Serum anti-Müllerian hormone levels remain high until late reproductive age and decrease during metformin therapy in women with polycystic ovary syndrome

BACKGROUND: Anti-Müllerian hormone (AMH) is secreted by granulosa cells of ovarian early developing follicles and its serum levels have been shown to correlate with small antral follicle number. Since the pronounced androgen secretion from follicles/stroma in women with polycystic ovary syndrome (PCOS) remains until late reproductive age, and since AMH reflects the number of antral follicles, it was of interest to study the possible age-related relationship between AMH, androgens and follicle number in women with PCOS and in control women. Moreover, the possible effect of metformin on serum AMH levels and the relationship to follicle count and volume were studied. METHODS: Forty-four healthy women (aged 21-44 years) and 65 women with previously diagnosed PCOS (aged 16-44 years) participated in the study. Serum basal AMH levels were correlated with those of serum androstenedione, testosterone, estradiol (E2), LH, FSH and inhibin B, and with follicle number. The effect of metformin on serum AMH concentrations, follicle number and ovarian volume was studied in 26 women (aged 20-41 years) with PCOS after 6 months of treatment. RESULTS: Serum AMH levels were 2- to 3- fold higher in PCOS women than in healthy women. In control women, serum AMH levels correlated positively with those of serum androstenedione (r = 0.564, P < 0.001) and testosterone (r = 0.328, P = 0.036) and negatively with serum FSH concentrations (r = -0.374, P = 0.012) and age (r = -0.691, P<0.001). In women with PCOS, serum AMH levels correlated positively with those of androstenedione (r = 0.311, P = 0.011) and testosterone (r = 0.310, P = 0.011) and with follicle count (r = 0.352, P = 0.012), and negatively with age (r = -0.300, P = 0.014). Serum AMH levels, the number of antral follicles and ovarian volume decreased significantly during metfromin treatment. CONCLUSIONS: Serum AMH levels decreased with age both in healthy women and in women with PCOS, although they were always 2- to 3-fold higher and remained elevated until 40 years of age in PCOS subjects. Thus, since serum AMH levels correlate well with antral follicle count and serum androgen levels, the measurement of AMH could be used as a tool to assess ovarian ageing, to diagnose polycystic ovaries/PCOS and to evaluate treatment efficacy.     

Serum anti-Müllerian hormone is more strongly related to ovarian follicular status than serum inhibin B,estradiol, FSH and LH on day 3

BACKGROUND: The study aim was to compare the relationship between serum anti-Müllerian hormone (AMH) levels and other markers of ovarian function with early antral follicle count on day 3. METHODS: A total of 75 infertile women was studied prospectively. On cycle day 3, serum levels of AMH, inhibin B, estradiol (E(2)), FSH and LH levels were measured, and the number of early antral follicles (2-10 mm in diameter) estimated at ultrasound scanning to compare the strengths of hormonal-follicular correlations. RESULTS: Median (range) serum levels of AMH, inhibin B, E(2), FSH and LH were 1.39 ng/ml (0.24-6.40), 90 (16-182) pg/ml, 31 (15-111) pg/ml, 7.0 (2.9-19.3) mIU/ml and 4.7 (1.2-11.7) mIU/ml respectively, and follicular count was 12 (1-35). Serum AMH levels were more strongly correlated (P < 0.001) with follicular count (r = 0.74, P < 0.0001) than were serum levels of inhibin B (r = 0.29, P < 0.001), E(2) (r = -0.08, P = NS), FSH (r = -0.29, P < 0.001) and LH (r = 0.05, P = NS). CONCLUSIONS: Serum AMH levels were more robustly correlated with the number of early antral follicles than inhibin B, E(2), FSH and LH on cycle day 3. This suggests that AMH may reflect ovarian follicular status better than the usual hormone markers.     

