• Clinical and Experimental Reproductive Medicine
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• v.33 no.3
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• pp.149-157
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• 2006

Objective: This study was to investigate the clinical efficiency of clomiphene citrate/GnRH antagonist protocol comparing with the clomiphene citrate only protocol in infertile women with normal ovulatory cycles. Method: Among 116 patients, 43 were received assisted reproductive technologies using natural ovulatory cycle, 38 and 35 were received clomiphene citrate only protocol and clomiphene citrate/GnRH antagonist combined protocol, respectively, and the clinical results were compared and analyzed Results: In each group, basal levels of LH, FSH, $E_2$ and FSH, $E_2$ on hCG day injected were not different, but LH level and endometrial thickness on hCG injected day were decreased significantly and the pregnancy rate was increased significantly in clomiphene citrate/GnRH antagonist group. Conclusion: The pregnancy rate was increased significantly in clomiphene citrate/GnRH antagonist group compared with natural ovulatory cycle and clomiphene citrate only group.

• Clinical and Experimental Reproductive Medicine
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• v.30 no.1
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• pp.15-21
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• 2003

Objective : Clomiphene citrate is one of the most commonly used drugs in the treatment of infertility, but the pregnancy rate achieved with clomiphene citrate is significantly lower than the ovulation rate due to its antiestrogenic effect on the endometrium. Endometrial prolactin is considered to be a marker and an inducer of predecidualization that is characteristic of secretory endometrium. The purpose of this study was to evaluate the association of clomiphene citrate and unsatisfactory endometrial differentiation to secretory endometrium by examining the endometrial expression of prolactin in clomiphene citratetreated infertile women with luteal phase defect. Methods : The endometrial samples from infertile women with luteal phase defect (n=27) were examined. Five cases during secretory phase and six cases during proliferative phase were obtained by biopsy. Sixteen cases were obtained by biopsy during secretory phase after clomiphene citrate treatment. By immunohistochemical staining for prolactin, all obtained endometrial tissues were examined. The differences in the endometrial expression of prolactin were evaluated between proliferative phase and secretory phase, and between clomiphene citrate treated group and no treatment group during secretory phase. Results: The staining of endometrial prolactin was significantly more intense in the glandular epithelial cells and stromal cells in the secretory endometrium than in the proliferative endometrium. The glandular expression of prolactin in the secretory endometrium was not significantly different between the clomiphene citrate-treated group and no treatment group (p=0.719), but the staining of prolactin in the stromal cells was significantly less intense in the clomiphene citrate-treated group than no treatment group (p=0.019). Conclusion: In this investigation, we demonstrated that the endometrial stromal expression of prolactin in the secretory phase was significantly lower in the clomiphene citrate-treated group campared with no treatment group in infertile women with luteal phase defect. And our finding suggests that clomiphene citrate may have an adverse effect on the endometrial predecidualization in infertile women.

• Asian-Australasian Journal of Animal Sciences
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• v.24 no.8
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• pp.1053-1059
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• 2011

The objective of this study was to assess the teratogenic and embryotoxic effects of clomiphene citrate in mice. The pregnant mice were administered a single dose of clomiphene citrate at different concentrations i.e 1.0, 2.0, 4.0 and 6.0 ${\mu}g/g$ BW on day 8 of gestation. Fetuses recovered on day 18 of gestation were analyzed on morphological, morphometric and histological basis. Morphological observations showed defects like open eyelids, anophthalmia, fore and hindlimb micromelia, meromelia, amelia, sacral hygroma, hydrocephaly, hemorrhagic spots, kyphosis and clubbed feet. Morphometric analysis indicated a significant (p<0.001) reduction in fetal body weight, crown rump length, head circumference, eye circumference, forelimb and hindlimb lengths and tail size against controls. The histological observations showed brain defects like hydrocephaly, enlarged ventricles and undifferentiated neuroglial cells in cerebellum. Cleft palate, underdeveloped pharynx and atrophy of jaw muscles were the common anatomical defects of pharyngeal region. It is concluded that the concentrations of clomiphene citrate used during the present study proved teratogenic in mice fetuses.

