Dose-finding study of daily GnRH antagonist for the prevention of premature LH surges in IVF/ICSI patients: optimal changes in LH and progesterone for clinical pregnancy

BACKGROUND: An optimal range of LH concentrations for achieving pregnancy has not been established. The aim of this study was to investigate the effect of various LH levels induced by different GnRH antagonist doses on IVF outcome. METHODS: This was a prospective, single centre study including 144 IVF patients, stimulated with recombinant FSH from cycle day 2, and co-treated with daily GnRH antagonist (antide/Iturelix) (2 mg/2 ml, 1 mg/ml, 0.5 mg/ml, 0.5 mg/0.5 ml or 0.25 mg/ml) from cycle day 7 onwards. Serum samples were taken three times daily. RESULTS: Clinical pregnancies were only observed within a particular range of change in LH levels. The upper and lower thresholds for the mean LH area under the curve (AUC), adjusted for the baseline LH level before the antagonist was started (LH AUC(-S6); S6=stimulation day 6) were -2.2 and 12.4 (IU/l) respectively (a negative value=below baseline levels). There were no clinical pregnancies outside these threshold values. Similar results were found for progesterone, the threshold levels of progesterone AUC(-S6) were 3.98 and -1.21 ng/ml. Moreover, there were no pregnancies with progesterone levels >0.26 ng/ml/follicle on the day of hCG. CONCLUSIONS: Excessive or insufficient suppression of LH and progesterone levels during GnRH antagonist administration and high progesterone/follicle on hCG day seems to be associated with impaired clinical pregnancy rates.