Evaluation of Serum Anti-Müllerian Hormone (AMH) Values for 28,016 Bulgarian Women: Prognostic Statistical Model of Age Specific AMH Declining

The present study aims to establish a relationship between serum AMH levels and age in a large group of women living in Bulgaria, as well as to establish reference age-specific AMH levels in women that would serve as an initial estimate of ovarian age. A total of 28,016 women on the territory of the Republic of Bulgaria were tested for serum AMH levels with a median age of 37.0 years (interquartile range 32.0 to 41.0). For women aged 20 - 29 years, the Bulgarian population has relatively high median levels of AMH, similar to women of Asian origin. For women aged 30 - 34 years, our results are comparable to those of women living in Western Europe. For women aged 35 - 39 years, our results are comparable to those of women living in the territory of India and Kenya. For women aged 40 - 44 years, our results were lower than those for women from the Western European and Chinese populations, close to the Indian and higher than Korean and Kenya populations, respectively. Our results for women of Bulgarian origin are also comparable to US Latina women at age 30, 35 and 40 ages. On the base on constructed a statistical model to predicting the decline in AMH levels at different ages, we found non-linear structure of AMH decline for the low AMH 3.5) the dependence of the decline of AMH on age was confirmed as linear. In conclusion, we evaluated the serum level of AMH in Bulgarian women and established age-specific AMH percentile reference values based on a large representative sample. We have developed a prognostic statistical model that can facilitate the application of AMH in clinical practice and the prediction of reproductive capacity and population health.

Anti-Müllerian Hormone and Its Utility in Cattle Reproduction

Reproductive biotechnologies offer us greater possibilities to improve animal genetics. However, the success of these depends on different factors such as the proper selection of the donor female. For this reason, endocrine markers have been used to evaluate the ovarian reserve, which allow a successful selection of donors. Recent research has shown, among other things, that concentrations greater than 0.130 ng/mL of anti-Mullerian hormone (also known as Muller-inhibiting substance, which is a member of the transforming growth factor beta superfamily of growth and differentiation factors) are related to donors of more than fifteen transferable embryos. Therefore, this review describes studies showing that the measurement of anti-Müllerian hormone concentrations, before superovulation programs, reduces the costs per embryo produced.

Seminal plasma anti-Müllerian hormone level correlates with semen parameters but does not predict success of testicular sperm extraction （TESE）

Aim： To assess seminal plasma anti-Müllerian hormone （AMH） level relationships in fertile and infertile males. Methods： Eighty-four male cases were studied and divided into four groups： fertile normozoospermia （n = 16）, oligoastheno- teratozoospermia （n = 15）, obstructive azoospermia （OA） （n = 13） and non-obstructive azoospermia （NOA） （n = 40）. Conventional semen analysis was done for all cases. Testicular biopsy was done with histopathology and fresh tissue examination for testicular sperm extraction （TESE） in NOA cases. NOA group was subdivided according to TESE results into unsuccessful TESE （n = 19） and successful TESE （n = 21）. Seminal plasma AMH was estimated by enzyme linked immunosorbent assay （ELISA） and serum follicular stimulating hormone （FSH） was estimated in NOA cases only by radioimmunoassay （RIA）. Results： Mean seminal AMH was significantly higher in fertile group than in oligoasthenoteratozoospermia with significance （41.5±10.9 pmol/L vs. 30.5±10.3 pmol/L, P 〈 0.05）. Seminal AMH was not detected in any OA patients. Seminal AMH wascorrelated positively with testicular volume （r = 0.329, P = 0.005）, sperm count （r = 0.483, P = 0.007）, sperm motility percent （r = 0.419, P = 0.021） and negatively with sperm abnormal forms percent （r = -0.413, p = 0.023）. Nonsignificant correlation was evident with age （r = -0.155, P = 0.414） and plasma FSH （ r = -0.014, P = 0.943）. In NOA cases, seminal AMH was detectable in 23/40 cases, 14 of them were successful TESE （57.5%） and was undetectable in 17/40 cases, 10 of them were unsuccessful TESE （58.2%）. Conclusion： Seminal plasma AMH is an absolute testicular marker being absent in all OA cases. However, seminal AMH has a poor predictability for successful testicular sperm retrieval in NOA cases.

