Higher anti-Müllerian Hormone Levels Research Articles

Characterization of women with elevated antimüllerian hormone levels (AMH): correlation of AMH with polycystic ovarian syndrome phenotypes and assisted reproductive technology outcomes

Serum Antimüllerian hormone (AMH) levels are elevated in polycystic ovarian syndrome and have been shown to be useful in its diagnosis. However, the clinical significance of extremely high AMH levels is understudied. We aimed to characterize a population of women with elevated AMH (>5 ng/mL). This was a retrospective cohort study of 134 women presenting to our fertility clinic for infertility evaluation and treatment who were found to have random serum AMH over 5 ng/mL. Women were divided into 3 groups according to AMH: 5-10 ng/mL, >10-14 ng/mL, and >14 ng/mL. Endocrine characteristics, polycystic ovarian syndrome (PCOS) phenotypes, fertilization rate, implantation rate, clinical pregnancy, and multiple pregnancy rates were compared between groups. AMH ranged between 5 to 48 ng/mL. Greater than 97% of women with ultrahigh AMH (>10 ng/mL) had PCOS. In addition, women with AMH >10 ng/mL had greater prevalence of polycystic ovarian morphology and oligoamenorrhea than women with AMH 5-10 ng/mL. Moreover, serum AMH correlated positively with luteinizing hormone, total testosterone, and dehydroepiandrosterone sulfate. Furthermore, AMH showed strong predictive ability for the presence of amenorrhea (area under the curve, 0.87; 95% confidence interval, 0.80-0.92; P < .0001). Despite similar age and mean number of transferred embryos, women with AMH >10 ng/mL showed higher rates of ovarian hyperstimulation syndrome and clinical pregnancy rates compared with women with AMH 5-10 ng/mL. These data characterize a population of women with elevated AMH levels, demonstrating that the vast majority of women with AMH >10 ng/mL have PCOS. Increased AMH levels correlated with PCOS severity and are associated with greater ovarian stimulation and higher clinical pregnancy rates following assisted reproductive technology.

The rate of high ovarian response in women identified at risk by a high serum AMH level is influenced by the type of gonadotropin

The aim was to compare ovarian response and clinical outcome of potential high-responders after stimulation with highly purified menotropin (HP-hMG) or recombinant follicle-stimulating hormone (rFSH) for in vitro fertilisation/intracytoplasmic sperm injection. Retrospective analysis was performed on data collected in two randomized controlled trials, one conducted following a long GnRH agonist protocol and the other with an antagonist protocol. Potential high-responders (n = 155 and n = 188 in the agonist and antagonist protocol, respectively) were defined as having an initial anti-Müllerian hormone (AMH) value >75th percentile (5.2 ng/ml). In both protocols, HP-hMG stimulation in women in the high AMH category was associated with a significantly lower occurrence of high response (≥15 oocytes retrieved) than rFSH stimulation; 33% versus 51% (p = 0.025) and 31% versus 49% (p = 0.015) in the long agonist and antagonist protocol, respectively. In the potential high-responder women, trends for improved live birth rate were observed with HP-hMG compared with rFSH (long agonist protocol: 33% versus 20%, p = 0.074; antagonist protocol: 34% versus 23%, p = 0.075; overall population: 34% versus 22%, p = 0.012). In conclusion, the type of gonadotropin used for ovarian stimulation influences high-response rates and potentially clinical outcome in women identified as potential high-responders.

Prenatal Exposures and Anti-Müllerian Hormone in Female Adolescents

Given that the primordial ovarian follicular pool is established in utero, it may be influenced by parental characteristics and the intrauterine environment. Anti-Müllerian hormone (AMH) levels are increasingly recognized as a biomarker of ovarian reserve in females in adulthood and adolescence. We examined and compared associations of maternal and paternal prenatal exposures with AMH levels in adolescent (mean age, 15.4 years) female offspring (n = 1,399) using data from the Avon Longitudinal Study of Parents and Children, a United Kingdom birth cohort study that originated in 1991 and is still ongoing (data are from 1991–2008). The median AMH level was 3.67 ng/mL (interquartile range: 2.46–5.57). Paternal but not maternal smoking prior to and during pregnancy were inversely associated with AMH levels. No or irregular maternal menstrual cycles before pregnancy were associated with higher AMH levels in daughter during adolescence. High maternal gestational weight gain (top fifth versus the rest of the distribution) was associated with lower AMH levels in daughters. Parental age, body mass index, and alcohol intake during pregnancy, child's birth weight, and maternal parity and time to conception were not associated with daughters' AMH levels. Our results suggest that some parental preconceptual characteristics and environmental exposures while the child is in utero may influence the long-term ovarian development and function in female offspring.

