Clomiphene Citrate Challenge Test Research Articles

Correlation of Serum Anti-Mullerian Hormone with Ovarian Follicle Output Rate in Infertile Females: A Clomiphene Citrate Challenge Test.

BackgroundFailure to achieve a successful pregnancy after 12 months of unprotected intercourse is a pathology of the reproductive system known as infertility. Anti-Mullerian hormone (AMH) not only reflects the ovarian reserve but also is known to be a predictor of several assisted reproductive techniques, e.g., in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), and clomiphene citrate challenge test. In this study, AMH levels are correlated with the follicular output rate after the clomiphene citrate challenge test.ObjectiveThe objective of this study is to correlate AMH with the follicular output rate (FORT) after the clomiphene citrate challenge test.Materials and methodsThis study included a total of 80 primary and secondary infertile females, divided into early (18-30) and late (31-45) reproductive age groups either currently under clomiphene citrate treatment or advised to start clomiphene treatment, culled from out-patient department and centers of assisted reproductive techniques. On the third day of the menstrual cycle, blood samples were taken to determine serum AMH levels by ELISA. Then on the fifth day of the menstrual cycle, antral follicular counts were calculated through transvaginal ultrasound and oral tablet clomiphene citrate was started, and on day 12 and then on day 5, transvaginal ultrasound was repeated to record the number and diameter of dominant follicles.ResultsThe pre-ovulatory (mature) follicle count was divided by the antral follicle count ×100 for calculating the FORT, which showed a negative Spearman Rho correlation (p = 0.048) with AMH. P-value ≤ 0.05 was considered significant. ConclusionIt is concluded that the most commonly administered drug, clomiphene citrate, may not be the treatment of choice for patients with high levels of AMH and may, in fact, interfere with the chances of achieving pregnancy. This study can provide guidelines to clinicians for patient counseling, given the results of the clomiphene citrate challenge test on the basis of AMH levels.

Differential Expression of Ovarian Superficial Epithelium Markers in Diminished Ovarian Reserve and Normal Women

In the last years, diminished ovarian reserve (DOR) is becoming a frequent pathology in the human reproductive system, which also has a major impact on quality of life and fertility of reproductive age women. However, DOR remains as a disease of unknown etiology. The aim of this study was to assess the differential expression levels of multipotent stem cell markers in the ovarian surface epithelium (OSE) of women with DOR and women with adequate ovarian reserve (AOR) that could be associated with the loss of ovarian functionality. Methods: The present study was performed by using ovary tissue samples from patients previously diagnosed as AOR and DOR according to the clomiphene citrate challenge test. The expression levels of multipotent stem cell and germline markers were analyzed by immunohistochemistry. Results: Our findings demonstrate that a small number of epithelial cells express the Oct4 stem cell marker and the specific germ line markers (Fragilis, Stella, and VASA) in the OSE of both AOR and DOR patients, but the number of immunostained cells were lower in the women with AOR than DOR individuals. On the other hand, the expression of SOX2 and Nanog stem cell markers was only observed in the OSE of DOR women but not in AOR patients. Conclusions: The overall results of this study show that there is a differential expression of stem cell markers in the OSE cells from DOR women as compared with AOR subjects, suggesting a possible compensatory mechanism for the generation of new multipotent cells to participate in the repair and/or renewal of the population of ovary cells in the OSE of DOR women.

Antimullerian hormone versus the clomiphene citrate challenge test for evaluation of ovarian reserve prior to in vitro fertilization

Antimullerian hormone versus the clomiphene citrate challenge test for evaluation of ovarian reserve prior to in vitro fertilization