Anti-Müllerian hormone and antral follicle count predict ovarian response in women less than 45 years following GnRH antagonist multiple-dose protocol

Objective:To speculate which of the following parameters:antral follicle count(AFC),anti-Müllerian hormone(AMH),follicle-stimulating hormone(FSH)and age can be used as a predictor of ovarian response to gonadotropin-releasing hormone(GnRH)antagonist stimulation multiple-dose protocol in women under 45 years,and to determine the cutoff value of these parameters and their correlations for predicting low and high ovarian response.Methods:This prospective study included 462 women with the mean age of(29.3±6.5)years.All women were subjected to the GnRH antagonist stimulation multiple-dose protocol.On the second day of the menstrual cycle,ultrasonography was conducted to determine AFC in both ovaries.Peripheral blood samples were collected to evaluate the level of estradiol,FSH,luteinizing hormone,prolactin,thyroid-stimulating hormone,and AMH.The women were divided into three groups:low response(AHH<1 ng/mL,n=173),normal response(AMH=1.0-3.5 ng/mL,n=175),and high response(AMH>3.5 ng/mL,n=114).Results:A significant decrease was found in the age and FSH level in the high response group compared to other groups(P<0.001).Conversely,a significant increase was shown in AMH,estradiol on human chorionic gonadotropin(hCG)day,AFC,mature oocytes,fertilized oocytes,and embryos transferred in the high response group compared to the other two groups(P<0.001).The receiver operating characteristic(ROC)curves demonstrated that AFC and AMH had the highest accuracy,followed by basal FSH level and age in the prediction of low ovarian reserves(P<0.001)with cutoff values of≤4.50 and≤0.95 for AFC and AMH,respectively.Moreover,the ROC analysis showed that AFC had the highest accuracy,followed by AMH level and age in the prediction of high ovarian reserves with a cutoff value of≥14.50,≥3.63,and≤27.50 years,respectively(P<0.01).A significant decrease was observed in women's age,estradiol level,and oocyte fertilization rate in pregnant women compared to non-pregnant women(P<0.001).Additionally,significant negative correlations were found between the AFC,the number of mature oocytes,fertilized oocytes,embryos transferred,and the age of pregnant women(P<0.001).Conclusions:AFC and AMH predict low and high ovarian response to GnRH antagonist stimulation multiple-dose protocol in women under 45 years.

Impact of Systemic Lupus Erythematosus on Ovarian Reserve in Premenopausal Women before Receiving Cyclophosphamide Therapy: Evaluation Using Anti-Müllerian Hormone

Introduction: Anti-Müllerian hormone (AMH) is shown to be a possible indicator of ovarian function. Severe systemic lupus erythematosus (SLE) patients exposed to high-dose cyclophosphamide (CTX) have a much higher risk of developing infertility and premature ovarian failure. Therefore, we performed a prospective case-control study to evaluate the impact of SLE on women’s ovarian reserve using AMH before CTX therapy. Methods: SLE patients before receiving CTX therapy were enrolled in our hospital. Age-matched healthy women were served as controls. Serum AMH level was measured using an enzyme-linked immunosorbent assay. Basal hormone levels were measured including follicle-stimulating hormone, luteinizing hormone, and estradiol on the third day of their menstrual periods. All participants underwent transvaginal ultrasonographic examination for the determination of total antral follicle count on the third day. Results: AMH value in SLE patients was significantly lower compared to healthy control with normal ovarian reserve. No significant difference in AMH levels was found between SLE and healthy control with low ovarian reserve. Conclusions: SLE patients not receiving CTX therapy even with normal menstruation, still had an impaired ovarian reserve. Therefore, early monitoring of AMH levels could better reflect the ovarian function and reproductive outcomes of SLE patients and relative protective strategy needed to reserve fertility.

Effect of modified laparoscopic salpingectomy on ovarian reserve:Changes in the serum antimüllerian hormone levels

Objective:To retrospectively estimate the impact of modified laparoscopic salpingectomy on the ovarian reserve in infertile women.Methods:There were 74 infertile women undergone modified laparoscopic salpingectomy from June 2016 to January 2017,and their levels of serum antimüllerian hormone,basal follicle-stimulating hormone and estradiol were reviewed retrospectively.Results:No significant change was detected in serum antimüllerian hormone at 3 months after surgery compared to preoperative level(p=0.857).Similar changes were observed for the basal follicle-stimulating hormone(p=0.102)and estradiol(p=0.233)level.Conclusions:Our results revealed that modified laparoscopic salpingectomy might be a valuable treatment for hydrosalpinx before in vitro fertilization.

