Investigating miscarriage

This is a response to another comment left on my 'Science of Infertility' page

Hi, my husband and I have been ttc for almost 2 years. I've had 2 m/c in the past year and am desperate to figure out why...my bloodwork came back normal and now i'm scheduled to have an hsg test in the next week or 2. I had to beg my gynecologist to put an order through for my Vitamin D levels. Finally she did and they are low (18L). Do you think this could be why I've been miscarrying? Should I still do the HSG testing?? Thanks for any help/advice! 

This is an impossible question to concretely answer. Most doctors would shrug and say, who knows? Me, I try to wildly speculate. But you need an incredibly detailed medical history to speculate and I do not have it for the commenter.

I can only offer my first miscarriage (the one that is still a complete mystery) try to speculate if vitamin D had a contributing roles.

This is a basic checklist one goes through, of examining risk factors for pregnancy loss. All issues were not tested, the full RPL panel covers more ground.

1) Was the embryo chromosomally normal? --Yes (no issue of mixup as was male)
2) Was there a structural uterine abnormality (determined by Ultrasound/hysteroscopy. I'm not sure if an HSG can contribute) -- No
3) Was diminished ovarian reserve a contributing factor miscarriage risk -- No, lots of eggs left
4) MTHFR mutations? -- unlikely, My homocysteine level was super low.
5)Autoimmune issues
Lupus anti-coagulant-No
Anti-phopsholipid antibodies- borderline positive then repeat negative so unlikely

Thyroid autoimmunity-yes

6)Progesterone Issues:  No, levels were excellent
7)Luteal phase defect:  borderline...11 day luteal phase in similar cycles.

8) PCOS:  Yes.

I do not know why my baby died, but I do know that a vitamin D deficiency is a risk factor for PCOS, all autoimmunity(including thyroid) as well as luteal phase defect. After becoming vitamin D replete, my ovaries are no longer poly/multicystic (My antral follicle count came down from 30-34 to around 16-18). More importantly, I consistently have a 14-16 day luteal phase.

Based on what was 'wrong' with me, do I think my D3 deficiency possibly contributed to my miscarriage? Yes. Can I be certain? Hell no. There is no way to know anything for certain.

About whether a HSG is useful: It can only be useful if it helps reveal anything about your uterus (not so sure about this) and tubes. So if you have not had this investigated, do so, because it is something off the checklist that must be crossed off.  

Also, this is by no means infallible or a comprehensive list,  but this is what I would suspect was a more likely cause depending on WHEN pregnancy loss happens.

Very early pregnancy loss risk factors: Bad egg quality (hindering growth of the embryo),  and immune factors that hinder implantation such as activated NK cells and T cells.

Mid-late first Trimester loss risk factors: Chromosomal/genetic abnormalities, anti-thyroid antibodies, and god knows what else.

Second trimester loss: autoimmune issues, anti-phospholipid antibodies, clotting issues.

Low AMH: Diminished ovarian reserve or a Vit D deficiency?

I received this email a few days ago. This post is to address this question and as well as the many people  who have come across my blog doing Google searches for "low AMH" or "AMH and Vitamin D."

"I came upon your blog while googling for information about low AMH levels, which I'm sure you know, is very difficult to find.  I'm curious whether you've found any other information about increasing AMH levels other than Vitamin D.  I was diagnosed with low AMH (all else normal) and my RE told me there is no way for it to increase and that it would only decrease.  He was pretty doom and gloom about everything.  I'm currently using royal jelly, acupuncture, Chinese herbs, sprirullina, and a general prenatal multi-vitamin.  I haven't had my Vitamin D level checked yet but am considering doing that and asking about DHEA next time I go to the doctor as I'm hesitant to add anything else to the mix right now.  Thanks for sharing your story online."

In addressing the question asked of me, I have to point out one important fact that I think falls between the cracks with most people.

