• Clinical and Experimental Reproductive Medicine
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• v.32 no.4
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• pp.301-314
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• 2005

Objective: Rebamipide is a propionic acid derivative that has an action of the inhibition of superoxide production and removal of hydroxyl radical with the sperm incubation and cryopreservation. In the present study, to investigate whether rebamipide is useful to treat male infertility and sterility, the author observed the antioxidative effects in patient with male infertility and also examined its absorption and distribution in rat genital organ. Methods: To measure the distribution of rebamipide in reproductive organ in the rat, carbon indicated rebamipide, $^{14}C-OPC-12759$, was orally administered to 10 Spraque-Dawley rats and its organ concentration in serum, liver, kidney, stomach, duodenum, colon, urinary bladder, seminal vesicle, epididymis and testicle were measured each time after 0.5, 1, 2, 4, 8 and 24 hours by using HPLC fluorescent method. The concentrations in semen were measured by HPLC fluorescent method in a sample of 50 infertile males who took 900 mg of rebamipide daily for 3 months. To measure the antioxidative effect and fertility rate for 3 months, each month before and after the treatment, sperm motility, vitality, the oxygen free radical formation, level of peroxidation, fetilizing capacity of semen sample which were obtained from infertile male patients by masturbation after at least 48 hours abstinence were analyzed by computer assisted semen analyzer, eosin-nigrosin stain, chemiluminescence, thiobarbituric acid method and hypo-osmotic swelling test. Simultaneously in a sample that wanted baby, both pregnancy and delivery were researched. Results: The $^{14}C-OPC-12759$ concentration in the body of white rats was highest in gastrointestinal organ like stomach, smal intestine and duodenum and followed by genital organ like seminal vesicle, testis and epididymis. The rebamipide concentration in semen of infertile males was $220.77{\pm}327.84ng/mL$ (SD) which showed a large deviation but it was higher than serum which was $126{\pm}76ng/mL$ (SD). In the infertile males, after the treatment with rebamipide, the level of seminal reactive oxygen species (ROS) and lipid peroxidation have significantly decreased in duration of the treatment (p<0.05) and sperm vitality and fertilizing capacity except sperm motility significantly improved on post treatment of 2~3 months (p<0.05). Out of the 41 cases who hoped for pregnancy, 15 cases (36.6%) became pregnant and 12 cases had childbrith, 2 cases had miscarriage and one case is ongoing. The side effect was observed in 1 case (2%) which experienced diarrhea but it was lost spontaneously. Conclusions: We conclude from this study that rebamipide showed relatively high tendancy of absorption and excretion in the genital organ. In infertile males who had elevated ROS in semen, by specifically inhibiting the cell damage from the antioxidation, a way to preserve sperm motility, vitality and fertilizing capacity was confirmed.

• The Korean Journal of Pharmacology
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• v.23 no.2
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• pp.143-149
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• 1987

We determined the maternal peripheral lymphocyte response to mitogen during the period of implantation and evaluated the effects of hormones, which are known to be involved in the process of implantation, on the lymphocyte activity in rabbits. As compared with peripheral lymphocyte activity in non-pregnant rabbits, lymphocyte activity was significantly depressed on days 6, 7 and 9 of pregnancy. Although concentrations of serum progesterone were gradually increased during the implantation period, progesterone did not inhibit lymphocyte activity at physiological concentration. Serum $PGF_{2{\alpha}}$ was significantly increased on day 7 while PGE was slightly increased. $PGF_{2{\alpha}}$ did not modify lymphocyte activity even with greater concentrations than physiological level. However, lymphocyte activity was significantly inhibited by PGE even with physiological doses. The treatment of indomethacin at doses of 0.1 or $1.0\;{\mu}g/ml$ tended to enhance lymphocyte response, which was depressed on day 8 of pregnancy, 28% or 23% respectively. Although in non-pregnant rabbit, enhancement of lymphocyte response was also shown after the treatment of indomethacin, this enhancement was much less than that in pregnant rabbits. These results strongly suggest that maternal immune response was depressed during the process of implantation and PGE might be one of factors for immunomodulation during this period.

