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      Extra- and intra-ovarian factors in polycystic ovary syndrome: impact on oocyte maturation and embryo developmental competence

      review-article
      1 , * , 2 , *
      Human Reproduction Update
      Oxford University Press
      polycystic ovary syndrome, oocyte, fertilization, embryo, IVF

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          Abstract

          BACKGROUND

          Polycystic ovary syndrome (PCOS) is a common metabolic dysfunction and heterogeneous endocrine disorder in women of reproductive age. Although patients with PCOS are typically characterized by increased numbers of oocytes retrieved during IVF, they are often of poor quality, leading to lower fertilization, cleavage and implantation rates, and a higher miscarriage rate.

          METHODS

          For this review, we searched the database MEDLINE (1950 to January 2010) and Google for all full texts and/or abstract articles published in English with content related to oocyte maturation and embryo developmental competence.

          RESULTS

          The search showed that alteration of many factors may directly or indirectly impair the competence of maturating oocytes through endocrine and local paracrine/autocrine actions, resulting in a lower pregnancy rate in patients with PCOS. The extra-ovarian factors identified included gonadotrophins, hyperandrogenemia and hyperinsulinemia, although intra-ovarian factors included members of the epidermal, fibroblast, insulin-like and neurotrophin families of growth factors, as well as the cytokines.

          CONCLUSIONS

          Any abnormality in the extra- and/or intra-ovarian factors may negatively affect the granulosa cell–oocyte interaction, oocyte maturation and potential embryonic developmental competence, contributing to unsuccessful outcomes for patients with PCOS who are undergoing assisted reproduction.

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          Most cited references294

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          Anti-Müllerian hormone expression pattern in the human ovary: potential implications for initial and cyclic follicle recruitment.

          Anti-Müllerian hormone (AMH) is a member of the transforming growth factor-beta superfamily, which plays an important role in both ovarian primordial follicle recruitment and dominant follicle selection in mice. However, the role of AMH in folliculogenesis in humans has not been investigated in detail. In the present study, AMH expression was assessed using immunohistochemistry in ovarian sections, obtained from healthy regularly cycling women. To this end, a novel monoclonal antibody to human AMH was developed. AMH expression was not observed in primordial follicles, whereas 74% of the primary follicles showed at least a weak signal in the granulosa cells. The highest level of AMH expression was present in the granulosa cells of secondary, preantral and small antral follicles
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            Oocyte-secreted factors: regulators of cumulus cell function and oocyte quality.

            Oocyte quality is a key limiting factor in female fertility, yet we have a poor understanding of what constitutes oocyte quality or the mechanisms governing it. The ovarian follicular microenvironment and maternal signals, mediated primarily through granulosa cells (GCs) and cumulus cells (CCs), are responsible for nurturing oocyte growth, development and the gradual acquisition of oocyte developmental competence. However, oocyte-GC/CC communication is bidirectional with the oocyte secreting potent growth factors that act locally to direct the differentiation and function of CCs. Two important oocyte-secreted factors (OSFs) are growth-differentiation factor 9 and bone morphogenetic protein 15, which activate signaling pathways in CCs to regulate key genes and cellular processes required for CC differentiation and for CCs to maintain their distinctive phenotype. Hence, oocytes appear to tightly control their neighboring somatic cells, directing them to perform functions required for appropriate development of the oocyte. This oocyte-CC regulatory loop and the capacity of oocytes to regulate their own microenvironment by OSFs may constitute important components of oocyte quality. In support of this notion, it has recently been demonstrated that supplementing oocyte in vitro maturation (IVM) media with exogenous OSFs improves oocyte developmental potential, as evidenced by enhanced pre- and post-implantation embryo development. This new perspective on oocyte-CC interactions is improving our knowledge of the processes regulating oocyte quality, which is likely to have a number of applications, including improving the efficiency of clinical IVM and thereby providing new options for the treatment of infertility.
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              Follicle dynamics and anovulation in polycystic ovary syndrome.

              Polycystic ovary syndrome (PCOS) is the commonest cause of anovulatory infertility and menstrual cycle abnormalities, but the factors responsible for failure to select a dominant follicle remain unclear. Source is authors' own studies and search of the relevant literature. Arrest of antral follicle growth is associated with an abnormal endocrine environment involving hypersecretion of luteinizing hormone and insulin (and perhaps hyperandrogenism). The net effect is secondary suppression of FSH, which leads to inhibition of maturation of otherwise healthy follicles in the cohort. There is, however, emerging evidence for an intrinsic abnormality of folliculogenesis in PCOS that affects the very earliest, gonadotrophin independent, stages of follicle development. There is an increased density of small pre-antral follicles and an increased proportion of early growing follicles. These abnormalities in anovulatory PCOS are further defined by abnormal granulosa cell proliferation and disparate growth of oocyte and surrounding granulosa cells. This suggests that the normal 'dialogue' between oocyte and granulosa cells in these early growing follicles is altered. There is evidence that abnormal, local (follicle-to-follicle) signalling of anti-Müllerian hormone may play a part in disordered folliculogenesis, but it is plausible that other local regulators that have been implicated in normal and abnormal pre-antral follicle development-such as insulin-like growth factors and sex steroids-have a role in aberrant folliculogenesis in PCOS. Significant abnormalities in the very earliest stages of folliculogenesis may be the root cause of anovulation in PCOS.
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                Author and article information

                Journal
                Hum Reprod Update
                humupd
                humupd
                Human Reproduction Update
                Oxford University Press
                1355-4786
                1460-2369
                Jan-Feb 2011
                16 July 2010
                16 July 2010
                : 17
                : 1
                : 17-33
                Affiliations
                [1 ]Department of Obstetrics and Gynecology, simplePeking University Third Hospital , Beijing 100083, People's Republic of China
                [2 ]Department of Obstetrics and Gynecology, simpleNorth Shore University Hospital , NYU School of Medicine, Manhasset, NY 11030, USA
                Author notes
                *Correspondence address. Fax: +1-516-562-1754; E-mail: hfeng@ 123456nshs.edu (H.L.F.)/Fax: +1-86-10-62013283; E-mail: jie.qiao@ 123456263.net (J.Q.)
                [†]

                Two equal first authors.

                Article
                dmq032
                10.1093/humupd/dmq032
                3001338
                20639519
                0cbf94fa-1f79-499b-bc2f-82ad97e9dabd
                © The Author 2010. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. For Permissions, please email: journals.permissions@oxfordjournals.org

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/2.5) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited

                History
                : 18 February 2010
                : 10 June 2010
                : 18 June 2010
                Categories
                Reviews

                Human biology
                embryo,oocyte,ivf,polycystic ovary syndrome,fertilization
                Human biology
                embryo, oocyte, ivf, polycystic ovary syndrome, fertilization

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