73 IUI success and prognosis of natural conception 4 was different in the previous study, in which the benefit of IUI-OS was dependent on prognosis. However, the later that treatment was started, the larger the expected benefit of treatment. This was the same finding as in the previous study. DISCUSSION We replicated the finding that in couples with unexplained subfertility, starting IUI-OS within one and a half years after completion of the fertility workup was associated with increased ongoing pregnancy rates over 6 months compared to expectant management. However, the estimated benefit of treatment did not depend on the prognosis of natural conception but did depend on when treatment was started after diagnosis. We replicated the finding that starting IUI-OS later yields a larger absolute and relative benefit of treatment. The main strength of this study was the use of trial data from the H2Oil study with a follow-up of 3–5 years, low loss-to-follow up and few missing data. For the purpose of triangulation i.e. the use of multiple approaches to address the same question (9, 10), we now have data from two RCTs comparing IUI-OS to expectant management in different patient selection, cohort data and data from a RCT in which couples could receive IUI-OS during follow up. Workup and treatment protocols differed between these three data sources. Via triangulation, our confidence in two findings has been strengthened: namely that starting IUI-OS later yields a larger absolute and relative benefit of treatment and that the absolute chance of an ongoing pregnancy after IUI-OS is less variable between couples than the chance of natural conception. We did not find significant evidence that the effect of IUI-OS depends on the prognosis for natural conception of a couple. Weaknesses are that the H2Oil trial was not designed with this secondary question in mind. In addition, the sample size was moderate which led to wide CIs and perhaps limited the power to show an interaction with prognosis. We observed that the chances of an ongoing pregnancy after 6 months of expectant management in the present study were much higher than what was found in previous studies, at 29% instead of approximately 18% (17, 27). This could be due to the fact that in the H2Oil study, all couples received HSG during the diagnostic work-up, which might increase their chances, especially when using oil-based contrast medium (11, 26). The pooled, i.e. overall effect of IUI-OS versus expectant management was less strong in the current study, with a point estimate for the hazard ratio of 1.50 compared to 1.96 that we found previously. The interaction that showed the dependency of the effect of IUI-OS on the prognosis for natural conception was in the same direction as the
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