• Clinical and Experimental Reproductive Medicine
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• v.38 no.3
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• pp.159-163
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• 2011

Objective: To compare the IVF outcomes of mild ovarian stimulation with conventional ovarian stimulation in poor responders. Methods: From 2004 to 2009, 389 IVF cycles in 285 women showed poor responses (defined as either a basal FSH level ${\geq}$12 mIU/mL, or the number of retrieved oocytes ${\leq}$3, or serum $E_2$ level on hCG day <500 pg/mL) were analyzed, retrospectively. In total, 119 cycles with mild ovarian stimulation (m-IVF) and 270 cycles with conventional ovarian stimulation (c-IVF) were included. Both groups were divided based on their age, into groups over and under 37 years old. Results: The m-IVF group was lower than the c-IVF group in the duration of stimulation, total doses of gonadotropins used, serum $E_2$ level on hCG day, the number of retrieved oocytes, and the number of mature oocytes. However, there was no significant difference in the number of good embryos, the number of transferred embryos, the cancellation rate, or the clinical pregnancy rate. In the m-IVF group over 37 years old, the clinical pregnancy rate and live birth rate were higher when compared with the c-IVF group, but this result was not statistically significant. Conclusion: In poor responder groups, mild ovarian stimulation is more cost effective and patient friendly than conventional IVF. Therefore, we suggest that mild ovarian stimulation could be considered for poor responders over 37 years old.

• Journal of Life Science
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• v.17 no.6 s.86
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• pp.859-866
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• 2007

The main objective of this study was to investigate the effects of exercise on serum insulin and leptin levels and GLUT-4 and VAMP-2 in skeletal muscles from the pregnant rats. F344 rats were randomly divided into four groups (n = 15 in each group): control group (CG), pregnant group (PG), pregnant running group (PR), and pregnant swimming group (PS). From the 15th day of pregnancy, animals in the running group were forced to run on treadmill for 30 min with a light intensity, while those in the swimming group were forced to swim in swimming pool for 10 min once a day for 6 consecutive days. The present result demonstrated that in pregnant rat group, serum insulin levels significantly in-creased and leptin levels significantly decreased. Skeletal GLUT-4 and VAMP-2 protein expression was significantly decreased in pregnant rats compared to non-pregnant rats. However, matenal running during gestational period alleviated pregnancy-induced changes in plasma insulin and leptin levels, and it significantly enhanced skeletal GLUT-4 and VAMP-2 protein expression. From those results, it can be suggested that running exercise during gestational period may improve glycemic control by up-regulating GLUT-4 and VAMP-2 protein expression.

• Clinical and Experimental Reproductive Medicine
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• v.19 no.2
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• pp.133-141
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• 1992

We examined effects of co-culture with human oviduct epithelial cells (HOEC) on the development of mouse and human embryos from early embryonic· stage to late morula or blastocyst stage (LM or B). In human, embryos were transferred and pregnancy rate was investigated. The HOEC, collected from surgically removed fallopian tube, were cultured in medium-199 supplemented with 20 % fetal cord serum (FCS). The HOEC were characterized by using immunocytochemical staining with anticytokeratin antibody and then used for cultures of mouse and human embryos. Results obtained from co-culture system were as follows. Development rate of mouse embryos was improved by co-culture system at late developmental stage (p<0.025). Human supernumerary embryos remained after transfer, unsuitable for freezing because of their poor quality, were co-cultured for 72hrs. Co-culture (78.79%) or conditioned medium (78.26%) system improved the developmemt rate, significantly, in comparision with control (11.11%)(p<0.00l). Co-cultured (85.71%) human zygotes for 24hrs showed the better development rate in comparision with control (50.00%) (p<0.01). When we transferred embryos cultured with the HOEC to patients, we obtained one pregnancy. Co-cultured human zygotes for 24hrs showed the better quality and viability for the replacement in comparision with control (p<0.01). In addition, improved pregnancy rate was obtained. Our results suggest that the co-culture system can rescue early degenerating embryos by improving early development and yield a resonable number of blastocyst for the appropriate replacement. The effect provided by cultured HOEC is not species specific for the development of embryos and it can be used to overcome in vitro blocks for the development. And also the co-culture system offers the possibility to freeze embryos at blastocyst stage which is more sucessful stage for the freezing. The HOEC monolayer may provide some stimulus via specific factor, which is unknown, to the development of embryos. Our results showed that the co-culture system with HOEC can be an alternative to conventional culture system.

