Serum anti-Müllerian hormone level as a predictor of poor ovarian response in in vitro fertilization patients

Purpose  

To evaluate the clinical value of day 3 serum anti-Müllerian hormone (AMH) compared with day 3 serum follicle-stimulating hormone (FSH) and human chorionic gonadotropin (hCG) day estradiol (E2) levels and antral follicle count (AFC) in the prediction of poor ovarian response in controlled ovarian hyperstimulation (COH).     

Anti-Müllerian hormone and antral follicle count for prediction of ovarian stimulation response in polycystic ovary syndrome

Abstract

Objective: To evaluate the ability of a combination of multiple ovarian reserve markers to predict ovarian stimulation response in polycystic ovary syndrome (PCOS).

Methods: On cycle Day 3 of 75 infertile patients with PCOS, serum follicle stimulating hormone (FSH), luteinizing hormone (LH), and anti-Müllerian hormone (AMH) were measured, and antral follicle count (AFC) and ovarian volume (OV) were evaluated by transvaginal sonography (TVS). All patients underwent the same mild ovarian stimulation protocol using clomiphene citrate and highly purified FSH. Ovulation was monitored by TVS and confirmed by midluteal serum progesterone level.

Results: AMH, AFC, and “ovulation index” [OI, serum AMH (ng/ml)?×?bilateral AFC] were significantly lower in the ovulatory group (n?=?57, 76%) compared with the anovulatory group, whereas LH, FSH, LH/FSH ratio, and OV were not significantly different. Using receiver-operating characteristic curve analysis, the OI at a cutoff value of “85” had a sensitivity of 73.7% and a specificity of 72.2% in the prediction of ovulation, with an area under the curve of 0.733. Patients with OI?<?85 had significantly higher ovulation rate (p?<?0.001).

Conclusion: The OI, combining both AMH and AFC, is a potentially useful predictor of the outcome of ovarian stimulation in PCOS.     

Different ovarian response by age in an anti-Müllerian hormone-matched group undergoing in vitro fertilization

Background  

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.     

Anti-Müllerian hormone levels and antral follicle count in women enrolled in in vitro fertilization cycles: Relationship to lifestyle factors,chronological age and reproductive history

The aims of this prospective study were to investigate the relationship between anti-Müllerian hormone (AMH) and antral follicle count (AFC), and to determine whether these markers of ovarian reserve correlate with lifestyle factors, ethnicity, chronological age and reproductive history. Participants were 136 normo-ovulatory women undergoing infertility work-up within 3 months of their first ovarian stimulation cycle for in vitro fertilization. On day 3 of a spontaneous menstrual cycle, a blood sample for measurement of plasma AMH levels was taken and a transvaginal ultrasound scan to determine the AFC (follicles measuring 2–5 mm in diameter) was performed. Information about smoking, body mass index, alcohol consumption, ethnic origin, chronological age, age at menarche, years since menarche and gravidity were recorded using a case report form. The main outcome measures were plasma AMH concentrations and total number of small antral follicles (AFC). Median plasma levels of AMH were 2.0 ng/ml (interquartile range 1.1–3.6) and AFC was 10 (interquartile range 7–15). A positive correlation between AMH and AFC (r = 0.54, p < 0.0001) was found. AMH and AFC correlated negatively with age (r = ?0.30, p < 0.001 and r = ?0.27, p = 0.001 respectively) and number of years since menarche (r = ?0.23, p = 0.007 and r = ?0.21, p = 0.015 respectively), but not with any of the other measures. Circulating AMH levels and AFC correlated with each other and declined significantly with age. There were only weak, non-significant, correlations with lifestyle factors and reproductive history. These putative markers could be used individually or together to assess the age-related decline of ovarian function in normo-ovulatory candidates for IVF.     

