Intercycle variability of ovarian reserve tests: results of a prospective randomized study

BACKGROUND: This study was designed to assess prospectively the intercycle variability (ICV) of basal FSH (bFSH), clomiphene citrate challenge test (CCCT) (analysis of the CCCT was performed by the parameter: sum bFSH + sFSH) and exogenous FSH ovarian reserve test (EFORT) (analysis of the EFORT included the following parameters: estradiol (E(2)) increment and inhibin B increment 24 h after administration of FSH), and secondarily to assess the influence of the variability of these ovarian reserve tests. METHODS: Eighty-five regularly menstruating patients, aged 18-39 years, participated in this prospective study, randomized, by a computer-designed four-blocks system into two groups. Forty-three patients underwent a CCCT, and 42 patients underwent an EFORT. Each test was performed 1-4 times in subsequent cycles, one test per cycle. During the first three cycles, patients were treated with intrauterine insemination (IUI). Follicle number and oocyte yield during IVF ovarian stimulation in the fourth cycle were taken as measures for ovarian reserve. RESULTS: The per cycle variance of bFSH ranged from 1.8 to 4.4 (maximum to minimum ratio of 2.44, P < 0.0001), while that of CCCT ranged from 21.3 to 70.6 (3.31, P < 0.0001). No significant change in per cycle variance was found for the E(2) increment (1.25, P > 0.2) and inhibin B increment (1.31, P > 0.2), which were the EFORT parameters. A large ICV of CCCT and bFSH test results was strongly associated with lower ovarian reserve. CONCLUSIONS: Our study shows that the ICV of the inhibin B increment and the E(2) increment in the EFORT is stable in consecutive cycles, which indicates that this reproducible test is a more reliable tool for determination of ovarian reserve than bFSH and CCCT. Women with limited ovarian reserve show a strong ICV of bFSH and FSH response to clomiphene citrate.     

Repeated clomiphene citrate challenge testing in the prediction of outcome in IVF: a comparison with basal markers for ovarian reserve

BACKGROUND: The aim of this study was to investigate the predictive accuracy and clinical value of performing either a single or a repeated clomiphene citrate challenge test (CCCT) in predicting poor response in IVF, compared to that of currently used basal ovarian reserve markers. METHODS: Sixty-three patients undergoing their first IVF treatment were prospectively included. After measurement of basal markers on cycle day 3 (cd3) [FSH, inhibin B and antral follicle count (AFC)], a CCCT was performed. FSH and inhibin B levels were measured on day 10 (cd10). A second CCCT was performed after a washout period of one cycle. In all patients the tests were followed by an IVF treatment. Poor response (<4 oocytes or cancellation due to impaired (<3 follicles) or absent follicular growth) was used as primary outcome measure. RESULTS: Both the single as well as the repeated CCCT markers had a rather good discriminative potential for the prediction of poor response (area under the receiver operating characteristic curve (ROCAUC): FSH cd10=0.79, inhibin B cd10=0.79, mean FSH cd10=0.82 and mean inhibin B cd10=0.88). This compared well with the performance of the basal markers (FSH 0.82, inhibin B 0.72 and AFC 0.83). In a multivariate analysis on only the basal variables, FSH cd3 and AFC were selected (ROCAUC 0.89). Only stepwise forward analysis on the repeated CCCT variables revealed a better discriminating potential for the prediction of poor response (ROCAUC 0.92). At a specificity level of approximately 0.97, sensitivity and the positive predictive value were marginally improved in the CCCT models. CONCLUSIONS: Performing a CCCT (single or repeated) has a rather good ability to predict poor response in IVF. However, it appears that the predictive accuracy and clinical value of the CCCT is not clearly better than that of basal FSH in combination with an AFC. Therefore, the use of the CCCT as a predictor of outcome in IVF should not be advocated.     

