Anti-Mullerian Hormone Induces Foxo1 and Sirt1 Genes Expression in Mouse Ovary.

BACKGROUND: Anti-Mullerian hormone (AMH) plays a pivotal role in follicular growth and atresia. Recent studies highlighted the role of AMH in attenuating granulosa cell apoptosis and subsequent follicular atresia. Despite the raising understanding of the role of AMH in folliculogenesis, and its contribution to the pathophysiology of certain diseases such as polycystic ovary syndrome, the effect of AMH on the expression of genes regulating folliculogenesis is stills limited. OBJECTIVE: This study aims to gain insights into the effect of AMH on atresia regulating genes. METHOD: In vivo study was performed on C57BL/6J mice injected with AMH for one month. Thereafter, relative gene expression quantification of Foxo1, Sirt1, p53, Bim, and Bax genes were performed using RT-PCR. RESULTS: In this study, AMH significantly enhanced the expression of Foxo1 and Sirt1 gene compared to the control group. On the contrary, AMH did not modulate the expression of p53, Bim, or Bax genes. AMH was also found to increase serum FSH and LH levels in a dosedependent manner. CONCLUSION: This study demonstrated the capability of AMH to induce Foxo1 and Sirt1 genes. Moreover, our study revealed the role of AMH in elevating LH serum level which is a main contributor to the pathophysiology of polycystic ovary syndrome, opening new avenues for the study of AMH as a main contributor to the stalled follicular atresia and growth associated with the disease.

Comparing Serum AMH, InhB, Testosterone Levels and Finger Length Ratio (2D/4D) of Male Children with Specific Learning Disorder and Controls.

Introduction: It has been suggested that inhibin B (InhB), Anti-Müllerian hormone (Müllerian-inhibiting substance, AMH) levels, and 2D/4D finger length ratios are related to sex differences in neurodevelopmental disorders. The aim of this study is to investigate the role of InhB, AMH levels, and 2D/4D finger length ratios in male children with specific learning disorder (SLD). Methods: The study included 38 male children diagnosed with SLD and 38 males of similar ages without SLD as the control group. Tests used in the evaluation were the Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime version, Specific learning disorder clinical observation battery, Wechsler Intelligence Scale for Children-Revised (WISC-R), and Conners' Parent Rating Scale. Revised: Short Form. Serum AMH, InhB, and Testosterone levels were measured using an enzyme-linked immunosorbent assay. Results: Male children diagnosed with SLD demonstrated significantly higher levels of serum InhB compared to controls (t= 2.59 p=0.009); both groups had similar levels of serum testosterone and AMH. The 2D/4D finger ratios in the SLD group were found to be lower than those in the control group (t= 2.92 p= 0.005). Serum InhB levels were positively correlated with WISC-R verbal scores (p= 0.003). Conclusion: Our findings suggest that serum InhB levels and the 2D/4D ratio, which is an indicator of prenatal testosterone exposure, may play a role in the male predominance of SLD.

Anti-Müllerian hormone type II receptor protein expression in non-small cell lung cancer and the effect of AMH/AMHR2 signaling on cancer cell proliferation.

BACKGROUND: Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths worldwide despite advances in cancer therapeutics. In several gynecological cancers, anti-Müllerian hormone receptor type 2 (AMHR2) mediates AMH-induced growth inhibition and is expressed at high levels. Furthermore, 5%-8% of NSCLCs exhibit high AMHR2 expression, suggesting that AMH may inhibit the progression of some lung cancers. However, the clinical relevance of AMHR2 expression and its role in lung cancer is not fully clarified. METHODS: Immunostaining was performed on 79 surgical specimens of NSCLC. The Cancer Genome Atlas RNA-seq data for lung adenocarcinoma were analyzed, and gene ontology and gene set enrichment analyses were performed. In cellular experiments, AMHR2-overexpressing NSCLC cell lines were established, and the role of the AMH-AMHR2 pathway in cell proliferation with recombinant human AMH protein treatment was examined. RESULTS: A total of 13 cases (16.5%) were positive for immunostaining in lung adenocarcinoma tissues; no positive signals were detected in lung squamous carcinoma tissues. Gene expression variation analysis using The Cancer Genome Atlas data showed that the expression of genes related to the cell cycle was downregulated in the AMHR2-high group. Cellular experiments showed that activation of the AMH-AMHR2 pathway suppressed cell proliferation. CONCLUSION: In lung adenocarcinoma tissues with high expression of AMHR2, activation of the AMH-AMHR2 pathway may suppress cell proliferation.

