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Clomiphene citrate did not induce glycogen deposition in the uterine luminal epithelium of pregnant rats as it did in ovariectomized rats. However, the drug did alter the epithelial morphology which may be a factor in its postcoital contraceptive action.
In vitro fertilization (IVF) and embryo transfer (ET) were successful in 24 clomiphene citrate stimulated cycles in 22 patients. Ovarian follicular growth was monitored by ultrasound (US) and serum estradiol (E2) concentrations in order to determine the most favorable time for the induction of ovulation by administration of human chorionic gonadotropin (hCG). The day of the hCG injection was considered day 0. After an almost linear growth the mean diameter of the dominant follicle reached 19.3 +/- 2 mm on day 0. Serum E2 concentrations also increased in almost linear fashion up to a maximum of 1,037 +/- 322 pg/ml on day +1. On day 0 the mean serum E2 concentration was 862 +/- 279 pg/ml. A mean serum E2 concentration per dominant and codominant follicle of 328 +/- 100 pg/ml was found on day 0. There was no linear correlation between the follicular diameters and the serum E2-values on the same day. The time of ovum recovery was often different to the time at which ovulation would have been expected in a normal cycle.
Primary pituitary cell cultures from adult female rats were incubated for 4 or 24 h with various concentrations of estradiol (E2) or the antiestrogens (AE) tamoxifen (TMX), 4-hydroxytamoxifen (OH-TMX), and clomiphene citrate (CC). The luteinizing hormone (LH)-response of these cultures to gonadotrophin releasing hormone (GnRH) was monitored. Treatment for 4 or 24 h with high concentrations (10(-5) M) of the AE significantly decreased the GnRH-induced LH-release by the gonadotrophs. The negative E2-effect, which is observed in this model after 4 h was enhanced and the positive E2-effect, which occurs after 24 h, was completely reversed into a negative effect by these high AE-concentrations. Treatment of pituitary cells with increasing concentrations of E2 (10(-13)-10(-6) M) or AE (10(-12)-10(-5) M) for 24 h led first to a dose dependent increase of the LH-response to 5 X 10(-10) M GnRH. At higher E2- or AE-concentrations this positive effect was lost, resulting in bell shaped dose-response curves. The following maximal effective concentrations (EDmax) were found: E2 = 10(-10) M, OH-TMX = 10(-9) M, CC = 10(-7) M, TMX = 10(-6) M. Incubation of pituitary cells for 24 h with concentrations of AE near their EDmax and stimulation with increasing concentrations (10(-11)-10(-7) M) of GnRH resulted in significant increases of LH-secretion over a wide range of GnRH-concentrations. It is concluded that AE possess marked intrinsic activities on pituitary LH-secretion: at extremely high concentrations they suppress the GnRH-induced release of the gonadotrophin. At lower concentrations they increase the pituitary LH-response to GnRH in a manner which is qualitatively indistinguishable from that of E2.
PURPOSE: This study was carried out to evaluate the potential role of the combination clomiphene citrate/human menopausal gonadotropin (CC/hMG) for patients who failed previous in vitro fertilization (IVF) attempts with gonadotropin-releasing hormone analogs (GnRH-a) and/or exogenous gonadotropins. METHODS: Patients were stimulated with CC/hMG (n = 93) after unsuccessfully undergoing 182 gonadotropin cycles with (n = 106) or without (n = 76) luteal-phase GnRH-a. Cancellation rate, length of stimulation, and peak estradiol levels did not differ significantly between the two regimens. RESULTS: Although fewer oocytes were retrieved when the CC/hMG combination was used, 16 patients were able to successfully achieve a pregnancy (26.2% delivery rate/transfer). When daily follicle stimulating hormone (FSH) levels were measured in two successive cycles in those women who conceived with the CC/hMG stimulation, baseline levels did not differ when compared with a previous GnRH-a/hMG cycle. Nevertheless, serum FSH levels rose rapidly and remained higher in the GnRH-a/hMG cycle, reaching significantly higher levels on day of human chorionic gonadotropin (hCG) administration. CONCLUSION: Selected patients who failed previous IVF attempts with gonadotropins with or without GnRH analogs may benefit from the addition of CC to their ovarian stimulation protocol.