Inhibin A, inhibin B and activin A concentrations in follicular fluid from women with polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is characterized by arrestedfollicle development at the early antral stage. Alterationsin inhibin production by developing follicles could be involvedin PCOS by suppressing follicle stimulating hormone concentrationsduring the follicular phase of the menstrual cycle as well asby increasing thecal androgen production. Inhibin B appearsto be more important than inhibin A during the follicular phase;however, there are no data regarding the follicular fluid concentrationsof inhibin B in PCOS. The purpose of this study was to compareinhibin A, inhibin B and activin A concentrations in the follicularfluid from regularly cycling women and women with PCOS. InhibinA, inhibin B and activin A were measured in the follicular fluidof 4–7 mm follicles from PCOS ovaries and size-matchedfollicles from normally cycling women by specific and sensitivetwo-site enzyme-linked immunosorbent assays. In both controland polycystic ovaries, inhibin B was approximately 10-foldhigher than activin A and more than 100-fold higher than inhibinA. There was no difference in activin A concentrations betweenPCOS and control follicles. In control ovaries, the inhibinB and inhibin A concentrations in dominant follicles were significantlyhigher than in cohort follicles. While inhibin A concentrationswere lower in PCOS follicles than in normal cohort follicles,there was no difference in inhibin B concentrations betweenPCOS follicles and normal cohort follicles. These data are consistentwith the concept that inhibin B is the physiologically mostimportant form of inhibin during the follicular phase of themenstrual cycle and indicate that PCOS is not associated withincreased inhibin B concentrations in follicular fluid.     

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.     

The ovarian markers of the FSH insufficiency in functional hypothalamic amenorrhoea

BACKGROUND: The purpose of this work was to revisit the gonadotrophin insufficiency of functional hypothalamic amenorrhoea (FHA) with the use of relevant ovarian markers. METHODS: Serum anti-Mullerian hormone (AMH), estradiol (E2), inhibin B, LH and FSH were immunoassayed in 31 women with FHA and in 30 healthy women in early follicular phase. The ovarian antral follicle number (FN) was determined within two distinct diameter ranges (2-5 and 6-9 mm) by ultrasound in real time, the same day as the blood sampling. RESULTS: The 2-5 mm FN was similar between the two groups, while the 6-9 mm FN was significantly less in FHA than in controls, in relation with lower serum FSH levels (r=0.428; P<0.024). Nine (29%) FHA patients had a low serum basal FSH level (i.e. <4.5 IU/l, 5th percentile of control values). In the 22 (71%) patients with apparently normal FSH, the mean 6-9 mm FN was similar to controls. However, in this sub-group, the mean AMH serum level and the AMH:2-5 mm FN ratio were significantly higher and the mean inhibin B serum level was significantly lower than in controls. No significant relationship was found between the serum LH levels and the FN, AMH or inhibin B values. CONCLUSION: Only a minority of patients with FHA have a low serum basal FSH level, and we show that this is associated with fewer 6-9 mm follicles at the ovarian level. Despite a normal serum FSH level and 6-9 mm FN in the majority of patients with FHA, the functional follicle markers are abnormal. This suggests that the FSH action on the ovary is incomplete and is not properly reflected by its serum level nor by FN at ultrasound.     

Changes in anti-Müllerian hormone serum concentrations over time suggest delayed ovarian ageing in normogonadotrophic anovulatory infertility

