Understanding my infertility: four years in retrospect

When I had my first miscarriage and then my second in rapid succession, I had no idea what was going on, and I made truly valiant efforts to understand. I went off on a lot of tangents, and some of them (the Vitamin D deficiency, understanding the connection between Vitamin D and AMH, the thyroid autoantibody issue) yielded a lot of valuable information. There were some indicators that all of these (the vitamin D deficiency combined with the TPO antibodies, often seen in women with PCOS) may be indicative of a very low level of autoimmunity that may have interfered maybe oh-so-slightly with the progress of a pregnancy, but at the end of the day, I think these things were not my central problem.

There are two aspects to egg quality, both of which decline with maternal age. One is the state of the egg cytoplasm, which has all the mitochondria and the nutrients required to survive, divide, and thrive for the first 8 days of life by itself. The second is the chromosomes itself, and this is governed by the meiotic division process where your 46 chromosomes are divided into two sets of 23 chromosomes each. I talk about how one or both of these may be affected in the "Science of Infertility" section.

What was my problem? My cytoplasm quality was, by all accounts, really gosh darned good. It may be that I have an issue with the meiotic chromosomal division process, as a result of which a high number of my eggs are aneuploid, and I may have come into this problem (which is usually seen in women in their 40s) ten years or so too early. Compounding the problem may have been my "superfertility," which may have caused my rather stupid uterus to implant embryos that a "normal" person's uterus may have rejected. I have come to these conclusions based on the following statistics:

• My pregnancy rate was 75% (3 out of 4 unmedicated cycles), which is FAR higher than the figure (20%) reported in "normal" women. Two of my three embryos were shown to be aneuploid, and one of these aneuplodies was a Trisomy 4, which is extremely rare because embryos with a trisomy of this ginormous chromosome almost always fail to make it to the blastocyst stage, or after, fail to implant or grow. 
• Normally, the implantation rate for high-grade blastocysts is around 40-50% (i.e., 1 out of 2 blasts is likely to implant). The implantation rate for my high-grade blasts in women with "normal" fertility (the two surrogates) was far lower (1 out of 5 blasts, from 3 transfers).  

This suggests that most of my embryos were abnormal, and I kept implanting them anyway. This pregnancy may have come about because J's uterus could perform the selection that mine could not.

Had I not the "superfertility" issue, I may have just taken much longer to get pregnant, but may have stayed pregnant when I finally got knocked up. That would have been so much better, but as I gaze at my baby girl, I'm still fine with this version of events.

Now WHY I had the meiotic division problem is really the gzillion dollar question, that remains completely unknown. There appear to be no biomarkers or tests to indicate this. One has to wonder if the common problems seen in infertile women (The MTHFR mutation, the PAI variant, various autoantibodies) are biomarkers (indicators) for this issue, or are linked to it in some way, but nobody has ever looked at these particular questions, I think.

The other thing I wonder if there is a "cross talk" between my embryos and uterus that was messed up, and a developmental "brake" that malfunctioned in my embryos. Each time I ever got pregnant, it was an ovulation from my left ovary. The one time I failed to get pregnant was a right ovary ovulation, and honestly, I fail to see how that embryo could have been more messed up than the left ovary-derived Trisomy 4 embryo that implanted in my next attempt.

During IVF, I asked the embryologist to culture the eggs from my right and left ovaries separately, and the results were interesting. Normally, around 40% of fertilized eggs become blasts, and I saw this in my right ovary eggs. In contrast, over 70% of the fertilized eggs from my left ovary became blasts, which is far higher than normal. My daughter (feels SO amazing to say that), came from a right ovary egg. All this makes me wonder if the fault (for the messed up crosstalk between the uterus and the embryos) is a problem that is a problem specifically in the eggs of my left ovary. Of course, this last bit is wild speculation (even more so than the first bits, which are a lot more likely). 

There...the last 3 paragraphs will probably give everybody a headache, but I had to put down my thoughts for posterity. There is a part of me that wants to go back and do research on this issue, because I feel so passionately about it. I've actually been thinking about whether there are openings at RMA-NJ (because they are such a research-oriented fertility group).

Anyway...all is well that ends well, and I hope this recounting will be of use to somebody someday.

