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

Abstract

To compare the effectiveness and safety of 1 cycle of assisted reproductive technology (ART) vs. 3 cycles of intrauterine insemination (IUI). Target trial emulation using observational data. A healthcare claims database (2011-2015). 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. 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. 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. 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%). 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.