Possibilities and Limits of Ovarian Reserve Testing in ART

Markers of ovarian reserve are associated with ovarian aging as they decline with chronologic age, and hence may predict stages of reproductive aging including the menopause transition. Assessment of ovarian reserve include measurement of serum follicle stimulating hormone (FSH), anti-M�llerian hormone (AMH), and inhibin-B. Ultrasound determination of antral follicle count (AFC), ovarian vascularity and ovarian volume also can have a role. The clomiphene citrate challenge test (CCCT), exogenous FSH ovarian reserve test (EFORT), and GnRH-agonist stimulation test (GAST) are dynamic methods that have been used in the past to assess ovarian reserve. In infertile women, ovarian reserve markers can be used to predict low and high oocyte yield and treatment failure in women undergoing in vitro fertilization. However the markers may have limitations when an in depth analysis of their accuracy, cost, convenience, and utility is performed. As ovarian reserve markers may permit the identification of both the extremes of ovarian stimulation, a possible role for their measurement may be in the individualization of treatment strategies in order to reduce the clinical risk of ART along with optimized treatment burden. It is fundamental to clarify the cost/benefit of its use in the ovarian reserve testing before initiation of an IVF cycle and whether the ovarian reserve markers-determined strategy of ovarian stimulation for assisted conception may be associated to improved live birth rate.

Comparison of Ovarian volume and Antral follicle count with Endocrine tests for prediction of responsiveness in ovulation induction protocols

Background:The aim of this study was to determine if the basal antral follicle number and ovarian volume contributes to the prediction of responsiveness in ovulation induction protocol and comparison of it with hormonal tests.Materials and Methods:52 irregularly-menstruating patients, aged 18-46 years, participated in this prospective study. All the patients underwent a transvaginal sonography to measure the basal ovarian volume and the basal antral follicles count (AFC). Clomiphene citrate challenge test was measured by summation of measurements of FSH on day 2 and 10. All the women received clomiphene citrate from day 2 to 6. Ovarian responsiveness was measured 1 week after termination of clomiphene citrate and was used as gold standard.Results:Multiple regression analysis revealed that AFC was the only significant factor for ovarian responsiveness prediction. The area under the curve for AFC to discriminate responder ovaries was 0.66 (95% confidence interval, 0.87-0.99). The cutoff value for predicting ovarian responsiveness was 15.5.Conclusion:AFC can contribute to the prediction of responsiveness in ovulation induction protocol better than ovarian volume and hormonal tests.

Day 10 estradiol level during the clomiphene citrate challenge test predicts pregnancy in an infertile population

The clomiphene citrate challenge test (CCCT), in which serum FSH is measured before (day 3) and after (day 10) administration of clomiphene citrate (CC), is used as a test of ovarian reserve in infertile women. Estradiol (E2) is often measured on day 3 but is rarely checked on day 10 despite the fact that the change in E2 reflects ovarian responsiveness and follicular growth in response to CC. The only previous study to explore the prognostic value of E2 found no correlation between day 10 levels and response to gonadotropins (Scott et al., 1993).

Use of letrozole challenge test to adjust gonadotropin dose in non–down-regulated cycles

The use of a letrozole challenge test to predict ovarian response is described. The authors show that a ratio of cycle day 7 to cycle day 3 post-letrozole FSH level >1.5 is associated with poor ovarian response.

Antral follicle count in clinical practice: building the bridge from ovarian reserve to in vitro fertilization outcome

Antral follicle count provides a useful assessment of ovarian reserve to predict ovarian response, estimate risk for cycle cancellation, optimize stimulation protocol selection, and confidently select suitable candidates for IVF.

The reproducibility of serum anti-Müllerian hormone in subfertile women: within and between patient variability

Serum anti-Müllerian hormone concentrations vary significantly over time and this should be taken into account when tailoring treatment protocols for patients undergoing controlled ovarian hyperstimulation (COH). Compared with FSH, serum anti-Müllerian hormone may have greater discriminatory power because of its modest intrapatient variation and the larger interpatient variation.