A prospective randomised controlled study of serum anti-mullerian hormone (AMH) as a predictive marker of ovarian hyperstimulation syndrome (OHSS) in IVF-ICSI cycles

A prospective randomised controlled study of serum anti-mullerian hormone (AMH) as a predictive marker of ovarian hyperstimulation syndrome (OHSS) in IVF-ICSI cycles

The predictive value of anti-mullerian hormone on embryo quality following in vitro fertilization

High AMH levels on Day 3 have been shown to be corelated with high numbers of mature oocytes, resulting in more embryos and higher clinical pregnancy rate, previously. As oocyte quantity and oocyte quality affect embryo quality, AMH might also correlate with embryo quality. In this study we aimed to evaluate the association between basal serum levels of anti-Mullerian hormone (AMH) and embryo quality following in vitro fertilization (IVF).

Characterization of women with ultra high serum anti-mullerian hormone (AMH) levels and its association with polycystic ovarian syndrome (PCOS) phenotype

Serum AMH levels are elevated in PCOS and have been shown to be useful in its diagnosis. However, the clinical significance of extremely high AMH levels is understudied, and some of these women may have granulosa cell tumors. Thus, we aimed to characterize a population of women with ultra high AMH (≥10ng/ml).

The Predictive Value of Circulating Anti-Müllerian Hormone in Women With Polycystic Ovarian Syndrome Receiving Clomiphene Citrate: A Prospective Observational Study

Elevated serum anti-Müllerian hormone (AMH) concentration in women with polycystic ovarian syndrome (PCOS) is known to lower sensitivity of ovarian follicles to circulating FSH. This effect may compromise the outcome of clomiphene citrate (CC) ovulation induction. The objective of the study was to investigate the impact of high circulating AMH on the outcome of CC ovulation induction in women with PCOS. This was a prospective cohort observational study. The study was conducted at the Fertility Unit, Derby, United Kingdom. Sixty anovulatory women with PCOS participated in the study. Serum AMH concentrations were measured on cycle day 2 during 187 CC cycles. These concentrations were compared between responders and nonresponders. The receiver-operating characteristic curve was used to evaluate the prognostic value of circulating AMH. The success rates of CC were compared between patients with high vs low AMH levels. The dose of CC required to achieve ovulation was correlated with serum AMH concentrations. Ovulation and pregnancy rates were measured. Serum AMH concentrations were significantly (P < .001) lower in responders (achieving ovulation) vs nonresponders (mean ± SEM, 2.5 ± 0.1 vs 5.8 ± 0.7 ng/mL, respectively). Similarly, serum AMH concentrations were significantly (P = .046) lower in pregnant (3.0 ± 0.4 ng/mL) vs nonpregnant patients (4.4 ± 0.5 ng/mL). There was a significant (P = .02) gradient increase of serum AMH levels with the increasing dose of CC required to achieve ovulation. The receiver-operating characteristic curve showed AMH to be a useful predictor of no ovulation (area under the curve, 0.809; P < .001) with a useful cutoff level of 3.4 ng/mL. Ovulation and pregnancy rates were significantly higher (97%, P < .001, and 46%, P = .034) in patients with low AMH (<3.4 ng/mL) vs women with AMH 3.4 ng/mL or greater (48% and 19%). PCOS women with high circulating AMH (≥ 3.4 ng/mL) seem to be resistant to CC and may require a higher starting dose.

Serum anti-Müllerian hormone (AMH) levels correlate with infrarenal aortic diameter in healthy older men: is AMH a cardiovascular hormone?

