AMH Measurement Research Articles

Ongoing Pregnancy Rates in Women with Low and Extremely Low AMH Levels. A Multivariate Analysis of 769 Cycles

BackgroundThe ideal test for ovarian reserve should permit the identification of women who have no real chance of pregnancy with IVF treatments consequent upon an extremely reduced ovarian reserve. The aim of the current study was to evaluate pregnancy rates in patients with low AMH levels (0.2–1 ng/ml) and extremely low AMH levels (<0.2 ng/ml) and to determine the cumulative pregnancy rates following consecutive IVF treatments.MethodsWe conducted an historical cohort analysis at a tertiary medical center. Serum AMH levels were measured at initial clinic visit and prior to all following treatment cycles in 181 women (769 cycles) with an initial AMH level ≤1 ng/ml, undergoing IVF-ICSI. Main outcome measures were laboratory outcomes and pregnancy rates.ResultsSeventy patients undergoing 249 cycles had extremely low AMH levels (≤0.2 ng/ml), whereas 111 patients undergoing 520 cycles had low AMH levels (0.21–1.0 ng/ml). Number of oocytes retrieved per cycle, fertilized oocytes and number of transferred embryos were significantly lower in the extremely low AMH levels group compared to the low AMH levels (P<0.003). Crude ongoing pregnancy rates were 4.4% for both groups of patients. Among 48 cycles of women aged ≥42 with AMH levels of ≤0.2 ng/ml no pregnancies were observed. But, in patients with AMH levels of 0.2–1.0 ng/ml, 3 ongoing pregnancies out of 192 cycles (1.6%) were observed. However, in a multivariate regression analysis adjusted for age and cycle characteristics, no significant differences in ongoing pregnancy rates per cycle between the two groups were evident. Cumulative pregnancy rates of 20% were observed following five cycles, for both groups of patients.ConclusionsPatients with extremely low AMH measurements have reasonable and similar pregnancy rates as patients with low AMH. Therefore, AMH should not be used as the criterion to exclude couples from performing additional IVF treatments.

Analysis of two assays for the measurement of amh in women with low ovarian reserve

The measurement of AMH is increasingly well validated as a marker of the functional ovarian reserve, but there is a lack of standardization of assays, which may be of particular importance at the extremes of the working range. In this study we have assessed the Ansh Labs and Beckman-Coulter GenII AMH assays in two groups of women with identified low ovarian reserve.

Have advancements in ovarian reserve testing resulted in a decline in the number of stopped cycles in art?

The choice of treatments and FSH starting dose are based on many female parameters of which ovarian reserve and age are the most relevant. AMH testing for ovarian reserve was introduced in our routine practice in 2009. The objective of this study was to establish if routine AMH measurement and adjustment of stimulation protocol impacts on cycle cancellation rate due to poor ovarian response.

Pretreatment anti-Müllerian hormone predicts for loss of ovarian function after chemotherapy for early breast cancer

AimImproving survival for women with early breast cancer (eBC) requires greater attention to the consequences of treatment, including risk to ovarian function. We have assessed whether biochemical markers of the ovarian reserve might improve prediction of chemotherapy related amenorrhoea. MethodsWomen (n=59, mean age 42.6years [(range 23.3–52.5]) with eBC were recruited before any treatment. Pretreatment ovarian reserve markers (anti-Müllerian hormone [AMH], follicle-stimulating hormone [FSH], inhibin B) were analysed in relation to ovarian status at 2years. ResultsPretreatment AMH was significantly lower in women with amenorrhoea at 2years (4.0±0.9pmol/L versus 17.2±2.5, P<0.0001), but FSH and inhibin B did not differ between groups. By logistic regression, pretreatment AMH, but not age, FSH or inhibin B, was an independent predictor of ovarian status at 2years (P=0.005; odds ratio 0.013). We combined these data with a similar cohort (combined n=75); receiver–operator characteristic analysis for AMH gave area under curve (AUC) of 0.90 (95% confidence interval (CI) 0.82–0.97)). A cross-validated classification tree analysis resulted in a binary classification schema with sensitivity 98.2% and specificity 80.0% for correct classification of amenorrhoea. ConclusionPretreatment AMH is a useful predictor of long term post chemotherapy loss of ovarian function in women with eBC, adding significantly to the only previously established individualising predictor, i.e. age. AMH measurement may assist decision-making regarding treatment options and fertility preservation procedures.

First Birth Achieved After In Vitro Maturation of Oocytes From a Woman Endowed With Multiple Antral Follicles Unresponsive to Follicle-stimulating Hormone

The association of primary amenorrhea, gonadotropin levels at menopausal range, and normal antral follicle endowment is a rare clinical condition that suggests unresponsiveness of antral follicles to FSH. This affection is frequently misdiagnosed ovarian failure and patients are referred to egg donation to treat their infertility. Because these patients notably have an age-compatible number of antral follicles, we hypothesized that in vitro maturation (IVM) of oocytes might constitute a useful approach for treating their infertility. We report the first pregnancy and live birth obtained after IVM of oocytes in a 29-year-old patient suffering from ovarian resistance to FSH. This is a case report. The work was conducted in a university hospital. Whereas serum FSH (40.3 and 38.4 mIU/mL) and LH (35.7 and 31.7 mIU/mL) levels were repeatedly around the menopausal range, serum anti-Müllerian hormone (4.50 and 4.36 ng/mL) levels and total counting of antral follicles (23 and 18 follicles) remained normal. We aspirated antral-stage follicles and subsequently matured the oocytes in vitro. We assessed the competence of oocytes retrieved in a patient suffering from ovarian resistance to FSH. Aspiration of antral-stage follicles allowed the retrieval of 15 immature oocytes. Following IVM, 12 of them reached metaphase II. Seven embryos were obtained and three of them were transferred into the uterus. This patient became pregnant and delivered a healthy baby at term. We report the first pregnancy and live birth achieved using IVM in a woman whose ovaries were resistant to FSH. This approach was based on the remarkable normalcy of AMH and antral follicle measurements in this patient. Therefore, IVM is a viable alternative to egg donation for women suffering from resistance to FSH. Importantly, this condition should be looked for as it may lurk undetected in women wrongly diagnosed with ovarian failure.

