• Clinical and Experimental Reproductive Medicine
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• v.36 no.4
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• pp.265-274
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• 2009

Objective: MicroRNAs (miR) are known to repress target genes at post-transcriptional level and play important roles in development and maturation of cell. However, the expression profiles of miR during ovarian follicle maturation have not been fully elucidated. Here, we designed this study to investigate the expression profiles of miR in oocytes and granulose cells (G-cells) after in vitro culture according to gonadotropins and adding hCG. Methods: Ovaries from 12-day-old mice (C57BL6) were removed and preantral follicles were isolated and cultured in $20\;{\mu}L$-drop of culture media with supplementation of either rFSH, rLH, or rFSH+rLH. After their full maturation, follicles were incubated with rhCG and rEGF. RNA was isolated from oocytes and G-cells, and real-time PCR were performed with primers of miR known to be expressed in the mouse ovary (mmu-miR-16, -miR-27a, -miR-126, -miR-721). Results: FSH+LH group showed the highest ovulation and MII rates among gonadotropin groups. The profiles of miRs in oocytes and G-cells differed according to gonadotropin groups and adding hCG. The profiles of miRs showed divergent changes between oocytes and G-cells. Conclusion: miR expression profiles are altered by gonadotropins and supplementation of hCG during in vitro maturation of murine follicles. Target gene study must be necessary to validate these findings.

• Clinical and Experimental Reproductive Medicine
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• v.37 no.1
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• pp.49-56
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• 2010

Objective: To investigate assisted reproductive technology (ART) outcomes in women with WHO class I anovulation compared with control group. Design: Retrospective case-control study. Methods: Twenty-three infertile women with hypogonadotropic hypogonadism (H-H) who undertook ART procedure from August 2003 to January 2009 were enrolled in this study. A total of 59 cycles (H-H group) were included; Intra-uterine insemination with super-ovulation (SO-IUI, 32 cycles), in vitro fertilization with fresh embryo transfer (IVF-ET, 18 cycles) and subsequent frozenthawed embryo transfer (FET, 9 cycles). Age and BMI matched 146 cycles of infertile women were collected as control group; 64 cycles of unexplained infertile women for SO-IUI and 54 cycles of IVF-ET and 28 cycles of FET with tubal factor. We compared ART and pregnancy outcomes such as clinical pregnancy rate (CPR), clinical abortion rate (CAR), and live birth rate (LBR) between the two groups. Results: There was no difference in the mean age ($32.7{\pm}3.3$ vs. $32.6{\pm}2.7$ yrs) and BMI ($21.0{\pm}3.1$ vs. $20.8{\pm}3.1kg/m^2$) between two groups. Mean levels of basal LH, FSH, and $E_2$ in H-H group were $0.62{\pm}0.35$ mIU/ml, $2.60{\pm}2.30$ mIU/ml and $10.1{\pm}8.2$ pg/ml, respectively. For ovarian stimulation, H-H group needed higher total amount of gonadotropin injected and longer duration for ovarian stimulation (p<0.001). In SO-IUI cycles, there was no significant difference of CPR, CAR, and LBR between the two groups. In IVF-ET treatment, H-H group presented higher mean $E_2$ level on hCG day ($3104.8{\pm}1020.2$ pg/ml vs. $1878.3{\pm}1197.7$ pg/ml, p<0.001) with lower CPR (16.7 vs. 37.0%, p=0.11) and LBR (5.6 vs. 33.3%, p=0.02) and higher CAR (66.7 vs. 10.0%, p=0.02) compared with the control group. However, subsequent FET cycles showed no significant difference of CPR, CAR, and LBR between the two groups. Conclusion: H-H patients need higher dosage of gonadotropin and longer duration for ovarian stimulation compared with the control groups. Significantly poor pregnancy outcomes in IVF-ET cycles of H-H group may be due to detrimental endometrial factors caused by higher $E_2$ level and the absence of previous hormonal exposure on endometrium.

• Journal of Chest Surgery
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• v.42 no.1
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• pp.119-122
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• 2009

Choriocarcinoma is a germ-cell tumor that originates from syncytiotrophoblastic cells and this tumor secrets beta-human chorionic gonadotropin. It has been reported that extragonadal primary pulmonary choriocarcinoma is extremely rare. We report here on a 28-years-old woman who underwent right lower lobectomy for extragonadal nongestational primary pulmonary choriocarcinoma and she has survived for 2 years without recurrence.

• Development and Reproduction
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• v.15 no.4
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• pp.349-357
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• 2011

Since nesfatin-1/NUCB2 involved in the control of appetite and energy metabolism was discovered for the first time in hypothalamus, many reports have shown its expression in various tissues. We also recently demonstrated that nesfatin-1/NUCB2 was expressed in the reproductive organs of mouse. However, no data exist on nesfatin-1/NUCB2 expression, regulation, and secretion in the uterus. Therefore, we examined the expression of nesfatin-1/NUCB2 in mouse uterus and the effects of PMSG and estrogen on its expression. NUCB2 mRNA expression in the uterus was determined by conventional and real-time PCR and nesfatin-1 protein expression was detected by western blotting. In immunohistochemistry staining, nesfatin-1 protein was localized at the epithelial cells of the uterine glands and endometrium. Nesfatin-1 protein binding sites were displayed at the epithelial cells of uterine glands and specific granulocytes including neutrophils. Additionally, to examine if the nesfatin-1/NUCB2 expression in the uterus is regulated by gonadotropin or estrogen, ovariectomized mice were treated with PMSG or $17{\beta}$-estradiol. The expression levels of NUCB2 mRNA in the uterus was significantly increased in the control mice after PMSG treatment, but not in the ovariectomized mice. In contrast, NUCB2 mRNA expression was dramatically increased in the ovariectomized mice after treatment with $17{\beta}$-estradiol. We report here for the first time that nesfatin-1/NUCB2 mRNA and protein express in the mouse uterus and its expression is regulated by estrogen secreted from the ovary, but not gonadotropin from the pituitary.

