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Anti-Müllerian Hormone Protein Expression Is Reduced during the Initial Stages of Follicle Development in Human Polycystic Ovaries

Institute of Reproductive and Developmental Biology (S.A.S., K.H., P.D.S.-B., L.J.W., S.F.), Wolfson and Weston Research Centre for Family Health, Imperial College London, Hammersmith Hospital, London W12 0NN, United Kingdom; Department of Mathematics (J.S.), Imperial College London, London SW7 2AZ, United Kingdom; Histopathology Department (A.M.F.), Division of Investigative Sciences, Imperial College London, St. Mary’s Hospital, London W2 1PG, United Kingdom; Department of Internal Medicine (A.P.N.T., J.A.V.), Erasmus Medical Center, 3015 GD Rotterdam, The Netherlands; and School of Biological and Molecular Sciences (N.P.G.), Oxford Brookes University, Headington Campus, Oxford OX3 0BP, United Kingdom

Address all correspondence and requests for reprints to: Kate Hardy, Institute of Reproductive and Developmental Biology, Wolfson and Weston Research Centre for Family Health, Imperial College London, Hammersmith Hospital, London W12 0NN, United Kingdom. E-mail: k.hardy{at}imperial.ac.uk.

Context: Polycystic ovary syndrome, the most common 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: The objective of this study is to investigate whether AMH is involved in accelerating the transition of follicles from primordial to primary stages in polycystic ovaries.

Design: This study compares AMH expression in archive tissue from normal and polycystic ovaries.

Setting: This is a laboratory-based study.

Patients: Ovarian tissue from seven normoovulatory women and 16 women with polycystic ovaries (five of whom were anovulatory) was used in this study. Ovaries were classified by histology and with reference to menstrual cycle history and ultrasound.

Main Outcome Measure: Presence and intensity of AMH expression in 1403 follicles was the main outcome measure.

Results: AMH was observed from the primordial stage onward. AMH immunostaining was observed in significantly fewer primordial (P = 0.007) and transitional follicles (P = 0.001) in ovaries from anovulatory women with polycystic ovaries compared with women with regular cycles and either normal or polycystic ovaries. AMH-negative follicles had fewer pregranulosa cells in the largest cross-section of the follicle at both the primordial (median, four and six for AMH-negative and -positive follicles, respectively; P < 0.0001) and transitional stages (median six and nine; P < 0.0007) in normal tissue, and fewer at the transitional stage (median, seven 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 polycystic ovary syndrome.

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