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PubMed1990

Normoprolactinemic anovulation nonresponsive to clomiphene citrate: ovulation induction with bromocriptine.

Ovulation under bromocriptine was studied in 14 women with normoprolactinemic amenorrhea (5 primary, 9 secondary), unresponsive to clomiphene citrate (CC). On bromocriptine alone, ovulation occurred in 4 (28.6%). In the same subjects, bromocriptine was subsequently associated with CC. Seven patients ovulated (50.0%), including 3 that had responded to bromocriptine alone. Ovulation occurred once or twice in 6 of the 9 cases of secondary amenorrhea (66.6%). In several occasions, when ovulation induction failed, luteinized unruptured follicles were found under ultrasonographic monitoring. Four patients who had a negative response to progestin challenge did not ovulate with the treatment. Women with plasma prolactin in the upper normal range had a greater probability of achieving ovulation induction.

Adolescent↗
PubMed1979

Effects of (Bu2)-cAMP and clomiphene on serum concentrations of several proteins and hormones in gonadectomized monkeys.

Sixteen mumol kg-1 of dibutyryl cyclic adenosine 3',5'-monophosphate [(Bu)2cAMP] given intramuscularly to gonadectomized green monkeys (Cercopithecus aetheops sabeus) for two-week periods, produced a significant elevation in the serum concentrations of thyroxine-binding globulin (TBG), fibrinogen, and haptoglobin. No changes were noted in cortisol-binding golbulin (CBG), cortisol, thyroxine, transferrin, total proteins, and albumin. Clomiphene citrate (12.5 mg orally) given concomitantly with (Bu)2cAMP blocked partially the (Bu)2cAMP-induced fibrinogen increment, but not the change in TBG concentration.

Administration, Oral↗
PubMed1990

Clomiphene citrate directly impairs endometrial receptivity in the mouse.

Clomiphene citrate (CC) has known antifecundity effects in animal models. To help define the site of action of this effect, we studied the direct effect of CC on endometrial receptivity by transferring embryos to hormonally prepared prepubertal mice. Prepubertal mice were begun on one of four blinded hormonal preparations consisting of two consecutive 3-day periods of daily injections: oil vehicle, oil-progesterone (P), estradiol (E2)-P, or CC-P. Blastocysts, which had not been exposed to CC, were then surgically transferred to these prepubertal recipients. Fourteen days after embryo transfer, implantations and term pregnancies were counted at necropsy. In this model, CC demonstrated no estrogen agonist effect, and had a significant adverse effect on endometrial receptivity. CC appeared to lower fecundity by a direct endometrial effect.

Animals↗
PubMed1990

Detection of the time of ovulation in clomiphene stimulated cycles with an easily applicable urine test.

40 cycles of 35 patients, 38 of which were stimulated with clomiphen, were monitored with the LH-Colortest. This urine test, which was applied by the patients themselves twice daily, detected the LH peak in 33 out of 34 cycles with proven ovulation. In 24 cycles, the LH peak was registered in urine already fourteen hours before it showed in the daily serum controls. The urine LH peak (the test becomes positive at an LH concentration of at least 50 IU/ml) was observed on cycle day 13.6. on average while the corresponding LH peak in serum occurred on cycle day 14.2 on average. The sensitivity of the LH-Colortest was 97.2% and its specificity was 100%.

Adult↗
PubMed1990

Ovulation induction with clomiphene and the rise in heterotopic pregnancies. A report of two cases.

Two women were treated for heterotopic pregnancies, the simultaneous occurrence of an intrauterine pregnancy and an ectopic pregnancy. The commonly accepted incidence is 1:30,000. The actual rate appears to be significantly higher; the two most prominent reasons are today's increased rate of ectopic pregnancies and the increased use of clomiphene in infertile women. A rigorous evaluation is required in all early pregnancies in which an ectopic is suspected to rule out the presence of a heterotopic pregnancy.

Adult↗
PubMedDate not supplied

[Ovulation induction using clomiphene and human gonadotropins in combined therapy].