Association between Metal(loid)Exposure and Risk of Polycystic Ovary Syndrome Mediated by Anti-Müllerian Hormone among Women Undergoing In Vitro Fertilization and Embryo Transfer

Objective To investigate the relationship and potential pathways between metal(loid)exposure and the risk of polycystic ovary syndrome(PCOS)in women of childbearing age.Methods This case-control study included 200 patients with PCOS(cases)and 896 non-PCOS controls with the age of 25-37 years.The concentrations of 29 metal(loid)s in the follicular fluid(FF)and clinical indicators in the serum were measured in all participants.Logistic regression analysis and mediation analysis were conducted to evaluate the associations between metal(loid)exposure and PCOS risk and investigate the possible roles of clinical indicators,respectively.Results Logistic regression analysis revealed an association between high copper levels in FF and increased PCOS risk(highest vs.lowest quartile:adjusted odds ratio=2.94,95%confidence interval:1.83-4.72).A high luteinizing hormone/follicle-stimulating hormone ratio and elevated levels of testosterone and anti-Müllerian hormone(AMH)were strongly associated with increased PCOS risk induced by high copper exposure.The mediation analysis indicated a mediating effect of AMH in the association between copper exposure and PCOS risk.Conclusion Copper may affect PCOS risk through the hypothalamic-pituitary-ovarian axis,mediated by AMH.Copper exposure and internal AMH levels are important indicators for early warning of PCOS development.

Potential Application of Anti-Müllerian Hormone in Polycystic Ovary Syndrome According to Chinese Classification Criteria:A Retrospective Analysis

Objective:Anti-Müllerian hormone(AMH)expression is elevated in patients with polycystic ovary syndrome(PCOS),however,its clinical significance is not clear.Owing to the strong correlation between AMH and polycystic ovarian morphology(PCOM),some studies believe that AMH alone can be used to diagnose PCOS.The aim of this study was to explore whether AMH can be used to diagnose PCOS and to differentiate the various PCOS subtypes.Methods:This was a retrospective study of 503 patients with PCOS.Patients were divided into eight subtypes based on the presence/absence of hyperandrogenemia(HA),insulin resistance(IR),or obesity(OB).The expression characteristics of AMH in each subtype were analyzed.Due to the small number of patients with subtypes 7 and 8,only patients with subtypes 1-6 were included in the analysis.Results:AMH showed a good positive correlation with PCOM(P=0.000)and negative correlations with OB(P=0.000)and IR(P=0.003).The free testosterone index showed no correlation with AMH(P=0.803).The percentages of patients with each subtype(excluding subtypes 7-8)and their respective AMH levels were as follows:Type 1(HA+NIR+OB)4.77% and 9.12 ng/mL;Type 2(HA+IR+NOB)20.68% and 10.34 ng/mL;Type 3(HA+NIR+NOB)23.66% and 9.47 ng/mL;Type 4(HA+IR+OB)30.82% and 8.32 ng/mL;Type 5(NHA+NIR+NOB)11.73% and 10.0 ng/mL;and Type 6(NHA+IR+NOB)6.16% and 9.76 ng/mL.The diagnostic rates of AMH(>8.09 ng/mL)and ultrasound for PCOM were 60.10% and 85.60% ,respectively,suggesting that AMH did not completely predict PCOM.Conclusions:High AMH levels can be used to evaluate the incidence trend of PCOS.However,due to clinical heterogeneity,accurately evaluating the severity of PCOS and identifying the subtype of PCOS in Chinese patients are difficult.Individualized treatment should be administered based on accurate clinical subtypes and other clinical characteristics.

Circulating anti-Müllerian hormone as predictor of ovarian response to gonadotrophins in women with polycystic ovary syndrome

Objective To investigate the impact of high circulating anti-Müllerian hormone（AMH）on the outcome of ovulation induction using human menopausal gonadotropin（hM G）in women with polycystic ovary syndrome（PCOS）.Methods This prospective study included 63 anovulatory women with PCOS who underwent hM G ovarian stimulation. Serum AMH concentrations were compared between responders and non-responders. The receiver-operating characteristic（ROC）curve was used to evaluate the prognostic value of circulating AMH.Results hM G responders had a significantly lower serum AMH concentration compared with non-responders（8.43±2.18 μg/L vs 11.05±2.85 μg/L, P〈0.001）. In multivariate Logistic regression analysis, AMH was an independent predictor of ovulation induction by hM G in PCOS patients. ROC curve analysis showed AMH was a useful predictor of ovulation induction by hM G in PCOS patients, having 91.7% specificity and 66.7% sensitivity when the threshold AMH concentration was 10.12 μg/L.Conclusion Serum AMH can be used as an effective parameter to predict ovarian response to hM G treatment in PCOS patients.