BACKGROUND: Anti-Müllerian hormone (AMH), produced by growing pre-antral and early antral ovarian follicles, has been shown to be a useful marker for ovarian ageing. Serum AMH concentrations are elevated during reproductive life in anovulatory women, especially in those patients exhibiting polycystic ovaries (PCO). The current study was designed to investigate whether the decrease in AMH serum concentrations over time is different comparing women with normogonadotrophic anovulation [World Health Organization (WHO) group 2 (including polycystic ovary syndrome (PCOS)] and normo-ovulatory controls. METHODS AND RESULTS: AMH serum levels were assessed on two occasions in 98 patients suffering from WHO 2 anovulatory infertility as well as in 41 normo-ovulatory premenopausal women. Median time interval between both visits was 2.6 years (range 0.3-9.0) for WHO 2 patients compared with 1.6 years (range 1.0-7.3) in controls. Serum AMH concentrations were significantly (P < 0.0001) elevated on both occasions in WHO 2 patients (AMH1, median = 7.5 microg/l, range 0.1-35.8; and AMH2, median = 6.7 microg/l, range 0.0-30.6) compared with controls (AMH1, median = 2.1 microg/l, range 0.1-7.4; and AMH2, median = 1.3 microg/l, range 0.0-5.0). Regression analysis, corrected for age, indicated a significant relative decrease in serum AMH concentrations over time for both groups (P < 0.001). However, the decline in serum AMH in WHO 2 patients was significantly less compared with controls (P = 0.03). CONCLUSION: The present longitudinal study shows that serum AMH concentrations decrease over time both in women presenting with WHO 2 anovulatory infertility and in normo-ovulatory controls. The decrease in WHO 2 patients is less pronounced despite distinctly elevated concentrations. This observation may suggest retarded ovarian ageing and hence a sustained reproductive life span in these patients.     

The role of LH and FSH in ovarian androgen secretion and ovarian follicular development: clinical studies in a patient with isolated FSH deficiency and multicystic ovaries.

Inactivating mutations have proven to be instructive in elucidating the role of FSH in human ovarian function. We performed a detailed reproductive endocrine evaluation of a patient with inactivating mutations in the FSH beta-subunit gene who was hypo-estrogenic and had LH excess. The patient underwent a pelvic ultrasound and overnight frequent blood sampling followed by a human chorionic gonadotrophin (HCG) stimulation test. One month later she received human recombinant FSH, followed 24 h later by a second HCG stimulation test. Despite a mean LH serum concentration and LH pulse characteristics typical for polycystic ovaries (PCOS), baseline and dexamethasone-suppressed free testosterone were low-normal. The administration of HCG led to minimal stimulation of 17-hydroxyprogesterone and androgens. The patient had multicystic ovaries containing follicles 3-5 mm in diameter and responded to FSH with prompt increases in estradiol and inhibin B. There were no clinical or laboratory consequences of LH excess in this FSH-deficient woman. These findings support the hypothesis that excessive LH stimulation alone does not cause ovarian hyperandrogenism. We also found that follicular development was present in the absence of FSH. These antral follicles had apparently developed normally, since estradiol and inhibin B increased promptly after FSH administration.     

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.     

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.     

Effect of laparoscopic ovarian diathermy on circulating inhibin B in women with anovulatory polycystic ovary syndrome

BACKGROUND: Laparoscopic ovarian diathermy (LOD) frequently induces ovulation in patients with polycystic ovary syndrome (PCOS). The mechanism by which this effect occurs remains largely unexplained. The aim of this study was to measure changes in inhibin B production in response to LOD to see whether this could explain the mechanism of action of LOD. METHODS: This prospective study included 50 anovulatory women with PCOS. All women underwent LOD. Blood samples were collected before and after LOD to measure plasma concentrations of inhibin B, gonadotrophins and androgens. RESULTS: The pre-operative median plasma concentration of inhibin B was 110.0 pg/ml (range 19.0-567.0 pg/ml). There was a statistically significant inverse correlation (r= -0.286; P < 0.05) between body mass index (BMI) and inhibin B. Non-obese women with PCOS (BMI 30 kg/m2; n=13). Following LOD, 39 women ovulated. No statistically significant change of inhibin B after LOD was observed in the overall group of women with PCOS or in the subgroup of non-obese PCOS women with higher pre-operative inhibin B. CONCLUSIONS: The lack of any change of inhibin B after LOD makes it unlikely that this hormone has any role to play in the mechanism of action of LOD.     