• Clinical and Experimental Reproductive Medicine
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• v.25 no.3
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• pp.239-244
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• 1998

The purpose of this study is compare IVF cycle outcome in poor responders between clomiphene citrate (CC) stimulated and controlled ovarian hyperstimulation (COH) protocol. A total of 94 patients responding poorly in previous IVF cycles (estradiol<600 pg/ml or less than 3 oocytes retrieved) subsequently underwent either COH (COH group: 122 cycles, 68 patients) or CC-stimulated cycles (CC group: 43 cycles, 26 patients). CC was administered for five consecutive days starting on cycle day 3 at a dose of 100 mg daily. Serial transvaginal ultrasound examination was done from cycle day 8. Urine was collected $3\sim4$ times before hCG injection for the detection of LH surge. The hCG was administered when serum estradiol reached greater than 150 pg/ml and mean follicle diameter>16 mm. In COH group, ovarian stimulation was done using short protocol (GnRH-a/FSH/HMG/hCG). No difference in age or number of transferred embryos was found between CC group and COH group. COH group had significantly (p<0.05) higher mean peak level of $E_2$ ($810{\pm}112$ vs $412{\pm}55$ pg/ml) and greater number of retrieved oocytes ($3.0{\pm}0.2$ vs $2.0{\pm}0.2$) than CC group. CC group had transferred embryos $(1.8{\pm}0.2)$ compared with $(2.1{\pm}0.2)$ in COH group. However, CC group had higher pregnancy rate than COH group per retrieval [26.9% (7/26) vs 6.2% (6/97)], or per transfer [31.8% (7/22) vs 7% (6/86)]. Although cycle cancellation rate in CC group (48.8%) was higher than that of COH group (21.3%), the pregnancy rate per cycle in CC group was still higher (16.3%) than COH group (4.9%). In addition, implantation rate in CC group was 17.5% (7/40), which was significantly (p<0.01) higher than 3.9% (7/180) in COH group. These data suggest that oocyte and embryo quality are lower in COH cycles of poor responders than CC cycles. We suggest that clomiphene citrate stimulated IVF cycle may be more efficient than COH IVF cycle in poor responders in terms of lower costs and higher pregnancy performance.

• The Korean Journal of Nuclear Medicine
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• v.15 no.1
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• pp.1-11
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• 1981

To evaluate the diagnostic accuracy of the measurement of free thyroxine (FT4) by radioimmunoassay, we measured free $T_4\;and\;T_4,\;T_3,\;T_3RU$, TSH and TBG serum levels by radioimmunoassay in 18 healthy persons and 52 patients with various thyroid diseases and 11 normal pregnant women. The results are as follows. 1. In 19 cases of overt hyperthyroidism, $T_3,\;free\;T_4$ and FTI, $T_4/TBG$ ratio reflect hyperfunction in all cases. $T_4$ is increased in 94% (18/19) and TBG and TSH are decreased in 79% (15/19). 2. In 8 patients with overt hypothyroidism, TSH is increased in all cases and free $T_4$ and FTI is decreased in all cases. $T_4$ is decreased in 87.5% (7/8), $T_3$ is decreased in 75% (6/8) and $T_4/TBG$ ratio is decreased in 62.5% (5/8). 3. In 5 patients who are clinically in euthyroid state after treatment of hyperthyroidism, $T_4,\;free\;T_4$, FTI and TSH are in the normal range in all cases and $T_3$ is normal in 60% (3/5) and slightly increased in 40% (2/5). 4. In 10 patients who showed clinically borderline hypothyroidism after treatment of hyperthyroidism, TSH is increased in all cases and free $T_4$ and FTI are decreased in all cases, but $T_4\;and\;T_3,\;T_4/TBG$ ratio are in the normal limit in all cases. So after treatment of hyperthyroidism, TSH, free $T_4$ or FTI are recommended as optimal thyroid function test. 5. In normal pregnancy, free $T_4$, FTI and $T_4/TBG$ ratio reflect normal function, but the other parameters revealed unreliable due to the influence of increased TBG. Also TBG and TSH level in pregnancy is increased significantly compared with normal healthy control group. 6. The coefficients of correlation between free $T_4$ and FTI were 0.862 (p<0.001) and 0.685 (p<0.001) between free $T_4\;and\;T_4/TBG$ ratio. In most patients, diagnostic value of free $T_4$ was comparable and even superior to FTI, so free $T_4$ measurement can be used routinely with thyrotropin assay in the diagnosis of hypothyrodism or with $T_3$ for the diagnosis of hyperthyroidism.

