Share your myo-inositol experiences!

This post is a very long answer to Josie's question in the last post, where she asked me how I picked my myo-insoitol dose. Well here goes my experience with this so far. Just some background information you need: In most studies, women receive 2000 mg myo-inositol twice a day, along with folic acid, in a prescription preparation, Infolic.

My experience with this supplement

Despite being aware of the dose used in studies, I arbitrarily went with a lower dose initially because, well, I was nervous about what it would do. I started with 1000 mg/day, of supplemental (and not the prescription preparation myo-inositol) and things looked great that cycle...I ovulated a bit later (CD 19) than my recent cycles (O day in the past year,  has been CD 17).

Just FYI, in my pre-vitamin D, pre-supplement days, my best-looking ovulations were on CD 20. Sadly, none of my pregnancies were conceived during these cycles, they happened in shorter, crappier-looking cycles where I ovulated on CD 16. 

Anyway, coming back to the present day, after that first great-looking cycle (with a nearly 16 day luteal phase) where I was taking 1000 g/day, I shifted to 2000 mg/day, and stuff pretty much went to hell the next cycle--no EWCM, or CM of any sort, no detectable LH surge. I was not even sure I'd ovulated, except my temperature did go up. The luteal phase was a markedly short 11 days.

Alarmed, I shifted back to the 1000 mg dose. The next cycle (still ongoing) is interesting...there was one alarming day where my temperature short up, making me think I had ovulated, and prompting my last post. But happily, I was wrong, I have not misplaced my surge, this turned out to be a nice-looking cycle; got lots of CM, did show a strong surge, ovulated a bit late (on CD 22).

So...phew.It looks like Myo-inositol may not be bad for me, but only at low doses. It has changed my O date Still have not settled into a pattern, but it will be interesting. How many women, if nothing changes, ovulate on a certain day every month? I'd really like to know.

Also, if you are a PCOSer, or a non-PCOS infertility case on myo inositol, I'd really love to hear your experience. Please do share, sometimes anecdotal information can also be useful!

Also, some information to note, if part of your issue is low progesterone, this may really be something to try out, since both published literature and my experience (with the 1000 mg/day dose) suggest that this really can increase progesterone levels.

On myo-inositol and new blogs

First, lets get the annoying news out of the way- I seem to have mislaid my LH surge. The ONE thing, which is dependably seen in every cycle ever the past 3 years, is gone. I can't see a pattern anymore; I did ovulate last month based on a temperature rise, but it was a shitty cycle in that there was no CM, and the LH was an itsy-bitsy 12 days. GRR. 

Given all the stuff I do, I have to say that I'm really good at figuring out what is responsible for which effect, and this one I'm blaming on myo-inositol (down from 2000 mg/day, to 1000 mg/day). Its playing havoc with my cycle. Its freaking amazing for my skin. Definitely cause for shaking my fist at the universe.

I'm not going to give up on it just yet through; I'm going to keep taking it over the next 2 months and see if things change/settle down, and maybe I'll keep taking it till IVF anyway, and just use a trigger. 

The amazingly frustrating part is that myo-inositol is supposed to do GOOD things

• It is great at fixing the issues in women with PCOS. It can, to a large extent, shown by multiple studies, fix acne and hirsuteism, bring down LH and androgens (definitely doing that with me) and restore ovulation in women with PCOS.
• It can increase the proportion of mature oozytes at pickup during IVF (!!!!).

 I'm not sure what to do. Yes, my cycle looks utterly shitty now, and what I took for gospel truth--that if you had perfect cycles, you would have good eggs--has not held true for me. Sure, I got pregnant almost everytime I tried with my natural cycle, but something was off, 2 out of 3 times, my eggs may have been aneuploid. So maybe the lower LH is good, and such crappy cycles may actually get me live babies. Unlikely, but knows right?

Plus, I like what its done for my skin. Don't want to stop taking it, at my current lowish dose, ever.

So there is my current conundrum. I'm ok despite it though. I really, really relax during my breaks from TTC, I have to say. Probably because TTC itself is such stress, and has never got me good news yet, not trying to make a baby makes me feel so much more better. Its like when the dentist stops drilling on the tooth with the exposed nerve. It is too bad I'm determined to have a child, and TTC will have to recommence at some point.

The other news is that I will be starting a wellness blog using my real name and identity. Having a widely- read blog is good for me professionally, given that I've started building a career in scientific communication. The face-palm moment arrives when I realize I've started a blog that is visited by people all over the word, has gone over 200,000 page views, shows up quickly in Google searches, and I most definitely cannot list it on my LinkedIn page about it because too much of it deals with deeply personal issues.

