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?

Fertilization report

Things are still looking good: Turns out I had 19 eggs, 15 of which were mature (M2).


16 of them became 2PN embryos (i.e., they fertilized)!!! All my M2 eggs, barring one  large "cyst" fertilized. Heck, even my immature eggs (M1), a total of 2, fertilized.

That is a total fertilization rate of 85% (93% for M2 and 100%, for M1), which is at the upper end of the ICSI range (70-85% of total eggs). Compared to the last IVF, where the overall fertilization rate was 29%  (75% for M2, and 0% for M1), this is awesome.

I also asked my RE to try an experiment: to dilute, aliquot (i.e., divide), and refreeze the sperm, and see how many survive per aliquot. This would be interesting, and may work for repeat IVFs, and is a great way of thwarting the evil sperm banks, who charge a fortune per vial, and for every service they can dream up. While this would not be advisable for IUIs or ICIs, it may work for IVF. This was my backup plan if I decided to go for natural cycle IVFs.

Now begins another stressful period- waiting to see how many will make it to blastocyst.

I also have OHSS, and yesterday was absolutely miserable. Today is slightly better, but I'm still as weak as a kitten.

But I've been wanting to say this for a while: despite everything I have gone through, I am a lucky person, when it comes to my family. My parents are the most amazing, selfless people. I met a woman recently at the fertility clinic. She was older, unmarried and wanted to freeze her eggs (no insemination). She told me her mom stopped communicating with her once she started going ahead with the IVF process. My mom, on the other hand, gave me all my injections (even the trigger at 3:30 am, due to which she had a mostly sleepless night), has drawn blood for me at home to send to the path lab, and was allowed into the OT to hold my hand when they put me under. And she has done all this without complaining, ever. Even though my plan wasn't her plan for me. I hope if I get children out of this journey, that I will be able to manage even a fraction of what my parents have done for me.

Retrieval update

It is not often that I get to post awesome news... If I wait till tomorrow to post, things may become less amazing again- so without further ado----They got 19 eggs! And a lot of them were very easy to obtain, as opposed to the last time, which was apparently a nightmare of flushing and re-flushing in the hopes of getting something.  This hopefully is a good sign, as apparently, the more immature eggs remain stuck to the follicle walls, resulting in the so-called empty follicle syndrome (Dr. Sher has a useful blogpost on this).

Dunno how many will be mature or will fertilize, have to wait till tomorrow to find out.

I posted today for one reason- I'm determined to celebrate any positive news, for as long as the universe lets me enjoy it. Find joy now- that is  my new, hard-learned philosophy.

IVF #2: One day from trigger

According to my doctors, my response has been *much* better than the last time.

I'm on CD13, and the 12th day of stims. I have around 16 follicles growing; around 10 in the left ovary and around 6-7 in the right ovary.

All 10 follicles in my left ovary are marching in ranks, they now range between 17-21 mm, and have been synchronous from the start. Unfortunately, its a different story in my right ovary, while the follicles within are synchronous, there the average follicle size is around 13 mm.

Basically, my right and left ovaries have not been communicating. My left ovary, interestingly, has always been the dominant player, atleast 2 of my 3 pregnancies came from this one.

E2 levels over this cycle:
CD08 E2 = 324, LH = 0.82
CD11 E2 = 1501, LH = 1.02
CD13 E2 = 2574, LH = 0.45

The last value is lower than what I expected. My RE, who uses a particular lab said they had been reporting lower than expected values all day for different patients, which makes her think that there are some testing-specific issues, and this crops up from time to time. I hope to god that is indeed true and my level is a bit higher than this.

Assuming a peak E2 of around 230 (remembering this from my IUI days), I have around 12ish follicles. Hopefully of these have pretty little mature eggs within...one can hope right?

Anyway, the truely cool part- all of this is on a MUCH lower dose of stims than the last time.

Last time, I was stimming with 300 rFSH for the first 4-5 days and 450 IU FSH and 300 IU LH (thanks to the menagon, which is equal parts of FSH and LH) for the remainder. It was like getting hit with a Mac truck of hormones, the multiple injections were a trial, and I had the mother of all breakouts. My EWCM abruptly went away around the 10th day of stims. And most importantly, though I got 11 eggs, only 3 managed to fertilize and only one made it to blastocyst.

This time, its 150 IU FSH/day, with an additional 75 IU LH on the last day of stimulation. With this itty-bitty dose, my response is similar, if not better. I have more follicles (albeit with a slightly lower E2), I have not broken out. I've had EWCM all throughout.

So far, this is what I am really pleased about, that I have had a better-looking response to a much lower, more physiological dose. There is some hope here now.

The biggest difference between this cycle and the last is that my LH levels this time around have been FARR lower. We'll see how that shakes out, in terms of a response.

Trigger is early Monday morning, at the ungodly hour of 3:30 am. All I can do at this point, is pray.

Your antral follicle count could vary depending on....

I'm now five days in to my IVF cycle. On CD1, I went to my RE's for the baseline scan. I was expected an antral follicle count of around 25, because that is what two scans in the past few months have shown.

