Does a hysterosalpingogram make you more fertile?

A hysterosalpingogram (HSG) is a procedure in which dye that blocks X-rays (radio-opaque dye) is injected through the cervix to see if the uterine cavity is normal and the fallopian tubes are open. An HSG is part of the basic infertility investigation. There are two kinds of HSG dye: oil-soluble dye, and water-soluble dye. More than forty years ago, a radiologist reported that when HSG dye was switched from oil-soluble dye to water-soluble dye, the pregnancy rate over the next 12 months in patients who had had the HSG dropped from 41% to 27%. When the use of oil-soluble dye was resumed, the pregnancy rate rose to 44%. It seems that using oil-soluble HSG dye increases the chance of subsequent pregnancy, but many physicians are either unaware of this effect, or choose to ignore it. I think this is an opportunity missed.

The only oil-soluble HSG dye in current use in the US is Ethiodol. Studies have shown that the subsequent pregnancy rates are twice as high when Ethiodol is used compared to when a water-soluble dye is used. This effect seems to be most pronounced in women with unexplained infertility or endometriosis. The reason for the beneficial effect is uncertain, but one study showed that Ethiodol altered the function of peritoneal macrophages, white blood cells that are normally found the peritoneal fluid (fluid that can be found in the pelvis around the ovaries and fallopian tubes). In women with endometriosis, peritoneal macrophages gobble up sperm, and this may be part of the reason for infertility in women with this disorder. In any case, the fertility-promoting effect of oil-soluble HSG dye seems pretty clear to me, and I think most every infertile woman getting an HSG should have this dye used. Nevertheless, in the hospital where I do most of my HSGs, I notice that most of the other physicians are using water-soluble dye, not Ethiodol, when they do an HSG. Why is this?

There are several reasons why oil-soluble dye is not used more frequently. First of all, there are some studies which failed to show the beneficial effect of oil-soluble dye. The problem here is that most (but not all) of these studies didn’t have enough patients to show the effect; that is, the sample size was too small. However, when you combine data from all the studies in one analysis, the beneficial effect can be detected. This is called meta-analysis, and it is a controversial statistical technique, but I believe it is valid in this setting.

Secondly, some physicians are concerned that there is a higher incidence of complications when an HSG is done using oil-soluble contrast dye. There have been serious complications, even deaths, associated with HSGs, using both water-soluble and oil-soluble dyes. Most of these problems occurred more than forty years ago, before the use of fluoroscopy (X-ray video) to monitor the dye injection. At that time, a very thick, viscous HSG dye was in use, and when this was inadvertently injected into the bloodstream, serious complications could occur. The last death from an HSG was thought to have occurred in the 1960’s. Recently, in a series of over 1,000 HSGs performed with oil-soluble dye using fluoroscopy, no serious reactions were reported. In my opinion, using oil-soluble dye is no riskier than using water-soluble dye. Oil-soluble HSG dye is incompatible with some catheters used to perform the procedure, but there are plenty of alternative catheters that don’t have this problem.

Probably the most significant reason why more people don’t use oil-soluble HSG dye is that it is more expensive. A 10 mL ampule of Ethiodol retails for about $90, whereas the same amount of water-soluble dye (such as Omnipaque-300) is about half the price. In my experience, most radiologists are not familiar with the fertility-promoting effect of oil-soluble HSG dye (ironic, since one of the early reports was from a radiologist), and the radiologist if often the one directing purchase of the supplies. However, if you figure that extra $45 doubles your pregnancy rate, this becomes one of the most cost-effective treatments for infertility available.

If you are an infertility patient planning to have an HSG, and you want to convince your doctor to use oil-soluble contrast medium, you’ll probably need a better reference than this blog to convince him/her. I suggest you go to the library and get the following references, or just print off the abstracts from PubMed:

Watson A, Vandekerckhove P, Lilford R, Vail A, Brosens I, Hughes E. A meta-analysis of the therapeutic role of oil soluble contrast media at hysterosalpingography: a surprising result? Fertility and Sterility 1994 Mar;61(3):470-7.

Luttjeboer F, Harada T, Hughes E, Johnson N, Lilford R, Mol BWJ. Tubal flushing for subfertility. Cochrane Database of Systematic Reviews 2007, Issue 3. Art. No.: CD003718. DOI: 10.1002/14651858.CD003718.pub3.

Johnson NP, Farquhar CM, Hadden WE, Suckling J, Yu Y and Sadler L .The FLUSH trial—Flushing with lipiodol for unexplained (and endometriosis-related) subfertility by hysterosalpingography: a randomized trial. Human Reproduction 2004; 19, 2043–2051.

MPS