Dynamic assays of inhibin B and oestradiol following buserelin acetate administration as predictors of ovarian response in IVF

The study was designed to examine whether dynamic measurements of inhibin B and oestradiol following single administration of buserelin acetate were correlated with the ovarian response to stimulation in IVF. A total of 37 patients undergoing IVF treatment was studied when the long protocol was started in the early follicular phase. Blood samples were taken twice: on day 2 of the menstrual cycle, before the first s.c. administration of buserelin acetate 0.5 mg and on day 3, 24 h later. Inhibin B and oestradiol concentrations were compared with the ovarian response to stimulation. The ovarian response was defined in two ways: 'number of oocytes/total recombinant (r) follicle stimulating hormone (FSH) dose'; and 'square-root (number of follicles/total rFSH dose)'. The following measurements were highly correlated with the ovarian response to stimulation: increase in oestradiol (day 3-day 2 oestradiol concentration) [correlation coefficient (r) = 0.68, P: < 0.0001] and sum of inhibin B (day 2 + day 3 inhibin B concentrations) (r = 0.6, P: < 0.0001). Age and basal concentrations of FSH and inhibin B were inferior to the above measurements in terms of correlation with the ovarian response. In conclusion, dynamic measurements of inhibin B and oestradiol following single administration of buserelin acetate were highly correlated with the ovarian response to stimulation for IVF treatment.     

Reproductive ageing and ovarian function: is the early follicular phase FSH rise necessary to maintain adequate secretory function in older ovulatory women?

BACKGROUND: Serum FSH elevations and decreases in inhibin B have been consistently demonstrated in the early follicular phase of cycles in women of advanced reproductive age. However, secretory products of the dominant follicle (estradiol and inhibin A) in the serum of older ovulatory women are maintained at levels similar to those of their younger counterparts. The goal of this investigation was to determine if ovarian secretory capacity is dependent on relative FSH levels and if basal measures of ovarian reserve reflect ovarian secretory capacity. METHODS: We administered equivalent low, but effective doses of recombinant FSH for 5 days to a group of older subjects (40-45 years, n=9) and younger controls (20-25 years, n=10) after pituitary suppression with a GnRH agonist. Outcome measures included follicular development as determined by serial transvaginal ultrasound examinations and serum levels of estradiol, inhibin A and inhibin B. RESULTS: Serum levels of estradiol and inhibin A were not statistically different between the two groups, while the number of large follicles formed was greater in the younger subjects. Basal parameters of ovarian reserve were not significantly correlated with ovarian secretory capacity, but did correlate with the number of follicles recruited in response to low-dose FSH. CONCLUSIONS: By providing equivalent serum levels of FSH in older and younger reproductive aged women, this study demonstrates that the secretory capacity of recruited follicles is maintained in older reproductive aged women.     

Day 3 serum inhibin B and FSH and age as predictors of assisted reproduction treatment outcome

Recent reports investigating the value of basal inhibin B determination as a predictor of ovarian reserve and assisted reproduction treatment have led to discordant results. This study was undertaken to further assess the relative power of day 3 inhibin B and follicle stimulating hormone (FSH) (defined before treatment) and the woman's age both as single and combined predictors of ovarian response and pregnancy in an in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) programme. A total of 120 women undergoing their first cycle of IVF or ICSI was included. Forty consecutive cycles cancelled because of poor follicular response were initially selected. As a control group, the nearest completed IVF/ICSI cycles before and after each cancelled cycle (i.e. the closest cycles in temporal relationship to the index cycle) were used. Mean age and basal FSH concentrations were significantly higher in the cancelled than in the control group (P: < 0.01 and P: < 0.001 respectively), whereas basal inhibin B was significantly higher in the latter (P: < 0.05). The association of basal FSH (with an accuracy or predictive value of ovarian response of 79%) with cancellation rate was significant, independent of, and stronger than the effects of age and inhibin B (P: < 0.05). Any two or all three of these variables studied did not improve the predictive value of FSH alone. Woman's age was the only variable independently associated with pregnancy rate. It is concluded that the stronger predictors of success in patients undergoing their first IVF/ICSI treatment cycle are age and basal FSH rather than inhibin B. Basal FSH concentration was a better predictor of cancellation rate than age, but age was a stronger predictor of pregnancy rate.     

