Association between infertility treatment and intrauterine growth: A multilevel analysis in a retrospective cohort study

Abstract

This study aimed to identify intrauterine growth differences according to infertility treatment compared with spontaneous conception and to describe intrauterine growth trajectories. Design Retrospective cohort study. Setting A single primary and tertiary medical centre in Japan. Participants This study included singleton pregnant women with prenatal check-ups and delivery at the University of Yamanashi Hospital between 1 July 2012 and 30 September 2017. Patients were divided into four groups: spontaneous conception, infertility treatment without assisted reproductive technology (ART), fresh-embryo transfer and frozen embryo transfer (FET). Interventions Differences in intrauterine growth according to the infertility treatment, including ART, and birth weight were evaluated. Multilevel analysis was employed to evaluate intrauterine growth trajectories stratified by the sex of the offspring. Primary outcome measure Estimated fetal weight (EFW) assessed by ultrasound examination. Results We assessed data from 37 239 prenatal examination results from 2377 pregnant women (spontaneous conception, n=1764; infertility treatment without ART, n=171; fresh-embryo transfer, n=112; and FET, n=330) in the final analysis. Multilevel analysis was adjusted for gestation duration, gestation period, parity, hypertensive disorders of pregnancy, type of infertility treatment, maternal age, smoking status, placenta previa, thyroid disease, gestational diabetes mellitus and the interaction between each potential confounding factor and gestation duration. In male fetuses, the interaction between FET and gestational duration (estimate: 0.36; 95% CI: 0.06 to 0.67) significantly affected the EFW. Similarly, in female fetuses, FET (estimate: -69.85; 95% CI: -112.09 to -27.61) and the interaction between FET and gestation duration (estimate: 0.57; 95% CI: 0.28 to 0.87) significantly affected the EFW. Conclusions This study shows that FET affects intrauterine growth trajectory from the second trimester to term, particularly in female fetuses. Our findings require further prospective research to examine the effect of infertility treatment on fetal growth.