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!

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.

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.

Craptastic diagnosis

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

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

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

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

SART Fresh IVF cycles Percentage of cycles resulting in live births

<35

35-37

38-40

41-42

>42

all diagnoses

40.1

31.9

21.6

12.2

4.2

ovulatory dysfunction

43.3

36.9

28.3

14.1

3.2

male factor

43.2

36.7

25.6

16.6

5.2

unknown

42.5

33.4

24.7

14.1

7.1

female & male factor

39.5

30.7

20.4

11

5.1

tubal factor

39.2

31.5

20.7

14.6

3.8

endometriosis

38.9

29.6

24.6

13.2

4.7

other

36.5

30.8

21.9

13.2

4.7

multiple female factors

35.2

27.2

18.9

10.4

2.6

uterine factor

33.6

33.8

19.3

15.4

5.9

DOR

27.5

24.2

17.8

11.1

3.8

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

SART FET cycles Percentage of transfers resulting in live births

<35

35-37

38-40

41-42

>42

all diagnoses

39.3

35.7

30.3

24.5

16.5

ovulatory dysfunction

42.1

38.4

34.5

19.4

33.3

DOR

40.8

32.6

25.9

23.3

13.1

unknown

40.8

37.3

33.1

28.7

21.3

male factor

39.9

35.6

29.3

28.1

16.7

other

39.5

37.3

34.1

31.8

16

female & male factor

38.6

35.7

29.3

21.7

17

endometriosis

37.7

33.6

32.7

28.9

3 of 12

tubal factor

37.2

35.4

24.8

12.5

28.3

mutliple female factors

35.3

33.3

31.2

26.3

18.6

uterine factor

31.8

32

31.5

17.9

17.4

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

Why CCRM?

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

What about CRMI?

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

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

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

<35

35-37

38-40

41-42

>42

all diagnoses

54.2%

43.4%

39.0%

10.0%

4 of 15

DOR

2 of 10

19.0%

6 of 19

10.7%

2 of 7

CCRM Fresh IVF cycles Percentage of cycles resulting in live births

<35

35-37

38-40

41-42

>42

all diagnoses

65.0%

45.5%

35.3%

32.4%

20.6%

DOR

8 of 17

52.4%

28%

5 of 14

4.8%

Cornell Fresh IVF cycles Percentage of cycles resulting in live births

<35

35-37

38-40

41-42

>42

all diagnoses

38.1%

29.2%

25.1%

14.3%

4.6%

DOR

14.6%

25.9%

25.0%

14.0%

5.3%

And a comparison of frozen transfers:

My clinic FET cycles Percentage of transfers resulting in live births

<35

35-37

38-40

41-42

>42

all diagnoses

50%

41.20%

29.20%

0 of 3

0 of 1

DOR

1 of 1

1 of 2

1 of 2

0 of 0

0 of 1

CCRM FET cycles Percentage of transfers resulting in live births

<35

35-37

38-40

41-42

>42

all diagnoses

67.90%

65.80%

58.90%

56.70%

33.30%

DOR

8 of 8

8 of 17

48.60%

51.70%

3 of 15

Cornell FET cycles Percentage of transfers resulting in live births

<35

35-37

38-40

41-42

>42

all diagnoses

38.30%

42.90%

34.80%

11.10%

1 of 15

DOR

2 of 5

5 of 8

5 of 11

2 of 11

1 of 8

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

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

A farewell to Lefty, politics, & acupuncture

Thanks again for all your well-wishes. I just got the call from Dr. Y, and he told me that Lefty stopped growing. 😦 In the words of IVFfervescent gal, I hope he enjoyed his few days on earth.

We have our WTF appointment scheduled for Friday at 9am.

*****

The news of the end of Lefty’s fight was somewhat softened by this morning’s Supreme Court rulings. I don’t mean to get political on y’all, but as an infertile heterosexual Californian, I’m grateful that SCOTUS rejected the argument that the ability to procreate was a prerequisite to a valid marriage… (No really, that was “the essential thrust of” the defendants’ position!) 