During cultivation of Saccharomyces cerevisiae clomiphene regulates both quantitative and qualitative production of sterols and fatty acids as identified by gas chromatography and mass spectrometry. The content of sterols decreases to 75%, the production of fatty acids is comparable with that in the control. The occurrence of sterols increases; sterols with methyl group in position 4, without double bond in position 22 and with double bond in position 24(25) or 24(28) predominate. Among fatty acids shorter saturated and monoene acids are primarily produced, 2-hydroxy acids practically disappeared.
A group of 12 sterile, azoospermic mink males were treated with clomiphene citrate (10 mg/kg/day) for 10 days during the mating season; 50% of the males showed improved sperm counts already after 2 days of treatment and the maximum effect was seen 4-6 days after the start of the treatment. The other half of the group did not respond to the treatment and their sperm counts remained near zero during the whole experiment.
The diagnosis of idiopathic delayed pubertal development in boys is difficult. A single GnRH test does not give information concerning hypothalamic maturity. After one week clomiphene citrate administration the LH reaction pattern is enhanced in subjects with maturing and depressed in subjects with immature hypothalamic-pituitary function.
The effect of clomiphene citrate (CC) on ovarian function in cycles subsequent to treatment withdrawal was studied. Thirty two out of 45 patients with anovulation due to polycystic ovarian syndrome (PCOS) and with no other factor affecting fertility who got pregnant were included. All patients received CC to induce ovulation. Pregnancies in CC treated cycles and after treatment were recorded. Twenty pregnancies were achieved during CC treated cycles and 12 in the cycles after it was withdrawn. In the latter group, eight pregnancies were achieved in the cycle following CC therapy, and four in the second subsequent cycle. In relation to pregnancy complications no significant statistical differences were found between the group of patients who became pregnant during the stimulation cycles and in the cycles after CC.
PURPOSE: To determine the optimal time for administration of human chorionic gonadotropin in clomiphene citrate induced intrauterine insemination cycles. METHODS: A retrospective analysis of 171 consecutive cycles was performed. An increase in luteinizing hormone level >100% over the mean of the preceding two days was defined as luteinizing hormone surge. Human chorionic gonadotropin was given in preparation for intrauterine insemination based on the follicle size and estradiol level prior to surge in 85 cycles (Group A), with the spontaneous surge in 64 cycles (Group B) and not given in 22 cycles (Group C) due to high luteinizing hormone levels. RESULTS: The overall pregnancy rate per cycle was 18.1% (31/171), 15.2% (Group A), 20.3% (Group B) and 22.7% (Group C), (p > 0.50). CONCLUSION: Although there may be physiological reasons to propose that timing the human chorionic gonadotropin to the luteinizing hormone surge will improve the success rate, they were not demonstrated.
Demand for inhibiting puerperal lactation has brought about a plethora of methods, none entirely satisfactory, in achieving successful and comfortable ablactation. In addition some were associated with untoward side effects. In this study administration of 100 mg. of clomiphene citrate daily for 5 days was effective in suppressing puerperal lactation. Response to the treatment was particularly pronounced, when this was started within the first 12 hours post partum.
Ovarian follicle development was investigated in 38 normally cycling women who received clomiphene citrate, 150 mg per day for 5 days, to maximize follicular development. Ultrasonic determination of follicle growth was performed on a daily basis with a real-time sector scanner and correlated with daily concentrations of estradiol (E2) in the peripheral serum as measured by rapid radioimmunoassay. Human Chorionic gonadotropin was given to induce ovulation, and the day of injection was considered day 0. Mean concentrations of E2 reached a maximum of 1,150 +/- 65 pg/ml on day 0. Mean diameter of the dominant follicle increased to 22.1 +/- 0.4 on day 0. When peripheral concentrations of E2 were correlated with diameter and total follicular volume it was found that plasma E2 levels varied, depending on the number of follicles seen on ultrasound examination, with a mean E2 value of 459 +/- 18.9 pg/ml per follicle per day. Multiple growth of follicles occur with artificial induction of ovulation; therefore, the use of ultrasound is an important parameter to assess follicular maturation and the timing of ovulation more precisely.