Serum anti-Müllerian hormone and basal serum FSH as predictors of poor ovarian response in assisted conception cycles

ObjectiveThe aim of the study was to correlate serum AMH and serum FSH levels with ovarian response to stimulation in IVF–ICSI cycles.Design and settingsThis was a prospective observational study conducted in a private assisted conception unit.Subjects and methodsOne hundred and two patients were selected on their first IVF cycle. Basal serum FSH and serum AMH were measured one month before the stimulation cycle. A fixed dose GnRH antagonist protocol was used in all cycles transferring a maximum of three day-3 cleavage stage embryos. We defined poor ovarian response as retrieval of fewer than four mature oocytes in cycles requiring ? 3000 IU of gonadotropins for stimulation or cycle cancellation due to poor response. The correlation between different parameters was expressed as a Spearman’s correlation coefficient. The clinical value of AMH and FSH as predictors of poor ovarian response as well as predictors of pregnancy was evaluated by constructing relevant receiver operator characteristics curves (ROC curves).ResultsOf these 102 cycles, 28 fitted our definition of poor response while the remaining 74 cycles all produced an adequate response to stimulation. There was a statistically significant difference between the adequate responders group and poor responders group regarding their mean age (31.5 versus 39.6, p < 0.001), the mean value of AMH (2.84 ng/ml versus 0.9 ng/ml, p < 0.0001) as well as the mean value of basal FSH (7.6 IU/ml versus 9.7 IU/ml, p < 0.0001). Serum AMH level had a positive correlation while serum FSH had a negative correlation with the number of oocytes collected while only serum AMH had a significant positive correlation with the occurrence of pregnancy. ROC curve analysis of our results showed that serum AMH with an optimal cut-off value of 1.2 ng/ml is a reliable predictor of poor ovarian response with an area under the ROC curve of 90.4%. Serum basal FSH with an optimal cut-off value of 8.9 IU/ml was of lower value than AMH as a predictor of poor ovarian response with an area under the ROC curve of 81.9%. However, neither serum AMH nor basal serum FSH was found to able to reliably predict the occurrence of pregnancy with an area under the ROC curve of 59.4% and 58.6% respectively.ConclusionOur results show that serum AMH level is more reliable than basal serum FSH as a predictor of poor ovarian response to stimulation with a cut-off value of 1.2 ng/ml shown to predict poor ovarian response with a sensitivity of 91.7%.     

Serum anti-Müllerian hormone and antral follicle count as predictive markers of OHSS in ART cycles

Objective  

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.     

Antral follicle count, anti-mullerian hormone and inhibin B: predictors of ovarian response in assisted reproductive technology?

OBJECTIVE: The objective of this study was to evaluate the relationship between anti-mullerian hormone (AMH), inhibin B and antral follicle count (AFC) with ovarian response. DESIGN: Retrospective study. SETTING: Fertility unit. SAMPLE: AFC was recorded, and a serum sample obtained on day 3 from all patients undergoing in vitro fertilisation (IVF). Patients were given 300 IU/L recombinant follicle stimulating hormone (FSH; Gonal F). The following day blood samples were collected. METHODS Serum samples were assayed for FSH, AMH and inhibin B using commercial immunoassay kits and oestradiol using an in house assay. MAIN OUTCOME MEASURES: Response to gonadotrophin stimulation and the number of eggs collected. RESULTS: AFC was negatively correlated to age (r=-0.426, P < 0.001). Delta inhibin B (levels of inhibin B on day 4 minus day 3) had the best association to the number of eggs collected (r= 0.533, P < 0.001) followed by basal AMH (r= 0.51, P < 0.001) and AFC (r= 0.505, P < 0.001). The number of eggs fertilised was significantly associated with basal AMH (r= 0.592, P < 0.001) and inhibin B (r= 0.548, P < 0.001). AMH with a cutoff of 0.2 ng/mL had the best sensitivity (87%) and specificity (64%) in predicting poor response. A cumulative score using basal FSH, basal AMH, delta E2 (levels of oestradiol on day 4 minus day 3), delta inhibin B, AFC and age gives the best predictive statistics to identify poor responders with 87% sensitivity and 80% specificity and a positive likelihood ratio of 4.36. CONCLUSION: Delta inhibin B had the best positive association with the number of eggs collected and basal AMH is the single best predictor of poor response. AFC has a significant association with the number of eggs collected and is predictive of clinical pregnancy. It is evident that a single parameter is of limited value in predicting ovarian response. However, we have demonstrated a cumulative score using all the above markers could be useful in predicting poor response.     

