Clomiphene Citrate Challenge Test Research Articles

Endometrial evaluation is not predictive for in vitro fertilization treatment.

The main purpose of this study was to evaluate ovarian function by clomiphene citrate (CC) challenge test in a group of tubal infertile women and to study endometrial morphological maturation in the early luteal phase of CC-stimulated cycles as compared to in vitro fertilization (IVF) treatment outcome. Four women presented with strongly retarded, proliferative endometrium in the luteal phase. Of these, three presented with impaired ovarian function, high basal follicle-stimulating hormone, and high follicle-stimulating hormone levels after clomiphene stimulation on cycle day 10. In the remaining 30 women, showing an in-phase endometrium after CC stimulation, a comparison of six morphological characteristics did not reveal any significant differences between the 14 women who did become pregnant and the 16 who did not. No significant differences in endometrial thickness were observed between the groups. Significant differences were found when comparing estradiol and progesterone area under the curve during the luteal phase (P < 0.001 and P < 0.01, respectively) between those who did and those who did not become pregnant. Luteal endometrium morphology was not a sharp instrument to detect differences between women who did and women who did not become pregnant following IVF treatment, while ovarian function, as measured by hormonal markers, seemed to be a more reliable prognostic factor for IVF treatment outcome.

Inhibin-B

Abstract Objective: To determine inhibin-B concentrations during ovarian reserve screening in women with normal and diminished ovarian reserve as determined by the clomiphene citrate challenge test. Design: Retrospective. Setting: Tertiary fertility center. Patient(s): Women undergoing ovarian reserve screening for a routine fertility evaluation. Intervention(s): Clomiphene citrate challenge test. Main Outcome Measure(s): Inhibin-B concentrations on menstrual days 3 and 10. Result(s): Nineteen patients with normal ovarian reserve and 15 with diminished ovarian reserve had serum inhibin-B concentrations determined during ovarian reserve screening. For all patients, day 10 inhibin-B concentrations were higher than day 3. Women with normal ovarian reserve had higher inhibin-B concentrations on both days 3 and 10 than women with diminished ovarian reserve. Inhibin-B concentrations demonstrated a negative correlation with FSH levels on both cycle days 3 and 10 and a positive correlation with E 2 on cycle day 10. Conclusion(s): Women with diminished ovarian reserve during ovarian reserve screening had reduced granulosa cell inhibin-B production compared with women with normal ovarian reserve. The lower inhibin-B concentrations may be responsible for the elevated FSH concentrations and may be indicative of the aging follicular apparatus.

Follicle stimulating hormone as a predictor of fertility

Tests for diminished ovarian reserve provide valuable prognostic information for women considering assisted reproductive technology. The best characterized screening tool for a general infertility patient is the clomiphene citrate challenge test. These screening tests do not have absolute sensitivity or specificity. Additionally, the predictive value of these tests can be low if used in a population at low risk. Patients with abnormal testing should be counselled that their chances of conception with assisted reproductive technology are poor. This may impact on the choice of aggressive treatment; however, the results of these tests should never be used to exclude patients from care.

Inhibin-B: The Physiologic Basis of the Clomiphene Citrate Challenge Test for Ovarian Reserve Screening

Objective: To determine inhibin-B concentrations during ovarian reserve screening in women with normal and diminished ovarian reserve as determined by the clomiphene citrate challenge test. Design: Retrospective. Setting: Tertiary fertility center. Patient(s): Women undergoing ovarian reserve screening for a routine fertility evaluation. Intervention(s): Clomiphene citrate challenge test. Main Outcome Measure(s): Inhibin-B concentrations on menstrual days 3 and 10. Result(s): Nineteen patients with normal ovarian reserve and 15 with diminished ovarian reserve had serum inhibin-B concentrations determined during ovarian reserve screening. For all patients, day 10 inhibin-B concentrations were higher than day 3. Women with normal ovarian reserve had higher inhibin-B concentrations on both days 3 and 10 than women with diminished ovarian reserve. Inhibin-B concentrations demonstrated a negative correlation with FSH levels on both cycle days 3 and 10 and a positive correlation with E 2 on cycle day 10. Conclusion(s): Women with diminished ovarian reserve during ovarian reserve screening had reduced granulosa cell inhibin-B production compared with women with normal ovarian reserve. The lower inhibin-B concentrations may be responsible for the elevated FSH concentrations and may be indicative of the aging follicular apparatus.

