Anti-Müllerian Hormone Levels In Women Research Articles

Correlation between anti-müllerian hormone in polycystic ovarian syndrome with metformin: a systematic review and meta-analysis

Objective This study aims to examine the short-term effects of oral metformin (MET) on serum anti-müllerian hormone (AMH) levels and to verify its impact on AMH concentrations in women with polycystic ovary syndrome (PCOS). Methods The literature search, extending from January 2000 to April 2023, was conducted using databases such as PubMed, Embase, and the Cochrane Central, resulting in the inclusion of 20 studies. These selected studies, evaluated for quality using the Newcastle–Ottawa Scale, investigated changes in AMH levels before and after treatment, with durations ranging from less than three months to over six months. The reported outcomes were quantified as standardized mean differences (SMD) with 95% confidence intervals (CI). This comprehensive systematic review and meta-analysis was registered with the International Prospective Register of Systematic Reviews (PROSPERO) under the registration number CRD42023420705. The statistical analyses were performed using Review Manager 5.4.1. Results ① The study incorporated 20 articles, consisting of 12 prospective studies, 7 randomized controlled trials (RCT), and 1 cross-sectional study. ② Serum AMH levels in patients with PCOS diminish subsequent to the oral administration of MET. ③ Across the spectrum of studies analyzed, a pronounced degree of heterogeneity is evident, potentially ascribed to differential parameters including body mass index (BMI), daily pharmacological dosages, the temporal extent of treatment regimens, criteria of PCOS, and detection Methods. ④ The impact of MET on AMH levels exhibits a dose-responsive trend, with escalating doses of MET being associated with progressively greater declines in AMH concentrations in the patient population. ⑤ For women with PCOS receiving MET therapy, a minimum treatment duration of three months may be necessary to observe a reduction in serum AMH levels. Conclusions The results of this meta-analysis indicate that MET treatment exerts a suppressive effect on serum AMH levels in women with PCOS. It appears that a treatment duration of at least three months is required to achieve a significant decrease in AMH concentrations. Furthermore, the influence of MET on AMH is dose-dependent, with higher doses correlating with more pronounced reductions in AMH levels among the patients studied.

Effect of metformin on anti-mullerian hormone levels in women with polycystic ovarian syndrome: a systematic review and meta-regression analysis of randomized controlled trials with

BackgroundSeveral interventional studies have evaluated the potential anti-Mullerian hormone (AMH)-reduction effect of metformin. However, the results are still contradictory. In order to obtain a better viewpoint from them, this study aimed to comprehensively investigate the effects of metformin on AMH in the women with with polycystic ovarian syndrome (PCOS).MethodsScopus, PubMed/Medline, Web of Science, Cochrane, and Embase databases were searched using standard keywords to identify all controlled trials investigating the AMH levels following metformin administration. Pooled weighted mean difference and 95% confidence intervals were achieved by random-effects model analysis for the best estimation of outcomes.ResultsSixteen studies with 484 participants’ were included in this article. The pooled findings showed that AMH levels in the single arm clinical trials were significantly reduced (pooled WMD of -3.06 ng/ml; 95% confidence interval [CI] -4.03 to -2.10; P < 0.001) after use of metformin. Furthermore, compared to the control group, in randomized clinical trials, a reduced significant effect on AMH levels was observed following use of metformin (pooled WMD of -3.47 ng/ml; 95% CI -7.14 to -0.19; P = 0.047). Furthermore, higher reduction in the AMH levels with a metformin dosage ≤ 1500 mg/day and duration of treatment ≤ 12 weeks when compared to higher dosages and duration of intervention, observed in this meta-analysis.ConclusionsIn conclusion, results this meta-analysis of clinical trials confirms the beneficial effect of the treatment with metformin in the reduction of the AMH levels in women.

The Correlation between Sex Hormone-Binding Globulin and Clinical Characteristics According to Anti-Müllerian Hormone in Women with Regular Menstrual Cycles: A Prospective Study.

