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Hum. Reprod. Advance Access published online on August 19, 2004
Human Reproduction, doi:10.1093/humrep/deh461
© 2004 by European Society of Human Reproduction and Embryology
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Received December 9, 2003
Revised April 26, 2004
Accepted July 16, 2004

Article

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

N. Massin 1, A. Gougeon 2, G. Meduri 3, E. Thibaud 4, K. Laborde 5, C. Matuchansky 1, E. Constancis 6, M.C. Vacher-Lavenu 7, B. Paniel 8, J.R. Zorn 9, M. Misrahi 10, F. Kuttenn 11, Ph. Touraine 11*

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

* To whom correspondence should be addressed. E-mail: philippe.touraine{at}nck.ap-hop-paris.fr.


  Abstract

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.

Keywords: ovarian biopsy; ovarian follicle; ovarian histology; premature ovarian failure.
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