Serum AMH in Physiology and Pathology of Male Gonads

AMH is secreted by immature Sertoli cells (SC) and is responsible for the regression of Müllerian ducts in the male fetus as part of the sexual differentiation process. AMH is also involved in testicular development and function. AMHs are at their lowest levels in the first days after birth but increase after the first week, likely reflecting active SC proliferation. AMH rises rapidly in concentration in boys during the first month, reaching a peak level at about 6 months of age, and then slowly declines during childhood, falling to low levels in puberty. Basal and FSH-stimulated levels of AMH, might become a useful predictive marker of the spermatogenic response to gonadotropic treatment in young patients with hypogonadotropic hypogonadism. After puberty, AMH is released preferentially by the apical pole of the SC towards the lumen of the seminiferous tubules, resulting in higher concentrations in the seminal plasma than in the serum. Defects in AMH production and insensitivity to AMH due to receptor defects result in the persistent Müllerian duct syndrome. A measurable value of AMH in a boy with bilateral cryptorchidism is predictive of undescended testes, while an undetectable value is highly suggestive of anorchia or ovaries, as would be the case in girls with female pseudohermaphroditism and pure gonadal dysgenesis. Lower serum AMH concentrations in otherwise healthy boys with cryptorchidism, who were compared with their age-matched counterparts with palpable testes, have been reported previously. AMH levels are higher in prepubertal patients with varicocele than in controls. This altered serum profile of AMH in boys with varicoceles may indicate an early abnormality in the regulation of the seminiferous epithelial function. Serum AMH is known to be valuable in assessing gonadal function. As compared to testing involving the administration of human chorionic gonadotropin, the measurement of AMH is more sensitive and equally specific. Measurement of AMH is very useful in young children, because serum gonadotropin concentrations in those who are agonadal are nondiagnostic in midchildhood and serum testosterone concentrations may fail to increase with provocative testing in children with abdominal testes.

Anti-Mullerian hormone levels decline under hormonal suppression: a prospective analysis in fertile women after delivery

BackgroundAMH's reported stability during periods of hormonal change makes it a practical tool in assessing ovarian reserve. However, AMH declines with age and age-specific cut-offs remain to be established in women with proven fertility. This study aims to determine age-specific ranges of AMH in women with proven fertility.MethodsTwo hundred-ten fertile women, aged 18-40 years, were prospectively recruited for AMH measurements within 14 days after delivery and age stratified into 3 groups (18-30, 31-36 and 37-40 years). Eligibility required spontaneous conception within a maximal period of six months. Autoimmune diseases, chemotherapy, radiation, ovarian surgery and polycystic ovary syndrome precluded inclusion.Results95% confidence intervals of AMH declined with advancing female age from 0.9-1.1 to 0.6-0.9 and 0.2-0.4 ng/mL (P < 0.001). AMH levels were not statistically associated with day of blood draw after delivery or pregnancy characteristics. Neither were they predictive of resumption of menses. They, however, at all ages were lower than reported in the literature for infertile patients.ConclusionsLike infertile populations, fertile women demonstrate declining AMH with advancing age. Uniformly lower levels than in infertile women suggest that AMH levels do not appear as stable under all hormonal influences as previously reported.

Extensive analysis of age-related hormonal changes shows a slowing in the pace of AMH decrease after 33 years of age, which contrasts with the expected follicle loss acceleration after mid-thirties

OBJECTIVE: Whereas undisputable evidence shows that the stockpile of ovarian follicles is progressively exhausted with advancing age, available data is conflicting on the actual rate of follicular depletion, at least in part due to heterogeneities of histological assessments. Since repeated studies have demonstrated that serum AMH measurements are a powerful reflector of not only growing but also non-growing follicles, we extensively analyzed time-dependent changes of serum AMH and other hormone levels in an effort to detect possible variations of follicle decay rate with age.

Increased gonadotrophin stimulation does not improve IVF outcomes in patients with predicted poor ovarian reserve

This retrospective study was carried out to evaluate whether increasing the starting dose of FSH stimulation above the standard dose of 150 IU/day in patients with low predicted ovarian reserve can improve IVF outcomes. A total of 122 women aged less than 36 years in their first cycle of IVF were identified as having likely low ovarian reserve based on a serum AMH measurement below 14 pmol/l. Thirty five women were administered the standard dose of 150 IU/day FSH, while the remaining 87 received a higher starting dose (200-300 IU/day FSH). There were no significant differences in age, BMI, antral follicle count, serum AMH, FSH or aetiology of infertility between the two dose groups. No significant improvement in oocyte and embryo yield or pregnancy rates was observed following an upward adjustment of FSH starting dose. While increasing the dose of FSH above 150 IU/day did not produce any adverse events such as OHSS, it did consume an extra 1,100 IU of FSH per IVF cycle. The upward FSH dose adjustment in anticipation of low ovarian reserve can not be advocated as it is both expensive and of no proven clinical value.