Tuesday, May 08, 2012

Overtesting and overtreatment by IVF specialists

I just received this e-mail from patient. He was looking for IVF treatment, and had been requested to do the following panel of tests by another IVF clinic , before going for a consultation.

For your wife,
-FSH done on day 1 or 2 of menses
-Thyroid peroxidase antibody
-Anti-thyroglobulin antibody
-Vit D 25 Dihydroxy
-Fasting and 2 hours post lunch blood sugar
-Trans vaginal pelvic USG between day 10-14 of menses.

For yourself,
-Semen analysis

Read more at www.drmalpani.com/overtesting-and-overtreatment-by-ivf-specialists.htm
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  1. I actually think a lot of the tests are a good idea, for example, AMH and follicle counts are necessary. And of course, vitamin D is a very good thing, and I am a firm believer in testing then supplementing accordingly.

    As for TSH and anti-thyroid antibodies, 10 % of all women (which is HUGE) test positive for this. Women who have ATA may have higher risks of overall autoimmunity and are also likely to have increased TSH, which puts them, according to many studies for higher risk of pregnancy loss. A TSH of over 2.5 is considered bad for pregnancy by many experts. I wish to god my first RE had looked at my TSH of 2.74 and tested me for anti-thyroid antibodies---but he did not and I turned out to have them, AND I had a pregnancy loss of a chromosomally normal embryo. It might have been subtle genetic defects not picked up by the karyotyping OR it could have been a thryoid-linked loss. I'll never know, but the intervention for thyroid is incredibly easy, safe and cheap.

    This treatment for thyroid issues (concocted by me, after reading about a gzillion studies is easy)- just thyroid hormone (with regular blood tests of TSH/ T4 and T3) and selinium and Vitamin D/prednisone (latter very optional) to calm an overactive immune system. On Vit D and thyroid, there is an interesting review linking vitamin D deficiency and thyroid autoimmunity and how they may come together to create a perfect storm.
    It definitely makes sense to me as an immunologist.

    As somebody who can afford it and does not mind getting poked and prodded, I say, bring on the tests. As a scientist and a patient who has lived through 2 painful miscarriages, I understand that we are flailing in the dark, but theoretically, some of these interventions, such as thyroid hormone treatment, intralipds, prednisone, etc may actually make the difference between success and failure.

    My motto now is, if its cheap/ affordable and many studies have shown that it does no harm, throw it in. In a game where nobody knows what is really going on, doing nothing and hoping that at somepoint, things work out is something I would not be able to do :(

  2. As long as patients understand the limitations of these tests upfront, it's not an issue. The real problem arises when you get false positives - and patients end up wasting a lot of time and money pursuing red herrings.

    It's also a question of worldviews. Some patients like getting loads of tests done - make sure you test me from head to toe, Doc. However, not everyone does - and lots of studies have shown that overtesting leads to overtreatment - not better outcomes.

    Doctors have a built in bias. They will remember the patients who do well after their "treatment" when they " fix" an abnormal test result - but patients who fail will usually drop out or switch doctors.

    Good doctors learn to be conservative as they mature !

  3. Anonymous12:31 PM

    Poor patients too learn to be conservative only when they mature! :)

    Jay, could you please look into this study (PMID: 20655528). As per my knowledge, this is the largest study conducted to find out the effect of different TSH cut-off values on conception, delivery and miscarriage. The study did not find any difference in outcome if the TSH cut-off value is set to 2.5 or 4.5. But I do agree thyroid auto antibody story is a bit different. But I have seen a couple (even more) of my friends get pregnant and carry baby to term with anti-thyroid antibody. But all their TSH is way off and they did take thyroxine supplement and nothing else.

