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Results for “CLOMIPHENE”

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PubMedDate not supplied

Reversal by human chorionic gonadotropin of the inhibitory effect of clomiphene on progesterone production by granulosa-luteal cells in culture.

The possibility of a direct ovarian effect of clomiphene citrate was assessed in vitro by measuring progesterone release from cultured human granulosa-luteal cells in both the presence and absence of hCG. Granulosa-luteal cells obtained by laparoscopic follicle aspiration following ovarian stimulation with hMG and hCG in women undergoing in vitro fertilization/embryo transfer were incubated for 72 hours in medium containing increasing concentrations of clomiphene (10(-9) - 10(-5) M) both without and with hCG (1 IU/mL). Clomiphene stimulated progesterone production in both the presence and absence of additional hCG at concentrations less than or equal to 10(7) M. In both the presence and absence of hCG a dose-dependent inhibition of progesterone production was observed with higher concentrations of clomiphene (greater than 10(6) M). hCG (1 IU/mL) significantly increased progesterone production in control cells and at all concentrations of clomiphene (10(-9)-10(-5) M) tested. Low clomiphene (10(-9)-10(-7) M) and hCG concentrations appeared to have a synergistic effect on progesterone production. Thus it appears that clomiphene has a direct ovarian effect on progesterone production, which is stimulatory at low concentrations and inhibitory at higher concentrations.

Adult↗

PubMed1987

[Indication and effect of bromocriptine in euprolactinemic amenorrhea--comparison with clomiphene].

Effect of bromocriptine on induction of ovulation and occurrence of pregnancy was examined in patients with normoprolactinemic ovulatory disturbances. The patients under study (53 in number) were divided into two groups, A and B, depending on the effect clomiphene had on the ovulatory responses and the occurrence of pregnancy. Of the group A, patients (21 in number), who had failed to show any ovulatory response to clomiphene, 8 patients ovulated on bromocriptine alone. Three out of 13 patients who complained of sterility became pregnant. Three out of 8 patients who had not ovulated on bromocriptine therapy alone ovulated on a combination of bromocriptine and clomiphene, and 2 out of these 3 cases became pregnant. Of the group B patients (31 in number), who had failed to become pregnant in spite of ovulatory responses to previous clomiphene therapies, 7 out of 23 became pregnant, who complained of sterility when on bromocriptine alone. Out of 12 cases who had failed to get pregnant on the bromocriptine alone, 2 patients became pregnant on the combination of bromocriptine and clomiphene. These data may indicate that the bromocriptine or the combined therapy of bromocriptine and clomiphene is useful for the treatment of patients with ovulatory disturbances or sterility who do not respond to the clomiphene therapy.

Adult↗

PubMedDate not supplied

A comparative study of clomiphene and epimestrol on plasma progesterone, CBG, TBG and SHBG, and salivary progesterone levels.

The plasma levels of CBG, TBG, SHBG and progesterone, and salivary progesterone levels were measured in eight young ovulatory volunteers. After the control cycle four subjects received 50 mg/day of Clomiphene from days 5 to 9 of the first treatment cycle, and 10 mg/day of Epimestrol from days 5 to 15 of the second treatment cycle. The other four subjects received the treatments in reverse order. Between the two treatments there was one cycle without medication as a "wash-out" period. Plasma and saliva samples were obtained on days +6, +8 and +10 (day of LH peak was denoted by 0), always between 08.00 and 09.00 h. Statistical evaluation was done by means of an analysis of variance (ANOVA), and correlation coefficients were also calculated. Evaluation of data on effects of Clomiphene and Epimestrol on the plasma levels of CBG and salivary progesterone showed that Clomiphene induced a highly significant rise (p less than 0.001) in the CBG levels and decrease (p less than 0.001) in salivary progesterone levels, while no changes were seen following administration of Epimestrol. Both Clomiphene and Epimestrol treatments led towards higher plasma progesterone levels, those following Clomiphene administration being higher. Neither treatment induced significant changes in TBG or SHBG levels. It is concluded that Clomiphene induces significant elevations of CBG and decrease in salivary progesterone, which is thought to reflect the free progesterone fraction and may have significance in relation to a discrepancy between the ovulation and pregnancy rates following Clomiphene therapy.