• Clinical and Experimental Reproductive Medicine
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• v.28 no.4
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• pp.255-264
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• 2001

Objective : This study was performed to investigate the effect of metformin therapy on ovulation induction & pregnancy rate in clomiphene citrate-resistant PCOS women. Method: This study used a randomized, single-blinded, case-controlled methods. Total study group consisted of 21 women who showed clomiphene citrate-resistant parttern on previous ovulation induction cycles. Patients of metformin group received metformin 500 mg three times daily, for 7 weeks. Control group received none. Metformin group was consisted of 10 women and control group was consisted of 11 women. Then clomiphene was administrated at daily 50 mg for 5 days to both groups. Clomiphene dosage was increased to daily 150 mg until ovulation was occurred. Before and After metformin treatment, blood samples for measurement of insulin, glucose, steroids were obtained. Results: In the metformin and control groups, 6 of 10 women (60%) and 2 of 11 women (18%) ovulated. And 4 of 10 women (40%) and 0 of 11 women (0%) conceived. Comparisons between the groups were significant. Conclusion: In PCOS women who are resistant to CC, metformin use increased the ovulation rate and pregnancy rate from CC treatment, significantly.

• Asian-Australasian Journal of Animal Sciences
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• v.2 no.1
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• pp.17-21
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• 1989

Four seasonal trials were conducted to study the effect of feeding clomiphene citrate on carcass composition of broilers. It was fed at 5, 10, 15 mg levels per kg feed for a period of two weeks, 3-4 weeks ($S_1$), 4-5 weeks ($S_2$) and 5-6 weeks ($S_3$) of age. Total carcasses were analysed for moisture, ether extract and protein. Clomiphene citrate significantly decreased the moisture with concomitant increase in ether extract content of the carcasses at all the ages and seasons. Carcass protein was significantly decreased at all the ages and seasons. The responses in the different level of clomiphene citrate is dose dependent. The carcass moisture decreased with age while protein and ether extract contents increased in all seasons. The females had more ether extract and less moisture contents than male. The carcass ether extract was higher in summer and rainy seasons followed by spring and winter seasons, and the differences were significant. A concomitant significant decrease of carcass moisture was observed. The effect of seasons on carcass protein varied at different ages but there appeared to be a trend towards decreasing carcass protein in summer and rainy seasons than winter and spring seasons.

• Clinical and Experimental Reproductive Medicine
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• v.12 no.2
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• pp.15-23
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• 1985

Therapy for anovulation represents one of the more gratifying and successful type of infertility management. Despite the introduction of bromocriptine, human menopausal gonadotropin (HMG), and gonadotropin releasing hormone (GnRH), clomiphene citrate remains the mainstay of ovulation induction therapy. There is wide variability in reported rates of ovulation induction (57-91%) and conception (25-43%) following clomiphene therapy. Factors contributing to this variability among different reports are the differences in dosage and duration of therapy, different criteria utilized in selecting patients for clomiphene therapy and different luteal phase parameters of presumptive ovulation. A review of recent experience with clomiphene citrate in the Department of Obstetrics and Gynecology in Seoul National University from January, 1983 to May, 1985 yields the following conclusions: 1. Ovulation rate per total patients treated was, 69.0% 2. Pregnancy rate per total patients treated was 31.7%, and that per total patients ovulated was 45.9%. 3. Ovulation rate at the dosage level up to 150 mg/day (50.3-53.8%) was somewhat higher than that at 200 mg/day or more (33.3-34.6%), and pregnancy rate per total patients treated was comparable at each dosage level. 4. Ovulation rate per total patients ovulated at each dosage level, where ovulation and conception occurred, showed a decreasing tendency as the dosage increased, but pregnancy rate per total patients conceived was comparable except at 200 mg/day. 5. Cumulative pregnancy rate per total patients conceived in each ovulatory cycle was 68.9% in 3 cycles, 88.9% in 4 cycles, and 100% in 6 cycles.

