• Clinical and Experimental Reproductive Medicine
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• v.8 no.2
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• pp.45-55
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• 1981

Clomiphene citrate. antiestrogen, was given to 39 infertile males whose spermatogenesis were disturbed and the efficacy of the drug was evaluated at the Department of Urology in 1980. (Table 1). Patients were divided into 3 clinical observation groups such as group I composed of 19 cases of idiopathic azoospermia, group II consisted of 15 cases of oligospermia following the vasovasostomy, and group III comprised 5 cases of testicular azoospermia. (Table 2). Clinical characteristics of these patients were as follows: Age of the patients ranged from 26 to 43 years old with mean of 34, and that of their wives ranged from 24 to 41 years old with mean of 31. Duration of marital life ranged from 1 to 21 years with mean of 5 years. Sizes of testis ranged from 6 to 25 ml with mean of 16 ml. Coital frequency ranged from 0.5 to 6 per week with mean of 2.4 per week. Levels of plasma FSH ranged from 3.15 to 23.06 lU/1 with mean of 8.15 lU/1, those of LH ranged from 2.98 to 19.89 lU/1 with mean of 8.18 lU/1 and those of testosterone ranged from 3.09 to 9.97 ng/ml with mean of 6.48 ng/ml. (Table 3). Clomiphene citrate was given in dosage of 50 mg per day (in d.) orally to 31 patients for 3 to 9 months and in dosage of 100 mg per day (b.i.d.) orally to 8 patients for 3 to 9 months. (Table 8). Semen samples were analysed monthly on each patient by routine analysis techniques. For the assessment of the efficacy of Clomiphene citrate on faulty spermatogenesis following empirical criteria were used: For semen quality: Improvement (I) represents that semen parameter increased more than 25% from basal level after the treatment, Unchange (U) expresses that semen parameter increased less than 25% of basal level or not changed after the treatment and Deterioration (D) means that semen parameter decreased from basal level after the treatment. For fertility unit (total counts ${\times}$ motility ${\times}$ morphology ${\div}10^6$): Improvement (I) represents that fertility unit increased more than 10 units after the treatment, Unchange (U) expresses that fertility unit increased less than 10 units or not changed after the treatment, and Deterioration (D) means that fertility unit decreased after the treatment. (Table 4). Results obtained from the Clomiphene therapy were as follows: Changes of spermiograme before and after the Oomiphene therapy shown in the Table 5. Sperm counts increased from 23 to 31 ${\times}10^6$/ml in group I, from 17 to 29 ${\times}10^6$/ml in group II. Other parameters of spermiogramme were not changed significantly after the treatment. Fertility units increased from 14 to 18 units after the treatment in group I, and from 16 to 18 units after the treatment in group II. Effectiveness of Clomiphene citrate on spermatogenesis was summarised in the Tables 6 and 7. After the treatment, sperm count increased in 11 patients, motility increased in 6 patients, morphology increased in 4 patients and fertility units increased in 9 patients. No sperm could be produced by Clomiphene citrate in group III of testicular azoospermia. Dosage of 50 mg of Clomiphene citrate per day for 3 to 6 months was proved to be the most effective in the present series. (Table 8). Pregnancy occurred in 2 patients after the treatment. No particular side effects were noted by the treatment. Pharmacologic compounds used for male infertility were shown in the Table 9. Reported results of Clomiphene citrate were shown in the Table 10.

• Journal of Embryo Transfer
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• v.25 no.1
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• pp.15-20
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• 2010

This study was performed to identify the optimal timing for oocyte donor replacement during OPU procedure. OPU was carried out to collect oocytes from every donor at an interval of $3{\sim}4$ days (2 times a week). The collected oocytes were matured in vitro in TCM-199 supplemented with 10% FBS, 10 mg/ml of FSH and 1 mg/ml of estradiol for 24 h. After 24 h of exposure to sperm, the presumptive zygotes were cultured in CR1aa medium supplemented with 4 mg/ml of BSA for 3 days before being changed to CR1aa medium with 10% of FBS for another $3{\sim}4$ days. The mean numbers of retrieved oocytes were remained constantly up to 3 months ($6.0{\pm}0.5$, $6.2{\pm}0.7$, $5.2{\pm}0.6$), but significantly decreased at over 4 to 6 months ($3.7{\pm}0.5$, $2.8{\pm}0.4$, $1.2{\pm}0.2$) (p<0.05). The blastocyst development potential was also very similar rate from 1 to 3 months (37.2%, 40.4% and 44.6%), but significantly decreased from 4 to 6 months (24.8%, 29.3% and 28.6%, respectively) (p<0.05). The production of OPU derived embryos in periods of 1 to 3 months ($2.2{\pm}0.3$, $2.5{\pm}0.3$ and $2.3{\pm}0.4$) were significantly higher than those in 4 to 6 months ($0.9{\pm}0.2$, $0.8{\pm}0.2$ and $0.3{\pm}0.2$, respectively) (p<0.05). In conclusion, the efficient periods for the production of OPU derived embryos was until 4 months, twice per week to produce over 64 transferable embryos and then replace new donor after 3 months use. The best replacement time is 3 months and could be maximized production of OPU derived embryos.