Gauri

She escaped the NICU on Monday (after spending 4 days in there), came to my hospital room on Monday, and we were discharged on Wednesday! We're home and are slowly settling in. The discharge day was especially rough...Hiranandani may be a nice hospital and the nursing staff is amazing and the doctors are pretty good, but they really don't pay any attention to infection control by keeping sick babies away from healthy babies: I was ordered to take her down from my nice clean hospital room to the OPD where we were surrounded by wailing children. I finally got to see the doctor, and when I was in the room with him, in came a baby with the viral flu! And all the doctor did down there was weigh her and pronounce her perfectly healthy.

The good news is that she is perfectly fine. The sucky bit is that I'm mildly ill, as is my father, but with different infections. I usually *never* fall ill, but given the stress of the first few days and the sleep deprivation (I also had horrible insomnia while being bone tired), I developed up a throat infection that has been slowly progressing. I was talking care of her while wearing a mask and suppressing my dry cough, but now that I'm bringing up phlegm every 15 mins, I've been barred from taking care of her.

She looks serene in the above shot (deleted), but this munchkin has a really mobile face...when she is awake she goes through a range of expressions that are amazingly comical. She smiles a lot in her sleep and while awake too...my favorite is the smile she gives just before she opens her mouth (like a shark) to attack that nipple.

I can't wait to get better, so I can be the one spending all day and night with her again, sans masks or worry.

Update

Sorry, this post is from my phone as well, so no pix. It kept telling me to download google plus, and I did, and it is still not working. Blaargh.

About my little miracle:At first, everbody thought that the respiratory issues stemmed from the c-section. However, soon after birth, it became increasingly apparent that Gauri had a infection, which, from the timeline, looks more like it was acquired in utero (the pediatrician says he sees this sometimes in babies born of surrogates--that is why he started antibiotics so very soon, which turned out to be the right call to make). It responded to antibiotics, and her respiration stabilized within 36 hours, letting them start feeding her.

She is now up to full feeds (she seems to be a good eater, knock on wood) and will be discharged to my hospital room tomorrow, where her antibiotics will have to be continued. Poor baby has been stuck with an iv in three different spots already, and I'm so sorry for that, and for the fact that she had this infection to start with.

Can't wait to get out of the hospital and go home! They are taking good care of us though, and NICU staff are awesome...I'm pretty impressed.

It is a girl!

Gauri was born yesterday evening: 5.5 pounds and a miracle all in all. Great apgars. J came through the c-section fine.

Will post about how things went down soon: she is doing well, but there are mild respiratory issues (mild to moderate transient tachapnea and maybe the beginnings of a lung infection) that are keeping her in the NICU.

The poor little thing has only saline so far: they will start feeds only when the respiratory rate stabilizes, and I'm praying that happens by tomorrow: she was started on antibiotics by the neonatologist within 12 hours of birth. The mildly high respiratory rate has not worsened, but it has not improved significantly either.

But she is beautiful, fiesty, alert, and fairly stoic about all the indignities we are subjecting her to.

Pics, more details, updates coming soon: this is posted from my phone.

To all my readers who have helped me cope and survive though this winding road to this beautiful destination, from the bottom of my heart, thank you.

No date set

I know some of you are checking back in for updates regularly, and I just wanted to keep you all in the loop: there is no date set for delivery. There was one (it was supposed to be the 9th), but it got scrapped. Long story, but I had little to do with this decision. J will come in for a checkup on the 9th, which is 37 weeks exactly, and the OB will decide what to do then.

I am trying be zen about things, but I will be slightly on tenterhooks till she gets checked.

It is really too bad I stopped working on the 1st of April, but the problem about that job was that it was all consuming, and I did need time off to prepare for various things.

With all this time on my hands, I really need distractions. I am reworking my way though the seasons of The Office (maybe my all-time favorite show, though I do have a lot of those). Fun ART-related piece of trivia: California Cryobank gives you the celebrity lookalike for a particular donor, and the celebrity with the most look-alikes in the CCB donor pool is apparently is John Krasinski. Sigh. That man would probably make very cute babies.

Wish me luck with the staying distracted!

The homemade goat milk formula revisited

This is a super technical post, and will be useful only for those who want to come up with a homemade goat milk formula.

First, here is an important point to take note of: Babies allergic to cow milk can ALSO be allergic to goat milk. The incidence of goat milk allergy and its severity relative to cow milk allergy appears to be a subject of some controversy. As previously noted, goat's milk has really low levels of the main culprit implicated in cow milk allergy, A1 casein, although it does have an another allerginic substance, beta-casein. I kind of got cross eyed when I tried to figure out what percentage of children with cow's milk allergy are also allergic to goats milk. One study puts this at 26%. There are also studies that show that infants that are not allergic to cow's milk may be allergic to goat's milk.

