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At least 19 recordsLinked to original sources
PubMed2006

A randomized controlled trial of the efficacy of rosiglitazone and clomiphene citrate versus metformin and clomiphene citrate in women with clomiphene citrate-resistant polycystic ovary syndrome.

OBJECTIVE: To compare the efficacy of rosiglitazone and clomiphene citrate (CC) with metformin and CC in women with CC-resistant polycystic ovary syndrome (PCOS). DESIGN: Randomized controlled trial (RCT). SETTING: A university teaching hospital in Jeddah, Saudi Arabia. PATIENT(S): Twenty-five women with CC-resistant PCOS. INTERVENTION(S): Twelve women were assigned to the rosiglitazone and CC group, and 13 women were assigned to the metformin and CC group for three treatment cycles. The first cycle was started on the first day of the period with either rosiglitazone (4 mg twice daily) or metformin (500 mg three times daily) and continued for three cycles. Clomiphene citrate (100 mg) from the third day for 5 days was added to each cycle. MAIN OUTCOME MEASURE(S): Ovulation rate, number of follicles and estradiol (E2) on day 12 of the cycle, pregnancy rate, and changes in fasting glucose, serum insulin, HbA(1C), total testosterone (T), free T, luteinizing hormone (LH), follicle-stimulating hormone (FSH), dehydroepiandrosterone sulfate (DHEAS), delta4-androstenedione (delta4-A), sex hormone-binding globulin (SHBG), insulin-like growth factor (IGF)-1, insulin-like growth factor binding protein (IGFBP)-1, and IGFBP-3. RESULT(S): No significant differences were found in the baseline characteristics of both groups. Ovulation rate was significantly higher in the rosiglitazone and CC group (18 out of 28 cycles [[64.3%]]) than the metformin and CC group (12 out of 33 cycles [[36.4%]]) (P=.035). Similarly, statistically significant differences were found in the number of follicles > or =14 mm in the rosiglitazone and CC group (2.2 +/- 1) compared with the metformin and CC group (1.1 +/- 0.9) (P=.02) and E2 on day 12 of the cycle in the rosiglitazone and CC group (1,991 +/- 1,389 pmol/L) compared with the metformin and CC group (548 +/- 327) (P<.001). The pregnancy rate was also higher in the rosiglitazone and CC group (6 out of 12 [[50%]] women) than the metformin and CC group (5 out of 13 [[38.5%]] women), but did not reach statistical significance (P=.58). Both groups showed no significant changes in fasting plasma glucose or HbA(1C) or IGFBP-3 values. However, in both groups, fasting serum insulin, total T, free T, LH, DHEA-S, delta4A, and IGF-1 levels decreased significantly, and SHBG and IGFBP-1 exhibited significant increases. CONCLUSION(S): These findings suggest that short-term use of rosiglitazone and CC is more efficacious than metformin and CC in ovulation induction in women with CC-resistant PCOS.

Adult↗
PubMed1993

Sequential clomiphene citrate and human menopausal gonadotrophin for ovulation induction: comparison to clomiphene citrate alone and human menopausal gonadotrophin alone.

The need for frequent injections and monitoring, the possibility of multiple gestations, and the higher cost compared to clomiphene citrate, prevents many clinicians from using human menopausal gonadotrophin (HMG) for ovulation induction. A sequential medication regimen, in which HMG is taken after clomiphene, overcomes these problems. We retrospectively compared per cycle fecundity and birth rates in 119 cycles of clomiphene-HMG, 524 cycles of clomiphene alone, 57 cycles of HMG alone, and 79 cycles of concurrent HMG and clomiphene in patients receiving intra-uterine insemination (IUI), who were free of endometriosis or tubal disease. Per cycle fecundity for clomiphene-HMG was 22% [95% confidence interval (CI) 12-34%], double that of clomiphene alone (11%) (95% CI 8-14%) (P < 0.01), and equal to HMG alone (18%) (95% CI 7-29%) or HMG and clomiphene together (19%) (95% CI 10-28%). The multiple birth rate for clomiphene-HMG (7/21) equalled that for HMG alone (3/12) and HMG and clomiphene together (3/8). The average number of ampoules of HMG required [follicle stimulating hormone (FSH) 75 mIU, luteinizing hormone (LH) 75 mIU] was decreased by 65% from 24.5 +/- 1.0 for HMG or HMG and clomiphene together to 8.6 +/- 0.3 for clomiphene-HMG (P < 0.001). Per cycle fecundity was identical when one, two or three ampoules of HMG per day were administered after clomiphene. We conclude that ovulation induction with sequential clomiphene-HMG results in fecundity double that of clomiphene alone and equal to HMG alone or concurrent with clomiphene, thereby reducing the requirement for HMG.

