• The Korea Journal of Herbology
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• v.30 no.6
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• pp.69-75
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• 2015

Objectives : This study was designed to investigate effects of the combination with Korean Red Ginseng (Panax ginseng C.A. Meyer), Gastrodia Rhizoma (Gastrodia elata Blume) and Polygoni Multiflori Radix (Polygonum multiflorum Thunberg) on metabolic disorders including cholesterol and erectile dysfunction in hyperlipidemia rats.Methods : Animals were divided into six groups; Control with normal diet, high fat/cholesterol-diet (HFCD), fluvastatin, Korean Red Ginseng treated (KRG), and the combination treated (Korean Red Ginseng, Gastrodia Rhizoma and Polygoni Multiflori Radix; 1:1:1 for KGP1 and 2:1:1 for KGP2). The experimental groups initially received HFCD for 10 weeks and then treated orally with fluvastatin, KRG, KGP1 and KGP2 during the final 6 weeks. Erectile function was determined by the measurements of intracavernosal pressure (ICP) and maximal arterial pressure (MAP) after electrical stimulation of the cavernosal nerve.Results : KGP2 decreased the level of total cholesterol and LDL cholesterol in the sera of HFCD rats without no changes of body weights. KRG, KGP1 and KGP2 decreased the level of C-reactive protein (CRP) levels except of fluvastatin, synthetic HMG-CoA reductase inhibitor. KRG, KGP1 and KGP2 significantly increased the ICP, ICP/MAP ratio, area under the curve (AUC) compared with those of normal rat. Morphometric analyses showed that KRG, KGP1 and KGP2 increased the volume of smooth muscle and the regular arrangement of collagen fibers in corpus cavernosum of HFCD rats. The penile expression of eNOS was increased by KRG, KGP1 and KGP2.Conclusions : Based on these results, we suggest that the combination with Korean Red Ginseng, Gastrodia Rhizoma and Polygoni Multiflori may improve hyperlipidemia through regulating the lipid profiles and erectile dysfunction in rats.

• Journal of Nutrition and Health
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• v.48 no.4
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• pp.299-309
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• 2015

Purpose: The purpose of this study was to examine the effect of black soybean (CJ-3) testa extracts on lipid profiles in streptozotocin (STZ)-induced diabetic rats. Methods: One control group and four STZ-induced diabetic groups with different doses of black soybean (CJ-3) testa extracts treatment [0 mg/kg (diabetic control, EX), 250 mg/kg (EX-250), 500 mg/kg (EX-500), 1,000 mg/kg (EX-1000)] were orally administered for 4 weeks. Results: All CJ-3 treatment groups had remarkably lower serum triglyceride (TG) levels than that of EX group (p < 0.05) whereas hepatic TG contents did not show any differences. Results from serum total cholesterol (TC) concentrations of EX-250 and EX-1000 groups were decreased compared to EX group (p < 0.05). Furthermore, protein levels of 3-hydroxy-3-methyl-glutaryl-Coenzyme A (HMG-CoA) reductase from the liver decreased in all treatment groups (p < 0.05). However, significant differences were not observed in serum glucose and insulin, and glucose transporter 4 (GLUT-4) protein expression in skeletal muscle tissue. Conclusion: These results suggest that black soybean testa extracts could be useful for improvement of hyperlipidemia and hypercholesteremia in diabetes.

• Korean Journal of Clinical Pharmacy
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• v.15 no.1
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• pp.41-45
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• 2005