Small antral follicle count (2–5 mm) and ovarian volume for prediction of pregnancy in in vitro fertilization cycles

Aims.?To assess the value of antral follicle count (AFC) and other parameters as predictors of pregnancy in in vitro fertilization (IVF).

Methods.?In a cohort study, unselected consecutive women in IVF treatment were evaluated. Pretreatment parameters included AFC (subpopulations of small (2–5?mm) and large (5–10?mm) AFC), ovarian volume, and ovarian stroma Doppler indices.

Results.?The study included 115 women of whom 38 (33%) were pregnant. Total AFC was significantly higher in the pregnant than in the non-pregnant group (13.7?±?5.8 vs. 11.3?±?5.3, p?=?0.034). On receiver operator characteristic (ROC) curve analysis, the pretreatment variables that were significantly associated with pregnancy were small AFC (2–5?mm), total AFC, and ovarian volume/AFC ratio. Women with a positive score (total AFC >15; small AFC (2–5?mm) >10; ovarian volume in mm³/AFC, <1400), had a significantly higher number of retrieved oocytes and a higher pregnancy rate than women with a negative score (12.1?±?5.1 vs. 8.7?±?5.0, p?=?0.027 and 58.3% vs. 30.1%, p?=?0.049, respectively). On multivariate logistic regression analysis, total AFC was the only significant and independent predictor of pregnancy (p?=?0.034).

Conclusion.?Pretreatment small AFC and ovarian volume may identify women with a higher probability to achieve pregnancy in IVF.     

Serum Anti-müllerian hormone, follicle stimulating hormone and antral follicle count measurement cannot predict pregnancy rates in IVF/ICSI cycles

Purpose

To investigate whether serum anti-müllerian hormone (AMH), follicle stimulating hormone (FSH), or antral follicle count (AFC) are predictive for clinical pregnancy in in vitro fertilization (IVF) patients.

Methods

Serum AMH, inhibin B, FSH, luteinizing hormone (LH), estradiol (E2), prolactin, and thyroid stimulating hormone (TSH) levels and AFC of 189 women under 40 years of age were investigated. Pregnant and non-pregnant women were compared.

Results

Forty-seven (24.8 %) clinical pregnancies were observed in 189 women. There was no significant difference in terms of mean age, duration of infertility, body mass index, AMH, LH, FSH, E2, TSH, Inhibin B, AFC and total oocyte number between women who did and who did not become pregnant. Additionally, there was no significant difference in clinical pregnancy rates between the quartiles of AMH, FSH and AFC. (P values were 0.668, 0.071, and 0.252, respectively.)

Conclusion

Serum AMH and FSH, and AFC cannot predict clinical pregnancy in IVF patients under 40; the pregnancy rate tends to increase as AMH increases, although this remains non-significant.     

Which cut-off value of serum anti-Müllerian hormone level can predict poor ovarian reserve,poor ovarian response to stimulation and in vitro fertilization success? A prospective data analysis

The aim of our study is to demonstrate which cut-off value of serum anti-Müllerian hormone (AMH) level can predict poor ovarian reserve, poor ovarian response to stimulation and IVF outcomes. About 311 of 520 women enrolled IVF treatment cycle that meets inclusion criteria were recruited for this prospective data analysis. Data were collected for: age, duration of infertility, basal FSH and AMH level, total dosage of gonadotropins, maximum estradiol levels, duration of stimulations, total number of oocytes retrieved and clinical PR. Mean AMH was 1.76?±?1.4?ng/ml and mean age was 33.25?±?5.5 years. Clinical PR was 39.8% (n?=?124). AMH was inversely correlated to total dosage of gonadotropins and age, AMH positively had a significant correlation with maximum estradiol levels, duration of stimulations and total number of oocytes retrieved. The patients in both categories of AMH levels, ≤0.5 and ≤1?ng/ml responded poorly to ovarian stimulation, had significantly higher total dosage of gonadotropins used and FSH levels on cycle day 3, lower maximum E2 levels and clinical PR. AMH could be an acceptable screening test in prediction of ovarian reserve, response to ovarian stimulation and PRs. AMH cut-off value ≤1?ng/ml may predict poor ovarian reserve, poor ovarian response to stimulation and IVF outcomes.     