To my dismay, this scan showed an count of around 16. I was depressed and did not know what the heck was happening. I had a scan at another place that had a prehistoric looking setup, and the count (after 1 minute of examination) was 15. This prompted a major crying jag and wondering if I should halt the IVF because there was something funky at work...again.

But then, a confirmation could only come from the place where I had  done the last scans, which  had  a much fancier 4D machine. So, I took myself back to the other place, and there the scan (done by another operator, as the ) revealed a count of 24. 

In other words, in the same cycle, 2 days apart, my counts were 16 or 24, depending on the machine used (!!!)

I just also realized...my big "drop" in follicle counts from 30 to 16, which I had thought was so momentous, and what I though represented a big shift in my physiology, may just be attributable to the machines used. A face palm moment, to be sure.

Here is a sum up of the scans I've done:

August 2010: San Diego RE, Dr G: 33
December 2010: India, 4D machine: 30
Mid 2011: New York, 2D machine Dr. L: 16
Late 2012: India, 2D machine, Dr. M:13
Jan 2013: India, 4D machine: 25
Feb 2013: India, 4D machine: 16 (big drop in the AFC in my left ovary)
March 2013: India, 4D machine: 25 (phew!)
June 2013: India, 2D machine, Dr. M: 16
June 2013: India, another 2D machine: 15
June 2013:  India, 4D machine: 24.

Note: what is really unknown here is what kind of machine my San Diego RE used. But, I have to give credit where it is due, I LOVED this guy's setup. Having gone to multiple different clinics around the world, I have to say that they had the most organized, systematic way of doing things. Every ultrasound scan was monitored by a nurse (standard practice) and the details were recorded in a form created for this purpose (only they did this). When I got my medical records from him, the minute details of each ultrasound I had ever done was printed out, without me having to memorize it.  Everybody does more or less the same thing, but what I am coming to value more than anything is the attention paid to the little details.

But I digress: here is the sum up: my ovaries have never stopped looking polycystic, or rather multi-cystic. I think that there could be a mild inverse correlation between my vitamin D level and my antral follicle count (in other words, the higher the blood Vit. D  level, the lower the number of AFC recruited), and there was a theory for that, but the drop may never been as dramatic as I thought it was.

I asked the doctor at the place with the fancy machine why there was a difference between 4D and 2D scanning, and she said well, the ovary is a 3D round structure, so  its possible that a 2D scan may miss some.I looked up papers on this subject which said that the fancier machines may be better at getting an accurate count in somebody with a higher AFC.

 The more you learn, you realize how little you knew. But anyway, this cycle is underway; wish me luck!

What matters in an antagonist IVF protocol

There have been many, many studies conducted to optimize the IVF protocol. I looked at some of the questions that seemed relevant to my situation, and this blogpost discusses what I found.

Fairly conclusive: Stimulation  with a lower dose (150 IU follistim/day) may be a good idea

• Study 1: The proportion of chromosomally normal embryos was higher in patients subjected to a mild stimulation (150 IU/day, antagonist started when lead follicle reached 14 mm) than in those subjected to a convention stimulation (long term downregulation with agonist, 225 IU FSH/day).
• Study 2: Another group (which compared 225 IU vs. 150 IU, with both groups receiving agonists) reported a similar finding, and also observed that the fertilization rate was higher.   

Note: As expected, the low stimulation dose elicited fewer eggs, with a greater frequency of cycle cancellation. But here is the striking part: the total number of chromosmally normal embryos was similar between the two groups.  So basically, stimming with a higher dose puts your body through the wringer
for no real advantage and even a possible disadvantage in that it may decrease the quality of the embryos you produce and make you go through the emotional and financial turmoil of more embryo transfers and possibly pregnancy losses, while not affecting the live birth rate.

No real difference evident:  Comparison of Follistim and Menagon

• Study 1: Study in women of advanced reproductive age: Comparison of Follistim and menagon on aneuploidy rates:  follistim is slightly better, but this difference did not reach statistical significance. The clinical pregnancy rate was significantly increased in the Follistim Group

Mixed findings: Agonist vs. Antagonist

• Study 1: The agonist protocol produces more embryos, but is associated with a lower clinical pregnancy rate.
• Study 2: No difference in the clinical pregnancy rate observed, but the antagonist protocol conclusively reduces the risk of OHS.

Conclusive: The antagonist dose can be reduced

• Study 1: Giving the antagonist (0.25 mg/day) daily or every other day does not appear to make a difference.
• Study 2: Doses of 0.25 mg/day (standard) or a 0.125 mg/day dose of the antagonist elicited similar results in IVF

Difficult to figure out: The best time to start giving the antagonist

The choices are Day 1-4 (with the FSH), Day 6, or individualized (when the lead follicle reaches 14 mm).

• Study 1: A study comparing the day 6 and the individualized protocols found that the individualized one worked better (generated more oozytes, while requiring a lower amount of FSH) 
• Study 2: No difference seen between Day 1 start and a day 6 start.
• Study 3: A day 4 start was better than a day 6 start. 