Day 5 inhibin B levels in a treatment cycle are predictive of IVF outcome

BACKGROUND: Day 5 serum inhibin B during IVF treatment has been investigated as a predictor of outcome. METHODS: A total of 54 women (< or = 39 years, normal menses and endocrine profiles) were treated with urinary gonadotrophins or recombinant FSH following pituitary down-regulation. Serum day 3 FSH in a preceding cycle was <8.5 IU/l. Plasma inhibin B, inhibin A and estradiol were determined after 4 days of gonadotrophin administration (day 5). RESULTS: Day 5 inhibin B was the most highly correlated with the number of mature follicles (>14 mm), oocytes retrieved and fertilized. Receiver operating characteristic analysis gave high accuracy for day 5 inhibin B in predicting ovarian response and indicated that a threshold of 400 pg/ml may be helpful in the decision as to whether to continue treatment. Women with <400 pg/ml (n = 16) had lower numbers of follicles, mature follicles, oocytes retrieved, fertilized and cleaved compared with those >400 pg/ml (n = 36) and this threshold gave a positive likelihood ratio of 30, 92.9% sensitivity, 95.0% specificity and 86.7% positive predictive value to detect poor ovarian response. Day 5 inhibin B was the best predictor of pregnancy (no live births and four cycles cancelled, low inhibin group; nine live births and no cancelled cycles, high inhibin group). CONCLUSIONS: Normogonadotrophic, normogonadal women with day 5 inhibin B <400 pg/ml in down-regulated cycles have a poor response to ovarian stimulation and are less likely to conceive compared with women with higher day 5 inhibin B.     

Dynamic assays of inhibin B, anti-Mullerian hormone and estradiol following FSH stimulation and ovarian ultrasonography as predictors of IVF outcome

BACKGROUND: We evaluated basal and dynamic hormonal markers [(FSH, inhibin B, estradiol and anti-Mullerian hormone (AMH)] during the follicular phase and luteal phase of the menstrual cycle and ultrasonic ovarian morphology as predictors of IVF outcome. METHODS: Fifty-six women, aged <38 years, with normal day 3 FSH levels were included prospectively. Serum estradiol, inhibin B and AMH were measured before and 24 h after administration of 300 IU of recombinant FSH on cycle day 3-4 and during the luteal phase. Ovarian volume and antral follicle count (AFC) were evaluated on cycle day 3-4. The predictive value of oocyte number and pregnancy were assessed using uni- and multivariate analysis. RESULTS:Poor responders (<6 oocytes) had significantly lower luteal AMH levels, while high responders (>20 oocytes) had significantly higher AFC, AMH and luteal stimulated inhibin B and estradiol than normal responders. Multivariate regression analyses showed that the best models for predicting oocyte number included AFC, follicular phase AMH and stimulated inhibin B. Only AMH showed a significant difference between pregnant and non-pregnant women at both cycle phases. CONCLUSIONS: In young women (<38 years), AFC or basal AMH and stimulated inhibin B predict ovarian response for IVF. The only predictor for pregnancy is follicular or luteal phase AMH.     

Serum inhibin B levels measured early during FSH administration for IVF may be of value in predicting the number of oocytes to be retrieved in normal and low responders

BACKGROUND: In a previous study we have found that in normal ovulatory women, serum inhibin B levels on days 4-6 of FSH administration correlated with the number of oocytes retrieved. In the current study we examined the significance of earlier inhibin B measurements in predicting the oocyte number, in both normal and low responders. METHODS: Study A consisted of 19 patients undergoing their first IVF cycle (n = 10) or had a normal response ( vertical line 6 oocytes retrieved, n = 9), while study B consisted of 15 patients with a previous low ovarian response (16. Study B: oocyte number correlated significantly with inhibin B and inhibin A on all days of FSH treatment, even on day 2 (r = 0.90, P < 0.001 and r = 0.65, P < 0.05 for inhibin B and A respectively). No significant correlation was found with E(2) levels. In both studies, all patients with inhibin B >100 pg/ml on treatment day 2 had >6 oocytes. CONCLUSIONS: Our data suggest that serum inhibin B measured early during FSH stimulation may indicate whether sufficient oocytes will be retrieved, in both normal and low responders. Serum inhibin B measured during early FSH treatment may be of predictive value in monitoring ovarian stimulation treatment for IVF.     