• Clinical and Experimental Reproductive Medicine
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• v.13 no.1
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• pp.67-75
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• 1986

Follicle monitoring in the normal and clomiphene·stimulated cycles were analyzed in the Seoul IVF and ET (In vitro fertilization and embryo transfer) program. Ovarian follicular diameters were measured by the real·time sector scanner and plasma estradiol levels were assayed by radioimmunoassay methods during periovulatory period. The maximum follicular sizes of the clomiphene-stimulated and normal cycles were 21.1+-3.4mm and 19.2+-0.8mm, respectively. The peak levels of plasma estradiol in the clomiphene-stimulated and normal cycles were 10538+-553.6ng/ml and 298.3+-39.6pg/ml, respectively. Daily growth rate of the follicular diameters of the clomiphene-stimulated and normal cycles were 2.1mm and 1.9mm, respectively. Mean follicular number of the clomiphene-simulated and normal cycles were 2.28+-1.12 and 1.12+-0.21, respectively. There was a good statistical correlation between the mean follicular diameters and the plasma estradiol levels in the normal ovulatory and c1omiphene-stimulated ovulatory menstrual cycles (p<0.05). Our data revealad that the mean follicular diameter and the plasma estradiol level prior to HCG administration in IVF and program should reach at the level of 17.8+-3.0mm and 949.4+-487.1 pg/ml, respectively.

• Clinical and Experimental Reproductive Medicine
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• v.37 no.1
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• pp.73-81
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• 2010

Objective: To examine the efficacy of letrozole in infertile women showing a poor endometrial development at previous ovulation induction cycle by using clomiphene citrate. Methods: Eighteen infertile women were selected who showed a poor endometrial development (endometrial thickness$\leq$6.5 mm) after clomiphene treatment (50~100 mg) as ovulation induction for timed coitus. The mean age of the patients was $30.7{\pm}2.8$ years old and the mean duration of infertility was $33.1{\pm}26.6$ months. The infertility factors were identified as corrected endometriosis (n=1), polycystic ovary syndrome (n=5) and unexplained (n=12). Letrozole was given orally in a dose of 2.5 mg for 5 days starting 3~5 of menstrual cycle. Results: The number of follicles was significantly lower in the letrozole cycle when compared with previous clomiphene cycle ($1.1{\pm}0.3$ vs. $2.2{\pm}1.5$, p=0.011). The endometrial thickness (mm) at the time of triggering or LH surge was significantly greater in the letrozole cycle ($8.4{\pm}1.7$ vs. $5.8{\pm}0.5$, p<0.001). The endometrial pattern 'type C' was significantly higher in the letrozole cycle (94.4% vs. 50%, p=0.036). The pregnancy was achieved in 11.1% of the letrozole cycle. Conclusion: Use of letrozole was associated with more thick and improved endometrium than previous clomiphene cycles in which thin endometrium was identified. Use of letrozole appears to be an effective strategy for second-line treatment in women with inadequate endometrial response to clomiphene.

• Clinical and Experimental Reproductive Medicine
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• v.14 no.1
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• pp.7-17
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• 1987

