This prospective study was designed to investigate whether anti-Müllerian hormone (AMH) levels at basal and ovulation triggering day are associated with ovarian response and pregnancy outcome for in vitro fertilization (IVF).
60 infertility women undergoing IVF were prospectively studied. On day 3 of the menstrual cycle (D3), measurements of AMH, inhibin B, FSH, LH, and E2 and ultrasound evaluation of antral follicle count (AFC) were performed. Serum AMH and inhibin B levels were remeasured on the day of hCG administration (DhCG). The outcome measures were the number of retrieved oocytes and clinical pregnancy.
Number of retrieved oocytes was statistically significant and correlated with D3 AMH, AFC, DhCG AMH, DhCG inhibin B, FSH, and age (r = 0.885, 0.874, 0.742, 0.732, −0.521, −0.385, respectively). Statistically significant differences were found between pregnant and non-pregnant women regarding D3 AMH and AFC. Multiple regression analysis for prediction of pregnancy showed D3 AMH to be a good predictor of clinical pregnancy.
AMH correlates better than age, FSH, and inhibin B with the number of retrieved oocytes. Serum basal AMH may offer a better prognostic value for clinical pregnancy than other currently available markers of IVF outcome in our preliminary study.
Anti-Müllerian hormone; IVF; Ovarian reserve; Pregnancy
The aim of this study was to investigate whether serum levels of anti-Müllerian hormone (AMH) and inhibin B at ovulation triggering day correlate with the number of immature oocytes obtained from stimulated in vitro fertilization (IVF) cycles. Fiftynine consecutive cycles of ovarian hyperstimulation and IVF were selected from 45 women who had tubal (n=18) or unexplained infertility (n=27) and obtained at least one oocyte. Serum levels of AMH and inhibin B at ovulation triggering day were measured by enzyme-linked immunosorbent assay (ELISA). Univariate analysis and multiple regressions revealed that serum AMH or inhibin B levels were significantly correlated with immature oocyte count and the correlation coefficients were higher compared to the mature oocyte count. Serum AMH and inhibin B levels on triggering day seems to be more closely related with the immature oocyte count and thus could be good predictors to determine the immature oocyte count in IVF cycle.
Anti-Müllerian Hormone; Inhibin B; Immature Oocyte; Fertilization In Vitro
BACKGROUND AND OBJECTIVES:
The prediction of in vitro fertilization (IVF) outcomes by anti-Müllerian hormone (AMH) measurement is getting increasing attention from clinicians. This study compares the relationship between serum or intrafollicular AMH levels and IVF outcomes in women with and without polycystic ovary syndrome (PCOS).
This prospective study was carried out in two university-based fertility clinics. Serum samples were collected on cycle day 3 and follicular fluid (FF) was collected on the day of oocyte retrieval from 26 women with PCOS and 42 normo-ovulatory controls. AMH levels were measured in the samples using immunoenzymatic assay. The relationship between serum or FF AMH levels and IVF outcomes, including number of oocytes retrieved, oocyte maturation rate, fertilization rate, implantation rate, high quality grade embryo rate, and biochemical and clinical pregnancy rates were further assessed.
Median serum basal AMH and FF AMH levels were significantly higher in the PCOS group as compared to controls, the values being 14.2 ng/mL vs. 3.2 ng/mL (P<.001) and 8.2 ng/g protein vs. 4.7 ng/g protein (P<.01), respectively. In both groups, serum basal AMH levels showed a positive correlation with number of oocytes retrieved (r=0.323; P=.037 in control vs. r=0.529; P=.005 in PCOS). In the control group, there was a positive relationship between serum basal AMH levels and percentage of matured oocytes (r = 0.331; P=.032) and implantation rate (r=0.305; P=.05).
Serum basal, and not intrafollicular, AMH levels may be a good predictive factor for quantitative and qualitative IVF outcomes in normo-ovulatory, but not in PCOS patients.
In 2009 anti-Müllerian hormone (AMH) assay was approved for clinical use in Korea. This study was performed to determine the reference values of AMH for predicting ovarian response to controlled ovarian hyperstimulation (COH) using the clinical assay data.
One hundred sixty-two women who underwent COH cycles were included in this study. We collected data on age, basal AMH and FSH levels, total dose of gonadotropins, stimulation duration, and numbers of oocytes retrieved and fertilized. Blood samples were obtained on cycle day 3 before gonadotropin administration started. Serum AMH levels were measured at a centralized clinical laboratory center. The correlation between the AMH level and COH outcomes and cut-off values for poor and high response after COH was analyzed.
