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.

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…

Family reunion

Sorry for being a bad bloggy friend this last week. I just got back from my family reunion in Colorado. My dad’s side of the family has a reunion in the mountains of Colorado every 3 years. This year, 65 of us – all direct descendants of my 90-year-old grandmother – made it to the YMCA of the Rockies in Estes Park.

This was my first post-infertility reunion. And it was hard. Our crew of 65 included 22 kids. And not just any kids, but freakin’ adorable, sweet, funny kids. The kind of kids that I want to have. The weekend also included a large amount of marveling at genetic parenthood – how virtually everybody there owed their life (or their spouse’s life) to this one woman – my grandma. Now don’t get me wrong, my grandma is awesome! But it still stings to think that I likely won’t have any genetic children…or grandchildren…or great grandchildren…

But enough of this pity party. There was a lot to be thankful for. For one thing, not one single person asked when we would have kids, or why we didn’t have any yet.

(I suspect this has something to do with a little incident last summer… After getting my positive pregnancy test, I texted my parents a photo…which my dad immediately posted on Facebook! I called him and made him take it down right away, but several relatives had already seen – and ‘liked’ or commented on – it. Seeing as there is now no baby, I can only assume they figured out what happened and had the decency not to comment on it. Either that, or everybody thinks I’m still in my twenties and have plenty of time – neither of which is true, but who can keep track when there are so damn many of us?!)

Another plus of the weekend: my adorable husband. A few weeks ago, I casually mentioned that wheatgrass juice is allegedly supposed to help with egg quality. The next week, I got home from church to find this in my kitchen:

Image

A couple weeks later, C decided that blending and straining the wheatgrass wasn’t good enough, and ordered a mechanical wheatgrass juicer.

This sweet man couldn’t imagine me going for almost a week without any wheatgrass, so he packed the juicer and a bag of wheatgrass in a little cooler, brought it along, and made me wheatgrass juice each day that we were there, cleaning the juicer in our room sink after each serving. 😉

Image

He also offered to “live like a monk” with me, giving up alcohol and unhealthy food for the next three months. (Okay, so part of the reason is that he wants to lose weight, but I still found it adorable.)

And on our last night there, after an abrupt and heavy downpour, the sun came out to reveal the most amazing double rainbow I’ve seen in years! (I would say ever, but I grew up in Hawaii, so I’ve seen some pretty amazing rainbows…)

Image

I’m not sure when or how, but in moments like this, I know that everything really is going to be alright!

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!

*****

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.