Prediction of ovarian response using the automated Elecsys anti-Müllerian hormone assay in gonadotrophin-releasing hormone antagonist cycles

Research questionWhat is the capability of serum anti-Müllerian hormone (AMH) measured using the automated Elecsys® AMH immunoassay to (Roche Diagnostics International Ltd) determine ovarian response after fertility treatment?DesignSingle-centre, retrospective, observational, cohort study including women undergoing ovarian stimulation. Serum AMH concentrations were determined using the Elecsys AMH immunoassay based on one blood sample drawn 6 months or less before treatment. Stimulation was conducted in accordance with a gonadotrophin-releasing hormone (GnRH) antagonist protocol. Patients were divided into four ovarian response categories based on their oocyte yield: low (0–3), suboptimal (4–9), optimal (10–15) and high (>15). Areas under the curve were calculated for each ovarian response group.ResultsOverall, 1248 patients were enrolled. The AMH concentration had a strong positive correlation with oocyte yield (Spearman's rho = 0.74, P < 0.001). Areas under the curve (95% CI) for AMH predicting ovarian response were 0.85 (0.83 to 0.88) for low and 0.89 (0.87 to 0.91) for high response. Optimal serum AMH cut-offs for predicting a low and high response using the Elecsys AMH immunoassay were 6.4 pmol/l (0.89 ng/ml) and 14.2 pmol/l (1.99 ng/ml), respectively. Multivariable regression analysis showed that 47% (R² = 0.470) of variation in ovarian response could be attributed to AMH alone, increasing to 50.9% (R² = 0.509) with the addition of age, body weight, and total dose of gonadotrophin.ConclusionOvarian response and oocyte yield after stimulation in a GnRH antagonist cycle can be predicted with high accuracy using a single determination of serum AMH before ovarian stimulation.     

Antimüllerian hormone predicts ovarian responsiveness, but not embryo quality or pregnancy, after in vitro fertilization or intracyoplasmic sperm injection

Antimüllerian hormone (AMH) and other markers of ovarian reserve were assessed to determine their predictive value with respect to treatment outcome. In a multivariate regression analysis, AMH was found to be predictive of the number of oocytes and the number of embryos, but not of embryo quality or the chance of a pregnancy, after IVF/ICSI.     

Prediction of high ovarian response to controlled ovarian hyperstimulation: anti-Müllerian hormone versus small antral follicle count (2–6 mm)

Purpose  

To evaluate the predictive value of basal serum anti-müllerian hormone level and small antral follicle count for high ovarian response to controlled ovarian hyperstimulation.     

Anti-Müllerian hormone is produced heterogeneously in primate preantral follicles and is a potential biomarker for follicle growth and oocyte maturation in vitro

Purpose

The main goals of this study were to investigate the expression of anti-Müllerian hormone (AMH) and its receptor (AMHR2) during follicular development in primates, and to evaluate the potential of AMH as a biomarker for follicle growth and oocyte maturation in vitro.

Methods

The mRNA and protein expression of AMH and AMHR2 were determined using isolated follicles and ovarian sections from rhesus macaques (n?=?4) by real-time PCR and immunohistochemistry, respectively. Isolated secondary follicles were cultured individually. Follicle growth and media AMH concentrations were assessed by ELISA. The mRNA expression profiles, obtained from RNA sequencing, of in vitro- and in vivo-developed antral follicles were compared. Secondary follicles from additional animals (n?=?35) were cultured. Follicle growth, oocyte maturation, and media AMH concentrations were evaluated for forecasting follicular development in vitro by AMH levels.

Results

AMH immunostaining was heterogeneous in the population of preantral follicles that were also stained for AMHR2. The mRNA expression profiles were comparable between in vivo- and in vitro-developed follicles. AMH levels produced by growing follicles were higher than those of nongrowing follicles in culture. With a cutoff value of 1.40 ng/ml, 85 % of nongrowing follicles could be identified while eliminating only 5 % of growing follicles. Growing follicles that generated metaphase II-stage oocytes secreted greater amounts of AMH than did those yielding immature germinal vesicle-stage oocytes.

Conclusions

AMH, co-expressed with AMHR2, was produced heterogeneously by preantral follicles in macaques with levels correlated positively with follicle growth and oocyte maturation. AMH may serve as a biomarker for primate follicular development in vitro.