Concentration of AMH was significantly correlated with the number of oocytes retrieved (OPU; r=0.700, p<0.001). The mean±SE serum AMH levels for poor (OPU≤3), normal (4≤OPU≤19), and high (OPU≥20) response were 0.94±0.15 ng/mL, 2.79±0.21 ng/mL, and 6.94±0.90 ng/mL, respectively. The cut-off level, sensitivity and specificity for poor and high response were 1.08 ng/mL, 85.8%, and 78.6%; and 3.57 ng/mL, 94.4%, and 83.3%, respectively.
Our data present clinical reference values of the serum AMH level for ovarian response in Korean women. The serum AMH level could be a clinically useful predictor of ovarian response to COH.
Anti-Müllerian hormone; Ovarian response; Outcome predictor; Controlled ovarian hyperstimulation
To evaluate predictive role of day–3 serum anti-Müllerian hormone (AMH) levels and antral follicle count (AFC) in ovarian hyperstimulation syndrome (OHSS) in patients undergoing IVF/ICSI cycles.
Materials and methods
Forty-one women with moderate/severe OHSS and 41 age matched women without OHSS were compared to evaluate the predictive value of certain risk factors for OHSS. AFC, and E2, FSH, LH, AMH, inhibin-B levels measured on day 3 of the menstrual cycle before controlled ovarian hyperstimulation.
Mean FSH was significantly lower (p < 0.0001); and mean LH, AFC and AMH were significantly higher in women with OHSS compared to women without OHSS (p = 0.049, p < 0.0001 and p < 0.0001, respectively). There was no significant difference in inhibin B (p = 0.112) and estradiol (p = 0.706) between the groups. The ROC area under curve (AUC) for AMH presented the largest AUC among the listed risk factors. AMH (AUC = 0.87) and AFC (AUC = 0.74) had moderate accuracy for predicting OHSS while Inhibin B (AUC = 0.58) and LH (AUC = 0.61) had low accuracy. The cut-off value for AMH 3.3 ng/mL provided the highest sensitivity (90%) and specificity (71%) for predicting OHSS. It’s positive (PPV) and negative predictive values (NPV) were 61% and 94%, respectively. The cut-off value for AFC was 8 with 78% sensitivity, 65% specificity, 52% PPV and 86% NPV.
Measurement of basal serum AMH and AFC can be used to determine the women with high risk for OHSS.
Antimullerian hormone; Ovarian hyperstimulation syndrome; Antral follicle count
Serum anti-Mullerian hormone (AMH) is currently considered the best marker of ovarian reserve and of ovarian responsiveness to gonadotropins in in-vitro fertilization (IVF). AMH assay, however, is not available in all IVF Units and is quite expensive, a reason that limits its use in developing countries. The aim of this study is to assess whether the "ovarian sensitivity index" precisely reflects AMH so that this index may be used as a surrogate for AMH in prediction of ovarian response during an IVF cycle.
AMH serum levels were measured in 61 patients undergoing IVF with a "long" stimulation protocol including the GnRH agonist buserelin and recombinant follicle-stimulating hormone (rFSH). Patients were divided into four subgroups according to the percentile of serum AMH and their ovarian stimulation was prospectively followed. Ovarian sensitivity index (OSI) was calculated dividing the total administered FSH dose by the number of retrieved oocytes.
AMH and OSI show a highly significant negative correlation (r = -0.67; p = 0.0001) that is stronger than the one between AMH and the total number of retrieved oocytes and than the one between AMH and the total FSH dose.
OSI reflects quite satisfactory the AMH level and may be proposed as a surrogate of AMH assay in predicting ovarian responsiveness to FSH in IVF. Being very easy to calculate and costless, its use could be proposed where AMH measurement is not available or in developing countries where limiting costs is of primary importance.
The aim of this study was to investigate whether anti-Mullerian hormone (AMH) levels could be predict ovarian poor/hyper response and IVF cycle outcome.
Between May 2010 and January 2011, serum AMH levels were evaluated with retrospective analysis. Three hundred seventy infertile women undergoing 461 IVF cycles between the ages of 20 and 42 were studied. We defined the poor response as the number of oocytes retrieved was equal or less than 3, and the hyper response as more than 25 oocytes retrieved. Serum AMH was measured by commercial enzyme-linked immunoassay.