However, overall, studies as well as anecdotal evidence suggest that goat milk allergy/intolerance is far less of a problem than cow milk allergy/intolerance. It comes down to how your child responds to it: many children who are miserable with cow's milk fare very well when they go to goat's milk. Also, food allergies are insanely complex: I was struck by one story I read a long time ago on Amazon. This child was having issues when on a cow milk formula, and they switched him/her to goat's milk and  found a huge improvement.  At the same time, they were having him tested for allergies, and testing revealed that he WAS allergic to goat's milk (based on IgE, I think). They then took him off it, but what was surprising to me was that they noted a real improvement in symptoms when he was switched to goat's milk.

I tried to find where I had read this, but was unable to. The point of this is it may be better to see what your child tolerates best, rather than just looking at what the clinical testing reveals. Sometimes, only one clinical parameter (like IgE levels) may not provide the full picture. This point is made by Dr. Sears, who states that clinical studies about goat milk allergenicity really do not appear to correlate with parental observations as to how well it is tolerated.

However, keep your pediatrician in the loop and always proceed with caution when introducing something new: anphylactic shock has been observed in very rare instances in response to a milk allergy, and there has been one documented case of it occurring in response to goat milk. However, I would emphasize that such a situation may be exceedingly rare.

Also, while we spend so much time talking about allergy, keep in mind that true cow milk allergy is low in frequency: maybe only 2% of the population. Even if you suppose this quoted study under-represents this issue and you double this figure, this is still not a very widespread problem.

The majority of the population should do okay with either goat or cow's milk. However, goat milk has some advantages, and moreover, most formula makers have made some really poor choices when coming up with baby formulas (even the organic ones), and hence I would want to go with a homemade formula.

Most of this goat milk formula recipe comes from the one recommended by Joe Stout from Mount Capra. The first thing I did when I was analyzing his formula was to make sure the protein level was okay, because goat milk has about 3 times the amount of protein as human milk, which can mess with a newborn's kidneys.

The biggest issue in coming up with a formula to replicate human milk is that the levels of the various components of human milk can vary, apparently (I have not verified this statement myself). I found one study which stated that human milk contained about 1.1 g protein/100 mL.  Based on my calculations, the amount of protein suggested for use on the Mt. Capra site (1 scoop Myenberg's powder/8 oz) would deliver a little more protein (1.7 g/100 mL).

I communicated this to Joe Stout, who very kindly explained that trying to come up with the "correct" amount to mimic that in human milk is a crapshoot, because the composition of human milk can vary.

Moreover, formula manufacturers have to follow an extremely unclear system (or so I think):
Based off of the regulations in the 1980 Infant Formula Act, the infant formula must contain at least 1.8 grams of protein and no more than 4.5 grams of protein per 100 kcal formula.

The fact that they did not specify this per volume, and did it per 100 kcal of formula,  is rather insane, I think. This system is immensely difficult to follow and allows wide variation, and I decided to go with a slightly different approach.

I tailored everything to mimic what little we know about human milk composition, on a per volume basis, and I used most of the calculations specified in the Mt. Capra formula. The end result may not resemble everybody's milk, but atleast it resembles somebody's milk. The thing to remember is, no matter what minor variations there may be in the protein composition between formulas and even in different human milk sources, babies do just fine generally on all of them, unless you really overshoot or undershoot.

It would be a smart idea to take a formula recipe (this one or the Mt. Capra one), as a starting source and modify it slightly if required, based on your baby's response, growth, and general well being. 

Here is a formula, if one is making it with Myenberg's goat's milk powder. Note that ingredients can be purchased from iHerb or Amazon.com

Notes:

• For people confused about ounces and mL, 1 oz = 28 mL. 
• The amount of goat milk powder added is not set in stone:  I was planning to start with 0.7 scoops per 8 oz, but I quickly had to work up to 1 scoop per 8 oz (this delivers 1.7 g protein per 100 mL, which is a bit more than human milk (1.1 g/100 mL) or the Nestle Nan formula (1.53 g protein/100 mL) she was originally on.
• Note that if you add 1 scoop of Myenberg's, you would have to decrease the amount of lactose to 2.26 tsp per 8 oz. You can slightly adjust the lactose as needed based on your baby's response (for example, if he/she has green frothy poops, they may be getting more lactose than they can handle comfortably: this was the case with Gauri, and I reduced it to 1.75 tsp lactose per 8 oz, and the greenish poop issue went away, and the gassiness also reduced slightly.
• Alternatives to lactose include turbinado sugar, maple syrup, or organic brown rice syrup. I prefer lactose as it is what is present in human milk, and it helps in the establishment of a healthy normal flora (this is incredibly important). The reason that formula companies use other things (corn solids, maltodextrin etc) is because they are cheaper. When making your own formula, unless your baby shows signs of intolerance, lactose is a good choice.
• Blackstrap molasses (NOT INCLUDED IN THE FORMULA CARD ABOVE) supplies minerals and B complex vitamins. It made my newborn daughter's poop green, suggesting that she was getting too much iron, so I dropped it like a hot potato. The Mt. Capra formula uses it. It may be more suitable for babies over 3 months of age, I think.
• I don't like this multivitamin supplement(Country Life baby maxi), honestly. They use cyanocobalamin instead of methyl cobalamin, and have sodium benzoate in combination with vitamin C, which drives me batty as the two can apparently combine to give benzene, a carcinogenic substance. I'm listing it here because I've found no better alternative.
• The Vitamin D dosage can be tailored to meet your baby's needs (you just need to ensure that the levels are above 30 ng/mL for optimal health)
• I'll be writing a blogpost on the probiotic (Biogaia Protectis) soon.See here.
• I added homemade organic ghee as an experiment, and to provide high quality fats. Interestingly, it seemed to increase the frequency of poops per day, from 1 to 2, which was nice, and unexpected side effect. Turns out ghee is used in ayurvedic medicine to treat constipation.
• Quick tips to make this formula: Use a Pyrex 16-oz measuring cup (this fits in the Phillips Avent sterilizer). Sterilize all bottles, cutlery, whisks, and measuring spoons (I use steel ones). Boil filtered water using an electric kettle (do this many hours before preparation, so it cools enough). Add the ingredients (goat milk powder, lactose or another source of sugar, oils). Add a little warm to hot water, and make a super concentrated solution (you would have to use a spoon or a whisk to dissolve the lumps). Then make it up to 16 oz, and distribute into bottles (I highly recommend the PURA KIKI steel bottles), and store in the fridge till use. I only make little more than one day's worth at a time: I make 40 oz using my 16-oz measuring cup thrice.

Update

My mom went and had a really long conversation with the OB, and got the true picture of what happened in the last few days. The situation (and getting the details we did not have) was reassuring: her bp was down, and she has been sent home with beta-blocker pills.

The reason I was stressed out yesterday was I had NO idea what was going on: I did not know if her BP had stabilized, I did not know if her infection had cleared, or even what sort of infection she had. Even if she has no access to decent care where she is now, she is atleast stable, and has promised to come back in time for her weekly appointment next week.

We now have to set a date for induction. Unfortunately, we cannot wait for long because her home environment is not the sort of place you want to be in, in the event of any emergency; I've driven there; getting vehicles in and out is a nightmare, it is far away from the hospital, and the local medical care is definitely un-vetted  and far from ideal (it is the local clinic in a seriously poor neighborhood). So we will have to pick a date for stuff to happen at or close after 37 weeks, which is the 9th.

I'll be so very glad when this is over, hopefully, with a healthy baby in my arms. This is when knowing the gender would have been a little useful in making a decision. Have you guys heard about the "wimpy white boy syndrome?" This is a term that may be somewhat hurtful if bandied about in the NICU; don't know who is the insensitive genius who came up with it. Basically, it has arisen from the fact that, in general, girls mature faster than boys, and the maturation in utero also depends on race. White male babies are the slowest to develop and hit all the landmarks (lung maturation and various reflexes, including the suck-swallow-breathe one). My baby is half-white, and if it is a boy, the odds of him needing those last 2-3 weeks more is higher, give the race-specific data. I have NO idea what the influence of his Indian genes would be: Asian, black, and white babies have been studied, but not south-east Asian. Irrespective of race, it is a girl, we could, in theory, breathe a little easier about inducing close after the 37-week-point. But bleh, this is India, so I can't bloody find out.

Sigh. But still, overall, I can breathe again. Yesterday was rough.

In need of sedation

I found out, mostly because I had an intuition that something was off, that J discharged herself against medical advice, and has gone home. Nobody even bothered informing me of this: I found out because I asked.

I don't know her medical condition and what was done in the past 4 days when she was in the hospital. Right now, I have to wonder if the baby would be safer out of her than in her, but we have to wait to talk to the OB to figure that out.

I have to take really deep breaths and pray that everything will be okay.