What I'm going to start doing, is take away all the science from here slowly, and move it to there, and incorporate it into the general health topics I will discuss. So there, I'll be talking about infertility, autoimmunity, fibromyalgia, autism, discussions on healthy practices, etc. What I do best is gather, assimilate and distill scientific information, and I flatter myself in saying that I do it rather well.  

When the new blog is started- most of the science on this blog (the stuff on vitamin D,  the science of infertility page) will go away. People who want the address of that blog, will have to contact me on an individual basis. I'm a little (actually very) leery about people linking the real me to all the deeply personal information that is on here, so I will have to think about how to handle things. Would have been so easy to just put a link on this site, but nothing in life is straightforward is it?

Hola

I'm hanging my head in shame--I've been such a bad, bad blogger. In my defense, I've been really busy, all in good ways. I'm loving my new job. Its a new direction for me, and if I stick with it, it will give me the contacts to launch a completely freelance career in writing, which seems like the ideal career to complement motherhood. Plus, my other green card application (the one that gets me my green card immediately without having to wait in queue) came through! Ridiculously happy about it. I miss America, and want to get back as soon as possible, but yet, have plan B to think about. Still, its nice to have the option.

As for Plan B, it is on ice while I settle into my new job. I'm in this curious state of peace. If you think about it, I've gone through a lot-- 3 miscarriages, 1 failed IVF. But, when not actually going through pregnancy or getting 5 injections a day, I'm actually fine. This feels bizarre- how can I be so totally okay, given all I have been through?

In a couple of months, when I've settled into my new gig, I'll think about the next round of IVF. In the meantime, I'm loading up on the supplement regimen of CCRM;well, atleast some of it.

L-argenine was very bad for me, it messed up my system so badly after 2 days of being on it that I had to stop.

Myo-inositol is something I'm taking, and this is a very interesting one. It seems the best choice for people with PCOS. Its definitely causing changes in my system- whether these will help, hinder or do nothing at all remains to be seen. One of these days, I'll do a literature review of this in fertility- overall, it seems really promising.

Two really interesting things have happened: My antral follicle count is now sustained at around 25 (over the past 3 months), up from the average of around 14 when my Vitamin D levels were very high. The other thing, my DHEAS levels are coming down. This was around 250 when I was vitamin D deficient, climbed to around 350 while  my levels were super high, and now are around 180. This high levels of this hormone was my only concrete sign of PCOS, so this change has the potential to be important. I HOPE this is a good sign, but my physiology is so weird, one can never say anything.

Anyway, I apologize for the long silence. Sadly, I cannot promise to be a frequent blogger, but I'll try to say something atleast once or twice a month. I also want to say congrats to Augusta, who was, at long last, blessed with motherhood. Augusta, you have had such a long road here, I'm SO glad you have made it!

Choosing the correct IVF protocol

My response to the IVF protocol, the agonist flare protocol, where I got a microdose of lupron from day 2 continuously followed by stims (with a mix of follistim and menagon, which contains equal amounts of both FSH and LH), was truly awful- we got a lot of eggs (11 eggs from 13 follicles), but most of them were immature and failed to mature and fertilize and even though we produced one 'good' Day 5 embryo, that failed to implant.


Why was this? I've always thought that maybe my protocol was not best suited for me, but never thought I'd be able to find a good (or any) explanation as to why and how.

However, I just found a recent opinion by Geoffrey Sher, which gave a plausible explanation of what may have been the issue:

Some background- there are two ways to shut down the pituitary gland, which is the master remote controller of ovulation:

1. The first method developed is through agonists- these work by a weird method- they first stimulate the pituitary gland, but such a strong stimulation however later shuts it down completely.
2. The second developed method is antagonists, which directly shut down pituitary activity (or is it just LH secretion?)

Dr. Sher makes that the point that if you start the agonist at day 2 or 3, it first produces a spike of LH at this point,  and THEN shuts it completely. His theory is that this increase in LH, on CD2/3  (which is, importantly, also out of time with this natural process, though he does not put it this way), may be bad, especially in vulnerable populations like PCOS patients or older women.

I really think this point makes sense for one reason, and here it is: What is associated with annovulatory PCOS? A really high ratio of LH to FSH, on CD3. This is a hallmark of this syndrome and if his interpretation that agonist use first causes that LH spike is right, it may actually mimic the natural situation that produces annovulation in PCOS, if first given on CD2/3.

He makes several other less important, and less strong, nonetheless plausible points:

Ideal curve of LH in a healthy ovulatory cycle, courtesy Wikipedia.

• Menagon (which is equal doses of FSH and LH) may be less than idea- This may be true- it deviates the natural bell shaped curve of LH found in nature in health, but nonetheless, it clearly works for many.
• Femara may also increase LH at the wrong point

Dr Sher's opinion really makes for interesting reading- I'm very glad I came across it. See above the bell shaped curve of LH in the natural cycle- maybe protocols that deviate from this may not serve optimally. Maybe too much LH at the spike or any other point may be bad too- its difficult to say

All i know is, if I'm doing IVF, I need to go away from what was done the last time. Based on what he said, I've also decided to avoid Femara and Clomid.