The number of oocytes retrieved was more correlated with the serum AMH level (r=0.781, p<0.01) than serum FSH (r=-0.412, p<0.01). The cut-off value of serum AMH levels for poor response was 1.05 ng/mL (receiver operating characteristic [ROC] curves/area under the curve [AUC], ROCAUC=0.85, sensitivity 74%, specificity 87%). Hyper response cut-off value was 3.55 ng/mL (ROCAUC=0.91, sensitivity 94%, specificity 81%). When the study group was divided according to the serum AMH levels (low: <1.05 ng/mL, middle: 1.05 ng/mL - 3.55 ng/mL, high: >3.55 ng/mL), the groups showed no statistical differences in mature oocyte rates (71.6% vs. 76.5% vs. 74.8%) or fertilization rates (76.9% vs. 76.6% vs. 73.8%), but showed significant differences in clinical pregnancy rates (21.7% vs. 24.1% vs. 40.8%, p=0.017).
The serum AMH level can be used to predict the number of oocytes retrieved in patients, distinguishing poor and high responders.
Anti-Müllerian Hormone; Ovarian Response; Poor Response; Hyper Reponse; In Vitro Fertilization; Human
Chronological age and oocyte yield are independent determinants of live birth in assisted conception. Anti-Müllerian hormone (AMH) is strongly associated with oocyte yield after controlled ovarian stimulation. We have previously assessed the ability of AMH and age to independently predict live birth in an Italian assisted conception cohort. Herein we report the external validation of the nomogram in 822 UK first in vitro fertilization (IVF) cycles.
Retrospective cohort consisting of 822 patients undergoing their first IVF treatment cycle at Glasgow Centre for Reproductive Medicine. Analyses were restricted to women aged between 25 and 42 years of age. All women had an AMH measured prior to commencing their first IVF cycle. The performance of the model was assessed; discrimination by the area under the receiver operator curve (ROCAUC) and model calibration by the predicted probability versus observed probability.
Live births occurred in 29.4% of the cohort. The observed and predicted outcomes showed no evidence of miscalibration (p = 0.188). The ROCAUC was 0.64 (95% CI: 0.60, 0.68), suggesting moderate and similar discrimination to the original model. The ROCAUC for a continuous model of age and AMH was 0.65 (95% CI 0.61, 0.69), suggesting that the original categories of AMH were appropriate.
We confirm by external validation that AMH and age are independent predictors of live birth. Although the confidence intervals for each category are wide, our results support the assessment of AMH in larger cohorts with detailed baseline phenotyping for live birth prediction.
AMH; Live birth prediction; IVF
Analysis of anti-Müllerian hormone (AMH) is becoming of recognized importance in reproductive medicine, but assays are not standardized. We have evaluated the correlation between the new Gen II ELISA kit (Beckman-Coutler) and the older ELISA kits by Immunotech (IOT) and Diagnostic Systems Laboratories (DSL).
A total of 56 archived serum samples from patients with subfertility or reproductive endocrine disorders were retrieved and assayed in duplicate using the three AMH ELISA kits . The samples covered a wide range of AMH concentrations (1.9 to 142.5 pmol/L).
We observed good correlations between the new (AMH Gen II) and old AMH assay kits by IOT and DSL (R2 = 0.971 and 0.930 respectively). The regression equations were AMH (Gen II) = 1.353 × AMH (IOT) + 0.051 and AMH (Gen II) = 1.223 × AMH (DSL) – 1.270 respectively.
AMH concentrations using the Gen II kit are slightly higher than those from the IOT and DSL kits. Standardization of assay results worldwide is urgently required but this analysis facilitates the interpretation of values obtained historically and in future studies using any of the 3 assays available. Meanwhile, adapting clinical cut-offs from previously published work by direct conversion is not recommended.
Anti-Mullerian hormone; ELISA kit
Granulosa cell tumors (GCTs) comprise 2–5% of ovarian tumors. Serum Müllerian Inhibiting Substance (MIS, also known as anti-Müllerian Hormone, or AMH) levels have been validated as a marker of GCT recurrence and progression. There has been little correlation between serum MIS/AMH levels several clinical parameters in GCTs, including tumor burden. We have performed a retrospective review correlating aggregate tumor mass as reported by pathologic examination or by radiology with serum MIS/AMH levels drawn on the date of examination.
