Improving pregnancy chances and patient experiences in infertility

Summary Infertility affects approximately one in six couples. Patients facing infertility are referred for fertility work-up. One of the tests often performed in the fertility work-up is the hysterosalpingogram (HSG). An oil-based or water-based contrast fluid is infused into the uterine cavity to delineate the uterine cavity and Fallopian tubes on X-ray images. Previous research (the H2Oil study) has shown that an HSG with use of oil-based contrast results in 10% more ongoing pregnancies than an HSG with use of water-based contrast. In Chapter 2 we conducted a secondary analysis using the database of the H2Oil long term follow-up study and discovered that the fertility enhancing effect is greatest immediately after HSG, and disappears after around 2 years. Three important groups of women were excluded from the H2Oil study: women of advanced age, women with ovulation disorders and women with a high risk for tubal pathology. We are repeating the H2Oil study but this time including exactly these groups of women. The protocol of this ongoing study, called ‘H2Oil2’, is presented in Chapter 3. In previous work, the prognosis for natural conception (poor, medium or good) was found to be a predictor for the benefit of intra-uterine insemination with mild ovarian stimulation (IUI-MOH) treatment as opposed to expectant management. After performing the same analysis on the H2Oil database, in Chapter 4, this interaction between prognosis and therapeutic effect of IUI-MOH was not found. Despite the convincing results of the H2Oil study, physicians were still hesitant to use oil-based contrast because of a fear of complications. When the contrast fluid enters the bloodstream through uterine vessels, this so-called intravasation can have severe complications. In Chapter 5 we performed a systematic literature review to obtain information on all possible complications of HSGs with oil-based contrast. The incidence of intravasation was found to be 2.7% during HSGs with oil-based contrast, in comparison to 2.0% with water-based contrast. Based on these results we conclude that safety concerns should not be a reason to withhold women an HSG with oil-based contrast. The HSG is an uncomfortable or painful procedure for most women. Multiple types of pain medication have been tried, including tablets, intravenous medication and local injections. None of these give a satisfactory reduction in pain without major side effects. In Chapter 6 we described our RCT in which we studied whether the use of Virtual Reality can reduce discomfort and/or pain. As Virtual Reality it distracts the user from their surroundings and takes them into a virtual world, the brain is focussed on the virtual reality instead of bodily sensations such as pain. Our study did not show a significant difference in overall pain, peak pain or satisfaction between the Virtual Reality group and the control group. HSG was introduced as a diagnostic test. The safety and comfort issues mentioned, but also radiation exposure, the use of iodine containing contrast and the need for a radiologic department were all reasons for the development of other types of visual tubal patency tests. These alternative tests have all been studied independently. In Chapter 7 we describe our study protocol for a review comparing the different tests with laparoscopy, the current gold standard. During the course of this PhD-tract, Coronavirus Disease 2019 became a pandemic. All non-essential healthcare was paused. For patients with infertility this was a very uncertain time. Scheduled appointments were converted to telephone or video appointments and new treatment cycles could not be started. In Chapter 8 we described the results of our national survey, showing a low fertility-related quality of life in women with infertility during the COVID-19 pandemic and lockdown