Polycystic ovarian syndrome (PCOS) can be diagnosed when the anti-Müllerian hormone (AMH) levels are high, but in clinic, women who do not meet the diagnosis of PCOS but have elevated AMH levels are often seen. This study aimed to compare the differences in menstrual cycle patterns and hormone levels in women with regular menstrual cycles, but not PCOS, by dividing them into high and low AMH groups. This multicenter prospective study included 68 healthy women. Participants with regular menstrual cycles were divided into two groups according to their AMH levels. The main outcome measures were menstrual cycle pattern, body mass index, and hormone levels (thyroid stimulating hormone, prolactin, testosterone, sex hormone-binding globulin, and free androgen index), which were compared between the groups according to AMH levels. The ovulation was assessed by performing pelvic ultrasound, and by assessing the hormone levels of the luteinizing hormone and progesterone. The criteria for determining normal and high AMH levels were based on previous literatures. The participants were divided into normal (39 people) and high (29 people) AMH group. No differences were found in age or BMI between the two groups, and no other differences were observed in TSH, prolactin, testosterone, or free androgen index. However, the high AMH group had significantly higher SHBG levels than the normal group (normal group: 65.46 ± 25.78 nmol/L; high group: 87.08 ± 45.05 nmol/L) (p = 0.025). This study is the first to analyze the association between SHBG and AMH levels in women with regular menstrual cycles. Elevated AMH levels are associated with increased levels of SHBG levels.

The Association of Anti-Mullerian Hormone and Infertility Hormonal Imbalance with Polycystic Ovarian Syndrome Among Iraqi Patients.

&lt;b&gt;Background and Objective:&lt;/b&gt; The pathogenesis of PCOS, which affects 5-15% of women of reproductive age, is still poorly understood and which characteristic might be considered essential for its diagnosis is still unknown. This study aimed to determine the significance and relationship between Anti-Mullerian Hormone (AMH) and other infertility hormones in the Polycystic Ovarian Syndrome (PCOS) diagnosis. &lt;b&gt;Materials and Methods:&lt;/b&gt; This study involves 200 women who visited Al-Ramadi Maternity and Child Teaching Hospital in Al-Ramadi, Iraq from October, 2022 to May, 2023. Study participants included 50 women as controls and 150 women with PCOS who were diagnosed using the Rotterdam criteria. The clinical history included oligomenorrhea and BMI. Laboratory investigations included blood tests for FSH, LH, prolactin and AMH levels done for all women who participated in this study. &lt;b&gt;Results:&lt;/b&gt; Age and BMI were comparable for PCOS cases and controls. The AMH levels in women with PCOS increased statistically with severity compared to controls, with the mean AMH level found to be 3.53 ng mL&lt;sup&gt;1&lt;/sup&gt; in controls, whereas it ranged from 6.19 for mild cases to 7.49 for moderate cases to 12.83 for severe cases in PCOS cases. The AMH alone had the highest diagnostic sensitivity (78.6%) and specificity (97.6%) for PCOS at a cut-off of 5.82 ng mL&lt;sup&gt;1&lt;/sup&gt;. All study participants had a positive correlation between AMH and LH (R&lt;sup&gt;2&lt;/sup&gt; = 0.391, p = 0.0031). &lt;b&gt;Conclusion:&lt;/b&gt; The AMH levels were noticeably higher in PCOS patients compared to controls. The AMH could not accurately diagnose PCOS when used as an independent marker. The AMH levels did, however, have good diagnostic potential in combination with current Rotterdam criteria for PCOS diagnosis.

Hyperhomocysteinemia and pregnancy outcomes in women with polycystic ovary syndrome: A case-control study.

One of the reproductive medicine challenges is to determine the role of hyperhomocysteinemia in the pathogenesis of polycystic ovary syndrome (PCOS), especially in women with recurrent pregnancy loss (RPL). Determine the correlation between hyperhomocysteinemia and pregnancy outcome in women with PCOS. This case-control study involved 245 women (20-30 yr) and was conducted in Georgia, Tbilisi from 2019-2022. Of these, 175 were women with PCOS (study group) and 70 were healthy women (control group). Women with PCOS were divided into group I with RPL (n = 90), and group II with live births (n = 85). Group I was divided into subgroups A and B with and without insulin resistance. The investigation measured homocysteine (Hcy), follicle-stimulating, luteinizing, anti-Mullerian hormones, total and free testosterone were determined. To determine the ovarian volume and antral follicle count, participants also underwent an ultrasound examination. In women with PCOS, the average Hcy level was significantly higher than in the controls, p 0.05. In group I, the average Hcy level was significantly higher than in group II and controls, p 0.05. There was no significant difference in average Hcy level between group II and controls. The average Hcy level in group I, subgroup A was significantly higher than in subgroup B, p 0.05. The average total, free testosterone levels, and homeostatic model assessment-insulin resistance levels (HOMA-IR) in group I was significantly higher than in group II and controls. HOMA-IR in group II and controls did not differ significantly. The average anti-Mullerian hormone levels in women with PCOS were significantly higher than controls, p 0.05. No significant difference was observed in average anti-Mullerian hormone level, ovarian volume, antral follicle count, and body mass index between the comparison groups of PCOS. In group I, a positive correlation between Hcy with HOMA-IR was detected. Serum Hcy levels are elevated in women with PCOS and RPL, which correlates with their insulin resistance status.

