• Clinical and Experimental Reproductive Medicine
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• 제32권4호
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• pp.315-324
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• 2005

Objectives: To compare the efficacy of GnRH antagonist multiple dose protocol (MDP) with that of GnRH agonist long protocol (LP) in controlled ovarian hyperstimulation for in vitro fertilization in patients with high basal FSH (follicle stimulating hormone) level or old age, a retrospective analysis was done. Methods: Two hundred ninety four infertile women (328 cycles) who were older than 41 years of age or had elevated basal FSH level (> 8.5 mIU/mL) were enrolled in this study. The patients had undergone IVF-ET after controlled ovarian hyperstimulation using GnRH antagonist multiple dose protocol (n=108, 118 cycles) or GnRH agonist long protocol (n=186, 210 cycles). The main outcome measurements were cycle cancellation rate, consumption of gonadotropins, the number of follicles recruited and total oocytes retrieved. The number of fertilized oocytes and transferred embryos, the clinical pregnancy rates, and the implantation rates were also reviewed. And enrolled patients were divided into three groups according to their age and basal FSH levels; Group A - those who were older than 41 years of age, Group B - those with elevated basal FSH level (> 8.5 mIU/mL) and Group C - those who were older than 41 years of age and with elevated basal FSH level (> 8.5 mIU/mL). Poor responders were classified as patients who had less than 4 retrieved oocytes, or those with $E_2$ level <500 pg/mL on the day of hCG injection or those who required more than 45 ampules of exogenous gonadotropin for stimulation. Results: The cancellation rate was lower in the GnRH antagonist group than in GnRH agonist group, but not statistically significant (6.8% vs. 9.5%, p=NS). The amount of used gonadotropins was significantly lower in GnRH antagonist group than in agonist group ($34.8{\pm}11.3$ ampules vs. $44.1{\pm}13.4$ ampules, p<0.001). The number of follicles > 14 mm in diameter was significantly higher in agonist group than in antagonist group ($6.7{\pm}4.6$ vs. $5.0{\pm}3.4$, p<0.01). But, there were no significant differences in clinical pregnancy rate (24.5% in antagonist group vs. 27.4% in agonist group, p=NS) and implantation rate (11.4% in antagonist group vs. 12.0% in agonist group, p=NS) between two groups. Mean number of retrieved oocytes was significantly higher in GnRH agonist LP group than in GnRH antagonist MDP group ($5.4{\pm}3.5$ vs. $6.6{\pm}5.0$, p<0.0001). But, the number of mature and fertilized oocytes, and the number of good quality (grade I and II) and transferred embryos were not different between two groups. In each group A, B, and C, the rate of poor response did not differ according to stimulation protocols. Conclusions: In conclusion, for infertile women expected poor ovarian response such as who are old age or has elevated basal FSH level, a protocol including a controlled ovarian hyperstimulation using GnRH antagonist appears at least as effective as that using a GnRH agonist, and may offer the advantage of reducing gonadotropin consumption and treatment period. However, much work remains to be done in optimizing the GnRH antagonist protocols and individualizing these to different cycle characteristics.

• Clinical and Experimental Reproductive Medicine
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• 제18권2호
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• pp.201-208
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• 1991

Recently the application of gonadotropin-releasing hormone (GnRH) agonist to superovulation in previous poor responders has resulted in the improved outcomes after in vitro fertilization (IVF) outcome. However, poor responders with poor estradiol $(E_2)$ rise or single dominant follicle are a particularly challenging group. Recent reports have also shown that patients with higher basal serum follicle stimulating hormone (FSH) level, result in poorer ovarian response and lower pregnancy rate. Analysis of the differences of superovulation outcomes according to the different protocols of GnRH agonist, long (L, n = 18) and short (S, n = 16) protocols, in patients with high basal FSH levels (>20mIU/ml) were undertaken at Seoul National University Hospital from June to October 1990. The administration of GnRH agonist was begun on day 21 of the cycle in long protocol, and on day 2 in short protocol. Ages of patients and husbands, basal FSH and luteinizing hormone (LH) levels and FSH/LH ratio did not differ significantly. Types and causes of infertility were evenly distributed. Whereas the duration of stimulation and the amounts of gonadotropins administered were significantly reduced in short protocol, the numbers of oocytes retrieved and cleaved, the cleavage rate and the number of embryos transferred were higher in long protocol without statistical signifieance. The pregnancy rate per ET was 16.7% (2/12) in short protocol, and 17.6% (3/17) in long protocol. These data suggest that both protocols result in the similar superovulation outcomes in patients with higher basal serum FSH levels.