심바스타틴은 cholesterol 생합성 과정에서 속도 조절 효소인 HMG-CoA reductase의 강력한 상경적 길항약으로서 고지혈증 치료에 널리 쓰이는 약물이다. 심바스타틴 제제인 MSD 사의 조코 20 mg정을 대조약으로 하여 시험약인 유영 제약의 엘바스타 20mg정의 생물학적 동등성 평가를 하기 위해 22명의 건강한 지원자를 모집하였다. 지원자를 두 군으로 나누어 2정씩 투여하였고 $2{\times}2$ 교차시험을 실시하였다. 심바스타틴의 혈장 중의 농도를 정량하기 위하여 발리데이션된 LC/MS/MS를 사용하였다. 채혈 시간은 투약 전 및 투약 후 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12 시간에 걸쳐 총 12시점에 걸쳐 시행하였다. 생물학적 동등성을 판정하기 위한 파라미터로 12시간까지의 혈장 중 농도곡선 하 면적 ($AUC_{12hr}$)과 최고 혈중 농도($C_{max}$)를 사용하였다. 12시간 까지의 혈중 농도 곡선 하 면적의 기하 평균은 $17.30ng{\cdot}ml/hr$(시험약)과 $17.35ng{\cdot}ml/hr$(대조약)으로 나타났다. 최고 혈중 농도의 경우 각 각 5.08 ng/ml(시험약)과 5.20 ng/ml(대조약)으로 관찰 되었다. $AUC_{12hr}$의 경우 로그변환한 평균치 차의 $90{\%}$ 신뢰구간이 log0.8510 - log1.1694이었고, $C_{max}$의 경우 log0.8176 - log1.1649로 계산되어 두 항목 모두 log0.8-log1.25이어야 한다는 식품의약품 안전청과 FDA의 기준을 모두 만족시켰다. 이상의 결과를 종합하면 시험약 엘바스타 정 20mg은 대조약 조코정 20 mg에 대하여 생물학적 동등한 것으로 판정되었다.트리머 전기비저항 탐사를 수행하였다. 이를 통해 하저에 케이블을 설치하는 방식에 비해 매우 신속하고 경제적으로 하저에 분포하는 이상대의 분포범위와 발달방향을 규명할 수 있었다.대에 대해 가장 효과적이다. 모델과 현장 적용 결과들을 통해 GRM SSM 방법을 이용하여 불규칙한 굴절면을 가진 지층들에 대해 좀 더 신뢰할 수 있는 정밀한 탄성파 속도를 산출할 수 있음을 보여주고 있다.별한 주의를 기울여야 한다.EX>$\alpha/\beta$=10인 경우 $62.0\~121.9\;Gy_{10}$ (중앙값: $93.0\;Gy_{10}$)의 분포를, ${\alpha/\beta}=3$인 경우 $93.6\~187.3\;Gy_3$ (중앙값=$137.6\;Gy_3$ )의 분포를 보였다. MD-BED $Gy_3$는 직장합병증 발생과의 관계는 통계적으로 유의하였고, 방광합병증과는 유의하지 않았다. 직장합병증과의 연관성은 MD-BED $Gy_3$보다 개별 환자의 직장전벽 총 선량 BED값인 R-BED $Gy_3$가 훨씬 더 높았다. 요도카테터 풍선의 후방지점이 대변하는 방광의 총 선량 BED값인 V-BED $Gy_3$도 방광합병증과 경향성 테스트에서 통계적 유의성을 보였다. 하지만, 어떠한 방사선선량도 골반제어율과 의미 있는 상관관계를 보이지 않았다. 본 기관에서 주치의의 선호도에 따라 강내근접치료가 외부방사선치료의 중간에 시행되는 형태인 샌드위치기법과 외부방사선치료 후반부에 시행되는 순차적 기법으로 구분하였을 때, 두 방식간 치료성적 및 합병증의 차이는 없었다. 총 치료기간에 대한 분석에서는 치료기간이 길어질수록 재발 위험이 커지는 경향을 보였으나, 나이 및 병기, 종양의 크기, MD-BED $Gy_{10}$

• Clinical and Experimental Reproductive Medicine
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• v.26 no.1
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• pp.75-81
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• 1999