Clomiphene↗
PubMed2000

Clomiphene citrate for unexplained subfertility in women.

OBJECTIVES: Clomiphene citrate appears to increase ovulation in women with oligo-ovulatory subfertility. It may also work in women with unexplained subfertility, perhaps by correcting an unidentifiable ovulatory dysfunction. The objective of this review was to assess the effects of clomiphene citrate in women with unexplained subfertility. SEARCH STRATEGY: The Cochrane Subfertility Review Group specialised register of controlled trials was searched". SELECTION CRITERIA: Randomised trials of clomiphene citrate (doses of 50 to 250 milligrams per day up to 10 days) compared to placebo or no treatment in women with unexplained subfertility. DATA COLLECTION AND ANALYSIS: Trial quality was assessed and data were extracted independently by two reviewers. MAIN RESULTS: Five studies were included. Four trials were of crossover design, and quality of the randomisation was variable. Compared to placebo, clomiphene citrate was associated with an increase in pregnancy rates. The odds ratio for pregnancy per patient was 2.38 (95% confidence interval 1.22 to 4.62). The odds ratio of pregnancy per cycle was 2.5 (95% confidence interval 1.35 to 4.62). REVIEWER'S CONCLUSIONS: Clomiphene citrate appears to modestly improve pregnancy rates in women with unexplained subfertility. However adverse effects include a possible ovarian cancer risk and risk of multiple pregnancy.

Clomiphene↗
PubMed2002

The effect of metformin plus clomiphene citrate on ovulation and pregnancy rates in clomiphene-resistant women with polycystic ovary syndrome.

OBJECTIVE: To study the effect of metformin in combination with clomiphene citrate, as compared with placebo plus clomiphene citrate, on the ovulation and pregnancy rates in clomiphene citrate-resistant women with polycystic ovary syndrome. METHODS: This study was carried out at King Hussein Medical Center, Amman, Jordan, during the period January 2001 through to July 2001. Twenty-eight clomiphene citrate-resistant polycystic ovary syndrome women were evaluated prospectively for 6 treatment cycles by receiving metformin, 850mg twice daily throughout the cycle along with 50 mg clomiphene citrate, starting on day 5-9 of the same cycle (N=16), or by taking placebo with clomiphene citrate (N=12). During cycles 2-6, clomiphene citrate was added with increments of 50mg (up to 200 mg/day) for both groups. Progesterone level on day 21 and 28 >5ng/dl was indicative of ovulation. RESULTS: A statistically significant increase in the rates of ovulation (68.6% versus 25%, p<0.05) and pregnancy (56.3% versus 16.6%, p<0.05) were observed in the metformin-clomiphene citrate group as compared with the placebo-clomiphene citrate controls. Insignificant increase in the rate of ovarian hyperstimulation was noted in the placebo-clomiphene citrate group. CONCLUSION: Metformin-clomiphene citrate regimen in resistant-clomiphene citrate polycystic ovary syndrome women significantly increases the ovulation and pregnancy rates, and decreases the occurrence of ovarian hyperstimulation syndrome.

Adult↗
PubMed1982

Clomiphene and dexamethasone in women unresponsive to clomiphene alone.