A systematic review of tests predicting ovarian reserve and IVF outcome

The age-related decline of the success in IVF is largely attributable to a progressive decline of ovarian oocyte quality and quantity. Over the past two decades, a number of so-called ovarian reserve tests (ORTs) have been designed to determine oocyte reserve and quality and have been evaluated for their ability to predict the outcome of IVF in terms of oocyte yield and occurrence of pregnancy. Many of these tests have become part of the routine diagnostic procedure for infertility patients who undergo assisted reproductive techniques. The unifying goals are traditionally to find out how a patient will respond to stimulation and what are their chances of pregnancy. Evidence-based medicine has progressively developed as the standard approach for many diagnostic procedures and treatment options in the field of reproductive medicine. We here provide the first comprehensive systematic literature review, including an a priori protocolized information retrieval on all currently available and applied tests, namely early-follicular-phase blood values of FSH, estradiol, inhibin B and anti-Müllerian hormone (AMH), the antral follicle count (AFC), the ovarian volume (OVVOL) and the ovarian blood flow, and furthermore the Clomiphene Citrate Challenge Test (CCCT), the exogenous FSH ORT (EFORT) and the gonadotrophin agonist stimulation test (GAST), all as measures to predict ovarian response and chance of pregnancy. We provide, where possible, an integrated receiver operating characteristic (ROC) analysis and curve of all individual evaluated published papers of each test, as well as a formal judgement upon the clinical value. Our analysis shows that the ORTs known to date have only modest-to-poor predictive properties and are therefore far from suitable for relevant clinical use. Accuracy of testing for the occurrence of poor ovarian response to hyperstimulation appears to be modest. Whether the a priori identification of actual poor responders in the first IVF cycle has any prognostic value for their chances of conception in the course of a series of IVF cycles remains to be established. The accuracy of predicting the occurrence of pregnancy is very limited. If a high threshold is used, to prevent couples from wrongly being refused IVF, a very small minority of IVF-indicated cases (approximately 3%) are identified as having unfavourable prospects in an IVF treatment cycle. Although mostly inexpensive and not very demanding, the use of any ORT for outcome prediction cannot be supported. As poor ovarian response will provide some information on OR status, especially if the stimulation is maximal, entering the first cycle of IVF without any prior testing seems to be the preferable strategy.     

Serum anti-Müllerian hormone levels: a novel measure of ovarian reserve

BACKGROUND: Anti-Müllerian hormone (AMH) is produced by the granulosa cells of preantral and small antral follicles and its levels can be assessed in serum. Since the number of ovarian follicles declines with increasing age, AMH levels might be used as a marker for ovarian ageing. Therefore, we studied the relationship between AMH levels and ovarian response during ovarian stimulation for IVF. METHODS: A total of 130 patients undergoing their first IVF treatment cycle using a long protocol with GnRH agonist was prospectively included. Blood withdrawal was performed and the number of antral follicles was assessed by ultrasound on day 3 of a spontaneous cycle. Poor response and the number of oocytes were used as primary outcome measures. In a random subset of 23 patients a GnRH agonist stimulation test was performed to investigate whether a rise in FSH and LH would affect AMH levels. RESULTS: The data of 119 patients were analysed. Serum AMH levels were highly correlated with the number of antral follicles (r = 0.77; P < 0.01) and the number of oocytes retrieved (r = 0.57, P < 0.01). A negative association was found between AMH levels and poor ovarian response (fewer than 4 oocytes or cycle cancellation; OR 0.82, 95% CI 0.75-0.90, P < 0.01). Inclusion of inhibin B and FSH concentrations to AMH in a multivariate model improved the prediction of ovarian response. The post GnRH agonist rise in FSH and LH levels did not influence AMH values. CONCLUSIONS: Poor response in IVF, indicative of a diminished ovarian reserve, is associated with reduced baseline serum AMH concentrations. In line with recent observations it appears that AMH can be used as a marker for ovarian ageing.     