The beneficial effect of glucose and phosphate ions in culture medium on the development of human embryos in vitro has not been fully elucidated. The purpose of this study was to evaluate the influence of fertilization and culture of embryos in glucose/phosphate-free m-TALP medium on pregnancy rates in IVF-ET program. The patients in 244 IVF-ET cycles received GnRH agonist + HMG regimens. A does of 10,000 IU HCG was administered when two or more dominent follicles reached 18mm in diameter. Thirty-six hours after HCG, oocytes were recovered transvaginally using ultrasound guidance. Aspirated oocytes were matured for 4 to 6 h in TCM-199 supplemented with 10% follicular fluid (FF). Insemination was carried out with 50,000 motile spermatozoa in TCM-199 + 10% FF or m-TALP + 5% FF + 5% fetal cord serum (FCS) according to experimental design. After 6 h, oocytes were washed 3 to 4 times and cultured in each fresh medium. After 20 h, oocytes were freed from cumulus/corona cells and examined for the presence of pronuclei. Fertilized oocytes were transferred into each co-culture drops and cultured for further incubation. On day 3, embryo transfer was performed with grade 1 and 2 embryos. Monolayers for co-culture of embryos were prepared by plating $1{\times}10^5$ cumulus cells/ml in 10ul drop of TCM-199 + 10% FF or m-TALP + 5% FF + 5% FCS media 24 h prior to the onset of co-culture. Development to 4 to 16 cell stage was observed at 70x magnification following two days of incubation. Pregnancy was confirmed by detecting increasing serum ${\beta}$-hCG concentrations for 11 days following embryo transfer. Data were analyzed by ${\chi}^2$-test. Oocytes from 244 IVF-ET cycles were randomized. The number of cycles and mean age of patients were 97 and 147, 31.3 yrs and 31.2 yrs for TCM-199 (control) and m-TALP groups, respectively. The mean number of retrieved oocytes/cycle, fertilization rates, number of embryos transferred/ET and pregnancy rates were 11.1 and 10.3, 65.1% and 67.3%, 4.1 and 4.7, 28.9% and 43.8% for TCM-199 and m-TALP groups, respectively. Differences in the pregnancy rates were found between control and m-TALP groups (p<0.05). The pregnancy rate of patients divided according to maternal age groups of ${\leq}30$, 31-35, $36{\leq}$ were 44.4% and 49.0%, 26.1% and 41.3%, 29.2% and 41.2% for control and m-TALP groups, respectively. These data indicate that culture of human embryos in glucose/phosphate-free m-TALP medium improves pregnancy rates.

• Journal of Food Hygiene and Safety
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• v.28 no.2
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• pp.89-94
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• 2013

The present study was undertaken to elucidate the mechanisms underlying the cholesterol-lowering effect of S-allylmercaptocysteine (SAMC) derived from aged garlic. Rat hepotocytes and HepG2 cells were used to determine the short-term effects of SAMC on [$^{14}C$] acetate incorporation into cholesterol, and several enzymatic steps. The cells were grown in Dulbecco's modified Eagle's medium supplemented with 10% fetal bovine serum and treated with 20, 40, 60 and 80 ${\mu}g/ml$ of SAMC. At concentration of 20~40 ${\mu}g/ml$, no significant cells viability effect was noted during those incubation periods. However, at a concentration 60 ${\mu}g/ml$, cell viability decreased approximately 50% compared with the control. The treatment of cells with 5, 10, 15, and 20 ${\mu}g/ml$ of SAMC resulted in a marked of [$^{14}C$]-acetate incorporation into cholesterol. At concentration of 15 ${\mu}g/ml$, the cholesterol synthesis was inhibited 79% in cells. The activities of lipogenic enzymes, fatty acid synthase (FAS), and glucose-6-phosphate dehydrogenase (G3PDH) were measured in culture hepatocytes treated with the inhibitors. The activity of FAS in cells treated with 0.95 nmol SAMC was 19% lower than that of nontreated cells, and no affected G6PDH activity, 3-hydroxy-3-methylglutaryl Co A activity was decreased at concentration dependant manner. The present study demonstrates that SAMC is effective in inhibiting cholesterol biosynthesis.

