13 General introduction 1 Another theory is modulation of peritoneal macrophage activity by oil-based contrast which affects the conception and implantation mechanism positively (30). In vitro studies have demonstrated that oil-based contrast inhibits phagocytosis of macrophages in humans and rats, perchance phagocytosis of sperm (30, 31). A study by Izumi et al. confirms that oil-based contrast is incorporated in dendritic cells in the peritoneal cavity (34). By promoting more mature dendritic cells, altering cytokine and chemokines profiles in dendritic cells and increasing the number of T-cells, this modulates the immunological environment in the peritoneal cavity. Mature dendritic cells are likely to show decreased activity in sperm phagocytosis. Furthermore, the cytokine IL-10 in the endometrium is upregulated by oil-based contrast while a low presence of IL-10 has been related to repeated implantation failure. Together these may contribute to the fertility enhancing effect of HSG with oil contrast (34). In addition to the above mentioned hypotheses, it is possible that tubal flushing during HSG improves sperm transport through the cervix (35) as HSG requires manipulation and instrumentation to the cervix. Further research, both fundamental and clinical, is needed in order to provide more insight into the true mechanism(s), duration and dynamics of action of oil-based contrast. Safety Shortly after the first reports on the use of HSGs for the treatment of infertility, publications reporting on complications of HSG with Lipiodol emerged. The main severe complication was flow of contrast into the myometrial vessels, potentially leading to contrast entering the venous or lymphatic system (36). This complication is referred to as intravasation and may cause allergic reactions and oil embolisms with potentially harmful or even fatal results (37). Intravasation was attributed to the high viscosity and hydrophobic qualities of Lipiodol and therefore less viscose contrast media were developed, resulting in Lipiodol Ultra Fluid and various types of water-based contrast media (19). In a recent survey study, intravasation of oil-based contrast during HSG was estimated to occur in 5% of the cases in the Netherlands (38). An overview of the complete literature on the differences in complication rates between HSG with oil-based contrast and waterbased contrast is lacking. Discomfort Aside from the complication risk, HSG comes with several other downsides. Performing an HSG exposes the woman to ionizing radiation and requires the presence of a radiology department and radiographer. Additionally, HSG is usually experienced as
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