Twelve oligomenorrhic women with polycystic ovary syndrome (PCO) in whom clomiphene (250 mg daily for 5 days) and 10,000 IU human chorionic gonadotropin had failed to induce ovulation were treated with clomiphene and dexamethasone. Eight of the 12 women underwent complete hormonal assessment during treatment. Six of the 12 ovulated and 1 conceived. Serum total and unbound estradiol and testosterone (T), serum dehydroepiandrosterone sulfate (DHEA-S), sex hormone binding-globulin binding capacity (SHBG-BC), luteinizing hormone (LH), follicle-stimulating hormone (FSH) and prolactin (PRL) were measured during clomiphene and dexamethasone therapy. SHBG-BC increased in response to clomiphene whether or not ovulation occurred. After treatment with clomiphene and dexamethasone there was a significant decrease in serum T, unbound T, and DHEA-S 2 weeks after dexamethasone administration, but there were no change in LH, FSH, or PRL. In patients who ovulated after clomiphene and dexamethasone, T and unbound T increased again after clomiphene was begun despite the continuation of dexamethasone. The women who ovulated after clomiphene and dexamethasone treatment had significantly higher pretreatment levels of DHEA-S than those who did not ovulate. Clomiphene and dexamethasone treatment may be beneficial to women who have elevated levels of DHEAS and who fail to ovulate with maximum doses of clomiphene.

Anovulation↗
PubMed2006

Efficacy of combined metformin-letrozole in comparison with metformin-clomiphene citrate in clomiphene-resistant infertile women with polycystic ovarian disease.

BACKGROUND: Adding metformin to clomiphene citrate in clomiphene-resistant polycystic ovary syndrome (PCOS) patients increases ovulatory response. However, because of anti-estrogenic effects of clomiphene it may be associated with lower pregnancy rate, offsetting the ovulation rate benefit. Letrozole is an aromatase inhibitor which induces ovulation without anti-estrogenic effects. METHODS: Infertile women with PCOS were randomly divided into metformin-letrozole (29 patients) and metformin-clomiphene groups (30 patients). After an initial 6-8 weeks of metformin, they received either letrozole (2.5 mg) or clomiphene (100 mg) from day 3-7 of their menstrual cycle. Estradiol (E2) levels, number of follicles, pregnancy rates and endometrial thickness were measured on the day of HCG administration. RESULTS: Mean total E2 and E2 per mature follicle were significantly higher in clomiphene group without a difference in mean number of mature follicles >18 mm and ovulation rate. Endometrial thickness was significantly higher in letrozole group. The pregnancy rate in letrozole group (10 patients, 34.50%) as compared with clomiphene group (5 patients, 16.67%) did not show significant difference, whereas full-term pregnancies were higher in letrozole group [10 patients (34.50%) versus 3 patients (10%)]. CONCLUSION: In clomiphene-resistant PCOS patients, the combination of letrozole and metformin leads to higher full-term pregnancies.

Adult↗
PubMed2006

Clomiphene citrate plus N-acetyl cysteine versus clomiphene citrate for augmenting ovulation in the management of unexplained infertility: a randomized double-blind controlled trial.

OBJECTIVE: To compare clomiphene citrate with N-acetyl cysteine vs. clomiphene citrate alone for augmenting ovulation in management of unexplained infertility. DESIGN: Prospective randomized double-blind controlled trial. SETTING: Department of obstetrics and gynecology in a university medical faculty in Egypt. PATIENT(S): Four hundred four patients as a study group (clomiphene citrate plus N-acetyl cysteine group) and 400 patients as a control group (clomiphene citrate-alone group). All women had unexplained infertility. INTERVENTION(S): Patients in the study group were treated with clomiphene citrate (50-mg tablets) twice per day and with N-acetyl cysteine (1,200 mg/d orally) for 5 days starting on day 2 of the cycle. Patients in the control group were treated with clomiphene citrate with sugar powder. MAIN OUTCOME MEASURE(S): The primary outcomes were number and size of growing follicles, serum E(2), serum P, and endometrial thickness. The secondary outcome was the occurrence of pregnancy. RESULT(S): There were no statistically significant differences between the two groups in the number of follicles sized >18 mm, mean E(2) levels, serum P, or endometrial thickness. Pregnancy rate was comparable in both groups (22.2% vs. 27%). Miscarriage rate was comparable in both groups (6.7% in the study group vs. 7.4% in the control group). CONCLUSION(S): N-Acetyl cysteine is ineffective in inducing or augmenting ovulation in patients with unexplained infertility and cannot be recommended as an adjuvant to clomiphene citrate in such patients.

