A Randomised Controlled Trial Comparing Expectant Management Versus Intrauterine Insemination In Couples With Unexplained Subfertility And A Poor Prognosis For Natural Conception

Abstract Study question Does 6 months expectant management reduces ongoing pregnancy rates compared to intrauterine insemination with ovarian stimulation (IUI-OS) in couples with unexplained subfertility? Summary answer In couples with unexplained subfertility and a poor prognosis for natural conception, 6 months of expectant management decreases ongoing pregnancy rates as compared to IUI-OS. What is known already In couples with unexplained subfertility and a poor prognosis, IUI-OS is a first line treatment. We have previously shown that in couples with unexplained subfertility and a good prognosis for natural conception (>30% in 12 months), 6 months expectant management does not reduce pregnancy changes. However, in couples with a poor prognosis for natural conception, effectiveness of IUI-OS is uncertain. Study design, size, duration We performed a non-inferiority multicentre randomised controlled trial (RCT) within the infrastructure of the Dutch Consortium for Healthcare Evaluation and Research in Obstetrics and Gynaecology. We studied couples with unexplained subfertility and a poor prognosis for natural conception. The couples were allocated in a 1:1 ratio to six months expectant management or six months IUI-OS with either clomiphene citrate or gonadotrophins. Participants/materials, setting, methods We intended to include 1091 couples. The trial was halted pre-maturely due to slow inclusion after randomisation of 178 couples. The primary outcome was ongoing pregnancy leading to a live birth with multiple pregnancy and miscarriage rate as important secondary outcomes. We calculated relative risks with 95% CI and a corresponding hazard-rate for ongoing-pregnancy-over-time based on intention-to-treat. Main results and the role of chance Between October 2016 and September 2020 92 couples were allocated to expectant management and 86 to IUI-OS. Baseline characteristics were equally distributed. Mean female age was 34 years, median duration of subfertility was 21 months. Within 6 months after randomisation, women allocated to expectant management had a lower ongoing pregnancy rate than women allocated to IUI-OS (12/92 [13.0%] vs 29/86 women [33.7%], risk ratio 0.39 (95%CI 0.21 to 0.71)). There were two ongoing twin pregnancies in the expectant management group versus none in the IUI-OS group. Of 15 clinical pregnancies in the expectant management group three miscarried (20%), of 36 clinical pregnancies in the IUI-OS group seven miscarried (19.4%) (RR 1.03 (95% CI 0.31 to 3.45)). For the outcome ongoing pregnancy, the hazard ratio for expectant management versus IUI-OS was 0.34 (95%CI 0.18 to 0.67). Limitations, reasons for caution Our trial did not reach the planned sample size and therefore the results are limited by the number of participants. As 8 women are still pregnant, in this abstract we report ongoing pregnancy rates. Live birth rates will be presented at the conference. Wider implications of the findings: In couples with unexplained subfertility and a poor prognosis for natural conception, expectant management is inferior to IUI-OS. We advise the basic work-up for subfertility to contain a prognostic assessment, and when subfertility is unexplained and natural fertility prospects are poor IUI-OS should be the preferred treatment. Trial registration number NTR5599