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At least 613 records · Page 34Linked to original sources
PubMed1989

Endocrine effects of laparoscopic ovarian electrocautery in patients with polycystic ovarian disease, resistant to clomiphene citrate.

Endocrine responses to laparoscopic ovarian electrocautery were studied in 14 patients with polycystic ovarian disease (PCOD), resistant to clomiphene citrate. Patients who did not conceive within 6 months of treatment were evaluated for up to that period. Testosterone and androstenedione levels decreased after electrocautery in a way which is comparable with the reduction in androgens after wedge resection of the ovary. Androstenedione levels tended to return to pretreatment values at 6 months; four of the five pregnancies were achieved within this period. The reduction in androgens may break the vicious circle of PCOD, and lead to normal menstrual cycles.

Clomiphene↗
PubMed1994

Heterotopic ovarian pregnancy after clomiphene ovulation induction.

Heterotopic pregnancy is a life threatening condition which seems to occur more frequently than previously estimated. We report a case of combined ovarian and intrauterine pregnancy after clomiphene treatment. Diagnosis was delayed because clinical presentation was atypical and ultrasound was falsely reassuring. The neonate was healthy but presented with a single umbilical artery. When an ectopic gestation is suspected after induction of ovulation or assisted reproductive technologies the presence of an intrauterine pregnancy can no longer be considered reassuring and an heterotopic pregnancy has to be ruled out.

Adult↗
PubMed1977

Clomiphene citrate: pharmacologic treatment of hypofertile male.

Thirty-two males were treated with clomiphene citrate for a minimum of six months, a maximum of twelve months, or until pregnancy occurred. Among these patients, thirteen pregnancies occurred. Climiphene citrate appears a reasonable pharmaceutical method for management of idiopathic oligospermia.

Clomiphene↗
PubMed1986

An ovulation inducing agent containing clomiphene citrate causes DNA-strand breaks without SOS responses in Escherichia coli.

Effects of Clomid, an ovulation-inducing drug containing clomiphene citrate, on Escherichia coli were investigated. Radiation-sensitive mutants, uvrA and recA, were more sensitive to Clomid than the parental wild-type strain. DNA synthesis in these two strains was more depressed by Clomid than that in the wild-type strain. Clomid caused DNA-strand breaks, but few SOS responses such as mutation, induction of prophage and expression of the umuC+ gene were induced.

Clomiphene↗
PubMed1982

Blockade of ovulation by clomiphene citrate and its reversal by human chorionic gonadotropin or prostaglandin F2 alpha in rats.

Clomiphene citrate (clomid), a nonsteroidal estrogenic compound, was found to be effective in blocking ovulation in rats when scheduled at a dose of 3.0 mg/kg on day 2 or late day 4 of the estrus cycle. Treatment with hCG or prostaglandin F2 alpha (PGF2 alpha) concurrently with clomid consistently reversed the antiovulatory effect of clomid. The possible mode of action of clomid in the interruption of ovulation has been discussed.

Animals↗
PubMed1991

Validation of protocols for assessing early pregnancy failure in the rat: clomiphene citrate.

A battery of protocols for the assessment of maternally mediated toxicity during early pregnancy in the rat is being evaluated for its utility in detecting and defining mechanisms of early pregnancy failure. In this report, clomiphene citrate (CC), an estrogen agonist/antagonist, was used as a model compound in this evaluation process. The protocols involve dosing rats with CC during, and evaluation of multiple endpoints following, (a) the first 8 days of pregnancy; (b) early pseudopregnancy, accompanied by decidual induction; and (c) the pre- and postimplantation intervals of early pregnancy. In addition, the effect of CC on embryo transport rate was assessed. Eight days of dosing with CC during early pregnancy produced a dose-dependent reduction in the number of implantation sites seen on Day 9, concomitant with alterations in maternal hormonal parameters. No effect on the decidual cell response was found, indicating that the mechanism of fertility reduction was not mediated via compromised uterine decidualization. The preimplantation period was highly vulnerable to the toxic effects of CC while no postimplantation resorptions were seen. When embryo transport rate was measured, a statistically significant embryo transport rate acceleration was detected, but this was insufficient to account for all of the observed preimplantation loss. The data suggest an effect of CC on embryo viability, on the embryo's ability to implant, or on the reproductive tract resulting in compromised embryo survival as the potential mechanism(s) mediating CC-induced early pregnancy failure. The battery of protocols was thus successful in identifying CC as a reproductive toxicant and in elucidating the causes of the observed early pregnancy failure.

