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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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…

This and that

AF arrived yesterday, so I went to see Dr. Y for a baseline ultrasound this morning. While we are waiting for my supplements to take effect, we figured it couldn’t hurt to do a few cycles of natural IUI. (As C puts it, “so we can feel like we’re doing something…”) Originally, Dr. Y had suggested taking Clomid during the IUI cycles, but I had second thoughts about pumping my body with drugs when I’m supposedly trying to use acupuncture, supplements and diet to achieve a monastic zen-like state that will maximize the quality of my remaining eggs (or something like that…) Dr. Y quickly jumped on board with the plan, especially since he spotted a large ovarian cyst on ultrasound. The cyst would have precluded using any drugs anyway, so natural cycle it is!

The plan is for me to use an over-the-counter ovulation predictor kit (I’ll probably just stick with my CBFM) to detect my natural LH surge, and then to call the office to schedule insemination (aka turkey baster) the next day. The way I figure it, each month we get a chance (however small) that this egg might be ‘the good one’. If this month’s is the good egg, delivering C’s little swimmers directly to my uterus might slightly increase the chance that it gets fertilized.

Plus, summer research is almost over, so I’ve got time to kill. And Kaiser covers it. So, why not?

*****

I went to my second Resolve meeting last week. It was awesome. I got a lot of support in my decision to schedule a phone consultation at CCRM. More importantly, I also got a healthy dose of “it could be worse.”

Not that anybody would have said anything so insensitive, but hearing stories from my sisters in infertility helped remind me that, crappy as DOR is, it is not the worst diagnosis possible. The fact remains that C & I still have one very good option – IVF with donor eggs. Yes, it would mean giving up on genetic offspring (those adorable little hapa babies with my nose and C’s hand-eye coordination…) But it would bring our odds of success with IVF up to 70% or more per cycle. It would also ‘stop the clock’ on our fertility issues, meaning that we could have as many kids as we want, and time them as far apart as we want (well, almost… I think legit clinics refuse to transfer once I turn 50…) And our risk for age-related chromosomal issues would drop to whatever they are for our twenty-something donor.

Oh, and while I’m counting my blessings, I should probably mention that we are in the fortunate position of being able to afford egg donation as an option. (The same might not be said for a gestational carrier, which runs around $100K per try. So, we’re thankful that my uterus seems to be in good shape!)

Don’t get me wrong, I’m not giving up on my eggs just yet, but it’s nice to know that we have a good option tucked away in the sock drawer, waiting for us to pull it out whenever we’re ready. It’s also nice to know that there will be a great group of gals (and guys) down in the trenches with us who will support us, whichever path we choose.

*****

Last but not least, I got the sweetest gift from our fertile friends, S & Q. (These are the same ‘thoughtful ninjas’ who dropped off gorgeous flowers the night before a doctors visit, and a delicious care package of tasty treats on retrieval day.) Last week, the ninjas struck again, this time leaving this St. Gerard keychain:

Image

(It was timely, as I got it a few hours after reading this post by Risa at Who Shot Down My Stork? about the St. Gerard medal she got from a friend.)

As many of you know, I’m a practicing Roman Catholic (which I wrote about here), and St. Gerard is the Patron Saint of Motherhood. The Church uses a rather broad definition of motherhood here, including expectant mothers and mother-wannabes like me; as a result, couples trying to conceive will often pray to St. Gerard. (Another option is St. Gianna Beretta Molla, Patron Saint of Mothers, Unborn Children, and Physicians.) For any of you who are Catholic (or just willing to try anything at this point), here’s a common Prayer to St. Gerard:

O good St. Gerard, powerful intercessor before God

and Wonder-worker of our day,

I call on you and seek your help.

You who on earth did always fulfill God’s design,

help me to do the Holy Will of God.

Beseech the Master of Life,

from whom all paternity proceeded,

to make me fruitful in offspring,

that I may raise up children to God in this life

and heirs to the Kingdom of His glory

in the world to come. Amen.

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!

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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…