Anti-Müllerian hormone (AMH) is a gonadal hormone present in the blood in men and pre-menopausal women. AMH regulates male sexual differentiation but has no putative function in adulthood. In recent studies, high AMH levels are associated with absence of cardiovascular disease in men and smaller atherosclerotic burden in monkeys. Mechanistically, AMH has downstream convergence with known regulators of the cardiovascular system, while the specific receptor for AMH is present in murine aorta and the human heart. Our primary objective was to examine whether AMH levels in healthy men correlated with the physical characteristics of their aorta. Our secondary aim was to document whether men with distinct vascular disorders expressed different levels of AMH. Serum AMH assayed by ELISA in 153 men (54-93 years) free from vascular disease inversely correlated with the ultrasonographic diameters of the distal- (r=-0.22, P=0.006) and mid-infrarenal aorta (r=-0.26, P=0.008). This association was similar in magnitude but opposite to that of body surface area (largest known determinant of aortic diameter) and independent of known cardiovascular risk factors. This relationship is specific to AMH, as inhibin B, a Sertoli cell hormone-like AMH, did not correlate with aortic diameter (r=-0.04, P=0.66) despite partially correlating with AMH. Among men with known vascular disease, higher AMH levels were associated with varicose vein disease, while men with higher levels of AMH were under-represented in the abdominal aortic aneurysm relative to the healthy cohort. These findings identify AMH as a novel putative regulator of the cardiovascular system.

Clinical Relevance of Combined FSH and AMH Observations in Infertile Women

FSH and anti-Müllerian hormone (AMH) are, individually, widely used to assess functional ovarian reserve (FOR) but demonstrate discrepancies in efficacy. How predictive they are combined is unknown. The purpose of this study was to assess predictive values of different FSH and AMH combinations on in vitro fertilization (IVF). FSH and AMH levels in patients were categorized as low, normal, and high, based on age-specific 95% confidence intervals. This allowed for establishment of nine combinations of low, normal, or high FSH/AMH patient categories. With use of various statistical methods, patients in individual categories were then compared in outcomes. We investigated 544 consecutive infertility patients in their first IVF cycles. IVF cycles were managed. Oocyte yields and implantation and pregnancy rates, adjusted for age and fragile X mental retardation 1 (FMR1) genotypes/subgenotypes, were measured. The most notable repeated finding was a strong statistical association of the FSH/AMH high/high category (characterized by abnormally high FSH and AMH levels) with favorable IVF outcomes compared with outcomes for other FSH/AMH variations (4.34 times odds of high oocyte yields and 1.93 times odds of clinical pregnancy). Addition of age to the model only minimally further improved the odds of pregnancy to 2.03 times. The positive association with high oocyte yields, however, turned negative (0.75 times lower yields) with addition of FMR1 to the model for women with FSH/AMH high/high and the het-norm/low FMR1 subgenotype compared with women with the norm FMR1 genotype and other FSH/AMH categories. In the absence of het-norm/low FMR1, abnormally high FSH and AMH, a seemingly contradictory combination, reflects highly beneficial outcomes in IVF compared with the other FSH/AMH categories, suggesting greater importance of FSH in early follicle maturation than currently recognized. The study also confirms adverse outcome effects of het-norm/low FMR1 and, therefore, the gene's importance for reproductive success.

Peripubertal changes in circulating antimüllerian hormone levels in girls

ObjectiveTo identify correlates and longitudinal changes in circulating antimüllerian hormone (AMH) levels as a marker of ovarian primordial follicle recruitment in normal peripubertal girls.DesignObservational study using mixed longitudinal and cross-sectional analyses.SettingNot applicable.Patient(s)Unselected girls assessed at ages 7–11 years.Intervention(s)None.Main Outcome Measure(s)AMH, inhibin B, and FSH levels were analyzed in blood samples collected at ages 7, 9, and 11 years for longitudinal analyses and at age 8 years for cross-sectional analyses.Result(s)In the cross-sectional analysis, AMH levels at age 8 years were lower in pubertal girls (median 25.0 pmol/L, interquartile range [IQR] 16.0–33.9; n = 39) than in prepubertal girls (33.5 pmol/L, IQR 22.3–49.1; n = 342). In prepubertal girls, higher AMH levels were associated with higher inhibin B levels, lower FSH levels, and larger body mass index at age 8 years and subsequently with later age at menarche. AMH levels were unrelated to birth weight or birth length. In the longitudinal analysis, AMH levels increased between ages 7 (median 27.0 pmol/L, IQR 19.2–34) and 9 years (32.0 pmol/L, IQR 26.5–42.7), then declined between 9 and 11 years (26.5 pmol/L, IQR 19–42.25) with high intraindividual correlation in AMH levels between ages 7 and 9 years and 7 and 11 years.Conclusion(s)Measurement of circulating AMH and inhibin B levels suggests that the rate of ovarian primordial follicle recruitment increases in the prepubertal years then declines again following the onset of puberty as follicular activity pattern changes.

