Custers, I.van Rumste, M.van der Steeg, J.van Wely, M.Hompes, P.Bossuyt, P.Broekmans, F.Renckens, C.Eijkemans, M.Van Dessel, T.van der Veen, F.Mol, B.Steures, P.CECERM,2014-12-152014-12-152012Human Reproduction, 2012; 27(2):444-4500268-11611460-2350http://hdl.handle.net/2440/88135BACKGROUND We recently reported that treatment with intrauterine insemination and controlled ovarian stimulation (IUI-COS) did not increase ongoing pregnancy rates compared with expectant management (EM) in couples with unexplained subfertility and intermediate prognosis of natural conception. Long-term cost-effectiveness of a policy of initial EM is unknown. We investigated whether the recommendation not to treat during the first 6 months is valid, regarding the long-term effectiveness and cumulative costs. METHODS Couples with unexplained subfertility and intermediate prognosis of natural conception (n=253, at 26 public clinics, the Netherlands) were randomly allocated to 6 months EM or immediate start with IUI-COS. The couples were then treated according to local protocol, usually IUI-COS followed by IVF. We followed couples until 3 years after randomization and registered pregnancies and resources used. Primary outcome was time to ongoing pregnancy. Secondary outcome was treatment costs. Analysis was by intention-to-treat. Economic evaluation was performed from the perspective of the health care institution. RESULTS Time to ongoing pregnancy did not differ between groups (log-rank test P=0.98). Cumulative ongoing pregnancy rates were 72–73% for EM and IUI-COS groups, respectively [relative risk 0.99 (95% confidence interval (CI) 0.85–1.1)]. Estimated mean costs per couple were €3424 (95% CI €880–€5968) in the EM group and €6040 (95% CI €4055–€8125) in the IUI-COS group resulting in an estimated saving of €2616 per couple (95% CI €385–€4847) in favour of EM. CONCLUSIONS In couples with unexplained subfertility and an intermediate prognosis of natural conception, initial EM for 6 months results in a considerable cost-saving with no delay in achieving pregnancy or jeopardizing the chance of pregnancy. Further comparisons between aggressive and milder forms of ovarian stimulation should be performed.en© The Author 2011.unexplained subfertilityintrauterine insemination and controlled ovarian stimulationexpectant managementlong-term outcomeeconomic analysisJournal article002013684210.1093/humrep/der3890002991318000172-s2.0-8485590219515314Mol, B. [0000-0001-6887-0262] [0000-0001-8337-550X]