• Journal of Nutrition and Health
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• v.39 no.2
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• pp.91-99
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• 2006

This study was conducted to investigate the effects of mulberry fruit, mulberry leaves and silkworm powder with different mixing ratios on hepatic antioxidative system and lipid metabolism in streptozotocin-induced diabetic rats. Sprague-Dawley male rats weighing $100{\pm}10g$ were induced diabetic by 50 mg/kg bw streptozotocin and randomly assigned to following experimental groups; normal diet group (DM), 0.3% and 0.6% mulberry fruit diet groups (F and 2F), 0.3% mulberry leaves diet group (M), 0.3% silkworm powder diet group (S), 0.15% mulberry fruit+0.15% mulberry leaves diet group (FM), 0.15% mulberry fruit+0.15% silkworm powder diet group (FS), 0.1 % mulberry fruit+0.1 % mulberry leaves+0.1% silkworm powder diet group (FMS). The experimental diets were fed for 4 weeks. Hepatic SOD activity was not changed significantly by any of single or combined supplementations of mulberry fruit, leaves and silkworm powder but GSH-px and catalase activities were increased by the groups supplemented with two or three of the test ingredients (FM, FS, FMS) as compared with the DM group. Hepatic TBARS value was not reduced significantly by any of the supplementations but lipofuscin contents were significantly reduced in the FM, FS and FMS groups as compared with the DM group. Hepatic mitochondria and microsomal carbonyl values were reduced by the single and combined supplementations of the test ingredients. Hepatic HMG-CoA reductase activities were increased in the all supplementation groups as compared with the DM group. Hepatic total lipid and triglyceride contents were increased but cholesterol contents reduced in the supplemented groups. The effects on the enzyme activities, peroxide or its products and lipid contents were most remarkable in the FMS group. In conclusion, mulberry fruit, mulberry leaves and silkworm powder have the favorable effects on antioxidative system and lipid metabolism in the diabetic liver and the mulberry fruit, leaves and silkworm powder with equal ratio exert the synergistic effect expectedly to prevent diabetic complications.

• The Korea Journal of Herbology
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• v.33 no.5
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• pp.89-103
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• 2018

Objectives : This study is aimed to compare the changes in Antioxidative capacity of Liriopis Tuber by steaming process and to compare the effects in hyperlipidemia induced rats fed high cholesterol diet between Simvastatin and Liriopis Tuber by steaming process. Methods : The SD rats were divided into six groups: normal diet (Nor), high cholesterol diet (Veh), high cholesterol diet plus Simvastatin 5 mg/kg (Sim), high cholesterol diet plus LT0 extract 200 mg/kg (LT0), high cholesterol diet plus LT6 extract 200 mg/kg (LT6) and high cholesterol diet plus LT9 extract 200 mg/kg (LT9). We compared the total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL), low density lipoprotein cholesterol (LDL) contents and reactive oxygen species (ROS) from each serums. Protein expression in liver tissues related to antioxidant and cholesterol was analyzed. Results : The Antioxidant activity of Liriopis Tuber increased by steaming process. In vivo, TC, TG, LDL-c, atherogenic index (AI) and cardiac risk factor (CRF) decreased and HDL-c increased with increasing steaming frequency. aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine, and blood urea nitrogen (BUN) decreased with increasing steaming frequency. ROS decreased only in LT9, and SOD, catalase and glutathione peroxidase (GPx) increased with increasing steaming frequency. phospho-AMP-activated protein kinase (p-AMPK) increased and sterol regulatory element-binding protein 2 (SREBP-2), Phospho-Acetyl-CoA Carboxylase (p-ACC) and HMG-CoA reductase (HMGCR) decreased with increasing steaming frequency. Liver staining showed a decrease in hepatic fat accumulation of LT9. LT9 showed significant results in all experiments. Conclusions : LT9 showed significance of anti-lipid effect and improved fatty liver of hyperlipemia induced rats fed on high cholesterol diet, In conclusion, LP9 can be effectively used for the treatment of hyperlipidemia.