Adult↗

PubMed1978

[Results of routine treatment with Clomiphen (author's transl)].

After 15 years of clinical experiences with Clomiphen treatment it seemed desirable to investigate the efficiency of this kind of therapy under routine conditions in a crowded out-patient clinic. 314 patients treated from 1972--1974 have been included in this study. From 242 sterility patients 730 cycles could be followed. 80.2% were ovulatory, but 23.5% had an insufficient luteal phase and 11.9% of these cycles ended with an anovulatory bleeding. The overall pregnancy rate was 30%. Side-effects were recorded in 4.5% but all of them were harmless, no overstimulation occurred. After discontinuation of Clomiphen therapy 8% of all patients had spontaneous cycles. In 36 patients with eugonadotropic secondary amenorrhea with a total of 115 treatment cycles ovulation was recorded in 58%. Pregnancy rate was 25%, the intensity of treatment 3.1. In 54 patients with anovulatory cycles 156 cycles (72,3%) became ovulatory, pregnancy rate was 24%, the intensity of treatment 3.5. In another group of 19 patients with oligomenorrhea ovulation occurred in 39 of 42 cycles, 4 patients became pregnant. In 108 patients with luteal phase defects in 338 cycles ovulation was found in 90.2%, with 26.6% of these cycles being still insufficient. The pregnancy rate was 18.5%, the intensity of treatment 3.7. 9.8% of these 338 cycles became anovulatory during clomiphen treatment. In 27 patients with "insufficient cycles" in 104 treatment cycles nearly all of them were ovulatory but 20% of them were found to have an insufficient corpus luteum phase. The pregnancy rate was 30%. The highest pregnancy rate was found during the first 3 treatment cycles (26%). It is consequently our policy to treat patients 4 to 6 times with clomiphen and when no pregnancy can be achieved, these patients should be treated with HMG/HCG. 65 of 73 pregnancies were followed, 52 patients were delivered with healthy babies, 12 patients aborted. Of the total number of 54 babies born, 47 were single, 6 were twins, 2 babies were stillborn. The sex ratio (male to female) was 2.2. No malformations were found. In our group of patients other factors besides ovarian dysfunction contributed to the relatively low pregnancy rate. Thus, in 116 out of 244 patients one tube was occluded, while adhesions were found in 99 treated with clomiphen as a diagnostic step to convince the patient, that stimulation of ovarian function will be possible whenever the patient desires to become pregnant. The ovulation rate in this group was 38% in addition 37% responded with anovulatory bleeding, thus, 74% of all patients experienced a positive reaction from their point of view. After discontinuation of clomiphen administration 18% of these patients continued to bleed with (7.5%) or without (10.6%) clinical signs of ovulation. A further observation is the obvious fact that clomiphen therapy free intervals can be interposed without risk of a lower success rate, compared to patients receiving continuous cycle to cycle treatment.

Adolescent↗

PubMed1995

A scanning and light microscope study comparing the effects of clomiphene citrate, estradiol 17-beta and progesterone on the structure of uterine luminal epithelial cells.

Scanning electron microscopy was used to evaluate the surface ultrastructure of uterine luminal epithelial cells from ovariectomized rats treated with either, high or low doses of Clomiphene citrate or estradiol-17 beta or progesterone given on consecutive days. Light microscopy was used to evaluate the surface epithelium and morphometric methods were used to measure cell height. It was found that clomiphene treatment produced ultrastructural surface features some of which were similar to those seen with hormone treatments and others unique to clomiphene alone. Features reminiscent of oestrogen treatment include hyperplasia and hypertrophy of the luminal epithelium, an increase in the length and density of microvilli and the formation of gland "hillocks". Features reminiscent of progesterone treatment include the development of pinopods and secretion droplets. Features unique to clomiphene treatment include possible stratification of the luminal epithelium, the presence of surface lesions, irregular and doughnut shaped cells, areas of microvilli free plasma membrane and an increase in cell height when compared to the effects of oestrogen and progesterone. It is clear that the effects of clomiphene are both dose and duration dependent; and that some of the morphological features elicited with clomiphene treatment are similar to those seen with the hormone treatments. Overall clomiphene induced features are different to those elicited with either of the hormone treatments tested.