We retrospectively identified 32 GCT patients at our institution over the last 15 years who had serum MIS/AMH measurements. Patients who had serum MIS/AMH measurements within three days of surgery or on the same day as abdominal computerized tomography scan (CT) or magnetic resonance imaging (MRI) were further evaluated.
We found a significant direct correlation between patient serum MIS/AMH levels and gross aggregate tumor mass determined by pathology (slope=15.4±6.06, r=0.65, p<0.04) or by radiographic aggregate tumor mass for all data points identified (slope=0.07±0.03, r=0.33, p<0.04) and after correcting for selection bias (slope=1.45±0.17, r=0.93, p<0.01). We also identified a significant difference between serum MIS/AMH levels between samples drawn the same day as negative and positive abdominal CT or MRI scans (8.16±1.54 vs. 158.7±32.2 ng/ml, p<0.0001).
These data indicate a significant direct correlation between serum MIS/AMH levels and both gross and radiographic aggregate tumor mass in GCT patients. Together with the current literature, the present data argues for a more prominent role for serum MIS/AMH in the management of GCTs.
The role of serum anti-Müllerian hormone (AMH) as predictor of in-vitro fertilization outcomes has been much debated. The aim of the present study is to investigate the practicability of combining serum AMH level with biological age as a simple screening method for counseling IVF candidates of advanced reproductive age with potential poor outcomes prior to treatment initiation.
A total of 1,538 reference patients and 116 infertile patients aged greater than or equal to 40 years enrolled in IVF/ICSI cycles were recruited in this retrospective analysis. A reference chart of the age-related distribution of serum AMH level for Asian population was first created. IVF/ICSI patients aged greater than or equal to 40 years were then divided into three groups according to the low, middle and high tertiles the serum AMH tertiles derived from the reference population of matching age. The cycle outcomes were analyzed and compared among each individual group.
For reference subjects aged greater than or equal to 40 years, the serum AMH of the low, middle and high tertiles were equal or lesser than 0.48, 0.49-1.22 and equal or greater than 1.23 ng/mL respectively. IVF/ICSI patients aged greater than or equal to 40 years with AMH levels in the low tertile had the highest cycle cancellation rate (47.6%) with zero clinical pregnancy. The nadir AMH level that has achieved live birth was 0.56 ng/mL, which was equivalent to the 36.4th percentile of AMH level from the age-matched reference group. The optimum cut-off levels of AMH for the prediction of nonpregnancy and cycle cancellation were 1.05 and 0.68 ng/mL, respectively.
Two criteria: (1) age greater than or equal to 40 years and (2) serum AMH level in the lowest tertile (equal or lesser than 33.3rd percentile) of the matching age group, may be used as markers of futility for counseling IVF/ICSI candidates.
Objective. To investigate the endocrine and/or clinical characteristics of women with low anti-Müllerian hormone (AMH) that could improve the accuracy of IVF outcome prediction based on the female age alone prior to the first GnRH antagonist IVF cycle. Methods. Medical records of 129 patients with low AMH level (<6.5 pmol/L) who underwent their first GnRH antagonist ovarian stimulation protocol for IVF/ICSI were retrospectively analyzed. The main outcome measure was the area under the ROC curve (AUC-ROC) for the models combining age and other potential predictive factors for the clinical pregnancy. Results. Clinical pregnancy rate (CPR) per initiated cycles was 11.6%. For the prediction of clinical pregnancy, DHEAS and age showed AUC-ROC of 0.726 (95%CI 0.641–0.801) and 0.662 (95%CI 0.573–0.743), respectively (P = 0.522). The predictive accuracy of the model combining age and DHEAS (AUC-ROC 0.796; 95%CI 0.716–0.862) was significantly higher compared to that of age alone (P = 0.013). In patients <37.5 years with DHEAS >5.7 pmol/L, 60% (9/15) of all pregnancies were achieved with CPR of 37.5%. Conclusions. DHEAS appears to be predictive for clinical pregnancy in younger women (<37.5 years) with low AMH after the first GnRH antagonist IVF cycle. Therefore, DHEAS-age model could refine the pretreatment counseling on pregnancy prospects following IVF.
