Cycle day, estrogen level, and lead follicle size: analysis of 27,790 in vitro fertilization cycles to determine optimal start criteria for gonadotropin-releasing hormone antagonist.

OBJECTIVE: To determine the optimal criteria at which to start GnRH antagonists during controlled ovarian hyperstimulation (COH) for in vitro fertilization (IVF).

DESIGN: Retrospective clinical cohort.

SETTING: IVF clinics.

PATIENT(S): Women undergoing fresh autologous IVF using GnRH antagonist for ovulation suppression during COH.

INTERVENTION(S): Measurement of lead follicle size, E2 level, and cycle day of stimulation on day of antagonist initiation.

MAIN OUTCOME MEASURE(S): Clinical pregnancy rate (PR).

RESULT(S): The highest clinical PR was achieved when the antagonist was started when a lead follicle reached 14-15.9 mm in size (mean clinical PR 21.3; 95% confidence interval [CI] 19.3, 23.6) on cycle day 6 (mean clinical PR 22.2; 95% CI 17, 28.4), or when the E2 level was between 500 and 599 pg/mL (mean clinical PR 25.4; 95% CI 19.5, 32.4). Starting antagonists when the E2 level was <300 or >1,100 pg/mL reduced the odds of clinical pregnancy by 40% (odds ratio 0.60, 95% CI 0.5, 0.7).

CONCLUSION(S): Cycle day, E2 level, and follicle size at time of antagonist start are all independent predictors of a clinical pregnancy after IVF. Initiating antagonists when the E2 level is extremely low (<300 pg/mL) or extremely high (>1,100 pg/mL) significantly reduces the odds of pregnancy.