The significance of the number of antral follicles prior to stimulation in predicting ovarian responses in an IVF programme

Multiple follicular development plays a major role in the successful outcome of IVF and embryo transfer treatment. Prediction of ovarian responses prior to stimulation is useful in counselling patients and helpful in tailoring the dosage of gonadotrophin to individual patients. The objective of this study was to compare age of women, body mass index (BMI), basal FSH concentration, volume of both ovaries and the number of antral follicles of both ovaries in predicting the number of oocytes obtained. A total of 128 consecutive women, who had no history of ovarian surgery, were non-smokers and undergoing the first cycle using a standard regimen of ovarian stimulation were examined. The total number of antral follicles achieved the best predictive value, followed by basal FSH, BMI and age of women. In those women with fewer antral follicles, a longer duration and higher dosage of human menopausal gonadotrophin were required but the number of eggs obtained was significantly less than for those with more antral follicles. Significantly more cycles were cancelled before egg collection in women with < or =6 antral follicles while more cycles of embryo transfer were postponed in order to reduce the risk of ovarian hyperstimulation syndrome in women with >9 antral follicles.     

Evaluation of the utility of multiple endocrine and ultrasound measures of ovarian reserve in the prediction of cycle cancellation in a high-risk IVF population

BACKGROUND: Unexpectedly poor response leading to IVF cycle cancellation is a distressing treatment outcome. We have prospectively assessed several markers of ovarian reserve in a high risk IVF population to determine their utility in predicting IVF cycle cancellation. METHODS: Eighty-four women at high risk of cycle cancellation due to raised FSH, previous poor response and/or age > or =40 years attending for high-dose short protocol IVF treatment had baseline measures of FSH, inhibin B, anti-Müllerian hormone (AMH), antral follicle count (AFC) and ovarian volume. A GnRH agonist was then administered and, 24 h later, estradiol (E(2)) and inhibin B measures were repeated. RESULTS: Fifty-seven per cent of patients in this study had a poor response to stimulation, and 15% were cancelled. Using multivariate logistic regression, we found that day 3 inhibin B levels were the best predictor of cycle cancellation with an area under the receiver operating curve (ROC AUC) = 0.78 (P = 0.017). When only considering baseline variables, mean ovarian volume was the best predictor of cycle cancellation (ROC AUC = 0.78; P = 0.016). AMH concentrations were the best predictor of a poor response (P = 0.003), and AMH was also predictive of cycle cancellation (P = 0.007) with very little inter-cycle variability. None of the parameters studied were predictive of ongoing pregnancy. CONCLUSIONS: This group of at-risk patients had a high rate of poor response to simulation and cancellation. Although several measures of ovarian reserve were able to predict cycle cancellation, none were able to predict pregnancy. AMH was predictive of both cycle cancellation and poor response with little inter-cycle variability.     

Basal and stimulation day 5 anti-Mullerian hormone serum concentrations as predictors of ovarian response and pregnancy in assisted reproductive technology cycles stimulated with gonadotropin-releasing hormone agonist--gonadotropin treatment

