Decision, and depressed as hell

Thank you all for your input on my last post- I agree with you in that 2 vitrifications should be off the table.  What I was hoping to do was collect the biopsy on day 5, and freeze the biopsied cells. But it looks like that won't be possible, even though I may have been able to get my hands on the materials needed in time.

Doing things in India has the advantage that it won't break the bank, and this is a tremendous advantage that should not be taken lightly. And then, there is the tremendous emotional support that is offered to me by my family.

But one can never have their cake and eat it too- this is a technologically retarded country. NICUs are primitive compared to the setup in the developed world. Fetal DNA analysis from maternal blood (like Sequenom's Tri21 test) during pregnancy is going to take years, if not decades to get here. There is probably one guy who can do a decent aminoicentesis, and I may have to fly my surrogate to another city to find him.  A trophectoderm biopsy is not here yet, or atleast, it is not there with my doctor, who expressed extreme reluctance in doing this procedure. My lack of preparation had an extremely large part to play in this, I just sprung this on him, so he did not have time to prepare, with dummy runs etc.


But there it is- no testing.  I have to just collect whatever grows till day 5, and transfer to the surrogate.

Atleast 40-50% of the day 5 blastocysts  (there was a study definitively showing this) are going to be abnormal. My RE countered that despite such odds, people get pregnant and deliver healthy babies. What was left unsaid was how this is achieved: you transfer multiples. Out of 2 or 3 embryos, 1 may be normal. I'm starting to believe the theory that most women's wombs can distinguish between a normal and abnormal embryo. This may very well be the reason for the high frequency of BFNs in IVF and in natural pregnancies as well. The transfer of 2-3 embryos can also sometimes result in a pregnancy with multiples, which may be slightly or tremendously detrimental to the lifelong health of the resulting children, even if the pregnancy is without complication.

So now, I may have to do what everybody else does: transfer 2 at a time, or I may be doing this for a while, at tremendous cost.  I just have to then pray that if my surrogate gets pregnant, it is with a singelton, not twins. A twin pregnancy is considered high risk in the developed world. Here, given the standards of management, you would have to rely on luck for everything to go ok, and I'm somebody who has had absolutely no luck in this process so far, and now, I have to pray that I find that luck. Scary as hell.

Day 2 report and a difficult decision to make: Need your input!

All but one of my 16 embryos are now 4-celled:


8 are 4-celled As
2 are 4-celled Bs
4 are 4-celled Cs
1 is a 2-celled A (this we can probably write off)

I think there is a good chance I'll get a decent number of blastocysts, of varying grades. This is the sort of thing where I'd want to do an embryo biopsy to see how many are aneuploid.

The issue is, I  was stupid and left it too late, because I did not envision getting anything, after my last experience. The only lab (the Spain-based company Iviomics) doing this in India is not functional yet. We could collect the biopsied cells and freeze them down, but we need a special medium and special tubes to do this.

I just got off the phone with the Spanish guy who is the India head for this organization, and I asked him if we can overnight this from Spain to get here by Day 5 (Sunday). He said he could talk to his people and get back to me.

The other option, which I really don't like, is freeze everything down on day 3, thaw them all, herniate, and biopsy on day 5, and freeze again. This involves double vitrification, which I'm not a fan of.

The other option is going with fate--- just freezing whatever we get on day 5,  transferring and seeing what happens.

Lets hope they can overnight. Even if things work out that ideally, there are still risks: the clinic does not do this routinely.

What would you guys do in my shoes- do the day 5 biopsy on Sunday (if I could get the materials on time) or go with hoping to get lucky?

Myo-Inositol for fertility and PCOS: Share your 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.

My experience with this supplement:

Despite being aware of the dose used in studies, I arbitrarily went with a lower dose initially, because I was frankly 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 that in my recent cycles (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 mg/day, I shifted to 2000 mg/day, and stuff pretty much went to hell the next cycle, in a manner never seen before - 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, with the longer luteal phase) suggest that this can increase progesterone levels.

