Utility of age-specific serum anti-Müllerian hormone concentrations

This study assessed whether age-specific (as-) cutoffs for anti-Müllerian hormone (AMH) have higher specificity in reflecting ovarian reserve than non-age-specific (nas-) AMH values. as-AMH values were defined in 792 consecutive infertility patients by establishing as-quartiles of AMH within five age groups. Oocyte yields were then compared among women with AMH below or above the 25th centile at each age group. AMH continually decreased with advancing female age (P<0.0001) and differed significantly in each of five selected age categories (P<0.001). In 442 women who reached IVF, as-AMH was predictive of lower oocyte yield if below as-25th centile and of higher oocyte yield if above as-75th centile. Combined normal and elevated as-AMH demonstrated 6.4 times (95% CI 3.9-20.6) odds of retrieving more than four oocytes than low as-AMH. Like as-FSH, as-AMH better reflects ovarian reserve than nas-ovarian reserve testing. However, in contrast to as-FSH, as-AMH defines risk for diminished ovarian reserve or high oocyte yields (i.e. ovarian hyperstimulation syndrome) and, therefore, may be a particularly useful ovarian reserve test in younger women in whom diminished ovarian reserved is most frequently overlooked, and who are at highest risk for ovarian hyperstimulation syndrome.     

Analyzing the possible involvement of anti-Müllerian hormone and anti-Müllerian hormone receptor II single nucleotide polymorphism in infertility

Purpose

We performed TaqMan genotyping assays of anti-Mullerian hormone (AMH) and anti-Mullerian hormone receptor type II (AMHRII) single nucleotide polymorphisms (SNPs) in order to investigate how their frequency and distribution affect infertility treatment outcome.

Methods

Eighty Japanese women (advanced age: n = 51, endometriosis: n = 18, male infertility as a control: n = 11) who undertook ART were included in the study, and all couples underwent a full infertility investigation protocol. In order to investigate the natural distribution of SNPs, a naturally pregnant group of 28 subjects was recruited from among women who conceived naturally and subsequently delivered in our department. Genomic DNA was extracted from peripheral blood and genotyping was conducted by TaqMan genotyping assay. The relationship of AMH and AMHRII SNPs and treatment outcome in infertile women. Comparison of allele and genotype frequencies of infertile patients with naturally pregnant women.

Results

AMHRII −482 A>G homozygote mutation was complicated with ISV 5–6 C>T homozygote mutation and showed a significantly lower oocyte retrieval rate compared with a wild type. Two of 3 cases of AMHRII −482 A>G homozygote mutation were poor responders, and the distribution and frequency of each allele of naturally pregnant women showed no statistical difference compared with infertile women.

Conclusions

This study revealed the possible involvement of AMHRII −482 A>G polymorphism on the malfunction of follicular development in Japanese women.     

Dynamics of anti-Müllerian hormone during controlled ovarian stimulation

Aim: To evaluate the dynamics of anti-Müllerian hormone (AMH) during controlled ovarian stimulation (COH) and to correlate changes in AMH to age, estradiol (E2) levels, and the presence of polycystic ovary syndrome (PCOS).

Methods: Data were retrospectively collected from women presenting for COH in the outpatient clinic of a university hospital between January and July 2011. Concentrations of AMH and E2 during COH with gonadotropins for in vitro fertilization (IVF) (n?=?68) and clomiphene or low-dose gonadotropin stimulation cycles (n?=?27) for intrauterine insemination were evaluated. Percentage change in AMH and E2 from pre-stimulation values was calculated. Dynamics of hormonal changes were analyzed using non-parametric tests. Correlations between changes in AMH and E2 were analyzed with Spearman correlation.

Results: During IVF stimulation, AMH declined steadily from pre-stimulation values. No significant change in AMH dynamics was observed during clomiphene or low-dose stimulation cycles. Percentage decline in AMH during IVF stimulation correlated with rise in E2 at all time points.

Conclusions: The observed phenomena contribute to an improved understanding of AMH expression and its role in the follicular development. Our data support the concept that AMH is produced by secondary, preantral and small antral follicles in the early part of stimulation and declines as these follicles are recruited into dominant growing follicles.     