Anti-Müllerian hormone as a promising novel biomarker for litter size in Romanov sheep.

Anti-Müllerian hormone (AMH) is a hormone produced by growing preantral and antral follicles of the ovary. AMH is accepted as an important biomarker for fertility and superovulation parameters in livestock species. This study aimed to evaluate changes in serum AMH level in the oestrous cycle, repeatability of AMH, the effect of age on serum AMH level and the effects of AMH on litter size in Romanov sheep. In the study, a total of 36 Romanov sheep were used as animal material. First blood samples (0th day) were collected from 36 ewes to evaluate AMH and progesterone levels. Second blood samples were collected randomly from 20 ewes 9 days after first sampling to compare AMH levels at two different periods of the oestrous cycle in Romanov ewes. The ewes were categorized into three groups as low, medium and high AMH based on their first AMH levels. Results indicated that serum AMH level did not change during the oestrous and dioestrous phases of the oestrous cycle and two random time points of the oestrous cycle (p > .05). Pearson correlation analysis revealed that there is a high (r = .95) and significant (p < .001) correlation between AMH levels at the 0th (AMH-1) and 9th (AMH-2) days. The effect of AMH level on litter size was found to be significant. Litter size was significantly higher in the high AMH group than in the low AMH group (p < .05). In addition, the age of ewes did not affect serum AMH levels (p > .05). ROC analysis indicates that AMH cut-off value >320 pg/mL with 70% sensitivity and 100% specificity can be used for litter size in Romanov ewes. In conclusion, AMH is highly repeatable and its serum AMH level did not change during the oestrous cycle in Romanov sheep. In addition, AMH affects litter size and can be reliably used as a marker for litter size in Romanov sheep.

Potential damage to ovarian reserve from laparoscopic electrocoagulation in endometriomas and benign ovarian cysts: a systematic review and meta-analysis.

PURPOSE: Laparoscopic cystectomy for ovarian endometriomas and benign ovarian cysts is often conducted through hemostatic methods, with bipolar electrocoagulation as a common approach. This study evaluated the impact of electrocoagulation, primarily through bipolar energy, versus nonthermal hemostatic methods on ovarian reserve in patients undergoing laparoscopic cystectomy for ovarian endometriomas and benign ovarian cysts. METHODS: A systematic review with meta-analysis was conducted by searching the Cochrane Library, PubMed, EMBASE, and Web of Science databases. Randomized controlled trials (RCTs) comparing the impact of nonthermal hemostatic methods and electrocoagulation on the ovarian reserve during laparoscopic cystectomy were included. The Cochrane Risk of Bias Tool for Randomized Controlled Trials (ROB 2.0) was utilized to assess the quality of the included studies. The meta-analysis included 13 RCTs involving 1043 patients. Postoperative serum anti-Müllerian hormone (AMH) levels and antral follicle counts (AFCs) were analyzed using Review Manager ver. 5.4. RESULTS: Compared with the bipolar group, patients with endometriomas in the nonthermal hemostatic group exhibited significantly higher postoperative AMH levels at 1, 3, 6, and 12 months. Conversely, no significant differences in AMH levels were observed in patients with benign ovarian cysts. Similarly, AFCs showed no significant differences, except for lower postoperative AFCs in patients with endometrioma in the electrocoagulation group. CONCLUSION: Nonthermal hemostatic methods are associated with more effective preservation of the ovarian reserve compared with bipolar electrocoagulation in laparoscopic cystectomy for ovarian endometriomas. However, no significant impact of bipolar electrocoagulation on the ovarian reserve was observed in patients with benign ovarian cysts. TRIAL REGISTRATION: Registered in PROSPERO on April 10, 2023; ID # CRD42023413158.

Impact of ultrasound-guided high-intensity focused ultrasound for the treatment of uterine fibroids on ovarian reserve and quality of life: a single-center prospective cohort study.