Falsely elevated serum antimüllerian hormone level in a context of heterophilic interference

To describe a case of falsely elevated serum antimüllerian hormone (AMH) level in an infertile 37-year-old woman with rheumatoid arthritis. Case report. Lille University IVF center. A 37-year-old woman with rheumatoid arthritis demonstrating a high serum AMH level (74.5 ng/mL) and a low antral follicle count. Assay with a Heterophilic Blocking Tube (HBT) to avoid heterophilic interference. Serum AMH level, ultrasound antral follicle count, hormonal assays on the 4th day of a spontaneous cycle. The results of the infertility workup were as follows: serum AMH: 74.5 ng/mL (15-fold the upper limit of normal) (immunoassay: Immunotech); LH: 3.2 IU/L; FSH: 4.5 IU/L; E2: 27 pg/mL; PRL: 10 ng/mL. The antral follicle count (follicles from 2 to 9 mm) at ultrasound was 7 for both ovaries. Because there were discrepancies between the serum AMH level and the results of the infertility workup using the bioassays, we suspected a case of falsely elevated AMH level due to heterophilic interference. An HBT tube revealed a serum AMH level of 0.63 ng/mL. This case illustrates, for the first time, the possibility of a falsely high serum AMH level due to heterophilic interference.

The Author Response: Serum anti-Müllerian hormone levels and phenotypes of polycystic ovary syndrome

Reply: We recently published an original article entitled Can high serum Anti-Mullerian hormone (AMH) levels predict the phenotypes of polycystic ovary syndrome (PCOS) and metabolic disturbances in PCOS patients? [1]. There are numerous reports on high serum AMH levels in patients with PCOS, and their serum AMH levels are much variable. We were curious about the possibility that high serum AMH levels are correlated with the phenotypes of PCOS and metabolic derangement. We did not find any significant difference according to the phenotypes of PCOS in the non-obese group. The correspondents pointed out that our result is different from a recent report from Sahmay et al. [2]. The study of Sahmay et al. [2] was a cross-sectional retrospective study and included 251 women with PCOS. They concluded that AMH levels seem to play a diagnostic role in determining the severity of PCOS. There are differences in this study population, who had over 75% hyperandrogenism (HA) and had a similar body mass index (BMI) among the groups. Our study group showed a relatively low percentage of HA (36%, 59/175) and significantly higher BMI in the PCOS patients who had 3 diagnostic criteria (anovulation+HA+polycystic morphology). PCOS women without HA are more common in Korea and are less likely to have metabolic dysfunction, insulin resistance, and elevated blood pressure [3]. PCOS without HA could be a mild phenotype of PCOS [3]. In another study, it was reported that Chinese women with PCOS showed lower rates of HA, hirsutism, obesity, and insulin resistance [4]. Furthermore, obese women have lower AMH levels compared to non-obese women [5]. Recently, it has been recommended that the follicle number per ovary for the diagnosis of polycystic ovary morphology be set at ≥25 [6]. The thresholds used to define follicle excess, particularly in diverse populations must be reconsidered. We suggest that ethnicity might contribute to variation. We value the comments of the correspondents and plan to perform a larger scale study to clarify these results.

Can high serum anti-Müllerian hormone levels predict the phenotypes of polycystic ovary syndrome (PCOS) and metabolic disturbances in PCOS patients?

ObjectiveTo evaluate correlations between serum anti-Müllerian hormone (AMH) levels, phenotypes of polycystic ovary syndrome (PCOS), obesity, and metabolic parameters in patients with PCOS.MethodsA total of 175 patients with PCOS were diagnosed according to the Rotterdam Consensus were included. Exclusion criteria were age over 40, FSH>25 mIU/mL, and 17a-OHP>1.5 ng/mL. The Phenotypes of PCOS were divided into a severe form (oligo-anovulation, ANOV/hyperandrogenism/polycystic ovary morphology [PCOM]; n=59) and a mild form without HA (ANOV/PCOM, n=105). The serum AMH levels were classified into 3 groups (<5 vs. 5-10 vs. >10 ng/mL). Obesity was defined as body mass index (BMI) ≥25 kg/m2 (n=34).ResultsThe mean age was 25.9±5.7 year and mean AMH level was 10.1±5.4 ng/mL. The BMI (kg/m2) was higher in group 1 (24.2±6.3) than in group 2 (21.9±4.3, p=0.046) or group 3 (21.6±3.3, p=0.019). There was no difference among the three groups in age, menstrual interval, antral follicle counts, androgens, or other metabolic parameters. The obesity group showed significantly lower AMH (7.7±3.9 ng/mL vs. 10.7±5.6 ng/mL), p=0.004) and low-density lipoprotein levels (93.1±21.2 mg/dL vs. 107.5±39.3 mg/dL, p=0.031), and showed higher total T (0.74±0.59 ng/mL vs. 0.47±0.36 ng/mL, p=0.001), free T (2.01±1.9 vs. 1.04±0.8 pg/mL, p=0.0001), and free androgen index (6.2±7.9 vs. 3.5±3.0, p=0.003). After controlling for age factors and BMI, the serum AMH levles did not show any significant correlations with other hormonal or metabolic parmeters.ConclusionFor PCOS patients under the age 40, serum AMH is not negatively correlated with age. High serum AMH levels can not predict the phenotype of PCOS and metabolic disturbances in PCOS patients in the non-obese group. Further study might be needed to define the relation more clearly.

