Long-term outcome in couples with unexplained subfertility and an intermediate prognosis initially randomized between expectant management and immediate treatment.

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.

Immobilisation versus immediate mobilisation after intrauterine insemination: randomised controlled trial.

OBJECTIVE: To evaluate the effectiveness of 15 minutes of immobilisation versus immediate mobilisation after intrauterine insemination. DESIGN: Randomised controlled trial. Setting One academic teaching hospital and six non-academic teaching hospitals. PARTICIPANTS: Women having intrauterine insemination for unexplained, cervical factor, or male subfertility. INTERVENTIONS: 15 minutes of immobilisation or immediate mobilisation after insemination. MAIN OUTCOME MEASURE: Ongoing pregnancy per couple. RESULTS: 391 couples were randomised; 199 couples were allocated to 15 minutes of immobilisation after intrauterine insemination, and 192 couples were allocated to immediate mobilisation (control). The ongoing pregnancy rate per couple was significantly higher in the immobilisation group than in the control group: 27% (n=54) versus 18% (34); relative risk 1.5, 95% confidence interval 1.1 to 2.2 (crude difference in ongoing pregnancy rates: 9.4%, 1.2% to 17%). Live birth rates were 27% (53) in the immobilisation group and 17% (32) in the control group: relative risk 1.6, 1.1 to 2.4 (crude difference for live birth rates: 10%, 1.8% to 18%). In the immobilisation group, the ongoing pregnancy rates in the first, second, and third treatment cycles were 10%, 10%, and 7%. The corresponding rates in the mobilisation group were 7%, 5%, and 5%. CONCLUSION: In treatment with intrauterine insemination, 15 minutes' immobilisation after insemination is an effective modification. Immobilisation for 15 minutes should be offered to all women treated with intrauterine insemination. TRIAL REGISTRATION: Current Controlled Trials ISRCTN53294431.

External validation of a prediction model for an ongoing pregnancy after intrauterine insemination.

OBJECTIVE: To assess the accuracy of our recently developed prediction model in a prospective validation study to predict the outcome of intrauterine insemination (IUI). DESIGN: Descriptive prospective validation study. SETTING: Seven fertility centers in the Netherlands. PATIENT(S): Couples treated with IUI of whom the female partner had a regular cycle. INTERVENTION(S): Intrauterine insemination with or without controlled ovarian hyperstimulation. MAIN OUTCOME MEASURE(S): Ongoing pregnancy after intrauterine insemination. Performance of the prediction model was assessed with calibration and discriminative capacity. Calibration was assessed by comparing the predicted ongoing pregnancy rate with the observed ongoing pregnancy rate. Discriminative capacity was assessed with receiver operation characteristic (ROC) analysis. For daily practice, a score worksheet of the validated model was developed to estimate the chance of an ongoing pregnancy after IUI per treatment cycle. RESULT(S): We included 1,079 subfertile couples who underwent 4,244 cycles of IUI. There were 278 ongoing pregnancies, that is, an ongoing pregnancy rate of 6.6% per cycle. External validation of the model showed good calibration. The predicted probability never differed by more than 1.5% of the mean observed probability. The area under the ROC curve was 0.56 (95% confidence interval, 0.53-0.59) at external validation. CONCLUSION(S): The prediction model was able to make a good distinction between couples with a good pregnancy chance and those with a poor pregnancy chance after IUI. This model can help in deciding which couples will benefit from IUI and which couples will not.