Clomiphene Citrate Challenge Test as a Prognosticator in an IVF Program

Clomiphene Citrate Challenge Test as a Prognosticator in an IVF Program

Clomiphene citrate challenge test in the assessment of ovarian reserve before controlled ovarian hyperstimulation for intracytoplasmic sperm injection

The objective of this study is to evaluate the performance of clomiphene citrate (CC) challenge test to predict diminished ovarian reserve before controlled ovarian hyperstimulation for intracytoplasmic sperm injection (ICSI). The 198 women who underwent the CC challenge test fulfilled the following criteria: over 35 years of age, removal of one ovary or previous ovarian surgery, the presence of ovarian endometrioma or previous poor response to ovarian hyperstimulation. Of the patients tested. 141 were found to have a normal CC challenge test while 57 had an abnormal result. The cancellation rate of the cycle with a poor response was significantly higher in women with an abnormal test (36.8%) than in those with a normal test (19.8%) ( P < 0.05). The sensitivity of CC test for cycle cancellation was found to be 43% with a specificity of 76%, positive and negative predictive values of 37 and 80%, respectively. The estradiol values on hCG day, the number of retrieved oocytes and metaphase II oocytes and the rate of transfer cycles were significantly lower in females with an abnormal test. Women with normal test results had higher pregnancy rates per embryo transfer than those with abnormal test results (21.5 vs. 13.3%) and the predictive value of an abnormal test for failing to conceive was 93% ( 53 57 ) with a sensitivity of 31%, specificity of 84% and negative predictive value of 15.6%. Of 57 women with an abnormal test result, 25 (43.8%) were abnormal due only to an elevated day 10 or 11 value of FSH, which could not be detected using only basal FSH screening. In this group, the cancellation rate (48 vs. 19.8%, P < 0.01), the rate of transfer cycles (48 vs. 72.3%, P < 0.05) and the mean number of retrieved oocytes (4.9 ± 2.5 vs. 6.4 ± 3.1, P < 0.01) were all significantly different from normal test group. Although the rate of pregnancies per started cycle (8 vs. 15.6%) did not show a statistically significant difference, this is most probably due to the low number of patients. In conclusion, an abnormal CC challenge test is a good predictor of diminished ovarian reserve and it is better than a basal FSH concentration on day 3. It provides valuable information for both patients as to their chances of achieving a pregnancy and also for the medical team deciding on options for stimulation protocols.

Fertility in the Mature Woman

It has been very well documented that fertility rates decrease with age in women. However, there appears to be a grey zone as to when this decrease commences. It would appear in general that this decline becomes pronounced over the age of 35 due to a decreased ovarian reserve. There have been numerous ways of assessing ovarian function including baseline estradiol and FSH levels, clomiphene citrate challenge test (CCCT), and GnRH agonists stimulation testing. These tests do have their drawbacks, however they appear to be a better indicator of ovarian reserve than age alone. Furthermore, there also appears to be a decline in endometrial receptivity with age although this is not as pronounced as the decrease in ovarian reserve. This decline in endometrial receptivity can be ameliorated to some extent by giving superphysiologic doses of progesterone.When decreased ovarian reserve is found in the mature woman, success rates are best with the use of donor eggs. In addition, there appears to be an increased risk of pregnancy complications in the mature gravida. These include an increased risk of spontaneous abortion, chromosomal abnormalities, hypertension, pre-eclampsia, and Caesarean section. Furthermore, with modem trends in obstetrical practice, the perinatal mortality has decreased with increasing age. Therefore, in mature women with decreased ovarian reserve there is a possiblity to achieve pregnancy with the use of donor eggs, and in patients who have been adequately screened for medical problems, and with close supervision in pregnancy, the risk of complications can be minimized.

Response to clomiphene citrate challenge test in normal women through perimenopause.