Lower anti-Müllerian hormone levels are associated with HIV in reproductive age women and shorter leukocyte telomere length among late reproductive age women.

We sought to better understand factors associated with ovarian aging in women with HIV (WWH). HIV has been associated with diminished fertility, younger age at menopause, and shorter leukocyte telomere length (LTL), a marker of cellular aging. We herein examine cross-sectional and longitudinal associations between LTL, anti-Müllerian hormone (AMH), and HIV. We included WWH and HIV-negative women 12-50 years of age in the CARMA cohort with one or more study visit(s). LTL and AMH were measured by qPCR and ELISA, respectively. Women were analyzed in peak reproductive (<35 years) vs. late reproductive (≥35 years) life phases. Using multivariable mixed-effect linear or logistic regressions, we assessed factors associated with AMH and ΔAMH/year while adjusting for relevant confounders. WWH had shorter LTL and lower AMH levels compared to HIV-negative controls despite being of similar age. After adjusting for relevant factors, HIV was associated with 20% lower AMH levels in women under 35 years of age and shorter LTL was associated with AMH levels below 2 ng/ml among women aged 35 years or older. Longitudinally, ΔAMH/year was largely related to initial AMH level among older women, and to age in younger women. Factors associated with AMH change across women's reproductive lifespan. Lower AMH among peak reproductive aged WWH suggests that HIV may have an initial detrimental effect on ovarian reserve, an observation that may warrant counseling around pregnancy planning. In women aged 35 years or older, the association between shorter LTL and lower AMH suggests that the immune and reproductive aging connections are more important in this age group.

Circulating Anti-Müllerian hormone in a cohort-study of women with severe obesity with and without polycystic ovary syndrome and the effect of a one-year weight loss intervention

BackgroundWomen with polycystic ovary syndrome (PCOS) have high circulating anti-Müllerian hormone (AMH) levels which is correlated with antral follicle count and polycystic ovarian morphology and negatively correlated with body mass index (BMI). Moreover, diet-induced weight loss in women with PCOS and overweight or obesity, reduce or normalize AMH-levels. There is, however, no previous study investigating the circulating AMH levels in women with severe obesity and how a structured diet-induced weight loss program affects circulating AMH levels in these women. Therefore, this study aims to investigate circulating AMH levels in a population of women with severe obesity (BMI ≥ 35 kg/m2) with and without PCOS, as diagnosed by the NIH-criteria, and to investigate the effect of a one-year weight loss program with a very low-energy diet (VLED) on circulating levels of AMH.MethodsIn a prospective cohort-study, were 246 women with severe obesity were screened for PCOS diagnosis with the NIH-criteria, circulating AMH and anthropometry were measured at baseline and after a 12-month weight loss intervention with very low-energy diet (VLED).ResultsMean BMI was 39.9 ± 4.7 (PCOS), 39.6 ± 4.3 (non-PCOS) P = 0.960. Circulating AMH was higher in women with PCOS (5.47 ± 4.89 µg/L) compared with non-PCOS (2.66 ± 3.71 µg/L) P < 0.001 and was positively correlated with circulating total testosterone in both groups. Next, we performed ROC-analyses, and show that circulating AMH could not discriminate women with PCOS and severe obesity from non-PCOS women with severe obesity. Finally, a one-year weight reduction program does not affect circulating AMH levels despite significant weight loss neither in women with PCOS, nor without PCOS and severe obesity.ConclusionWomen with severe obesity and PCOS have elevated levels of circulating AMH compared to women without the syndrome. AMH-levels could not discriminate women with PCOS from non-PCOS because of low sensitivity and specificity. Significant weight loss was not associated with changes in circulating AMH levels, neither in women with, nor without PCOS and severe obesity. These results imply that in women with severe obesity, a greater weight loss may be needed to improve reproductive features, independent of PCOS diagnosis.Trial registration number:Clinical trial.gov: NCT01319162.