Animals↗

PubMed1993

A prospective evaluation of clomiphene citrate challenge test screening of the general infertility population.

OBJECTIVE: To assess the results of screening an unselected general infertility population for diminished ovarian reserve with the clomiphene citrate challenge test. METHODS: Two hundred thirty-six couples were followed prospectively and studied for the relationship between clomiphene citrate challenge test screening and final diagnoses and long-term fertility rates. RESULTS: Abnormal clomiphene citrate challenge tests were found in two of 61 (3%) of the patients younger than 30 years, in five of 72 (7%) aged 30-34, in seven of 68 (10%) aged 35-39, and in nine of 35 (26%) aged 40 or older. An abnormal test predicted lower pregnancy rates; conception occurred in 92 of 213 (43%) of patients with normal results, but only two of 23 (9%) of patients with abnormal results (P < .004). Unexplained infertility (not considering the clomiphene citrate challenge test) was a common finding in patients with abnormal clomiphene citrate challenge test results (12 of 23). This incidence was significantly higher than that in patients with normal clomiphene citrate challenge test results (20 of 213) (P < .001). CONCLUSIONS: Approximately 10% of the patients in the general infertility population had abnormal clomiphene citrate challenge tests. The incidence of abnormal results increases with age beginning in the early 30s, occurs with a higher frequency in patients who would otherwise be diagnosed with unexplained infertility, and prognosticates decreased long-term pregnancy rates.

Adult↗

PubMed1995

Visual disturbance secondary to clomiphene citrate.

OBJECTIVE: To identify a distinctive constellation of persistent visual abnormalities secondary to treatment with clomiphene citrate. DESIGN: Description of the clinical findings in three patients with visual disturbance secondary to clomiphene treatment. SETTING: A neuro-ophthalmology referral center. PATIENTS: Three women aged 32 to 36 years treated for infertility with clomiphene for 4 to 15 months. RESULTS: All three patients experienced prolonged afterimages (palinopsia), shimmering of the peripheral field, and photophobia while undergoing treatment with clomiphene. The results of the neuro-ophthalmologic examination and electrophysiologic studies were normal in all three patients. Unlike previously reported cases, visual symptoms did not resolve on cessation of treatment. Patients remain symptomatic from 2 to 7 years after discontinuing treatment with the medication. CONCLUSIONS: Treatment with clomiphene can cause prolonged visual disturbance. Patients who develop such symptoms should be advised that continued administration may cause irreversible changes. Women with characteristic visual symptoms should be questioned about past use of clomiphene.

Adult↗

PubMed2002

A prospective, double-blind, randomized, placebo-controlled clinical trial of bromocriptin in clomiphene-resistant patients with polycystic ovary syndrome and normal prolactin level.

OBJECTIVE: The purpose of this study was to examine the effects of of bromocriptin combined with clomiphene citrate in clomiphene-resistant patients with polycystic ovary syndrome and normal prolactin level. DESIGN: Prospective, double-blind, controlled study. SETTING: University teaching hospital. PATIENTS: One hundred polycystic ovary patients and normal prolactin (PRL) who were clomiphene citrate resistant. INTERVENTIONS: Treatment group received 150 mg clomiphene citrate on days 5-9 and 7.5 mg bromocriptin continuously. Control group received the same protocol of clomiphene citrate combined with placebo. MAIN OUTCOME MEASURES: Hormonal status, follicular monitoring, ovulation rate. RESULTS: Follicular development (follicular size greater than 15 mm) was observed in 12 (25.5%) and eight (15.1%) women in treatment and placebo group respectively ( P=0.29). The serum prolactin level was within normal limits in all patients before treatment. After 3 and 6 months of treatment with bromocriptin, there was a significant decrease in serum level of prolactin ( P=0.000001). No any significant differences was seen in ovulation, and serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), dehydroepiandrosterone sulfate (DHEAS), progesterone (P) between treatment and placebo group after treatment. CONCLUSIONS: The only significant effect of long-term bromocriptin therapy in clomiphene citrate resistant polycystic ovary women was to lower the serum prolactin concentration. It was also concluded that 10-15% of patients with polycystic ovaries experienced occasional ovulatory cycles and pregnancy whether or not they were on treatment.

