The role of serum anti-Müllerian hormone (AMH) in the hormonal diagnosis of polycystic ovary syndrome

Abstract

Background: The study was performed to validate the threshold for anti-Müllerian hormone (AMH) that suggests the presence of polycystic ovaries in women with polycystic ovary syndrome (PCOS).

Methods: This prospective observational study included 59 infertile women: (A) 22 PCOS with hyperandrogenism (HA) and oligo-anovulation, (B) 15 suspected PCOS with either HA or oligo-anovulation and (C) 22 asymptomatic control women. The diagnosis of PCOS was made according to the NIH classification.

Results: For serum AMH and follicle number, respectively, the areas under the receiver operating characteristic curve (A versus C) were 0.97 and 0.93. The best compromise between specificity (95% and 91%) and sensitivity (95% and 82%) was obtained with threshold values of 33?pmol/l and 13 follicles, respectively. Using a serum AMH?>?33?pmol/l as a surrogate for either HA or oligo-anovulation in group B would lead to the diagnosis of PCOS in seven (46.6%) patients from this group.

Conclusions: Our data confirms that the AMH assay has a high diagnostic potential, providing that an appropriate threshold is used. AMH measurement may be included as an ultimate diagnostic criterion for the diagnosis of PCOS when either HA or anovulation is missing and/or when no reliable antral follicle count can be obtained.     

Sibutramine administration decreases serum anti-Müllerian hormone (AMH) levels in women with polycystic ovary syndrome

Objective

To investigate the effect of diet, physical exercise and sibutramine administration on serum anti-Müllerian hormone (AMH) levels, hormonal and metabolic parameters in overweight and obese patients with polycystic ovary syndrome (PCOS).

Study design

Prospective clinical study, in an outpatient clinic setting, of 76 overweight and obese women with PCOS. All patients were placed on a hypocaloric diet, physical exercise plus sibutramine (10 mg per day) for the first month and then on either a hypocaloric diet, physical exercise plus sibutramine (10 mg per day) or a hypocaloric diet and physical exercise for the subsequent 6 months. Serum AMH levels, body composition, hormonal and metabolic features and insulin sensitivity indices were evaluated at baseline and at 4 and 7 months of treatment.

Results

Body weight reduction was greater in the sibutramine group. Moreover, serum FSH and testosterone levels decreased, and SHBG, free androgen index and all indices of insulin resistance significantly improved at 4 and 7 months. Serum AMH levels decreased only in PCOS women who received sibutramine, at both 4 and 7 months of treatment.

Conclusion

A hypocaloric diet and a diet plus sibutramine both resulted in significant weight loss in overweight and obese women with PCOS. Patients who received sibutramine showed greater weight loss and improvement in hyperandrogenemia and insulin sensitivity after 7 months of treatment. Serum AMH levels significantly decreased at both 4 and 7 months of treatment only in PCOS women who received sibutramine, indicating a possible direct, gonadotropin independent effect of sibutramine on the ovarian production of AMH.     

Expression of anti-Müllerian hormone in letrozole rat model of polycystic ovary syndrome

Background: Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women of reproductive age with anti-müllerian hormone (AMH) two to three times higher, but the mechanism of increased AMH, excessive follicles and follicle stagnation in PCOS still needs further research.

Methods: Female Sprague–Dawley rats were treated with a gavage of 1.0?mg/kg of letrozole carboxymethylcellulose solution once daily for 21 consecutive days. Serum steroid concentrations, ovarian morphology, ovarian expression of AMH and AMH-RII protein were determined and their relationships were studied.

Results: According to the morphology and endocrinology, the letrozole model group was a successful PCOS model. Serum AMH and ovarian local expression of AMH and AMH-RII were both increased in letrozole model group. The elevated AMH had a positive correlation with T, growing follicle count and a negative correlation with body weight.

Conclusions: The letrozole model group is a good animal model for the study of AMH in PCOS patients with obesity or insulin resistance. The increased serum AMH level in PCOS is the consequence of the androgen-induced excess of small antral follicles. These results lead to the hypothesis that reducing AMH may become a therapeutic target of PCOS, which is worth further research.     

