Effect of in vitro fertilization on human chorionic gonadotropin serum concentrations and Down's syndrome screening

Objective: To investigate the association between IVF and Down's syndrome screening analytes (alpha-fetoprotein [AFP] and hCG) during the second trimester. Design: Retrospective analysis. Setting: University-based tertiary care infertility clinic. Patients: Data on 41 consecutive singleton IVF pregnancies and 4,935 naturally occurring singleton pregnancies. Results: Maternal serum hCG concentrations were elevated (mean 1.52 multiples of the median [MoM]) in IVF pregnancies, whereas there were no significant differences in AFP levels (mean 1.02 MoM). The mean maternal age was higher in the subjects than in controls (33.8 compared with 28.7 years). In relation to Down's syndrome risk assessment, the pattern of the two markers, together with maternal age, indicated high risk more often in the study subjects than in the controls. In vitro fertilization patients had a false-positive rate of 26.8% compared with 6.6% in women without fertility problems. Conclusion: The increased false-positive rate in Down's syndrome screening is related not only to advanced maternal age but also, in part, to the elevated hCG concentrations observed in pregnancies after assisted reproduction. The mechanism behind increased hCG production remains to be elucidated, but it may be an effect associated with infertility or the procedures by which these women conceive. To provide an objective assessment of an individual patient's risk of fetal abnormality, the impact of IVF on hCG biochemistry should be studied further in larger samples and adjustments made if appropriate.