314 RELATIONSHIP BETWEEN SERUM ANTI-MULLERIAN HORMONE (AMH), OVARIAN RESERVE, AND EMBRYO PRODUCTION IN SUPEROVULATED HOLSTEIN COWS

The relations between serum anti-Mullerian hormone (AMH), oocyte numbers, and in vivo embryo production in Holstein heifers were evaluated. The AMH levels of 15 unstimulated cows were followed at weekly intervals during their oestrous cycles and monthly for 4 months. Forty-one superovulated heifers were evaluated at ovum pick-up (OPU) performed 20 h after cystorelin administration, and 125 others were evaluated at embryo recovery. Animals were followed over 3 consecutive cycles induced using a modified Ovsynch protocol with 4 days of FSH (Pluset H, Minitube of America, Verona, WI, USA). Blood samples were collected in serum tubes and spun within 2 h. The samples were stored at –20°C until evaluation using the Minitube of America AMH-bovine specific immunoassay (AMH Fertility Assay™). The statistical analyses (ANOVA and data correlation) were performed using Statview 5 with P &lt; 0.05. Serum AMH ranged from 43 to 960 pg mL–1. The average AMH level of all cows was stable during the oestrous cycle and for each of the 4 monthly measurements. There was a high correlation between all values per animal (r2 = 0.9077; P &lt; 0.01), suggesting that AMH levels are consistent during the cycle and for at least 4 consecutive months. Animals that were repeatedly stimulated showed decreasing AMH levels (509 ± 295, 299 ± 210, 211 ± 119) and a decrease in recovered embryos (7.4 ± 4, 5.6 ± 3.8, 4.2 ± 3.2; P = 0.02). The number of oocytes was not altered by multiple stimulations (10.4 ± 9.8, 11.3 ± 6.2, 8.5 ± 7.6; P = 0.75). As AMH and embryo numbers decreased after multiple stimulations, only the first AMH value and results of the first OPU or flush were used to establish following correlation. Serum AMH showed a positive correlation to the number of oocytes (r2 = 0.245) and embryos collected (r2 = 0.27).When separated into AMH categories, low (&lt;100), normal (100–400), and high (&gt;400 pg mL–1), high-AMH OPU animals yielded significantly higher numbers of oocytes than the animals in the normal or low AMH groups (13.8 ± 9.2 v. 9.2 ± 5.2 and 5.6 ± 3.9; P = 0.001). Flushed animals with high AMH levels had significantly higher numbers of embryos than those with low AMH (10.9 ± 7.9 v. 5.7 ± 5; P = 0.002). Comparison of the first AMH value to the average number of oocytes or embryos collected over the course of 3 collections/animal showed a positive correlation to the average number of oocytes/collection from individual OPU donors (r2 = 0.436) and a positive correlation to the average number of embryos/collection from individual donors (r2 = 0.176). When separated into AMH groups, high-AMH flushed animals had significantly higher numbers of embryos than the normal- or low-AMH animals (9.3 ± 3.1 v. 5.7 ± 3.4 and 4.5 ± 2; P = 0.0001). As OPU animals with low AMH were used only once, average oocyte/collection data was not available for this category. A significant difference was observed between the high- and normal-AMH categories (12 ± 3.6 v. 7 ± 2; P = 0.0001). Circulating AMH is stable over time in unstimulated animals but decreases in repetitively stimulated animals. Anti-Mullerian hormone is highly associated with superovulation response and oocyte and embryo production, and its use should improve animal selection to achieve improve efficiency of multiple-ovulation embryo transfer.