Stimulation of ovulation combined with the clomiphene therapy and human gonadotropins is presented. Follicular maturation was followed by changes of the cervical score and ultrasonic folliculometry from the tenth day of the stimulating cycle. Ovulation was proved by the change of quality of the cervical mucus, the increase of the BBT, the increase of the progesterone concentration in serum, then by ultrasonically proved changes inside the follicle and in endometry, and finally by pregnancy. With the combined therapy the authors stimulated ovulation in a group of 14 females, altogether 21 cycles. In all the patients, before the application of the combined therapy, induction of ovulation with clomiphane alone through at least 6 cycles proved unsuccessful. Ovulation was proved in the 20 cycles of the combined stimulation. Altogether 11 pregnancies of all induced cycles were obtained: 6 pregnancies with term delivery, 2 extrauterine pregnancies, 1 spontaneous abortion in the 24th week, 1 missed abortion, and 1 blighted ovum. Two twin pregnancies were recorded. In one patient the syndrome of hyperstimulation of the first degree occurred, while in the others there were no complications at all.

Adult↗
PubMed1989

[The use of clomiphene and menotropins as inducers of multiple follicular growth in a program of in vitro fertilization].

In our IVF & related techniques program, clomiphene 50 mg was used from days 2 to 6 of the cycle in 20 patients and 20 cycles. (17 IVF patients and 3 GIFT patients) menotropins were also used in 2 different schemes: a) 2 ampules in alternated days (12 cases) and b) one ampule daily (8 cases). The patients with the daily scheme required lesser total dose of menotropins and developed higher estradiol levels, although this had none statistic significance, and they also developed a greater number of follicles. There were 16 laparoscopies for ovum capture and 53 oocytes were retrieved (30.2% mature) 10 oocytes were from the GIFT patients. 16 oocytes were fertilized and 8 cleaved. There was only one pregnancy from and IVF patient with the alternated scheme that ended with a first trimester abortion.

Adult↗
PubMedDate not supplied

Follicular fluid cyclic nucleotides, prostaglandin E2, leukotriene B4, oestradiol, progesterone and luteinizing hormone in women stimulated by clomiphene and gonadotropins.

The concentrations of cyclic AMP, cyclic GMP, prostaglandin E2 (PGE2), leukotriene B4 (LTB4) oestradiol, progesterone and luteinizing hormone (LH) were determined in 30 follicular fluid samples from 25 women in an IVF programme. Multiple follicular development was induced by clomiphene citrate and human menopausal gonadotropin. Laparoscopic aspiration of follicular fluid was performed 36 hours after injection of human chorionic gonadotropin. The mean concentration of LH was significantly lower (p less than 0.05) in the follicular fluid with ova developing to embryos that cleaved than in those without cleavage. The mean concentrations of cAMP, cGMP, PGE2, LTB4, oestradiol and progesterone were not significantly different. PGE2 and LH concentrations in the follicular fluids showed significant correlation (r = 0.56; p = 0.004). Significant correlation was also seen between cAMP and progesterone concentrations (r = 0.50; p = 0.006). The presence of cyclic nucleotides, PGE2 and LTB4 in human follicular fluid suggests that these factors may have a role in the function of the follicular fluid.

Adult↗
PubMedDate not supplied

Comparative fates of clomiphene and tamoxifen in the immature female rat.

The triarylethylene antiestrogens clomiphene (CLO) and tamoxifen (TAM) have each been shown to be converted in vitro to "active" metabolites which may contribute to their antiestrogenic effects. We have studied the disposition of CLO and TAM in the immature female rat, the animal model with which the majority of biochemical studies of the effects of antiestrogens have been conducted. Both drugs were eliminated mainly by the feces after ip administration, with CLO being eliminated three times as efficiently (57%) as TAM (19%) over 24 hr. Most of the dose of CLO was eliminated unchanged; most of the dose of TAM was eliminated as metabolites, especially 4-hydroxy-TAM. TAM was accompanied by an array of metabolites in liver and uterine tissues 24 hr after ip injection. In contrast, injection of CLO resulted in negligible recoveries from these tissues of metabolites demonstrated to be produced in the presence of liver microsomal homogenates. Instead, a polar material of unidentified composition accompanied unchanged CLO in these tissues. These results reconfirm the fact that the effects of TAM are due in part to its metabolites and suggest that, in contrast, the effects of CLO are due mainly to unchanged drug.