Adult↗

PubMed1991

Effect of clomiphene citrate treatment on endometrial estrogen and progesterone receptor induction in women.

A direct adverse effect of clomiphene citrate on the endometrium has been presumed, and interference with estrogen receptor-mediated endometrial estrogen receptor and progesterone receptor induction has been implicated as the mechanism responsible for an increased incidence of luteal phase deficiency in association with clomiphene citrate treatment. To clarify the net influence of clomiphene administration on endometrial steroid receptor induction, we studied five normal ovulatory women, in both a spontaneous and clomiphene-induced (150 mg/day, cycle days 5 to 9) ovulatory cycle. From cycle day 11 blood samples were obtained daily and urinary luteinizing hormone determinations were performed twice daily. Endometrial biopsy was performed on the day of the urinary luteinizing hormone surge and again 13 days after the surge. Serum levels of follicle-stimulating hormone and luteinizing hormone were determined by immunoradiometric assay, estradiol and progesterone by radioimmunoassay, and clomiphene citrate isomer concentrations in treatment cycles by reversed-phase high-performance liquid chromatography and fluorescence detection. Total, cytosolic, and salt-extracted nuclear endometrial estrogen receptor and progesterone receptor concentrations were determined by enzyme-linked immunoassay. Serum estradiol was threefold to fivefold higher (p less than 0.05) in clomiphene-induced than in spontaneous cycles 8 and 10 days before the luteinizing hormone surge, and progesterone was increased (p less than 0.05) from the day of the surge to end of the cycle. Serum enclomiphene rose to plateau between 12 and 6 days before the luteinizing hormone surge (4.1 +/- 0.8 ng/ml, mean +/- SE, n = 19) and fell thereafter to less than 1.0 ng/ml. Zuclomiphene levels increased rapidly between 14 and 8 days before the surge (53.9 +/- 2.8 ng/ml, mean +/- SE, n = 5) and then decreased gradually but remained elevated throughout the luteal phase (29.0 +/- 1.2 ng/ml, mean +/- SE, n = 33). Late luteal endometrial histology was abnormal in one of four available treatment cycle specimens, but the endocrine characteristics and number and subcellular distribution of estrogen receptor and progesterone receptor in the abnormal cycle were not different from those of normal, in-phase cycles.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1983

Effects of clomiphene citrate on the pituitary gland in chronically estrogenized rat.

Effects of clomiphene citrate (clomiphene) on the pituitary gland of chronically estrogenized ovariectomized rats were investigated. Estradiol-17 beta (E2) pellet implanted subcutaneously in castrated rats for 7 days caused significant increases in pituitary weight and serum prolactin (PRL) level but suppressed serum luteinizing hormone (LH) level. In the estrogenized rats about 40% of estrogen receptor (ER) found in whole pituitary cells (65 +/- 7 fmol/10 mg tissue) was observed in the nucleus, while 60% of ER was present in the cytosol fraction. A single injection of 5 micrograms E2 translocated cytosol ER immediately to nuclear compartment; amounts of ER found in cytosol and nuclear fractions were 16 +/- 1 and 37 +/- 4 fmol/10 mg tissue, respectively, at 1 h. However, the distribution of ER returned to the pre-injection level within 4 h. In the non-estrogenized castrated rats, the nuclear retention of ER was significantly longer than that in the estrogenized rats. A single administration of 200 micrograms clomiphene in the estrogenized rats, on the other hand, increased nuclear ER gradually. Nuclear ER reached the peak level at 4 h (62 +/- 5 fmol/10 mg tissue) and the level remained almost unchanged for 24 h. Cytosol ER decreased and reached a nadir at 4 h (4.3 +/- 0.3 fmol), and the replenishment of cytosol ER could not be detected for 24 h. Similar patterns of cytosol and nuclear ER following the clomiphene injection were also found in the castrated rats. The clomiphene administration in the estrogenized rats resulted in a significant reduction of the pituitary weight 48 h after the administration. The present results seem to show the antiestrogenic action of clomiphene in the pituitary gland.

