• Clinical and Experimental Reproductive Medicine
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• v.20 no.2
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• pp.125-130
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• 1993

Polycystic ovarian syndrome (PCOS) patients have a characteristic of high leuteinizing hormone (LH) to follicle -stimulating hormone (FSH) ratio. Usually, human menopausal gonadotropin (hMG) is used to induce ovulation in clomiphene citrate-resistant PCOS patients. However, HMG contains two components, namely, LH and FSH, with 50%, respectively. Therefore, FSH is theoretically recommended to stimulate follicular maturation. From the pituitary, LH is secreted by pulsatile pattern. So, we have been using intermittent subcutaneous injection of pure FSH for ovulation induction in 10 PCOS patients from March, 1990 to August, 1992. We obtained good results by intermittent subcutaneous injection of pure FSH. Ovulation is 100% per patient, and 88.2% per cycle. Pregnancy rate is 80% per patient, and 23.5% per cycle. Ovarian hyperstimulation syndrome (OHSS) is 50% per patient, 41.2% per all cycles, and 46.7% per all ovulated cycles. In comparison with HMG, pregnancy rate per cycle is relatively low. But, ovulation rate and pregnacy rate per person is higher than HMG. Because of the strict check of ovaries by the vaginal ultrasonography, OHSS rate is relatively high.

• Tuberculosis and Respiratory Diseases
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• v.44 no.3
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• pp.684-691
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• 1997

1be ovarian hyperstimulation syndrome is a rare but serious complication of ovulation induction therapy with gonadotropin. The clinical manifestations are generalized edema, ascites with pleural effusion and may become life-threatening in severe cases. The pathophysiology is still unknown, therefore, the treatment should be symptomatic and conservative. We report a case of severe OHSS with massive right pleural effusion in excess of ten liters after human menopausal gonadotropin therapy because of secondary infertility. Fluid and electrolyte imbalances were corrected and albumin was administered. A right chest tube was placed for a total of sixteen days, draining eleven liters of pleural effusion totally, resulting a dramatic decrease of pleural effusion and improvement of symptoms.

• Clinical and Experimental Reproductive Medicine
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• v.44 no.2
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• pp.63-72
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• 2017

Objective: Hyperstimulation methods are broadly used for in vitro fertilization (IVF) in patients with infertility; however, the side effects associated with these therapies, such as ovarian hyperstimulation syndrome (OHSS), have not been well studied. N-glycoproteomes are subproteomes used for the remote sensing of ovarian stimulation in follicular growth. Glycoproteomic variation in human follicular fluid (hFF) has not been evaluated. In this study, we aimed to identify and quantify the glycoproteomes and N-glycoproteins (N-GPs) in natural and stimulated hFF using label-free nano-liquid chromatography/electrospray ionization-quad time-of-flight mass spectrometry. Methods: For profiling of the total proteome and glycoproteome, pooled protein samples from natural and stimulated hFF samples were selectively isolated using hydrazide chemistry to obtain the total proteomes and glycoproteomes. N-GPs were validated by the consensus sequence N-X-S/T (92.2% specificity for the N-glycomotif at p<0.05). All data were compared between natural versus hyperstimulated hFF samples. Results: We detected 41 and 44 N-GPs in the natural and stimulated hFF samples, respectively. Importantly, we identified 11 N-GPs with greater than two-fold upregulation in stimulated hFF samples compared to natural hFF samples. We also validated the novel N-GPs thyroxine-binding globulin, vitamin D-binding protein, and complement proteins C3 and C9. Conclusion: We identified and classified N-GPs in hFF to improve our understanding of follicular physiology in patients requiring assisted reproduction. Our results provided important insights into the prevention of hyperstimulation side effects, such as OHSS.

• Clinical and Experimental Reproductive Medicine
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• v.35 no.1
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• pp.83-88
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• 2008

Thromboembolic disease associated with assisted reproductive techniques is considered to be extremely rare but most serious complication. The reasons for this are thought to hypercoagulable state characteristic of OHSS due to high serum levels of estrogen, hemoconcentration and reduced circulating blood volume, but is still unclear. The risk is increased those with rare hypercoagulable conditions such as antiphospholipid antibody syndrome, protein C deficiency, protein S deficiency, antithrombin III deficiency, and those with a personal or family history of thromboembolic disease. The majority of thrombosis reported were venous site but arterial thrombosis mostly intracerebral was reported 5 cases in Korea so far. We present a case of basilar a. thrombosis at 11 days after hCG injection. The patient developed the right hemiparesis, and recovered after intraarterial thrombolysis and transluminal angioplasty. Protein S activity was decreased and vWF antigen was increased. Decreased protein S activity was also found in previous reported 4 cases, so we suggest screening test for protein S in OHSS patients.

