Polycystic ovary syndrome (PCOS) is the most common ovarian disorder associated with androgen excess in women, which justifies the growing interest of endocrinologists. Great efforts have been made in the last 2 decades to define the syndrome. The presence of three different definitions for the diagnosis of PCOS reflects the phenotypic heterogeneity of the syndrome. Major criteria are required for the diagnosis, which in turn identifies different phenotypes according to the combination of different criteria. In addition, the relevant impact of metabolic issues, specifically insulin resistance and obesity, on the pathogenesis of PCOS, and the susceptibility to develop earlier than expected glucose intolerance states, including type 2 diabetes, has supported the notion that these aspects should be considered when defining the PCOS phenotype and planning potential therapeutic strategies in an affected subject. This paper offers a critical endocrine and European perspective on the debate on the definition of PCOS and summarises all major aspects related to aetiological factors, including early life events, potentially involved in the development of the disorder. Diagnostic tools of PCOS are also discussed, with emphasis on the laboratory evaluation of androgens and other potential biomarkers of ovarian and metabolic dysfunctions. We have also paid specific attention to the role of obesity, sleep disorders and neuropsychological aspects of PCOS and on the relevant pathogenetic aspects of cardiovascular risk factors. In addition, we have discussed how to target treatment choices based according to the phenotype and individual patient's needs. Finally, we have suggested potential areas of translational and clinical research for the future with specific emphasis on hormonal and metabolic aspects of PCOS.

/pdf/the-polycystic-ovary-syndrome-a-position-statement-from-the-2dody5vdfy.pdf

The polycystic ovary syndrome: a position statement from the European Society of Endocrinology

Context Anti-mullerian hormone (AMH) is produced by granulosa cells of small, growing follicles in the ovary. Serum AMH levels strongly correlate with the number of growing follicles, and therefore AMH has received increasing attention as a marker for ovarian reserve. This review summarizes recent findings and limitations in the application of serum AMH in ovarian reserve assessment. Evidence acquisition A PubMed search was conducted to find recent literature on the measurements and use of serum AMH as a marker for ovarian reserve. Evidence synthesis Serum AMH levels are measured to assess the "functional ovarian reserve," a term that is preferred over "ovarian reserve," since AMH levels reflect the pool of growing follicles that potentially can ovulate. Serum AMH levels are used in individualized follicle-stimulating hormone dosing protocols and may predict the risk of poor response or ovarian hyperstimulation syndrome but has limited value in predicting ongoing pregnancy. Serum AMH levels are studied to predict natural or disease-related age of menopause. Studies show that the age-dependent decline rates of AMH vary among women. The generalized implementation of serum AMH measurement has also led to an increase in diagnostic assays, including automated assays. However, direct comparison of results remains problematic. Conclusion Serum AMH remains the preferred ovarian reserve marker. However, the lack of an international standard for AMH limits comparison between AMH assays. Furthermore, little is known about endogenous and exogenous factors that influence serum AMH levels, which limits proper interpretation of AMH values in a clinical setting.

/pdf/anti-mullerian-hormone-and-ovarian-reserve-update-on-4zcgnk7bad.pdf

Anti-Müllerian Hormone and Ovarian Reserve: Update on Assessing Ovarian Function

Role of vitamin D in ovarian physiology and its implication in reproduction: a systematic review.

Multi-system reproductive metabolic disorder: significance for the pathogenesis and therapy of polycystic ovary syndrome (PCOS).

In the last decades several studies suggested that vitamin D is involved in the modulation of the reproductive process in women due to the expression of VDR and 1α-hydroxylase in reproductive tissues such as ovary, uterus, placenta, pituitary and hypothalamus. Vitamin D has also a role in the regulation of sex hormone steroidogenesis. Increasing evidence suggests that vitamin D might have a regulatory role in polycystic ovary syndrome (PCOS)-associated symptoms, including ovulatory dysfunction, insulin resistance and hyperandrogenism. Vitamin D deficiency also has been reported to contribute to the pathogenesis of endometriosis due to its immunomodulatory and anti-inflammatory properties. Although most of the studies supported a role of vitamin D in the onset of these diseases, randomized controlled trials to assess the efficacy of vitamin D supplementation have never been performed. In this review we critically discuss the role of vitamin D in female fertility, starting from in vitro and in vivo studies, focusing our attention on the two most frequent causes of female infertility: PCOS and endometriosis.

Shedding new light on female fertility: The role of vitamin D

Context: Vitamin D deficiency is common among reproductive-aged women and has a role in female reproduction. Objective: This study evaluated the role of 1,25-dihydroxyvitamin D3 (vit D3) in ovarian follicular development and steroidogenesis by using a human granulosa cell (GC) model. Design, Setting, and Participants: Fifty-four women who underwent in vitro fertilization were enrolled. Intervention: Follicular fluid (FF) and mural and cumulus GCs were collected from small and large follicles. In separate experiments, primary cumulus GCs were cultured with or without vit D3 followed by RT-PCR for mRNA expression levels. The effect of recombinant anti-Mullerian hormone (AMH) on nuclear localization of phospho-Smad 1/5/8 was evaluated in the presence or absence of vit D3 by using immunofluorescence. 25-Hydroxyvitamin D levels in FF as well as cell culture media AMH, progesterone, and estradiol (E2) concentrations were determined by ELISA and RIA. Main Outcome Measures: The following were measured: 1) mRNA ex...

/pdf/vitamin-d-alters-genes-involved-in-follicular-development-2w5ipenub8.pdf

Vitamin D alters genes involved in follicular development and steroidogenesis in human cumulus granulosa cells.

Context: The interaction of advanced glycation end-products (AGEs) with their cellular receptor (RAGE) is implicated in the pathogenesis of abnormal ovarian follicular growth RAGE has a circulating secretory receptor form, soluble RAGE (sRAGE), which neutralizes the action of AGEs and might exert a protective role on the follicular environment Objective: The objective of the study was to investigate whether serum or follicular fluid (FF) sRAGE levels are associated with markers of ovarian reserve Design, Setting, and Participants: Serum anti-Mullerian hormone (AMH) and sRAGE protein levels were correlated in 31 reproductive-aged women An additional 33 women who underwent oocyte retrieval for in vitro fertilization were enrolled AMH and its receptor (AMHR-II) mRNA levels were quantified in cumulus granulosa cells and FF sRAGE and AMH protein levels were measured Main Outcome Measures: Granulosa cell AMH and AMHR-II gene expression, serum and FF AMH and sRAGE protein concentration, and number of oocyt

/pdf/follicular-fluid-soluble-receptor-for-advanced-glycation-end-19gxrhs7n7.pdf

Follicular fluid soluble receptor for advanced glycation end-products (sRAGE): a potential indicator of ovarian reserve.

Diagnostic testing for and detection of physical abuse in infants with brief resolved unexplained events.

/pdf/circle-time-health-curriculum-designed-for-pre-schoolers-z7mbw375jt.pdf

Circle Time Health Curriculum Designed for Pre-Schoolers

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Vitamin D alters genes involved in follicular development and steroidogenesis in human cumulus granulosa cells.

Follicular fluid soluble receptor for advanced glycation end-products (sRAGE): a potential indicator of ovarian reserve.

Diagnostic testing for and detection of physical abuse in infants with brief resolved unexplained events.

Circle Time Health Curriculum Designed for Pre-Schoolers