Anti-Müllerian hormone, antral follicle count and folliclestimulating hormone for predicting the number of oocytes retrieved in IVF/ICSI cycles

Objective To evaluate the efficacy of anti-Müllerian hormone（AMH）, antral follicle count（AFC） and follicle-stimulating hormone（FSH） for predicting the number of oocytes retrieved in in-vitro fertilization/intracytoplasmic sperm injection（IVF/ICSI）cycles.Methods In this retrospective study, a total of 122 infertile women were divided into two groups： group A, 〈35 years（n=71）; group B, ≥35 years（n=51）. AMH and FSH were determined on 2-5 d of the early menstrual cycle. AFC was tested on the second day of the menstrual cycle before the start of stimulation.Results Group B had higher FSH levels compared with group A（8.2±3.5 IU/L vs 6.8±2.4 IU/L, P〈0.05）. However, levels of AMH and AFC in group B were lower than those of group A（AMH： 4.2±3.5 μg/L vs 2.7±2.7 μg/L; AFC： 9.0±3.9 vs 5.4±3.3, P〈0.05）. The number of oocyte retrieved in the two groups was not significantly different（11.5±6.8 vs 9.6±6.9, P〉0.05）. The level of AMH was more strongly correlated with the number of oocytes retrieved than that of AFC or FSH level. The strengths of the correlation degrees were AMH level, AFC, and FSH level in turn（r=0.600, 0.511,-0.369）.Conclusion AMH would be a useful predictor for ovarian response.

Comparison of body mass index, anti-müllerian hormone and insulin resistance parameters among different phenotypes of polycystic ovary syndrome

Background:Diagnosis of polycystic ovary syndrome(PCOS)depends on 2003 Rotterdam Criteria.According to these criteria there are four possible combinations resulting in various phenotypes.We aimed(i)to confirm that the levels of body mass index(BMI),anti-müllerian hormone(AMH)levels and insulin resistance(IR)are higher in PCOS patients and higher in phenotype-A among PCOS patients,and(ii)to determine cut-off values for the diagnosis of PCOS and phenotype-A.Materials and methods:This study was conducted in an IVF Center,between November 2019 and January 2021.Data of infertile women participating in the study was evaluated retrospectively.Parameters such as menstruation pattern,clinical hyperandrogenism,age,BMI,follicle stimulating hormone(FSH),luteinizing hormone(LH),estradiol,thyroid stimulating hormone(TSH),prolactin,AMH,dehydroepiandrosterone sulphate(DHEA-S),fasting blood glucose,fasting insulin levels,antral follicle counts(AFC)and ovarian volumes were recorded for each patient.Women were grouped as PCOS and non-PCOS,and PCOS group was further divided into 4 subgroups according to their phenotypes.Data of infertile patients with PCOS patients were compared with infertile non-PCOS patients and PCOS phenotypes were compared among each other.Results:Data of 244 infertile patients was included in the study.BMI,AMH,AFC,and HOMA-IR were statistically higher in PCOS patients,compared to non-PCOS patients.We found the AMH level of>3.105 ng/ml to be having 90.8%sensitivity and 90%specificity to diagnose a patient as PCOS.Among different phenotypes,also BMI,AMH,and insulin resistance index(HOMA-IR)levels were significantly higher in infertile PCOS phenotype-A when compared to other three phenotypes(p:0.003,p:0.000,and p:0.000,respectively).The AMH cut-off value to estimate phenotype-A was found as 6.095 ng/ml with 69.2%sensitivity and 86.7%specificity.We did not found threshold levels of BMI and HOMA-IR with high sensitivity to identify phenotype-A.Conclusion:Properly diagnosing PCOS and determining the phenotype are crucial due to the long-term health conditions.Therefore,we suggest that serum AMH level could be included in PCOS diagnosis criteria,and the value of 3.105 ng/ml would have a 90.8%sensitivity and 90%specificity.Also,to identify phenotype-A,AMH level could be used.Therefore,we speculate that AMH may serve to identify PCOS and PCOS phenotype-A in places where ultrasound imaging is not straightforward to perform or not easily accessible.