To identify the physiological changes that discriminate subgroups of women along the reproductive continuum. This prospective study was carried out at the outpatient facility of George Washington University Medical Center and the outpatient clinic of the National Institutes of Health Clinical Center. Twenty-five female subjects were divided into 4 biologically distinct groups: group 1 (n = 4) regular menstrual cycles and under age 35; group 2 (n = 11) regular cycles and over age 35; group 3(n = 6) irregular cycles and over age 35, and group 4(n = 4) menopausal. Measurements of basal and stimulated gonadotropins (immunoactive LH, LH-I; bioactive LH, LH-B; immunoactive FSH, FSH-I) and E2 were obtained before and after administration of clomiphene citrate. Basal and stimulated gonadotropins and E2 were analyzed to discriminate between subject groups 1-4. The relationship of menstrual cyclicity to hormone levels was evaluated. Basal levels of LH-I, LH-B, FSH-I could discriminate only group 4 vs. groups 1-3. Stimulated levels of FSH-I and E2 were significantly different for group 2 vs. 3 and group 2 vs. 4. Group 1 was similar to group 2. Both stimulated FSH-I and stimulated LH-I and LH-B differentiated group 4 vs. groups 1-3. The LH-B:LH-I (B:I) ratio was not discriminatory after the clomiphene citrate challenge test (CCCT). Baseline hormone values were useful in distinguishing only group 4. CCCT unmasked differences in FSH and E2 between irregularly and regularly cycling older women; these differences were not scen with LH-B or B:I ratio. Stimulated FSH was the most useful hormone parameter and paralleled menstrual cycle regularity as a useful discriminator in older women.

Comparison of a blocking vs. a flare-up protocol in poor responders with a normal and abnormal clomiphene citrate challenge test

This study aimed to standardize the clomiphene citrate test (CC-t) in our laboratory while comparing two different protocols of controlled ovarian stimulation in poor responders.One hundred and forty-four patients scheduled for assisted reproductive techniques were submitted to the CC-t within 3 months before starting stimulation; 133 underwent controlled ovarian stimulation with a blocking protocol. Poor responders in the first cycle (n = 30) were subsequently treated with a flare-up protocol. Although it was not statistically significant, more patients reached oocyte retrieval with the flare-up protocol. In the completed cycles, more gonadotropin ampules (55 ± 15 vs. 34 ± 13; p < 0.001) and more stimulation days (12.6 ± 1 vs. 11.6 ± 1.2; p < 0.005) were needed in the blocking than in the flare-up protocol. No difference was observed in peak 17ß-estradiol levels, preovulatory follicles, oocytes retrieved or pregnancy rate between the two protocols.According to the threshold values, established on CC-t of patients who obtained a clinical pregnancy (n = 44), the incidence of abnormal results was 10%. All but one patient with abnormal CC-t were poor responders during the first stimulation cycle. The flare-up protocol did not improve the ovarian response in these patients.

P-209 Clomiphene citrate challenge test as a prognosticator in an IVF program

P-209 Clomiphene citrate challenge test as a prognosticator in an IVF program

Luteal phase oestradiol and progesterone levels are stronger predictors than follicular phase follicle stimulating hormone for the outcome of in-vitro fertilization treatment in women with tubal infertility.

Basal follicle stimulating hormone (FSH) in a natural cycle, FSH on cycle days 3 and 10 in a clomiphene citrate-stimulated cycle and oestradiol and progesterone area under the curve (AUC) in the luteal phase of the clomiphene citrate-stimulated cycle were evaluated as hormonal predictors for the outcome of IVF treatment in 53 normally cycling women with tubal infertility. The pregnant women had significantly fewer treatment cycles (P < 0.001) and needed fewer ampoules of gonadotrophins (P < 0.001). They also had more oocyte retrievals (P < 0.001), more oocytes per retrieval (P < 0.01), higher fertilization rate (P < 0.001) and more replaced pre-embryos per replacement (P < 0.01) as compared with non-pregnant women. Significant differences were found in FSH concentrations on cycle days 3 (P < 0.05) and 10 (P < 0.001) after clomiphene citrate stimulation and for oestradiol and progesterone AUC in the luteal phase (P < 0.001) between those women who became pregnant and those who did not become pregnant after IVF treatment. Luteal oestradiol and progesterone had considerably stronger predictive value for the outcome of IVF treatment as compared to basal FSH and clomiphene citrate challenge test.

Evaluation and treatment of low responders.

Identification and treatment of low responders to ovulation induction is one of the most frustrating challenges in reproductive medicine. Because complex ovulation induction is required so frequently and is so expensive, efficient diagnosis of hyporesponders is critical. At present, the best techniques of evaluating ovarian reserve are basal follicle-stimulating hormone/Estradiol levels early in the proliferative phase and the clomiphene citrate challenge test. When poor responders are identified, strong consideration should be given to adjunctive approaches such as gonadotropin-releasing hormone analog and microdose flare or possibly, embryo hatching in those women undergoing in vitro fertilization.