Insulin-like peptide 5 (INSL5) positively correlates with anti-Müllerian hormone (AMH) in women with the polycystic ovary syndrome: a case-control study

BackgroundInsulin-like peptide 5 (INSL5) is involved in both reproductive and metabolic processes in polycystic ovary syndrome (PCOS). This study aimed to evaluate the relationship between INSL5 and anti-Müllerian hormone (AMH).MethodsA retrospective case–control study was conducted in a university-based reproductive centre between December 2019 and January 2021. We included 117 women with PCOS and 100 healthy subjects from Zhejiang Province. All subjects were divided into four groups (1st–4th) based on quartiles of serum INSL5 levels. Serum INSL5 concentration was assayed using an enzyme-linked immunosorbent assay.ResultsA significant direct association was observed between serum INSL5 and AMH levels in women with PCOS. The mean AMH level in the 1st–4th INSL5 level quartiles were 4.64, 5.20, 6.46, and 9.48 ng/ml, respectively (P < 0.001). After adjusting for age, body mass index, metabolic indices, and serum levels of oestradiol and total testosterone, AMH levels remained positively and significantly associated with INSL5 levels (P for trend < 0.001). The diagnostic value of AMH was better than that of INSL5.ConclusionsINSL5 and AMH levels were significantly correlated and elevated in women with PCOS. INSL5 and AMH might be associated with increased androgen secretion and chronic anovulation in PCOS.

Investigating the relationship between body composition, lifestyle factors, and anti-Müllerian hormone serum levels in women undergoing infertility assessment.

The impact of lifestyle factors such as adiposity, smoking, stress, exercise, and nutrition on anti-Müllerian hormone (AMH) levels remains an unresolved question. This study aims to examine the anthropometric and lifestyle characteristics of women undergoing infertility investigations and to examine the relationship between serum AMH levels and body fat percentage, body mass index (BMI), and lifestyle factors including smoking, alcohol intake, nutrition, exercise, and stress. Only women undergoing infertility investigations were included in the study. Those with a diagnosis of polycystic ovary syndrome (PCOS) were excluded. Body fat percentage was measured using the Tanita Body Composition Monitor and BMI calculated. Lifestyle factors were evaluated using the Simple Lifestyle Indicator Questionnaire (SLIQ). Ninety-six women took part in the study. Of these, 35.4% (n = 34) were obese, and 28.1% (n = 27) were overweight according to their BMI. According to body fat percentage, 47.9% (n = 46) were classified as obese. An "unhealthy " SLIQ score was measured in 25% (n = 24) of participating women. There was no relationship between AMH and anthropometric or lifestyle factors, namely, body fat percentage (B = - 0.11, p = 0.76), BMI (B = - 0.14, p = 0.76), smoking [currents smokers (B = - 1.86, p = 0.56), ex-smoker (B = 3.07, p = 0.41)], SLIQ score (B = 0.1.96, p = 0.29), stress (B = 0.12, p = 0.96), exercise (B = - 0.94, p = 0.77), alcohol (B = - 0.94, p = 0.77), or nutrition (B = - 3.14, p = 2.44). Body fat percentage, BMI, lifestyle choices, and high stress levels do not correlate with AMH levels in women seeking infertility investigations. We identified a high incidence of obesity and low levels of healthy lifestyle scores in our study population. Our study highlights the urgent need for patient education and optimization of pre-pregnancy health.

Association between an AMH promoter polymorphism and serum AMH levels in PCOS patients.

