Effectiveness and safety of intrauterine insemination vs. assisted reproductive technology: emulating a target trial using an observational database of administrative claims.

OBJECTIVE:To compare the effectiveness and safety of 1 cycle of assisted reproductive technology (ART) vs. 3 cycles of intrauterine insemination (IUI). DESIGN:Target trial emulation using observational data. SETTING:A healthcare claims database (2011-2015). PATIENT(S):The patients were 29,021 women aged 18-45 years with an infertility diagnosis and no history of IUI or ART within the past 12 months. INTERVENTION(S):One ART cycle immediately, with no more cycles of ART or IUI within the next 4 months; or 1 IUI cycle immediately, with 2 additional consecutive cycles of IUI within the next 4 months unless pregnancy occurred. MAIN OUTCOME MEASURE(S):Live births, multiple births, congenital malformations, preterm births, small-for-gestational-age newborns, large-for-gestational-age newborns, admission to neonatal intensive care unit (NICU), gestational diabetes, preeclampsia, and gestational hypertension. RESULT(S):The probability of live birth was 27.3% for ART and 26.3% for IUI. The observational analogue of per-protocol risk difference (95% confidence interval) for ART compared with IUI was 1.0% (-0.1%, 2.2%) for live births, 4.3% (3.7%, 4.9%) for multiple births, 3.4% (2.8%, 4.0%) for preterm births, 1.5% (0.9%, 2.1%) for NICU admissions, and 0.6% (0.2%, 1.0%) for gestational diabetes. The risk differences for the other outcomes were <0.5%. The results of the 2 strategies were similar in women ≤40 years, but in women >40 years the probability of live birth was greater for ART (14.4%) than for IUI (7.4%). CONCLUSION(S):Compared with 3 cycles of IUI, 1 cycle of ART was estimated to have a similar probability of live birth but slightly higher risks of multiple gestations, preterm births, and NICU admissions.