Animals↗
PubMedDate not supplied

Ovulation induction for in vitro fertilisation using clomiphene citrate and low-dose human menopausal gonadotrophin.

Ovulation induction using a low dose of human menopausal gonadotrophins and clomiphene citrate for in vitro fertilisation and embryo transfer is described. Sixty-two cycles of ovulation induction were initiated in 37 patients. Forty-six laparoscopies were performed, yielding 116 oocytes. Of these, 90 (77.6%) cleaving embryos developed, and in 36 transfers 10 pregnancies (27.8%) were established. The use of low-dose hMG in conjunction with a programme on an outpatient basis may prove to be optimal for the purpose of in vitro fertilisation and embryo transfer.

Cleavage Stage, Ovum↗
PubMedDate not supplied

Effect of the mode of clomiphene citrate administration on ovarian response in an in vitro fertilization program.

To increase oocyte recovery for in vitro fertilization, superovulation treatment combining clomiphene citrate (CC) and human menopausal gonadotropin (hMG) is often used. However, CC may also have undesirable effects, e.g., on the endometrium, and therefore, high CC doses should be avoided. We studied the effects of three different modes of CC administration on ovarian estradiol (E2) responses and additive follicular diameters developed during 42 stimulated cycles. The treatments were (1) 150 mg CC on cycle days 5 to 9, (2) 50 mg CC on cycle days 3 to 7, or (3) 50 mg CC on cycle days 5 to 9. On the seventh cycle day, 300 IU hMG was given to all patients and this was continued for 3 to 4 days in decreasing doses depending on the ovarian responses, followed by daily E2 analyses and ultrasound measurements. The peripheral E2 concentrations during the different modes of CC administration were identical on cycle days 7 to 12. In addition, the additive follicular diameters on the day of hCG administration and the total hMG doses used did not differ significantly between the three CC-administration groups. Thus, a dose of 50 mg CC daily seems to be large enough to lead to maximal ovarian response in combination with hMG, and a treatment period of cycle days 3 to 7 appears to be suitable. In this way the interval between the cessation of CC and embryo transfer is maximal, and possible deleterious effects on the endometrium are minimized.

Adult↗
PubMed1988

The effect of clomiphene citrate and tamoxifen on the cervical mucus.

The anti-estrogenic effect of clomiphene citrate (CC) and tamoxifen (TMX) on cervical mucus was evaluated in a prospective crossover study. Ten women underwent randomized alternate cyclical treatment with either 100 mg CC, 40 mg TMX daily, or with placebo. The effect of CC, TMX and placebo on serum estradiol (E2), cervical mucus secretion and on the development of ovarian follicles was evaluated. Compared with placebo, treatment with CC and TMX significantly increased the number of mature ovarian follicles on the day of assumed ovulation (p less than 0.05), elevated E2 secretion (p less than 0.05) and decreased cervical score (p less than 0.05). It can be concluded that anti-estrogenic agents reduced the secretion of cervical mucus. However, in most cases, the excessive E2 production due to multiple follicular growth overcomes the anti-estrogenic effect.

Adult↗
PubMedDate not supplied

[Results of low-dose treatment of oligozoospermia with clomiphene citrate].

30 oligozoospermia patients from the andrologic outpatient service of the University-Hospital for Gynecology and Obstetrics, Graz, Austria, received a treatment with clomiphene-citrate. A doses of 25 mg daily was given for 25 days, followed by a break of 5 days. This treatment cycle was repeated three times, providing a total of 4 months of therapy. Rigid criteria of selection were applied for the patients in this trial, pretreatment serum levels of FSH, LH, testosterone, prolactin and estradiol had to be in normal or low-normal range. After treatment FSH, LH and testosterone were re-evaluated and a semen analysis was performed. Six to eight weeks afterwards another spermiogram was done. A significant raise of sperm density was observed immediately after treatment and at the control 6-8 weeks after therapy. Motility and morphologic quality remained unchanged after the therapeutic course. Fructose content of seminal plasma raised significantly 6-8 weeks after therapy. FSH, LH and testosterone increased also on a significant level. 6 pregnancies could be achieved, no negative side effects of treatment had to be registered.