Anti-Müllerian hormone (AMH) is secreted by immature testicular Sertoli cells. Clinical studies have demonstrated a negative correlation between serum AMH and testosterone in puberty but not in the neonatal period. We investigated AMH regulation using mouse models mimicking physiopathological situations observed in humans. In normal mice, intratesticular, not serum, testosterone repressed AMH synthesis, explaining why AMH is downregulated in early puberty when serum testosterone is still low. In neonatal mice, AMH was not inhibited by intratesticular testosterone, due to the lack of expression of the androgen receptor in Sertoli cells. We had shown previously that androgen-insensitive patients exhibit elevated AMH in coincidence with gonadotropin activation. In immature normal and in androgen-insensitive Tfm mice, follicle stimulating hormone (FSH) administration resulted in elevation of AMH levels, indicating that AMH secretion is stimulated by FSH in the absence of the negative effect of androgens. The role of meiosis on AMH expression was investigated in Tfm and in pubertal XXSxrb mice, in which germ cells degenerate before meiosis. We show that meiotic entry acts in synergy with androgens to inhibit AMH. We conclude that AMH represents a useful marker of androgen and FSH action within the testis, as well as of the onset of meiosis.
Follicle stimulating hormone (FSH) and anti-Müllerian hormone (AMH) represent the two most frequently utilized laboratory tests in determining ovarian reserve (OR). This study determined the clinical significance of their concordance and discordance in female infertility patients.
We investigated 366 consecutive infertility patients (350 reached IVF), excluding women with polycystic ovarian syndrome (PCOS). They were considered to have normal FSH and AMH if values fell within age-specific (as-) 95% confidence intervals (CI), and to suffer from diminished ovarian reserve (DOR) if FSH exceeded and/or AMH fell below those. The two hormones, thus, could be concordant (Group I), both normal (IA) or abnormal (IB), show normal AMH/abnormal FSH (Group II) or normal FSH/abnormal AMH (Group III). Oocyte yields, stratified for age categories, were then studied in each group as reflection of OR.
Oocyte yields significantly decreased from groups IA to II to III and IB. Predictive values of as-FSH/AMH patterns changed, however, at different ages. Except at very young and very old ages, normal as-AMH better predicted higher oocytes yields than normal as-FSH, though above age 42 years normal as-FSH predicts good oocyte yields even with abnormally low AMH. Under age 42 discrepancies between as- FSH and as-AMH remain similarly predictive of oocyte yields at all ages.
Concordances and discordances between as-FSH and as-AMH improve OR assessments and predictability of oocyte yields in IVF.
Recently, serum anti-Müllerian hormone (AMH) has been used as a good marker of ovarian response during in vitro fertilization (IVF). However, in the clinical setting, we felt that ovarian response was clearly different by age with the same AMH level. Then in this study we evaluated the relationship between serum AMH, age and parameters related to ovarian response and compared these parameters in regard to age within serum AMH-matched group.
Methods and results
The relationship of these parameters were evaluated retrospectively in patients undergoing their first IVF cycle under a GnRH agonist flare up protocol (n = 456) between October 2008 and October 2010 in our clinic. To understand the relations between variables described above, principal component analysis (PCA) was performed. PCA revealed patients’ age was at the different dimension from serum AMH and other variables. Therefore at first we segregated all patients into Low, Normal and High responder groups by their serum AMH using cut-off value of receiver operator characteristics curve analysis. Secondary, we divided each responder group into four subgroups according to patients’ age. The high aged subgroups required a significantly higher dose of gonadotropin and a longer duration of stimulation; however, they had significantly lower peak E2 and a smaller number of total oocytes as well as M2 oocytes compared to the low aged subgroups.
The influence of aging on the ovarian response was clearly seen in all groups; the ovarian response tended to decrease as patients’ age increased with the same AMH level. Therefore serum AMH in combination with age is a better indicator than AMH alone.
AMH; Anti-Müllerian hormone; Age; IVF; GnRH agonist flare up protocol; Ovarian response
To determine the age specific serum anti-Müllerian hormone (AMH) reference values in Korean women with regular menstruation.
Between May, 2010 and January, 2011, the serum AMH levels were evaluated in a total of 1,298 women who have regular menstrual cycles aged between 20 and 50 years. Women were classified into 6 categories by age: 20-31 years, 32-34 years, 35-37 years, 38-40 years, 41-43 years, above 43 years. Measurement of serum AMH was measured by commercial enzyme-linked immunoassay.