• Clinical and Experimental Reproductive Medicine
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• v.36 no.4
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• pp.275-281
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• 2009

Objective: This study was performed to evaluate the effect of oxytocin antagonist on the outcome of IVF/ICSI cycles in infertile patients with repeated failure of IVF/ICSI treatment. Method: Forty patients who had experienced two or more failures of IVF/ICSI treatment without low ovarian reserve, were recruited for this prospective randomized study. All patients received controlled ovarian stimulation (COS) using GnRH antagonist multidose protocol (MDP). For the intervention group, intravenous administration of atosiban (mixed vasopressin $V_{1A}$/oxytocin antagonist) started with a bolus dose 6.75 mg one hour before embryo transfer (ET) and continued at an infusion rate of 18 mg/hour. After ET, administered atosiban was reduced to 6 mg/hour and continued for 2 hours. The main efficacy endpoints were clinical pregnancy rate and implantation rate. Results: Patients' characteristics were comparable in the intervention and control groups. COS parameters and IVF results were also similar. The number of uterine contractions for 3 minutes measured just before ET was significantly lower in the intervention group than control group ($3.5{\pm}1.4$ vs $8.7{\pm}2.2$, p<0.001). While there was no statistically significant difference in the clinical pregnancy rate between control group and intervention group (20.0% and 40.0%, p=0.168), the implantation rate was significantly higher in the intervention group, with 16.9% (11/65) compared with 6.0% (4/67) in the control group (p=0.047). There were no differences in ectopic pregnancy rate and miscarriage rate between the two groups. Conclusion: This study demonstrates that administration of oxytocin antagonist during ET can improve the implantation rate probably by decreasing the frequency of uterine contractions in infertile patients undergoing IVF/ICSI treatment.

• Development and Reproduction
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• v.13 no.4
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• pp.353-362
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• 2009

GnRH and its receptor are known to express locally in the ovary and to regulate the ovarian function by affecting on granulosa and lutein cells. It has been reported that GnRH directly causes apoptosis in the granulosa and lutein cells of the ovary. However, whether the apoptosis of the cells by GnRH is recovered by FSH as an anti-apoptotic factor is not yet known. In this study, we evaluated the apoptosis and the production of progesterone $(P_4)$ and estradiol $(E_2)$ after treatment with 5, 50, and 100 ng/$m\ell$ GnRH and 1 IU/ml FSH in the granulosa-lutein cells that are obtained during oocyte-retrieval for IVF-ET. Results of DNA fragment analysis and TUNEL assay demonstrated that DNA fragmentation and the rate of apoptotic cells were increased in a dose-dependent manner showing a significant increase in the cells treated with 100 ng/$m\ell$ GnRH. In addition, we found that FSH suppresses the apoptosis of the cells induced by GnRH. In the results of chemiluminescence assay for $P_4$ and $E_2$, $P_4$ production was decreased by GnRH treatment, whereas $E_2$ production was not changed. We also demonstrated that FSH inhibits the suppressive effect of GnRH on $P_4$ production as the result of apoptosis. The present results suggest that GnRH agonist using in ovarian hyperstimulation protocol might induce the dysfunction of the ovary, but its function could be recovered by FSH. These results also will be expected to use as the basic data to elucidate the physiological role of GnRH and to develop new ovarian hyperstimulation protocols for IVF-ET.

• Clinical and Experimental Pediatrics
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• v.52 no.12
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• pp.1377-1382
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• 2009

Purpose:The gonadotropin-releasing hormone (GnRH) test results of girls with precocious puberty were analyzed to determine whether this test can efficiently and clearly differentiate between central precocious puberty (CPP) and other disorders. Methods:Clinical and laboratory data of 54 girls with precocious pubertal signs were reviewed. Intravenous GnRH test was performed with blood samples obtained at 0, 30, 60, and 90 minutes. A peak luteinizing hormone (LH) level of ${\geq}5.0IU/L$ was indicative of CPP. Results:Of the 40 girls with CPP, 36 (90.0%), 3 (7.5%), and 1 (2.5%) showed peak LH levels at 30, 60, and 90 minutes, respectively. A percentage of girls whose peak LH ${\geq}5.0IU/L$ up to 30, 60, and 90 minutes was 92.5%, 100%, and 100%, respectively. The peak LH/follicle stimulating hormone (FSH) ratio of girls with CPP was 0.89${\pm}$0.49 and was <1 in 16 of the 40 girls (40.0%). Girls with peak LH/FSH ratio of >1.0 showed higher chronological age (CA) ($8.3{\pm}0.6$ vs. $7.7{\pm}1.0$ years, P=0.033), bone age (BA) ($10.9{\pm}0.8$ vs. $9.7{\pm}1.1$ years, P=0.001), and BA-CA difference ($2.6{\pm}0.7$ vs. $2.0{\pm}0.7$ years, P=0.009) than those of girls with peak LH/FSH ratio of ${\leq}1.0$. Higher percentage of girls with peak LH/FSH ratio of >1.0 showed advanced breast development (${\geq}TannerIII$) (93.7% vs. 41.7%, P=0.001). Conclusion:LH levels after 30 and 60 minutes of intravenous GnRH administration are the most useful for diagnosing CPP in girls.