Clomiphene↗
PubMed1987

Evidence against the involvement of opiate neurons in mediating the effect of clomiphene citrate on gonadotropin-releasing hormone neurons.

This study was designed to assess whether the hypothalamic action of clomiphene citrate (CC) on gonadotropin-releasing hormone (GnRH) neurons required activity of opiate neurons. Ten women were studied in two successive cycles. In the first cycle they received infusion of saline or naloxone (2 mg intravenous bolus followed by 1.6 mg/hour) for 9 hours, in random order on days 5 and 6 of the cycle. In the second cycle each woman was treated with CC (100 mg) for 5 days before study on day 6. In each study, blood samples were collected at 15-minute intervals for 9 hours; during the last hour 10 micrograms GnRH was given to test the pituitary response. After CC, luteinizing hormone (LH) pulse frequency was accelerated, and mean serum LH, serum follicle-stimulating hormone, and estradiol increased, but the pituitary response to GnRH was unchanged. These changes are best explained by an increase in activity of GnRH neurons. Conversely, naloxone had no effect on LH pulsatility or the pituitary response to GnRH. This indicates that the action of CC at least during the early follicular phase is exerted primarily at the levels of the hypothalamic GnRH pulse generator and does not depend on the activity of opiate neurons.

Clomiphene↗
PubMed1977

Gonadotropic responsiveness to clomiphene, LRH, estradiol, and bromocriptine in galactorrheic women.

Twenty hyperprolactinemic patients with galactorrhea were studied to determine their gonadotropic responses to various stimuli. Five women lacked response to gonadotropin following the administration of clomiphene citrate. Ten patients who had luteinizing hormone releasing hormone (LRH) tests before and during bromocriptine administration exhibited varied FSH and LH responses that apparently were unaffected by bromocriptine therapy. A loss of the normal positive feedback of estrogens at the level of the hypothalamus was demonstrated in most patients before and during bromocriptine therapy. Long-term treatment with bromocriptine in 11 women resulted in a decrease of serum prolactin, cessation of lactation in all, and pregnancy in 8. These results suggest that the failure of normal secretion of gonadotropins in hyperprolactinemic women may result from 1) inadequate release of endogenous LRH, and 2) loss of the positive feedback of estrogens, as a result of the same hypothalamic disturbance that provokes the hyperprolactinemia. In turn, the elevated prolactin levels may exert a short-loop negative feedback at the hypothalamic level, inhibiting cyclic gonadotropin release.

Bromocriptine↗
PubMed1988

Clomiphene blocks the effect of intravenous estradiol on the firing rate of rat nigral dopamine neurons.

Intravenous 17-beta-estradiol (BETA) has a potent, stereo-specific, and rapid effect on dopamine (DA) neuron firing rate in the substantia nigra compacta (SNC). Our data demonstrate that immediate intravenous pretreatment with the anti-estrogen clomiphene (CLOM) blocks the action of subsequent intravenous BETA administration. Our results provide further physiologic evidence for membrane-bound estradiol (E2) receptors within the rat brain.

Animals↗
PubMed1988

Effect of the exposure of intrafollicular oocytes to clomiphene citrate on pregnancy outcome in the rabbit.

This study was designed to determine if exposure of rabbit intrafollicular oocytes to clomiphene citrate (CC) affects pregnancy outcome after in vitro ovulation, in vitro fertilization (IVF), and embryo transfer (ET). Ovaries were perfused in the presence or absence of CC (10(-5) M) and estradiol (E2, 100 ng/ml). Human chorionic gonadotropin (hCG, 50 IU) was added to the perfusate of all ovaries. In vitro ovulated ova were retrieved, inseminated, and transferred to host rabbits. Neither CC nor CC + E2 significantly affected hCG-induced ovulation or fertilization. CC significantly reduced (P less than 0.025) percentage of ovulated ova resulting in offspring. Addition of E2 significantly (P less than 0.05) reversed the reduction in offspring associated with CC alone. These results may be due to the antiestrogenic effects of CC on the intrafollicular oocyte, which compromises postfertilization development.

Animals↗