Clomiphene Citrate For Ovulation Induction Research Articles

Hormonal Changes Related to Impairment of Cervical Mucus in Cycles Stimulated by Clomiphene Citrate

The levels of luteinizing hormone (LH), follicular stimulating hormone (FSH), 17-oestradiol (E2), progesterone (P), and testosterone (T) were determined for the early, midfollicular and periovulatory phase of spontaneous and clomiphene citrate (CC) induced cycles in 5 patients who responded with appearance of hostile cervical mucus (Group A) and 5 patients whose cervical mucus remained unchanged during the same treatment (Group B). The patients with hostile mucus were further investigated during a third cycle stimulated by CC and ethinyloestradiol (EE). Patients treated with CC for induction of ovulation who developed hostile cervical mucus showed higher levels of LH and T in the midfollicular phase of the menstrual cycle and significantly higher levels of T in the periovulatory period compared to patients with unchanged mucus. EE treatment induced a drop in the elevated LH and T levels and improved the cervical score. No change in E2 levels was noted. A direct effect of EE on the cervical glands together with the centrally mediated lowering of serum T are suggested to be responsible for improving the cervical mucus.

Diagnosis and Management of Out-of-Phase Endometrial Biopsies among Patients Receiving Clomiphene Citrate for Ovulation Induction

Eighty-seven patients who underwent a late secretory phase endometrial biopsy while taking clomiphene citrate (CC) for ovulation induction were studied. Of the endometrial biopsies, 21 (24%) showed an endometrium > 2 days out of phase (OOP) with respect to the subsequent menstrual cycle. All 87 patients were categorized by age, weight, CC dosage, and underlying disease entity. The patients then were evaluated by these categories in relation to the incidence of an OOP biopsy while taking CC. Patients with a diagnosis of hypothalamic amenorrhea were statistically more likely to have an OOP endometrium. No other subgroup showed an increased or decreased incidence of OOP biopsies. Conception and spontaneous abortion rates were similar among patients with in-phase biopsies and those with out-of-phase biopsies, which subsequently were corrected with further medical therapy. An aggressive approach to the diagnosis and treatment of luteal phase insufficiency in patients who receive CC for ovulation induction is recommended.

Diagnosis and management of out-of-phase endometrial biopsies among patients receiving clomiphene citrate for ovulation induction

Eighty-seven patients who underwent a late secretory phase endometrial biopsy while taking clomiphene citrate (CC) for ovulation induction were studied. Of the endometrial biopsies, 21 (24%) showed an endometrium greater than 2 days out of phase (OOP) with respect to the subsequent menstrual cycle. All 87 patients were categorized by age, weight, CC dosage, and underlying disease entity. The patients then were evaluated by these categories in relation to the incidence of an OOP biopsy while taking CC. Patients with a diagnosis of hypothalamic amenorrhea were statistically more likely to have an OOP endometrium. No other subgroup showed an increased or decreased incidence of OOP biopsies. Conception and spontaneous abortion rates were similar among patients with in-phase biopsies and those with out-of-phase biopsies, which subsequently were corrected with further medical therapy. An aggressive approach to the diagnosis and treatment of luteal phase insufficiency in patients who receive CC for ovulation induction is recommended.

The OVEIA assay, a simultaneous measurement of oestrone and pregnanediol glucuronides, for studying the treatment of infertility patients.

A new simple assay developed for establishing the limits of the fertile period was evaluated in infertility patients. This assay is a colorimetric method for measuring the oestrone glucuronide/pregnanediol glucuronide ratio. Steroid levels were assayed simultaneously and an index of their ratio was obtained in this dual analyte assay (DAA). Twenty subfertile women, receiving clomiphene citrate for ovulation induction, were monitored for the DAA index using early morning urine samples. Ten of these women were also monitored in a pretreatment cycle. A further 10 patients on an in-vitro fertilization (IVF) programme were assessed with the same assay. DAA ratios were found to correlated with follicular phase serum oestradiol levels. Peak DAA ratios dropped dramatically when significant rises in urinary luteinizing hormone concentrations occurred prior to ovulation. An association between high DAA ratios and adequate luteal phase activity was also established. In addition, the total volume of the three largest ovarian follicles, as measured by ultrasound, in IVF patients was found to correlate with DAA measurements.

