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.     

Correlation between the Serum Luteinizing Hormone to Folliclestimulating Hormone Ratio and the Anti-Müllerian Hormone Levels in Normo-ovulatory Women

Serum anti-Müllerian hormone (AMH) levels are regarded as an age-specific marker for predicting the ovarian reserve in women of reproductive age. Some studies have shown that the luteinizing hormone (LH)/follicle stimulating hormone (FSH) ratio can be used as a predictor of ovarian reserve. The purpose of this study was to assess the variation of LH/FSH ratio with aging and to evaluate the correlation between serum LH/FSH ratio and AMH levels as a predictor of the ovarian reserve in normo-ovulatory women. We retrospectively analyzed the day 3 serum hormone levels in 1,251 patients (age range: 20-50 yr) between January 2010 and January 2011. We divided the patients into 6 groups according to their age. Relation between serum AMH level and LH/FSH ratio was analyzed statistically. The serum AMH level was inversely correlated with age (r = -0.400, P < 0.001). A significant negative correlation was found between serum LH/FSH ratio and age (r = -0.213, P < 0.001). There was a significant partial correlation between serum LH/FSH ratio and AMH level when adjusted by age (r = 0.348, P < 0.001). The LH/FSH ratio could be considered as a useful marker for the ovarian reserve and could be applied to the clinical evaluation with AMH.     

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 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.     

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.     

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 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.     

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.     

Circhoral fluctuations of serum total renin, inhibin and related hormones around the mid-cycle in normal human females.

Total renin and inhibin are secreted by the ovary. Although luteinizing hormone (LH) and/or follicle stimulating hormone (FSH) may stimulate their secretion, the close relationship between fluctuations of gonadotrophins, oestradiol, progesterone, renin and inhibin during the cycle is still conjectural. To investigate the temporal relationship between the short-term fluctuations in the circulating concentrations of LH and FSH and the ovarian hormones (oestradiol, progesterone, renin and inhibin), blood samples were collected at 15-min intervals for 6 h from 15 normal women in the late follicular (n = 4), early luteal (n = 5) or luteal (n = 6) phases of the menstrual cycle. LH levels showed the well-known pulsatile secretion with decreasing frequency and increasing relative amplitude from the late follicular to the luteal phase. Progesterone and oestradiol serum levels were pulsatile, 25% and 35-50% of which were linked to LH pulses, with time lags of 30 and 12-15 min respectively. Renin levels presented significant pulses, 26% of which were related to LH pulses with a time lag of less than 10 min; no coincidence was found between renin and oestradiol pulses. Inhibin levels presented only scattered pulses of small amplitude, which were unrelated to LH or FSH. These results show that, besides the LH-related pulses, pulsatile secretion of some ovarian hormones (oestradiol, progesterone and renin) may also occur independently of LH pulses and may be unrelated to one another. Moreover, contrary to the other ovarian hormones, inhibin seems to follow a tonic, not a pulsatile type of secretion around the mid-cycle.     

Inhibin A and B in adolescents and young adults with Turner's syndrome and no sign of spontaneous puberty

BACKGROUND: The aim of this study was to assess levels of inhibin A and B, FSH and LH in Turner's syndrome (TS) without signs of spontaneous ovarian activity. METHODS: Twenty-four girls with TS (median age, 14.7 years) without signs of spontaneous ovarian function were included in the study. Sixty prepubertal girls (PPG) (10.3 years) that had not yet experienced menarche (all Tanner stage 1), and 34 pubertal girls (PG) (13.8 years) (Tanner stage 3-4), who were regularly menstruating, served as controls. The levels of inhibin A and B, FSH, LH, and pubertal stage were determined. RESULTS: Inhibin A was not detected in females with TS, or in almost all PPG (59 of 60) (P = not significant), and inhibin B in TS females, while most PPG produced inhibin B (53 of 60, P < 0.0005). FSH and LH were elevated in TS, but with overlapping values. In follow-up samples in TS, three of twenty-four females showed detectable levels of inhibin A and/or B. In one of these, 6 serial samples were available. At 20 years this patient had a high level of LH and FSH, which declined, and concurrently inhibin A and inhibin B rose, only later to decrease, when FSH and LH started to rise again. In comparison with PG baseline levels of inhibin A and B were lower in TS, with inhibin A detectable in 23 of 34, and inhibin B detectable in 32 of 34 PG. Levels of FSH and LH were also different, although with overlapping values. CONCLUSION: The result raises the possibility that functional or partly functional ovaries are present in some females with TS, without apparent menstrual cycling.     