Animals↗
PubMed1988

Uterine abnormalities in rats exposed neonatally to diethylstilbestrol, ethynylestradiol, or clomiphene citrate.

The toxicity of the synthetic estrogens diethylstilbestrol (DES), and ethynylestradiol (EE), and the antiestrogen clomiphene citrate (CC) was evaluated by assessing postnatal uterine growth and development prior to the onset of puberty in the rat. Both DES and EE, administered during the neonatal period (postnatal days 1-5), initially increased uterine weight and luminal epithelium hypertrophy. However, uterine weight declined in both DES- and EE-treated animals and fell below controls beyond day 11. Luminal epithelium stimulation generally paralleled uterine weight changes. Precocious development of uterine glands occurred after estrogenization (compared to untreated controls), but subsequently gland numbers were approximately 60% of control levels. Neonatal CC exposure induced only slight uterine weight gain but caused prolonged luminal epithelium hypertrophy and inhibited uterine gland genesis. Luminal epithelium hypertrophy appears to be a useful measure of antiestrogen activity. These data demonstrate the toxicity of DES and EE as assessed by altered prepubertal uterine gland development. Additionally, the inhibition of uterine gland genesis after neonatal CC exposure occurs in conjunction with prolonged luminal epithelium hypertrophy.

Animals↗
PubMed1989

Induction and promotion of gamma-glutamyltranspeptidase-positive foci in the liver of female rats treated with ethinyl estradiol, clomiphene, tamoxifen and their associations.

The objective of the present study was to determine whether a short exposure (6 weeks) to high doses of ethinyl estradiol (EE) could not only promote but also initiate hepatocarcinogenesis, and whether two antiestrogens, clomiphene (C) and tamoxifen (T), could influence EE activity. 2-Acetylaminofluorene (AAF), which has been shown to produce rat liver hyperplastic lesions characterized by the presence of estrogen receptors, was used either as a promoter to test for initiating activity, or as an initiator to test for promoting activity. Putative preneoplastic lesions were identified by means of a positive gamma-glutamyltranspeptidase (GGT) reaction. The results revealed that when administered alone in female Sprague-Dawley rats, not only E, but also C and T were clearly active in both initiating and promoting the development of GGT-positive foci. Moreover, in rats of the same strain treated with EE + C or EE + T a significant increase in the incidence of GGT foci demonstrated the occurrence of an additive effect in terms of both initiating and promoting activity. Fischer 344 rats were more susceptible than Sprague-Dawley rats to promotion by EE, C and T, but any substantial evidence of an additive effect was absent when the two anti-estrogens were administered in association with the estrogen.

Animals↗
PubMed1996

The effect of medroxyprogesterone acetate and clomiphene citrate on platelet function in menopausal women.

OBJECTIVE: We sought to determine if antiestrogens such as clomiphene citrate (CC) and medroxyprogesterone acetate (MPA) affect platelet activity in postmenopausal patients before and after treatment with estrogens. METHODS: Using an incubation study, we analyzed the effects of CC and MPA on adenosine diphosphate and adrenaline-induced platelet aggregation and on the release of adenosine triphosphate in postmenopausal patients, using a platelet study, we analyzed the effect of these drugs on platelet function. RESULTS: Platelets were inhibited by MPA and CC in the incubation study but not significantly affected in the platelet study. Platelets previously incubated with estrogen were less inhibited by CC than by MPA. DISCUSSION: Thus, platelet study to determine the optimal combination therapy for menopausal patients has indicated that CC has a non-significantly less beneficial in vitro effect on platelet function than MPA.

Adenosine Diphosphate↗
PubMed1996

Multivariate analysis of capillary electrophoresis separation conditions for Z-E isomers of clomiphene.

Plackett-Burman (P-B) experimental design has been used to optimize the factors affecting separation of Z and E isomers of clomiphene (zuclomiphene and enclomiphene respectively) using capillary electrophoresis. The P-B design was used to simultaneously investigate the following five factors: buffer ionic strength, buffer pH, heptakis (2,3,6-tri-o-methyl) beta-cyclodextrin (TMCD) concentration, methanol concentration and injection time, each at three levels. In addition to these, a dummy variable was added to estimate the variability of the system. Effects on resolution and analysis time were calculated. Based on the information gained from the P-B design, the following set of conditions was chosen: 100 mM phosphate buffer pH 2.3, 5 mM TMCD, 5% methanol, and 1.7 s hydrodynamic injection time. These conditions gave well-resolved peaks for zuclomiphene and enclomiphene.