Diagnosis of premature menopause measuring circulating anti-Müllerian hormone

The production of anti-müllerian hormone for the ovarian follicles begins near the puberty and the circulating levels begin to descend progressively in the stage of the pre-menopause coinciding with the depletion follicular and in consequence the menstrual cycles become irregular, frequently anovulatories. Therefore, concentration of anti-müllerian hormone shows a close correlation with follicular reserve and reproductive capacity, more than FSH and estradiol measurements. We described two patients that developed premature ovarian failure without previous diagnosis and therefore just were treated pharmacologically with estrogen-progestagen to induce menstrual bleeding. In blood of both patients was found low levels (< or = 4 ng/mL) of anti-müllerian hormone, and by means of sonography the absence of follicles was demonstrated in the ovaries. Has intended that premature ovarian failure could be of a chromosomal dysfunction, similar to other gonadal dysgenesias, another explanation of the mechanism is that it could be for development of some autoimmunity dysfunction. Therefore, the combined hormonal substitution of estrogen with progestagen should stay during several years to avoid the complications for the lack of estrogens; in some cases, could be informed on offering the pregnancy possibility by means of the attended fertilization using ovules donor.     

Early-life factors and adult anti-Müllerian hormone levels

Journal of Assisted Reproduction and Genetics - This study aims to examine whether early-life factors are associated with adult ovarian reserve, measured by anti-Müllerian hormone (AMH)...     

Molecular analysis of the anti-Müllerian hormone,the anti-Müllerian hormone receptor,and galactose-1-phosphate uridyl transferase genes in patients with the Mayer-Rokitansky-Küster-Hauser syndrome

Introduction. Müllerian agenesis, also named the Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) or vaginal aplasia, is the second most common cause of primary amenorrhea. It is characterized by the congenital absence of the Müllerian structures including the Fallopian tubes, the uterus, and the internal portion of the vagina in an otherwise normally feminized 46,XX subject. Most cases are sporadic in inheritance, but the occurrence of some patients with chromosomal translocations or even familial aggregates suggest a genetic basis for the disease, although the etiology of the disease is still unknown. It has been suggested that activating mutations in the anti-Müllerian hormone (AMH) or in its receptor (AMHRII) are potential sources for the defect. Methods. In this study we describe the molecular analysis of both the AMH and AMHR genes in a group of 15 patients with Müllerian agenesis. After sequencing all exons and exon/intron junctions of both genes, we were not able to detect any deleterious mutation. Results. Five new polymorphisms, 2 of them in the AMHRII gene and 3 of them in the AMH gene, were identified. No significant differences between patients and controls were observed in the frequency of a given polymorphism. Conclusion. This work reinforces the view that molecular defects in the AMH or AMHR are unlikely sources for the MRKHS syndrome.     

Effect of long-term using of hormonal contraception on anti-Müllerian hormone secretion

Anti-Müllerian hormone (AMH) is an important factor associated with female fertility and the ovarian reserve. There are several past studies available concerning the influence of hormonal contraception (HC) on serum AMH levels. Recent studies have reported that AMH levels in women using HC can be about 30% lower compared to those not using HC. However, earlier studies showed no reduction in AMH levels in HC users. We decided to evaluate the effects of long-term HC use (mean duration of HC use: 11.4 years) on AMH levels in women. To exclude potential shorter and reversible decreasing effects of HC on fertility function, we decided to include women in the study who had stopped using HC 1 year before the AMH sample collection. We examined 105 women who used HC and 44 women who had never used HC. The median concentration of AMH in the group of long-term users of HC was 2.89 and 3.37 ng/ml in the group of women who had never used HC. We found no statistically significant difference (p?=?0.3261). In conclusion, we observed no negative impact of HC on the AMH serum levels. AMH can be used as an ovarian reserve marker for these women.     

Serum anti-Müllerian hormone and inhibin B in disorders of spermatogenesis

This study investigates circulating concentrations of AMH and inhibin B in men with azoospermia. Serum AMH and inhibin B are significantly lower in the men with nonobstructive azoospermia compared to the controls and the men with obstructive azoospermia, suggesting that these hormones could be markers of nonobstructive azoospermia.     

Inhibin B and anti-Müllerian hormone in spermatic vein of subfertile men with varicocele

