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!

Old procrastinating reneger

I have a confession to make. I’ve been procrastinating from writing a sequel to my post on Supplements. I’m long overdue on an entry about antioxidants (a category that includes most of the pills I’m taking).  I’ve been working on it off and on for a few weeks, but just can’t seem to find the motivation to finish it!

In place of that post (for now), here are a few odds and ends:

1)      I forgot to mention that Dr. Y gave me copies of all my medical records at my appointment on Monday. I had asked for these to send to CCRM in advance of my upcoming phone consultation. Of course, I couldn’t resist the temptation to read the records in detail. Most of it seemed run-of-the mill but I noticed two things that caught me off guard. The first was that I was listed as having a diagnosis of “secondary infertility”. I thought this term referred to people who already had one or more kids. Does one early miscarriage really mean I don’t qualify as “primary infertility”? The other surprise was that the embryology report listed me as having “Advanced Maternal Age”. I’m 34. I thought I had at least a few more months before graduating to the “Advanced Maternal Age” club. I did a Google search and learned that apparently the definition applies to women who are 35 or older at the time of childbirth. So apparently I do belong…assuming I ever get pregnant. I feel old! (No offense…)

2)      AF arrived today, making this a whopping 18-day cycle. (Has anybody else had such a short cycle after egg retrieval?) Anyway, that leads me to believe that my fertility monitor was actually working properly, and I didn’t ovulate this month. We’ll try natural IUI again next month…

3)      I planned poorly and just realized that I am going to be a bad ICLW-er this week. Tomorrow we’re leaving for a camping trip to Pinecrest in northern California. I just learned that they don’t have WiFi or reliable cell service, so I’m probably not going to be able to blog or comment until I get back next Wednesday. I’ve been trying to ‘bank’ lots of extra comments in the first half of the week, but I still feel like a schmuck for reneging on my commitment… Sorry!

Have a great week everybody!

Message to my fertile friends

Not too much has been happening here. We finally finished up the 10-week summer research session, and I am officially “off” for the rest of the summer. (By “off,” I mean I get to sit on my couch in my PJs working on my promotion portfolio and prepping for fall classes…) It’s nice.

As many of you know, our current plan, in the wake of failed IVF#1, is to spend three months trying to improve egg quality through supplements, while also doing natural cycle IUIs. I’ve been using my CBFM, and was supposed to call the office to schedule insemination as soon as the monitor indicated impending ovulation (by displaying a little egg). We also made a just-in-case appointment for cycle day 16, in the event that the egg never appeared in the monitor window.

Today was cycle day 16, so I went in for that just-in-case appointment. The dildo cam showed no lead follicle: either this is an anovulatory cycle, or we missed ovulation. (Once again, I find myself regretting getting lazy on the BBT charting; if I had kept up, I’d know for sure which it is.) But I’m actually not that disappointed. There’s a very slim chance that we could get pregnant this month, but if not, I’m fine trying again next month.

I’ve also been dutifully taking my long list of supplements. While I have definitely NOT been “living like a monk,” I have been trying to eat well whenever possible. I’ve cut back on coffee, Diet Coke and alcohol – to 2-3 servings of each per week…instead of 1-2 servings per day. (Shoot! Does that make me sound like a lush? I just like my nightly glass of wine!) Thanks to my sister’s persistence, I’ve also started running again. We’ve gone three times in the last week; it’s only been 2.5 to 3 miles each time, but a huge improvement over the absolutely nothing that I’ve been doing for the last year and a half…

*****

But the real reason for this post is that I got an email this week that was equal parts delightful and heartbreaking, and made me want to think carefully about how my words are received.

I hope A will forgive me for sharing parts of her email here:

Hi K,

I’ve been following your blog and seeing that things are not going as you might have wanted.  I’m sorry.  I also realize you sometimes feel ‘ill-will’ according to one of your previous posts about people who have some success.  Knowing that — I still need to tell you …

that we are 18 weeks pregnant and close to going ‘facebook public.’  I didn’t want you to find out on facebook. What you’re going through is emotionally and physically draining, but as you well know — I don’t really know… I don’t understand — regardless of how much I think I might or try.  It’s very personal and I’m really happy for you that you’ve found a support network of women through your blog who do understand.  It’s also wonderful to read about how your relationship with ‘C’ has strengthened and deepened through this difficult time.

…Anyway, I’m emailing you because I didn’t want you to be surprised on facebook and wanted to tell you that you do not need to respond.

I look forward to seeing you again (someday) and I am always thinking happy, reproductive, follicular, warm fuzzy thoughts in your direction.  🙂

Your friend,

A

This message was delightful, because I’m so happy for my friend, who had been trying for awhile for a second child, and suffered a sad loss shortly before ours. I was also deeply touched that she had given so much thought and time to writing such a compassionate message.

It was heartbreaking that such an amazing friend could possibly think I might feel the slightest bit of ill-will towards her or her baby.

So this message is intended for my fertile friends. (The sentiment is equally true for my ‘lucky’ infertile bloggy friends who are now expecting.)

When I shared my blog with you, I made a choice to let you in on my most personal, raw, and unfiltered thoughts. I didn’t do this by accident. It was a sign of just how much I love and trust you.

So, please believe me when I say that I do not, will not bear you or your children any ill-will.

  • If you decide to outdo the Duggars and have 30 kids,
  • If, in your genuine attempts to comfort me you say all the wrong things,
  • If you go on to have an absolutely perfect life full of glitter and unicorn farts with your gorgeous brood of children,*

I will NOT bear you any ill will.

Believe me. It’s the truth. (And if you know me well enough for me to have shared this blog with you, then you know that I’m a terrible liar!)

Now, you may wonder, to whom do I direct all my anti-fertility ill will? Most fall into one of the following groups:

  1. Anonymous pregnant women that I see everywhere. Yes, I know. It’s totally unfair. I have no idea what they’ve been through, or the kind of parents they’ll be. I’m sure if I meet them in the future, I’ll be happy for them then. But for now, I hate them.
  2. People I never liked in the first place. If they never bothered to make time for me or show the slightest interest in developing a friendship before they were pregnant, then I feel no obligation to wish them well in their baby-making efforts now.
  3. Bad parents. These include stupid and/or oversharing parents (STFU, Parents has all the examples you never wanted to know), neglectful-to-abusive parents (Tan Mom gets to be fertile? Seriously?), and truly evil ones (The rumor that World’s Worst Mom Casey Anthony is pregnant again may have been a hoax, but that doesn’t change the fact that she never deserved to be a mom in the first place!)

As you can see, there is no shortage of targets for my infertility bitterness and ill-will.

You, dear reader, are not one of them!

——————————————————————————————————

* References to glitter and unicorn farts are shamelessly stolen from the amazing Jenny at Stupid Stork.

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…

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…