• Clinical and Experimental Reproductive Medicine
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• 제35권4호
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• pp.309-317
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• 2008

목 적: 체외수정을 위한 과배란유도 시 난소 반응성의 예측 인자로서 항뮬러리안 호르몬 (AMH)의 효용성을 FSH와 비교하여 알아보고, 체외수정 결과와의 관계도 알아보고자 하였다. 연구방법: 2007년 1월부터 2007년 8월까지 단기 요법이나 GnRH antagonist 요법을 이용하여 체외수정을 시행하는 111명을 대상으로, 생리주기 3일째 혈중 AMH 및 FSH를 전향적으로 측정하였다. 과배란유도 후 채취된 난자 개수와 AMH 또는 FSH의 상관관계를 분석하였고, 채취된 난자 수 및 AMH 수치에 따라 과배란유도 결과와 체외수정 결과를 비교하였다. 저반응군 및 과반응군의 예측을 위한 AMH의 임계치를 알아보기 위해 ROC curve 분석을 시행하였다. 결 과: AMH는 채취된 성숙 난자 수와 밀접한 양의 상관관계를 나타냈으며 (r=0.792, p<0.001), FSH (r=-0.477, p<0.001) 보다 더 높은 상관관계를 보였다. 난소 반응성에 따라 저반응군 (성숙난자수 ${\leq}2$), 정상반응군 ($3{\sim}16$), 과반응군 (${\geq}17$)으로 나누어 AMH와 FSH 수치는 유의한 차이를 보였으며, 저반응군 (채취된 성숙 난자 수${\leq}2$) 및 과반응군 (채취된 성숙 난자 수${\geq}17$)을 예측하는데 ROC curve 상 AMH의 임계치는 각각 <0.50 ng/ml (sensitivity 88.9%, specificity 89.5%), 및 ${\geq}2.60\;ng/ml$ ((sensitivity 85.7%, specificity 87.0%)였다. AMH level에 따라 low AMH group (${\leq}0.60\;ng/ml$), normal AMH group ($0.60{\sim}2.60\;ng/ml$), high AMH group으로 구분하여, 각 군간 채취된 성숙 난자 수와 ($2.7{\pm}2.2$, $8.1{\pm}4.8$, $16.5{\pm}5.7$, p<0.001), 투여된 성선자극호르몬제의 용량에 ($3530.5{\pm}1251.0$, $2957.1{\pm}1057.6$, $2219.2{\pm}751.9\;IU$, p<0.001) 유의한 차이를 보였다. 성숙 난자의 비율과 수정율에 유의한 차이는 없었으며 임신율도 23.8%, 34.0%, 37.5%로 각 군간 유의한 차이는 없었다. 결 론: 혈중 기저 AMH는 과배란유도 시 채취되는 성숙 난자 수와 높은 상관관계가 있어 난소 반응성의 예측 인자로서 유용할 것으로 생각된다. AMH 수치에 따라 체외수정 결과에는 차이가 없었으나, 저반응군 및 과반응군의 예측에 유용하여 체외수정 시 주기의 취소나, 환자별 적정 용량의 결정 및 난소과자극 증후군의 위험을 감소시키는데 도움이 될 것으로 사료된다.

