Neonatal characteristics of children conceived with in vitro fertilization or intrauterine insemination compared with sibling births from unassisted conceptions

Abstract

Objective: To examine birth outcomes between children conceived with in vitro fertilization (IVF) or intrauterine insemination (IUI) and sibling births from unassisted conceptions.

Design: Retrospective sibling cohort.

Subjects: Live born children conceived via IVF, with or without intracytoplasmic sperm injection, or IUI at the Utah Center for Reproductive Medicine, 1999-2018, and sibling births from unassisted conceptions (born 1985-2018). The main analysis included singleton births (460 IVF, 666 IUI, and 1,579 unassisted siblings).

Exposure: In vitro fertilization, with or without intracytoplasmic sperm injection, or IUI.

Main outcome measures: Preterm birth, low birth weight, small for gestational age, large for gestational age (LGA), and major congenital anomalies.

Results: Compared with unassisted siblings, singleton children conceived via IVF had gestational ages shorter by nearly half a week (95% confidence interval [CI], -0.6 to -0.3), birth weights of 72.1 g lower (95% CI, -118.8 to -25.4), and higher proportions of preterm birth (IVF, 11.1%; IUI, 8.7%; unassisted siblings, 6.8%), LGA (IVF, 9.1%; IUI, 4.5%; unassisted siblings, 5.9%), and major congenital anomalies (IVF, 3.7%; IUI, 2.0%; unassisted siblings, 1.4%). Models adjusted for maternal age, infant sex, infant birth year, previous pregnancy, and birth order showed that children conceived via IVF were more likely to be preterm (adjusted risk ratio [aRR], 1.6; 95% CI, 1.2-2.2; absolute difference, 4.3%) and LGA (aRR, 1.8; 95% CI, 1.2-2.5; absolute difference, 3.2%). Children conceived via IVF had a higher risk of major congenital anomalies than unassisted siblings adjusted for maternal age, infant sex, and birth order (aRR, 1.9; 95% CI, 1.0-3.8; absolute difference, 2.3%). Children conceived via IUI had birth weights 55.8 g lower (95% CI, -95.6 to -15.9) than unassisted siblings.

Conclusion: We observed an increased risk of preterm birth, low birth weight, LGA, and major congenital anomalies among singleton children conceived with IVF compared with that among unassisted siblings; however, absolute differences remain small. For children conceived via IUI, lower birth weights were observed. These results suggest that treatment-related factors in addition to underlying subfertility may contribute to adverse birth outcomes.

Keywords: Preterm birth; birth defects; birth weight; large for gestational age; small for gestational age.