Introduction: The pathophysiology of subfertility in men with varicocele remains unclear as well as the role of inhibin B (Inh-B) and anti-Müllerian hormone (AMH). The aim of this study was to evaluate Inh-B and AMH concentrations in the spermatic vein of subfertile men with varicocele. Patients and Methods: A total of 61 subfertile men with varicocele and 31 fertile controls underwent standard andrological evaluation. All subfertile men underwent varicocelectomy, during which blood samples were obtained from the spermatic vein to evaluate Inh-B and AMH concentrations. Results: Peripheral vein Inh-B concentrations in men with varicocele were lower as compared to controls (52.9 [8.3-136.0) vs 116±9.7 ng/dL, P = .001). There was no difference in AMH concentrations (10.2 [4.4-45.4]) vs 10.4±0.8 pg/dL, P = 0.9). Spermatic vein Inh-B concentrations in men with varicocele were higher compared to those of peripheral vein (87.6±4.4 vs 52.9 [8.3-136.0] ng/dL, P = .001). On the contrary, spermatic vein AMH concentrations were lower compared to those from peripheral vein (8.84 [3.9-47.7] vs 10.2 [4.4-45.4] pg/dL, P = .013). Conclusions: Inh-B constitutes a reliable marker of Sertoli cell function as well as spermatogenesis. On the contrary, the clinical significance of AMH in men with varicocele remains to be elucidated.     

Elevated serum thyroid-stimulating hormone is associated with decreased anti-Müllerian hormone in infertile women of reproductive age

Purpose

Thyroid dysfunction and autoimmune thyroiditis are associated with fertility in women of reproductive age. Anti-Müllerian hormone (AMH), a known biomarker of ovarian function, may be affected by impaired thyroid function; however, the relationship between AMH and thyroid hormone has not been elucidated.

Methods

In this case–control study, to identify the impact of thyroid hormone on ovarian reserve, we recruited 67 consecutive Japanese infertile patients and 27 normal fertile women aged 30–39 years without impact factors on thyroid and ovarian functions between 2012 and 2013. We assessed patient age, BMI and AMH, prolactin, TSH and FT4 levels of all study participations as independent variables. To evaluate the relationship between AMH and thyroid hormone, we matched patients by age and body mass index as confounding factors using 1:1 matching for statistical analysis of healthy fertile women and infertile patients and obtained 23 pairs. Then, independent variables were subjected to multiple regression analysis.

Results

Multiple regression analysis showed that both thyroid-stimulating hormone (TSH) levels and patient age were negatively correlated with AMH levels in infertile patients (patient age and TSH: standardized partial regression coefficient (β), −0.534 and −0.361; p = 0.003 and 0.036, respectively), but not in normal fertile women.

Conclusions

AMH levels were inversely correlated with TSH levels in infertile women of reproductive age.     

Random anti-Müllerian hormone predicts ovarian response in women with high baseline follicle-stimulating hormone levels

Objective

To evaluate the predictive value of random serum anti-Müllerian hormone (AMH) in the assessment of ovarian response in patients with diminished ovarian reserve (DOR; diagnosed after the observation of elevated baseline levels of early follicular follicle-stimulating hormone [FSH]) who were undergoing intracytoplasmic sperm injection-embryo transfer (ICSI-ET) and to compare the random serum AMH and baseline FSH levels in these patients for the prediction of poor ovarian response.

Design

Retrospective study.

Setting

University hospital.

Patients

One hundred and thirty-nine patients who were undergoing ICSI-ET cycles with early follicular FSH level >9 IU/mL.

Intervention(s)

None.

Main Outcome Measure(s)

Poor ovarian response in ICSI-ET cycles.

Results

For the identification of women at risk of cycle cancellation, an AMH cut-off level ≤1.2 ng/mL had 97.3 % sensitivity, 31.3 % specificity, 33.9 % positive predictive value, and 96.9 % negative predictive value in the women with high baseline FSH levels. An AMH cut-off level ≥1 ng/mL had a sensitivity of 58.7 % and specificity of 95.1 % for prediction of retrieval of 4 or more oocytes. By using a serum AMH cutoff level of 1.5 ng/mL, the ongoing pregnancies were predicted with 83.3 % sensitivity and 82.5 % specificity and yielded a positive predictive value of 31.2 % and a negative predictive value 98.1 %.

Conclusion

Measurement of random serum AMH level is a useful tool in the prediction of ovarian response in patients with high serum early follicular FSH levels.     

Clinical utility of different anti-Müllerian hormone – AMH assays for the purpose of pregnancy prediction

Purpose: Comparison of outcomes of IVF cycles where the AMH levels was measured with five different AMH kits: Immunotech (IOT), Beckman Coulter II Gen. RUO, Beckman Coulter II Gen. IVD (BC II IVD), Ansh Labs ultrasensitive (Ansh) and the automated Elecsys Roche assay.

Methods: Retrospective analysis of clinical data for 3693 cycles.