STUDY QUESTIONDo polymorphisms in the anti-Müllerian hormone (AMH) promoter have an effect on AMH levels in patients with polycystic ovary syndrome (PCOS)?SUMMARY ANSWERWe have identified a novel AMH promoter polymorphism rs10406324 that is associated with lower serum AMH levels and is suggested to play a role in the mechanism of regulation of AMH gene expression in women.WHAT IS KNOWN ALREADYFollicle number is positively correlated with serum AMH levels, reflected by elevated AMH levels in women with PCOS. In addition, it is suggested that AMH production per follicle is higher in women with PCOS than in normo-ovulatory women, implying an altered regulation of AMH in PCOS.STUDY DESIGN, SIZE, DURATIONA discovery cohort of 655 PCOS women of Northern European ancestry and both an internal and external validation PCOS cohort (n = 458 and n = 321, respectively) were included in this study. Summary-level data of an AMH genome-wide association study meta-analysis including 7049 normo-ovulatory women was included as a control cohort. A genetic approach was taken through association analysis and in silico analysis of the associated variants in the AMH promoter. In vitro analysis was performed to investigate the functional mechanisms.PARTICIPANTS/MATERIALS, SETTING, METHODSAll common two-allelic single-nucleotide polymorphisms (SNPs) in the region Chr19:2 245 353–2 250 827 bp (Build 37) were selected for the analysis. Linear regression analyses were performed to determine the association between SNPs in the AMH promoter region and serum AMH levels. For the in silico analysis, the webtools ‘HaploReg’ v4.1 for ENCODE prediction weight matrices and ‘atSNP’ were used. In vitro analysis was performed using KK1 cells, a mouse granulosa cell line and COV434 cells, a human granulosa tumor cell line. Cells were transfected with the reference or the variant human AMH promoter reporter construct together with several transcription factors (TFs). Dual-Glo® Luciferase Assay was performed to measure the luciferase activity.MAIN RESULTS AND THE ROLE OF CHANCEPolymorphism rs10406324 was significantly associated with serum AMH levels in all three PCOS cohorts. Carriers of the minor allele G had significantly lower log-transformed serum AMH levels compared to non-carriers (P = 8.58 × 10−8, P = 1.35 × 10−3 and P = 1.24 × 10−3, respectively). This result was validated in a subsequent meta-analysis (P = 3.24 × 10−12). Interestingly, rs10406324 was not associated with follicle count, nor with other clinical traits. Also, in normo-ovulatory women, the minor allele of this variant was associated with lower serum AMH levels (P = 1.04 × 10−5). These findings suggest that polymorphism rs10406324 plays a role in the regulation of AMH expression, irrespective of clinical background. In silico analysis suggested a decreased binding affinity of the TFs steroidogenenic factor 1, estrogen-related receptor alpha and glucocorticoid receptor to the minor allele G variant, however in vitro analysis did not show a difference in promoter activity between the A and G allele.LIMITATIONS, REASONS FOR CAUTIONFunctional analyses were performed in a mouse and a human granulosa cell line using an AMH promoter reporter construct. This may have limited assessment of the impact of the polymorphism on higher order chromatin structures. Human granulosa cells generated from induced pluripotent stem cells, combined with gene editing, may provide a method to elucidate the exact mechanism behind the decrease in serum AMH levels in carriers of the −210 G allele. We acknowledge that the lack of follicle number in the external validation and the control cohort is a limitation of the paper. Although we observed that the association between rs10406324 and AMH levels was independent of follicle number in our discovery and internal validation PCOS cohorts, we cannot fully rule out that the observed effects on serum AMH levels are, in part, caused by differences in follicle number.WIDER IMPLICATIONS OF THE FINDINGSThese results suggest that variations in serum AMH levels are not only caused by differences in follicle number but also by genetic factors. Therefore, the genetic context should be taken into consideration when assessing serum AMH levels in women. This may have clinical consequences when serum AMH levels are used as a marker for the polycystic ovarian morphology phenotype.STUDY FUNDING/COMPETING INTEREST(S)No external funding was used. J.S.E.L. has received consultancy fees from the following companies: Ferring, Roche Diagnostics and Ansh Labs and has received travel reimbursement from Ferring. J.A.V. has received royalties from AMH assays, paid to the institute/lab with no personal financial gain. The other authors declare no competing interests.TRIAL REGISTRATION NUMBERN/A.

East Asian Herbal Medicine (EAHM) Alone for the Treatment of Women with Diminished Ovarian Reserve (DOR): A Systematic Review and Meta-analysis

Objectives: The aim of this study was to find out whether east asian herbal medicine (EAHM) treatment alone is effective in improving pregnancy-related indicators compared to conventional medicine in women with Diminished Ovarian Reserve (DOR).Methods: We searched eligible studies from PubMed, Cochrane Library, EMBASE, Chinese National Knowledge Infrastructure Database, CiNii, Korean Medical Database, Korean Studies Information Service System, Oriental Medicine Advanced Searching Integrated System, ScienceOn. GRADE pro was used to evaluate the current evidence of the study.Result: A total of 5 studies, 325 women with DOR were included. EAHM showed a significant effect on improvement of pregnancy rate (n=270, RR 2.13 [95% CI 1.44 to 3.15], Z=3.78, p=0.0002, I2=0%) and Anti-Mullerian Hormone (AMH) level (n=211, SMD 0.82 [95% CI 0.40 to 1.25], Z=3.80, p=0.0001) compared to conventional medicine. In ovulation rate (n=156, RR 0.86 [95% CI 0.70 to 1.06], Z=1.43, p=0.15, I2=0%), Antral Follicle Count (n=245, SMD 0.27 [95% CI -0.25 to 0.79], Z=1.01, p=0.31), and follicle stimulating hormone (n=245, SMD 0.29 [95% CI -0.13 to 0.70], Z=1.36, p=0.17) level, EAHM showed similar effects to conventional medicine. In this study, the most frequently used herbal medicines were Cuscutae Semen, Dipsaci Radix, and Angelicae Gigantis Radix.Conclusion: This meta-analysis showed that EAHM could improve pregnancy rates and AMH levels in women with DOR. However, more well-designed RCTs will have to be performed further in the future.

Effect of Reproductive and Lifestyle Factors on Anti-Mullerian Hormone Levels in Women of Indian Origin.