BACKGROUND: Anti-Müllerian hormone (AMH) has been recently proposed as a marker for ovarian ageing and poor ovarian response to controlled ovarian hyperstimulation in assisted reproduction cycles. The present study was undertaken to investigate the usefulness of baseline cycle day 3 AMH levels and AMH serum concentrations obtained on the fifth day of gonadotropin therapy in predicting ovarian response and pregnancy in women undergoing ovarian stimulation with FSH under pituitary desensitization for assisted reproduction. METHODS: A total of 80 women undergoing their first cycle of IVF/intracytoplasmic sperm injection (ICSI) treatment were studied. Twenty consecutive cycles which were cancelled because of a poor follicular response were initially selected. As a control group, 60 women were randomly selected from our assisted reproduction programme matching by race, age, body mass index, basal FSH and indication for IVF/ICSI to those in the cancelled group. For each cancelled patient, three IVF/ICSI women who met the matching criteria were included. RESULTS: Basal and day 5 AMH serum concentrations were significantly lower in the cancelled than in the control group. Receiver-operating characteristic (ROC) analysis showed that the capacity of day 5 AMH in predicting the likelihood of cancellation in an assisted reproduction treatment programme was significantly higher than that for basal AMH measurement. However, the predictive capacity of day 5 AMH was not better than that provided by day 5 estradiol. In addition, neither basal nor day 5 AMH or estradiol measurements were useful in the prediction of pregnancy after assisted reproductive treatment. CONCLUSIONS: AMH concentrations obtained early in the follicular phase during ovarian stimulation under pituitary suppression for assisted reproduction are better predictors of ovarian response than basal AMH measurements. However, AMH is not useful in the prediction of pregnancy. Definite clinical applicability of AMH determination as a marker of IVF outcome remains to be established.     

Serum anti-Müllerian hormone dynamics during controlled ovarian hyperstimulation

BACKGROUND: The study aim was to investigate possible changes in serum anti-Müllerian hormone (AMH) levels during controlled ovarian hyperstimulation (COH), and their possible relationship with follicular development and other ovarian hormones. METHODS: A total of 93 women undergoing COH with GnRH agonist and FSH was studied prospectively. Serum levels of AMH, inhibin B, estradiol (E(2)), progesterone, testosterone and Delta(4)-androstenedione were measured when pituitary suppression was achieved (baseline), on days 6 and 8 of FSH treatment, and on the day of hCG. The number of small (<12 mm) and large (>/=12 mm) antral follicles were estimated using ultrasound. RESULTS: Serum AMH levels declined progressively (baseline, 1.21 +/- 0.11 ng/ml; day 6, 0.91 +/- 0.09 ng/ml; day 8, 0.77 +/- 0.08 ng/ml; and day of hCG, 0.53 +/- 0.06 ng/ml), whereas-as expected-the other hormone levels increased during FSH treatment. Throughout COH, serum AMH levels correlated positively with the number of small but not large antral follicles, and with inhibin B serum levels. No correlation between AMH and the other hormones was observed. CONCLUSIONS: Serum AMH levels decline gradually during multiple follicular maturation, probably reflecting the dramatic reduction in the number of small antral follicles due to COH, and confirming the scarce AMH expression by larger follicles.     

A prospective study of predictive factors of ovarian response in 'standard' IVF/ICSI patients treated with recombinant FSH. A suggestion for a recombinant FSH dosage normogram

BACKGROUND: The aim was to identify independent predictors of ovarian response to recombinant (r)FSH through a multiple regression analysis. METHODS: Prospective study including 145 'standard' patients treated with 150 IU/day of rFSH during their first IVF/ICSI cycle. Down-regulation was achieved with long agonist protocol. The following were examined as possible predictive factors: age, body mass index, cycle length, smoking status and on day 2-5: total ovarian volume, total number of antral follicles (<10 mm), total Doppler score of the ovarian stromal blood flow, serum FSH, LH, estradiol, inhibin B, and testosterone. RESULTS: Total number of antral follicles, total Doppler score, serum FSH, LH, estradiol, inhibin B, smoking status and cycle length were independent predictors of the number of aspirated follicles. The number of oocytes was predicted by the total number of antral follicles, total Doppler score, serum testosterone and smoking status. In bivariate linear regression analyses ovarian volume was a highly significant predictor of both the number of follicles (P < 0.001) and the number of oocytes (P < 0.001). CONCLUSIONS: Among 12 investigated possible predictive factors in 'standard' patients, the total number of antral follicles and ovarian stromal blood flow assessed by total Power Doppler score are the two most significant predictors of ovarian response. Suggestion for an rFSH dosage normogram is presented.     