Animals↗

PubMed1995

Interference with uterine blood flow by clomiphene citrate in women with unexplained infertility.

OBJECTIVE: To investigate the effect of clomiphene citrate on the uterine blood flow in women with unexplained infertility. METHODS: Twenty-one women who had normal uterine blood flow (pulsatility index [PI] less than 3 from the LH peak to the middle luteal phase of a natural ovulatory cycle) were enrolled in this study. Patients were given clomiphene citrate (100 mg/day) from days 5-9 of the next ovulatory cycle. The PI values measured in the natural and clomiphene citrate-treated cycles were compared using repeated measures analysis of variance. Their correlations with the estradiol (E2) and progesterone concentrations in the treatment cycle were calculated using the Pearson correlation coefficient. RESULT: In the natural cycles of those with normal uterine blood flow, the highest impedance of uterine blood flow was detected at the late follicular phase, then blood flow increased during the luteal phase. In the clomiphene citrate-treated cycles, a statistically significant decrease in uterine blood flow also occurred during the early luteal phase (P < .05). No significant correlation of E2 or progesterone serum concentrations with PI values of the uterine artery could be found in either natural or clomiphene citrate-treated cycles. CONCLUSION: The use of clomiphene citrate decreases the uterine blood flow during the early luteal phase, a periimplantation stage.

Adult↗

PubMedDate not supplied

Fluoro-clomiphene and its synthetic precursors: synthesis and receptor binding.

In an attempt to synthesize compounds with selective estrogen-receptor binding, fluoro- and amino-clomiphene were totally synthesized from benzyl chloride, and their estrogenic/antiestrogenic activity as well as that of some of their chemical intermediates was evaluated. The triazene prepared from the amino-clomiphene was converted into fluoro-clomiphene with 39% yield. In the uterotropic test, both amino- and fluoro-clomiphene exerted mild equipotent estrogenic activity, with minimal saturation doses being 50 and 100 micrograms/rat/day for three days. In the receptor binding test both derivatives demonstrated similar displacement, with an A50% value in the 10(-5) M range, as compared to 10(-6) M for clomiphene and 10(-9) M for diethyl-stilbestrol. This synthesis may be useful for the preparation of 18F-labeled clomiphene for biodistribution studies.

Animals↗

PubMed1990

Effects of clomiphene and tamoxifen in vivo on the bone-resorbing effects of parathyroid hormone and of high oral doses of calcitriol (1,25(OH)2D3) in rats with intact ovarian function consuming low calcium diet.

Two experiments were undertaken to study the abilities of clomiphene citrate (20 mg/kg body wt/wk s.c.) and tamoxifen citrate (20 mg/kg body wt/wk s.c.) to slow bone resorption mediated by (a) endogenous parathyroid hormone (PTH) and (b) exogenous calcitriol (1,25(OH)2D3) in vivo in rats with intact ovarian function. Groups of rats with 45Ca-labelled bones were fed a low-calcium (0.01% Ca) diet to stimulate secretion of PTH. Neither clomiphene nor tamoxifen showed the mobilization of 45Ca from femoral bone or prevented the reduction in bone calcium induced by feeding this diet. Moreover these drugs did not depress the urinary excretion of 45Ca or hydroxyproline. These observations indicated that clomiphene and tamoxifen did not inhibit PTH-mediated bone resorption. Administering calcitriol (50 ng/day) orally for 14 days raised plasma calcium, increased urinary 45Ca and its specific activity and decreased femur 45Ca: all these responses were similar in animals receiving calcitriol alone and calcitriol with clomiphene or tamoxifen. The femur 45Ca values (dpm X 10(-3) were: (mean +/- SD, n = 8) placebo, 1901 +/- 127; 1,25(OH)2D3, 1727 +/- 96**; clomiphene + 1,25(OH)2D3, 1694 +/- 93**; tamoxifen + 1,25(OH)2D3, 1664 +/- 61**. (** = P less than 0.01). Thus neither clomiphene nor tamoxifen prevented calcitriol-mediated bone resorption in vivo in the rat.