Nine women with chronic anovulation caused by polycystic ovarian disease, which was unresponsive to clomiphene citrate therapy, were given a gonadotropin-releasing hormone agonist (buserelin) to induce pituitary desensitization. After 4 weeks induction of ovulation was attempted with a step-up administration of urinary follicle-stimulating hormone. Buserelin treatment was discontinued only in the presence of a positive pregnancy test result. Different responses were observed between the first and subsequent cycles. Whereas estradiol production and follicular growth were closely correlated in the first attempt, we recorded a dissociation between these two parameters of ovarian response during subsequent stimulations. Four clinical pregnancies occurred in these nine patients, and there was one abortion. This therapeutic approach can be successfully used to induce ovulation; however, prolonging pituitary suppression between treatment cycles changes the type of ovarian response and is not followed by better results.
Anordiol (2 alpha,17 alpha-diethynyl-A-nor-5 alpha-androstane-2 beta,17 beta-diol) has been variously characterized as an estrogen and as an antiestrogen. To more completely understand the pharmacological properties of this contraceptive steroid, simultaneous responses were studied in uterine, vaginal, and hepatic tissues. Rats received 4 daily sc injections with either anordiol, clomiphene citrate (CC), or the vehicle alone (C+) starting on the first day of pseudopregnancy. Uteri were traumatized on day 4 of pseudopregnancy, and rats were sacrificed 5 days later. A pseudopregnant group without uterine trauma served as a negative control (C-). Mean uterine weights per animal and cytosolic estrogen (EcR) and progesterone (PcR) receptor activities per g of DNA were all 5- to 7-fold greater in the C+ group than in the other groups (all p < 0.05). However, anordiol and CC suppressed uterine weight without suppressing the stromal proliferative response; the DNA content of the uteri of anordiol- and CC-treated rats was similar to that of C+ rats. Vaginal tissue exhibited estrogenic responses to anordiol and CC with an increase in epithelial stratification compared to the C+ and C- groups even though no difference in levels of EcR/g of DNA were expressed 5 days after the last antiestrogen dose. Binding affinities and serum E2 and progesterone (P) concentrations were not statistically different among the groups. In conclusion, anordiol produced responses in the uterus and vagina of the pseudopregnant rat which were indistinguishable from those of CC, and, therefore, we conclude that anordiol acts on these tissues as an antiestrogen.
Luteinizing hormone-releasing hormone (LH-RH) was used to induce ovulation following clomiphene priming to stimulate follicular growth. Ovulation was assumed to have occurred following LH-RH injection when progesterone levels started to rise within 48 h following treatment and LH pretreatment levels were below 8 mIU/ml. Ovulation occurred in eight of 10 patients following the administration of LH-RH and six pregnancies were achieved in the first 4 months of treatment.
Sixty-eight anovulatory women were divided into three groups according to the administered doses of clomiphene citrate (CC) (A 250 mg, B 500 mg, C 750 mg). Daily follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E2) measurements were performed. Follicular maturation was monitored by ultrasound. In the high-CC dose group, a statistically significant FSH rise was noted. As a result, earlier selection of the dominant follicle (DF), faster increase in the DF diameter and increased E2 production was found.
We compared ovulatory changes in fertile and preceding infertile cycles in 21 patients with unexplained infertility conceiving after clomiphene citrate treatment. No significant differences were observed in follicular growth, cervical score and follicle stimulating hormone (FSH) levels. Progesterone was higher (P less than 0.05) in the 2 days preceding ovulation in fertile cycles, luteinizing hormone (LH) higher (P less than 0.05) the day before, and 17-beta-estradiol lower (P less than 0.05) 4 days before. Stimulating progesterone secretion by systematic LH administration before ovulation could improve secretory endometrial transformation and thus reproductive prognosis.
A case of the combination of a complete hydatidiform mole and a coexisting, living fetus arising from a twin pregnancy, subsequent to clomiphene citrate therapy for ovulation induction, is presented. The diagnostic problems of this combination as well as the incidence of molar pregnancy following the use of ovulation inducers are discussed.
Follicular growth in the last 24 h preceding laparoscopic oocyte pick-up for in vitro fertilization purposes was studied in 46 clomiphene citrate/human chorionic gonadotrophin-stimulated cycles by means of real-time sector ultrasound. A linear increase in mean follicular diameter of 2.5 mm was established. Growth rates under monofollicular and multifollicular conditions did not differ significantly. However, the absolute dimensions of the dominant follicle in the multifollicular subgroup exceeded those observed in the monofollicular subgroup (P less than 0.01) for each observation point. A fixed CC/hCG treatment scheme results in a wide range of ultimate preovulatory follicular dimensions, without any correlation between the individual follicular size and growth rate values (r = 0.075).