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Human Reproduction Update Advance Access published online on May 22, 2008

Human Reproduction Update, doi:10.1093/humupd/dmn015
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© The Author 2008. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Follicle dynamics and anovulation in polycystic ovary syndrome

Stephen Franks1,3, Jaroslav Stark2 and Kate Hardy1

1 Institute of Reproductive and Developmental Biology, Imperial College London, Hammersmith Hospital, London W12 0NN, UK 2 Department of Mathematics, Imperial College London, London SW7 2AZ, UK

To whom correspondence should be addressed at: 3 Correspondence address. E-mail: s.franks{at}imperial.ac.uk

BACKGROUND: 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.

METHOD: Source is authors' own studies and search of the relevant literature.

RESULTS: 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.

CONCLUSIONS: Significant abnormalities in the very earliest stages of folliculogenesis may be the root cause of anovulation in PCOS.

Key words: mathematical modelling / statistics / assisted reproduction

Received on December 22, 2007; revised April 7, 2008; accepted on April 21, 2008


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