The most sensitive and specific first-trimester Down syndrome screening test employs a combination of maternal age, nuchal translucency (NT) thickness, fβhCG, and PAPP-A. First trimester NT measurements do not differ significantly between pregnancies resulting from assisted reproductive technology (ART) and those resulting from spontaneous conception, but maternal blood levels of free beta human chorionic gonadotropin (fβhCG) are higher following in vitro fertilization-embryo transfer (IVF-ET), and levels of pregnancy-associated plasma protein-A (PAPP-A) are lower. Whether or not this results in a higher rate of false positive screening test results is controversial. The investigators compared the screen-positive rates of the first trimester Down syndrome screening test in women with singleton ART pregnancies to those of women whose pregnancies resulted from spontaneous conception. Participants included 130 women who were pregnant after IVF-ET (group 1); 54 who conceived after intracytoplasmic sperm injection (ISCI; group 2); and 914 control women who conceived spontaneously. Fetal NT thickness was estimated at 10–14 weeks’ gestation. Women who conceived via ICSI were 2.8 times as more likely to be screen positive than control women. Although ovarian stimulation in group 1 and group 2 women was associated with significantly lower PAPP-A levels than were present in the control group, women who conceived via IVF-ET were not more likely to be screen positive than control women. Levels of PAPP-A declined significantly as the number of retrieved oocytes or transferred embryos increased, but the levels of other markers were not affected. When a single embryo was transferred, or when ART conception occurred without ovarian stimulation, marker levels were similar to those following spontaneous conception. Although ICSI appears to be associated with a higher rate of false positive first trimester screening test results than that in spontaneously conceived pregnancies, women who conceive by other ART methods are not at increased risk.