GnRH Agonist Stimulation Test (GAST) for Prediction of Ovarian Response in Controlled Ovarian Stimulation (COH)

난소기능평가를 위한 Gonadotropin Releasing Hormone Agonist Stimulation Test (GAST)의 효용성에 관한 연구

Objectives: The aims of this study are 1) to determine if GAST is a better indicator in predicting ovarian response to COH compared with patient's age or basal FSH level and 2) to evaluate its role in detecting abnormal ovarian response. Design: Prospective study in 118 patients undergoing IVF-ET using GnRH-a short protocol during May-September 1995. Materials and Methods: After blood sampling for basal FSH and estradiol $(E_2)$ on cycle day two, 0.5ml (0.525mg) GnRH agonist ($Suprefact^{(r)}$, Hoechst) was injected subcutaneously. Serum $E_2$ was measured 24 hours later. Initial $E_2$ difference $({\Delta}E_2)$ was defined as the change in $E_2$ on day 3 over the baseline day 2 value. Sixteen patients with ovarian cyst or single ovary or incorrect blood collection time were excluded from the analysis. The patients were divided into three groups by ${\Delta}E_2$; group A (n=30):${\Delta}E_2$<40 pg/ml, group B (n=52): 40 pg/ml${\leq}{\Delta}E_2$<100 pg/ml, group C (n=20): ${\Delta}E_2{\leq}100$ pg/ml. COH was done by GnRH agonist/HMG/hCG and IVF-ET was followed. Ratio of $E_2$ on day of hCG injection over the number of ampules of gonadotropins used ($E_2hCGday$/Amp) was regarded as ovarian responsiveness. Poor ovarian response and overstimulation were defined as $E_2$ hCGday less than 600 pg/ml and greater than 5000 pg/ml, respectively. Results: Mean age $({\pm}SEM)$ in group A, B and C were $33.7{\pm}0.8^*,\;31.5{\pm}0.6\;and\;30.6{\pm}0.5^*$, respectively ($^*$: p<0.05). Mean basal FSH level of group $A(11.1{\pm}1.1mlU/ml)$ was significantly higher than those of $B(7.4{\pm}0.2mIU/ml)$ and C $(6.8{\pm}0.4mIU/ml)$ (p<0.001). Mean $E_2hCGday$ of group A was significantly lower than those of group B or C, i.e., $1402.1{\pm}187.7pg/ml,\;3153.2{\pm}240.0pg/ml,\;4078.8{\pm}306.4pg/ml$ respectively (p<0.0001). The number of ampules of gonadotropins used in group A was significantly greater than those in group B or C: $38.6{\pm}2.3,\;24.2{\pm}1.1\;and\;18.5{\pm}1.0$ (p<0.0001). The number of oocytes retrieved in group A was significantly smaller than those in group B or C: $6.4{\pm}1.1,\;15.5{\pm}1.1\;and\;18.6{\pm}1.6$, respectively (p<0.0001). By stepwise multiple regression, only ${\Delta}E_2$ showed a significant correlation (r=0.68, p<0.0001) with $E_2HCGday$/Amp, while age or basal FSH level were not significant. Likewise, only ${\Delta}E_2$ correlated significantly with the number of oocytes retrieved (r=0.57, p<0.001). All four patients whose COH was canceled due to poor ovarian response belonged to group A only (Fisher's exact test, p<0.01). Whereas none of 30 patients in group A (0%) had overstimulation, 14 patients among 72 patients (19.4%) in group B and C had overstimulation (Fisher's exact test, p<0.01). Conclusions: These data suggest that initial $E_2$ difference after GAST may be a better prognostic indicator of ovarian response to COH than age or basal FSH level. Since initial $E_2$ difference demonstrates significant association with abnormal ovarian response such as poor ovarian response necessitating cycle cancellation or overstimulation, GAST may be helpful in monitoring and consultation of patients during COH in IVF-ET cycle.