Clomiphene↗
PubMed1991

Effects of long-term treatment with estradiol or clomiphene citrate on bone maintenance, and pituitary and uterine weights in ovariectomized rats.

Long-term estrogen replacement therapy in postmenopausal women can bring relief to hot flushes and reduce loss of bone mass due to osteoporosis, however, such treatment often can cause uterine hyperplasia and other undesirable effects. This study compared changes in bone mineral content (BMC), uterine weight, pituitary weight and pituitary gonadotropin content in the ovariectomized rat model following treatment with estradiol (E2) or two levels of clomiphene citrate (CC), an estrogen agonist/antagonist. Groups (n = 8-12) of adult ovariectomized (OVX) rat were implanted with E2 pellets (5 micrograms/day) or injected subcutaneously with CC at 1 mg/kg body wt (CC-1) or 5 mg/kg body wt (CC-5) twice weekly for 12 months. Placebo implanted OVX and intact (INT) female rats served as negative and positive controls, respectively. Following treatment, the uterus, pituitary gland and right femur were collected from each animal. E2 treatment increased (P less than 0.05) uterine weight compared to all other treatment groups, while both CC doses increased uterine weight over the OVX group only (E2, 0.24 +/- 0.03; INT, 0.14 +/- 0.01; CC-1, 0.06 +/- 0.01; CC-5, 0.07 +/- 0.01; and OVX, 0.02 +/- 0.01 g per 100 g body wt). Pituitary weight was increased 15-fold (P less than 0.05) by E2 treatment over all other treatment groups (E2, 65.7 +/- 13.9; INT, 4.0 +/- 0.5; CC-1, 3.3 +/- 0.03; CC-5, 2.7 +/- 0.02; and OVX, 2.9 +/- 0.02 mg per 100 g body wt). Both E2 and CC treatments reduced pituitary luteinizing hormone and follicle stimulating hormone content (micrograms/pit) to INT levels and were lower (P less than 0.05) than OVX levels. Mean BMC of E2, CC-1- or CC-5-treated rats was greater (P less than 0.05) than that of either the INT or OVX groups, while INT animals had a higher BMC compared to OVX animals (E2, 0.027 +/- 0.003; CC-1, 0.026 +/- 0.001; CC-5, 0.028 +/- 0.001; INT, 0.021 +/- 0.001; and OVX, 0.017 +/- 0.001 g/cm per 100 g body wt). These data indicate that CC has the potential to reduce bone mineral loss without causing other undesirable effects, including uterine hyperstimulation, and thus needs to be further investigated.

Animals↗
PubMed2006

Apoptosis is not altered by clomiphene citrate in pseudopregnant rat uteri.

Clomiphene citrate (CC) remains one of the most often prescribed synthetic oestrogens used in the treatment of infertility even though the ensuing pregnancy rates are low. CC alters the uterine environment on most levels. Ovariectomised rats were treated with 5 mg progesterone (P) for 3 days and a 0.5 microg injection of oestrogen (E) on the third day (PP(PE)) thus inducing pseudopregnancy and rendering the uterus receptive to implantation 24 h later. Using this model, we investigated apoptosis in the rat uterus treated with 0.25 mg CC given prior to the PP(PE) treatment. Apoptotic cells in the uterus were localised using TUNEL and visualised with a FITC marker. There was a similar increase in apoptosis in the uterine luminal epithelium in the PP(PE) and CCPP(PE) treated animals; no changes were observed in apoptosis in the other uterine compartments when compared to the control. The CCPP(PE)-treated tissue showed tall epithelial cells with long microvilli while the PP(PE) tissue had short microvilli and low cuboidal epithelium. These results suggest that CC does not disrupt the normal apoptotic activity seen at implantation, but does change the morphology of the luminal epithelium, suggesting that these cellular changes could influence successful implantation.

Animals↗
PubMed2005

Use of micro-dose human chorionic gonadotropin (hCG) after clomiphene citrate (CC) to complete folliculogenesis in previous CC-resistant anovulation.

