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Hum. Reprod. Advance Access originally published online on August 19, 2004
Human Reproduction 2004 19(11):2555-2560; doi:10.1093/humrep/deh461
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Human Reproduction vol. 19 no. 11 © European Society of Human Reproduction and Embryology 2004; all rights reserved

Significance of ovarian histology in the management of patients presenting a premature ovarian failure

N. Massin1, A. Gougeon5, G. Meduri6, E. Thibaud2, K. Laborde3, C. Matuchansky1, E. Constancis8, M.C. Vacher-Lavenu10, B. Paniel9, J.R. Zorn11, M. Misrahi7, F. Kuttenn1,4 and Ph. Touraine1,4,12

1 Department of Endocrinology and Reproductive Medicine, 2 Department of Endocrinology, Gynecology and Pediatrics, 3 Department of Physiology Necker Hospital, 75015 Paris, 4 INSERM U584, Faculté Médecine Necker, 75015 Paris, 5 INSERM U407, 69921 Oullins, 6 Department of Hormonal Biochemistry, 7 INSERM E120, Bicêtre Hospital, 94275 Le Kremlin-Bicêtre, 8 Department of Pathology, 9 Department of Gynecology and Obstetrics, Centre Hospitalier Intercommunal de Créteil, 94000, Créteil, 10 Department of Pathology, 11 Department of Obstetrics, Cochin Hospital, 75014 Paris, France

12 To whom correspondence should be addressed: Department of Endocrinology and Reproductive Medicine, Necker Hospital, 149, rue de Sèvres, 75743 Paris Cedex 15, France. Email: philippe.touraine{at}nck.ap-hop-paris.fr

BACKGROUND: Premature ovarian failure (POF) is a heterogeneous syndrome, possibly due to mutations of genes involved in the normal development of the ovary and/or follicles. Based essentially on animal models, these mutations are associated with various ovarian phenotypes, from a complete absence of follicles to a partial follicular maturation. The aim of the present study was to determine whether ovarian histology, compared to pelvic ultrasonography, would be helpful in identifying which patients display an impaired follicular reserve and/or growth, and in orientating the search for POF aetiology. METHODS AND RESULTS: We studied a cohort of 61 patients suffering from POF with a normal karyotype. Their median age (range) at diagnosis was 26 years (15–39). The FSH plasma level was high, 67.0 IU/l (13–155). Estradiol and inhibin B plasma levels were low: 18.5 pmol/l (18.5–555) and 5 pg/ml (5–105) respectively. Both pelvic ultrasonography and ovarian biopsies were performed in each patient. The presence of follicles suggested at ultrasonography was confirmed at histology in 56% of the patients. Ovarian histology led to the distinction of two phenotypes: (i) small-sized ovaries, deprived of follicles; and (ii) normal-sized ovaries with partial follicular maturation. To confirm the value of ovarian biopsies, samples from 20 normal women were studied. These demonstrated that ovarian biopsy at random enables reliable assessment of follicular presence, especially when their size is <2 mm. CONCLUSION: Ovarian histology appears to be a reliable tool in evaluating the follicular reserve, and helpful and complementary to clinical and hormonal phenotyping in orienting the search for the various genetic causes of POF syndrome.

Key words: ovarian biopsy/ovarian follicle/ovarian histology/premature ovarian failure


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