Smaller fetal size in singletons after infertility therapies: The influence of technology and the underlying infertility

In vitro fertilization and other assisted reproductive technologies (antiretroviral therapy [ART]) have been linked to adverse perinatal outcomes. The underlying pathologic reasons for the subfertility/infertility may also contribute to smaller fetal size during development and other adverse ART outcomes.The aim of this retrospective observational study was to test the hypothesis that neonates of women with underlying infertility are smaller in utero and at delivery compared with the offspring of fertile women. Fetal growth in singleton live births was compared among otherwise healthy matched infertile (n = 461) and fertile (n = 1246) cohorts of women with singleton live births over a 10-year period. The study was conducted at a tertiary care center and affiliated community hospitals. To reduce unrecognized bias, propensity score analysis was used to identify the fertile patients who were most similar to the infertile patients; the score was estimated from a logistic regression model. The infertile cohort comprised 3 subgroups: without medical assistance, in vitro fertilization, and ovulation induction. The primary study outcome measure was birth weight. Secondary outcomes included fetal size in the first trimester measured by crown-rump length, estimated fetal birth weight in the second trimester, low birth weight, and preterm delivery.Neonates from infertile women were smaller at birth than neonates of fertile women (3231 ± 21 vs. 3375 ± 21 g; P < 0.0001). Infertile women also had more low-birth-weight infants (relative risk, 1.68; 95% confidence interval, 1.06-2.67). Compared with the neonates of fertile women, the lowest birth weight among the infertile groups occurred in neonates conceived via ovulation induction (3397 ± 44 vs. 3092 ± 46 g).First-trimester fetal size in the neonates of infertile women was smaller than in neonates of fertile women (crown-rump length: 7.9 ± 0.1 vs. 8.5 ± 0.1 mm). There were no differences between any of the infertile subgroups in fetal or neonatal size.These findings suggest that the pathologic mechanisms underlying the infertility may have a larger impact than ART techniques on fetal growth.