AMH is a surrogate marker. Why it is considered a good indicator of your ovarian reserve is because it tells you how many antral follicles are present in your ovaries each cycle. The antral follicles actually make your AMH. So more the antral follicles you have, the more your AMH, or at least, that is the logical stream of thought. Women with a failing or low ovarian reserve have very few follicles left, so their AMH is low. In other words, the problem is not that their AMH is low, but it is that they have few follicles left.

The question is, can your AMH be falsely low? To find this out, you must have an antral follicle count done. AMH alone, or AMH + FSH/E2 cannot give you the full picture.

If you have a low AMH and very few follicles left, then the probability, sadly, is indeed that you do have a case of diminished ovarian reserve.However, if your antral follicle count is normal/good/high and your AMH is too low, then something may be wrong.

One of two possibilities may account for this:

1) The lab messed the test up
2) The tantalizing Vitamin D theory: Now----I came up with the theory only based on the finding that the AMH gene is turned on by Vitamin D. This is solid, irrefutable science here.  What is still unclear is whether a vitamin D deficiency leads to suboptimal AMH production in the antral follicles. My findings imply that it did, but we cannot rule out that the first lab really messed up my AMH test. It needs to be studied clinically.
Updated 2 years later: Yes, this has been studied, and it is now fairly certain that your vitamin D level affects your AMH level. If your AMH level is too low when compared with your AFC, Vitamin D may be the culprit.

Overall, if you have a low AMH, then your plan of action must be to test for both vitamin D and your antral follicle count.

If your vitamin D is normal and your antral follicle count is low, then that just means you do have few eggs left.  DHEA seems to have some little success at improving the success rate in cases of diminished ovarian reserve, but its horribly unclear as to what is happening. Is it increasing recruitment of antral follicles from the diminished supply left? Is it improving egg quality as well? There was a study which actually showed that DHEA decreases the rate of aneuploidy. I don't know how solid the data is, but that is tantalizing if it is indeed so.

When you truly have DOR, then it is what it is. There is no way to fix it. You can, however, improve your chances with supplements (look for the CCRM cocktail).

I'll end on this note, and this is purely an informed opinion on my part: If  you want to have a baby, it is folly not to investigate your vitamin D3 levels. Its not just to treat infertility, but it is also proving to be very relevant in preventing pregnancy-related complications stemming from infection, autoimmunity, or pre-eclampsia. Just taking supplements is not the best way to go, because you don't know how much to take: you could end up taking too little, or in rare cases, too much.  

In which I meet my future baby's half-sibling......

This, as the title suggests, is a tale of staggering cosmic coincidence. Around November 2009, I found my donor. On seeing his profile, I knew within an hour that this was just perfect for me. That moment of perfect clarity came after months of indecision and trolling entire databases of multiple banks and wringing my hands trying to make a decision. The relief was indescribable. I bought a few vials, opened a yahoo donor sibling group, and hoped that women using my donor would run google searches and show up.  Not much happened for a while.

I was also a member of Wendy Kramer's Yahoo DSR group. I never ever visited it though. One day, late at night, I was aimlessly browsing. Something made me open up that Yahoo DSR. One of the first few posts had a link to an article in Marie Claire, where this woman talks about her donor. No bank name or donor ID was mentioned, but this was what was said.

His voice sounded warm and kind. I listened to stories about his family, friends, wife, and life experiences. He said he became a donor not for the financial incentive, but to give an amazing gift to an individual or a couple, which was great news after hearing so many guys say flat-out they were doing it for the money. [A donor can make up to $100 per sample.] It was really moving. During the last minute, I had tears rolling down my face, and I knew this was right for me.  

I read this, and I was like, huh, she has my donor. I just knew.  Thankfully, the article gave her full name. I found her on facebook and contacted her. She was extremely enthusiastic and YES, we had the same donor!

She had had multiple failed IUIs at that point. She went for her first IVF a little after I went for my first IUI. We both got pregnant, she had her baby, I lost mine. But we kept in touch, though our contact has been almost nil this year.