*****

In other news, I did something very unscientific yesterday. I went to see an acupuncturist who specializes in infertility, let’s call her J. I learned about her on the forum of my local Resolve support group, where she has rave reviews. She is also conveniently located 7 minutes from my house, and had an evening appointment available for the next day.

C and I arrived at J’s office at 5:30 and went in. She read over my forms (9 pages of them!) and asked some questions about me and my future treatment plans. The stuff she said sounded reasonable. She didn’t promise to cure my diminished ovarian reserve or improve egg quality. She said that our goal would be to increase blood flow to my lady organs, and hopefully achieve subtle improvement in my antral follicle count. She expressed interest in hearing what Dr. Y says to us at our upcoming appointment so she can adjust our treatment plan accordingly. We also discussed coffee and alcohol and supplements (more on those in a future post). C asked her whether she could do anything for his rib and back pain from the accident. She said she would be glad to once she got me set up.

The mood of the office was very spa-like: dim lighting, relaxing New Age music, faint smell of incense and massage oil. J had me strip except for bra & underwear and lay on my back on the table (which resembled a massage table), covered by towels. She directed a heat lamp at my feet; put needles in my tummy, arms, hands and feet; and covered my eyes with an eye pillow. I didn’t feel much as the needles went in. Then she did moxibustion (burning a cigar-like stick of mugwort to warm the regions where the acupuncture needles were). Lastly, J started a CD of ‘Meditations for the Fertile Soul’ by Randine Lewis and placed a bell in my hand, in case I needed anything. Then she left and took C to another room.

I’m not a very good meditator. I tried, but my mind would wander after a few minutes each time. But I was pretty relaxed, and the heat lamp felt good.

J came back (30 minutes later? 45 minutes?), removed the needles, put a heat pad on my belly, and massaged my back, shoulders, and feet with a peppermint-scented massage oil. And that was it!

With the support group discount ($10 off), she charged me $115 for this visit, with future visits costing $75. She didn’t charge at all for C’s treatment, which included acupuncture and cupping therapy. (C is Vietnamese, and despite usually being pretty skeptical, he seems to have inherited a belief in the efficacy of Eastern medicine from his parents.)

Overall, we were both pleased and plan to go back once a week for the time being.

*****

So, why do I say acupuncture is unscientific?

Here’s what I learned about acupuncture from a few hours of PubMed searching and reading abstracts. (As I mentioned before, I am not an expert. Specifically, I have no idea whether certain journals or researchers are more or less credible, though I speculate below about their possible biases…)

First, I looked for PubMed articles about acupuncture and diminished ovarian reserve:

Well…There aren’t many. A PubMed search of “acupuncture diminished ovarian reserve” turned up no hits; modifying the search to “acupuncture ovarian reserve” returned a whopping three hits. “Acupuncture AMH” returns a single article about treating PCOS. “Acupuncture FSH” turned up more, but most were about PCOS or treating menopausal symptoms…

In conclusion, I don’t think a lot of people have studied the effect of acupuncture on egg quality or quantity, but here are promising quotes from the abstracts of a few of the articles I found:

  • “Electroacupuncture therapy has a good clinical effect for IVF patients with poor ovarian reserve, and can improve oocyte quality and pregnancy outcome.”
  • There was “no statistical difference in the number of retrieved oocytes and the fertilization rate…Acupuncture combined CM-MTSSG [Chinese materia medica for tonifying shen and soothing gan] could obviously alleviate unfavorable emotions as anxiety and depression in patients with IVF-ET, effectively improve the treatment outcomes. Its effects might be correlated with lowering the excitability of the sympathetic nervous system, elevating the quality of oocytes, and improving the endometrial receptivity.” [my emphasis]
  • “The results suggest that electroacupuncture could decrease serum FSH and LH levels and increase serum E2 level in women with primary ovarian insufficiency with little or no side effects; however, further randomized control trials are needed.”

Next, I tried to find PubMed articles about acupuncture and IVF:

A PubMed search of “acupuncture IVF” returned 63 hits. Most of these were about the effect of acupuncture on embryo transfer, some were about acupuncture analgesia during egg-retrieval, and others were about acupuncture and male factor infertility.