It appears that a major determinant of the success of in vitro fertilization is the selection of the optimal follicle containing an oocyte capable of being fertilized and producing a normal pregnancy. However, the hormonal basis of oocyte maturation is not well substantiated by the as yet available informations. It has been suggested that prolactin(PRL) may stimulate the formation of an oocyte maturation inhibitor and thus inhibit the maturation of oocyte. During the hyperstimulated menstrual cycles serum estradiol($E_2$) levels are markedly elevated, and it seems justified to assume that serum prolactin levels may be elevated since estrogens are potent stimulators of prolactin secretion. This study was carried out to ascertain the effect of the elevated serum estradiol levels on the serum prolactin levels in women undergoing ovarian hyperstimulation with either hMG and/or clomiphene citrate. Serum estradiol and prolactin profiles were measured from third menatrual cycle day to ovulation or ovum aspiration day in 11 normal menstruating women and 30 women who underwent an in vitro fertilization procedure with ovarian hyperstimulation by hMG, clomiphene citrate/hMG, clomiphene citrate. Ovum aspiration was performed 36 hours after hCG administration. The day of ovum aspiration or ovulation was designated Day 0. Serum estradiol levels increased progressively during the follicular phase and this rise peaked on Day-1 at a mean concentration of 1,204${\pm}$189.0pg/ml in Group II(hMG), 1,194${\pm}$167.9pg/ml in Group III(clomiphene citrate/hMG), 1,035${\pm}$195.1pg/ml in Group IV(clomiphene citrate) respectively and on Day -2 of 336${\pm}$34.5pg/ml in Group I(normal control). The elevated estradiol levels fen rapidly after ovulation or ovum aspiration. Serum estradiol values of hyperstimulated groups(Group II, III, IV) were significantly higher than that of control group(Group I) from Day -6 to Day +1, but there was no significant difference of estradiol values among the hyperstimulated groups. Serum prolactin levels increased and peaked on Day +1 at a mean concentration of 60.8${\pm}$14.4ng/ml in Group II, 34.2${\pm}$7.0ng/ml in Group III, 30.1${\pm}$5.7ng/ml in Group IV respectively, but no significant elevation was observed in Group I. Levels of estradiol and prolactin can be positively and significantly correlated in the hyperstimulated groups. However, the increase of serum prolactin levels in hMG group was significantly higher than those in clomiphene citrate/hMG or clomiphene citrate group.

• Clinical and Experimental Reproductive Medicine
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• v.26 no.1
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• pp.31-41
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• 1999

To evaluate the effectiveness of intrauterine insemination (IUI) in the treatment of infertility, timed-intercourse and intrauterine insemination by husband in stimulated cycles with clomiphene citrate and gonadotropins were compared in a total of 105 cycles. Patients received 100mg of clomiphene citrate daily for 5 days starting on day 3 of the menstrual cycle followed by hMG or FSH. Doses of exogenous gonadotropins were adjusted by the follicular development and concentrations of serum estradiol $(E_2)$. More than 3 follicles reaching >16 mm were present in the ovary, 5,000 IU of hCG was administered intramusculary. Patients received a maximum of three intercourse or IUI cycles for the treatment. Severe male (<$10{\times}10^6$ motile sperm) or age factor (>39 y) patients were excluded in this study. Pregnancy was classified as clinical if a gestational sac or fetal cardiac activity was seen on ultrasound. The overall clinical pregnancy rates were 17.1% per cycle (18/105) and 21.2% per patient (18/85). The pregnancy rates (per cycle) were 17.5% (11/63) in intercourse and 16.7% (7/42) in IUI groups, respectively. IUI had no significant improvement in pregnancy rate compared with timed-intercourse. The multiple pregnancy rates were 11.1% (1 twin and 1 triplet). No patient developed ovarian hyperstimulation. Abortion rate was 28.6% (2/7) in IUI group only. The delivery and ongoing pregnancy rates were 15.2% per cycle (16/105) and 18.8% per patient (16/85). There were no differences in age, duration of infertility, follicle size and level of estradiol $(E_2)$ on the day of hCG injection in pregnant and non-pregnant groups. However, total doses of gonadotropins were higher in pregnant group than in non-pregnant group (p<0.01). Pregnancy rate was not affected by ovulatory status at the time of insemination. These results indicate that well timed-intercourse in stimulated cycles is as effective as IUI for infertile couples.