Infertility is a world-wide problem and one third females. Over the years, anti-mullerian hormone (AMH) has emerged as a major marker of ovarian reserve. There is also increasing interest in determining the factors which can impact AMH levels. To correlate the association of reproductive and lifestyle factors on AMH levels in women of Indian origin. Multicentric cross sectional study. The study was conducted using data extracted from the patient records of seven private fertility practices located in North India. Women who were attending these clinics for fertility treatment were requested to fill the questionnaire related to reproductive and lifestyle factors. Our outcome variable was level of AMH measured in the past 3 months, and was assessed as normal or low. All analyses were conducted using STATA 17. We found a direct association of low AMH with increasing age, short cycles, amenorrhea and women with family history of premature menopause. We found a direct correlation of high AMH and women with polycystic ovary syndrome and those whose partners had Oligoasthenoteratozoospermia (OATS) or azoospermia. There was no correlation with smoking, sleep, diet, body mass index, cell phone or laptop use in our study. Reproductive and lifestyle factors may affect ovarian reserve and but there was a dearth of human studies in this area. To the best of our knowledge this is the first human study on the effect of AMH on Laptop and Cell phone use. We urgently need more studies to confirm or refute our findings so that we can counsel our patients well.

Evaluation of Ovarian Reserve in Women With Rheumatoid Arthritis.

Objective: Subfertility is commonly observed in patients with rheumatoid arthritis (RA). Although the causes are not well established, the alteration of the ovarian reserve is thought to contribute to the lower chances of pregnancy. This cross-sectional study aimed to evaluate the ovarian reserve in patients with RA. Materials and methods: Two parameters associated with ovarian reserves such as the antral follicle count (AFC) and the anti-müllerian hormone (AMH) were assessed in 38 patients with RA. We also analyzed the correlation of these parameters with the medication used to treat this pathology and with the illness severity. Results: The AMH levels in women with RA were comparable to those found on healthy individuals although the RA patients were more likely to have a low AFC. Ovarian reserve and RA were neither influenced by parameters of disease activity nor by the use of medication. Conclusion: The ovarian reserve in women with RA was similar to that found in healthy individuals.

Do baseline AMH levels in women with polycystic ovary syndrome predict ovulation rate and time to ovulation: a secondary analysis of PCOSAct trial?

ObjectiveTo assess the association of baseline anti‐Müllerian hormone (AMH) levels with ovulation, time to ovulation and fertility outcomes in women with polycystic ovary syndrome (PCOS) receiving clomiphene citrate (CC) and compare this with placebo.DesignSecondary analysis of the PCOSAct trial (NCT01573858).Setting27 trial centres in mainland China.Population or sample1000 infertile women with PCOS receiving either CC or placebo.MethodsBaseline serum AMH was measured and analysed as a continuous and as a categorical variable. Interaction between AMH and CC was tested. Predictive values of AMH for ovulation, time to ovulation and fertility outcomes were assessed.Main outcome measuresOvulation and time to ovulation.Results900 baseline AMH data were available for analysis. There were no significant interactions with ovulation or conception for AMH and CC treatment (P = 0.782 and 0.419, respectively). Women in the upper quartile of AMH &gt;15.88 ng/ml had significant lower ovulation (odds ratio [OR] 0.34, 95% CI 0.20–0.58) and conception rates (OR 0.65, 95% CI 0.42–1.00) compared with women in the lower quartile. Associations of AMH with clinical pregnancy (OR 0.98, 95% CI 0.95–1.01) and live birth (OR 0.98, 95% CI 0.96–1.01) were not significant. Ovulation rate increased until baseline AMH levels ≥7.0 ng/ml in women treated with CC but decreased when AMH increased in women with placebo. When AMH &lt;7.0 ng/ml, an AMH threshold at 4.11 ng/ml predicted ovulation in women receiving CC (area under the curve [AUC] 0.64, 95% CI 0.42–0.86), with a sensitivity of 64% and a specificity of 62%, whereas prediction was poor for AMH ≥7.0 ng/ml (AUC 0.38, 95% CI 0.28–0.47). Median time to ovulation was 35 days in the lower quartile for women with placebo but this was significantly prolonged up to 98 days in the upper quartile. CC significantly shortened the time to ovulation up to 56 days.ConclusionsAmong women with PCOS, high baseline AMH levels were associated with a 20.1% lower chance of ovulation with a 63‐day longer time to ovulation. AMH can predict ovulation only when the baseline AMH level was &lt;7.0 ng/ml in women with PCOS undergoing ovulation induction with CC.Tweetable abstractOvulation rate increased until baseline AMH levels ≥7.0 ng/ml in women treated with CC; a successful ovulation and time to ovulation was highly associated with baseline AMH level in these women.