Efficacy of selection criteria for ovarian reserve screening using the clomiphene citrate challenge test in a tertiary fertility center population

To examine selection criteria for ovarian reserve screening. Retrospective study. Two hundred nineteen women underwent testing for ovarian reserve for woman's age > 35 years, any age with unexplained infertility, one ovary, or a poor response to hMG. Clomiphene citrate challenge test. Frequency of abnormal ovarian reserve screening, menstrual cycle parameters, response to hMG, and pregnancy outcome by screening criteria. One hundred eighty-four (84.0%) women had a normal ovarian reserve screening test; 35 (16.0%) had an abnormal ovarian reserve screening test. Twenty-six had abnormal ovarian reserve screening when screened by age, 14 for unexplained infertility, 5 for poor response to hMG, and 6 for one ovary. Fifteen women with abnormal ovarian reserve screening had more than one indication for screening. For women attempting pregnancy (n = 182), 49 of 148 (33.1%) with normal ovarian reserve screening became pregnant compared with 2 of 34 (5.9%) with abnormal ovarian reserve screening. Within each screening category, women with abnormal ovarian reserve had menstrual cycle parameters associated with a short follicular phase, required more hMG, and responded poorly to hMG. One of six women undergoing ovarian reserve screening had an abnormal test, which was associated a poor reproductive outcome. Age was the most important single criteria. Selected ovarian reserve screening is simple and inexpensive and should be offered to all fertility patients meeting the specific screening criteria listed above.

Infertility: Life table analysis of pregnancy rates in a general infertility population relative to ovarian reserve and patient age*

This study evaluated the impact of age and ovarian reserve status on cumulative pregnancy rates. Approximately 1200 women from a general infertile population underwent ovarian reserve screening with the clomiphene citrate challenge test in the first few months of their initial evaluation. All patients then underwent a thorough infertility evaluation with therapy appropriate for their specific diagnoses. Patients with evidence of tubal disease, peritoneal adhesive disease, or male factor were eliminated. The 588 remaining patients were evaluated based on their age and ovarian reserve status, and their long-term pregnancy rates were compared using life table analyses. There was a dramatic decrease in pregnancy rates associated with an abnormal clomiphene citrate challenge test which was uniformly poor independent of age. Patients with normal ovarian reserve had much higher pregnancy rates, but a significant age-related decline in pregnancy rates was clearly identified. We conclude that women with evidence of diminished ovarian reserve have uniformly poor pregnancy rates independent of their age, but that age remains an important prognostic factor among those with a normal ovarian reserve. The combined use of maternal age and ovarian reserve screening should be used when counselling individual patients regarding their long-term prognoses for conception.

Evaluation of the reproductive performance of women with elevated day 10 progesterone levels during ovarian reserve screening

To evaluate the relationship of elevated day 10 P levels (> or = 1.1 ng/mL, conversion factor to SI unit, 3.18) during ovarian reserve screening and reproductive performance. Prospective screening with longitudinal follow-up. One hundred seven women underwent ovarian reserve screening with a clomiphene citrate challenge test. Serum FSH, LH, and E2 levels were determined on cycle day 3 and FSH, LH, and P levels were determined on day 10. A fertility evaluation was completed and a treatment plan was instituted. Twenty-two of 107 (20.6%) women had day 10 P levels > or = 1.1 ng/mL. Women with elevated day 10 P levels were similar in age to women with normal day 10 P levels (< or = 0.9 ng/mL) but had significantly shorter menstrual cycles, higher day 3 and day 10 FSH levels, higher day 3 E2 levels, and higher day 10 LH levels than women with normal day 10 P levels. During ovarian hyperstimulation, women with elevated day 10 P levels required more ampules of hMG, had lower peak E2 levels, and had fewer mature follicles than women with a normal day 10 P level. Sixteen of 85 (18.8%) women with normal day 10 P levels became pregnant, but none of the 22 women with elevated day 10 P levels became pregnant. The incidence of diminished ovarian reserve was higher in women with elevated day 10 P levels (13/22; 59%) when compared with women with a normal day 10 P levels (9/85; 10.6%). Elevated day 10 P levels (> or = 1.1 ng/mL) during ovarian reserve screening is associated with diminished ovarian reserve and correlates with menstrual cycle parameters associated with a short follicular phase and poor reproductive performance.

