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Infertility, Infertility Treatment, and Fetal Growth Restriction

From the ¹Danish Epidemiology Science Centre, Department of Epidemiology, Institute of Public Health, University of Aarhus, Aarhus C, Denmark; ²Perinatal Epidemiological Research Unit, Department of Gynaecology and Obstetrics, Aarhus University Hospital, Aarhus N, Denmark; ³Department of Epidemiology, School of Public Health, University of California Los Angeles, Los Angeles, California; and ⁴Epidemiology Branch, National Institute of Environmental Health Sciences, Department of Health and Human Services, National Institutes of Health, Research Triangle Park, North Carolina.

OBJECTIVE: To examine the association between infertility, with or without treatment, and fetal growth, as well as perinatal and infant mortality.

METHODS: From the Danish National Birth Cohort (1997–2003), we identified 51,041 singletons born of fertile couples (time to pregnancy 12 months or less), 5,787 born of infertile couples conceiving naturally (time to pregnancy more than 12 months), and 4,317 born after treatment. We defined small for gestational age (SGA) as the lowest 5% of birth weight by sex and gestational age.

RESULTS: Crude estimates suggested an increased risk of perinatal mortality and SGA among infertile couples (treated and untreated), but the odds ratios (ORs) of perinatal mortality among infertile couples were attenuated after adjustment for maternal age and body mass index (1.32, 95% confidence interval [CI] 0.95–1.84 among untreated and 1.26, 95% CI 0.86–1.85 among treated couples). The elevated risk of SGA among infertile couples persisted after adjustment for maternal age, parity, and smoking (OR 1.24, 95% CI 1.10–1.40 among untreated, and OR 1.40, 95% CI 1.23–1.60 among treated). The risk of SGA increased with time to pregnancy, and a longer time to pregnancy was associated with a small reduction in birth weight across the whole distribution.

CONCLUSION: The increased risk of SGA observed among infertile couples with or without infertility treatment suggests that infertility may be a risk factor for intrauterine growth restriction. Treatment per se may have little effect on fetal growth. A small-to-moderate increased risk of perinatal mortality in infertile couples cannot be ruled out due to the small number of cases.

LEVEL OF EVIDENCE: II

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