Acetylcysteine↗
PubMed1986

Comparison between clomiphene plus pulsatile human menopausal gonadotrophin and clomiphene plus pulsatile follicle stimulating hormone in induction of multiple follicular development in women.

Eighteen normally cycling women with tubal infertility undergoing in-vitro fertilization and embryo transfer were treated with clomiphene only (nine cycles), clomiphene plus human menopausal gonadotrophin (HMG) (18 cycles) and clomiphene plus follicle-stimulating hormone (FSH) (12 cycles). Clomiphene was given from day 2 to 6 (150 mg daily). HMG and FSH were injected s.c. in a pulsatile manner via a pump (28 IU every 3 h). Plasma FSH and oestradiol levels and the number of follicles greater than or equal to 16 mm in diameter were similar in the clomiphene/HMG and the clomiphene/FSH cycles, but significantly higher than in the clomiphene-only cycles. In contrast, luteinizing hormone and progesterone levels during the treatment did not differ significantly among the three regimens. Twelve of the 18 women were treated with clomiphene/HMG in one cycle and clomiphene/FSH in another and eight of them with clomiphene only in a third cycle (a total of 32 cycles). In the clomiphene/HMG cycle seven of these 12 women (58%) had plasma FSH levels during treatment similar to those in the clomiphene/FSH cycle and six of them (86%) had the same number of follicles in both cycles. A significant, but not very strong correlation was found between FSH treatment levels and the number of follicles greater than or equal to 16 mm when all 32 cycles were combined (r = 0.40). It is suggested that pulsatile HMG and FSH in combination with clomiphene are in general equally effective in inducing multiple follicular development in normal women. However, individual responses show great variability.

Clomiphene↗
PubMed2003

Sequential treatment of metformin and clomiphene citrate in clomiphene-resistant women with polycystic ovary syndrome: a randomized, controlled trial.

BACKGROUND: Recognition of the importance of insulin resistance in clomiphene-resistant women with polycystic ovary syndrome (PCOS) has led to the use of insulin sensitizers. METHODS: A randomized, controlled trial was conducted to compare efficacy of sequential treatment with metformin and clomiphene citrate with conventional gonadotrophins. Sixty clomiphene-resistant women with PCOS were randomized to two groups (n = 30 each), using computer-generated tables. Group I received metformin for 6 months, followed by ovulation induction with clomiphene citrate; group II received hMG for ovulation induction. Hormonal profiles were evaluated at the onset and after completion of treatment. RESULTS: There was no significant difference in pregnancy rates between the two groups (16.7 versus 23.3%). In group I, there was a significant improvement in menstrual function and ovulation after treatment (40%, P < 0.001; and 46.7%, P < 0.001), with a significant decrease in fasting insulin levels (P < 0.05). There were no changes in other biochemical parameters. The ovulation rate in group II was 43.3%, with a high drop-out rate. The cost-effective analysis for medications per pregnancy in group I was US$ 71 +/- 3 versus US$ 277 +/- 171 in group II. CONCLUSIONS: Sequential treatment with metformin and clomiphene citrate is an effective and safe option for clomiphene-resistant women with PCOS.

Adult↗
PubMed1980

[Combined clomiphene-dexamethasone therapy in cases with resistance to clomiphene (author's transl)].

Combined clomiphene-dexamethasone treatment was applied to 13 patients with clomiphene-resistant anovulation which had been caused by androgenic hyperactivity of ovarian or adrenal origin. The women, following induced withdrawal bleeding, received 200 mg/die clomiphene over five days, from the fifth through the ninth days of their cycles, plus 2 mg/die dexamethasone over ten days, from the fifth to 14th days of cycle, after they had failed to conceive in response to clomiphene alone administered in rising doses up to 200 mg/die. Nine pregnancies were successfully induced by that treatment. Two of them ended in abortion and one in premature twin delivery. Combined clomiphene-dexamethasone treatment is recommended for clomiphene-resistant cases with ovarian or adrenal hyperandrogenism, particularly for patients with polycystic ovaries (Stein-Leventhal syndrome).