The articles fell into four major categories:

  1. Articles that said acupuncture is effective
  2. Articles that said acupuncture is ineffective
  3. Articles that said acupuncture is effective, but that its effectiveness can be attributed to the placebo effect
  4. Articles that said there is not enough evidence to say

The majority of articles in Category 1 appear in journals with titles like Acupuncture in Medicine, Journal of Alternative and Complementary Medicine, Complementary Therapies in Clinical Practice, Zhonguo Zhen Jiu [translation: Chinese Acupuncture & Moxibustion], Zhongguo Zhong Xi Yi Jie He Za Zhi [translation: Chinese Journal of Integrated Traditional and Western Medicine], Evidence-Based Complementary and Alternative Medicine, and Clinical Journal of Integrated Medicine.

Now, I don’t want to say that these journals are suspect, but I think it’s fair to say that their titles at least suggest a belief in the efficacy of acupuncture…

Some quotes from abstracts that supported acupuncture:

  •  “The results mainly indicate that acupuncture, especially around the time of the controlled ovarian hyperstimulation, improves pregnancy outcomes in women undergoing IVF.”
  • “Transcutaneous electrical acupoint stimulation, especially double transcutaneous electrical acupoint stimulation, significantly improved the clinical outcome of embryo transfer.” (I think it’s worth noting that this was an article in Fertility and Sterility.)
  • “acupuncture can improve the outcome of IVF-ET, and the mechanisms may be related to the increased uterine blood flow, inhibited uterine motility, and the anesis of depression, anxiety and stress. Its effect on modulating immune function also suggests helpfulness in improving the outcome of IVF-ET. Even though a positive effect of acupuncture in infertility has been found, well-designed multi-center, prospective randomized controlled studies are still needed to provide more reliable and valid scientific evidence.”
  • “In this study, there appears to be a beneficial regulation of cortisol and prolactin in the acupuncture group during the medication phase of the IVF treatment with a trend toward more normal fertile cycle dynamics.” (Another article in Fertility and Sterility.)
  • “Limited but supportive evidence from clinical trials and case series suggests that acupuncture may improve the success rate of IVF and the quality of life of patients undergoing IVF and that it is a safe adjunct therapy. However, this conclusion should be interpreted with caution because most studies reviewed had design limitations, and the acupuncture interventions employed often were not consistent with traditional Chinese medical principles. The reviewed literature suggests 4 possible mechanisms by which acupuncture could improve the outcome of IVF: modulating neuroendocrinological factors; increasing blood flow to the uterus and ovaries; modulating cytokines; and reducing stress, anxiety, and depression.”
  • “Luteal-phase acupuncture has a positive effect on the outcome of IVF/ICSI.”

The majority of articles in Categories 2-4 appear in journals with names like Fertility and Sterility, Human Reproduction, BJOG – An International Journal of Obstetrics and Gynaecology, and Clinical and Experimental Obstetrics & Gynecology.

One might argue that these journals – which focus on Western medical interventions – might be biased against acupuncture and other alternative therapies.

Some quotes from abstracts that did not support acupuncture:

  • “When studies with and without placebo controls were analyzed separately, a placebo effect was suggested.”
  • “No significant benefits of acupuncture are found to improve the outcomes of IVF or ICSI.” (Perhaps also worth noting that this was an article in the Journal of Alternative and Complementary Medicine.)
  • “New emerging evidence from clinical trials demonstrates that acupuncture performed at the time of embryo transfer does not improve the pregnancy or live birth outcome after treatment.”
  • “There was no statistically significant difference in the clinical or chemical pregnancy rates between both groups [true acupuncture vs. sham acupuncture]… There were no significant adverse effects observed during the study, suggesting that acupuncture is safe for women undergoing ET.”
  • “Currently available literature does not provide sufficient evidence that adjuvant acupuncture improves IVF clinical pregnancy rate.”
  • “The use of acupuncture in patients undergoing IVF was not associated with an increase in pregnancy rates but they were more relaxed and more optimistic.”
  • “Acupuncture performed twice weekly during the follicular and luteal phase does not seem to improve pregnancy rates following IVF-ET.”