• The Korean Journal of Nuclear Medicine Technology
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• v.12 no.1
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• pp.62-65
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• 2008

Purpose: Vitamin $B_{12}$ and folic acid are type of water-soluble vitamin and those work as a secondary vital enzyme, but especially those are involved in the nuclear DNA synthesis. Those are mainly measured in order to diagnose megaloblastic anemia and to assess the storage of folic acid during pregnancy. It is generally known that the hemolyzed serum is useless for folic acid and vitamin $B_{12}$, but it is not easy to abide by this information because our lab (Samkwang Medical Laboratories) is reference laboratory. We tested how much the extent of hemolyzed serum had influence on the results. Materials and Method: We performed the tests of vitamin $B_{12}$, folic acid. For the hemolysis effect study, we used 40 cases. According to the level of A, B and C groups, each group had 10 samples which were mechanically hemolyzed serum. Results: Hemolysis did not affect the vitamin $B_{12}$ results. However in case of folic acid, the value increased according to the degree of hemolysis. And severe hemolyzed cases had the highest value (greater than 20 ng/ml). Conclusions: Preventing the hemolysis, it has to be informed that blood-collecting, separation and storage are performed more carefully. As you see from the above results, hemolyzed serum is not proper for folic acid test, and hemolysis does not affect the results of vitamin $B_{12}$. However, for the more accurate results, it is necessary to avoid hemolysis.

• Korean Journal of Veterinary Research
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• v.44 no.4
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• pp.523-532
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• 2004

The present study was carried out to investigate the potential adverse effects of amitraz on pregnant dams after maternal exposure during the gestational days (GD) 1 through 19 in Sprague-Dawley rats. The test chemical was administered orally to pregnant rats at dose levels of 0, 3, 10, or 30 mg/kg/ day. During the test period, clinical signs, mortality, body weights, food consumption, serum biochemistry, gross findings, organ weights and reproductive findings on GD 20 were examined. In the 30 mg/kg group, an increase in the incidence of abnormal clinical signs and death, a suppression in the body weight gain, and a decrease in the food consumption were observed. A decrease in the liver weight and increases in the kidneys, adrenal glands and heart weights were also found. Serum biochemical investigations revealed increases in the aspartate aminotransferase (AST), total bilirubin, and chloride. In addition, an increase in the fetal death and decreases in the litter size and fetal body weight were seen at caesarean section. Inthe 10 mg/kg group, an increase in the incidence of abnormal clinical signs, decreases in the food consumption and liver weight, increases in the total bilirubin and chloride, and a decrease in the fetal body weight were observed. There were no adverse effects on clinical signs, mortality, body weights, food consumption, serum biochemistry, gross findings, organ weights and reproductive findings in the 3 mg/kg group. Based on the results, it was concluded that the 19-day repeated oral dose of amitraz to pregnant rats caused increases in the clinical signs, kidneys, adrenal glands and heart weights, AST, total bilirubin and chloride and decreases in the body weight gain, food consumption and liver weight at the dose levels of above 10 mg/kg/day. Under the present experimental conditions, the no-observed-adverse-effect level (NOAEL) of amitraz was considered to be 3 mg/kg/day.

• Clinical and Experimental Reproductive Medicine
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• v.14 no.2
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• pp.127-137
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• 1987

Steroid hormone profiles during luteal phases after in vitro fertilization(IVF) and embryo transfer(ET) have been evaluated in 83 cycles stimulated by pure follicle-stimulating hormone/human menopausal gonadotropin/human chorionic gonadotropin, in which 13 patients became pregnant. Serum estradiol($E_2$) and progesterone($P_4$) levels were determined on days 2, 5, 7 and 9 after laparoscopic follicle aspiration. The follicular $E_2$ peak was slightly higher in pregnancies than in failures. Positive correlations were observed between the follicular $E_2$ peaks and the $P_4$ levels on days 5 and 7 of the luteal phase in pregnancies, but no correlation was found in failures. The $E_2$ and $P_4$ levels on days 5 and 7 of the luteal phase were significantly higher in pregnancies than in failures, but not different on days 2 and 9. Values of the $P_4/E_2$ ratio were similar between the two groups. The luteal phase durations were 12 to 19 days and no correlation was observed between the lengths of luteal phase and the luteal $E_2$ or $P_4$ concentrations. These data suggest that high $P_4$ levels in the mid-luteal phase, which have positive correlations with the follicular $E_2$ peaks, might have a favorable influence on the pregnancy success in human IVF.