Animals↗

PubMed2004

Potent inhibition of human cardiac potassium (HERG) channels by the anti-estrogen agent clomiphene-without QT interval prolongation.

The acquired form of the long-QT syndrome (LQTS) is a major safety consideration for the development and subsequent use of both cardiac and non-cardiac drugs; it is usually associated with pharmacological inhibition of cardiac HERG-encoded potassium channels. Clomiphene is an anti-estrogen agent used extensively in the treatment of infertility and is not associated with a risk of QT interval prolongation, in contrast to a structurally related compound tamoxifen. We describe here a potent inhibitory effect (IC(50) = 0.18 microM) of clomiphene on HERG ionic current (I(HERG)) recorded from a mammalian cell line expressing HERG channels. Inhibition of I(HERG) by clomiphene showed voltage-dependence and developed quickly following membrane depolarisation, indicating contingency of block on HERG channel gating. At 100 nM, clomiphene and the related anti-estrogen tamoxifen produced similar levels of I(HERG) blockade (p > 0.05). Experiments on guinea-pig isolated perfused hearts revealed that, despite its inhibitory action on I(HERG), clomiphene produced no significant effect at 1 microM on uncorrected QT interval (p > 0.1) nor on rate-corrected QT interval (QT(c); p > 0.1 for QT(c) determined using Van de Water's formula). The disparity between clomiphene's potent I(HERG) inhibition and its lack of effect on the QT interval underscores the notion that I(HERG) pharmacology may best be used alongside other screening methods when investigating the QT-prolonging tendency and related cardiotoxicity of non-cardiac drugs.

Animals↗

PubMed2006

A prospective randomized trial comparing anastrozole and clomiphene citrate in an ovulation induction protocol using gonadotropins.

OBJECTIVE: To compare the ovarian and endometrial effects of anastrozole and clomiphene when used with gonadotropins in a combination protocol. DESIGN: Prospective randomized trial. SETTING: Academic infertility center. PATIENT(S): Fifty infertile women. INTERVENTIONS(S): Women were randomized to receive either 1 mg anastrozole or 100 mg clomiphene citrate for 5 days (cycle days 3-7) followed by FSH injections (days 7-11) for ovulation induction. A subset participated in a crossover arm of the study. MAIN OUTCOME MEASURE(S): Ovarian follicle number and size, E(2) levels, endometrial thickness, pregnancy, and cancellation rates. RESULT(S): On cycle day 12, anastrozole cycles were associated with fewer total follicles (1.4 vs. 3.6, P=0.01), fewer mature follicles (0.6 vs. 1.6, P<.01), lower serum E(2) (131 pg/mL vs. 613 pg/mL, P<.01,) and the same endometrial stripe thickness compared with clomiphene citrate cycles. Cycle cancellation rates were similar between the two groups. On the day of hCG administration in noncancelled cycles, anastrozole cycles were associated with fewer total follicles (1.6 vs. 3.8, P<.01), fewer mature follicles (1.3 vs. 2.1, P<.01), and an equal endometrial stripe thickness compared with clomiphene citrate cycles. Pregnancy rates were similar between clomiphene (20%) and anastrozole (12%) cycles. CONCLUSION(S): Anastrozole when used in conjunction with gonadotropins results in lower E(2) levels and fewer follicles than clomiphene citrate. A combination protocol of anastrozole and gonadotropins may be a safer protocol for patients at higher risk of hyperstimulation and multiple births after infertility treatments.

Administration, Oral↗

PubMed1986

The primary treatment of luteal phase inadequacy: progesterone versus clomiphene citrate.