• 핵의학기술
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• 제20권2호
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• pp.54-61
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• 2016

1. 목적 성조숙증은 2차성징의 발달이 여아에서는 8세 이전 남아에선 9세 이전에 조기 2차성징이 출현하는 증상으로 골단의 조기 폐쇄를 일으켜 결국 최종 성인 신장의 감소를 가져오는 질환이다. 본 연구는 성조숙증으로 내원한 여아들의 GnRH(Gonado-tropin-releasing Hormone) 자극검사 결과와 의무기록을 후향 분석하여 진단별 차이를 알아보고자 하였다. 2. 방법 2015년 2월부터 2015년 12월까지 분당서울대병원 소아청소년 내분비내과를 내원한 여아 118명을 대상으로 하였다. 의무기록을 후향 분석하여 대상 환아들은 진성 성조숙증(true precocious puberty) 57명, 조기사춘기(early puberty) 39명, 유방 조기발육군(premature thelarche) 22명을 진단별로 분류하였다. 진단 당시의 신장, 체중, Tanner stage, 골연령, 역연령, 부모의 키, GnRH 검사에서 LH, FSH와 E2 (Estradiol) Basal 값도 함께 조사하였다. 성선 자극호르몬 결과값 LH (Basal,30min,45min,60min) FSH(Basal,30min,60min)을 비교하여 각 그룹별 LH, FSH Peak치 분포도와 LH 최고치/LH 기저치 비율에 대한 평균${\pm}$표준편차와 LH 최고치/FSH 최고치 비율에 대한 평균${\pm}$표준편차를 비교하여 각 3그룹 간 유의확률(P-value) 값을 구하였다. 골연령의 측정은 Greulich-Pyle법(왼쪽 수근골 X선 사진을 촬영하여 골성숙도를 평가하는 방법- 6개월 단위의 표준손목사진을 보고 비교해서 골연령을 유추하는 방식)을 이용한 소아 청소년 내분비내과 교수가 직접 판독한 결과로 사용하였고 GnRH 검사는 합성 LHRH 100 ug을 정맥 주사하여 LH는 Basal, 30분, 45분,60분 후에 채혈된 결과값과 FSH는 Basal, 30분, 60분후에 채혈된 결과값을 조사하였다. 3. 결과 진성성조숙증그룹의 평균 키는$131{\pm}14.85$, 평균체중은 $8.80{\pm}4.93$, 평균역연령은 $7.1{\pm}0.81$, 평균 골연령은 $9.9{\pm}0.9$, 조기사춘기 그룹의 평균키는 $134{\pm}5.10$, 평균체중은 $28.50{\pm}4.43$, 평균역연령은 $8.05{\pm}0.03$, 평균 골연령은 $10.0{\pm}0.62$, 유방조기발육군의 평균 키는 $129{\pm}6,01$ 평균체중은 $28.65{\pm}5.98$, 평균역연령은 $7.02{\pm}0.58$ 평균 골연령은 $8.04{\pm}1.29$로 세 그룹간에 키와 체중 비교 시 유의한 차이가 없었고 역연령(P < 0.0001), 골연령( P< 0.0001), 골연령과 역연령과의 차이(P < 0.0002 )에서는 그룹간 유의한 차이가 있었다. 각 그룹별 LH, FSH Peak치 분포도 비교시 진성성조숙증 그룹은 LH 30분-82.5%, 45분-12.3%, 60분-5.3%, FSH 30분-8.8%, 60분-91.2%로 높은 Peak치를 보였고 조기사춘기 그룹은 LH 30분-79.5%, 45분-17.9%, 60분-2.6%, FSH 30분-7.7%, 60분 -92.32%로 높은 Peak치를 나타내었다. 유방조기 발육군 그룹에서는 LH 30분-30%, 45분-59%, 60분-9.09%, FSH 30분 -0%, 60분-100%로 Peak치를 나타내었다. LH Peak/LH basal ratio 비교시 진성성조숙증 그룹은 $19.09{\pm}17.15$, 조기사춘기 그룹은 $15.23{\pm}10.88$ 유방조기 발육군 그룹은 $4.93{\pm}4.36$으로 3 그룹간 유의한 차이를 보였다(P < 0.0001). LH Peak/FSH Peak ratio 비교시 진성성조숙증 그룹은 $1.222{\pm}0.77$, 조기사춘기 그룹은 $1.34{\pm}1.23$ 유방조기 발육군 그룹은 $0.3{\pm}0.09$로 3 그룹간 유의한 차이(P < 0.0001)를 보였다. 4. 결론 여아들의 진성성조숙증을 진단하기 위한 GnRH Test 검사는 자극 후 30분과 60분 사이에 LH 최고치가 기저치에 비해 2~3배 이상 증가 되어 있거나 또는 5~10 IU/L 이상 증가되었을 때 유용한 판정 자료로 이용 될 수 있는 핵의학 연속검사라고 사료되어진다.