Diet,physical exercise and Orlistat administration increase serum Anti-Müllerian Hormone (AMH) levels in women with polycystic ovary syndrome (PCOS)

The present study investigates the combined effect of diet, physical exercise and Orlistat for 24 weeks, on serum Anti-Müllerian Hormone (AMH) levels in overweight and obese women with polycystic ovary syndrome (PCOS) and in overweight and obese controls. Sixty-one (61) selected women with PCOS and 20 overweight and obese controls followed an energy-restricted diet, physical exercise plus Orlistat administration (120?mg, 3 times per day) for 24 weeks. At baseline, week 12 and week 24, serum levels of AMH, FSH, LH, PRL, androgens, sex hormone–binding globulin (SHBG), glucose, and insulin were measured and Free Androgen Index (FAI) and Insulin Resistance (IR) indices were calculated. In PCOS women, serum AMH levels increased after 12 and 24 weeks of treatment. After 12 weeks LH and SHBG were increased, while Testosterone decreased. After 12 and 24 weeks, FAI was decreased and all indices of IR were significantly improved. We concluded that in overweight and obese women with PCOS Orlistat administration, combined with diet and physical exercise, for 24 weeks, resulted in significant weight loss, improvement of hyperandrogenism and insulin sensitivity, and increased serum AMH levels.     

Serum anti-Müllerian hormone and insulin resistance in the main phenotypes of non-obese polycystic ovarian syndrome women in China

Objectives: Objective was to evaluate anti-Müllerian-hormone (AMH) and parameters for insulin resistance (IR) in the main phenotypes of polycystic ovarian syndrome (PCOS), and to investigate their correlation for the first time in non-obese Chinese women.

Methods: Within this prospective study, 160 PCOS cases and 40 healthy women, matched by age and BMI, were included. In four groups (n?=?40) according to the four phenotypes of PCOS by definition of the National Institute of Health (2012), AMH, ovarian volume and number of follicles 2–9?mm were assessed as well as insulin resistance indexes (Homeostatic Model Assessment) (HOMA-IR) and Quantitative Insulin Sensitivity Check Index (QUICKI).

Results: AMH levels were higher in PCOS than in controls, with differences comparing the phenotypes, highest in the group with all three criteria for PCOS. However, for HOMA-IR and QUICKI and correlation to AMH no significant differences were found.

Conclusions: AMH is a useful parameter to assess in the different phenotypes the severity of PCOS, and to compare with healthy women, for the first time demonstrated in Chinese patients. In contrast, the parameters for IR and their relation to AMH did not show clear differences comparing the four phenotypes, and need further investigation.     

Accuracy of anti-Müllerian hormone and total follicles count to diagnose polycystic ovary syndrome in reproductive women

Objective

Recently, there was a new recommendation of ultrasonographic criteria to diagnosis polycystic ovary syndrome (PCOS). In addition, serum anti-Müllerian hormone (AMH) was proposed as a surrogate marker for diagnosis of PCOS, but AMH cut-off level for diagnosis of PCOS is unclear. This study aimed to investigate the accuracy of serum AMH and evaluate new ultrasonographic criteria, follicle number per ovary (FNPO) threshold ≥ 25 follicles and ovarian volume (OV) > 10 mL, for diagnosis of PCOS.

Clinical significance of serum concentration of anti-Müllerian hormone in obese women with polycystic ovary syndrome

In the human ovary, expression of anti-Müllerian hormone (AMH) is detected primarily in granulosa cells of preantral and small antral follicles. The aim of this study was to compare serum AMH measurements in obese women with polycystic ovary syndrome (PCOS) with those in obese normo-ovulatory women and to evaluate the role of AMH as a predictor of ovulation induction by clomiphene citrate compared to FSH. Sixty-eight obese women with PCOS were compared to 17 normoovulatory obese women. All women had a body mass index greater than 30 kg/m(2). Women with PCOS received clomiphene citrate (150 mg/day) for 5 days starting from day 3 of cycle and were subdivided into responsive and non-responsive groups. There was a significant difference in AMH concentration between women with PCOS and the control group (P < 0.05) and also between women with PCOS who responded to clomiphene citrate and those who did not (P < 0.01). A value of 1.2 ng/ml AMH could be used to predict response to clomiphene citrate in obese women with PCOS (sensitivity 71%, specificity 65.7%). AMH production increases in women with PCOS compared to controls. AMH measurement could also be useful in the prediction of ovarian response to clomiphene citrate.     

Is the plasma anti-Müllerian hormone (AMH) level associated with body weight and metabolic, and hormonal disturbances in women with and without polycystic ovary syndrome?

Objective

The aim of the study was to analyze interrelation between AMH levels and body weight, metabolic, and hormonal status in normal and overweight weight women with and without polycystic ovary syndrome (PCOS).

