74 Chapter 4 previous study, with lower prognoses having more benefit of IUIOS, but this did not reach statistical significance in terms of AIC or P-value. It could be that we lacked the power, owing to a less strong main treatment effect and sample size restrictions, to show this dependency as we did in the previous study, which had a larger sample size of 1896 with 800 couples treated with IUI (7). It remains unknown why couples with better prognoses would benefit less from IUI-OS. A possible mechanism is that there is a ‘ceiling’ to the chance of conception for subfertile couples in terms of a maximum and that some unexplained subfertile couples with good prognoses remain around this ceiling whereas couples with different indications are further below their fertility potential, which is increased by IUI-OS (28). Not all couples who received IUI-OS conceived or continued IUI-OS over the 6 months follow up of a ‘mimicked’ trial dataset. In the previous study, there was no follow-up of natural conception after IUI-OS dropout. We repeated this approach in the current study. In contrast to the previous study, we found that the effect of IUI-OS depended on when treatment was started independent of the decreasing prognosis of natural conception after failed cycles. This might be due to additional selection over time that is not explained by the dynamic prediction model (7, 18, 25). We found that when accounting for this time effect, the absolute chances after IUI-OS were much more stable over time than chances after expectant management, as the latter clearly decreased over time whereas the former did not. This provides more evidence that the chance after IUI-OS is less dependent on individual factors i.e. that couples’ chances become more similar when receiving IUI-OS. This can be important for counselling couples, as it suggests that further expectant management will not come at a great loss in terms of a decreased chance of pregnancy when receiving IUI-OS later. CONCLUSION We replicated the finding that on average, IUI-OS increases the chance of an ongoing pregnancy compared to expectant management and that when IUI-OS is started later, the expected benefit in terms of the absolute and relative difference with expectant management was larger. We did not replicate the finding that the benefit of IUI-OS depends on the prognosis of natural conception. Couples with unexplained subfertility still have good chances of natural conception at the time of diagnosis and treatment is thus not always necessary. Clinicians should counsel couples on the option to prolong expectant management before commencing with IUI-OS.
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