• Journal of Embryo Transfer
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• v.26 no.1
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• pp.19-25
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• 2011

This study was carried out to evaluate the effect of early pregnant cow as donor for Ovum Pick-Up (OPU) derived oocyte aspiration and embryo production in Holstein heifers. Four non-pregnant and 2 pregnant Holstein heifers were used as donor and then carried out total 17 OPU session for 10 weeks (2 times per week). Recovered cumulus-oocyte-complexes (COCs) were classified into 4 grade by oocyte cytoplasm and cumulus cells and matured in vitro in TCM-199 supplemented with 10% FBS, 10 mg/ml FSH and 1 mg/ml estradiol in 5% $CO_2$ and over 99% humidity for 24 h. After 24 h co-incubation with post-thaw sperm, the presumed zygotes were cultured in CR1aa medium with 4 mg/ml BSA for 3 days and then changed CR1aa medium with 10% of FBS for another 3~4 days. The Mean number of aspirated follicles and collected oocytes in the early stage pregnant and non-pregnant heifers were $13.0{\pm}4.3$ and $10.6{\pm}3.9$, $5.4{\pm}3.4$ and $7.7{\pm}3.6$ per session, respectively. Rate of collected oocyte from aspirated follicles were 59.2% and 50.5%, respectively. The average number of good quality oocytes (Grade I and II) in the early stage pregnant and non-pregnant heifers was $3.7{\pm}2.7$ and $4.9{\pm}2.6$ (Mean${\pm}$SD). Cleavage and blastocyst developmental rates in Grade I and II were 22.2% and 25.5%, and then $1.7{\pm}0.9$ and $1.4{\pm}1.1$ blastocyst per session, respectively. In conclusion, OPU technology can be used in early stage pregnant and non-pregnant heifers without any problem and so applied OPU derived embryo production to maximize the ability of genetically valuable females.

• Clinical and Experimental Reproductive Medicine
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• v.36 no.2
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• pp.111-119
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• 2009

Objective: The aim of this study was to compare the clinical efficacy of clomiphene citrate (CC) and letrozole combined with gonadotropins for controlled ovarian stimulation (COS) in patients with CC-induced thin endometrium Methods: Fifty-one intrauterine insemination cycles performed in patients who previously had a thin endometrium (<8 mm) to ovulation induction using CC were included in this study. A CC 100 mg/day (CC+gonadotropin group, n=26) or letrozole 2.5 or 5 mg/day (letrozole+gonadotropin group, n=25) was administered on day 3~7 of the menstrual cycle, combined with gonadotropins at dose 75~150 IU every other day starting on day 5~7. We compared total dose of gonadotropin used, endometrial thickness, endometrial pattern, number of follicles ${\geq}14\;mm$ on hCG day, pregnancy rate and multiple pregnancy rate between the two groups, which were statistically analyzed using Mann-Whitney U test or Fisher's exact test, where appropriate. Results: There were no significant differences in clinical characteristics such as age, duration of infertility, number of previous IUI cycles, basal serum hormone levels and cause of infertility between the two groups. In both groups, the endometrium was significantly thicker than that of previous ovulation induction cycles using CC. No significant differences were found in the total dose of gonadotropin used, day of hCG administration, the rate of triple endometrium and pregnancy rate. The number of follicles ${\geq}14\;mm$ was significantly lower ($3.7{\pm}1.7$ vs. $2.8{\pm}1.7$, p=0.03) and the endometrium on hCG day was significantly thicker ($7.7{\pm}1.5$ vs. $9.1{\pm}1.7$, p=0.001) in letrozole+gonadotropin group compared to CC+gonadotropin group. Conclusion: The clomiphene citrate and letrozole combined with gonadotropins appear to avoid the undesirable effects on the endometrium frequently seen with CC for ovulation induction. However, in terms of adequate endometrial development or optimal follicular growth, letrozole may be more beneficial than CC for gonadotropin-combined COS in patients with CC-induced thin endometrium. Further prospective randomized controlled studies in a larger scale will be necessary to confirm our 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.