Updated: I did an IVF cycle a few months after this post: I took myo-inositol for THREE CYCLES at least, and then went for IVF. Myo-inositol is supposed to increase the percentage of oocytes that are mature at pickup. We got 14 M2 eggs, 2 M1 eggs, and 3 that crapped out, from a total of 19 follicles.All my M2s and my M1s fertilized too. Overall, this was pretty darned amazing: My first IVF, where the protocol used on me was far from ideal, produced 4 M2 and a few M1 eggs out of 11 eggs, and only the M2s (3 out of 4) and none of M1s fertilized, in contrast to my second cycle, where everything did. I attribute the improvement from IVF#1 to IVF#2 to two things: a very different protocol, and maybe, in part, the myo-inositol.

I have gotten emails asking about a good supplement: I would recommend this (see above),
which combines myo-insoitol and folic acid, and appears to have been used by many women with PCOS successfully.

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?

Meiotic non-disjunction strikes again

After a great deal of haranguing, I got the results.  Meiotic non-disjunction (which, in English means, the chromosomes did not separate properly during the process of making an egg or sperm) has happened again.

During my second pregnancy, it happened in the form of a monsomy of the X chromosome, which means either the egg or sperm had one less X chromosome that it should have. Monosomies are considered to be more likely a sperm error (a sperm that is missing a chromosome is lighter, can swim faster, yada, yada).

This time, it was most likely to be an egg error- a Trisomy, of chromosome 4. And it was a girl.

On googling, my blood ran cold- trisomy 4 appears be one of the rarer ones, and more often its a partial trisomy, (you have a 3rd copy of only one half of that chromosome) and the child can make it to birth, but obviously, with major, major issues. Thank god  my baby and I was spared that. Often, miscarriage is not about nature being cruel, its about nature being kind, and nature was kind here, but only AFTER the bloody trisomy had resulted. Bloody nature.

I'd had a bad feeling about this pregnancy from the time that the first beta and progesterone values had come in, because they were both far lower than my levels for the first 2 pregnancies (though, in normal range for the population) and the progesterone fell sharply by the 7th-8th week period-this was all in keeping  with the observation that some (but not all aneuploidies) can have lower progesterone and beta-HCG levels. Its fascinating, apparently trisomy 21 has higher HCG levels, but Trisomies 13 and 18 have lower progesterone and beta-HCG levels---wow, this suggests that complex mechanisms behind aneuploidy of different chromosomes, just because we don't understand it in the slightest, does not necessarily mean that its completely random. Chromosome 4 aneuploidy has not been studied, because its too rare, but my scenario also points to reduced hormone levels with this one.

What next? IVF with PGD obviously, but I'm trying to end up with a method more accurate than FISH, which does not analyze all the chromosomes, and would (probably?) have not caught this one.  The goal is to get microarray done with IVF in India-- this one has several logistical issues, lets see how they can get worked out. 

But as for now, I'm so very glad to have an answer. The point where we get grateful for small mercies is a sad one indeed.

Three short months

I checked the date yesterday and I was shocked that it was exactly 3 months after discovering my second pregnancy had ended.  It blows me away that it has only been such a short time, I’ve changed so much, my situation has changed so much that it feels almost like years have passed.

I’ve traveled 1000s of miles in this time, and I’ve spent one month each in drastically different places, India, California and now New York.

My first month was in India. It was the happiest of these past 3 months, which is mindboggling given that it was immediately after my loss. But---being with family was going into this incredibly comfortable cocoon. It’s the same one I will return to, to fight out this battle of trying to create another human being.

The next month was spent in California, with the stress of moving cross-country while dealing with my new reality. 

The third has been spent in NYC, and here it is the stress of settling into a new place.