Study design

Eighty-seven women (54 normal weight and 33 overweight) diagnosed with PCOS and 50 apparently healthy women – Non-PCOS (28 normal weight and 22 overweight) were enrolled. The body weight and height were measured and BMI was calculated. In addition to serum glucose, lipids, androgens, FSH, LH, SHBG and insulin, AMH were assessed in fasting state and free androgens index (FAI) was calculated. The insulin resistance was assessed based on the homeostasis model of assessment-insulin resistance (HOMA-IR).

Results

Plasma AMH levels were similar in normal weight and overweight PCOS groups (9.6 ± 3.5 vs. 11.2 ± 4.5 ng/mL, respectively), and as expected markedly higher than in both Non-PCOS groups (2.5 ± 0.8 and 2.3 ± 0.7 ng/mL, respectively). There were no correlations between BMI and AMH levels in all study groups. A significant positive correlation between HOMA-IR, free testosterone concentrations or FAI and AMH levels were found (R = 0.31, p < 0.001; R = 0.91, p < 0.001 and R = 0.62, p < 0.001, respectively). Moreover, there was positive correlation between total or LDL cholesterol and AMH levels (R = 0.22, p < 0.05 and R = 0.31, p < 0.05, respectively) and a negative one between HDL cholesterol and AMH levels (R = −0.17, p < 0.05) in all study subjects.

Conclusions

The plasma AMH level is associated with insulin resistance but not with BMI per se. Increased circulating AMH level seems to reflect the disturbances of gonadotrophins release in PCOS. It seems that AMH level may be used not only as new surrogate marker of ovarian hyperandrogenism in PCOS but also as a potential new cardiovascular risk factor.     

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.     

Correlation between three assay systems for anti-Müllerian hormone (AMH) determination

Purpose

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).

Methods

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).

Results

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.

Conclusions

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.     

Pregnancy and neonatal complications in women with polycystic ovary syndrome in relation to second-trimester anti-Müllerian hormone levels

Research questionAn association has been found between high anti-Müllerian hormone (AMH) levels during pregnancy and the development of polycystic ovary syndrome (PCOS)-like phenotypic traits in mouse offspring. The aim of this study was to determine whether AMH levels are associated with maternal testosterone levels, and whether high AMH concentration influences the risk of developing PCOS-related adverse pregnancy outcomes.DesignMaternal serum AMH, testosterone and sex hormone binding globulin levels were measured in blood samples taken in early second-trimester pregnancies from women with PCOS (n = 159) and healthy controls matched for body mass index (n = 320). Possible associations with preeclampsia, gestational hypertension, gestational diabetes, preterm birth and birthweight was explored by logistic and linear regression models.ResultsWomen with PCOS had higher AMH, higher total testosterone levels and higher free androgen index than controls (P < 0.001 for all three parameters). Among women with PCOS, high testosterone levels (B = 2.7; β = 0.26; P = 0.001) and low first trimester body mass index (B = –0.5; β = –0.17; P = 0.043) remained independently associated with AMH. High AMH levels were associated with decreased risk of gestational hypertension (adjusted OR 0.55; 95% CI 0.34 to 0.87), but no association was found with other adverse pregnancy outcomes or birthweight.ConclusionsWomen with PCOS had higher AMH levels during pregnancy compared with controls, but high AMH was not associated with increased risk of adverse pregnancy outcomes or birthweight.     

Effect of laparoscopic endometrioma cystectomy on anti-Müllerian hormone (AMH) levels

Abstract

Objective: To investigate temporary or long-term changes of AMH after laparoscopic endometrioma cystectomy and its dependency on characteristics of endometriomas.

Methods: One hundred and seventy-one women, open-labeled prospective study; five groups divided according age ≤/> 35, uni-/bilateral, cyst ≤/> 7?cm, coagulation/suture surgery, stage III/IV; between- and within-group analyses after 1, 3, 6, and 12?months.

Results: After 12?months, compared to pretreament, AMH decreased significantly for patients with bilateral cysts, cyst size >7?cm and endometriosis stage IV. In the between-group analysis all comparisons were significant, with exception of the surgery type. However, this was different performing the multiple linear regression analysis suggesting lower postoperative decrease using suturing technique. This analysis also showed higher age at pretreatment and bilateral cysts as risk factor for AMH decline.

Conclusions: Effects of endometrioma cystectomy on AMH are dependent on characteristics of the endometrioma, showing long-term a decrease in patients with larger, bilateral cysts and in stage IV endometriosis, but only short-time decrease in smaller, unilateral cysts and stage III which sometimes also can fully recover in AMH production within one year. In our study suture compared to coagulation surgery was protective, i.e. may lead to lower postoperative AMH decline.     