The serum AMH levels correlated negatively with age. The median AMH level of each age group was 4.20 ng/mL, 3.70 ng/mL, 2.60 ng/mL, 1.50 ng/mL, 1.30 ng/mL, and 0.60 ng/mL, respectively. The AMH values in the lower 5th percentile of each age group were 1.19 ng/mL, 0.60 ng/mL, 0.42 ng/mL, 0.27 ng/mL, 0.14 ng/mL, and 0.10 ng/mL, respectively.
This study determined reference values of serum AMH in Korean women with regular menstruation. These values can be applied to clinical evaluation and treatment of infertile women.
Anti-Müllerian Hormone; Ovarian Reserve; Korean; Human
Early prenatal androgenization (PA) accelerates follicle differentiation and impairs embryogenesis in adult female rhesus monkeys (Macaca mulatta) undergoing FSH therapy for IVF. To determine whether androgen excess in utero affects follicle development over time, this study examines whether PA exposure, beginning at gestational days 40–44 (early treated) or 100–115 (late treated), alters the decline in serum anti-Mullerian hormone (AMH) levels with age in adult female rhesus monkeys and perturbs their ovarian response to recombinant human FSH (rhFSH) therapy for IVF.
Thirteen normal (control), 11 early-treated and 6 late-treated PA adult female monkeys had serum AMH levels measured at random times of the menstrual cycle or anovulatory period. Using some of the same animals, basal serum AMH, gonadotrophins and steroids were also measured in six normal, five early-treated and three late-treated PA female monkeys undergoing FSH therapy for IVF during late-reproductive life (>17 years); serum AMH also was measured on day of HCG administration and at oocyte retrieval.
Serum AMH levels in early-treated PA females declined with age to levels that were significantly lower than those of normal (P ≤ 0.05) and late-treated PA females (P ≤ 0.025) by late-reproductive life. Serum AMH levels positively predicted numbers of total/mature oocytes retrieved, with early-treated PA females having the lowest serum AMH levels, fewest oocytes retrieved and lowest percentage of females with fertilized oocytes that cleaved.
Based on these animals, early PA appears to program an exaggerated decline in ovarian reserve with age, suggesting that epigenetically induced hormonal factors during fetal development may influence the cohort size of ovarian follicles after birth.
prenatal androgens; anti-Mullerian hormone; aging; ovarian reserve; IVF
This study was designed to assess the capability of ovarian reserve markers, including baseline FSH levels, baseline anti-Müllerian hormone (AMH) levels, and antral follicle count (AFC), as predictors of live births during IVF cycles, especially for infertile couples with advanced maternal age and/or male factors.
A prospective cohort of 336 first IVF/ICSI cycles undergoing a long protocol with GnRH agonist was investigated. Patients with endocrine disorders or unilateral ovaries were excluded.
Among the ovarian reserve tests, AMH and age had a greater area under the receiving operating characteristic curve than FSH in predicting live births. Furthermore, AMH and age were the sole predictive factors of live births for women greater than or equal to 35 years of age; while AMH was the major determinant of live births for infertile couples with absence of male factors by multivariate logistic regression analysis. However, all the studied ovarain reserve tests were not preditive of live births for women < 35 years of age or infertile couples with male factors.
The serum AMH levels were prognostic for pregnancy outcome for infertile couples with advanced female age or absence of male factors. The predictive capability of ovarian reserve tests is clearly influenced by the etiology of infertility.
We recently associated ovarian FMR1genotypes and sub-genotypes with distinct ovarian aging patterns. How they impact older females is, however, unknown. We, therefore, investigated 217 consecutive first in vitro fertilization (IVF) cycles in women >40 assessing oocyte yields, stratified for better (anti-Müllerian hormone, AMH >1.05 ng/mL) or poorer (AMH≤1.05 ng/mL) functional reserve (FOR)). Mean age was 42.4±2.0 years, mean AMH 0.76±0.92 ng/mL and mean oocyte yield 5.3±5.4. Overall, and in women with better FOR, FMR1 did not affect oocyte yields. With poorer FOR (AMH≤1.05 ng/mL) women with het-norm/high, however, demonstrated higher oocyte yields (5.0±3.8) than those with het-norm/low sub-genotype 3.1±2.5; P = 0.03), confirmed after log conversion. Known associated with low FOR at young age, het-norm/high, thus, appears to preserve FOR into older age, and both het sub-genotypes appear to expand female reproductive lifespan into opposite directions.