BACKGROUND: We aimed to evaluate changes in ovarian reserve and quality of life in women treated with ultrasound-guided high-intensity focused ultrasound (USgHIFU) for uterine fibroids. METHODS: In this single-center prospective study, a total of 69 patients with uterine fibroids treated with USgHIFU from October 2018 to November 2021 were enrolled. Fibroid volume, anti-Müllerian hormone (AMH) levels, uterine fibroid symptom scores, and uterine fibroid symptoms and quality of life (UFS-QOL) questionnaire scores before and 1, 3, and 6 months after USgHIFU treatment were analyzed. Correlations between AMH levels and age, fibroid type, and fibroid location were assessed. RESULTS: Data from 54 of the 69 patients included in the present study were analyzed. The UFS-QOL scores at baseline and at 1 month and 6 months after USgHIFU treatment were 70 (50.75-87.50), 57 (44.75-80.00), and 52 (40.75-69.00) points, respectively (p < 0.001). The rate of fibroid volume reduction increased significantly at the 3-month follow-up compared with the 1-month follow-up (p < 0.001), and no significant change was observed between the 3-month and 6-month follow-ups (p > 0.99). The median AMH levels before and at 1, 3 and 6 months after treatment were 1.22 (0.16-3.28) ng/ml, 1.12 (0.18-2.52) ng/ml, 1.15 (0.19-2.08) ng/ml and 1.18 (0.36-2.43) ng/ml, respectively (p = 0.2). Multivariate linear regression analyses revealed that age was independently associated with AMH levels. CONCLUSIONS: USgHIFU treatment for uterine fibroids can significantly improve quality of life with minimal adverse effects on ovarian function.

Analytical performances of a novel fluorescent immunoassay of anti-Müllerian hormone and establishment of the reference intervals in Chinese children.

Background: AMH is important in child growth and the concentrations change with age and gender. This study aimed to evaluate the performance of the Pylon AMH assays and establish pediatric reference intervals. Methods: The experiments on imprecision, sensitivity, linearity, reportable range, interference and comparison were carried out to evaluate the analytical performance. The AMH reference ranges were calculated in 238 females and 346 males aged 0-18 years using robust methods. Results: The repeatability and the within-laboratory imprecision CVs of the assay were 3.7 % and 6.4 % at 2.25 ng/mL, and 4.6 % and 6.4 % at 15.49 ng/mL, respectively. The sensitivity (LoB = 0.05 ng/mL, LoD = 0.1 ng/mL and LoQ = 0.3 ng/mL) was verified. The linearity was 0.1-19.55 ng/mL and report up to 391 ng/mL with 20x pre-dilution. There was no significant interference from hemoglobin (500 mg/dL), triglyceride (500 mg/dL), bilirubin (10 mg/dL), cholesterol (800 mg/dL) and biotin (3000 ng/mL). The AMH measured by the Pylon assays correlated to those measured by the Elecsys assays. In males, the AMH levels were high at birth (0 d-1 m: median 95.10 ng/mL) and increased to a peak (7 m-1y: median 158.80 ng/mL) before they decreased with age (15-18 y: median 6.31 ng/mL). In females, the AMH concentrations were low at birth (0 d-1 m: median 0.20 ng/mL) and increased with age (15-18 y: median 3.03 ng/mL). Conclusion: The Pylon AMH assays showed good analytical performance and the AMH reference intervals in chinese children determined may provide a basis in clinical diagnosis and treatment of related diseases.

Conditional loss of Brca1 in oocytes causes reduced litter size, ovarian reserve depletion and impaired oocyte in vitro maturation with advanced reproductive age in mice.

BACKGROUND: An estimated 1 in 350 women carry germline BRCA1/2 mutations, which confer an increased risk of developing breast and ovarian cancer, and may also contribute to subfertility. All mature, sex steroid-producing ovarian follicles are drawn from the pool of non-renewable primordial follicles, termed the 'ovarian reserve'. The clinical implications of early ovarian reserve exhaustion extend beyond infertility, to include the long-term adverse health consequences of loss of endocrine function and premature menopause. We aimed to determine whether conditional loss of Brca1 in oocytes impacts ovarian follicle numbers, oocyte quality and fertility in mice with advancing maternal age. We also aimed to determine the utility of AMH as a marker of ovarian function, by assessing circulating AMH levels in mice and women with BRCA1/2 mutations, and correlating this with ovarian follicle counts. METHODS: In this study, we addressed a longstanding question in the field regarding the functional consequences of BRCA1 inactivation in oocytes. To recapitulate loss of BRCA1 protein function in oocytes, we generated mice with conditional gene deletion of Brca1 in oocytes using Gdf9-Cre recombinase (WT: Brca1fl/flGdf9+/+; cKO: Brca1fl/flGdf9cre/+). FINDINGS: While the length of the fertile lifespan was not altered between groups after a comprehensive breeding trial, conditional loss of Brca1 in oocytes led to reduced litter size in female mice. Brca1 cKO animals had a reduced ovarian reserve and oocyte maturation was impaired with advanced maternal age at postnatal day (PN)300, compared to WT animals. Serum anti-Müllerian hormone (AMH) concentrations (the gold-standard indirect marker of the ovarian reserve used in clinical practice) were not predictive of reduced primordial follicle number in Brca1 cKO mice versus WT. Furthermore, we found no correlation between follicle number or density and serum AMH concentrations in matched samples from a small cohort of premenopausal women with BRCA1/2 mutations. INTERPRETATION: Together, our data demonstrate that BRCA1 is a key regulator of oocyte number and quality in females and suggest that caution should be used in relying on AMH as a reliable marker of the ovarian reserve in this context. FUNDING: This work was made possible through Victorian State Government Operational Infrastructure Support and Australian Government NHMRC IRIISS. This work was supported by funding from the Australian Research Council (ALW - DE21010037 and KJH - FT190100265), as well as the National Breast Cancer Foundation (IIRS-22-092) awarded to ALW and KJH. LRA, YML, LT, EOKS and MG were supported by Australian Government Research Training Program Scholarships. LRA, YML and LT were also supported by a Monash Graduate Excellence Scholarship. YC, SG and XC were supported by Monash Biomedicine Discovery Institute PhD Scholarships. LRA was also supported by a Monash University ECPF24-6809920940 Fellowship. JMS was supported by NHMRC funding (2011299). MH was supported by an NHMRC Investigator Grant (1193838).

