INTRACERVICAL INSEMINATION AND INTRAUTERINE INSEMINATION FOR DONOR SPERM TREATMENT IN THE NATURAL CYCLE: A RANDOMIZED CONTROLLED TRIAL

Both ICI and IUI in the natural cycle are performed as first line treatments in women who are eligible for donor sperm treatment. IUI is more costly than ICI, due to the involvement of sperm processing. The aim of this study was to determine if six cycles of ICI are non-inferior to six cycles of IUI in donor sperm treatment in terms of ongoing pregnancy. We performed a multicenter, non-blinded, non-inferiority randomized controlled trial in six fertility clinics in the Netherlands and Belgium. Based on our retrospective cohort study we assumed a live birth rate of 40% after six cycles of IUI. To assess a non-inferiority margin of 12%, we needed to include 416 women. All women scheduled for donor sperm treatment were eligible, regardless of the indication for treatment. Women were allocated to receive either ICI or IUI in a natural cycle during six cycles within a time horizon of eight months. Eligible women were informed about the study by their doctor or by a dedicated research nurse. After written informed consent women were randomized using a central password protected Internet-based randomization program. In ICI cycles, one insemination was performed with unprocessed semen by straw or by cervical cap within 24 hours after the LH surge in urine or blood. In IUI cycles, one intra-uterine insemination was performed with processed semen one day after the LH surge in urine or blood. The primary outcome was conception within eight months after randomisation leading to a live birth. Secondary outcomes were multiple pregnancy, miscarriage and time to ongoing pregnancy. We calculated relative risks (RR) and risk difference (RD) and 95% CI. We analysed the data both on an intention to treat and a per protocol basis. The per protocol analysis was limited to women who were treated according to the study protocol, who did not switch treatment and who had either become pregnant or completed six treatment cycles in case of treatment failure. Between June 2014 and February 2019, we included 421 women, of whom 211 women were randomly allocated to ICI and 210 to IUI. Women’s age was on average 34 years (SD ± 4) in both groups. Ongoing pregnancy occurred in 52 women (25%) in the ICI group and 82 women (39%) in the IUI group (RR 0.63, 95% CI: 0.47 to 0.84). Live birth rate occurred in 51 women (25%) in the ICI group and 81 women (39%) in the IUI group (RR 0.63, 95% CI: 0.47 to 0.84)). ICI was inferior to IUI; the left boundary of the 95% confidence interval was minus 0.24 and crossed the pre-set absolute difference of 12% (RD of -0.14, 95% CI: -0.18 to -0.30). In the per protocol analysis ongoing pregnancy occurred in 50 women (39%) in the ICI group and 80 women (56%) in the IUI group (RR 0.69, 95% CI: 0.53 to 0.90). Live birth rate occurred in 49 women (38%) in the ICI group and 80 women (56%) in the IUI group (RR 0.68, 95% CI: 0.52 to 0.88). The time to pregnancy was longer in the ICI group compared to the IUI group after six cycles (HR 0.58, 95% CI: 0.41-0.82). In women undergoing donor sperm treatment in a natural cycle, ICI results in lower ongoing pregnancy rates than IUI. Therefore, IUI should be the preferred treatment.