Cigarette smoking accelerates the development of diminished ovarian reserve as evidenced by the clomiphene citrate challenge test

To test whether the reduced fecundity in women who smoke cigarettes may be attributed to the accelerated development of diminished ovarian reserve. Retrospective evaluation of clomiphene citrate (CC) challenge tests in women from a general infertility population who did and did not smoke cigarettes (part 1) and retrospective evaluation of the impact of smoking on pregnancy rates (PRs) in IVF among women with normal ovarian reserve (part 2). Large military tertiary care center. Sixty-five women who smoked cigarettes and 145 women who did not smoke cigarettes in the general infertility population (part 1) and women undergoing IVF for strict tubal factor infertility with normal ovarian reserve who did (n = 29) and did not (n = 73) smoke (part 2). Clomiphene citrate challenge tests, composed of FSH levels on cycle days 3 and 10 with 100 mg of CC administered on cycle days 5 through 9. Comparison of the incidence of abnormal CC challenge test results between women who did and did not smoke, and comparison of peak E2 levels, number of mature follicles, number of mature oocytes retrieved, fertilization rates, and total and ongoing PRs. The incidence of diminished ovarian reserve was increased in women who smoked (8 of 65 [12.31%]) when compared with age-matched controls who did not smoke (7 of 145 [4.83%]). Among women with normal CC challenge tests who were undergoing IVF, there were no differences in peak E2 levels, the number of mature follicles, the number of mature oocytes retrieved, fertilization rates, or total and ongoing PRs. Women who smoke have an accelerated development of clinically detectable diminished ovarian reserve. Additionally, the fact that women who smoke cigarettes with normal ovarian reserve have ovarian responses and PRs that are equivalent to age-matched nonsmoking controls suggests that diminished ovarian reserve may be a principal mechanism reducing fecundity among women who smoke cigarettes.

Danazol influences gonadotropin secretion acting at the hypothalamic level

OBJECTIVES: The purpose of the study was to determine the influence of danazol on gonadotropin secretion. METHODS: Ten endometriotic patients were treated with danazol for 6 months. To evaluate gonadotropin and estradiol secretion, a gonadotropin-releasing hormone (GnRH) test and a clomiphene citrate (CC) challenge test were carried out in the follicular phase before treatment, during the sixth month of treatment and after the reappearance of the second menses. The same tests were also performed, only once, in the follicular phase of ten normal women. RESULTS: GnRH-stimulated gonadotropin response during danazol treatment was significantly higher than that in the same group of women before and after danazol treatment, as well as in controls. Gonadotropin increase after clomiphene citrate administration during danazol treatment was not significant; moreover, LH response was significantly lower than that in the same group of patients before and after danazol treatment, as well as in controls. CONCLUSIONS: Our results suggest that danazol exerts a suppressive effect on gonadotropin secretion acting at the hypothalamic level.

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.(Obstet Gynecol 1993; 82:539-44)

A Prospective Evaluation of Clomiphene Citrate Challenge Test Screening of the General Infertility Population

To assess the results of screening an unselected general infertility population for diminished ovarian reserve with the clomiphene citrate challenge test. 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. 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). 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.

Evaluation of the significance of the estradiol response during the clomiphene citrate challenge test

To evaluate the relationship between the E2 response during the clomiphene citrate (CC) challenge test and ovarian responsiveness to exogenous gonadotropins. Performance of a CC challenge test followed by ovulation induction with exogenous gonadotropins as part of participation in an assisted reproduction program. Assisted reproduction program in a large military tertiary care center. Two hundred forty-seven women between the ages of 24 and 39 years with normal CC challenge tests within 1 year of their assisted reproduction cycle. Performance of CC challenge tests and ovulation induction with exogenous gonadotropins as a component of an assisted reproduction cycle. Correlation of the E2 response during the CC challenge test and peak E2, the duration of stimulation, number of ampules of exogenous gonadotropins, number of mature follicles, number of mature oocytes recovered, and fertilization and pregnancy rates in an assisted reproduction program. No correlation exists between the E2 response during the CC challenge test and any of the parameters evaluated. Monitoring of the E2 response during the CC challenge test did not predict ovarian responsiveness or pregnancy rates in patients participating in an assisted reproduction program and one may choose not to include it in routine testing.