Anti-Müllerian hormone does not predict cumulative pregnancy rate in non-infertile women following four IUI cycles with donor sperm.

PURPOSE: To evaluate the predictive value of serum AMH for clinical pregnancy in non-infertile population undergoing intrauterine insemination with donor sperm (ds-IUI). METHODS: This multicenter prospective study (ClinicalTrials.gov ID: NCT06263192) recruited all non-infertile women undergoing ds-IUI from June 2020 to December 2022 in three different fertility clinics in Spain and Chile. Indications for ds-IUI included severe oligoasthenoteratozoospermia, female partner, or single status. Clinical pregnancy rates were compared between women with AMH ≥ 1.1 and < 1.1 ng/mL. The main outcome measure was the cumulative clinical pregnancy rate after up to 4 ds-IUI cycles. RESULTS: A total of 458 ds-IUI cycles were performed among 245 patients, of whom 108 (44.08%) achieved clinical pregnancy within 4 cycles, 60.2% of these occurring in the first attempt and 84.2% after two attempts. We found no significant differences in AMH levels or other parameters (such as age, BMI, FSH, AFC) between women who became pregnant and those who did not. Cumulative pregnancy rates and logistic regression analysis revealed that AMH ≥ 1.1 ng/mL was not predictive of ds-IUI success. While a high positive correlation was observed between AFC and AMH (r = 0.67, p < 0.001), ROC curve analyses indicated that neither of these ovarian reserve markers accurately forecasts cumulative ds-IUI outcomes in non-infertile women. CONCLUSIONS: The findings of this multicenter study suggest that AMH is not a reliable predictor of pregnancy in non-infertile women undergoing ds-IUI. Even women with low AMH levels can achieve successful pregnancy outcomes, supporting the notion that diminished ovarian reserve should not restrict access to ds-IUI treatments in eligible non-infertile women.

Women's interest, knowledge, and attitudes relating to anti-Mullerian hormone testing: a randomized controlled trial.