Adrenocortical Hyperfunction↗
PubMed1978

Induction of ovulation with clomiphene and estradiol benzoate in anovulatory women refractory to clomiphene alone.

Twenty-two infertile and clomiphene-nonresponding patients received a course of clomiphene, 100 mg/day for 5 days, followed 7 days later by an intramuscular injection of 1 mg of estradiol benzoate. The diagnosis of idiopathic chronic anovulation had been established. None of these patients had galactorrhea, hirsutism, or ovarian enlargement. Thirteen of the twenty-two women had surges of both luteinizing hormone and follicle-stimulating hormone after the estradiol injection; the peak gonadotropin levels occurred within 72 hours of the injection. These 13 patients ovulated and pregnancy ensued in 10 of them. The estradiol benzoate injection also elicited a significant increase in serum prolactin levels- This enhanced prolactin release had no apparent effect on the gonadotropin surge. These results suggest that the association of clomiphene and estradiol benzoate potentiates the action of clomiphene and may prove useful in clomiphene nonresponders.

Adult↗
PubMed2003

A randomized clinical trial of treatment of clomiphene citrate-resistant anovulation with the use of oral contraceptive pill suppression and repeat clomiphene citrate treatment.

OBJECTIVE: The purpose of this study was to evaluate the effectiveness and endocrine response of oral contraceptive ovarian suppression followed by clomiphene citrate in patients who previously were clomiphene citrate resistant. STUDY DESIGN: Forty-eight patients from a private tertiary infertility clinic were assigned randomly prospectively to either group 1 (oral contraceptive/clomiphene citrate), which received continuous oral contraceptives followed by clomiphene citrate, or to group 2 (control) received no treatment in the cycle before clomiphene citrate treatment. On day 3, 17 beta-estradiol, follicle-stimulating hormone, luteinizing hormone, and androgens were assayed before and after treatment. Follicle growth, ovulation, and pregnancy were evaluated. The Student t test and analysis of variance were used for statistical significance. RESULTS: The oral contraceptive/clomiphene citrate group had a significantly higher percentage of patients who ovulated and of ovulatory cycles and pregnancies. Significantly lower levels of 17 beta-estradiol, luteinizing hormone, and androgen levels were seen in the oral contraceptive/clomiphene citrate group, with no significant changes in group 2. CONCLUSION: Suppression of the ovary with oral contraceptives results in excellent rates of ovulation and pregnancy in patients who previously were resistant to clomiphene citrate. The decreases in ovarian androgens, luteinizing hormone, and 17 beta-estradiol may be responsible for the improved response.

Adult↗
PubMed1992

Clomiphene-dexamethasone treatment of clomiphene-resistant women with and without the polycystic ovary syndrome.

We used clomiphene and dexamethasone in 40 infertile women to treat chronic anovulation resistant to the use of clomiphene alone. Eighteen (45%) of the women had the polycystic ovary (PCO) syndrome; the remaining 22 (55%) had clomiphene-resistant anovulation from idiopathic causes. Both groups of women were similar in regard to age, parity, duration of infertility and absence of other causes of infertility besides chronic anovulation. Ovulation could be induced in approximately 90% of the women in each group. Altogether, 19 of 36 women (52.8%) conceived without any side effects or complications. The cumulative probability of conception at nine months of treatment was 87.5% in PCO patients and 46% in the non-PCO group. Clomiphene plus dexamethasone was highly effective in the treatment of clomiphene-resistant anovulation associated with infertility in women with and without the PCO syndrome.

Adult↗
PubMed1983

Metabolism of clomiphene in the rat. Estrogen receptor affinity and antiestrogenic activity of clomiphene metabolites.

