The study evaluated the impact of elevated oestradiol concentrations on pregnancy loss during the first trimester in singleton gestations conceived via ovarian stimulation and intracytoplasmic sperm injection (ICSI). Following determination of oestradiol concentrations during 6478 ICSI cycles, patients were assorted by oestradiol percentile. Hyper-responders were defined as patients having peak oestradiol concentrations over the 90th percentile (>4200 pg/ml, 685 cycles), moderate responders were defined as patients having peak oestradiol concentrations between the 75th and 90th percentiles (3250-4200 pg/ml, 958 cycles) and normal responders were defined as patients having peak oestradiol concentrations between the 25th and 75th percentiles (1350-3250 pg/ml, 3325 cycles). The relationship between first trimester miscarriage rates and oestradiol percentiles was analysed in 1184 singleton gestations. Pregnancy rate was significantly lower in normal responders (54.4%) than in moderate (58.8%, P = 0.02) and hyper-responders (60.9%, P = 0.003), but there were no intergroup differences in miscarriage rate (19.6%, 17.1%, and 16.8%, respectively). Although women with severe ovarian hyperstimulation syndrome had a miscarriage rate of 40%, this rate did not differ significantly from the miscarriage rates of the other groups. The findings suggest that high oestradiol concentrations during ovarian stimulation do not expose singleton pregnancies to an increased risk of miscarriage during the first trimester.