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Endometrial proliferative lesions (EPL) usually refer to endometrial hyperplasia (EH) and endometrial cancer (EC). Among patients with premenopausal EPL who wish to preserve their fertility, only those with EH and early-stage EC have the possibility to undergo fertility preservation therapy. However, there is currently a lack of specific and reliable screening criteria and models for identifying these patients.
There is a need for a reference material to support the development and ensure the quality of immunoassays for human AMH. A batch of ampoules, coded 16/190, containing lyophilised recombinant AMH was evaluated in a WHO Collaborative Study. The aims of the study were to determine the AMH content in terms of the calibration of each immunoassay method, to predict long-term stability and to assess the suitability of the preparation to calibrate AMH immunoassays.
The Mullerian ducts are the embryological precursors of the female reproductive tract, including the uterus; anti-Mullerian hormone (AMH) has a key role in the regulation of foetal sexual differentiation. Anti-Mullerian hormone inhibits endometrial tumour growth in experimental models by stimulating apoptosis and cell cycle arrest. To date, there are no prospective epidemiologic data on circulating AMH and endometrial cancer risk.
Anti-Mullerian hormone (AMH) is expressed by both male and female fetuses during mammalian development, with males expressing AMH earlier and at significantly higher concentration. The aim of the current study was to explore the potential impact of pregnancy and fetal sex on maternal AMH and to determine if plasma (Pl) AMH or placenta intercotyledonary membrane and cotyledonary AMH receptor 2 (AMHR2) mRNA expression differ in pregnant cows carrying male vs. female fetuses. AMH levels in blood were measured using a bovine optimized ELISA kit. Cows pregnant with a male fetus were observed to have a significantly greater difference in Pl AMH between day 35 and 135 of gestation. Average fetal AMH level between 54 and 220days of gestation was also observed to be significantly higher in male vs. female fetuses. Intercotyledonary membranes and cotyledons were found to express AMHR2 between days 38 and 80 of gestation at similar levels in both fetal sexes. These findings support the hypothesis that fetal sex alters maternal Pl AMH during pregnancy in cattle.
AMH as a promising predictor of ovarian response has been studied extensively in women undergoing assisted reproductive technology treatment, but little is known about its prediction value in monkeys undergoing ovarian stimulation. In the current study, a total of 380 cynomolgus monkeys ranging from 5 to 12 years received 699 ovarian stimulation cycles. Serum samples were collected for AMH measure with enzyme-linked immunosorbent assay. It was found that serum AMH levels were positive correlated with the number of retrieved oocytes (P < 0.01) in the first, second and third stimulation cycles. In the first cycles, area under the curve (ROCAUC) of AMH is 0.688 for low response and 0.612 for high response respectively, indicating the significant prediction values (P = 0.000 and P = 0.005). The optimal AMH cutoff value was 9.68 ng/mL for low ovarian response and 15.88 ng/mL for high ovarian response prediction. In the second stimulation cycles, the significance of ROCAUC of AMH for high response rather than the low response was observed (P = 0.001 and P = 0.468). The optimal AMH cutoff value for high ovarian response was 15.61 ng/mL. In the third stimulation cycles, AMH lost the prediction value with no significant ROCAUC. Our data demonstrated that AMH, not age, is a cycle-dependent predictor for ovarian response in form of oocyte yields, which would promote the application of AMH in assisted reproductive treatment (ART) of female cynomolgus monkeys. AMH evaluation would optimize candidate selection for ART and individualize the ovarian stimulation strategies, and consequentially improve the efficiency in monkeys.
While serum anti-mullerian hormone (AMH) levels are inversely associated with all-cause mortality in men, the underlying mechanisms are unclear. Elevated levels of inflammation, also associated with all-cause mortality, and may be the link between AMH and mortality. Hence, we examined the association of AMH with serum c-reactive protein (CRP), a biomarker of inflammation, in men. We included men ≥20 years from the National Health and Nutrition Examination Survey (1999-2004). We used survey weight-adjusted linear regression to examine the association between AMH and CRP without and with adjustment for age, race, body mass index (BMI), smoking, hypertension, diabetes, cholesterol, glomerular filtration rate (GFR), testosterone, androstenedione, and sex hormone binding globulin. Of the 949 men, 212 (22%) were elderly, 493 (52%) Caucasian, 254 (27%) current smokers, 100 (10%) diabetics, and 312 (33%) had hypertension. Mean (SD) AMH was 8.4 (7.2) ng/mL and median (IQR) CRP level was 0.17 (3) mg/L. Using linear regression, each 10 ng/mL rise in AMH was associated with 0.09 mg/dL (95%CI = -0.14 to -0.03; p = 0.002) decrease before and 0.08 mg/dL (95%CI = -0.13 to -0.02; p = 0.004) decrease in CRP after adjusting for potential confounders. Similarly, men in the highest quartile of AMH had significantly lower CRP compared to those in the lowest quartile (unadjusted difference = -0.19 mg/dL; 95%CI = -0.31 to -0.06; p = 0.006, adjusted difference = -0.16 mg/dL; 95%CI = -0.3 to -0.01; p = 0.035). We found an independent, robust, and inverse association between CRP and AMH in men. Effect of AMH on mortality may be through amelioration of inflammation.