Day 5 inhibin B serum concentrations as predictors of assisted reproductive technology outcome in cycles stimulated with gonadotrophin-releasing hormone agonist-gonadotrophin treatment

The present study investigates the usefulness of inhibin A, inhibin B and serum oestradiol concentrations obtained in the fifth day of gonadotrophin therapy in predicting ovarian response and assisted reproductive treatment outcome in women undergoing ovarian stimulation under pituitary desensitization. A total of 80 women undergoing their first cycle of in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) treatment were studied. Twenty consecutive cycles which were cancelled because of a poor follicular response were initially selected. As a control group, 60 women were randomly selected from our assisted reproductive treatment programme matching by race, age, body mass index, and indication for IVF/ICSI to those in the cancelled group. For each cancelled cycle, three IVF/ICSI women who met the matching criteria were included. Basal follicle stimulating hormone (FSH) concentrations were significantly higher in the cancelled than in the control group, whereas basal inhibin B was significantly higher in the latter. Basal oestradiol concentrations were similar in both groups of patients. On day 5 of gonadotrophin therapy serum concentrations of oestradiol, inhibin A and inhibin B were significantly lower in the cancelled group as compared with controls. Logistic regression analysis showed that the association for day 5 inhibin B (with a predictive value of ovarian response of 91.03%) with cancellation rate was significant, independent of, and stronger than, the effects of any other hormone variable investigated. In addition, day 5 inhibin B concentrations were correlated directly with parameters of ovarian response, ovum retrieval and oocyte and fertilization outcome. However, day 5 inhibin B was not a better predictor of pregnancy than the other hormone variables studied on this day. It is concluded that inhibin B concentrations obtained early in the follicular phase during ovarian stimulation under pituitary suppression for assisted reproductive treatment are highly predictive of ovarian response.     

卵泡输出率的应用研究

目前卵巢反应性的预测指标包括AMH、抑制素B、年龄、窦卵泡、基础性激素、卵巢敏感性（OSI）、卵泡敏感性（FSI）等,而这些指标在预测卵巢对外源性促性腺激素（Gn）的反应存在一定的局限性。在近年生殖医学预测IVF/ICSI妊娠结局及卵巢反应性的相关研究中,提出卵泡输出率（FORT）是一个客观、较新且热门的指标。控制性超促排卵（COH）个体化治疗方案的制定在治疗各种不孕症的过程中具有重要的意义,可以通过FORT评估每个患者卵巢反应性来制定合适的COH方案,从而改善妊娠结局。本文就FORT在卵巢低反应、多囊卵巢综合征（PCOS）、子宫内膜异位症（EMs）、不明原因不孕症、高龄及肿瘤患者对卵巢反应性及IVF/ICSI妊娠结局的相关性研究进行综述。     

The number of small antral follicles (2-6 mm) determines the outcome of endocrine ovarian reserve tests in a subfertile population

BACKGROUND: Ovarian reserve is related to age and can be estimated by ovarian reserve tests (ORTs), such as antral follicle count (AFC) and various endocrine parameters. The endocrine function of a follicle is related to its size. The aim of this study is to evaluate which sizes of antral follicles are most closely correlated with age and the outcome of endocrine ORTs. METHODS: In total 474 subfertile, ovulatory patients, recruited from two fertility centers in The Netherlands, participated in this prospective cohort study. The following ORTs were performed: AFC (follicles from 2 to 10 mm), basal FSH, basal inhibin B (bInhB), clomiphene citrate challenge test and inhibin B after stimulation with clomiphene citrate. RESULTS: The number of small follicles (2-6 mm) declined with age; the number of larger follicles (7-10 mm) remained constant. Independent of age, the number of small follicles was significantly related to all ORTs (P<0.001, except bInhB P=0.005). The number of larger follicles was only significantly related to bInhB (P=0.009). CONCLUSIONS: The number of small antral follicles (2-6 mm) is significantly related to age and also, independent of age, to all endocrine ORTs tested, suggesting the number of small antral follicles represents the functional ovarian reserve.     