Ovarian reserve tests and their utility in predicting response to controlled ovarian stimulation in rhesus monkeys

Controlled ovarian stimulation (COS) is an alternative to natural breeding in nonhuman primates; however, these protocols are costly with no guarantee of success. Toward the objective of predicting COS outcome in rhesus monkeys, this study evaluated three clinically used ovarian reserve tests (ORTs): day 3 (d3) follicle-stimulating hormone (FSH) with d3 inhibin B (INHB), the clomiphene citrate challenge test (CCCT), and the exogenous FSH Ovarian Reserve Test. A COS was also performed and response was classified as either successful (COS+) or unsuccessful (COS-) and retrospectively compared with ORT predictions. FSH and INHB were assessed for best hormonal index in conjunction with the aforementioned tests. INHB was consistently more accurate than FSH in all the ORTs used. Overall, a modified version of the CCCT using INHB values yielded the best percentage of correct predictions. This is the first report of ORT evaluation in rhesus monkeys and may provide a useful diagnostic test before costly follicle stimulations, as well as predicting the onset of menopause.

Ovarian Reserve After Surgical Treatment of Unilateral Benign Ovarian Cyst

Objective: To evaluate some ovarian reserve markers in women having unilateral benign ovarian cyst before and after surgical treatment. Ovarian reserve markers used in this study are basal follicle stimulating hormone (FSH), basal estradiol level (E2), antral follicle counting (AFC), total ovarian volume (TOV) and Clomiphene citrate challenge test (CCCT). The surgical treatment of the ovarian cyst is either ovarian cystectomy or oophorectomy.

Effect of Body Mass Index on Post Cystectomy Ovarian Reserve Markers

Objective: To evaluate five ovarian reserve markers in patients with different body mass index who recently had unilateral ovarian cystectomy. Ovarian reserve markers used in this study are basal follicle stimulating hormone (FSH), basal estradiol level (E2), antral follicle counting (AFC), total ovarian volume (TOV) and Clomiphene citrate challenge test (CCCT).

Cervical mucus status can be accurately estimated by transvaginal ultrasound during fertility evaluation

Examinations of the cervical mucus for determining its quantity and physical characteristics are used to provide a clinical marker for the timing of ovulation. We propose that transvaginal ultrasound, which is routinely used as a tool for monitoring follicular growth in patients undergoing ovulation induction, might also be used simultaneously for estimating cervical mucus measurements. With no additional effort or expense, these data may help to optimize individual patient management.

The predictive value of ovarian reserve tests for miscarriage in a population of subfertile ovulatory women

The increase in miscarriage rate with female age is attributed to a decline in oocyte quality. This age-related decrease of oocyte quality is accompanied by a decrease in oocyte quantity. Assessment of the number of oocytes by ovarian reserve tests (ORTs) may therefore also represent their quality. The objective of our study was to assess the predictive value of ORTs for miscarriage in subfertile women. This study was a subanalysis within a prospective cohort study of 474 subfertile ovulatory couples in two hospitals in Groningen, The Netherlands. The ORTs performed were: antral follicle count (AFC), basal and stimulated levels of follicle-stimulating hormone (FSH) and inhibin B, and the clomiphene citrate challenge test (CCCT). Women who achieved an ongoing pregnancy (n = 233) were compared with women experiencing miscarriage (n = 72) on the results of their ORTs and patient characteristics. In univariate analysis, the outcome of the ORTs did not differ between the groups. Logistic regression analysis including patient characteristics such as female age did not reveal an association between the ORT results and miscarriage either. Neither AFC, basal and stimulated levels of FSH and inhibin B, nor the CCCT have a statistically significant predictive value for miscarriage in subfertile ovulatory women.

Serum markers and dynamic tests in ovarian reserve investigation: practical analysis