OBJECTIVE: The purpose of this study was to compare the effectiveness of low-dose human chorionic gonadotropin (hCG) in the late follicular phase to induce ovulation and its endocrine response in patients who had previously failed to ovulate on clomiphene citrate (CC) alone. DESIGN: A total of 67 patients from a private tertiary infertility clinic, who had produced a dominant follicle 12 mm or larger but 20 mm or smaller on a prior CC cycle at 100 mg but had failed to ovulate, were prospectively randomly assigned to groups. Group 1 repeated the 100 mg dose of CC but started a 200 IU hCG intramuscular injection daily when the largest follicle was 12 mm or larger mean diameter. Group 2 received a 150 mg dose of CC and both groups were monitored with transvaginal ultrasound and serum levels of E 2 , P 4 , and testosterone. Ultrasound measurements of follicle number and growth, ovulation, pregnancy rates, and serum hormonal levels were recorded and compared between the 2 groups. Analysis of variance and Student t test were used for statistical significance. RESULTS: The low-dose hCG group had significantly higher percentage of ovulatory cycles (57% vs 7% P < .001), peak E 2 levels (378 pg/mL vs 125 pg/mL P < .01), and pregnancy rates (18% vs 0% P < .001). This group showed no evidence of premature leutinization from the hCG with preovulatory P 4 levels less than 1.0 ng/mL and a slight increase in androgen levels. CONCLUSION: The use of micro-dose hCG after CC in the late follicular phase results in continued follicle growth, increased E 2 levels, ovulation, and pregnancies. This treatment offers an efficient and cost-effective alternative before gonadotropin therapy for this type of patient.

Adult↗
PubMed2005

Prognostic factors for ovulatory response with clomiphene citrate in polycystic ovary syndrome.

OBJECTIVE: To evaluate prospectively the prognostic factors for ovulatory responses following clomiphene citrate (CC) administration in polycystic ovary syndrome (PCOS). STUDY DESIGN: Fifty-nine infertile patients with a diagnosis of PCOS were recruited. Ovulation was induced using 100 mg/day CC administered daily from days 5 to 9 of the cycle. Endocrine and metabolic parameters between responder and non-responder groups were analyzed. RESULTS: For a 75-g fasting glucose load (75-g OGTT), blood glucose levels at 60 and 120 min, the area under the curve (AUC) and blood insulin levels at 120 min in the non-responder group (n=25) were significantly higher than those in the responder group (n=34), although the measurements of fasting blood glucose and insulin were not significantly different between the two groups. In the receiver operating characteristic curves, the most appropriate cutoff point was 120 mg/dl for the blood glucose level at 120 min and 9000 for the blood glucose x insulin level at 120 min. There were no significant differences in the clinical characteristics or in the endocrine and metabolic parameters between conceived (n=9) and non-conceived groups (n=21). CONCLUSION: The levels of blood glucose and blood glucose x insulin at 120 min after 75-g OGTT could be good biochemical markers of CC resistance in PCOS. No predictors of conception following CC therapy were identified by this study.

Administration, Oral↗
PubMed2004

Clomiphene citrate intrauterine insemination (IUI) before gonadotropin IUI affects the pregnancy rate and the rate of high-order multiple pregnancies.

OBJECTIVE: To determine if previous treatment with clomiphene citrate intrauterine insemination (CC-IUI) affects pregnancy and high-order multiple pregnancy (HOMP) rates in subsequent hMG-IUI or FSH-IUI cycles. DESIGN: Retrospective cohort study. SETTING: Private infertility clinic. PATIENT(S): Five hundred fifty-one patients (age <38 years) without tubal factor infertility, treated with 918 cycles of hMG/FSH-IUI after one or more unsuccessful cycles of CC-IUI; 908 patients treated with 1459 cycles of hMG/FSH-IUI without prior CC-IUI. INTERVENTION(S): CC-IUI, hMG-IUI, FSH-IUI. MAIN OUTCOME MEASURE(S): Pregnancy rate per cycle, HOMP (three or more gestational sacs). RESULT(S): Pregnancy rates during the first three hMG-IUI or FSH-IUI cycles averaged 21.8 +/- 1.1% without previous CC-IUI, 19.6 +/- 1.3% after one to four cycles of CC-IUI, and 3.6 +/- 2.6% after >or= five previous CC-IUI cycles. The HOMP rates were 8.8% without previous CC-IUI, 7.5% after one, 5.7% after two and <2.6% (0 out of 38) after >or= three previous CC-IUI cycles. CONCLUSION(S): Pregnancy rates in hMG/FSH-IUI cycles are significantly reduced after four unsuccessful CC-IUI cycles. High-order multiple pregnancies due to hMG/HMG-IUI are reduced following previous unsuccessful CC-IUI cycles.