I’m just amazed at the speed at which my life has been moving, and the utter lack of control I have over anything.  Its also just bewildering how much I’ve learned in this short time. The most shocking revelation was that my baby had Turners syndrome. Then came the vitamin D story. Then finally came the PCOS story.

Ever so often, you learn something new, often entirely by accident. You start to tug on one chain, and it takes you someplace you had never intended to go. Sprogblogger had recommended Dr. Barad at the Center for Human Reproduction (thank you, sprogblogger!).  Absolutely by accident, I ended up looking for papers Dr. Barad had authored, and found a pretty darned interesting one.

I’ve remarked on this on ‘The science of infertility’ page : I found it very interesting that a lot of woman who had PCOS also had anti-thyroid peroxidase antibodies. I could never think of or find a link.

This paper I just found says, YES, there IS a link between the two, and it comes down to this gene on the X chromosome, called FMR1.

Women who have low copies of this gene product have both manifestations of PCOS and autoimmunity (often anti- thyroid peroxidase antibodies) and have, according to the good doctor, a much lower chance of pregnancy in IVF cycles.

Just another thing for woman having these 2 issues together to check out, if you feel up to it. However, I should add, if you do discover you have this, I think it would end up being a face-palm moment because I don’t see what you can do to fix this. But still, having this information has to give you better clarity in figuring out what your path forward is.

Despite the fact that I have both PCOS AND thyroid issues, my microarray results (gotten a while back) suggest I’m normal for this gene- still, I have to confirm that with an expert. Also, I have no issues in getting pregnant whatsoever, and this paper is all about low pregnancy rates in women mutant for this gene.

But yet, I do have a little piece of my X chromosome missing. Interestingly it is the cytoband adjoining the one that has FMR1. And I’m starting to read more and more that some of the X-linked abnormalities contributing to fertility issues- I think I’m going to have to see a top notch geneticist, just for my own peace of mind.

It never ends.

And a lot can happen in one day, let alone 3 months. I should not be so surprised  (nor unhappy) on account of  the volume of change in this short time.

Stasis sucks.  Rapid change, although disconcerting, is better.

Meeting with the Genetics Counsellor

This meeting ended like my consults with doctors usually do-- with them telling me that I've already thought of every possibility and managed to test it all by myself. He looked at my 'normal' karyotype and said we could rerun it if I wanted (because one X chromosome looked a little shorter than the other) but most likely its nothing and such findings are common because of the way they do the tests.

But the one staggering thing to come out the meeting-- he told me that the fault was more likely to be the donors. My baby had Turners syndrome, one sex chromosome was missing. I had assumed that it was most likely that it had been the egg that came missing a chromosome. He informed me that in cases of Turner's syndrome, its more likely that it was the the sperm lacking the chromosome.

They assume this because a sperm lacking a chromosome is lighter, so it can swim faster than anybody else there and get to the egg first . So by this theory, monosomy is more likely to be a sperm error, while trisomy is more likely to be an egg error. If it really was a crappy sperm that  jumped my egg, then its just sheer, horrible, bloody bad luck.

People have often asked me whether my losses are happening because I'm doing IUI with frozen donor sperm and my answer has always been a very indignant negative. But now I have to wonder.

What is the advantage with natural conceptions? In a way, it is that the timing is often off. Intercourse may occur well before ovulation, and only the fittest sperm are still left swimming by the time the egg makes its appearance. In a perfectly timed IUI (where you just inject the sperm into the uterus instead of making them swim their way through a hostile vagina and through the cervix and then make them hang around waiting for the egg)  you are removing a lot of the negative selection process that allows only the fittest to survive, and just sometimes, you might end up paying for it

Still, this stuff is completely inconclusive. It very well might have been the egg (I was informed that with an X monosomy, 70% of the time its the sperm, 30% of the time its the egg).  It could still be PCOS messing up my eggs (likely explanation for both losses), it could have been thyroid issues responsible for my first loss and sheer bad luck the second time. OR--- it could be that both the thyroid and the turners are red herrings, that I have more than one big problem and there is another stealthy culprit we have no idea about just yet.