• Clinical and Experimental Reproductive Medicine
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• v.30 no.4
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• pp.333-340
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• 2003

Objective: This study was performed to examine the maturation and the development to the blastocyst stage of immature oocytes collected from patients with high risk of ovarian hyperstimulation syndrome (OHSS). Materials and Methods: Cumulus-oocyte complexes (COCs) were collected following only HCGpriming for non stimulated IVF-ET cycles of the patients. At the time of oocyte collection, COCs were classified into three groups in accordance with their appearance (Group I: oocytes with dispersed cumulus cells; Group II: oocytes with compacted cumulus cells; Group III: oocytes with sparse cumulus cells). The in vitro maturation and blastocyst development rates of the COCs were compared among these groups. From August 2001 to June 2002, 48 IVM/IVF-ET cycles from 42 patients (mean age: $32.4{\pm}3.8$ years) were performed. To prevent the occurrence of OHSS, the patients were primed with 10, 000 IU HCG alone 36 h before oocyte collection without gonadotropin stimulation. Oocytes were aspirated on cycle days from 7 to 13. The normal COCs were classified into three groups according to their appearance. The aspirated immature oocytes were cultured in YS maturation medium containing 30% (v/v) human follicular fluid (HFF), 1 IU/ml FSH, 10 IU/ml HCG and 10 ng/ml rhEGF. Fertilization was induced by intracytoplasmic sperm injection (ICSI). All zygotes were co-cultured with cumulus cells in $10{\mu}l$ YS medium containing 10% HFF until day 7 after oocyte collection. Blastocyst transfer was performed on day 5 after ICSI. Results: Th e mean number of oocytes cultured in the IVM/IVF cycles was $24.7{\pm}10.6$. Of 1185 COCs, those assigned to Group I, II and III were 470 (39.7%), 414 (35.0%) and 301 (25.4%), respectively. The maturation rate (94.5%, 444/470, p<0.05) in Group I was significantly higher than those of Group II (62.8%, 260/414) and Group III (73.1%, 220/301). Especially, 30.9% of COCs in Group I (145/470) was matured on the day of oocyte aspiration. There were no differences in the rates of fertilization and cleavage among the three groups. The development rate to the blastocyst stage in Group I (54.6%, 206/377, p<0.05) was also significantly higher than those in Group II (33.0%, 68/206) and Group III (30.1%, 52/173). Twenty-four clinical pregnancies (50.0%) was obtained and 22 pregnancies (45.8%) are ongoing. Implantation rate in the present study was 24.6%. Conclusion: These results suggest that there is a positive correlation between the appearance of COCs and the developmental competence of the immature oocytes in non stimulated IVM/IVF cycles.

• Clinical and Experimental Reproductive Medicine
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• v.29 no.4
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• pp.251-258
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• 2002

Objective : The aim of this study was to evaluate the outcomes of the GnRH antagonist (Cetrotide) minimal stimulation protocol comparing with GnRH agonist combined long step down stimulation protocol in PCOS patients. Materials and Method: From Apr 2001 to May 2002, 22 patients (22 cycles) were performed in controlled ovarian hyperstimulation using by GnRH antagonist and GnRH agonist for PCOS patients. GnRH antagonist (Cetrotide) combined minimal stimulation protocol was administered in 10 patients (10 cycles, Study Group) and GnRH agonist long step down stimulation protocol was administered in 12 patients (12 cycles, Control Group). We compared the pregnancy rate/cycle, total FSH (A)/cycle, Retrieved oocyte/cycle, the incidence of ovarian hyperstimulation syndrome, multiple pregnancy rate between the two groups. Student-t test were used to determine statistical significance. Statistical significance was defined as p<0.05. Results: Group of GnRH antagonist (Cetrorelix) minimal stimulation protocol produced fewer oocytes (6.4 versus 16.3 oocytes/cycle) using a lower dose of FSH (22.2 versus 36.1 Ample/cycle) and none developed OHSS and multiple pregnancy. Although the trends were in favour of the GnRH antagonist (Cetrorelix) protocol, the differences did not reach statistical significance. This was probably due to small sample size. Conclusion: The use of GnRH antagonist reduce the risk of ovarian hyperstimulation and multiple pregnancy. We suggest that GnRH antagonist might be alternative controlled ovarian hyperstimulation method, especially in PCOS patients who will be ovarian high response.

• Clinical and Experimental Reproductive Medicine
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• v.31 no.3
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• pp.191-200
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• 2004

Objective: To compare the clinical efficacy of double intrauterine insemination with single intrauterine insemination in GnRH antagonist combined ovarian hyperstimulation (Mild ovarian hyperstimulation) Materials and Methods: From Jan. 2001 to Jul. 2004, a retrospective clinical analysis was done of a total of 295 cycles in 170 patients who underwent ovarian hyperstimulation for ART (assisted reproductive technique). Subjects were divided into three groups; only clomiphene citrate ovarian hyperstimulation (n=55, 95cycles), GnRH antagonist combined ovarian hyperstimulation (soft ovarian hyperstimulation) (n=66 99cycles), and GnRH agonist combined ovarian hyperstimulation (short protocol) (n=49, 101cycles) Each group were randomly devided into two subgroups. One group underwent single IUI and the other group underwent double IUI. Results: GnRH antagonist group and GnRH agonist group had similar pregnancy rate. In GnRH antagonist Group, pregnancy rate was 36.1% in single IUI subgroup and was 36.6% in double IUI subgroup. These finding were not statistically significant. And Pregnancy rate was 20.8% in single IUI subgroup and was 19.3% in double IUI subgroup in single clomiphene citrate group, and 36.3% in single IUI subgroup and was 33.3% in double IUI subgroup in GnRH agonist group. These finding were not statistically significant, too. Conclusion: Pregnancy rate of GnRH antagonist was high and complication rate such as OHSS and multiple pregnancy was lower. In GnRH antagonist group, to compare with single IUI and double IUI, the result do not statistically differ. So GnRH antagonist single injection with single IUI was relatively comparable ART in infertiliry patient.