Obesity negatively impacts reproductive health, including ovarian function. Obesity has been posited to alter Anti-Müllerian hormone (AMH) production. Understanding biological factors that could impact AMH levels is necessary given the increasing use of AMH for predicting reproductive health outcomes in response to controlled ovarian stimulation, diagnosing ovulatory disorders, onset of menopause, and natural conception. In this narrative review, we evaluated the impact of obesity on AMH levels in healthy, regularly cycling reproductive-age women (18-48 years). Thirteen studies (n = 1214 women; (811, non-obese (body mass index; BMI < 30 kg/m2); 403, obese (BMI > 30 kg/m2))) were included, of which five reported decreased AMH levels with obesity, whereas eight showed comparable AMH levels between groups. Inclusion of women with higher obesity classes (Class 3 versus Class 1) may have been a factor in studies reporting lower AMH levels. Together, studies reporting AMH levels in otherwise healthy women remain limited by small sample sizes, cross-sectional designs, and lack of representation across the entire adiposity spectrum. Ultimately, the degree to which obesity may negatively impact AMH levels, and possibly ovarian reserve, in otherwise healthy women with regular menstrual cycles should be deemed uncertain at this time. This conclusion is prudent considering that the biological basis for an impact of obesity on AMH production is unknown.
Vitamin D3 (1,25-dihydroxyvitamin D3, VD3) in vitro attenuates the effect of the pro-inflammatory advanced glycation end products (AGEs) on steroidogenesis in human granulosa cells (GCs) by downregulating the receptor for AGEs (RAGE). It has been shown that VD3 alone downregulates anti-Mullerian hormone (AMH) type 2 receptor (AMHR-2) gene expression and suppresses AMH-induced SMAD 1/5/8 phosphorylation in granulosa cells. However, the effect of AGEs, in the absence or presence of VD3, on AMH action in GCs has not been studied. Using human GCs, this study showed that human glycated albumin (HGA), an in vitro representative for AGEs, upregulated AMHR-2 mRNA but did not alter AMH mRNA expression levels. VD3 inhibited the HGA-induced increase in AMHR-2 mRNA expression levels. In KGN granulosa cell line, recombinant AMH induced SMAD 1/5/8 phosphorylation. HGA augmented the recombinant AMH-induced SMAD 1/5/8 phosphorylation while the addition of VD3 to HGA attenuated the recombinant AMH-induced SMAD 1/5/8 phosphorylation. Thus, AGEs could potentially affect folliculogenesis as reflected by changes in AMH signaling. These findings have significant implications for women with polycystic ovary syndrome who have significantly elevated serum and ovarian AGEs.
FMR1 premutation (55-200 CGG repeats) results in fragile X-associated primary ovarian insufficiency (FXPOI). We evaluated expression levels of folliculogenesis-related mediators, follicle-stimulating hormone (FSH) receptor and anti-Mullerian hormone (AMH), to gain insights into the mechanisms underlying the reduced ovarian function. Mural granulosa cells (MGCs) were collected from FMR1 premutation carriers and noncarriers undergoing IVF treatments. At baseline, MGCs of carriers demonstrated significantly higher mRNA expression levels of AMH (3.5 ± 2.2, n = 12 and 0.97 ± 0.5, n = 17, respectively; p = 0.0003) and FSH receptor (5.6 ± 2.8 and 2.7 ± 2.8, respectively; p = 0.02) and higher AMH protein expression on immunostaining. Accordingly, FMR1 premutation-transfected COV434 cells exhibited higher AMH protein expression than COV434 cells transfected with 20 CGG repeats. We conclude that FMR1 premutation may lead to dysregulation of AMH expression levels, probably due to a compensatory mechanism. Elucidating the pathophysiology of FXPOI may help in early detection of ovarian dysfunction and tailoring IVF treatments to FMR1 premutation carriers.