• Clinical and Experimental Reproductive Medicine
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• v.23 no.1
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• pp.103-108
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• 1996

Through the previous studies(I,II), it was observed that human follicular fluid(HFF) was more effective than human fetal cord serum(HFCS) on promoting meiotic resumption of oocytes and improving embryonic development of mouse in vitro. On the basis of these results, we have gradually exchanged HFCS with HFF as protein supplement in human ART. This study was performed to investigate the efficiency of HFF on improving the pregnancy rate in ART. Oocytes were retrieved transvaginally from patients treated with pituitary suppression with GnRH-agonist and ovarian stimulation with human menopausal gonadotro-pin(HMG) and pure follicle stimulating hormone(FSH). Aspirated oocytes were rinsed and cultured in TCM-199 containing HFF, and the concentrations of HFF were adjusted to 10, 20, and 30% according to the use for insemination, embryo growth and embryo transfer, respectively. As possible as, we tried to do embryo transfer into fallopian tube to mimic the coincidence of the cell stage with the place of sojourn in vivo, so we performed various ART programs(IVF & ET; in vitro fertilization, ZIFT; zygote intra fallopian-tube transfer, ZIFT & ET) according to the tubal conditions of patients. On the while, intra cytoplasmic sperm injection(ICSI) was used to assist IVF of the patients who had shown poor standard IVF results by immunological or severe male factor. Of the 255 cycles of ART programs using HFF as protein supplement, 118 cycles were turn out to be succeeded in pregnancy(46.2%, per cycle, p<0.05), while 21 pregnancies were achieved in the 69 cycles using HFCS(30.4%). The 255 cycles using HFF were subdivided into cycles with the type of ART programs, and each pregnancy rate of the ART programs were 44.7% (IVF & ET, 76/170 cycles), 53.4%(ZIFT, 31/58 cycles) and 40.7% (ZIFT & ET, 11/27 cycles), respectively. In the 61 ICSI cycles using HFF, 28 cycles succeed in pregnancy(45.9%), while 7 pregnancies were obtained in the 17 ICSI cycles using HFCS. Also the ongoing pregnancy rate in the group using HFF(78.8%, 93/118 cycles) was higher than that in the group using HFCS(61.9%). Therefore, we found that the use of HFF as protein supplement was more suitable and effective than the use of HFCS to improve the pregnancy rate in ART.

• Korean Journal of Clinical Pharmacy
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• v.21 no.2
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• pp.90-99
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• 2011

Health Insurance Review & Assessment Service (HIRA) claims database has a high potential to detect signals of new drug interactions. The aim of this study was to evaluate the usefulness of information component (IC) and relative risk (RR) as a tool for signal detection, and to analyze the possible drug interactions caused by clopidogrel using HIRA claims database. This study was performed in elderly patients over 65 years of age who administered clopidogrel from January 2005 to June 2006 in South Korea. Serious Adverse Events (SAEs) as drug interactions of clopidogrel were defined as any ambulatory hospitalization for ischemic diseases within comcomitant medication period of clopidogrel. Information Component (IC) and Relative Risk (RR) were calculated to compare the proportion of drug-SAE pairs in order to select drug specific SAEs. IC and RR signals of clopidogrel drug interaction were screened when IC's 95% confidence interval was greater than 0 and RR's 95% confidence interval was greater than 1 respectively. All detected signals were compared to references such as $Micromedex^{(R)}$ and 2010 Drug Interaction $Facts^{TM}$. Sensitivity, specificity, positive predicted value and negative predicted value were used to evaluate usefulness of this method. Among 13,252,930 cases of elderly patients who co-administered clopidogrel and other drugs, 47,485 cases were detected as SAE. Of these, one-hundred nine cases were detected by the IC-based data-mining approach and ninety one cases were detected by the RR-based data-mining approach. Total One-hundred sixty three unrecognized signals were detected by IC or RR. Twelve signals from IC-based data-mining (57.1%) were corresponded with drug interactions from references and eight signals from RR-based data-mining (38.1%) were corresponded with drug interactions from references. These signals include proton pump inhibitors, calcium channel blockers and HMG CoA reductase Inhibitors, which were known to affect CYP450 metabolism. Further studies using HIRA claims database are necessary to develop appropriate data-mining measure.

• Clinical and Experimental Reproductive Medicine
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• v.26 no.2
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• pp.163-170
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• 1999

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.