The objective of the present commentary is to suggest that epidemiologists explore the use of anti-Müllerian hormone (AMH) as a new measurement tool in fecundability studies. The authors briefly summarize the advantages and limitations of the 3 current approaches to studies of fecundability. All 3 approaches involve the collection of time-to-pregnancy or attempt-time data, and most are limited to participants who plan their pregnancies. AMH is produced by ovarian follicles during their early growth stages and is measured clinically to assess ovarian reserve (the number of remaining oocytes). Unlike time to pregnancy, serum AMH level can be assessed regardless of pregnancy-attempt status. Measurements are not significantly affected by phase of the menstrual cycle, oral contraceptive use, or early pregnancy. The authors suggest that AMH measurement can be a valuable addition to traditionally designed fecundability studies. In addition, this hormone should be investigated as an independent measure of fecundability in studies that focus on exposures hypothesized to target the ovary.
anti-Mullerian hormone; epidemiology; fertility; research design
Others have studied acupuncture treatment for polycystic ovary syndrome (PCOS). Anti-müllerian hormone (AMH) is positively correlated with the ovarian follicle pool, thus making it a useful ovarian reserve measure. AMH is elevated in women with PCOS and has been suggested as a diagnostic tool. This study examined the impact of electroacupuncture on AMH concentration in women with PCOS. Seventy-one women with PCOS participated in a randomized, double-blind, sham-controlled clinical trial of acupuncture. Three longitudinal AMH samples over the 5-month protocol were compared with objective ovulation parameters primarily using nonparametric statistics. Results indicated that AMH levels in PCOS were higher than published norms in women without PCOS. There was no difference between the true and sham acupuncture arms in the change in AMH longitudinally. Baseline AMH, but not the change in AMH over time, was inversely correlated with ovulation and menstrual cycle frequencies in both arms combined (P < 0.001). In conclusion, AMH correlated with an increased likelihood of monthly ovulation, as expected from the literature on women without PCOS. The lack of difference by intervention in AMH was consistent with the underlying clinical trial. AMH may be clinically useful to predict which PCOS women are more likely to respond to an intervention.
The objective was to present a new ovarian response prediction index (ORPI), which was based on anti-Müllerian hormone (AMH) levels, antral follicle count (AFC) and age, and to verify whether it could be a reliable predictor of the ovarian stimulation response.
A total of 101 patients enrolled in the ICSI programme were included. The ORPI values were calculated by multiplying the AMH level (ng/ml) by the number of antral follicles (2–9 mm), and the result was divided by the age (years) of the patient (ORPI=(AMH x AFC)/Patient age).
The regression analysis demonstrated significant (P<0.0001) positive correlations between the ORPI and the total number of oocytes and of MII oocytes collected. The logistic regression revealed that the ORPI values were significantly associated with the likelihood of pregnancy (odds ratio (OR): 1.86; P=0.006) and collecting greater than or equal to 4 oocytes (OR: 49.25; P<0.0001), greater than or equal to 4 MII oocytes (OR: 6.26; P<0.0001) and greater than or equal to 15 oocytes (OR: 6.10; P<0.0001). Regarding the probability of collecting greater than or equal to 4 oocytes according to the ORPI value, the ROC curve showed an area under the curve (AUC) of 0.91 and an efficacy of 88% at a cut-off of 0.2. In relation to the probability of collecting greater than or equal to 4 MII oocytes according to the ORPI value, the ROC curve had an AUC of 0.84 and an efficacy of 81% at a cut-off of 0.3. The ROC curve for the probability of collecting greater than or equal to 15 oocytes resulted in an AUC of 0.89 and an efficacy of 82% at a cut-off of 0.9. Finally, regarding the probability of pregnancy occurrence according to the ORPI value, the ROC curve showed an AUC of 0.74 and an efficacy of 62% at a cut-off of 0.3.
The ORPI exhibited an excellent ability to predict a low ovarian response and a good ability to predict a collection of greater than or equal to 4 MII oocytes, an excessive ovarian response and the occurrence of pregnancy in infertile women. The ORPI might be used to improve the cost-benefit ratio of ovarian stimulation regimens by guiding the selection of medications and by modulating the doses and regimens according to the actual needs of the patients.