Particularly interesting were the articles that explored the possible placebo effect of acupuncture. Many of these studies used “sham” acupuncture needles that don’t actually penetrate the skin (in one case referred to as the Streitberger control). What they generally found is that patients who did sham acupuncture got the same benefit as (or in one case greater than) those receiving real acupuncture. Here are some quotes from abstracts that addressed the placebo effect of acupuncture:

  • “Placebo acupuncture was associated with a significantly higher overall pregnancy rate when compared with real acupuncture. Placebo acupuncture may not be inert.”
  •  “Acupuncture improves clinical pregnancy rate and live birth rate among women undergoing IVF based on the results of studies that do not include the Streitberger control. The Streitberger control may not be an inactive control.” (In Fertility and Sterility.)
  • “Even if adjuvant acupuncture were to increase IVF success rates only through a psychosomatic effect mechanism, such as by reducing stress, this stress-reduction effect would be integral to the working mechanism by which adjuvant acupuncture increases IVF pregnancy rates; therefore, it seems inappropriate to control for and separate out any such stress-reduction effect by using a sham control.” (In Reproductive Medicine Online.)

So why am I doing acupuncture?

Not one of the studies I saw in my search showed a negative impact of acupuncture on pregnancy rates. And very few said there was no improvement relative to no acupuncture. Rather, they said that there was no improvement relative to sham acupuncture. They also seemed to agree that patients enjoyed acupuncture, and that there was likely a psychological benefit. The fact also remains that the Chinese have been performing acupuncture for thousands of years, which in my mind affords it a level of credibility beyond that of other ‘unproven’ treatments.

So, I think that acupuncture might help – either by “correcting my flow of qi” and thereby increasing blood flow to my lady organs (as J tells me), or by simply forcing me to lie still and relax for an hour or so each week, or via the placebo effect. The scientist in me thinks the latter two mechanisms are more likely, even as the romantic in me (and the 20-year-old who studied abroad in the People’s Republic of China) would love to think that it might work via the former.

But frankly, I don’t really care why it might work; I’m just looking for it to work. Worst case scenario, I spend $75 per week for an hour of quiet relaxation.

 

p.s. If you want to read a different take on gay marriage and acupuncture, check out Stupid Stork’s latest post.

Slowly growing

Thanks everyone for your well-wishes and words of encouragement. You all make infertility suck a little bit less…

Well, at 6:15 pm today the embryologist finally called to give us the status update on Lefty. He did fertilize, but is growing verrryyyy sloooooooooooowwlyyyyyyyyyyyyyyyyy. He is currently two cells, when he should be at least six cells by now…

Here’s a random photo I found online of what a two-cell embryo looks like:

Image

Here’s what Lefty should look like by now:

ImageThe embryologist was not very encouraging; she said, “most likely it will go nowhere”, but they are going to check again in two more days to see.

Dr. Y was also on the phone for the call (which is probably why they waited until 6:15 to do it), and so I asked him if we should make an appointment to sit down with him and plan the next step.

I also made an appointment with an acupuncturist, and spent a couple hours at work searching PubMed for articles about supplements to treat diminished ovarian reserve. (I’ll write a post about what I learned sometime soon.)

I figure if we’re going to throw away another $12K+, I’d like to have some reason (however improbable) for expecting a different result…

Bust

Got the call from the embryologist today. The two “intermediate” eggs didn’t mature, so they only ICSI-ed the one. And they “can’t confirm that it fertilized”. They’ll know for sure on Monday, but at this point it looks like IVF#1 is a bust.

Ugh.

Bring on the margaritas…

Three’s company

I’ll jump to the punchline and let you know that Dr. Y got all three eggs!

Here’s a breakdown of the day:

6:15 am – Woke up & showered…but skipped deodorant, lotion, or anything scented. (Apparently perfume is not good for eggs.)

7:23 am – Checked in at the surgery center with C.

8:00 am – Got IV sedative placed. Lights out.

~9:30 am – Woke up with a slight headache and waited a long time for C’s chance to give his sample. (Apparently the “collection room” got backed up…)

~10:45 am – The embryologist came by and gave us the egg report. She said one egg is “mature” and two are “intermediate”. She said that there’s a “good chance” that one of the two intermediate eggs will mature today in time for intracytoplasmic sperm injection (ICSI). She also told us that they’ll be growing our embryos in coculture with some cumulus cells from my ovaries (a technique called cumulus coculture). This is supposed to “detoxify” the medium that the embies are growing in, and provide some growth factors to help my embryos grow better.