STUDY QUESTION: What is the impact of co-designed, evidence-based information regarding the anti-Mullerian hormone (AMH) test on women's interest in having the test? SUMMARY ANSWER: Women who viewed the evidence-based information about the AMH test had lower interest in having an AMH test than women who viewed information produced by an online company selling the test direct-to-consumers. WHAT IS KNOWN ALREADY: Online information about AMH testing often has unfounded claims about its ability to predict fertility and conception, and evidence suggests that women seek out and are recommended the AMH test as a measure of their fertility potential. STUDY DESIGN, SIZE, DURATION: An online randomized trial was conducted from November to December 2022. Women were randomized (double-blind, equal allocation) to view one of two types of information: co-designed, evidence-based information about the AMH test (intervention), or existing information about the AMH test from a website which markets the test direct-to-consumers (control). A total of 967 women were included in the final analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants were women recruited through an online panel, who were aged 25-40 years, living in Australia or The Netherlands, had never given birth, were not currently pregnant but would like to have a child now or in the future, and had never had an AMH test. The primary outcome was interest in having an AMH test (seven-point scale; 1 = definitely NOT interested to 7 = definitely interested). Secondary outcomes included attitudes, knowledge, and psychosocial and behavioural outcomes relating to AMH testing. MAIN RESULTS AND THE ROLE OF CHANCE: Women who viewed the evidence-based information about the AMH test had lower interest in having an AMH test (MD = 1.05, 95% CI = 0.83-1.30), less positive attitudes towards (MD = 1.29, 95% CI = 4.57-5.70), and higher knowledge about the test than women who viewed the control information (MD = 0.75, 95% CI = 0.71-0.82). LIMITATIONS, REASONS FOR CAUTION: The sample was more highly educated than the broader Australian and Dutch populations and some measures (e.g. influence on family planning) were hypothetical in nature. WIDER IMPLICATIONS OF THE FINDINGS: Women have higher knowledge of and lower interest in having the AMH test when given evidence-based information about the test and its limitations. Despite previous studies suggesting women are enthusiastic about AMH testing to learn about their fertility potential, we demonstrate that this enthusiasm does not hold when they are informed about the test's limitations. STUDY FUNDING/COMPETING INTEREST(S): This project was supported by an NHMRC Emerging Leader Research Fellowship (2009419) and the Australian Health Research Alliance's Women's Health Research, Translation and Impact Network EMCR award. B.W.M. reports consultancy for ObsEva and Merck and travel support from Merck. D.L. is the Medical Director of, and holds stock in, City Fertility NSW and reports consultancy for Organon and honoraria from Ferring, Besins, and Merck. K.H. reports consultancy and travel support from Merck and Organon. K.M. is a director of Health Literacy Solutions that owns a licence of the Sydney Health Literacy Lab Health Literacy Editor. No other relevant disclosures exist. TRIAL REGISTRATION NUMBER: ACTRN12622001136796. TRIAL REGISTRATION DATE: 17 August 2022. DATE OF FIRST PATIENT'S ENROLMENT: 21 November 2022.

Reproductive outcome after in vitro fertilization in endometriosis - key factors and implications.

Endometriosis is a benign chronic disease with a major impact on a woman's quality of life, mainly due to painful physical symptoms. Endometriosis is also a common cause of infertility caused by low ovarian reserve, distorted pelvic anatomy, and severe local inflammation with a direct negative impact on the quality of oocytes, embryos, and endometrium. We conducted a retrospective study between January 2019 and December 2023, including women with a history of surgery for endometriosis who underwent in vitro fertilization (IVF) to achieve pregnancy. Their reproductive outcome was compared with a group of patients with documented tubal obstruction. The aim of our study was to identify the factors associated with a positive impact on the pregnancy rate, specifically age, anti-Mullerian hormone (AMH), ovarian stimulation protocol, and types of gonadotropins used. We analyzed a group of 175 patients with endometriosis compared with 189 patients with tubal obstruction. The average age was similar between the two groups but with a difference in the average AMH value (1.63 ± 1.09 ng/mL vs. 2.55 ± 1.67 ng/mL). The most utilized ovarian stimulation protocol in both groups was the short gonadotropin-releasing hormone (GnRH) antagonist. The clinical pregnancy rate was 27.2% in the endometriosis group and 54.7% in the tubal obstruction group. Our study revealed that treatment with corifollitropin alfa in the endometriosis group was associated with a higher clinical pregnancy rate. AMH and age proved to be significant independent factors for the reproductive outcome.

Reduced anti-Müllerian hormone levels in males with inherited bone marrow failure syndromes.

Fanconi anemia (FA), dyskeratosis congenita-related telomere biology disorders (DC/TBD), and Diamond-Blackfan anemia (DBA) are inherited bone marrow failure syndromes (IBMFS) with high risks of bone marrow failure, leukemia, and solid tumors. Individuals with FA have reduced fertility. Previously, we showed low levels of anti-Müllerian hormone (AMH), a circulating marker of ovarian reserve, in females with IBMFS. In males, AMH may be a direct marker of Sertoli cell function and an indirect marker of spermatogenesis. In this study, we assessed serum AMH levels in pubertal and postpubertal males with FA, DC/TBD, or DBA and compared this with their unaffected male relatives and unrelated healthy male volunteers. Males with FA had significantly lower levels of AMH (median: 5 ng/mL, range: 1.18-6.75) compared with unaffected male relatives (median: 7.31 ng/mL, range: 3.46-18.82, P = 0.03) or healthy male volunteers (median: 7.66 ng/mL, range: 3.3-14.67, P = 0.008). Males with DC/TBD had lower levels of AMH (median: 3.76 ng/mL, range: 0-8.9) compared with unaffected relatives (median: 5.31 ng/mL, range: 1.2-17.77, P = 0.01) or healthy volunteers (median: 5.995 ng/mL, range: 1.57-14.67, P < 0.001). Males with DBA had similar levels of AMH (median: 3.46 ng/mL, range: 2.32-11.85) as unaffected relatives (median: 4.66 ng/mL, range: 0.09-13.51, P = 0.56) and healthy volunteers (median: 5.81 ng/mL, range: 1.57-14.67, P = 0.10). Our findings suggest a defect in the production of AMH in postpubertal males with FA and DC/TBD, similar to that observed in females. These findings warrant confirmation in larger prospective studies.

