Friday, May 04, 2012

Why have IV Intralipids become so popular for IVF patients ?

A number of clinics are now prescribing intravenous intralipids for patients who have failed an IVF cycle. The hypothesis is that intravenous intralipids will help to increase the chances of successful embryo implantation . Intralipids are said to suppress the activity of NK cells in the uterus , thus preventing rejection of the embryo.

This is yet another example of the large number of empirical treatment options which are being offered to patients who have failed IVF treatment cycles . Many of these fashions and come and go – and after practicing for over 20 years, I am quite skeptical about the value of most of these. It’s not that I am jaundiced – it’s just that a lot of these interventions which are tom-tommed and hyped when they are new will soon be proven to be ineffective and worthless. A handful of small isolated studies that cannot be duplicated on a large scale by other doctors/researchers means it doesn't work. That's where intralipids is right now. As a conservative doctor, I’d rather other clinics tried them out on their patients, rather than use my patients as guinea pigs.

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  1. Anonymous9:11 PM

    Dear Dr,

    I do agree with your stand point. Thanks for this post because it made me to sit and educate myself about this topic which I am avoiding all the time. I did end up with a nice finding but it seems that the extremely intelligent infertility community already have immense knowledge about it :)

    Progesterone is considered as one of the nature's best immunosuppresant. It is shown that progesterone at the concentration present at the materno-fetal interface inhibits NK cell activity. Placenta also secretes several factors which act as immunosuppressant. Even human embryo was shown to produce certain chemicals which inturn stimulate maternal system to produce Early Pregnancy Factor which acts as an immunosuppressant too. Trophoblast cells also express certain receptors which prevent NK cells from attacking them.

    Inorder to find out whether NK cells have overt cytotoxic activity, the NK cells (mostly from peripheral blood) are removed from our body's natural environment where progesterone, placental factors and other immunosuppressants are present in plenty. Then an invitro assay is carried out using k562 cells-which is a myelogenous leukemia cell line. The percentage of k562 cells lysed or killed by NK cells gives an idea how vigorously active your NK cells are. Using the result of this NK cell cytotoxicity assay it is decided whether a particular woman should undergo immune therapy or not.

    There are certain important points to be noted here: K562 are cancerous cells and such cancerous cells are readily recognized by healthy NK cells. It is the normal function of NK cells to kill cancer causing cells. The use of K562 lysis assay to determine whether your NK cells have the capability to attack your embryo is a very crude, vague and controversial method. Even if a particular woman’s NK cells are overactive to cancer cell (K562) it doesn’t necessarily mean that the cells behave the same with her embryo or her placenta. As I have already said an invitro environment is extremely different from invivo condition. Uterus environment (invivo environment) is extremely rich in natural immunosuppressant (like progesterone) and when a competent embryo enters the uterus it also for its part signals the maternal system to secrete immunosuppressant. How come an assay conducted without simulating a natural invivo environment used to predict NK cell cytotoxicity against human embryo? How could one correlate a cancer cell with a human embryo? How many studies were done to determine the cut-off value for determining NK cell cytotoxicity? As per my knowledge a very few studies were done and all of them were published in low-ranking journals! On the whole it is wise to ask a lot of questions and research a lot before undergoing such skeptical therapies.

  2. Anonymous9:12 PM

    The use of intralipids to suppress the overactive(!) NK cell is another ill defined hypothesis. Intralipid is a mixture of 30% Soybean Oil, 1.2% Egg Yolk Phospholipids, 1.7% Glycerin, and Water. For what purpose intralipid is used originally? Intralipid is used to as a parenteral nutrition to correct Essential Fatty Acid Deficiency and to improve caloric intake. What does it have to do with immune cells or NK cells? Dietary fatty acids are shown to modulate immune cell function and some studies have shown that it suppresses NK cell activity. I should also emphasize here that intralipid infusion makes animals prone to infection because of its immunosuppressive effect. Is there an alternate to intralipid infusion? There seems to be a way! I am not talking about IVIG- a very costly alternative. I am talking about FISH OIL! Fish oil is well documented for its immunosuppressive effects. Greenland Eskimos who consume large amount of fish oil in their diet have very low incidence of inflammatory and auto immune disease in their population (PMID:7457208). Flax seed oil and evening primrose oil too seem to have such NK cell lowering effects. Why no one wants to make human trials with easily available, easy administrable fish oil (or with flax seed oil or EPO) which has less side-effect and is as effective as intralipid is something to be pondered. Isn’t a dietary lipid administration better than parenteral route if both of them can achieve the same effect?



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