

37.2

35.4

24.8

12.5

28.3

mutliple female factors

35.3

33.3

31.2

26.3

18.6

uterine factor

31.8

32

31.5

17.9

17.4

Now, we both still really like Dr. Y, but I am somewhat concerned about blindly repeating IVF with someone who (I think) doesn’t believe it will work. So on Friday afternoon, I called the Colorado Center for Reproductive Medicine (CCRM) and scheduled a phone consultation with Dr. Schoolcraft. The earliest phone consultation he had available was September 16, but I figure that’s fine, since I need to take supplements for at least 3 months before trying IVF again. I can see what Dr. Schoolcraft says, and then decide whether to try again here one more time…or try at CCRM.

Why CCRM?

I have a good friend, N, who did IVF at CCRM, which is how I knew about it. (She didn’t have DOR, but had three failed cycles at her local clinic, prior to the successful one at CCRM.) I also read (and liked) Dr. Schoolcraft’s book. While my local IVF clinic is very good (maybe the best in California), CCRM is on another level. They perform 4.5 times as many IVF cycles each year as my local clinic. And their stats (as compiled by SART) are pretty amazing…even if you sort them by the diagnosis of DOR. Most importantly, my friend N is certain that Dr. Schoolcraft will be straight with me and tell me whether he thinks it’s worth continuing with treatment, or if I should give up and move on. (The skeptic in me thinks that this bluntness may explain the almost unbelievably high SART stats, as they probably don’t take cases with too low a probability of success…Still, I think it would be worth knowing whether my case is one they would take.)

What about CRMI?

The Center for Reproductive Medicine and Infertility (CRMI) at Cornell Weill Medical College is another place I am thinking about. Their stats aren’t as good (even sorted for DOR) as CCRM…and traveling to New York City would be notably less convenient than traveling to Colorado, (more time zone changes and no family nearby), but from what I can tell, it is the place for treating women with DOR. In 2011, they performed 3379 cycles (that’s more than 6 times as many as my local clinic), of which 776 were diagnosed with DOR. (By comparison, out of 2464 total cycles at CCRM, only 98 were DOR; and out of 545 total cycles at my local clinic, 85 were DOR.) So I also filled out an online form to be contacted by CRMI. If I’m feeling extravagant, I might even pay for phone consults at both clinics, just to see what they each say.

For your viewing pleasure, here’s a comparison of the fresh IVF stats for my clinic vs. CCRM vs. Cornell. You can see why CCRM is so popular:

My clinic Fresh IVF cycles Percentage of cycles resulting in live births

<35

35-37

38-40

41-42

>42

all diagnoses

54.2%

43.4%

39.0%

10.0%

4 of 15

DOR

2 of 10

19.0%

6 of 19

10.7%

2 of 7

CCRM Fresh IVF cycles Percentage of cycles resulting in live births

<35

35-37

38-40

41-42

>42

all diagnoses

65.0%

45.5%

35.3%

32.4%

20.6%

DOR

8 of 17

52.4%

28%

5 of 14

4.8%

Cornell Fresh IVF cycles Percentage of cycles resulting in live births

<35

35-37

38-40

41-42

>42

all diagnoses

38.1%

29.2%

25.1%

14.3%

4.6%

DOR

14.6%

25.9%

25.0%

14.0%

5.3%

And a comparison of frozen transfers:

My clinic FET cycles Percentage of transfers resulting in live births

<35

35-37

38-40

41-42

>42

all diagnoses

50%

41.20%

29.20%

0 of 3

0 of 1

DOR

1 of 1

1 of 2

1 of 2

0 of 0

0 of 1

CCRM FET cycles Percentage of transfers resulting in live births

<35

35-37

38-40

41-42

>42

all diagnoses

67.90%

65.80%

58.90%

56.70%

33.30%

DOR

8 of 8

8 of 17

48.60%

51.70%

3 of 15

Cornell FET cycles Percentage of transfers resulting in live births

<35

35-37

38-40

41-42

>42

all diagnoses

38.30%

42.90%

34.80%

11.10%

1 of 15

DOR

2 of 5

5 of 8

5 of 11

2 of 11

1 of 8

As you can see, DOR women don’t often have an frozen embryos to transfer, hence the small numbers here.

As you can probably tell, I’m not feeling super optimistic about having my own genetic offspring at this point. I welcome any encouraging DOR stories, 2nd IVF stories, CCRM or CRMI stories, supplements improving egg quality stories, etc.

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.

*****

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!) 

*****

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.

*****

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:

Image

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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