Antimüllerian hormone levels are associated with time to pregnancy in a cohort study of 3,150 women.

OBJECTIVE: To study the association between antimüllerian hormone (AMH) levels and time of pregnancy. Although it has been hypothesized that serum AMH levels may indicate the chance of conception, findings have been mixed. Given that any association is expected to be modest, and it is possible that previous studies have been underpowered, we investigated this relationship in the largest prospective cohort to date. DESIGN: Prospective time-to-pregnancy cohort study. SETTING: Community. PATIENT(S): A total of 3,150 US women who had been trying to conceive for <3 months and had purchased a Modern Fertility hormone test. INTERVENTION(S): We developed a discrete time-to-event model using a binomial complementary log-log error structure within a generalized additive modeling framework, adjusting for confounding factors such as age, body mass index, parity, smoking status, polycystic ovary syndrome, and others. Sensitivity analyses were performed in women with regular menstrual cycles (21-35 days), who did not report using fertility treatments, using alternate AMH level categories (<0.7, 0.7-8.5, >8.5 ng/mL), and AMH levels as a continuous measure. MAIN OUTCOME MEASURE(S): Primary outcomes included cumulative conception probability within 12 cycles and relative fecundability per menstrual cycle. Conception was defined by a self-reported positive pregnancy test. RESULT(S): Participants contributed 7.21 ± 5.32 cycles, with 1,325 (42.1%) achieving a pregnancy. Women with low AMH levels (<1 ng/mL, n = 427) had a lower chance of natural conception (adjusted hazard ratio [adjHR], 0.77; 95% confidence interval [CI], 0.64-0.94) compared with women with normal AMH levels (1-5.5 ng/mL). There was no difference between high (5.5+ ng/mL) and normal AMH level categories (adjHR, 1.11; 95% CI, 0.94-1.31). The inclusion of AMH improved the model (net reclassification index 0.10 [0.06-0.14]). The instantaneous probability of conception was highest in cycle four across all AMH categories: the probability of natural conception was 11.2% (95% CI, 9.0-14.0) for low AMH levels, 14.3% (95% CI, 12.3-16.5) for normal AMH levels, and 15.7% (95% CI, 12.9-19.0) for high AMH levels. In the regular cycles sensitivity analysis (n = 1,791), the low AMH group had a lower chance of conception (adjHR, 0.77; 95% CI, 0.61-0.97) in the low AMH group compared with normal AMH, and similarly in the continuous model (adjHR, 0.90; 95% CI, 0.85-0.95). CONCLUSION(S): Low AMH levels (<1 ng/mL) are independently associated with a modest but significant reduction in the chance of conception.

Lack of causative mutation in the AMH and AMHR2 genes in a cat (38,XY) with persistent Mullerian duct syndrome (PMDS).

A 1-year-old European shorthair male cat with a normally developed penis was subjected to genetic, endocrinological and histological studies due to unilateral cryptorchidism. The blood testosterone level was typical for males, while the level of anti-Mullerian hormone (AMH) was very low. Surgical removal of internal reproductive organs was followed by a histological study, which revealed inactive testicles with neoplastic changes and derivatives of Mullerian ducts. Cytogenetic analysis showed a normal XY sex chromosome complement and molecular analysis confirmed the presence of Y-linked genes (SRY and ZFY). Although the level of AMH was low, two normal copies of the AMH gene were found using droplet digital PCR (ddPCR). Analysis of the coding sequences of two candidate genes (AMH and AMHR2) for persistent Mullerian duct syndrome (PMDS) in the affected cat and in control male cats (n = 24) was performed using the Sanger sequencing method. In the affected cat, homozygosity was found for three novel missense variants in Exon 1 (one SNP) and Exon 5 (two SNPs) of AMH, but the same homozygous genotypes were also observed in one and two control cats, respectively, whose sex development was not examined. Three known synonymous variants with homozygous status were found in AMHR2. We conclude that the DNA variants identified in AMH and AMHR2 are not responsible for PMDS in the affected cat.

