Anti-Müllerian hormone levels during hormonal contraception in women with polycystic ovary syndrome

OBJECTIVE: The use of oral contraceptive (OC) pills alters the characteristic features of polycystic ovary syndrome (PCOS) complicating the diagnosis of this disease. Anti-Müllerian hormone (AMH) levels are high in PCOS patients and are stable throughout the menstrual cycle in healthy subjects. This study examined the influence of hormonal suppression with OC therapy on the serum AMH levels in women with PCOS and with normal menstrual cycles. STUDY DESIGN: Thirty women with PCOS and 15 women with normal menstrual cycles were enrolled in this prospective study. Serum was collected from the subjects during the early follicular phase of the menstrual cycle and after the sixth cycle of oral contraceptive therapy, and stored frozen until assayed. The effect of OC therapy on the serum AMH, estradiol (E(2)), luteinizing hormone (LH), follicle-stimulating hormone (FSH), free testosterone, total testosterone, and dehydroepiandrosterone sulfate (DHEA-S) levels was studied. In addition, ovarian volume and follicle count were assessed. RESULTS: The serum AMH levels in PCOS patients were significantly higher than in healthy women at baseline (+/-S.D.; 5.49+/-2.26 and 1.93+/-0.51 ng/ml, respectively; p=0.001). After six cycles of OC therapy, no significant changes in the AMH levels were observed in either the PCOS patients or normally cycling women. Ultrasound showed significant reductions in ovarian volume and follicle number and size at 6 months in both groups. CONCLUSION: Although significant reductions were observed in ovarian volume and follicle number, 6 months of contraceptive therapy did not change the serum AMH concentration in either group. AMH may be considered a new marker in PCOS patients who are already on contraceptive treatment.     

Anti-Müllerian hormone as a driving force of polycystic ovary syndrome,independently from insulin resistance

Research questionWhich clinical features, along with biological features, ultrasound features, or both, are the most strongly associated with either high or low anti-Müllerian hormone (AMH) levels in patients with polycystic ovary syndrome (PCOS)?DesignA retrospective cross-sectional study conducted within a university-affiliated reproductive endocrinology unit in Lille, France. A total of 639 patients with PCOS according to the Rotterdam Criteria and 137 control women were included. A comparison of clinical, hormonal, metabolic and ultrasound data in patients with PCOS and controls belonging to the first (Q1) and fourth (Q4) quartiles of their respective AMH ranges (discriminant analysis) was conducted.ResultsIn the PCOS group, patients in Q4 had higher LH levels and a more severe phenotype, but they were thinner and had lower levels of hyperinsulinaemia than patients in Q1. In the PCOS group, discriminant analysis yielded a highly significant model in which follicle number per ovary (FNPO) and serum LH were strongly and equally discriminating between Q4 and Q1 (R² at 0.371 and 0.304, respectively, both P < 0.0001), whereas body mass index had less, although significant, effect (R² = 0.075, P < 0.0001). In control women, discriminant analysis yielded a significant discriminant model, including only FNPO and age (R² at 0.62 and 0.27, both P < 0.0001).ConclusionHigh serum AMH levels are associated with high serum LH levels and more severe features of PCOS. Conversely, the effect of hyperinsulinism may be greater in patients with lower serum AMH levels, suggesting independent effects of AMH and insulin on the phenotypic expression of PCOS.     

Anti-Müllerian hormone and fertility disturbances in obese women and women with polycystic ovary syndrome

Anti-Müllerian hormone (AMH) belongs to a family of growth and differentiation factors beta (TGF-beta). In male fetuses AMH induces regression of Müller's ducts whereas in female ones this hormone plays an important role during adolescence and reproductive period. AMH participates in regulation of folliculogenesis by inhibiting the recruitment of prenatal and antral follicles. The aim of the present study was to summarize the current knowledge of the role of AMH in menstrual and fertility disturbances in obese women and those with polycystic ovary syndrome.     

Anti-Müllerian hormone and polycystic ovary syndrome: assessment of the clinical pregnancy rates in in vitro fertilization patients

Abstract

Objective: The purpose of this study is to investigate the role of serum anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH) and antral follicle count (AFC) for the prediction of clinical pregnancy rates (CPR) in women with polycystic ovary syndrome (PCOS) undergoing IVF treatment.

Design: Prospective cohort study.

Setting: University hospital.

Patients: One hundred and fifty consecutive women with PCOS.

Interventions: All women underwent controlled ovarian stimulation with long agonist protocol followed by IVF procedure. Outcomes of pregnant and non-pregnant groups were compared.

Main outcome measure: CPR; AMH, FSH and AFC means and percentiles.

Results: Fifty-one (34%) clinical pregnancies were observed in 150 women. Mean AMH was 6.7?±?2.8 and 7.1?±?4.3?ng/mL in pregnant and non-pregnant women, respectively (p?=?0.594). The CPR were 27.8%, 35.0% and 37.8% in <25%, 25%–75% and >75% AMH percentiles, respectively (p?=?0.656). There were also no significant difference in mean FSH and AFC between pregnant and non-pregnant women (p?=?0.484 and p?=?0.165, respectively).

