198 Chapter 9 Despite the similar inclusion criteria and comparable design, there are also some notable differences between this replication study and the Dutch H2Oil study. In the study by Zhang et al, the ongoing pregnancy rates were much lower (29.1% after oil-based contrast and 20.1% after water-based contrast) than in the H2Oil study (39.7% after oil-based contrast and 29.1% after water-based contrast), and the pain scores were also much lower. The differences in ongoing pregnancy rates between the two studies might be explained by the proportion of primary infertility (67.4% in H2Oil study and 83.3% in the replication study). In any case, this study provides critical information for health care providers all over the world; due to differences in availability, different types of oil-based and water-based contrast were used in this study compared to the H2Oil study. This means that the treatment effect is most likely independent of the type of oil-based or water-based used. The Cochrane review from 2020 already showed clear results on the fertility enhancing effect of oil-based versus water-based contrast (4). Addition of the replication study to a systematic review on this topic will most likely create more certainty of evidence and a smaller confidence interval, making the results even more robust. The long-term follow-up of the H2Oil study demonstrated that the fertility enhancing effect of oil-based contrast is long lasting and the effect is still visible over a time span of 5 years, with a significant difference in live births in favour of the use of oil contrast (RR 1.11; 95% CI 1.03-1.20) (15). The cost effectiveness analysis showed that the overall costs between oil-based contrast and water-based contrast are comparable and therefore an HSG with oil-based contrast is deemed the better choice in the evaluated population of couples with unexplained infertility or subfertility based on a mild male factor (16). It is unclear whether the fertility enhancing effect and its cost-effectiveness holds for other populations and especially for couples with other types of infertility. It is possible that within the group of couples with unexplained infertility, there is a large group of women with a yet unidentified pregnancy hindering factor that is remedied by use of oil-based contrast during HSG. All other couples have at least one identified factor that reduces their chance of conception and it is thinkable that these couples might benefit less from the oil-based contrast as the role of the unidentified pregnancy hindering factor might be smaller. While the fertility enhancing effect of oil-based contrast has been proven in women with unexplained infertility, this is not implemented into practice in all centres in the Netherlands. The Dutch guideline for infertility work-up dates from 2015 and describes the HSG as a diagnostic test, without taking into account the fertility enhancing effect
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