Endocrinology: Insulin-like growth factor binding proteins in a natural pre-ovulatory follicle from a woman with polycystic ovary syndrome

Insulin-like growth factor binding protein (IGFBP) concentrationsin the follicular fluid of ovarian follicles have been shownto correlate with dominance and atresia. IGFBP-2 and IGFBP-4are increased in atresia, and IGFBP-3 is decreased in dominantfollicles. The purpose of this study was to compare the IGFBPconcentration in follicular fluid from a natural pre-ovulatoryfollicle of a woman with polycystic ovarian syndrome (PCOS)with other PCOS follicles and dominant follicles from normallycycling women. Follicular fluid was collected from 5–7mm diameter follicles and a natural pre-ovulatory follicle fromwomen with PCOS, and healthy and atretic follicles from normalwomen. The IGFBP profiles were analysed using Western ligandblotting. The IGFBP concentrations in the 5–7 mm diameterfollicles from the polycystic ovaries containing a pre-ovulatoryfollicle were similar to those in follicles from other womenwith PCOS, and comparable with androgenic cohort follicles fromnormal women. In particular, the IGFBP-2 and IGFBP-4 concentrationswere elevated significantly compared with the oestrogenic cohortfollicles. The concentrations of all IGFBP detected in the follicularfluid from the PCOS pre-ovulatory follicle were significantlyless than those of the 5–7 mm diameter follicles fromthe same subject. The IGFBP concentrations were within the rangeof normal dominant follicles, and IGFBP-2 and IGFBP-3 were atthe lower end of the normal range. The results indicate thatthe PCOS pre-ovulatory follicle contained a normal pattern ofIGFBP expression even though the other follicles exhibited apattern typical of PCOS. These data support the hypothesis thatdecreased concentrations of IGFBP, in particular IGFBP-3, maybe involved in selection of the dominant follicle, and thatwhen a spontaneous pre-ovulatory follicle develops in PCOS,the underlying cause of the polycystic ovaries is not resolvedbut the rest of the ovary remains polycystic.     

Basal and day 12 inhibin concentrations in the prediction of ovarian response to gonadotrophins in women with PCOS

BACKGROUND: In this study, we aimed to investigate whether basal and day 12 serum total inhibin concentrations in women with polycystic ovarian syndrome (PCOS) were of predictive value for the estimation of the ovarian response to gonadotrophins. METHODS: Ovulation induction with a very low dose gonadotrophin protocol, starting with 37.5 IU/day, was performed for 40 cycles on 35 patients with PCOS. Day 3 (basal) serum total inhibin, FSH and oestradiol concentrations; day 12 dominant follicle diameter, inhibin and oestradiol concentrations and midluteal serum progesterone concentrations were measured during the 40 cycles. The correlations between basal and day 12 inhibin concentrations and some critical ovulation monitoring parameters were investigated. RESULTS: Ovulation was obtained in 14 out of 40 cycles: 21% of cycles with basal inhibin <1.0 IU/ml; 33.3% of cycles with basal inhibin between 1.0-1.9 IU/ml; and 83.3% of those with inhibin concentrations > or =2 IU/ml were ovulatory (P < 0.05). Ovulation was achieved in 91.6% of the cycles with a day 12 inhibin concentration > or =4 IU/ml. CONCLUSIONS: Basal inhibin concentrations may determine poor and good responders to ovulation induction with very low dose gonadotrophin protocol in patients with PCOS. The day 12 inhibin concentration was found to be a more sensitive parameter than the oestradiol concentration in the prediction of follicular maturation.     