Association between anti-mullerian hormone and metabolic syndrome: insights from a prospective community-based study.

BACKGROUND: Limited studies have investigated the relationship between Anti-Müllerian hormone (AMH) and metabolic syndrome (MetS), yielding inconclusive results. This study aimed to examine the relationship between AMH levels and MetS and its components in women from a general population. METHODS: This prospective study recruited 769 women. Generalized Estimating Equation (GEE) models analyzed longitudinal trends of MetS components. Cox proportional hazard models evaluated effect of age-specific AMH tertiles on MetS occurrence, adjusting for confounders. RESULTS: The GEE analysis indicated that women in the third tertile exhibited higher mean FPG compared to those in the first tertile of age-specific AMH (3 mg/dL; 95% CI: 0.40, 5.60; P = 0.024); however, this association became non-significant after adjustment. Notably, the second tertile showed a significant decrease in FPG mean changes over time (-0.69 mg/dL; 95% CI: -1.31, -0.07; P Interaction = 0.030). Women in the second and third tertiles of age-specific AMH demonstrated lower mean HDL-C compared to the first tertile (-2.96 mg/dL; 95% CI: -4.67, -1.26; P < 0.001 and -2.63 mg/dL; 95% CI: -4.31, -0.96; P = 0.002, respectively). The association between HDL-C changes and the second tertile remained significant after adjustment (-1.91 mg/dL; 95% CI: -3.68, -0.14; P = 0.034). No significant associations were observed between age-specific AMH tertiles and TG and SBP/DBP. Cox models revealed no significant differences in the hazard ratio of MetS between AMH tertiles after adjusting for confounders. CONCLUSION: Despite minor variations in MetS components, AMH levels did not affect MetS risk in women from a general population.

Elecsys® AMH assay: Determination of Anti-Müllerian hormone levels and evaluation of the relationship between superovulation response in Holstein dairy cows.

BACKGROUND: Anti-Müllerian Hormone (AMH) serves as a crucial parameter in assessing the reproductive herd life and ovarian reserve in cattle. Consequently, extensive research is conducted on AMH levels. Various measurement methods can be employed to determine AMH levels. However, to our knowledge, no study has been conducted on Holstein donors using the Elecsys® AMH kit. OBJECTIVE: This study was designed to determine AMH levels in donors utilising the Elecsys® AMH kit and to evaluate the relationship between superovulation response parameters and AMH levels. METHODS: In this study, we measured the serum AMH levels of 36 cows using the Elecsys® AMH automated assay before the superovulation protocol (1st sample) and FSH injections (2nd sample). The cows were categorised into three groups based on their AMH levels: low, medium, and high AMH. RESULTS: Positive correlations were identified between AMH and parameters associated with superovulation response. The high AMH level group exhibited significantly greater numbers of corpus luteum, total embryos, transferable embryos, and grade 1 embryos compared to the medium and low AMH groups (p < 0.05) There was no significant difference between AMH levels before the superovulation protocol and FSH injections(p > 0.05). Body condition score and parity did not significantly affect AMH levels in cows (p > 0.05). Also, AMH cut-off values for the number of corpus luteum, total embryo, and transferable embryos were detected as 234, 227, and 210 pg/mL, respectively. CONCLUSION: These findings demonstrate that a high serum AMH level has a positive influence on the superovulation response. AMH can be used as a reliable marker for the selection of donors in Holstein cows.

Effect of serum anti-Müllerian hormone levels on the superovulation response in Holstein heifers.

BACKGROUND: Anti-Müllerian hormone (AMH) holds potential as a biomarker for assessing the superovulation (SO) response in cattle. Nonetheless, there exists scant information regarding this aspect in the literature concerning dairy heifers. Given this gap, our objective is to explore the viability of AMH as an indicator for gauging the SO response specifically in Holstein heifers. Furthermore, our aim encompasses examining the variations in AMH levels within the same individuals before and after undergoing SO. METHODS: The study included 41 Holstein heifers. All heifers were superovulated and blood samples were taken both before and after the SO protocol. RESULTS: The findings revealed that the mean values of serum AMH concentrations before and after SO were 0.122 ng/mL (0.093-0.248 ng/mL) and 0.119 ng/mL (0.084-0.170 ng/mL), respectively. AMH concentrations in heifers were stratified into low (<0.106 ng/mL), medium (0.107-0.126 ng/mL) and high (>0.127 ng/mL) categories both before and after SO. CONCLUSIONS: There was no significant correlation between AMH levels in the heifers both before and after SO treatment with the number of follicles, corpora lutea, total embryos collected or embryos transferred (p > 0.05). Furthermore, this study showed that serum AMH concentrations in Holstein heifers did not change after SO treatment. In this study, as AMH levels in Holstein heifers were in a narrow range, a relationship between AMH and SO response could not be determined. In future studies, we believe that it would be more useful to plan more studies in Holstein donor heifers, taking into account the number of animals and AMH levels.