She joined our little donor group. Quite a few other women found us as well. Some of them went on to have kids and now, all of these women are in touch with each other. Their kids will meet each other, and hopefully forge relationships.  I am so glad so many good things came out of that entirely random stream of events.

Last weekend, I went to the New York SMC conference. It was totally a last minute decision. It was a roomful of about 200 women maybe. I step out for lunch, people milling around everywhere, this woman comes up out of nowhere and introduces herself. Even though she is a facebook friend, I did not recognize her-- but it was M, with her baby! My jaw literally hit the floor and stayed there. I hung out with her, I got to play with her son who is just the most delightful baby.. it was surreal. I don't know if I can ever have a baby with my donor--- but if I indeed do get to do that, I just met my baby's half-sibling before meeting my baby!!!

I've just been floored by the incredible coincidences that keep connecting me, time and again, to M. I keep thinking, the universe must have a grand plan in engineering all of this, and I drive myself nuts trying to figure out what it is.....

Turning into a hermit again...

The last time I initiated serious planning for TTC was Jan 2010. At that point, even though I was about months away from the actual process, my routines started changing. I no longer felt like going out.  I became more of a stay-home-in-my-jammies kind of person. Now, to my dismay,  the very same process is restarting. I should be getting ready to go out and help somebody celebrate graduating. I don't WANT to.  I have done nothing the entire day other than catch up on chores, watch TV and work.  I should be getting ready to go out and mingle with other human beings. But I can't bring myself to and I'm feeling bad because there is another person inside of me who actually does want to go out, but TTC me won't let her.

I don't like this version of myself, because I'm much more of a hermit than I normally am.  And NYC is going to be even more isolating than San Diego- people go out late and they stay out till the wee hours of the morning.Nobody stays in and plays boardgames and watches movies. I'm going to be spending SO much time by myself once the TTC process actually begins- I don't want this exile to begin even earlier, but that is what it looks like its going to be.

And sometimes, I wonder for what it all is. The last time I jumped into this process, I was so very certain I'd get to take a baby home. Now, no such confidence exits, only a hope.  Its going to be a bloody scary, and quiet few months (hopefully, an entire year). Thank god for this virtual universe and you guys!

Please go give support..

Anna was pregnant with a boy when preeclampsia struck in full horrifying force at 20 weeks. She lost her baby. Her story is heartrending- please go offer support here

Thanks to the 'miracles' of science, we can now tell what genes predispose to preeclampsia. Both maternal AND paternal genes contribute. Sometimes the greater, higher risk gene actually comes from the father. Someday, I hope medical science evolves enough to the point where they include these genes in routine pre-pregnancy screens- they might help avoid such horror stories.

I'm so sad-life can be so bloody unexpectedly horrible.

Catching up

I'm amazed and gratified that this blog still gets people coming by even when there is absolutely nothing happening I am so, so very glad I connected with all of you, it may just rank among the most positive things that have happened to me in the past two years---thank you so much for being there!!

Now for a pent-up rant--- the  NYU Fertility Center has not been making me too happy. I called the last time my period rolled around to schedule a HSG, only to find out that my doctor (Dr L,the purported genius at the HSG) would be on vacation for the next 10 days. Its not the first time I've heard that either. So, I'm sitting this cycle out. I'm still not over the fact that he does not think anti-thyroid antibodies even might be a contributing factor to miscarriage and does not even want to treat with synthyroid (!!!!!!!). If I get started on my opinion of this, I may go on for a while. I pray I have the sense not to tell him how I really feel, that would be a very bad move.