The number of antral follicles in normal women with proven fertility is the best reflection of reproductive age

BACKGROUND: The purpose of this study was to compare the predictive capacity of several markers of reproductive age in normal women. METHODS: Healthy female volunteers (n = 162) aged 25-46 years with proven, normal fertility and regular menstrual cycles were recruited. In this selected group, chronological age was assumed to approximate reproductive age and, therefore, was taken as the proxy-variable for reproductive age. The number of antral follicles with 2-10 mm diameter, total ovarian volume, total follicular volume, mean follicular volume, and volume of either the smallest or largest ovary were estimated by transvaginal sonography of the ovaries. Serum levels of early follicular FSH, estradiol and inhibin B, as well as the response of estradiol and inhibin B to exogenous GnRH agonist administration (GAST), were also evaluated. RESULTS: Regression analysis revealed that the antral follicle number showed the highest correlation with age (r = -0.68, P = 0.001), and explained 46% of its variance. All other variables, except inhibin B, were moderately correlated with age. Responses of estradiol and inhibin B to the GnRH agonist were moderately correlated with age, but highly correlated with the number of antral follicles. CONCLUSIONS: It is concluded that the number of antral follicles has the closest association with chronological age in normal women with proven fertility. As stimulated estradiol and inhibin B clearly reflect the size of the antral follicle cohort, the GAST may be considered the second best single test to predict reproductive age.     

Comparison of ovarian stromal blood flow between fertile women with normal ovaries and infertile women with polycystic ovary syndrome

BACKGROUND: Conflicting information exists in the literature with respect to ovarian stromal blood flow in women with polycystic ovary syndrome (PCOS). We compared the ovarian stromal blood flow and serum vascular endothelial growth factor (VEGF) concentration between fertile women with normal ovaries and infertile women with PCOS. METHODS: In the second to fourth day of the menstrual period, they underwent transvaginal scanning with three-dimensional (3D) power Doppler to determine total antral follicle count (AFC), total ovarian volume, total ovarian vascularization index (VI), flow index (VFI) and vascularization flow index (VFI). Serum FSH, LH and VEGF concentrations were also checked. RESULTS: 107 fertile controls and 32 PCOS women were recruited. Fertile controls and PCOS women had similar total ovarian VI/FI/VFI after controlling for age of the woman, although PCOS women had significantly higher total AFC, total ovarian volume and serum LH concentration than fertile controls. Total ovarian VI/FI/VFI were significantly higher in normal weight (BMI < 25 kg/m2) PCOS women than their overweight (> or = 25 kg/m2) counterparts. CONCLUSIONS: Fertile controls and PCOS women had similar total ovarian 3D power Doppler flow indices. Normal weight PCOS women had significantly higher total ovarian 3D power Doppler flow indices than their overweight counterparts.     

Immunolocalization of Fas and Fas ligand in the ovaries of women with polycystic ovary syndrome: relationship to apoptosis

Both Fas (APO-1, CD95), an apoptosis-inducing receptor, and its ligand, Fas ligand (FasL, CD95L), have been localized to the ovary. Granulosa cell apoptosis occurs in antral follicular atresia. In polycystic ovary syndrome (PCOS), antral follicles accumulate with some atretic features. The ovarian expression of Fas and FasL was examined in PCOS by immunohistochemistry and correlated with immunodetection of apoptotic cells. Fas immunostaining was present in pre-antral follicle oocytes, some primary and secondary pre-antral follicle granulosa cells, and both granulosa and theca of antral follicles. Thecal staining persisted with advancing atresia, while granulosa staining declined. In antral follicles, abundant Fas-positive cells co-localized with scattered nuclei immunopositive for apoptosis. Ovarian vascular myocytes were strongly Fas-immunopositive. FasL immunostaining was present in pre-antral follicles in oocytes and variably in granulosa. In antral follicles, granulosa and thecal FasL staining increased with advancing atresia. Normal control ovaries showed follicular Fas and FasL staining patterns similar to those in PCOS, but vascular staining was less prominent. In one healthy follicle, Fas immunostaining was seen in the oocyte and weakly in mural granulosa and theca interna. The results suggest that in PCOS, an alteration in Fas-mediated apoptosis, does not cause abnormal folliculogenesis, but may promote ovarian vascular remodelling.     