• Clinical and Experimental Reproductive Medicine
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• 제25권1호
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• pp.93-102
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• 1998

Normal and abnormal follicular growth and steroidogenesis depend on gonadotropins as well as intraovarian peptides, which may mediate or potentiate gonadotropin action. Inhibin also affect follicular development and steroidogenesis and may play a role in dominant follicle selection and follicular atresia. Therefore, we studied the differences of serum inhibin, gonadotropin and androgen levels in the women with only the ultrasound findings and no disorder, and polycystic ovary (PCO) with ovulatory disturbance. We prospectively analysed forty-three women with PCO. The diagnosis of PCO was based on typical appearance of the ovaries on TVS. Twelve women with regular menstrual cycle and normal ovarian morphology were selected as control. Basal levels of inhibin, luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol $(E_2)$, testosterone (T), androstenedione (ADD), dehydroepiandrosterone-sulfate (DS), prolactin and TSH in serum were determined. There were significant differences in basal LH levels and LH/FSH ratio between the control and the women with PCO. The basal levels of inhibin and $E_2$ in the oligo-amenorrheic PCO (N=34) were significantly higher than those in the control. There was higher negative correlation between the inhibin and T levels in the oligo-amenorrheic PCO, but, not in the regular cycling PCO. Also, there was higher positive correlation between the LH and T levels in the oligo-amenorrheic PCO, but not in the regular cycling PCO. These data presume that the initial event of PCO is elevated pituitary LH secretion. Elevated levels of LH may down-regulate LH receptors on granulosa cells and also cause hypertrophy of the thecal layer. High level of androgen secreted by the hypertrophied thecal layer may stimulate inhibin secretion from granulosa cells and can be converted to estrogen by extraovarian tissues and could serve to augment pituitary sensitivity to GnRH with a resultant secretion of more LH than FSH. Inhibin may inhibit FSH action on granulosa cell in the PCO follicle, impairing follicular development and dominant follicle selection resulted in ovulatory disturbance.

• Clinical and Experimental Reproductive Medicine
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• 제39권4호
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• pp.176-181
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• 2012

Objective: In 2009 anti-M$\ddot{u}$llerian hormone (AMH) assay was approved for clinical use in Korea. This study was performed to determine the reference values of AMH for predicting ovarian response to controlled ovarian hyperstimulation (COH) using the clinical assay data. Methods: One hundred sixty-two women who underwent COH cycles were included in this study. We collected data on age, basal AMH and FSH levels, total dose of gonadotropins, stimulation duration, and numbers of oocytes retrieved and fertilized. Blood samples were obtained on cycle day 3 before gonadotropin administration started. Serum AMH levels were measured at a centralized clinical laboratory center. The correlation between the AMH level and COH outcomes and cut-off values for poor and high response after COH was analyzed. Results: Concentration of AMH was significantly correlated with the number of oocytes retrieved (OPU; r=0.700, p<0.001). The mean${\pm}$SE serum AMH levels for poor ($OPU{\leq}3$), normal ($4{\leq}OPU{\leq}19$), and high ($OPU{\geq}20$) response were $0.94{\pm}0.15$ ng/mL, $2.79{\pm}0.21$ ng/mL, and $6.94{\pm}0.90$ ng/mL, respectively. The cut-off level, sensitivity and specificity for poor and high response were 1.08 ng/mL, 85.8%, and 78.6%; and 3.57 ng/mL, 94.4%, and 83.3%, respectively. Conclusion: Our data present clinical reference values of the serum AMH level for ovarian response in Korean women. The serum AMH level could be a clinically useful predictor of ovarian response to COH.