Assisted reproductive technology and perinatal outcomes: conventional versus discordant-sibling design

The discordant-sibling study found an increased risk of low birth weight and preterm birth associated with assisted reproductive technology, but with a lower magnitude of effect, compared with the general population.

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Volume 106, Issue 3, Pages 710-716


Nafeesa N. Dhalwani, Ph.D., Sheree L. Boulet, Dr.P.H., Dmitry M. Kissin, M.D., Yujia Zhang, Ph.D., Patricia McKane, M.P.H., Marie A. Bailey, M.S.W., Maria-Elena Hood, M.P.H., Laila J. Tata, Ph.D.



To compare risks of adverse perinatal outcomes between assisted reproductive technology (ART) and naturally conceived singleton births using a dual design approach.


Discordant-sibling and conventional cross-sectional general population comparison.


Not applicable.


All singleton live births, conceived naturally or via ART.



Main Outcome Measure(s)

Birth weight, gestational age, low birth weight, preterm delivery, small for gestational age (SGA), low Apgar score.


A total of 32,762 (0.8%) of 3,896,242 singleton live births in the three states were conceived via ART. In 6,458 sibling pairs, ART-conceived singletons were 33 g lighter (adjusted β = −33.40, 95% confidence interval [CI], −48.60, −18.21) and born half a day sooner (β = −0.58, 95% CI, −1.02, −0.14) than singletons conceived naturally. The absolute risk of low birth weight and preterm birth was 6.8% and 9.7%, respectively, in the ART group and 4.9% and 7.9%, respectively, in the non-ART group. The odds of low birth weight were 33% higher (adjusted odds ratio [aOR] = 1.33; 95% CI, 1.13, 1.56) and 20% higher for preterm birth (aOR = 1.20; 95% CI, 1.07, 1.34). The odds of SGA and low Apgar score were not significantly different in both groups (aOR = 1.22; 95% CI, 0.88, 1.68; and aOR = 0.75; 95% CI, 0.54, 1.05, respectively). Results of conventional analyses were similar, although the magnitude of risk was higher for preterm birth (aOR, 1.51; 95% CI 1.46, 1.56).


Despite some inflated risks in the general population comparison, ART remained associated with an increased likelihood of low birth weight and preterm birth when underlying maternal factors were kept constant using discordant-sibling comparison.

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Fertility and Sterility

Editorial Office, American Society for Reproductive Medicine

Fertility and Sterility® is an international journal for obstetricians, gynecologists, reproductive endocrinologists, urologists, basic scientists and others who treat and investigate problems of infertility and human reproductive disorders.