The general lack of attention of detail in this practice pisses me off. Lots of little things, but one thing stands out- at my original consult, when they were counting my antral follicles, I committed to memory what numbers he came up with, but since I could not remember which ovary had how many, I asked for my medical records from that visit.   My numbers were 14 and 4. Instead of writing down the numbers the doctor had called out, the nurse decided to use adjectives (very good and normal, respectively). When I read this, my jaw fell open.Good and normal?!!!? That could mean just about anything. I'm a scientist, I know how important it is to note the details, and I know that it is something important in the medical community as well. Dr. Garzo's practice would have done no such thing. They have done multiple antral follicle counts for me and at each count, the numbers are recorded into a form meant for this purpose.Their record keeping overall was far superior, this is a far more meticulous practice. When you think about why, say, an IVF cycle succeeds or fails, its mostly biology of the patient and the suitability of that particular cycle design for that patient, but a small but significant portion is about how the staff and doctor handle the little details. I cannot say how many times I've seen an experiment fail or work based on one tiny detail - the devil IS very much in the bloody details!

Somebody asked me what I miss most about San Diego- the diplomatic answer was - the beaches, but the real answer is, I miss my RE. I miss my lovely, compassionate, infinitely smarter nurse.


As to where things stand: I'm revving up for an IUI (no meds), for the first good (based on fertility signs) cycle I see in 2012.About Plan A, the quest to do this with a real live man and not a catheter inserted by a gloved hand- its not going too well. I dated quite a bit, thanks to Eharmony, but nothing came out of it. I've had an on again-off again flirtation at work, with somebody who is a lot of fun but with absolutely no relationship potential. I spoke to (and am still speaking with) a couple of eligible Indian boys, who I'm supposed to meet in October. One of them irritates me when we talk on the phone, but he is a nice guy and my parents love him. Sigh.  The other I like and have fun talking to, but I have a feeling I'd want him as a friend but would not have chemistry when we met up. Even if we do 'like' each other, this process is very difficult. Unless I fall head over heels, committing is going to be very hard. It takes time to build a relationship, and its much harder if you are in different geographical locations.

So yeah, astrologer's predictions of marriage notwithstanding, I have a feeling I will be going to be trying to make babies with my dreamboat of a donor, who has helped  4 women produce 5 beautiful, healthy babies. I hope I'm similarly blessed someday.

Indecision 2011

Boy, you do not fully appreciate how relatively stress-free your existence is until you decide to jump back in the gladiator ring of TTCing again. I'm sitting here with this gigantic decision to make- to start metformin or not???

I talked to my Indian RE about it.  What he told me took me back to my first thought about this: he deals with a different ethnic group than REs in America and PCOS figures very heavily there.  Its not terribly surprising, you cannot throw a stone in India without hitting somebody with Type 2 diabetes- its really, really common. PCOS is related to Type II diabetes. Its all logical.

He reiterated he does not really know if metformin works. His reasoning is its cheap and safe- so why not? I'm not so sure its safe though. My body functions perfectly, medication-free right now. I'm really nervous about upsetting that cart.

The other reason I'm hesitating is that if you lined up all the possible causes of my 2 miscarriages, examining each and every detail , I'd say the highest probability is that it was the vitamin D deficiency, which *probably* made for crappier eggs more likely to have genetic defects. Its also possible that my second loss was not even my fault- It could have been the universe really not wanted me to have a kid at that point and letting the one sperm with a missing chromosome impregnate my poor egg.

For the millionth time, I'm going to discuss all the changes that have come about, when my vitamin D3 blood levels are in the 30-40 ng/ml range, as opposed to the deficiency range I was in (17 ng/ml) just post miscarriage # 2.


My bbt patterns have changed.  My temperature used to vary from maybe 97.4-96.7 in the preovulatory phase- now it flatlines at 97.3. And when I say flatline, I mean it. Maybe for one day, every 3rd cycle, a really strong estrogen surge will push my temperature down to 97.1, but that is it. Nothing can be made of it, but I think its very interesting.


Breast tenderness- nearly constant - ie- more progesterone and estrogen, overall. That is good :-)


My luteal phase has gotten longer. MUCH longer. This has to be the most startling, and clear indicator that things have changed. The two cycles I conceived in had an early day 16 ovulation, with a luteal phase of 11-12 days. If I ovulated at day 20, my luteal phase would be 13-14 days. Now, almost all my ovulations have been at day 20 or later.  The luteal phase in such cycles is now increased to 14-16 days, with average being 15. 