Adult↗
PubMed2004

Comparison of basal follicle-stimulating hormone versus the clomiphene citrate challenge test for ovarian reserve screening.

OBJECTIVE: To compare the value of basal follicle-stimulating hormone (FSH) measurement vs. the clomiphene citrate challenge test (CCCT) in predicting the ability to achieve a pregnancy in women who are undergoing infertility treatment. DESIGN: Meta-analysis. SETTING: All studies that evaluated either basal FSH or the CCCT for determining the likelihood of pregnancy. PATIENT(S): Infertility population undergoing treatment, which was defined as patients undergoing ovulation induction, IUI, or in vitro fertilization (IVF). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Diagnostic test characteristics were calculated and pooled using standard methods. Inability to achieve a pregnancy with treatment was considered as the "disease." RESULT(S): Twelve studies on basal FSH (with 6296 patients, mean age 33.8) and seven studies on the CCCT (with 1352 patients, mean age 34.5) fit our criteria and were analyzed. For basal FSH and the CCCT, the sensitivities were 6.6% (95% confidence interval [CI] 5.9, 7.3%) and 25.9% (95% CI 23.0, 29.0%), respectively, and specificities were 99.6% (95% CI 99.1, 99.9%) and 98.1% (95% CI 96.5, 99.1%), respectively. For "disease" prevalence ranging from 40%-100%, for basal FSH and the CCCT, the positive predictive values ranged from 91.7%-100% and 90.1%-100%, respectively, and negative predictive values ranged from 61.5%-0.0% and 66.5%-0.0%, respectively. CONCLUSION(S): Basal FSH and the CCCT are similar in predicting the ability to achieve a clinical pregnancy in women undergoing infertility treatment. With either test, a normal result is not useful, but an abnormal result virtually confirms that pregnancy will not occur with treatment.

Clomiphene↗
PubMed2004

A novel protocol of ovulation induction with delayed gonadotropin-releasing hormone antagonist administration combined with high-dose recombinant follicle-stimulating hormone and clomiphene citrate for poor responders and women over 35 years.

OBJECTIVE: To evaluate the efficacy of a novel protocol of ovulation induction for poor responders. DESIGN: Prospective, controlled, clinical study. SETTING: Research institute's reproductive unit. PATIENT(S): One hundred forty-five infertile women, aged 27-39 years, candidates for assisted reproductive techniques (ART). INTERVENTION(S): Before undergoing ART, 85 patients received clomiphene citrate, high-dose recombinant human FSH, and a delayed, multidose GnRH antagonist, whereas 60 patients underwent a standard long protocol. MAIN OUTCOME MEASURE(S): Estradiol levels (pg/mL), cancellation rate, oocyte retrieval, embryo score, and fertilization and pregnancy rates. RESULT(S): Patients undergoing the study protocol obtained lower cancellation rates (4.7% vs. 34%) and higher E(2) levels (945.88 +/- 173.2 pg/mL vs. 169.55 +/- 45.07 pg/mL), oocyte retrieval (5.56 +/- 1.13 vs. 3.36 +/- 1.3), and pregnancy (22.2% vs. 15.3%) and implantation rates (13.5% vs. 7.6%) compared with those receiving the long protocol. Age negatively correlated with ovarian response in the latter, whereas the ovarian outcome results were comparable in younger (<35 yrs) and older (>35 yrs) women treated with the study protocol. CONCLUSION(S): The proposed protocol of ovulation induction can be usefully administered in poor responders as well as in aged woman, probably because the delayed administration of GnRH antagonist prevents its adverse effects on ovarian paracrine activity and on oocyte maturation.

Adult↗
PubMed2004

Characteristics of baseline ovarian cysts in clomiphene citrate ovulation cycles.

To evaluate the incidence and factors associated with ovarian cysts in infertile patients receiving clomiphene citrate (CC), we performed a retrospective cohort study involving 466 CC treatment cycles. Ovarian cysts are a common finding in patients presenting for CC, with approximately one in five patients having a baseline ovarian cyst >10 mm.

Adult↗