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Submitted on April 26, 2005
Accepted on July 8, 2005
Institute of Reproductive and Developmental Biology, Wolfson and Weston Research Centre for Family Health, Imperial College London, Hammersmith Hospital, London, W12 0NN, UK; Department of Mathematics, Imperial College London, London SW7 2AZ UK; Histopathology Department, Division of Investigative Sciences, Imperial College London, St. Mary's Hospital, London W2 1PG; Department of Internal Medicine, Erasmus MC, 3015 GD, Rotterdam, The Netherlands; School of Biological and Molecular Sciences, Oxford Brookes University, Headington Oxford, UK
* To whom correspondence should be addressed. E-mail: k.hardy{at}imperial.ac.uk.
Context: Polycystic ovary syndrome (PCOS), the commonest cause of anovulatory infertility, is characterized by disordered folliculogenesis, notably increased progression from the primordial to the primary stages. This ovarian phenotype is similar to that observed in mice lacking anti-Müllerian hormone (AMH).
Objective: To investigate whether AMH is involved in accelerating the transition of follicles from primordial to primary stages in polycystic ovaries.
Design: Comparison of AMH expression in archive tissue from normal and polycystic ovaries.
Setting: Laboratory-based study.
Patients: 7 normo-ovulatory women and 16 women with polycystic ovaries (5 of whom were anovulatory), classified by ovarian histology and with reference to menstrual cycle history and ultrasound.
Main outcome measure: Presence and intensity of AMH expression in 1403 follicles.
Results: AMH was observed from the primordial stage onwards. AMH immunostaining was observed in significantly fewer primordial (P = 0.007) and transitional follicles (P = 0.001) in ovaries from anovulatory women with PCO compared with women with regular cycles and either normal or polycystic ovaries. AMH-negative follicles had fewer pre-granulosa cells in the largest cross-section of the follicle at both the primordial (median 4 and 6 for AMH-negative and positive follicles respectively, p = <0.0001) and transitional stages (median 6 and 9, p = <0.0007) in normal tissue, and fewer at the transitional stage (median 7 and 11, p = <0.0001) in tissue from anovulatory women with polycystic ovaries. This suggests that AMH expression is associated with granulosa cell mitosis.
Conclusions: These findings indicate a relative deficiency of AMH in primordial and transitional follicles in ovaries from anovulatory women with polycystic ovaries. This may contribute to disordered early follicle development in PCOS.
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