11 General introduction 1 uterus (18). Although this provided good diagnostic images, the suspension remained in the body for a long time and therefore another type of contrast medium was sought to replace bismuth. Lipiodol (Guerbet, Villepinte, France), an iodinated oil-solution, was developed in 1901 as a treatment for goiter, syphilis, cardiovascular problems and other diseases (19). Its first use as contrast medium during HSG was described in 1922. HSG with Lipiodol as oil-based contrast became a common tubal patency test in the investigation of infertility, suspected anomalies in the female genital tract and even to visualize and confirm intrauterine pregnancy in an era where pregnancy tests were lacking. Over the following decades, water soluble contrast media were developed as an alternative to oil-based contrast in HSG. The use of the less viscose water-based contrast media facilitated the implementation of serial HSG, during which a series of X-ray images are taken to evaluate the progression of contrast through the reproductive system. This dynamic approach provides more information than the initial HSG procedure where only one image is obtained hours or even a day after infusion of contrast medium to determine whether there is tubal patency (20). In the 1970’s this technique was implemented by tubal surgeons. Before IVF was introduced, tubal surgery was the only option for patients with tubal infertility and serial HSG allowed the surgeon to assess whether surgery could improve fertility. Especially, the visual appearance of water-based contrast made it possible to determine more accurately the preoperative chances of successful tubal reconstructive surgery when compared to the use of oil-based contrast as it is able to show more clearly the mucosal folds in the ampullar part of the tubes. Fertility enhancing effect of tubal flushing Since the 1930’s it has been reported that Lipiodol and later Lipiodol Ultra Fluid during HSG seemed to have a positive effect on the chance of pregnancy (21, 22). This potential pregnancy enhancing effect of oil-based contrast was the topic of interest in the H2Oil study (23). The H2Oil study was a multicentre randomized controlled trial (RCT) in the Netherlands, investigating the difference in ongoing pregnancies in couples with unexplained or mild male infertility within 6 months after tubal flushing during HSG with oil-based or water-based contrast. The 27 participating hospitals included a total of 1119 women, of which 557 women were randomized for HSG with use of oil-based contrast and 562 for water-based contrast. The ongoing pregnancy rate was significantly higher in the group receiving oil-based contrast (39.7 versus 29.1%, rate ratio (RR) 1.37; 95% confidence interval (CI) 1.16 to 1.61; P<0.001). A recent network meta-analysis included the H2Oil study and showed that the chance of clinical pregnancy within six months was significantly higher after tubal flushing with oil-based contrast than after tubal flushing with water-based contrast (five studies included, OR 1.67, 95% CI 1.38-2.03) (24). Live birth as outcome was only reported in two RCT’s (OR 2.18, 95% CI 1.30-3.65) and the certainty of evidence was low. The studies in this network meta-analysis mostly included
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