Intrauterine insemination with ovarian hyperstimulation vs. expectant management for unexplained subfertility

In an RCT «Steures P, van der Steeg JW, Hompes PG, Habbema JD, Eijkemans MJ, Broekmans FJ, Verhoeve HR, Bossuyt PM, van der Veen F, Mol BW, Collaborative Effort on the Clinical Evaluation in Reproductive Medicin»1 253 couples with unexplained subfertility and a 30–40% probability of a spontaneous ongoing pregnancy within 12 months were randomly assigned either to intrauterine insemination with controlled ovarian hyperstimulation (IUI-OS) for 6 months or to expectant management (EM) for 6 months. In the intervention group, 42/127 (33%) women conceived and 29 (23%) pregnancies were ongoing. In the expectant management group, 40/126 (32%) women conceived and 34 (27%) pregnancies were ongoing (RR 0.85, 95% CI 0.63–1.1). There was one twin pregnancy in each study group, and one woman in the intervention group conceived triplets.

In 3 years follow-up of the above mentioned RCT «Custers IM, van Rumste MM, van der Steeg JW et al. Long-term outcome in couples with unexplained subfertility and an intermediate prognosis initially randomized between expectant management and immedi»2 the effectiveness and cumulative costs were assessed. 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-OS groups, respectively (RR 0.99, 95% CI 0.85 to 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-OS group resulting in an estimated saving of € 2616 per couple (95% CI € 385-€ 4847) in favour of EM.

A network meta-analysis «Wang R, Danhof NA, Tjon-Kon-Fat RI et al. Interventions for unexplained infertility: a systematic review and network meta-analysis. Cochrane Database Syst Rev 2023;(9):CD012692. »3 included 27 RCTs with 4 349 couples. Ten RCTs including 2 725 couples reported on live birth. For differences between OS, IUI, OS-IUI, or vitro fertilisation with or without intracytoplasmic (IVF/ICSI) versus expectant management see table (table «Expectant management vs other interventions for infertility»1). This suggests that if the chance of live birth following expectant management is assumed to be 17%, the chance following OS, IUI, OS-IUI, and IVF would be 9% to 28%, 11% to 33%, 15% to 37%, and 14% to 47%, respectively. When only including couples with poor prognosis of natural conception (3 trials, 725 couples) OS‐IUI and IVF/ICSI increased LBR compared to expectant management (OR 4.48, 95% CI 2.00 to 10.1; moderate‐certainty evidence; OR 4.99, 95 CI 2.07 to 12.04; moderate-certainty evidence), while there was insufficient evidence of a difference between IVF/ICSI and OS-IUI (OR 1.11, 95% CI 0.78 to 1.60; low-certainty evidence). Compared to expectant management, other treatments increased the odds of multiple pregnancy (11 RCTs, 2564 couples).

Comment: The quality of evidence is downgraded by imprecise results (few patients and wide confidence intervals).