Inhibin A and inhibin B reflect ovarian function in assisted reproduction but are less useful at predicting outcome

To test the hypothesis that dimeric inhibin A and/or inhibin B concentrations represent improved markers of in-vitro fertilization (IVF) outcome over follicle stimulating hormone (FSH), 78 women who achieved pregnancy within three assisted reproduction treatment cycles were matched to 78 women who underwent at least three assisted reproductive treatment cycles and failed to achieve pregnancy. Baseline serum inhibin B and FSH were obtained between days 1 and 4 in a cycle prior to ovarian stimulation, and inhibin A and B were measured immediately before the ovulatory stimulus and in follicular fluid from the lead follicle. Comparing pregnant and non-pregnant subjects at baseline, younger age (34.0 +/- 0.5 versus 36.0 +/- 0.5 years; P < 0.003) and a combination of FSH lower than the median value (11.2 IU/l) and inhibin B higher than the median value (76.5 pg/ml) were associated with pregnancy (P < 0.03), but FSH (11.7 +/- 0.5 versus 12.9 +/- 0.9 IU/ml) and inhibin B (89.0 +/- 10.2 versus 79.7 +/- 7.7 pg/ml) were not independently associated. At the time of the ovulatory stimulus, serum inhibin A (52.8 +/- 3.8 versus 40.0 +/- 2.7 IU/ml; P < 0.004), inhibin B (1623.8 +/- 165.1 versus 859.2 +/- 94.8 pg/ml; P < 0.0009) and the number of oocytes retrieved (14.6 +/- 0.8 versus 10.1 +/- 0.6; P < 0.0001) were predictive of pregnancy when controlled for age. Inhibin A was correlated with the number of embryos (r = 0.4; P < 0.0001). However, neither inhibin A nor inhibin B provided additional information in predicting successful outcome over age and number of oocytes. We conclude that: (i) in patients undergoing assisted reproductive technology, age and number of oocytes retrieved are the strongest predictors of success; (ii) of the parameters available prior to cycle initiation, a combination of lower FSH and higher inhibin B was associated with a greater chance for a successful outcome but an absolute cut-off could not be defined; and (iii) during ovarian stimulation, higher concentrations of inhibin A and inhibin B in serum are associated with successful IVF and mark ovarian reserve as a measure of oocyte number and quality.     

Previous cycle cancellation due to poor follicular development as a predictor of ovarian response in cycles stimulated with gonadotrophin-releasing hormone agonist-gonadotrophin treatment

BACKGROUND: There is scanty information analysing the predictive value of a poor response, in terms of cancellation of the IVF cycle because of poor follicular development, as a predictor of ovarian response in a subsequent treatment cycle. This study, where logistic regression analysis was used, was undertaken to investigate the relative power of the woman's age, basal FSH, and previous cycle cancellation both as single and combined predictors of ovarian response in an IVF program where pituitary desensitization is routinely used. METHODS: One hundred and twenty-nine consecutive patients having their first cycle of IVF/ICSI treatment cancelled because of poor follicular response and undergoing a second attempt within 6 months after the failed treatment cycle were initially selected (group 1). Group 2 comprised 129 patients undergoing the first cycle of IVF/ICSI treatment and who were randomly selected from our assisted reproductive treatment program matching by BMI and indication for IVF/ICSI to those in group 1. RESULTS: Cancellation rate was significantly higher but ovarian response significantly lower in group 1 as compared with group 2. As indicated by the AUC(ROC) determined with ROC analysis, such a poor outcome in patients having a previous IVF/ICSI cycle cancelled due to poor response was observed whatever the level of basal FSH. In a logistic regression analysis and according to the odds ratio values, the predictive capacity of a previous poor response was 9 and 7.6 times higher than the predictive capacity of age and basal FSH, respectively. Any two or all three variables studied did not improve the predictive value of previous cycle cancellation alone. CONCLUSIONS: The history of an IVF/ICSI cancelled cycle due to poor follicular response in a standard stimulation protocol is a better predictor of cancellation in subsequent treatment cycles than age or FSH. The poor ovarian response associated with previous cycle cancellation occurs whatever the level of basal FSH.