title: Long-term outcome in couples with unexplained subfertility and an intermediate prognosis initially randomized between expectant management and immediate treatment.
abstract: BACKGROUND
  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.
authors: Centre for Reproductive Medicine, Academic Medical Centre, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. i.m.custers@amc.uva.nl
authors: Inge M
authors: IM
authors: Custers
authors: Minouche M E
authors: MM
authors: van Rumste
authors: Jan Willem
authors: JW
authors: van der Steeg
authors: Madelon
authors: M
authors: van Wely
authors: Peter G A
authors: PG
authors: Hompes
authors: Patrick
authors: P
authors: Bossuyt
authors: Frank J
authors: FJ
authors: Broekmans
authors: Cees N M
authors: CN
authors: Renckens
authors: Marinus J C
authors: MJ
authors: Eijkemans
authors: Thierry J H M
authors: TJ
authors: van Dessel
authors: Fulco
authors: F
authors: van der Veen
authors: Ben W J
authors: BW
authors: Mol
authors: Pieternel
authors: P
authors: Steures
mesh_terms: D000328:Adult; D017046:Cost Savings / Q000191:economics; D003362:Cost-Benefit Analysis; D005260:Female; D005306:Fertilization; D005307:Fertilization in Vitro / Q000191:economics; D005500:Follow-Up Studies; D017048:Health Care Costs; D006801:Humans; D007246:Infertility / Q000175:diagnosis / Q000191:economics / Q000503:physiopathology / Q000628:therapy*; D007317:Insemination, Artificial, Homologous / Q000191:economics; D057194:Intention to Treat Analysis; D008297:Male; D009426:Netherlands / Q000453:epidemiology; D010062:Ovulation Induction / Q000191:economics; D011247:Pregnancy; D018873:Pregnancy Rate; D011379:Prognosis; D012720:Severity of Illness Index; D013997:Time Factors