Use of a high-sensitivity anti-Mullerian hormone (AMH) assay to determine ovarian function after chemotherapy for early breast cancer.

552 Background: It is now well established that AMH can indicate the extent of chemotherapy-induced damage on the ovarian reserve. Very low AMH levels in women after chemotherapy for early breast cancer (eBC) may indicate treatment-induced premature ovarian failure (POI), but the evidence to implement its routine clinical use remains limited. Methods: AMH was measured (Roche cobas autoanalyser) in 197 women aged 40-45 years at diagnosis treated with anthracycline/cyclophosphamide/taxane based chemotherapy for eBC, with no previous endocrine therapy and no subsequent aromatase inhibitor exposure or ovarian suppression. 76% were ER positive and received tamoxifen. The primary objective was to assess the relationships between AMH levels at 6 months after chemotherapy (AMH6) with subsequent ovarian function at 30 months. This included accuracy of prediction of loss of ovarian function at 30 months (E30) after chemotherapy by AMH levels at 6 months (AMH6) and the value of other endocrine/clinical factors pretreatment and at 6 months. Multivariate analysis was performed with data were split into 70% training and 30% testing sets with results reported for model performance on the test set. Results: AMH fell from a median of 0.62 (IQR 0.21-1.31) ng/ml pretreatment to become undetectable ( &lt; 0.01ng/ml) in 137 (70%) of women at 6 months. AMH showed very little recovery, being undetectable in 115 women at 18 months and 119 at 30 months. In those with detectable AMH at 30 months, it remained very low, median 0.07ng/ml, max 0.82ng/ml but nevertheless it reflected ovarian function. Thus median estradiol at 30 months (E30) was 50 pmol/l (IQR 34-68) in women with undetectable AMH at that time, vs 313 pmol/l (IQR 102-1052) in the 80 women with detectable AMH. AMH at 6 months was predictive of ovarian function at 30 months, as E30 was 56 pmol/l (IQR 40-104) in women with undetectable AMH6 vs 258pmol/l (IQR 69-780; p &lt; 0.0001) in women with detectable AMH6, and the positive predictive value (PPV) of AMH being undetectable at 6 months and remaining so at 30 months was 77%. Random forest analysis identified BMI as a non-endocrine predictive factor of E30. Using a stringent cutoff of ≤50pmol/l (13.6 pg/ml) and adding 1:9 weighting to improve PPV gave a test validated PPV of 79.0% while maintaining AUC at 83.7% for prediction of E30. Other classifiers performed less well than random forests. Conclusions: Measurement of AMH at 6 months after chemotherapy has predictive value for later ovarian function, and combining this with other endocrine and baseline data improves discriminative ability. This approach indicates the potential role of multivariate analysis based on AMH measured shortly after chemotherapy to helping optimise subsequent endocrine therapy.

The relationship between vitamin E level and premature ovarian insufficiency.

The aim of this study is to investigate the role of vitamin E in the etiology of premature ovarian insufficiency (POI). This study included a total of 96 matched cases and controls, including the case group composed of 40 women with POI, and the control group composed of 56 women with normal menstrual cycles. Serum levels of vitamin E (also known as α-tocopherol), total cholesterol, follicle stimulating hormone (FSH), luteinizing hormone (LH) and anti-Müllerian hormone (AMH) were determined. The relationship of α-tocopherol with FSH, LH and AMH levels in women were evaluated using regression models. We found a negative association of α-tocopherol levels with FSH and LH levels, and a positive correlation between a-tocopherol and AMH levels in the whole study population. In this study, α-tocopherol levels were significantly lower in women with POI than those in women with normal menstrual cycles. Vitamin E levels showed significantly statistical difference between the POI and control group (P < 0.001). Therefore, vitamin E is correlated to POI.

Skin Mediates the Aphrodisiac Effect of UVB Light Via a Skin-Brain-Gonad Axis

Ultraviolet (UV) light affects endocrinological and behavioral aspects of human sexuality via an unknown mechanism. Using a unique male-female comparative approach, we discovered that the sexual behavioral and hormonal features enhanced by UVB are mediated by the skin. In mice, UV exposure increases hypothalamus-pituitary-gonadal axis hormone levels, resulting in enhanced ovary size, extended estrus days, and anti-Mullerian hormone (AMH) expression. It likewise enhances sexual responsiveness and attractiveness of females and heterosexual interactions of both males and females. Conditional knockout of p53 specifically in skin keratinocytes abolished UV’s effects. In humans, UV exposure enhanced romantic passion in both genders, increased testosterone levels in men and correlated with heightened plasma AMH levels in women. Our data, revealing that UVB triggers a skin-brain-gonadal axis through skin p53 activation, offers therapeutic opportunities for sex-steroid-related dysfunctions. We speculate that during human furless skin evolution, the skin became the front-line regulator of the response to UVB.