OBJECTIVE: To compare the efficacy of the ovarian reserve serum markers and dynamic tests as a predictor of poor response in ovarian hyperstimulation for Assisted Reproduction Technique (ART).DESIGN: Prospective cohort study.MATERIALS AND METHODS: Thirty infertile women submitted to ART procedure after ovarian hyperstimulation were included. Serum samples for ovarian reserve evaluation (FSH, estradiol, inibin B and AMH) and dynamic tests (the Clomiphene Citrate Challenge Test (CCCT) and the Gonadotropin Analogue Stimulation Test (GAST)) were collected from all patients in the initial follicular phase of the cycle preceding ART procedure. Patients were than submitted to ovarian hyperstimulation and ovarian response was considered to be poor when less than 5 follicles ≥ 14mm were recruited (observed by ultrasound on the day of hCG). Receiver Operator Characteristic (ROC) Curves were calculated for all tests (basal measurements and dynamic tests).Table 1Statistical characteristic of all tested serum markers of ovarian reserve based on Receiver Operator Characteristic (ROC) CurvesCut-offAUC (IC95%)Sens (%)Specif (%)PV+ (%)PV-(%)AMH (pmol/ml)13.70.80 (0.61-0.09)66.788.975.772.7FSH (mIU/ml)4.90.80 (0.62-0.92)76.288.987.378.9Estradiol (pg/ml)38.80.55 (0.35-0.73)42.988.979.460.9Inibin B (pg/ml)8.00.57 (0.38-0.75)8144.459.370.0CCCT (mIU/ml)26.80.81 (0.63-0.93)85.777.879.484.5GAST (pg/ml)10.50.76 (0.75-0.89)69.7100.0100.056.3AUC= area under the curve; Sens= sensitivity; Specif= specificity; PV+=positive predictive value; PV-=negative predictive value; AMH= anti-mullerian hormone; FSH=follicle stimulating hormone; CCCT= Clomiphene Citrate Challenge Test; GAST= Gonadotropin Analogue Stimulation Test. Open table in a new tab CONCLUSIONS: There was no difference between the tested serum markers of ovarian reserve, including the dynamic tests. Therefore, costs and effectiveness of each marker may be taken into account when ovarian reserve is being evaluated during infertile couple's investigation. OBJECTIVE: To compare the efficacy of the ovarian reserve serum markers and dynamic tests as a predictor of poor response in ovarian hyperstimulation for Assisted Reproduction Technique (ART). DESIGN: Prospective cohort study. MATERIALS AND METHODS: Thirty infertile women submitted to ART procedure after ovarian hyperstimulation were included. Serum samples for ovarian reserve evaluation (FSH, estradiol, inibin B and AMH) and dynamic tests (the Clomiphene Citrate Challenge Test (CCCT) and the Gonadotropin Analogue Stimulation Test (GAST)) were collected from all patients in the initial follicular phase of the cycle preceding ART procedure. Patients were than submitted to ovarian hyperstimulation and ovarian response was considered to be poor when less than 5 follicles ≥ 14mm were recruited (observed by ultrasound on the day of hCG). Receiver Operator Characteristic (ROC) Curves were calculated for all tests (basal measurements and dynamic tests). AUC= area under the curve; Sens= sensitivity; Specif= specificity; PV+=positive predictive value; PV-=negative predictive value; AMH= anti-mullerian hormone; FSH=follicle stimulating hormone; CCCT= Clomiphene Citrate Challenge Test; GAST= Gonadotropin Analogue Stimulation Test. CONCLUSIONS: There was no difference between the tested serum markers of ovarian reserve, including the dynamic tests. Therefore, costs and effectiveness of each marker may be taken into account when ovarian reserve is being evaluated during infertile couple's investigation.

The clomiphene citrate challenge test (CCCT) in women with elevated basal FSH: Biological significance and predictive value

Objective The rationale of the clomiphene citrate challenge test (CCCT) is that day 10 serum FSH is influenced by the quality of the recruited oocytes. Biological evidence supporting this assumption is, however, lacking. The aim of this study is to investigate the relationship between results from the CCCT and the quantity and the quality of the recruited oocytes. Study design Patients selected for in vitro fertilization (IVF) and who were found to have elevated basal FSH ( n = 114) underwent an IVF cycle using follicles developing during CCCT. Subsequently, a subgroup of patients ( n = 89) underwent a second cycle receiving high doses of gonadotropins. The main outcome considered was the transfer of viable embryos. Results During the CCCT cycle, the area under the receiver operating characteristics (ROC) curves for day 3 and day 10 serum FSH to predict embryo-transfer was 0.48 (95% CI, 0.37–0.60) and 0.74 (95% CI, 0.63–0.82), respectively. In the subsequent cycle, the area under the ROC curves for the two variables was 0.58 (0.43–0.72) and 0.58 (0.43–0.72), respectively. Conclusions CCCT effectively mirrors the quantity and the quality of the recruited oocytes but its predictive value is low.