Anti-Mullerian hormone (AMH) and testosterone (T) both play distinct roles in the early stages of folliculogenesis. However, the relationship between serum T and AMH levels is poorly understood. This study aimed to investigate the association between serum T and AMH levels in infertile women. A total of 1935 infertile women aged 20-46 years were included in the cross-sectional study and divided into four quartile groups (Q1 to Q4) based on serum T levels. Compared to the subjects in the highest T quartile (Q4), those in the lowest T quartile (Q1) showed significantly lower AMH levels. After adjustment for age, body weight, body mass index and FSH, increasing T quartile categories were associated with higher AMH levels. Binary logistic regression analyses revealed that the odds for the risk of diminished ovarian reserve (DOR) were 11.44-fold higher in Q1 than in Q4 and the odds for the risk of excess ovarian reserve (EOR) were 10.41-fold higher in Q4 than in Q1. Our data show that serum T levels are positively associated with serum AMH levels and suggest that androgen insufficiency may be a potential risk factor for DOR; androgen excess may lead to EOR in infertile women.
Hyperandrogenism is the primary manifestation of polycystic ovary syndrome (PCOS), which appears to be caused by excess exposure to androgen. As such, androgenized animal models have been developed and investigated to study the etiology of PCOS. Anti-Mullerian hormone (AMH) is known to be associated with follicle growth, and its levels are two to three times higher in women with PCOS than in those with normal ovaries. We studied how duration of androgen administration affects folliculogenesis and AMH expression.
Background: Efforts in reproductive preservation for cancer patients have become one of the important aspects of cancer management. In fact, decline in reproductive function is known to occur after exposure to anti-cancer treatments. Measuring anti-Müllerian hormone (AMH) levels is known to be the best parameter in predicting ovarian reserves, which indicates reproductive function. In total, 68% of cancer survivors of reproductive age who underwent anti-cancer treatments suffer from infertility. Meanwhile, ovarian reserves also decrease with increasing age. There is ongoing debate on whether the ovarian reserves of cancer patients could be reduced long before exposure to anti-cancer therapy. Therefore, it is important to know whether ovarian reserves in cancer patients decrease before or after anti-cancer therapy. This can help predict the reproductive function in such cases and the effectiveness of ovarian preservation efforts. Methods: A cross-sectional study was conducted, comparing the AMH levels of 44 female cancer patients of reproductive age before cancer therapy, to 44 non-cancer patients of reproductive age (age matched) . The AMH was determined from blood.The biological ages from both groups were adjusted using the Indonesian Kalkulator of Oocytes. Results: The median age in both groups was 28 years old. The AMH levels in the blood of the cancer group were found to be significantly lower in contrast to those in the non-cancer group (1.11 [0.08-4.65] ng/ml vs. 3.99 [1.19- 8.7]; p- value <0.001). Therefore, the biological age in the cancer group was 10 years older than that of the non-cancer group, indicating that ovarian aging occurs earlier in cancer patients. Conclusions: AMH levels of cancer patients of reproductive age were already reduced before cancer therapy, given an older biological age, in contrast to that of the non-cancer patients. Proper counseling and implementation of fertility-preserving methods is highly recommended in this group of patients.
Energy drinks have an impact on concentration levels, physical performance, speed of reaction, and focus, but these drinks cause many adverse effects and intoxication symptoms. The main goal of this study was to determine the effect of energy drink consumption on ovarian reserve and serum anti-mullerian hormone (AMH) levels.
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.
The objective of this study is to investigate a possible correlation between anxiety status and anti-Mullerian hormone (AMH) levels among healthcare professionals who provide medical care directly to COVID-19-positive patients during the recent pandemic. Fifty-two healthcare professionals (nurses, midwives, and residents) who provide medical care directly to COVID-19-positive patients in inpatient clinics or intensive care units were enrolled in this study. Serum AMH levels were analyzed to reflect ovarian reserve. The Beck Anxiety Inventory (BAI) and the State-Trait Anxiety Inventory (STAI-S and STAI-T, respectively) were completed by participants to assess their anxiety status. A linear regression model with participant age as the constant variable was applied to analyze the relationship between inventory scale scores and AMH levels. P-values less than 0.05 were considered statistically significant. The mean AMH value was significantly lower for the participants in the moderate/severe anxiety group compared to the minimal/mild anxiety group (p = 0.007). A linear regression analysis revealed a significant negative correlation between AMH levels and both BAI (B = -0.030, standard error = 0.010, p = 0.004) and STAI-S and STAI-T scores when age was controlled (both p = 0.003). The severity of anxiety experienced during the recent COVID-19 pandemic among healthcare professionals, who provide medical care directly to COVID-19-positive patients, is found to be related to low AMH levels.
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age. Anti-Mullerian hormone (AMH) is a valid indicator of ovarian function and is used for PCOS diagnosis. Some studies have shown that adipokines affect the synthesis of AMH, and therefore they are somehow related in function. The aim of the present study was to determine the relationship between serum levels of AMH, adiponectin and oxidative stress markers in PCOS patients.
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