The uptake of prenatal diagnosis in 436 singleton and 146 twin pregnancies following assisted reproduction was compared with a matched group of spontaneous conceptions. The first and second trimester ultrasound examination included target fetal anatomic evaluation and screening by specific markers described for fetal aneuploidy. Women with assisted conception attended significantly more often for first trimester prenatal diagnosis (57.9 versus 34.9%, P < 0.01), but had fewer examinations in the early second trimester at 15-18 weeks (37.8 versus 48.8%, P < 0.01) than those with spontaneous conception. Screen positive results of 6.5 and 6.9% for first trimester examination and 6.0 and 7.3% for second trimester examination were found in assisted conceptions and controls respectively. A significantly higher rate of invasive prenatal diagnosis was observed in the second trimester for spontaneous conceptions, 20.0 versus 11.8% (P < 0.01) compared with assisted conceptions. This was attributed to the higher rate of invasive procedures in advanced maternal age ≥35 years of 40.7 versus 28.6% (P = 0.01) in spontaneous and assisted conceptions respectively. With the purpose of avoiding invasive testing, women with assisted conception were more likely to use the results of the ultrasound examination to guide their final decision about invasive testing, rather than undergo genetic amniocentesis as a first option.