Luteal phase defect (9-10 days or less) has been implicated as a miscarriage risk factor, which again, is logical. Shorter luteal phases are indicative of less effective progesterone mechanisms, which is in turn indicative of poorer quality eggs, which of course means you have a lower chance of seeing that pregnancy succeed. Though to qualify for LPD, you have to have a really short luteal phase, maybe for somebody like me, a 11 day LP was probably indicative of an issue- who knows?

So basically, I really think that it was highly likely that my problems were tied, principally, to a vitamin D deficiency, that has now been fixed. What makes it even more interesting is that a lot of women with PCOS are vitamin D deficient, and I think its likely that some part of the PCOS presentation can stem from vitamin D deficiency. So- I do not know if I need metformin, and I'm really don't want to take it, but I don't want to end up regretting that I did not do it.

In less scientific matters- I'm going on a cruise in December! I am so excited and I really, really wanted to go snorkel in some really blue waters- but I calculated ahead because some dreaded instinct told me this may be an issue.... Going with my current cycle patterns, bloody AF is going to show up on the day we dock at the Bahamas! My frustration knows no bounds...Eff You Universe!

Do we listen to the experts?

About Irene, I think a facebook friend said it best- her status update was' Irene, you bore me'. Thank god for boredom. I was in the mandatory evacuation zone, I packed up, stayed with a friend, had a tranquil weekend and came home to a perfectly untouched apartment. I did get to talk to many branches of my far flung family who called up panic stricken, because of CNN,  who were making it sound like the apocalypse was coming.  The majority of the reporters, were of course in Manhattan, trying to make as big a deal as they could of 1 foot of water. It would have been funny if it had not been annoying. From what I could see, Irene did very little to Manhattan, but did stir up trouble (though hardly as much as had been anticipated) to places like Long Island. Hope everybody is ok.

Even though many of the precautions seemed over the top in retrospect, I'm glad everybody played it safe.  But that is my nature. I got to witness an interesting example of the choice between playing it safe versus the alternative this weekend.  A friend cooked dinner, and one of the things she made was fish. Since I never eat fish without first finding out what kind it is, I asked, and was told, swordfish.  I definitely would not eat that. The reason I declined was because swordfish (along with shark) is one the the fish varieties that is very high in methyl mercury. My friend had no idea about that fact, and was completely taken aback that I would not even have a tiny bite of the fish.  She was like, well, what harm can eating it once do? The answer is, probably not that much, if you are not pregnant. Mercury is deadly during a pregnancy- tiny quantities can disrupt neuronal migration and hence can cause major defects in brain development. There is that ill-understood, poorly defined possible link between mercury and autism. The deal is, once you take mercury into your body, it is very hard to expel completely.  A good portion will go sit in your cells, in some corner of your body. If that cell is every broken down and recycled during pregnancy (low probability), mercury can renter your blood stream, and travel past the placenta, where it can wreck havoc.  So there is no way I will ever eat shark or swordfish or even tuna (certain varieties are kind of high) not until I close the door on having any children in the future.  I explained all of this to my friend, who ate all the swordfish anyway, and will probably continue to do so.  She served it to everybody else there- all women. One of them asked why I was not eating fish and I told them what I had told my friend. All the  women there were of child bearing age, 4 of us were single (it IS new york) and one woman was married, and I think, from her alarmed reaction, plans to TTC soon. Nonetheless, after initially bypassing the fish, she went and ate a few slices.  Honestly, the odds of any harm coming of eating it, this once, is pretty low. But because of my training and my knowledge and my own personal history of pregnancy loss, I could not help but be alarmist. Everybody ate the fish, and I'm glad, for my friends sake, that they did.  But it struck me, that, despite knowing how bad it is (the FDA counsels against any woman of childbearing age consuming any seafood species high in mercury, and I told them this), everybody went ahead with it anyway.  Maybe they will not repeat the process, now that they know, but who can say? Overall, the thing I was surprised by that none of them knew about the dangers of mercury and certain seafoods. Making a choice is fine- its your body, your life but I just want people to be educated before making that choice.

