The prognostic value of the oestradiol flare-up in response to gonadotrophin-releasing hormone (GnRH) agonist was evaluated in 140 in-vitro fertilization (IVF) cycles programmed by progestogen pretreatment. Three days after the end of administration of norethisterone, a routinely used short-term DTRP6 GnRH agonist protocol was started (designated day 1), gonadotrophins being introduced from day 4. Serum oestradiol flare-up values were evaluated on days 1, 2 and 3 to study their relationship with the subsequent IVF outcome. On day 2, 87.9% of the cycles exhibited a significant rise in serum oestradiol concentration from baseline (delta E2 > or = 5 pg/ml). Compared to cycles without any significant oestradiol increase, they had a higher pregnancy rate per transfer (33.3 versus 9.1%, P = 0.02), although the number of transferred embryos did not differ significantly. Taking into account the previously described cut-off value (doubling from baseline), we found that less than half of the cycles (45.7%) involved a doubling of oestradiol values during flare-up, and we did not observe any significant difference in IVF outcome in these cycles compared to those without doubling. In conclusion, progestogen pretreatment, by inducing ovarian quiescence, may lower the oestradiol cut-off value that is predictive of the subsequent pregnancy rate. Nevertheless, determination of the absolute oestradiol response (delta E2) to GnRH agonist after progestogen pretreatment could allow a further adaptation of the protocol to achieve an optimum response in each cycle. Another alternative for patients with a lower delta E2 could be the suppression of progestogen pretreatment.