This study aimed to evaluate the prognostic value of the baseline serum oestradiol E2 level on the cycle pregnancy rate (PR) in women with unexplained infertility (UI) undergoing controlled ovarian hyperstimulation (COH). This study is unique in that it evaluates the effect of cycle day 1 (rather than day 3) E2 levels on cycle PR in a COH setting (without IVF) in women with UI (rather than multiple causes of infertility). Structured as a retrospective cohort study, the setting was the Ovulation Induction Clinic at an academic tertiary care hospital. One hundred and forty-five patients with UI underwent 374 cycles of COH with either human menopausal gonadotrophin (hMG) alone or hMG and clomiphene citrate. Outcome was measured as cycle pregnancy rate (PR) according to the cycle day 1 level of E2. Patients with an E2 level > 150 pmol/l on cycle day 1 of COH achieved a significantly lower PR (4%) compared with those with E2 levels < or = 150 pmol/l (13%). Logistic regression analysis demonstrated that women with day 1 E2 levels below 150 pmol/l were 3.2 times more likely to conceive than those with day 1 E2 levels above 150 pmol/l. Also, the impact of day 1 E2 levels on the chance of pregnancy was independent of day 1 serum FSH levels. Women with UI undergoing COH in our unit with an elevated baseline serum E2 > 150 pmol/l have a significantly lower PR and should be counselled regarding the decreased likelihood of pregnancy.