In other news- I got browbeaten by my doctor into agreeing to get the HSG done. I've protested to him time and time again, that an HSG is not supposed to be the best test to reveal scarring in the tubes/uterus. His rejoinder each time has been, the people who are doing it have not been using the test correctly, they do not know how to read it, an HSG, in the right hands, done by me, will tell us what we need to know.  What can I say? He IS the RE, I hope he knows what he is talking about. So, while I'm with him, the HSG is what I will have. 

Gray

Big chunks of the east coast seem to be cold and gray and rainy, and in a way, it echoes my mood. Nature can be an evil, capricious bitch sometimes, I think there are no words to express the rage and helplessness we feel when babies are targeted by that capriciousness- Shannon's news has left us all reeling. But still, there is definitely room for optimism, and while the coming period might be a harrowing one, there is a high likelihood that things will end WELL. I'm praying.

I want to apologize to whoever shared reviews of their doctors with me- I've procrastinated putting it up for so long it has been inexcusable. Still, better late than never, its up now, in its own page, with plenty of room for more if others wish to contribute.

The Glucose Tolerence Test...

They ordered the 2 hour GTT for me, instead of the 3 hour.  One part of me was fairly unhappy about this because I wanted more data points and the other part was resoundingly relieved that I'd have to just give blood twice, instead of being jabbed 3 times. After the first blood draw, I realized I had never confirmed that they were going to also check for insulin, I just assumed this would be so. Nope. They just had been ordered to do the bare needful, just glucose. And they collected blood in the wrong kind of tube, so they could not even add it on. This is when I wanted to just SCREAM.  The people ordering the tests knew I was worried about insulin resistance, but no, they did not bother adding insulin to the panel. ARGH!!!!

First, before moving on to the results- When I got the glucose drink, instead of being disgusted and sickened by it like most normal people, I tolerated it just fine, because its about a slight shade sweeter than my morning cup of coffee. That was when I realized I about give my body about half (in terms of volume) a GTT every bloody day! Scary stuff.

Anyway- I passed. With flying colors. My fasting glucose was 80, and the 2 hour was  lower, at 78. These are very good numbers, my body apparently is a champ at putting away sugars.

Should I take metformin? The majority of doctors would say no. Not with such clearcut evidence that I do not have any issues metabolizing glucose.. I'm stumped, I don't know what to do.

I had a quick phone conversation with Dr. L, where he said he does not want me on metformin. He also said he does not believe anti-thyroid antibodies are linked to miscarriage, and does not beleive in treating for them. I'm glad I get to call the shots there, thats all I can say.  I then asked him, if nothing is wrong with me, if I have a fantastically good ovarian reserve, make lots of estrogen and progesterone, and PCOS does not appear to be having a negative effect on my fertility, why did I lose 2 babies?? No answers were forthcoming, obviously. I should not blame him for that, this is a situation where nobody has answers, but his confident waving away of thyroid autoantibodies irked me a bit- atleast show some degree of uncerainity, because these is evidence both pro and con for that one.  

Sometimes this certain aspects of this debate on infertility and pregnancy loss seems like an atheist, an agnostic and a believer sitting there arguing about god. Nobody has any concrete answers, but everybody sure as hell has opinions. My Indian RE would want me on metformin. About 4 other doctors have said no. I'm conflicted. 

In the meantime- I have to call and order an HSG, to make sure my 2 D&Cs left no scarring in the uterus and fallopian tubes- last thing I need, is an ectopic. This is probably the one thing I can get an answer for, though I'm dreading the test. If anybody has an HSG done, or has heard an opinion about the usefulness of this test to evaluate scarring and is inclined to share, please do so!