    We do have very different world-views. I am like you few years before. But now my experience in the field of infertility has taught me to be conservative. I no more obsess about my lab-values. I try hard to listen to my body and act accordingly. Perhaps everyone will learn this with time. I think a good doctor will look at the clinical picture first and then order lab tests only when absolutely necessary and not the other way around. Age of the patient, her menstrual history and her AFC count can tell a lot about her fertility than her AMH count or FSH value. Her physical fitness (whether she is obese or thin), her hair texture and thickness and many more physical traits can tell a lot about her thyroid status. A hand shake with the patient can also give a doctor clue about his patient’s thyroid status (I recently read a book written by an AIDS specialist and I am very impressed when he stated how trivial things can give clue about patient’s disease! A good doctor will have the passion to study their patient and not the lab tests!) The place where the patient lives, her food habits, her skin colour and her daily routine can give an idea about her Vit D status. Her family history of diabetes, her age, her physical fitness and food habits can be used to decide whether she needs blood glucose testing or not. Testing to be sure will only give patients lot of heartache!

    Jay, as a scientist you know that our body is a very complex entity and all the events happening inside are intertwined and inseparable. I wonder when patients undergoing infertility take so many different things like steroid, anti-coagulants, IVIG etc! Are we really doing any good by doing this or doing more harm? We should not judge the entire field of infertility by reading real-life experiences from women who got success after doing all this. We should not forget that for every 50 woman who gets success by following unproven therapies there are 50 more woman who did not find success. Somehow when we are desperate for a baby we tend to be biased and try to see only the sunny side of the story!

  4. Pretty good post. I just stumbled upon your blog and wanted to say that I have really enjoyed reading your blog posts. Any way I will be subscribing to your feed and I hope you post again soon. Thanks!

  5. It IS a question of worldviews, absolutely. But, at the end of of the day, a lot of this is very murky, and when so much is uncertain, I want to make the decisions about my treatment myself- I do believe well-informed patients should be granted the facts and then allowed to judge for themselves.

    To anonymous: My comment on your take on the thyroid issue: the rate of miscarriage, even in patients with anti-thyroid antibodies, is still really low. The majority of women with antibodies go on to have normal pregnancies. As do the women with higher TSH, but certain studies have noted lower IQ in the offspring. As severe hypothyroidism results in cretinism in the offspring, this is not too illogical, though I suspect, the effect is miniscule at best. But, none of us wants our child's IQ lowered, even by a few points.

    But what these conflicting studies show is merely increased risk, and I'm not willing to take that risk, not when the intervention is so easy and so safe. And that is my call to make- I just believe any patient who is capable of grasping the facts should be provided those by her doctor.

    At the end of the day, when nobody has a clue as to what is really going on, the best approach is to look at risk/vs cost + safety of treatment/vs efficacy and make the choice yourself. That way, you can sleep at night.

    I have conflicting opinions on different modalities. As you said, we are not really in a position to gauge whether many of these can hinder or help, but then, we have to make a decision based on the facts available.

    Here is my opinion on multiple modalities- controversial or not, the fact remains that many women with recurrent pregnancy loss have been treated with some/many of these and have finally gone on to have a viable pregnancy. Whether they have really helped if something that will never be concretely known, and anybody who claims that they KNOW the answer is just plain arrogant. None of us know much:)

    -Thyroid hormone- easy, cheap, safe, no brainer. I cannot help but disapprove of anybody who does not prescribe this to a patient with high TSH, with or without the antibodies, because if the doctor is wrong and it really was problem, its a shame, because the treatment would have been so easy.
    -heparin/lovenox- risky because it can increase risk of bleeding, though I've seen it anecdotal help a lot of women.
    Prednisone at time of implantation- Cheap,supposedly safe as it does not cross the placenta, but still makes me nervous.
    Intralipids- attractive because it is cheap and seemingly safe. Efficacy hard to judge.
    IVIG- Cost is horrendous, has shown effects in controlling autoimmunity (I'm an immunologist, it doe wonders in certain conditions), but I would be very leery of it.