Incubation of the nonsteroidal antiestrogen clomiphene with rat liver microsomes resulted in the formation of the 4-hydroxy-, N-desethyl-, and N-oxide metabolites, in qualitative contrast to results previously obtained analogously with rabbit microsomes, with which only the first two metabolites were detected. Metabolites were characterized by thin-layer chromatography in comparison with synthetic standards. They were similarly compared using low resolution electron ionization mass spectrometry, except for the N-oxide which was best characterized by fast atom bombardment mass spectrometry. Oral administration of clomiphene resulted in no detectable urinary elimination of the drug or its metabolites; 4-hydroxyclomiphene was the sole detectable elimination product in fecal extracts. The relative uterine cytosol estrogen receptor binding affinities, at 4 degrees, of 4-hydroxyclomiphene and the E-isomers of clomiphene, desethylclomiphene, and clomiphene N-oxide were, in turn, 331, 0.71, 0.62, and 0.88 (estradiol = 100). In the 3-day immature rat uterotropic assay, 4-hydroxyclomiphene had no significant uterotropic effect at doses up to 50 micrograms/day, but substantially inhibited that of estradiol (0.5 micrograms/day) at doses of 2 micrograms/day.

Animals↗
PubMed1997

Successful induction of ovulation in normogonadotrophic clomiphene resistant anovulatory women by combined naltrexone and clomiphene citrate treatment.

Patients suffering from normogonadotrophic anovulation and infertility are initially treated with clomiphene citrate. Those who do not respond to clomiphene citrate usually receive gonadotrophin treatment which is labour-intensive, expensive, and associated with an increased risk of multiple pregnancies and ovarian hyperstimulation syndrome. We treated 22 patients with clomiphene resistant normogonadotrophic anovulation with naltrexone (an opioid receptor blocker) alone or naltrexone in combination with an antioestrogen. In 19 patients ovulation and resumption of a regular menstrual cycle was achieved and in 12 out of 19 a singleton pregnancy was observed. In conclusion, ovulation can be induced successfully using naltrexone alone or naltrexone in combination with an anti-oestrogen in clomiphene citrate resistant anovulatory patients. Compared to gonadotrophin induction of ovulation, this method is safe, simple and inexpensive.

Administration, Oral↗
PubMed1979

Clomiphene test and clomiphene therapy in idiopathic male infertility.

Clomiphene citrate, 50 mg/day, was administered to 105 patients with idiopathic azoospermia or oligoasthenospermia. Plasma FSH, LH, testosterone, and in a few cases estradiol were evaluated on day 0 and day 15 of therapy. Twelve other patients with no treatment were assayed in the same way. Statistical analysis demonstrated that, as a group, the infertile male population responds normally to clomiphene administration. On the other hand, three types of individual responses were recorded: complete positive response, dissociated positive response, and negative response. Sixty-nine patients were randomly selected for clomiphene therapy, 50 mg/day for 100 days; however, of 54 who completed the treatment schedule, only 11 showed elevated sperm counts. A study of correlations between hormonal and semen responses to clomiphene indicates that a complete or dissociated endocrine response is not an accurate predictor of possible semen amelioration on long-term therapy; on the other hand, sperm characteristics did not improve in those patients who did not demonstrate a positive hormonal response, mainly testosterone, on the 15th day of therapy.

Adult↗
PubMed1977

Menometrorrhagia of the puberty: therapy with Clomiphene (Clomiphene and puberal menometrorrhagia).

The authors administrated the Clomiphene, in different doses, to 8 patients among 27 observed. These patients were checked for a long time by basal body temperature and in some cases, measuring total urinary estrogens and pregnandioluria. The therapy was administrated in 38 cicles of the 163 cicles observed. This drug got evident results on flux duration, less significant results on the cicle length. The Clomiphene produced ovulatory cicles in 58 per cent of the cases, against 7 per cent of spontaneous ovulatory cicles of the same patients. The drug effect is better in the cases with normo or moderate hypo or hyper estrogenism, not so good in the cases with a remarcable hypoestrogenism. The therapy with Clomiphene did not produce any inconvenient. The results got were put in comparison with those of the other drug (Ciclophenile) and the superiority of Clomiphene was confirmed.

Adolescent↗