The excess in 2-5 mm follicles seen at ovarian ultrasonography is tightly associated to the follicular arrest of the polycystic ovary syndrome

BACKGROUND: We previously hypothesized that the excess of 2–5 mmfollicles seen at ovarian ultrasonography might be involvedin the follicular arrest (FA) of polycystic ovary syndrome (PCOS),independently from the main putative contributors of FA, namelyhyperandrogenism and hyperinsulinism. METHODS: A multivariate statistical analysis was applied retrospectivelyto clinical, biological and ultrasound data that were consecutivelycollected during 5 years in 457 patients with polycystic ovariesand in 188 age-matched non-hyperandrogenic and regularly cyclingcontrols without PCO at ultrasound. RESULTS: Stepwise discriminant analysis indicated that in PCOS the 2–5 mmfollicle number (FN) gave the strongest correlation to severityof the FA, followed by age and then by fasting insulin level.The other variables [waist circumference (WC), 6–9 mmFN, serum testosterone, FSH, LH and ovarian area] were rejectedby the analysis. Multiple linear regression indicated a significantand independent negative relationship between the 2–5and 6–9 mm FN in the PCOS (r = – 0.186, P <0.01) and control groups (r = – 0.281, P < 0.01). InPCOS only, the 6–9 mm FN was negatively and independentlyrelated to the WC (r = – 0.108, P < 0.05). CONCLUSIONS: The size of the 2–5 mm follicle pool is an independentand important contributor to the FA of PCOS. This result couldbe explained by an exaggerated physiological inhibitory effectfrom this pool on the terminal follicle growth. The metabolicderangement of PCOS that also contributes to the FA would actthrough a different mechanism.     

The effects of chemotherapy and long-term gonadotrophin suppression on the ovarian reserve in premenopausal women with breast cancer

BACKGROUND: Reproductive function following cancer treatment is of increasing importance with improving survival rates. We therefore assessed the markers of the ovarian reserve in premenopausal women, to investigate and compare the effects of chemotherapy and long-term gonadotrophin withdrawal on ovarian function. METHODS: Fifty premenopausal (age range 28-52 years) women with early breast cancer were recruited. Serum hormone and ovarian ultrasound measurements were taken before treatment and at intervals up to 1 year during chemotherapy or gonadotrophin suppressive therapy. RESULTS: Pretreatment samples indicated a fall in anti-Müllerian hormone (AMH) concentration with age before changes in other hormone concentrations. AMH concentration showed a rapid and marked fall during chemotherapy, with undetectable concentrations in many women (P<0.0001). Inhibin B concentration showed a lesser fall (P<0.0001), whereas estradiol (E2) concentrations were maintained. Both antral follicle count (AFC) and ovarian volume fell (P<0.0001 and P<0.05 respectively). Regimens containing taxanes in addition to cyclophosphamide showed increased gonadotoxicity. Gonadotrophin suppression resulted in expected falls in E2 (P<0.05) and inhibin B (P<0.001) levels, but also resulted in a delayed fall in AMH level after 6 months (P<0.0001). CONCLUSIONS: These data confirm the value of AMH concentration as an early indicator of ovarian ageing including assessment of chemotherapy-induced ovarian follicle loss. FSH and AMH concentration measurements may be useful for the comparison of ovarian toxicity of different chemotherapy regimens.     

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.     

Stable serum levels of anti-Müllerian hormone during the menstrual cycle: a prospective study in normo-ovulatory women

BACKGROUND: Anti-Müllerian hormone (AMH), secreted by the granulosa cells of preantral and small antral follicles, has been described as a potential marker of the ovarian reserve. The aim of this prospective study is to investigate the variations of AMH during the menstrual cycle in a young selected population of normo-ovulatory women and to analyse the correlation with other cyclic hormones. METHODS: Twenty healthy volunteers from 19 to 35 years old, with regular menstrual cycles (26-31 days), normal ovulation (day 10-16), normal hormonal profile and normal body mass index (18-26 kg/m2) were recruited. AMH, inhibin B, LH, FSH, estradiol and progesterone were measured on days 3, 7, 10, 11, 12, 13, 14, 15, 16, 18, 21 and 25 of a spontaneous cycle. RESULTS: AMH serum levels, either expressed by cycle day or aligned according to the ovulation day, did not show any significant variations during the menstrual cycle. CONCLUSIONS: No significant fluctuation of the AMH level during the menstrual cycle was observed. Therefore, this hormone is particularly interesting for clinical evaluation of the ovarian reserve as it may be used at any time during the cycle.     

Serum anti-Mullerian hormone throughout the human menstrual cycle

BACKGROUND: The anti-Mullerian hormone (AMH) is a member of the transforming growth factor (TGF) superfamily. In women, AMH serum levels can be almost undetectable at birth, with a subtle increase noted after puberty. Data are lacking with regard to menstrual cycle day-to-day fluctuations. This longitudinal study was designed to investigate the pattern of secretion of AMH throughout the menstrual cycle in regularly cycling women. METHODS: Twelve healthy female subjects aged 18-24 years participated in this study. Blood samples were taken every other day throughout one menstrual cycle. Serum FSH, LH, estradiol (E(2)), progesterone, inhibin B and AMH levels were assayed by double-antibody radioimmunoassay using commercial kits. RESULTS: Serum AMH in the first days of the menstrual cycle (days -14 to -12) was 3.8 +/- 1.2 ng/ml (mean +/- SD). No significant changes were observed in serum AMH levels throughout the menstrual cycle. The highest value was 3.9 +/- 1.3 ng/ml at day -12 and the lowest value was 3.4 +/- 1.1 ng/ml at day 14, and the difference was not significant. CONCLUSION: In this study, we demonstrated that serum AMH levels do not change significantly throughout the menstrual cycle. Hence, AMH exhibits a relatively stable expression during the menstrual cycle, making it an attractive determinant of ovarian activity.     