Estrogen receptor binding material in blood of patients after clomiphene citrate administration: determination by a radioreceptor assay

The aim of the current study was to assess whether clomiphene citrate (CC) and/or active metabolites are present at presumed time of ovulation, nidation, or steroid-sensitive organogenesis, in serum of patients receiving CC for induction of ovulation. A radioreceptor assay, based on competitive replacement of 3 H-estradiol on the rat uterus estrogen receptor, by ligands present in serum of patients after CC administration, was developed. Ligands reached maximal concentration 4 to 5 hours after a single dose of CC was administered, and declined with a half-life of 4.5 to 10 hours. In patients receiving CC on day 5 to day 9 in the cycle, ligands are still present on day 14 in the cycle and in some patients on day 22 of the cycle, but no ligands were detected 60 days after CC treatment.

Clomiphene citrate augments follicle-stimulating hormone-induced luteinizing hormone receptor content in cultured rat granulosa cells

Although clomiphene citrate (CC) has been widely used for ovulation induction, the mechanism of its pro-fertility effect is not entirely clear. Because CC augments ovarian aromatase activity, the effect of CC on follicle-stimulating hormone (FSH)-induced luteinizing hormone (LH) receptor content was examined in primary cultures of rat granulosa cells. Control cultures contained low LH receptor content, whereas FSH stimulated LH receptor formation in a dose-dependent manner. The concomitant addition of CC enhanced FSH potency as shown by a decrease in the ED50 for FSH by 2.2-fold. Some cells were treated with a low concentration of FSH (12 ng/ml) in the presence or absence of increasing concentrations of CC (10(-8) M to 10(-6) M). The enhancement of FSH-stimulated LH receptor formation was found to be CC dose dependent, with an ED50 of 6 X 10(-8) M. Thus, CC may play a direct ovarian role in the enhancement of FSH-stimulated LH receptors. The gonadal action of this compound may be relevant in understanding the efficacy of CC in ovulation induction.

The effect of laparoscopic follicular aspiration on ovarian steroidogenesis during the early preimplantation period

Seventeen patients were studied for the first 72 hours of the luteal phase after spontaneous ovulation or follicle aspiration. Nine patients (group I) underwent follicle aspiration after clomiphene citrate (CC) administration, three women were studied after CC for ovulation induction (group II), and five spontaneous ovulating subjects served as controls (group III). Serum progesterone (P) concentrations were significantly elevated in stimulated cycles with or without follicle aspiration, compared with subjects. Moreover, when aspirated subjects were compared with nonaspirated stimulated subjects, a significant difference in P concentration was identified. It can be concluded that with follicle aspiration, P decreases can be observed, but with multiple follicle development, inadequate P levels are not seen in these stimulated subjects. On the contrary, with such elevated P levels, endometrial advancement may play a role in poor implantation success with human in vitro fertilization procedures.

Relationship between endogenous urinary estrogen levels and progestogen withdrawal bleeding

Endogenous estrogen levels and progesterone withdrawal bleeding are useful in predicting the response to clomiphene citrate in ovulation induction in patients with secondary amenorrhea. In an attempt to correlate the two, 20 women with secondary amenorrhea had 24 hour urinary estrogen assays performed before administration of 17α-hydroxyprogesterone caproate. In 8 women, with estrogen levels above 11 μg bleeding occurred but did not in 5 with levels below 8 μg; between 8 and 11 μg the response was unpredictable. There was no correlation between estrogen levels and duration of amenorrhea or to the interval between progestogen administration and bleeding.