Serum anti-müllerian hormone (AMH) concentration during pregnancy: a longitudinal study.

A prospective longitudinal cohort study aimed to longitudinally examine the kinetics of Anti-müllerian hormone (AMH) during the first two trimesters of pregnancy. Pregnant women with stored 1st trimester serum samples were recruited at 24-28 weeks gestation during their gestational diabetes testing, where they provided an additional serum sample. The samples were analysed for AMH, oestradiol and progesterone concentrations. A decrease in serum AMH was observed in 40 out of 45 (88.9%) (95% CI 75.9% to 96.3%) of the participants in this study. The median serum AMH concentration was 10.9 pmol/L in the 1st trimester and 6.5 pmol/L during the 2nd trimester, with a significantly different distribution of the values between the 1st and the 2nd trimester AMH samples (p<0.001). The median percentage of AMH difference of -39.8%. This study demonstrated a significant decrease in serum AMH levels from the 1st to the 2nd trimester of pregnancy. The absolute decrease in AMH levels seems to be positively associated with 1st trimester AMH levels, whereas the percentage of AMH difference is not. Further studies are required to elucidate the potential physiological mechanisms of this finding.

Translational Physiology of Anti-Müllerian Hormone: Clinical Applications in Female Fertility Preservation and Cancer Treatment.

Background: Whilst the ability of AMH to induce the regression of the Müllerian ducts in the male fetus is well appreciated, AMH has additional biological actions in relation to steroid biosynthesis and ovarian follicle dynamics. An understanding of the physiology of AMH illuminates the potential therapeutic utility of AMH to protect the ovarian reserve during chemotherapy and in the treatment of female malignancies. The translation of the biological actions of AMH into clinical applications is an emerging focus of research, with promising preliminary results. Objective and Rationale: Studies indicate AMH restrains primordial follicle development, thus administration of AMH during chemotherapy may protect the ovarian reserve by preventing the mass activation of primordial follicles. As AMH induces regression of tissues expressing the AMH receptor (AMHRII), administration of AMH may inhibit growth of malignancies expressing AMHR II. This review evaluates the biological actions of AMH in females and appraises human clinical applications. Search Methods: A comprehensive search of the Medline and EMBASE databases seeking articles related to the physiological functions and therapeutic applications of AMH was conducted in July 2021. The search was limited to studies published in English. Outcomes: AMH regulates primordial follicle recruitment and moderates sex steroid production through the inhibition of transcription of enzymes in the steroid biosynthetic pathway, primarily aromatase and 17α-hydroxylase/17,20-lyase. Preliminary data indicates that administration of AMH to mice during chemotherapy conveys a degree of protection to the ovarian reserve. Administration of AMH at the time of ovarian tissue grafting has the potential to restrain uncontrolled primordial follicle growth during revascularization. Numerous studies demonstrate AMH induced regression of AMHR II expressing malignancies. As this action occurs via a different mechanism to traditional chemotherapeutic agents, AMH has the capacity to inhibit proliferation of chemo-resistant ovarian cancer cells and cancer stem cells. Wider Implications: To date, AMH has not been administered to humans. Data identified in this review suggests administration of AMH would be safe and well tolerated. Administration of AMH during chemotherapy may provide a synchronistic benefit to women with an AMHR II expressing malignancy, protecting the ovarian reserve whilst the cancer is treated by dual mechanisms.

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.

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.