Polycystic ovary syndrome (PCOS)-like phenotypes in the d-galactose-induced aging mouse model

The d-galactose (d-gal)-induced animal model, which is established by consecutive subcutaneous d-gal injections for approximately 6weeks, has been frequently used for aging research. This animal model has been shown to accelerate aging of the brain, kidneys, liver, and blood cells. However, aging of the female reproductive organs in this animal model has not been reported. The aim of this study was to investigate changes in the ovary in the d-gal-induced aging mouse model. First, we evaluated anti-Müllerian hormone (AMH) as a marker of ovarian aging in blood plasma. We speculated there would be lower AMH levels in d-gal-treated mice because ovarian aging would be induced by d-gal, as reported for other tissues. However, the results showed that AMH levels in d-gal-treated mice were approximately four-fold higher than control mice. Abnormally high AMH levels are detected in ovarian cancer and polycystic ovary syndrome (PCOS) patients. Therefore, we examined PCOS-related markers in this mouse model. Total testosterone levels were high and abnormal estrous cycles were induced in d-gal-treated mice. These changes, including AMH levels, in d-gal-treated mice were inhibited by aminoguanidine treatment, an advanced glycation end product reducer. In addition, ovarian cysts were observed in some d-gal-treated mice. These results indicate that with respect to female reproduction, d-gal-treated mice are suitable for PCOS studies, rather than aging studies.

Is the measurement of anti-Müllerian hormone essential?

Over the past decade, a large number of studies examining the multiple roles of anti-Müllerian hormone (AMH) have been published. The purpose of this article is to focus on the clinical usefulness of AMH in the fields of current gynecological clinical practice. AMH has entered clinical practice in terms of poor ovarian response definition. It prevents folliculogenesis by reducing follicle sensitivity to follicle-stimulating hormone (FSH), and leads to anovulation when secreted in excess amounts in polycystic ovary syndrome (PCOS). Better results might be obtained in the assisted reproductive technique cycle in the presence of high AMH levels even though FSH is increased in women diagnosed with diminished ovarian reserve. In a more recently published study it has been reported that AMH can also predict the outcome of pregnancy in assisted reproduction. AMH levels accurately reflect the ovarian follicular reserve and might, therefore, be considered as a sensitive marker of ovarian aging and ovarian reserve. Evaluation of the level of AMH has clinical value in predicting the success of in-vitro fertilization (IVF). Hyper-response/ovarian hyperstimulation syndrome (OHSS) might be anticipated as about 3.5 ng/ml or above. The cycle stability and operator independency make AMH a most appealing single marker of ovarian reserve. Use of AMH to paint tailored stimulation protocol could result in a reduced risk of OHSS, optimized treatment burden and maintained pregnancy rates. Cost-effectiveness of the use of AMH as a single test before initiating an IVF program should be determined.

Antimüllerian hormone levels are independently related to ovarian hyperandrogenism and polycystic ovaries

To determine the relationship of antimüllerian hormone (AMH) levels to polycystic ovaries and ovarian androgenic function. Prospective case-control study. General clinical research center. Eumenorrheic asymptomatic volunteers without (V-NO; n = 19; reference population) or with (V-PCO; n = 28) a polycystic ovary and hyperandrogenemic anovulatory subjects grouped according to ovarian function into typical PCOS (PCOS-T; n = 37) and atypical PCOS (PCOS-A; n = 18). Pelvic ultrasonography, short dexamethasone androgen-suppression test (SDAST), and GnRH agonist (GnRHag) test. Baseline AMH levels were related to polycystic ovary status, testosterone response to SDAST, and 17-hydroxyprogesterone response to GnRHag test. AMH levels correlated with SDAST and GnRHag test outcomes. AMH was elevated (>6.2 ng/mL) in 32% of V-PCO versus 5% V-NO. The 21% of V-PCO who met Rotterdam PCOS criteria all had functional ovarian hyperandrogenism, but AMH levels were similar to nonhyperandrogenic V-PCO. AMH >10.7 ng/mL discriminated V-PCO from PCOS with 96% specificity and 41% sensitivity for PCOS-T, and insignificantly for PCOS-A. AMH levels are independently related to ovarian androgenic function and polycystic ovaries. Very high AMH levels are specific but insensitive for PCOS. In the absence of hyperandrogenism, moderate AMH elevation in women with normal-variant polycystic ovaries seems to indicate an enlarged oocyte pool.