Conclusion: AMH, FSH and AFC are not predictive for CPR in women with PCOS undergoing IVF treatment. Mean AMH values were not significantly different between pregnant and non-pregnant women. Although CRP increased in parallel with the raise in AMH percentiles, this remained insignificant.     

Anti-Müllerian hormone levels in women with polycystic ovarian syndrome compared with normal women of reproductive age in China

Objectives: Aim was to evaluate anti-Müllerian-hormone (AMH) in women with polycystic ovary syndrome (PCOS) comparing with normo-ovulatory women, and to assess for the first time AMH levels across reproductive lifespan in Chinese women.

Methods: Within the prospective cross-sectional study in PCOS cases and in normal subjects, AMH and other hormone levels were measured in early follicular phase in five age groups. Additionally ovarian ultrasound parameters were assessed.

Results: A total of 437 PCOS patients and 150 normo-ovulatory women matched by age were included. AMH levels were 2- to 3-fold higher in PCOS cases. In both groups AMH decreased with age in a non-linear pattern. In normo-ovulatory women AMH levels were relatively constant from 18 to 25 years and then declined with age. In contrast, AMH in PCOS cases declined with an increasing rate from 18 to 45 years, narrowing the difference in older women.

Conclusions: AMH may be a useful parameter to assess the severity and prognosis of PCOS since certain differences exist to normo-ovulatory women. Further studies may improve the understanding of the relationship between AMH levels and age, providing more scientific basis for fertility counselling for both healthy women and PCOS cases.     

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.     

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.     

Anti-Müllerian hormone in polycystic ovary syndrome and normo-ovulatory women: Correlation with clinical,hormonal and ultrasonographic parameters

BackgroundAlthough the ultimate pathogenesis of polycystic ovary syndrome (PCOS) remains obscure, the distinctive feature is failure of follicular maturation resulting in anovulation and accumulation of preantral and small antral follicles which contribute significantly to the production of anti-Müllerian hormone (AMH).ObjectivesTo compare serum AMH levels between PCOS and normo-ovulatory women; and to investigate whether AMH correlates to clinical, hormonal and ultrasonographic parameters in both groups.DesignComparative observational cross-sectional study.SettingDepartment of Obstetrics and Gynecology, Kasr El-Aini Teaching Hospital, Faculty of Medicine, Cairo University.SubjectsThirty-five women with PCOS according to the Rotterdam consensus; and 35 normo-ovulatory-matched controls with male, tubal or unexplained infertility.MethodsSerum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, androstenedione, estradiol, fasting insulin and AMH were measured in the early follicular phase (day 3–4) of natural cycle or progestin-induced withdrawal bleeding (in PCOS); together with transvaginal sonography for detection of the number of small follicles (<10mm) and calculation of ovarian volume.Main outcome measuresCorrelation between AMH and clinical, hormonal and ultrasonographic parameters in both groups.ResultsAMH was significantly higher in the PCOS group. In the whole group of patients and in each group separately, AMH was positively correlated to LH, LH/FSH, number of follicles <10mm and ovarian volume; and negatively correlated to FSH. No correlation was found between AMH and age, BMI, estradiol or fasting insulin. Testosterone and androstenedione were positively correlated to AMH in the PCOS group exclusively (r=0.557; P=0.001 and r=0.451; P=0.007, respectively). Multiple regression analysis demonstrated that testosterone was the only determinant for AMH level (r=0.485; P<0.001).ConclusionsHyperandrogenism is associated with increased AMH secretion in PCOS patients, possibly due to increased number of small antral follicles. Assessment of AMH levels before and after the treatment of hyperandrogenism should be recommended in the plan of management of PCOS.     

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.     

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.     

β cell function and insulin resistance in lean cases with polycystic ovary syndrome

Obesity is a major factor in development of insulin resistance (IR) and metabolic features in polycystic ovary syndrome (PCOS) patients. Nearly two-thirds patients with PCOS (30 of 37 confirmed cases of PCOS) in our previous community based study were lean, in contrast to Caucasians. Metabolic parameters including IR and β cell function have not been characterized well in this group of lean PCOS. To study the metabolic features including IR and β cell function in lean PCOS patients, 53 patients with BMI, <23?kg/m² were compared with 71 obese PCOS and 45 age and body mass index matched controls. Lean patients had similar β cell function and IR as compared to controls and obese patients, though the latter group had more metabolic abnormality. Fasting c-peptide and its ratio to glucose were significantly higher in lean patients compared to controls. In subset of subjects with five point OGTT, disposition index and Matsuda index (MI) showed significant negative correlation with BMI and blood pressure. MI also negatively correlated with waist, WHR, and HOMAB. High fasting C-peptide is probably a class effect as is seen in both lean and obese PCOS.     

Response to ovulation induction treatments in women with polycystic ovary syndrome as a function of serum anti-Müllerian hormone levels

Journal of Assisted Reproduction and Genetics - To assess whether anti-Müllerian hormone (AMH) can predict response to ovulation induction (OI) with clomiphene citrate (CC), letrozole (LET),...