I may go straight to low dose FSH from an early point. I'm going to figure out if I want to use antagonists or not. The reason I'm vacillating on this point is that LH IS important- the gradual increase of this as ovulation nears, resulting in that spike, may be a good thing. But too much LH may be a problem too, and the reason pituitary shutdown was introduced was that 51 % of women had a premature LH surge which resulted in cycle cancellation.

Trying natural cycle IVF is so very alluring- except I have 2 IUI and 1 IVF vial of swimmers, and the really steep costs of IVF come in during the pickup and fertilization. Finances are not a problem, yet nor can I act like money grows on trees.

There are many choices to be made, but the good news is, right now, I'm pursuing the next option without the angst and hand-wringing and feeling that time crunch. Other people are always telling me my attitude is awesome, and I have to say, I'm impressing myself at this point.

Making a case for not messing too badly with nature

This is a hopelessly  technical post- its mostly a prelude for the discussion with my RE.

I'm somebody in whom, the natural process, at a surface glace, works beautifully.

• My ovulation are extremely predictable. 
• My estradiol levels per mature follicles are bang on target(around 250/ single mature follicle) .
• My LH surge is huge, regular and easy to identify. My levels are super low on CD 3 (around 2.5 in one test) and go up to around 40 on day of surge. 
• The appearance of the uterine lining elicits extravagant praise from doctors. 
• My natural progesterone levels  (only during pregnancy) are usually perfect, over 40 ng/ml.
•  And since I've corrected my vitamin D levels , my luteal phases have been perfect in length, usually around 15 days (Note: In my days of vitamin D deficiency, they were much shorter, around 10-11 in a particular cycle pattern)
• Most importantly, all of this usually results in a pregnancy rate/cycle far above the population average.

On the other hand, when I did IVF, everything went to hell. Basically, shutting down my pituitary and hitting me with monster doses of FSH had a shitty outcome.

• While my E2 levels were even higher than normal (3521 pg/ml, with 11 eggs being extracted, translating to around 320 pg/ml per follicle), only 3 of these eggs managed to fertilize, even with ICSI.
• As my estrogen levels got higher and higher, my cervical mucus disappeared- it was abundant during the first 4-5 days of FSH injections and then as my E2 climbed, it just vanished. It actually makes sense- whatever stimulates a process at one concentration can inhibit the same process at a much higher concentration.
• My luteal phase was a short 10 days- very striking. 

My RE blames my weird response to the drugs on the fact that my AFC, which was 30 in 2010, had dropped in half. Few issues with this line of thought---

• My AFC has maintained around 16 for an entire year before the IVF and its drop correlates to the time when my Vitamin D levels tripled. Its hard to correlate a drop in AFC to a bad response to  FSH- After all I managed to get pregnant  naturally in response to the FSH my pituitary manufactured, well after the drop.
• I think MY RE is stuck on this theory because it is natural for an RE to connect a poor response to IVF protocol to ovarian aging because these 2 normally do go hand in hand, a 40 year old woman would have had a large decrease in AFC in the past few years of her life and she may be a poor responder as well by this age . However, mine is not the typical scenario: I believe my drop in AFC was the end result of the reactions caused by the increase in my vitamin D levels and is conclusively NOT due to ovarian aging, so trying to link the two is trying to compare apples to oranges- there is no logical connection.  

I think that my protocol really did not suit me. Why that is hard to say. How to fix it is even harder.

What we all forget- the natural process has about a 1000 intricate layers, and is beautifully controlled- in comparison the IVF protocol, which often shuts down the pituitary and all feedback mechanisms, is like a caveman with a club- I'm not disputing that it works, only noting that in me, the natural process appears to be superior to IVF.

So what I'm trying to do with my next IVF cycle:

• Keep my stimulation to a minimum, using a mini-IVF
• I really want to keep my pituitary gland in play for as long as possible. During IVF, this is shut down with agonists/antagonists. I want my body to tell me when the the follicles it is making are mature, through all the feedback mechanisms it possesses- In other words, I want to trigger when my body decides to go with its LH surge.  I don;t want the doctor to decide this just through just looking at follicle size/E2 levels- this worked really badly the last time, but maybe it was also because of asychronization of follicles- I believe that the first 6 follicles that grew first yielded the 4 M2 and 2 M1 eggs and these were kept waiting for about 3-4 days while we tried to get other follicles to grow.
• Option 1: I'm debating trying to get my doctor to agree to avoid pituitary suppression using antagonists and allow a natural surge. I recognize that this is entirely antithetical to the nature of IVF itself and most people may say I'm nuts to risk 'premature luteinization' of follicles  and  yes, there is a good chance it may end badly, in cycle cancellation. However, in the indian system you don't end up loosing too much--- meds cost very little, and anyway I'm going with low doses.The real investment is in the pickup of follicles and subsequent in vitro fertilization steps. However, I need to understand the role of LH and how it rises in me. I know that In normal cycles my baseline LH is super low and rises gradually to a full surge. How will it be in an IVF cycle? Will such a natural rise make better eggs compared than suppressing it entirely? What causes the LH surge? Is it only the rising Estrogen or is it other factors as well, which 'tell' the pituitary when the egg is ready? 
• Option 2: Alternate to avoiding antagonist use completely, as a compromise, can one delay its administration as far as possible?Here is an interesting article about women who showed a premature surge (which was then suppressed through antagonist admistration), who actually ended up making decent eggs..so it brings in to question the benefit of LH in a cycle. I think this is really multifaceted issue...

All my worldly belongings for a crystal ball..

I honestly was not expecting a BFN, given that the embryo had gotten to day 5, and the embryos I make naturally show an excellent capacity to implant. Statistically, I thought implantation was likely, with a strong probability of pregnancy loss.

So now, I'm asking the questions-

• Was it an embryo issue? How did the embryo I made during superovulation compared to the ones I make during a natural cycle? 

• Is it that the surrogates womb is less receptive than mine?

To discuss the embryo quality in my natural vs superovulatory cycles, lets look at the following percentages:

20 %  : The probability of anybody's getting pregnant, say, while being in their late 20s, in any particular cycle (correct me if needed, I'm citing from dim memory)

50-60 % : The probability of a high quality Day 5 blastocyst implanting in any given cycle. I've asked my RE to provide the stats from his clinic as well.

75% : Probability of my getting pregnant, naturally. Calculated using an average of 4 cycles, where I've gotten to clinical pregnancy stage through a natural cycle, 3 out of the 4 times.

So going just by this, the odds were really in favor of the embryo implanting, unless it was different from those I make in a natural cycle.

It is always possible that mine is one of those high fertility wombs that just allows all embryos to survive and implant, not just the best quality ones, making me a candidate for recurrent pregnancy loss. This possibility is derived from this study.

But there is the other possibility- that the superovulation produced poorer quality embryos than what I make naturally. I clearly respond badly to higher doses of FSH- In the start, I was on 300 IU follistim and 6 eggs were on the route to responding, and in the end, possibly gave my 4 M2 and 2 M1 eggs. On increasing that dose (to 450) and using a mix of menagon and follistim, we got up to 11 eggs, but I believe those later growing  follicles yielded the immature eggs, even though my estradiol levels rose appropriately.

I beleive, no matter what I do next, that if I go for another round of IVF, stimulating me very gently would be a more sensible option. I'm also going to elaborate on the role on myo-inositol, that I've started taking, in a later post/ Please, anybody who is an armchair RE or a real one, fee free to weigh in here. I'm thinking about 2 things

-Agonist/Antagonist (with or without conversion) with a low dose of FSH.
-Natural cycle, or very close to it, with mimimum stimulation, with a transfer to the surrogate.

I've also started thinking about donor eggs. I went and looked at this website, and I was pretty aghast- although it says Indian egg donors, the majority are caucasian and well, though a lot of them are very pretty, they don't appear to have done too much with their lives.Ditto the few indians there- a few of them look and sound like those girls that pop up on the websites where you download torrents. Plus the website does not seem very well run- one girl listed her height as 5.2 cm. What is she, Thumbelina?

 A really good friend talked about offering her eggs yesterday, and she is like my dream donor, smart, good looking, accomplished, determined and I think I would really be able to identify with her genetic babies, because god, we think alike. But she is a really good friend I'd want to keep always, and I've always believed that if you do these things, its best to use people who will not be in your life afterwards. Sigh- I just wish the strangers I am finding were more like her, but that is a really tall order.

If I go the donor egg route, I'd probably have to place an ad in the papers and pray I get lucky. Then there is that million dollar question- do I carry the baby or use a surrogate?  Honestly, when people talk about the joy and intimacy of a pregnancy, I no longer feel it. To me, pregnancy is terror, stress and the possibility of losing my figure, my baby, and my even keel, which has managed to hold through through all this, at 24 weeks. I can get past this, and god knows, things may even go well, but I don't at all feel like I want to do it.

What do I do?!

Negative

R is not pregnant. I'm mystified as to why that is, because if anything, my embryos formed naturally showed a higher than average ability to implant in a fertile uterus, and R had no issues there. Plus, going by embryo quality, it did not get much better than 3AA.

But biology presents too many variables to predict what was different and its impossible to say where the mojo went here. Regrouping, reassessing, will be back with options later.