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。     

Predictors of antral follicle count during the reproductive years

BACKGROUND: We sought to identify indicators of antral follicle count which would be serviceable to clinicians seeking to estimate the number of ovarian follicles without relying on sonographic counts. METHODS: We examined the relations of chronological age and four potential indicators of ovarian age-ovarian volume, FSH, dimeric inhibin B and estradiol-to antral follicle count in 176 recently pregnant women. We identified the regression models which best predict low antral follicle count (< or =10 follicles). RESULTS: Chronological age, ovarian volume, FSH and inhibin B were each significantly associated with antral follicle count. Fifty-three (30.1%) women had < or =10 antral follicles. In the total sample, at the cutpoint corresponding to 80% sensitivity, the positive predictive value for a regression model with all four variables was 60%. All regression models performed less well in women <35 years (13.9% with low count) than in women > or =35 years (52.0% with low count). In older women, the positive predictive value for the model with all four variables was 79%, compared with 60% for a model with chronological age alone. CONCLUSIONS: Our models provide a basis for advising women aged > or =35 years who are either trying to conceive or wish to learn whether they may postpone childbearing.     

Three-dimensional assessment of ultrasound features in women with clomiphene citrate-resistant polycystic ovarian syndrome (PCOS): ovarian stromal volume does not correlate with biochemical indices

BACKGROUND: Polycystic ovarian syndrome (PCOS) is a heterogeneous endocrine disorder affecting women of reproductive age. The syndrome is characterized by a combination of polycystic ovarian morphology, clinical features and biochemical indices. The objective of this prospective observational study was to investigate the relationship between the total ovarian volume and the ovarian stromal volume, measured using a three-dimensional (3D) ultrasound scan, with biochemical indices of PCOS. METHODS: Twenty-three infertile women (mean age +/- SD: 31 +/- 3.1 years; range: 26-37) with clomiphene citrate-resistant PCOS were examined. Early follicular phase (days 2-4) serum FSH, LH and testosterone concentrations were measured following a withdrawal bleed. Total ovarian volume, stromal volume, pre-antral follicle (<10 mm) number and total follicular volume were measured by 3D transvaginal ultrasound. RESULTS: Total ovarian volume, follicular volume and follicle number correlated positively with serum FSH and LH, but not testosterone, concentrations. Ovarian stromal volume correlated strongly with total ovarian volume only, but not with serum FSH, LH or testosterone concentrations. CONCLUSIONS: These findings demonstrate an association of the total ovarian volume, pre-antral follicle number and total follicular volume with some of the biochemical indices of PCOS, but no association was observed between ovarian stromal volume and these indices.     

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.     

High reproducibility of serum anti-Mullerian hormone measurements suggests a multi-staged follicular secretion and strengthens its role in the assessment of ovarian follicular status

BACKGROUND: Our aim was to compare the intercycle reproducibility of serum anti-Mullerian hormone (AMH) measurements with that of other markers of ovarian follicular status. METHODS: Forty-seven normo-ovulatory, infertile women underwent serum AMH, inhibin B, estradiol and FSH measurements and early antral follicle (2-12 mm in diameter) counts by transvaginal ultrasound on cycle day 3 during three consecutive menstrual cycles. Reproducibility of measurements was estimated using intra-class correlation coefficient (ICC) calculation. We also assessed the number of replicate measurements theoretically needed to reach satisfactory reliability of results. RESULTS: Serum AMH showed significantly higher reproducibility (ICC, 0.89; 95% confidence interval, 0.83-0.94) than inhibin B (0.76; 0.66-0.86; P < 0.03), estradiol (0.22; 0.03-0.41; P < 0.0001) and FSH levels (0.55; 0.39-0.71; P < 0.01), and early antral follicle counts (0.73; 0.62-0.84; P < 0.001), and reached satisfactory reliability with a single measurement. CONCLUSIONS: The improved cycle-to-cycle consistency of AMH as compared with other markers of ovarian follicular status is in keeping with its peculiar production by follicles at several developmental stages and further supports its role as a cost-effective, reliable marker of ovarian fertility potential.