Relationship Between Anti-Müllerian Hormone (AMH) and Insulin Levels During Different Tanner Stages in Daughters of Women With Polycystic Ovary Syndrome

We have previously described increased serum levels of anti-Müllerian hormone (AMH) and stimulated insulin in daughters of women with polycystic ovary syndrome (PCOS), suggesting that these girls may have an altered ovarian follicular development which may be modulated by insulin. However, the specific relationship between serum AMH and insulin levels during each Tanner stage of puberty in this cohort has not been established. The aim of our study was to establish the relationship between AMH and poststimulated insulin serum concentrations during each stage of puberty in daughters of women with PCOS (PCOSd), compared to daughters of control women (Cd). We studied 135 PCOSd and 93 Cd classified according to their Tanner stage. Gonadotrophins, sex steroids, sex hormone-binding globulin (SHBG), and AMH were determined in a fasting sample. Ovarian volume was measured by pelvic ultrasound. In addition, in both groups we performed an oral glucose tolerance test with measurements of glucose and insulin. Anti-Müllerian hormone levels were significantly higher in PCOSd compared to Cd at all Tanner stages. Daughters of women with PCOS having AMH concentrations greater than 2 standard deviation (SD) above the mean AMH value for the Cd group showed decreased serum follicle-stimulating hormone (FSH) concentrations and increased stimulated levels of insulin during Tanner stages I, II, and III. Anti-Müllerian hormone levels are increased in PCOSd during all stages of puberty. We suggest that those PCOSd with the highest AMH levels probably represent a group of girls with more severe ovarian dysfunction and metabolic derangements.

PCOS and peripheral AMH levels in relation to FSH receptor gene single nucleotide polymorphisms

Objectives: To determine if an association exists between the follicle-stimulating hormone receptor (FSHR) gene p.Asn680Ser polymorphism and polycystic ovary syndrome (PCOS) or with high anti-mullerian hormone (AMH) levels without PCOS. Patients: Fifty-eight women with PCOS, 24 women with high AMH (>44.5 pmol/L) without PCOS and 80 healthy ethnically matched female controls. Main outcome measures: Prevalence of the FSHR p.Asn680Ser polymorphism, baseline serum AMH levels and response to ovulation induction with clomiphene citrate. Results: The frequency of FSHR p.Asn680Ser genotypes were not significantly different between PCOS patients, patients with high AMH without PCOS and controls (p = 0.88). Of the women with PCOS, 34/58 were on clomiphene citrate treatment and 12/34 were resistant. There was no association between sensitivity or resistance to clomiphene and p.Asn680Ser genotypes (p = 0.38). Conclusions: There is no evidence that FSHR p.Asn680Ser genotypes are associated with PCOS, high AMH levels or response to clomiphene citrate.

Correlation of serum Anti-Müllerian hormone concentrations on day 3 of the in vitro fertilization stimulation cycle with assisted reproduction outcome in polycystic ovary syndrome patients.

To investigate whether serum Anti- Müllerian hormone (AMH) on day 3 could predict controlled ovarian stimulation and reproductive outcomes in women with polycystic ovary syndrome. A total of 164 PCOS patients undergoing their first IVF treatment cycle were prospectively included. Serum AMH levels on cycle day 3 was measured. The controlled ovarian stimulation and clinical outcomes for the study population were divided according to the <25th, 25 to 75th, or >75th percentile of serum day-3 AMH. Estradiol levels on hCG day and the number of retrieved oocytes significantly increased with increasing serum AMH levels, while total consumption of gonadotropin dose showed a significant decrease (P < 0.05). Fertilization rate and the number of good quality embryos were comparable among the low, average and high groups (P > 0.05). Embryo implantation rates in the high AMH group was significantly inferior to those with low and average AMH concentration (27 versus 48.8 and 50%, P < 0.01). Clinical pregnancy rates was lower in the high AMH group than that of the low and average group (45.9 versus 65 and 66.7%, P = 0.09), but this difference was only close to statistical significance. In addition, ordinal regression analysis indicated that LH level was the only independent predictor of embryo implantation rates (P = 0.017). In PCOS women, AMH levels on day 3 of the IVF stimulation cycle positively predict ovarian response to gonadotrophins. However, the women with high AMH levels had a significantly decreased IR, which may be due to remarkably increased LH concentrations.