Depletion of ovarian reserve in young women after treatment for cancer in childhood: detection by anti-Müllerian hormone, inhibin B and ovarian ultrasound

BACKGROUND: Treatment of cancer during childhood may result in loss of primordial follicles from the ovary. METHODS: Ten cancer survivors and 11 controls with regular menstrual cycles, in addition to 10 cancer survivors and 10 controls taking the combined oral contraceptive pill (COCP) were recruited. Subjects were investigated on days 3-5 of a menstrual cycle, or week 3 of COCP administration before and 24 h after administration of 225 IU FSH. RESULTS: Serum FSH levels were elevated in cancer survivors with regular menstrual cycles (7.5 +/- 1.4 versus 4.2 +/- 0.3 IU/l; P = 0.02), while anti-Müllerian hormone (AMH) levels were lower (13.0 +/- 3.0 versus 21.0 +/- 3.4 pmol/l; P < 0.05). Other hormone levels were unchanged. Ovarian volume was smaller in cancer survivors than controls (3.0 +/- 0.5 versus 5.0 +/- 0.8 ml; P < 0.05), but antral follicle count (AFC) was similar. During COCP administration, inhibin B remained undetectable in six cancer survivors after FSH administration, whereas all controls showed a rise in inhibin B levels. The AFC was lower in cancer survivors than in controls (4.2 +/- 0.8 versus 7.2 +/- 0.8; P = 0.02). Ovarian volume was low in both groups, but did not differ between them. CONCLUSIONS: The study results demonstrate both hormonal and biophysical evidence of partial loss of the ovarian reserve in young cancer survivors. This was detected both in women with normal menstrual cycles and during COCP administration.     

Basal level of anti-Müllerian hormone is associated with oocyte quality in stimulated cycles

BACKGROUND: Serum anti-Müllerian hormone (AMH) levels provide a powerful means for predicting ovarian response, which is reflected not only by the size of the primordial follicle pool but also by the quality of the oocytes. Considering a mutual interdependence between AMH-expressing somatic cells and gametes, this prospective morphological study was set up to evaluate whether extreme AMH levels represent diminished oocyte quality and developmental incompetence. METHODS: A total of 141 consecutive ICSI patients were subdivided into three groups using the 25th and 75th percentiles of the serum AMH levels (cycle day 3). In these three groups, morphology of all oocytes and fertilization rate, embryo quality and blastocyst formation were evaluated, and FSH, LH and estradiol (E(2)) levels were also measured. RESULTS: Cycle cancellation rate was correlated with AMH levels (P < 0.05). AMH groups 1 (<1.66 ng/ml) and 3 (>4.52 ng/ml) showed oocytes of lower quality [dark central granulation, aggregation of smooth endoplasmic reticulum (sER)] compared with the median group 2 (1.66-4.52 ng/ml). Basal serum FSH did not allow for adequate prognosis in terms of gamete appearance. Fertilization and further cleavage up to blastocyst stage was not affected by AMH levels. CONCLUSIONS: AMH seems to be superior to FSH in predicting both oocyte number and quality.     

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.     

Low-dose exogenous FSH initiated during the early, mid or late follicular phase can induce multiple dominant follicle development

This prospective, randomized trial in normo-ovulatory women was designed to test whether administration of low-dose exogenous FSH initiated during the early, mid to late follicular phase can induce multiple dominant follicle development. Forty normal weight women (age 19-35 years, cycle length 25-32 days) participated. A fixed dose (75 IU/day) of recombinant FSH was started on either cycle day 3 (n = 13), 5 (n = 13) or 7 (n = 14) until the induction of ovulation with human chorionic gonadotrophin. Frequent transvaginal ultrasound scans and blood sampling were performed. Multifollicular growth occurred in all groups (overall in 60%), although day 7 starters showed less multifollicular growth. Age, cycle length and initial FSH and inhibin B concentrations were similar between subjects with single or multiple follicle development. However, for all women the lower the body mass index (BMI), the more follicles emerged (r = -0.44, P = 0.007). If multifollicular growth occurred, the length of the luteal phase was reduced (P = 0.002) and midluteal serum concentrations of LH (P = 0.03) and FSH (P = 0.004) were decreased and oestradiol (P = 0.002) and inhibin A (P = 0.01) were increased. In conclusion, interference with decremental serum FSH concentrations by administration of low dose FSH starting on cycle day 3, 5 or as late as day 7, is capable of disrupting single dominant follicle selection. The role of BMI in determining ovarian response suggests that differences in pharmacokinetics of exogenous FSH are involved. Multifollicular growth per se has a distinct effect on luteal phase characteristics. These observations may be relevant for the design of mild ovarian stimulation protocols.     

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.