11 am – “Collection room” finally free. C did his part.

11:30 am – Headed home.

In summary, we got pretty much the best result we could hope for at this point, given how things looked going in. Now we just pray that they all fertilize and grow.

Stay tuned for tomorrow’s fertilization report!

Catching up

Today’s ultrasound went better than Monday’s. Dr. Y seemed much more upbeat. Lefty is at 22 mm, with Righty catching up at 17 mm. The third follicle has also been growing, and is now at 12 mm. Dr. Y said it could grow enough before retrieval to be good, but the chance of this is definitely less than for the other two. My estradiol was at 781 (whatever that means…)

The net result is that we’ll trigger tonight at 9:30, with egg retrieval scheduled for 7:30 on Friday morning!

Given the fact that we have only two good-looking follicles, Dr. Y explained a few special precautions he’s taking with the retrieval.

First, he added another drug called indomethacin.

ImageIndomethacin is a non-steroidal anti inflammatory drug (NSAID) that apparently is also useful for preventing ovulation. Dr. Y said this would be extra insurance (in addition to the ganirelix) to make sure that Lefty waits around until Saturday.

Second, he said he’ll use a double lumen needle in place of the usual single lumen one. Dr. Google informs me that the double lumen needle looks like a needle within a needle:

ImageI think the inner (bigger) hole is used to aspirate up the egg (like with a single lumen needle), but the double lumen needle has the added functionality of being able to squirt water from the outer hole into the follicle and ‘rinse’ it out. The rinse can be aspirated out again to catch the egg if it wasn’t sucked up the first time.

Dr. Y seemed to think we have a good chance of retrieving the two big eggs. Either way, he said he will be able to tell us how many he got immediately after surgery. (C is not looking forward to the responsibility of being first to know the news…) If we get something on Friday, then we’ll find out on Saturday whether it/they fertilized. And if something fertilizes, then we’ll find out on Monday whether it survived to Day 3 for freezing. Given the small number of follicles, Dr. Y doubts that we would risk letting them grow to Day 5, but he didn’t rule it out completely.

So today is my last day of stims, ganirelix, dexamethasone, aspirin and prenatals. I’m also supposed to do a Follistim ‘boost’ tonight right after C gives me my hCG trigger shot at 9:30 tonight. That makes a total of 5 shots today! Tomorrow I continue the indomethacin and growth hormone (which I haven’t written anything about yet…sorry!)

Here’s an updated version of my protocol that reflects the adjustments:

Image

Antagonistic

The ultrasound today seemed to go fine. Lefty is at 17 mm, with Righty lagging behind… still measuring 11 mm. (Dr. Y also measured a third at 8 mm, but didn’t say anything about it.) C and I think that Dr. Y was disappointed with Righty’s slow growth, but felt sorry for us and refrained from saying anything… He recommended continuing stims + Antagon for a couple more days to give them more time to grow. He’d like Lefty to be at 20 mm for retrieval.

The next ultrasound will be Wednesday, with tentative retrieval on Friday – possibly later. Back when we started the cycle, Dr. Y said that it will be good if we can get a couple extra stim days prior to retrieval, so I’m going to stick with that and say this is a good thing…

*****

So, Antagon

I’m on day 3 of Antagon (aka ganirelix), which I inject into my belly every morning by way of a prefilled syringe with an annoyingly dull needle. (It doesn’t hurt that much, but it actually bounces off of my skin if I don’t shove it hard enough!) Aside from looking like a human pincushion, I haven’t observed any side-effects.

Despite my disappointing Saturday, I didn’t want to put off writing about Antagon for too much longer, since it is actually the drug that I find the most interesting, but first:

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

*****

Before explaining what Antagon does, it’s probably worth reviewing how this whole sex hormone signaling cascade is supposed to go normally.

Image

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

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

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

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

Here’s where Antagon comes in.

Image

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

Image

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

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

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

Image

What about Lupron?

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

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

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

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

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

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

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

What does DOR have to do with it?

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

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

*****

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