Can an X-ray examination overcome tubal infertility?

Quite a number of media organizations toward the end of July picked up on a study published in the prestigious New England Journal of Medicine, in which colleagues from The Netherlands reported that hysterosalpingograms (HSGs) (an X-ray examination) performed with oil-based contrast dies were followed by more spontaneous pregnancies than those performed with water-based contrast media (Dreyer et al., N Engl J Med 2017;376(21):2043-2052). The New York Times even dedicated a whole “Mind and Matter” column to the study (Konner M, July 29-30, 2017).

First some background: HSGs are performed to determine whether the uterine cavity is normal and fallopian tubes are normal in outline and patency. For spontaneous pregnancies and pregnancies after insemination procedures, normally functioning tubes are essential since egg and sperm “meet” in the distal part of the tube, where fertilization takes place. The fertilized egg then wanders proximally through the tube toward the uterus. If tubes are obstructed, egg and sperm can’t meet and the couple will be infertile. If the integrity of the tubal mucosa is disturbed, the fertilized egg may get stuck on the way into the uterus, and an ectopic tubal pregnancy may ensue.

HSGs are, therefore, routinely performed in every basic infertility work up, unless there are reasons to take patients straight into IVF, in which case patency of the fallopian tubes becomes irrelevant and only the quality of the endometrial cavity remains to be determined. In such cases, a HSG, therefore, is no longer required, and a so-called sonohysterogram (ultrasound rather than X-ray examination of the uterus, or HSN) is sufficient.

A HSG is performed by injecting a contrast die through the cervix into the uterus, from where the contrast freely flows through (open) fallopian tubes into the peritoneal cavity. While this happens, X-ray pictures are taken, outlining endometrial cavity and fallopian tubes (like blood vessels are outlined in an angiogram) and allowing determinations whether cavities and fallopian tubes are normal or not in contour and are patent or not.

The procedure just celebrated its 100th birthday, and, paradoxically, was first performed using almost exclusively oil-based contrast dies. From very early on, it was well known that the month following a HSG procedure, a small bump in spontaneous pregnancies occurred. The procedure, thus, very obviously exerted in some patients a positive effect on their spontaneous fertility. Over the last 30 years or so, oil-based dies were, however, almost universally replaced by water-based dies. This switch had two major reasons: First, injection of oil-based dies was significantly more painful to patients since due to their higher fluid density, they elicited more uterine cramping. In addition, however, some studies also suggested that oil-based dies caused more tubal infections and subsequent tubal scarring than water-based dies.

Already in 1983 Alan DeCherney, MD, then still at Yale University, started to resurrect the idea of using oil-based contrast to enhance pregnancy chances (Fertil Steril 1983;39(1):115-116), claiming more pregnancies following oil-based HSGs.  Investigators at CHR (then still in Chicago), under the guidance of CHR’s Medical Director and Chief Scientist, Norbert Gleicher, MD, a few years later started experimenting with tubal catheterization procedures, which revealed that many tubal obstructions diagnosed by HSG were the consequence of accumulations of crystalized tubal secretions (“tubal slush”) within the lumen of fallopian tubes that with relatively little efforts could be re-canalized (Confino et al., Am J Obstet Gynecol 1988;159(2):370-375 and Confino et al., JAMA 1990.264(1):2979-2082). These observations explained the pregnancy bump observed following HSGs because the pressure exerted by the injected fluid column during HSG very obviously flushed out many of these “thlushy” obstructions.

The attention the recent study in the New England Journal of Medicine received, therefore, came as somewhat of a surprise to us. That oil-based contrast results in more force in the flushing process should, of course, not surprise since it is so much denser a fluid. It is reassuring that complications did not differ between oil- and water-based contrast, suggesting that, at least in Dutch populations, oil-based contrast studies do not increase post-HSG salpingitis risks. Whether that also applies to populations with higher risk for pelvic inflammatory disease, remains, however, to be confirmed. And whether patients, who often even without paracervical blocks have difficulties withstanding the cramping following water-based studies, will now flock toward even more painful oil-based contrasts, is more than questionable.

We here at CHR, therefore, suggest caution in switching back to oil-based contrast dies, even if they slightly increase spontaneous pregnancy rates in comparison to water-based dies.  Patients may hate you for it after the HSG if you do it!

This is a part of the September 2017 CHR VOICE.

Norbert Gleicher, MD, leads CHR’s clinical and research efforts as Medical Director and Chief Scientist. A world-renowned reproductive endocrinologist, Dr. Gleicher has published hundreds of peer-reviewed papers and lectured globally while keeping an active clinical career focused on ovarian aging, immunological issues and other difficult cases of infertility.