Challenges in Measuring AMH in the Clinical Setting.

Serum anti-Mullerian hormone (AMH) is a widely used marker of functional ovarian reserve in the assessment and treatment of infertility. It is used to determine dosing of gonadotropins used for superovulation prior to in vitro fertilization, as well as to determine the degree of damage to ovarian reserve by cytotoxic treatments such as chemotherapy. AMH is also now used to predict proximity to menopause and potentially provides a sensitive and specific test for polycystic ovarian syndrome. Twenty one different AMH immunoassay platforms/methods are now commercially available. Of those compared, the random-access platforms are the most reliable. However, to date there has not been an agreed common international AMH reference preparation to standardize calibration between the various immunoassays. Recently, a purified human AMH preparation (code 16/190) has been investigated by the World Health Organization as a potential international reference preparation. However, this was only partially successful as commutability between it and serum samples was observed only in some but not all immunoassay methods. Development of a second generation reference preparation with wider commutability is proposed.

Interrelationships among reproductive hormones and antral follicle count in human menstrual cycles.

It is recognised that ovarian factors, including steroid and protein hormones, are critical in the feedback regulation of pituitary gonadotropins; however, their individual contributions are less defined. The aim of this study was to explore the reciprocal relationships between ovarian and pituitary hormones across the normal ovulatory menstrual cycle as women age. FSH, LH, oestradiol, progesterone, inhibin A, inhibin B and anti-mullerian hormone (AMH) were measured in serum collected every 1-3 days across one interovulatory interval (IOI) from 26 healthy women aged 18-50 years. The antral follicle count (AFC) for follicles 2-5 mm, >6 mm and 2-10 mm were tabulated across the IOI. Independent associations between ovarian hormones/AFC vs pituitary follicle-stimulating hormone (FSH) and luteinising hormone (LH) were investigated using multivariate regression analysis. The data were sub-grouped based on the presence or absence luteal phase-dominant follicles (LPDF). Serum oestradiol and AMH were inversely correlated with FSH in both follicular and luteal phases. Inhibin B correlated inversely with FSH and LH in the late follicular phase and directly in the luteal phase. AFC, inhibin A and progesterone were not key predictors of either FSH or LH. The strong association between AMH and FSH with age implies that AMH, as well as oestradiol and inhibin B are important regulators of FSH. The change in feedback response of inhibin B with both FSH and LH across the cycle suggests two phases of the negative feedback.

Random start or emergency IVF/in vitro maturation: a new rapid approach to fertility preservation.

There is a need to develop rapid protocols for ovarian stimulation for women who wish to preserve their fertility following diagnosis of cancer. Conventional gonadotropin stimulation protocols are lengthy and are delayed until the start of the next menstrual period, potentially compromising cancer treatments. The development of random start IVF/in vitro maturation has made significant strides for enabling couples undergoing cancer therapy to achieve a family. However, several unanswered questions still remain. What do we know about the endocrinology of stimulating ovarian follicular activity outside the established protocols of stimulation during the follicular phase? This article explores what is known about antral follicle development during the menstrual cycle, novel ovarian stimulation proposals for optimizing assisted reproductive therapies in women, and direction.

Associations Between Antral Ovarian Follicle Dynamics and Hormone Production Throughout the Menstrual Cycle as Women Age.

BACKGROUND: The physiological origins of age-related changes in hormone production during the menstrual cycle are uncertain. OBJECTIVE: The objective of the study was to test the hypothesis that changes in antral follicle dynamics are associated with changes in hormone production as women age. METHODS: A prospective, observational study was conducted in ovulatory women of midreproductive age (MRA; 18-35 y; n = 10) and advanced reproductive age (ARA; 45-55 y; n = 20). The numbers and diameters of all follicles of 2 mm or greater were quantified ultrasonographically every 1-3 days for one interovulatory interval; the growth profiles of individually identified follicles of 4 mm or greater were tabulated. Blood samples were assayed for FSH, LH, estradiol, progesterone, inhibin A and B, and anti-Mullerian hormone. RESULTS: Fifty percent of women in both the MRA and ARA groups developed one to two luteal-phase dominant follicles (LPDFs). MRA women with typical LPDFs had greater luteal-phase inhibin B (44.2 vs 17.0 ng/L) and estradiol (91.3 vs 51.7 ng/L) compared with those without LPDFs (P < .05). Luteal-phase estradiol was greater (184 vs 79 ng/L), inhibin B was greater (25.3 vs 12.7 ng/L), and progesterone was lower (6.98 vs 13.8 µg/L) in ARA women with atypical vs no LPDFs (P < .01). CONCLUSION: Changes in antral follicle dynamics are associated with changes in hormone production as women age. The development of LPDFs in women of MRA was associated with elevated luteal-phase estradiol. A similar but exaggerated elevation in late luteal-early follicular-phase estradiol, accompanied by lower progesterone, was observed in ARA women with atypically large and persistent LPDFs.