    About vitamin D deficiency, I disagree that one can figure out whether one is deficient just from their skin color, diet and where they live. During my 2nd pregnancy, I lived in sunny California,I'd been out of the beach on multiple occasions, I was drinking gallons of vitamin D-fortified milk AND was taking prenatals and fish oil that contained very healthy doses of vitamin D. I was STILL clinically deficient,which tells you that the ONLY indicator of how much vitamin D you have to do do a test. And if that had not been accidentally ordered, a lot of us would still be in the dark, so there is definitely a time and place for testing :) Everybody just has different opinions on it and I thank god I have the knowledge and the ability to call the shots myself- at the end of the day, its whatever lets you be at peace.

  6. Yes, this is an approach which makes sense - explain the options to the patient, and then let them decide. Doctors need to emphasise how little we understand about some of these problems ( and this ignorance is not something many doctors are willing to share with their patients).

    My worry is that few doctors do this. Most just take a cookie-cutter "one size fits all" attitude - and this is what I am criticising.

    Ticking boxes from a checklist is easy to do - but is not often in the patient's best interests !

  7. Anonymous8:54 PM

    Jay, I do appreciate your views. But the original argument is whether a TSH of 2.5 and 2.74 (or for that matter 4.5) makes a difference. In my opinion not and as per your view it does make a difference. Of course severe hypothyroidism (or anyone with overt hypothyroid symptom) must be treated accordingly. When a doctor studies only the lab test of a person who has a TSH of 4.5 and tells the patient to take thyroxine supplement then it is totally wrong. There is not enough evidence to do that. But if the patient has hypothyroid symptoms at a TSH of 4.5 definitely the patient has to be treated accordingly. What I insist is, a number on the paper is not important and what you feel or how your body reacts to a TSH of 4.5 is very, very important. There is still a lot of hype about bringing the TSH value of women who are trying to conceive to 1-2. But that is total craziness to do if they really do not have any symptoms. When I say craziness I am also part of that craziness once. When I am always in the grip of fear I did everything which might give me a chance of a pregnancy without second thought. I somehow did not respect my body and the clues it gave me. Hyperthyroidism can do more harm to your fertility and to your pregnancy than a mildly elevated TSH value. In my opinion a higher metabolic rate when pregnant can cause havoc to the foetus. Every body has its own threshold level. Why don’t people think that a mild (not overt!) decrease in TSH value when pregnant is a nature’s way of protecting the fetus and pregnancy? Yea my crazy hypothesis but I believe it (if I do not believe my ideas whoelse will ;)Just because we have the methodology to test everything it doesn't mean we have to invent new treatments and treat everything crazily.

    Regarding Vitamin D – When did you check your Vitamin D status, after or before m/c? If it is after m/c, how long after m/c? I did have a reason for asking it. If it is immediately after m/c I would suspect that the m/c itself could have had a negative effect on your Vitamin D status. If I am you, if I have felt that I had a great diet that is rich in Vitamin D and good sunshine – I wouldn’t have believed that single test result. If I have tested Vitamin D immediately say for example within one or two months of m/c I would have got my Vitamin D value re-checked again before coming to any conclusion. Did you recheck it? Every function in our body is interconnected and a problem in one system can make other functions go haywire. I too have the same opinion regarding your AMH value. How many times it is rechecked? As a scientist you will be well aware of the importance that you can give to a single experiment! Take me as an example my first AMH is 3.5 (first), the second AMH close to 7 (somewhere in middle) and the third (last) 1.8. The outcome of my IVF- I had 9 times more egg yield in my last IVF than my first (believe it or not I am telling only the truth!!!!).

    I still believe a light skinned lady who is in a decent diet and has enough sun exposure, without any recent trauma to her body system will have enough Vitamin D and there is no reason to order a stupid test! I wish I were a doctor too!!!!

  8. Good read. There is currently quite a lot of information around this subject on the net and some are most definitely better than others.

    Ross Finesmith


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