Ovarian response prediction index; Individualised controlled ovarian stimulation; Anti-Müllerian hormone; Antral follicles; Age
This study evaluated the predictive value of serum and follicular fluid (FF) concentrations of anti-Müllerian hormone (AMH) with respect to treatment outcome variables in an IVF cycle.
A retrospective analysis was performed with data from 731 normogonadotrophic women undergoing controlled ovarian stimulation after stimulation with highly purified menotrophin (HP-hMG) or rFSH following a long GnRH agonist protocol.
In both treatment groups, the serum AMH concentration at the start of the stimulation was significantly (P < 0.001) positively correlated with the serum levels of estradiol (HP-hMG: r = 0.45; rFSH: r = 0.55), androstenedione (HP-hMG: r = 0.50; rFSH: 0.49) and total testosterone (HP-hMG: r = 0.40; rFSH: r = 0.36) at the end of the stimulation as well as the number of oocytes retrieved (HP-hMG: r = 0.48; rFSH: r = 0.62), the AMH concentration in FF (HP-hMG: r = 0.55; rFSH: 0.61) and the serum progesterone concentration (HP-hMG: r = 0.39; rFSH: r = 0.50) at oocyte retrieval. For both treatments, serum AMH at the start of the stimulation was a good predictor of the need to increase or decrease the gonadotrophin dose on stimulation day 6 and of ovarian response below (<7 oocytes) or above (>15 oocytes) the target. No significant relationships were observed between serum AMH and embryo quality or ongoing pregnancy.
The serum AMH concentration at the start of the stimulation in IVF patients down-regulated with GnRH agonist in the long protocol revealed a positive relationship with ovarian response to gonadotrophins in terms of oocytes retrieved and accompanying endocrine response. AMH is a good predictor of the need for gonadotrophin-dose adjustment on stimulation day 6 for patients with a fixed starting dose, but a poor predictor of embryo quality and pregnancy chances in individual patients.
AMH; gonadotrophins; ovarian response; prediction; IVF cycle
To investigate the relationship between antimullerian hormone (AMH) and steroidogenesis in follicles of normoandrogenic ovulatory women undergoing FSH therapy for IVF-ET.
26 normoandrogenic ovulatory women. All women received GnRH analog and ovarian stimulation for IVF-ET.
Follicle fluid was aspirated at oocyte retrieval from the first follicle of each ovary.
Main Outcome Measures
Follicle fluid was assayed for AMH, E2, P, androstenedione, T, dihydrotestosterone, insulin and FSH.
Intrafollicular AMH levels positively and negatively correlated with E2 and FSH concentrations in follicles, respectively, causing a positive relationship between follicle fluid AMH levels and E2/FSH ratios as a measure of follicle sensitivity to FSH. A positive relationship also existed in follicles between AMH levels and E2/androgen ratios as a marker of aromatase activity.
AMH levels in follicles of IVF patients positively correlate with follicle sensitivity to FSH.
antimullerian hormone; mullerian-inhibiting substance; intrafollicular steroidogenesis; E2; IVF-ET
Describe anti-Müllerian hormone (AMH) variation across normal menstrual cycles.
Twenty regularly-menstruating women
Serum AMH and inhibin B assayed daily during one normal menstrual cycle
Main Outcome Measures
Intracycle variability of AMH and inhibin B
Data was classified into quartiles of AMH area-under-the-curve (AUCs). Mean AMH AUC was 15.7 ng/ml for Quartile 1 vs. 43.5, 80.9 and 144.9 ng/ml for Quartiles 2, 3 and 4. Mean AMH levels (ng/ml) were 0.67, 1.71, 3.02, and 5.33, respectively. There was no variation in Quartile 1 AMH rate of change from stochastic modeling, but in Quartiles 2–4, there were increased rates of change in days 2–7. Women in Quartile 1 had the lowest mean inhibin B (24.2 pg/ml vs. 44.3, 43.2, and 42.2 pg/ml) and had shorter menstrual cycles (24.6 days) than women in Quartiles 3 and 4 (28.2 and 28.4 days).
There were two menstrual cycle patterns of AMH. The “aging ovary” pattern included low AMH levels with little variation, lower inhibin B and shorter cycle lengths. The “younger ovary” pattern included higher AMH levels with significant variation days 2–7, suggesting that for women with AMH >1 ng/ml, the interpretation of AMH levels is contingent upon the day of the menstrual cycle on which specimen is obtained.
AMH; menstrual cycle variability; ovarian aging; reproductive aging; ovarian reserve