Ovarian stromal blood flow following clomiphene citrate challenge test in infertile women

To compare ovarian stromal blood flow indices in the follicular phase and after clomiphene citrate (CC) in infertile women. Pulsatility index (PI), resistance index (RI), and peak systolic blood flow velocity (PSV) of ovarian stromal vessels were determined by spectral Doppler analysis in the early follicular phase and on day 10 after CC. Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol concentrations were determined. A total of 69 infertile women were included in the analysis. No significant differences in the average PI, RI, and PSV of ovarian stromal blood flow were demonstrated in the follicular phase and after CC despite a significant increase in serum estradiol concentration after CC. Serum FSH concentration was similar in the follicular phase and after CC, while serum LH concentration was significantly higher after CC. In the right ovary, ovarian stromal blood flow was absent in 13 (18.8%) patients in the follicular phase and in 6 (8.7%) patients after CC, but the difference did not reach statistical significance. In the left ovary, ovarian stromal blood flow was absent in 13 (18.8%) and 12 (17.4%) patients in the follicular phase and after CC, respectively. Ovarian stromal blood flow indices were similar in the follicular phase and after CC.

The predictive value of ovarian reserve tests for spontaneous pregnancy in subfertile ovulatory women

The predictive value of ovarian reserve tests (ORTs) for spontaneous pregnancy is unclear. Our study aimed to determine whether ORTs have added value to previously identified prognostic factors for spontaneous pregnancy in subfertile ovulatory couples. A prospective cohort study was performed on 474 subfertile ovulatory couples in two hospitals in Groningen, The Netherlands. The ORTs performed were: antral follicle count (AFC), follicle-stimulating hormone (FSH), inhibin B (basal levels and after stimulation with clomiphene citrate) and the clomiphene citrate challenge test. For each couple, the probability of spontaneous pregnancy was retrospectively calculated using the validated Hunault prediction model which includes the main known prognostic factors for spontaneous pregnancy. Outcome measure was time to spontaneous pregnancy resulting in a live birth. When added to the Hunault model, only basal FSH and AFC significantly improved the prediction of spontaneous pregnancy (P-values of 0.05 and 0.04). Absolute changes in predicted probabilities after adding basal FSH or AFC were small: the predicted probability of spontaneous pregnancy shifted >or=10% in only 3.8% and 7.9% of the couples, respectively. Although basal FSH and AFC significantly improved the validated prediction model for spontaneous pregnancy, the clinical relevance of this finding is limited. We recommend that none of the ORTs studied should be used routinely in the subfertility evaluation of ovulatory couples to predict spontaneous pregnancy chances.

Ovarian Reserve Screening: What the General Gynecologist should Know

Ovarian reserve tests are an indirect measurement of a woman's remaining follicular pool and give an estimate of her sensitivity to ovarian stimulation and her prognosis for success with fertility treatments. They cannot be used to predict future fertility or the exact timing of the decline or cessation of fertility. It is important to become familiar with these tests and understand their correct performance and interpretation, including their limitations. We review the correct timing and interpretation of the most commonly accepted tests of ovarian reserve, and suggest which patient populations will benefit most from screening. Discussed in detail are the natural age-related decline in fecundity, basal follicle stimulating hormone and estradiol levels, the clomiphene citrate challenge test, and use of transvaginal ultrasound for antral follicle counts. Other tests, such as for ovarian volume, anti-Müllerian hormone, gonadotropin-releasing hormone agonist and exogenous follicle-stimulating hormone, are discussed briefly.

Clomiphene citrate challenge test and serum anti-MĂźllerian hormone levels in women with menstrual irregularities and/or infertility.

Clomiphene citrate challenge test and serum anti-MĂźllerian hormone levels in women with menstrual irregularities and/or infertility.