Anti-müllerian hormone as a diagnostic biomarker for polycystic ovary syndrome and polycystic ovarian morphology: a systematic review and meta-analysis.

IMPORTANCE: As part of the 2023 international evidence-based polycystic ovary syndrome (PCOS) guideline, this meta-analysis investigated the inclusion of Anti-Müllerian hormone (AMH) levels in the diagnostic criteria for PCOS. OBJECTIVE: To answer the following three questions: 1) Are AMH levels effective in diagnosing PCOS in adult women? 2) Are AMH levels effective in diagnosing PCOS in adolescents? Are AMH levels effective in diagnosing polycystic ovarian morphology (PCOM)? DATA SOURCES: Searches were conducted in six databases until July 31, 2023. STUDY SELECTION AND SYNTHESIS: Eligible studies were those conducted in humans, published in English, and reporting sensitivity, specificity, and/or area under the curve values. Extracted data included study population, age, body mass index, AMH assay, cut-off value of AMH levels, sensitivity, specificity, and area under the curve values. The risk of bias was assessed using the quality assessment of diagnostic accuracy studies tool. A random effects model was used to test diagnostic accuracy. MAIN OUTCOMES: Pooled sensitivity and specificity to use AMH levels for PCOS diagnosis in adults as well as adolescents and for detecting PCOM in adults. RESULTS: Eighty-two studies were included. The adult AMH-PCOS meta-analyses (n = 68) showed a pooled sensitivity and specificity of 0.79 (95% confidence interval [CI], 0.76-0.82; I2 = 86%) and 0.87 (95% CI, 0.84-0.89; I2 = 91%). The adolescent AMH-PCOS meta-analysis (n = 11) showed a pooled sensitivity and specificity of 0.66 (95% CI, 0.58-0.73; I2 = 74%) and 0.78 (95% CI, 0.71-0.83; I2 = 45%). The adult AMH-PCOM meta-analysis (n = 7) showed a pooled sensitivity and specificity of 0.79 (95% CI, 0.72-0.85; I2 = 94%) and 0.87 (95% CI, 0.78-0.93; I2 = 94%). CONCLUSION AND RELEVANCE: This study investigated the most profound change in the 2023 international evidence-based PCOS guideline, which now recommends AMH levels for defining PCOM in adults in accordance with the diagnostic algorithm. Antimüllerian hormone levels alone are insufficient for PCOS diagnosis and are nonspecific for PCOM in adolescents. Multiple factors influence AMH levels and cause heterogeneity as well as limitations in this study. Consequently, no international cut-off value could be recommended, emphasizing the need for research on more individualized cut-off values.

Pigment epithelium-derived factor expression and role in follicular development.

RESEARCH QUESTION: What is the involvement of pigment epithelium-derived factor (PEDF), expressed in granulosa cells, in folliculogenesis? DESIGN: mRNA expression of PEDF and other key factors [Cyp19, anti-Müllerian hormone receptor (AMHR) and vascular endothelial growth factor (VEGF)] in mice follicles was examined in order to typify the expression of PEDF in growing follicles and in human primary granulosa cells (hpGC), and to follow the interplay between PEDF and the other main players in folliculogenesis: FSH and AMH. RESULTS: mRNA expression of PEDF increased through folliculogenesis, although the pattern differed from that of the other examined genes, affecting the follicular angiogenic and oxidative balance. In hpGC, prolonged exposure to FSH stimulated the up-regulation of PEDF mRNA. Furthermore, a negative correlation between AMH and PEDF was observed: AMH stimulation reduced the expression of PEDF mRNA and PEDF stimulation reduced the expression of AMHR mRNA. CONCLUSIONS: Folliculogenesis, an intricate process that requires close dialogue between the oocyte and its supporting granulosa cells, is mediated by various endocrine and paracrine factors. The current findings suggest that PEDF, expressed in granulosa cells, is a pro-folliculogenesis player that interacts with FSH and AMH in the process of follicular growth. However, the mechanism of this process is yet to be determined.