This study was undertaken in order to evaluate the superiority, if any, of progesterone or clomiphene citrate in treatment of infertile women with luteal phase inadequacy. Eighty-two patients were randomly treated with progesterone or clomiphene citrate. Some patients with failure of progesterone were changed to clomiphene citrate treatment; some patients with failure of clomiphene citrate were changed to progesterone treatment. A life-table analysis was used for evaluation of the results. No statistical difference was noticed between the two treatments. Seventeen of 57 patients treated with progesterone and 13 of 62 patients treated with clomiphene citrate conceived. It is recommended that: patients with luteal phase inadequacy can be treated primarily with progesterone; an endometrial biopsy should be performed if the patients fail to conceive; if endometrial biopsy continues to be abnormal the patients can be treated again with clomiphene citrate. Some alternative treatments for luteal phase inadequacy are needed.

Biopsy↗

PubMed1998

E-cadherin and its messenger ribonucleic acid in periimplantation phase human endometrium in normal and clomiphene-treated cycles.

OBJECTIVE: The purpose of this investigation was to determine whether treatment with clomiphene citrate, which is estrogenic and antiestrogenic, affects the expression of the cell adhesion molecule E-cadherin in human periimplantation phase endometrium. STUDY DESIGN: Five healthy women were studied for two cycles each, a control and a treated (clomiphene 50 mg daily, days 5 through 9) cycle. A biopsy specimen of endometrial tissue was studied (8 to 10 days post luteinizing hormone surge) for immunohistochemical localization, Western analysis of E-cadherin with use of a highly specific monoclonal antibody to human E-cadherin, and determination of messenger ribonucleic acid for E-cadherin by reverse transcription-polymerase chain reaction by use of oligonucleotide primers specific to E-cadherin and amplifying a 432 bp fragment. RESULTS: Luteal phase plasma progesterone levels were significantly higher in clomiphene cycles. E-cadherin was immunocytochemically present in endometrium of control and treated cycles with no apparent difference in staining intensity. Western blots revealed the presence of E-cadherin. It was relatively more abundant in clomiphene-treated than control cycles but not significantly different. The message for E-cadherin gene is expressed in endometrium of control (n = 5) and clomiphene cycles (n = 4). CONCLUSIONS: E-cadherin and its gene transcripts are expressed in periimplantation phase endometrium and are not significantly affected by clomiphene treatment.

Adult↗

PubMed2002

Metformin therapy improves ovulatory rates, cervical scores, and pregnancy rates in clomiphene citrate-resistant women with polycystic ovary syndrome.

OBJECTIVE: To evaluate the effect of metformin therapy on hyperandrogenism, insulin resistance, cervical scores, ovulation, and pregnancy rates in clomiphene citrate-resistant women with polycystic ovary syndrome (PCOS). DESIGN: Prospective, randomized, double-blind, placebo-controlled study. SETTING: Infertility clinic of a tertiary referral center. PATIENT(S): Fifty-six women with clomiphene citrate-resistant PCOS. INTERVENTION(S): Two cycles of oral metformin therapy (850 mg, twice daily) in group I and placebo therapy (twice daily) in group II. Clomiphene citrate (100 mg/day) on cycle days 3-7 of the second cycle in both groups. MAIN OUTCOME MEASURE(S): Insulin, T, DHEAS, FSH, LH, body mass index (BMI), waist-to-hip ratio, endometrial thickness, cervical score, ovulation, and pregnancy rates in clomiphene-induced cycles after metformin therapy. RESULT(S): Metformin therapy resulted in a significant decrease in total T, LH level, LH/FSH ratio, insulin resistance, and mean BMI. No difference in waist-to-hip ratio, DHEAS level, and fasting insulin level was observed. Clomiphene citrate induction resulted in higher ovulation rates and thicker endometrium in the metformin group than in the placebo group. There was higher cumulative pregnancy rate in the metformin group; however, there was no significant difference in the pregnancy rate between the two groups. CONCLUSION(S): Metformin therapy not only decreases hyperandrogenism and insulin resistance but also improves ovulation rates, cervical scores, and pregnancy rates in clomiphene citrate-resistant women with PCOS.

Adult↗