Safety of oil-based contrast medium for hysterosalpingography : a systematic review

Acknowledgements We would like to thank Mr B de Vries, Clinical Librarian at the Máxima MC for his assistance in developing the search strategies and his perseverance in retrieving the old manuscripts and Mrs J Dieleman for her statistical assistance. We want to thank our colleagues who helped to translate the non-English articles: Mrs G Bach, Professor JH Barker, Mrs IA Fomichev, Mrs L Jongmans, Dr C Nagata, Dr I Nedelcu, Dr MM Porath, Dr A Romano and Dr R Wang. This work was an investigator-initiated study and partly funded by Guerbet, France. Guerbet is the manufacturer of Lipiodol® Ultra Fluid. The funders had no influence in the study design, data collection, the analyses performed or the interpretation of the study data.Peer reviewedPublisher PD

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

How long does the fertility-enhancing effect of hysterosalpingography with oil-based contrast last?

Research question: Does the fertility-enhancing effect of tubal flushing during hysterosalpingography (HSG) with oil-based contrast change over time? Design: This was a secondary analysis of the H2Oil (long-term follow-up) study, a multicentre randomized controlled trial evaluating the effectiveness of oil-based and water-based contrast during HSG. The main outcome was ongoing pregnancy. Cox proportional hazards models for time to ongoing pregnancy were fitted over 3 years of follow-up. Results: Data on 1107 couples were available; 550 couples had oil-based contrast and 557 water-based contrast at HSG. Ongoing pregnancy rates after 3 years were 77% and 71%, respectively. Median follow-up was 9–10 months (5th—95th percentile: <1 to 36). The hazard ratio for ongoing pregnancy for oil versus water over 3 years of follow-up was 1.26 (95% confidence interval [CI] 1.10–1.45). The scaled Schoenfeld residual plots showed a decrease in hazard ratio that was linear with log-transformed time. After including an interaction with log-transformed time, the hazard ratio immediately after HSG was 1.71 (95% CI 1.27–2.31) and reduced to no effect (hazard ratio of 1) at approximately 2 years. There was no evidence for a change in hazard ratio over time in a subgroup of women who experienced pain during HSG. Conclusions: The hazard ratio for ongoing pregnancy of oil-based versus water-based contrast was 1.71 immediately after HSG, gradually decreasing and plateauing towards a hazard ratio of 1 (indicating no effect) after approximately 2 years. This supports the hypothesis that oil-based contrast might dislodge debris or mucus plugs from the Fallopian tubes, but this has yet to be definitively proved

The impact of the COVID-19 pandemic on infertility patients and endometriosis patients in the Netherlands

Research question: How do infertility patients, endometriosis patients and health-care providers rate virtual care as an alternative to physical consultations during the first lockdown of the coronavirus disease 2019 (COVID-19) pandemic in the Netherlands, and how does this influence quality of life and quality of care? Design: Infertility patients and endometriosis patients from a university hospital and members of national patient organizations, as well as healthcare providers in infertility and endometriosis care, were asked to participate between May and October 2020. The distributed online questionnaires consisted of an appraisal of virtual care and an assessment of fertility-related quality of life (FertiQol) and patient-centredness of endometriosis care (ENDOCARE). Results: Questionnaires were returned by 330 infertility patients, 181 endometriosis patients and 101 healthcare providers. Of these, 75.9% of infertility patients, 64.8% of endometriosis patients and 80% of healthcare providers rated telephone consultations as a good alternative to physical consultations during the COVID-19-pandemic. Only 21.3%, 14.8% and 19.2% of the three groups rated telephone consultations as a good replacement for physical consultations in the future. A total of 76.6% and 35.9% of the infertility and endometriosis patients reported increased levels of stress during the pandemic. Infertility patients scored lower on the FertiQol, while the ENDOCARE results care seem comparable to the reference population. Conclusions: Virtual care seems to be a good alternative for infertility and endometriosis patients in circumstances where physical consultations are not possible. Self-reported stress is especially high in infertility patients during the COVID-19-pandemic. Healthcare providers should aim to improve their patients’ ability to cope