Molecular analysis of the anti-Müllerian hormone,the anti-Müllerian hormone receptor,and galactose-1-phosphate uridyl transferase genes in patients with the Mayer-Rokitansky-Küster-Hauser syndrome

Introduction. Müllerian agenesis, also named the Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) or vaginal aplasia, is the second most common cause of primary amenorrhea. It is characterized by the congenital absence of the Müllerian structures including the Fallopian tubes, the uterus, and the internal portion of the vagina in an otherwise normally feminized 46,XX subject. Most cases are sporadic in inheritance, but the occurrence of some patients with chromosomal translocations or even familial aggregates suggest a genetic basis for the disease, although the etiology of the disease is still unknown. It has been suggested that activating mutations in the anti-Müllerian hormone (AMH) or in its receptor (AMHRII) are potential sources for the defect. Methods. In this study we describe the molecular analysis of both the AMH and AMHR genes in a group of 15 patients with Müllerian agenesis. After sequencing all exons and exon/intron junctions of both genes, we were not able to detect any deleterious mutation. Results. Five new polymorphisms, 2 of them in the AMHRII gene and 3 of them in the AMH gene, were identified. No significant differences between patients and controls were observed in the frequency of a given polymorphism. Conclusion. This work reinforces the view that molecular defects in the AMH or AMHR are unlikely sources for the MRKHS syndrome.     

The impact of oral contraceptives and metformin on anti-Müllerian hormone serum levels in women with polycystic ovary syndrome and biochemical hyperandrogenemia

Objective.?To assess the impact of metformin and of two different oral contraceptives (OCs) containing cyproterone acetate and drospirenone, on serum anti-Müllerian hormone (AMH) levels, in a cohort of women with polycystic ovary syndrome (PCOS) with hyperandrogenism.

Design.?Prospective randomised study.

Setting. Division of Endocrinology and Human Reproduction, Aristotle University of Thessaloniki.

Patients.?Forty-five (45) women with PCOS diagnosed according to the criteria proposed in 1990 by the NIH.

Interventions.?Women with PCOS were randomised into three groups, all treated for 6 months: Group A received an OC containing 35?μg ethinylestradiol plus 2?mg cyproterone acetate, Group B received an OC containing 30?μg ethinylestradiol plus 3?mg drospirenone and Group C received metformin 850?mg?×?2.

Main outcome measure(s).?Anti-Müllerian hormone levels were measured by a specific ELISA.

Results.?AMH was significantly decreased under treatment with 35?μg ethinylestradiol plus 2?mg cyproterone acetate (p?=?0.002 at 3 months and p?<?0.001 at 6 months). Treatment with 30?μg ethinylestradiol plus 3?mg drospirenone, and treatment with metformin 850?mg?×?2 did not significantly affect serum AMH levels. AMH was significantly decreased under OCs treatment compared to metformin 850?mg?×?2 (p?=?0.005).

Conclusion(s).?AMH serum levels were significantly decreased under treatment with 35?μg ethinylestradiol plus 2?mg cyproterone acetate, due to decrease in androgens and suppression of gonadotropins.     

Clinical utility of different anti-Müllerian hormone – AMH assays for the purpose of pregnancy prediction

Purpose: Comparison of outcomes of IVF cycles where the AMH levels was measured with five different AMH kits: Immunotech (IOT), Beckman Coulter II Gen. RUO, Beckman Coulter II Gen. IVD (BC II IVD), Ansh Labs ultrasensitive (Ansh) and the automated Elecsys Roche assay.

Methods: Retrospective analysis of clinical data for 3693 cycles.

Results: In women 1.4?ng/ml) AMH concentrations, and in those >?39?years with medium (≥0.6 and ≤1.4?ng/ml) and high AMH concentrations the clinical pregnancy rate differed significantly among groups of patients whose AMH level was measured with different kits. In those subgroups, the highest rates were recorded for the BC II IVD and Ansh groups, while the lowest in the IOT group. AMH concentrations differed significantly between different kits in all age groups (the highest in each age group was for the IOT kit and the lowest for BC II IVD). AMH correlates positively with antral follicle count, MII and number of oocytes retrieved.

Conclusions: This study demonstrated that we could expect very different pregnancy rates with the same AMH results depending on the AMH kit used. That would means, different values of AMH could similarly lead to misleading clinical decisions in IVF.