I wonder if I really have PCOS and should be on metformin.  I wonder if it would be a good idea to actually mess up the timing of the IUI a bit,  that is, inseminate the day I see surge and not 24 hours later, when ovulation is likely to occur?Or should I do an ICI? Worth the risk of a BFN? I wonder if I should be changing donors, though at this point there is no logical indication for that.

I have no idea what is the best route to take.  Despite the science and all the information I have (far, far more than the average person would in this position), the path forward is still unclear. I'm horribly aware that I'll have to take another leap of faith, knowing that another crash landing is highly possible. 

ARGH!!!!!!!!!!!!!!!!!

Shattering my preconceived notions (karyotyping results)

I got the karyotyping results back and they were what I had been praying for since I heard my child's heart had just  stopped- a chromosomal abnormality, Turners syndrome (45 X0).   It does not seem that way, but I actually got lucky. Turners is a genetic condition with wide variation. In the least severe cases,  the child can survive, but have some serious physical issues, including heart defects and sterility.  Chances are, had this loss not occurred, I would have detected it in  the 5 month ultrasound and would have been faced with the agonizing decision whether to terminate or not. I thank god, the universe, whatever, that it did not take me to that place.

I would put this down to really crappy luck, except, though, as an effort to determine the PCOS diagnosis, we finally tested my AMH.  To my absolute amazement, it came back  on the low end, at 1.1 ng/ml. The reference range for the testing lab is 1.23- 8 ng/ml. AMH is touted to be the most accurate predictor of your ovarian reserve. The lower it is, the fewer eggs you have and the closer you are to menopause. My value, while not abysmally low, indicates that my ovarian reserve may not be as good as I thought it to be.

What this has told me- don't have preconceived notions about your own biology. I always thought that I had plenty of good reproductive years left. My grandma gave birth to my dad, her 9th child, at 45.  My cousin conceived her one and only child (a perfectly healthy boy) at the age of 43!  My mom got pregnant every time she wanted to, and produced 3 healthy children. Reproduction is NOT an issue with my family. When I had confessed my plans to that cousin who reproduced  (by accident) at 43, she tore into me for not waiting any longer, because according to her, I could have have done this comfortably even when I was skimming 40, given our history. At that point, I thought I could too. Now I don;t know anything anymore.

We have not yet confirmed that its a failing reserve we are dealing with here.  Overall, my test results can be summed up in one word- confounding. I'm baffled, nothing seems to add up.Adding weight to the PCOS diagnosis,  I have high-ish male hormones (though still within normal reference ranges). PCOS is associated with insulin resistance, with fits with my family history of type 2 diabetes. Because the universe has decreed that nothing should ever add up, I have the opposite,  insulin sensitivity- low insulin, normal sugar in fasting levels. With respect to ovarian reserve too I'm scratching my head.  At the last test around 4 months ago, the other good indicator of ovarian reserve, antral follicle count came back ridiculously high at 34. So we don't have the full picture yet, we need to determine if I have PCOS, or a close-to-failing reserve. Of the two problems, I'd pick PCOS I think, though its choosing between the devil and the deep sea.

Sometimes, things happen that really make you wonder if there is a gran plan to things, even if  a particularly perverse, slightly evil one. The day Turbulence was conceived, something told me it was a girl. After the loss,I've been praying it was a boy because then I thought, for some weird reason it would not hurt so much. It also it takes the guesswork out- if your karyotyping results are a chromosomally normal female, you will always be left a little in doubt, it might have been your cells they examined by mistake. But all in all, I was really anticipating an answer that would definitively give me the gender of my child. I've even been very mildly obsessive about this point.  When I got this result, I started laughing (the alternative was to cry). With an XO genotype, my child was essentially genderless.  Talk about the universe telling you, in a creative, slightly evil way of course, that sometimes, there are no answers.