• Clinical and Experimental Reproductive Medicine
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• v.16 no.1
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• pp.57-68
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• 1989

Some infertile patients who need IVF-ET for conception have small ovarian cysts diagnosed in pelvic ultrasonography. It is well known that it is impossible or very difficult to perform controlled ovarian hyperstimulation(COH) for such patients because of the poor ovarian response or the possibility of ovarian hyperstimulation syndrome(OHSS). To remove or to decrease the size of ovarian cysts, estrogen and progesterone (E-P) therapy with oral contraceptives for 2 cycles and transvaginal aspiration of ovarian cysts using transvaginal ultrasonography were performed in 36 IVF-cancelled infertile patients with ovarian cysts from February to October, 1988 at Seoul National University Hospital. Thirty-nine ovarian cysts($32.8{\pm}9.6$mm in mean diameter) were treated with E-P therapy, and their size decreased to $28.2{\pm}11.0mm$ after 1 cycle and significantly to $24.8{\pm}14.7mm$ after 2 cycles. After E-P therapy for 2 cycles, 7(17.9%) ovarian cysts disappeared in ultrasonography, 9(23.1%) decreased in size significantly, 18(46.2%) had no change in size and 5(12.8%) increased in size. Thirty-two ovarian cysts($30.2{\pm}9.7mm$) in 30 patients were aspirated transvaginally, and there was no significant decrease in size after follow-up transvaginal ultrasonography($27.8{\pm}12.5mm$). After transvaginal aspiration, 3(9.4%) ovarian cysts disappeared and 28(87.5%) had no change in size. The mean amount of the transvaginally aspirated cystic fluids was $19.6{\pm}13.2ml$, and there was no malignant cells in aspiration cytology. Four endometrioid cysts, one dermoid cyst and one mucinous cyst could be diagnosed in consideration of the findings of transvaginal ultrasonography and the characteristics and cytology of aspirated fluids. Therefore E-P therapy and transvaginal aspiration of ovarian cysts had made it possible to restart IVF program earlier in the IVF-cancelled patients with ovarian cysts.

• Clinical and Experimental Reproductive Medicine
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• v.35 no.4
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• pp.309-317
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• 2008

Objectives: The aim of this study was to evaluate the usefulness of Anti-mullerian hormone (AMH) as a predictive marker for ovarian response and cycle outcome in IVF cycles. Methods: From Jan., to Aug., 2007, 111 patients undergoing IVF/ICSI stimulated by short or antagonist protocol were selected. On cycle day 3, basal serum AMH level and FSH level were measured. The correlation between basal serum AMH or FSH, and COH outcome was analyzed and IVF outcome was compared according to the AMH levels. To determine the threshold value of AMH for poor- and hyper-response, ROC curve was analyzed. Results: Serum AMH showed higher correlation coefficient (r=0.792, p<0.001) with the number of retrieved mature oocyte than serum FSH (r=-0.477, p<0.001). According to ovarian response, FSH and AMH leves showed significant differences among poor, normal, and hyperresponder. For predicting poor (${\leq}2$ oocytes) and hyperresponse (${\geq}17$ oocyets), AMH cut-off values were 0.5 ng/ml (the sensitivity 88.9% and the specificity 89.5%) and 2.5 ng/ml (sensitivity 85.7%, specificity 87.0%), respectively. According to the AMH level, patients were divided into 3 groups: low (${\leq}0.60\;ng/ml$), normal ($0.60{\sim}2.60\;ng/ml$), and high AMH (${\geq}2.60\;ng/ml$). The number of retrieved mature oocytes was significantly higher ($2.7{\pm}2.2$, $8.1{\pm}4.8$, $16.5{\pm}5.7$) and total gonadotropin dose was lower ($3530.5{\pm}1251.0$, $2957.1{\pm}1057.6$, and $2219.2{\pm}751.9\;IU$) in high AMH group (p<0.001). There was no significant difference in fertilization rates and pregnancy rates (23.8%, 34.0%, 37.5%) among the groups. Conclusions: Basal serum AMH level correlated better with the number of retrieved mature oocytes than FSH level, suggesting its usefulness for predicting ovarian response. However, IVF outcome was not significantly different according to the AMH levels. Serum AMH level presented good cut-off value for poor- or hyper-responders, therefore it could be useful in prediction of cycle cancellation, gonadotropin dose, and OHSS risk in IVF cycles.