 Difficult to figure out: To supplement or not with LH?

• Study 1: A analysis of a large number of clinical trials examining the effect of LH supplementation in an antagonist protocol showed a benefit (increase in pregnancy/live birth rate) only in the poor responder/pregnancy loss group.

So--- based on all that, all I know is that a low dose FSH regimen is a good idea, and I should not get greedy and increase this, because quantity (growing follicles seen on the ultrasound) is not what matters, it is the quality of what is recovered in the end. Additionally, I could take the antagonist every other day without it making a difference.

Where I am in the dark about: When should I start the antagonist? Should I take any additional LH? In other words, am I a poor responder, who may benefit from a little, but not a lot of it?

Here are my choices....

Protocol choice 1
Start Follistim (150 IU/day) CD2 onwards
Start antagonist (0.25 mg every other day) on the day when the lead follicle hits 14 mm.

Trigger 10,000 units HCG

Pros: super easy on me, only 1 injection/day for a while.

Cons: A higher LH level early on may be detrimental.

Protocol Choice 2

Start Follistim  (150 IU/day) CD2 onwards
Start antagonist (0.25 mg every other day) CD2 onwards
Trigger 10,000 units HCG

Pros: Not so many injections

Cons: A total lack of LH early on may be detrimental.

Protocol Choice 3

Start Follistim (150 IU/day), CD2 onwards
Start antagonist (0.25 mg every day) CD2 or 3 onwards
Low dose Luveris (37.5 IU/day) CD4 onwards
Trigger 10,000 units HCG
Pros: Everything is very controlled; you cut off LH almost completely and supplement with a measured small quantity every day. This has shown to do no harm, and there is the slight chance it will help.

Cons: Luveris is expensive. Many more injections required.  Plus, it comes in an ampoule form containing 75 IU, which means I'd either waste half an ampoule, or have to take 1 injection every 2 days.

If anybody can wade through this knowledge dump and offer any feedback after, please do. Please, please, please, share your own experiences with regard to any of the points discussed in here: FSH dose, Antagonist dose and regimen, and the choice of adding back LH.

Moving ahead...finally

First, this is to the person who commented in my last post that myo-insoitol helped with anxiety-that is one of its very well demonstrated uses, apparently.

I'm ready to move ahead with the next step down this road, another round of IVF.

There has been a reason for this sort of extended break; I started talking to somebody through the Indian arranged marriage route a few months ago. I'm always being introduced to one person or the other, usually, I'm bored senseless with 5 seconds of looking at their profile or 10 minutes of conversation with them. This was different...we hit it off and talked to each other extensively for months. For once, I knew that many of the ingredients of that magic mix were here. It was like sighting a unicorn, frankly. He came around the world just to see me, and we hit it off.

Everything was going great, until I sat him down and dragged out the gory skeleton of Plan B, telling him everything that has happened in the past 3 years. I couldn't go ahead without telling him, keeping him in the dark about something so big. For some reason, I thought he could take it, because at the surface, he seemed like a truly unconventional person. But he couldn't, and broke things off. I'm not going to say all of this did not hurt, but this was also the ultimate litmus test to see if  someone is capable of going through some hard times with you, and he turned to not be that sort of person.

I liked a lot of things about him a lot, but I think it hurt more because going ahead with him was the easier way of doing things, not just for me, but also any children I might have and my family.

So now, its back to Plan B. I keep thinking about why things have been so hard. There are 2 ways to look at it; there is something insidiously wrong that is not showing up on any test and will keep screwing things up, by screwing up my eggs.

Or the second, that I've just been thwarted by really bad luck so far.

The first pregnancy, where I lost a chromsomally normal fetus could have been a hostile gestation because of an angry immune system (because of the vitamin D deficiency plus the thyroid). The second, when the thyroid issue was fixed, may have been doomed from the start because a gimpy X-chromsome lacking sperm jumped my poor egg (80% of Turners cases are male-linked apparently). Then, when I got too vitamin D high during the next 2 attempts, things went to hell; failed to get pregnant once, made an egg with a triploidy the next time. The failure of my IVF could have been that the agonist protocol was unsuitable for me, and the menopour made it worse, and my reproductive system were still in that too high Vitamin D-induced funk.

Now, I've been taking folic acid (5 mg/day), vitamin D (2000 IU/day instead of 5000 IU/day), myo-inositol (1000 mg/day), and dear god, I hate to say it, but things are looking good. Of course, things may just go to hell the next cycle because I'm picking it to have my IVF in. God knows what kind of game the universe is playing with me, I'm starting to feel like something my cat plays with...catch, release, catch, release...argh!


Anyway, the IVF will start soon, have many details to iron out, but it will be a lowish follistim dose +  the antagonist; when we start giving the antagonist is the gzillion dollar question, that is what I will have to thrash out with my RE.

More soon, and my pace of blogging and hopefully blog reading will pick up. I'm so sorry for having been such an awful blogger lately.