Serum kisspeptin levels correlated with anti-mullerian hormone levels in women with and without polycystic ovarian syndrome

Objective: To determine serum kisspeptin and anti-mullerian hormone (AMH) levels in women with and without polycystic ovary syndrome (PCOS). Materials and methods This was a prospective, cross-sectional, comparative study that included 70 women with PCOS and 58 non PCOS controls. PCOS patients were diagnosed according to the Rotterdam criteria. Age, body mass index (BMI), number of menstrual cycles per year, and the Ferriman-Gallwey Score were determined for each woman. Serum levels of kisspeptin, follicle stimulating hormone (FSH), luteinizing hormone (LH), thyroid stimulating hormone (TSH), estradiol, total testosterone, dehydroepiandrosterone sulfate (DHEA-S), AMH, fasting glucose and insulin were determined. Results Women with PCOS were younger (p < .001), with higher BMI (p = .027) and glucose values (p < .001); while displaying less number of menstrual cycles per year (p < .001). Although serum kisspeptin levels were similar in both groups, age was negatively (r= −0.33, p = .00018) and serum AMH levels were positively correlated (r = 0.25, p = .0039) with the serum kisspeptin levels in women with the PCOS. After adjusting for age, serum kisspeptin levels were comparable in both groups (p > .05). Serum LH, AMH, DHEA-S and total testosterone glucose, insulin levels and HOMA-IR values were significantly higher in women with PCOS as compared to controls (all p < .05). Conclusions Serum kisspeptin levels were similar in women with and without PCOS but positively correlated with AMH serum levels in PCOS women.

Insulin Sensitivity Indices in Patients with Polycystic Ovary Syndrome with Different Body Mass Index Categories.

This study aimed to determine the prevalence of insulin resistance among women with polycystic ovary syndrome (PCOS), describe the clinical and biochemical characteristics of women with PCOS, and determine the association between Antimullerian Hormone (AMH) and PCOS. In a clinical case series, 544 women with PCOS were included in this study. Body mass index (BMI), Homeostasis Model Assessment (HOMA), Quantitative Insulin Sensitivity Check Index (QUICKI), and Matsuda index were calculated. Sixty-three women with PCOS and 50 age- and BMI-matched control patients underwent blood sampling for AMH level. The most common clinical presentation of PCOS in this study was menstrual irregularity followed by hirsutism and infertility. There was no statistically significant difference in the clinical presentation or hormonal profile in women with PCOS according to different BMI categories. The prevalence of insulin resistance among women with PCOS was 37.7%, 69.3%, and 75.8% using HOMA, QUICKI, and Matsuda index, respectively. Furthermore, the Matsuda index had the highest detection rate of insulin resistance, especially in underweight women with PCOS (94.1%). AMH levels in women with PCOS were significantly higher than that in the control group (P-value = 0.015). Insulin resistance is prevalent among women with PCOS. The detection rate of insulin resistance varies according to the insulin sensitivity index used. Menstrual irregularity was the most common presentation of PCOS. Women with PCOS have significantly higher levels of AMH levels compared to women in the control group.

Could art cycles have a detrimental effect on ovarian reserve? A retrospective case control study.

Even if it is supposed damage of repeated ART (assisted reproductive technology) cycles on oocyte pool, there is still no evidence in literature. Aim of the study is to investigate whether infertile women who undergo to several ART cycles can show a lower ovarian reserve measured by AMH (Anti-Mullerian hormone) levels. The study includes 282 infertile women, between 18 and 42 years, and allocated into two groups: 159 women previously submitted to two or more ART cycles (group A) and 123 women never submitted naïve to-ART cycles (group B). We tested whether AMH, FSH, LH and E2 levels were significantly different between the two groups, stratifying according to age. Regardless to the age ranges bands, the AMH in group A was statistically significant lower than in group B with a statistical significance (P=0.047). In particular women aged over 35 previously submitted to one or more ART cycles showed lower AMH levels, than those paired with age, which had never been treated with ART. Despite the limitations of the study, our data demonstrate a reduced AMH levels in women aged over 35 previously submitted to two or more repeated ART-cycles compared to patients never treated before. The strength of this study is the actuality of the topic that has not been discussed before in detail.