Results: In women 1.4?ng/ml) AMH concentrations, and in those >?39?years with medium (≥0.6 and ≤1.4?ng/ml) and high AMH concentrations the clinical pregnancy rate differed significantly among groups of patients whose AMH level was measured with different kits. In those subgroups, the highest rates were recorded for the BC II IVD and Ansh groups, while the lowest in the IOT group. AMH concentrations differed significantly between different kits in all age groups (the highest in each age group was for the IOT kit and the lowest for BC II IVD). AMH correlates positively with antral follicle count, MII and number of oocytes retrieved.

Conclusions: This study demonstrated that we could expect very different pregnancy rates with the same AMH results depending on the AMH kit used. That would means, different values of AMH could similarly lead to misleading clinical decisions in IVF.     

Large ovarian endometriomas are associated with high pre-operative anti-Müllerian hormone concentrations

Research questionAre large ovarian endometriomas associated with high pre-operative anti-Müllerian hormone (AMH) concentrations?DesignData from 332 women who underwent AMH measurement before surgery for endometriosis were prospectively recorded in a large database. Univariate analysis compared AMH concentrations in terms of the patients’ baseline characteristics. A multivariate model was used to identify variables having an independent relationship with AMH concentration.ResultsAmong 332 women included in the study, 47.6% were aged 18–30 years, 67.8% were infertile and 85.5% were nulliparous. A total of 66.3% had ovarian endometriomas, and 10.8% had cysts measuring over 6 cm. Bilateral cysts over 3 cm were recorded in 24.7% of the women. Univariate analysis identified two variables that had a statistically significant relationship with AMH concentration: the woman's age (P = 0.01) and cyst size (P < 0.001). Multivariate analysis revealed that ages of 36–40 years and over 40 years showed a significant association with lower AMH concentrations (P = 0.02 and P = 0.009, respectively), while a cyst size of over 6 cm was statistically associated with high AMH concentrations (P < 0.001), after adjustment for smoking, parity, rectosigmoid endometriotic nodules and a bilateral location of endometriomas.ConclusionsPre-operative AMH concentration was significantly increased in women with large endometriomas of over 6 cm, independent of their age or the presence of bilateral endometriomas. This is relevant for both surgeons and patients when planning surgery in women with an intention to conceive post-operatively.     

Pregnancy prognosis in women with anti-Müllerian hormone below the tenth percentile

Abstract

Although serum anti-Müllerian hormone (AMH) is considered a good predictor of ovarian response during in vitro fertilisation (IVF), pregnancies have been reported with low values, questioning its usefulness as a predictor of treatment outcome. A retrospective study was therefore carried out to assess the IVF treatment outcomes in women with AMH below the tenth percentile of the study population. In all, 134 women with AMH ≤3?pmol/L underwent 180 IVF cycles. The mean age at the time of treatment was 37?±?5 years. Fifty-three (29.4%) cycles were abandoned because of poor response to gonadotrophins, 12 (6.7%) due to absence of eggs at oocyte retrieval and 18 (10%) due to fertilisation failure. Seven (3.8%) had a biochemical pregnancy, 4 (2.2%) had a missed miscarriage and 8 (4.4%) had a live birth. When stratified by age, women older than 42 years had less number of follicles (p?<?0.05) and those older than 39 years had less oocytes (p?<?0.01) compared to those 35 years and younger. Live births declined with increasing age, when age was assessed as a continuous variable (p?=?0.023). Women with low AMH levels have a high probability of treatment cancellation, failure to proceed to embryo transfer and a low chance of achieving a viable pregnancy.     

Clinical significance of serum concentration of anti-Müllerian hormone in obese women with polycystic ovary syndrome

In the human ovary, expression of anti-Müllerian hormone (AMH) is detected primarily in granulosa cells of preantral and small antral follicles. The aim of this study was to compare serum AMH measurements in obese women with polycystic ovary syndrome (PCOS) with those in obese normo-ovulatory women and to evaluate the role of AMH as a predictor of ovulation induction by clomiphene citrate compared to FSH. Sixty-eight obese women with PCOS were compared to 17 normoovulatory obese women. All women had a body mass index greater than 30 kg/m(2). Women with PCOS received clomiphene citrate (150 mg/day) for 5 days starting from day 3 of cycle and were subdivided into responsive and non-responsive groups. There was a significant difference in AMH concentration between women with PCOS and the control group (P < 0.05) and also between women with PCOS who responded to clomiphene citrate and those who did not (P < 0.01). A value of 1.2 ng/ml AMH could be used to predict response to clomiphene citrate in obese women with PCOS (sensitivity 71%, specificity 65.7%). AMH production increases in women with PCOS compared to controls. AMH measurement could also be useful in the prediction of ovarian response to clomiphene citrate.