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Hum. Reprod. Advance Access published online on September 29, 2008
Human Reproduction, doi:10.1093/humrep/den358
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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

Ovarian epithelial dysplasia after ovulation induction: time and dose effects

G. Chene1,6, F. Penault-Llorca2, G. Le Bouëdec1, F. Mishellany2, M.M. Dauplat3, P. Jaffeux4, B. Aublet-Cuvelier4, J.L. Pouly5, P. Dechelotte3 and J. Dauplat1

1 Department of Oncology and Surgery, Centre Jean Perrin, Clermont-Ferrand, France 2 Department of Histopathology, Centre Jean Perrin, Clermont-Ferrand, France 3 Department of Histopathology, CHU of Clermont-Ferrand, Clermont-Ferrand, France 4 Department of Medical Information, CHU of Clermont-Ferrand, Clermont-Ferrand, France 5 Department of Obstetric, Gynecology and Reproductive Medicine, CHU of Clermont-Ferrand, Clermont-Ferrand, France

6 Correspondence address. Tel: +33-6-07-08-17-86; E-mail: chenegautier{at}yahoo.fr

BACKGROUND: Ovarian epithelial dysplasia was first described after prophylactic oophorectomies for genetic risk. Ovarian stimulation has been considered as a risk factor of ovarian cancer by Fathalla's incessant ovulation theory. In this study, we have investigated the risk of ovarian dysplasia after ovulation induction.

METHODS: We reviewed 99 oophorectomies or cystectomies between 1990 and 2005 divided them into two groups: previous in vitro fertilization (n = 37) and a panel of fertile controls (n = 62). Eleven epithelial cytological and architectural features were defined and an ovarian epithelial dysplasia score was calculated to quantify the degree of ovarian epithelial abnormalities.

RESULTS: All the ovaries were macroscopically non-cancerous except in two patients (one endometrioid cancer and one borderline tumour). The mean ovarian dysplasia score was significantly higher in the ovulation induction group than in the control group (7.64 versus 3.62, P = 0.0002). We also found a relationship between the number of ovulation-inducted cycles and the severity of ovarian dysplasia (‘dose-effect’) and a relationship between time after the end of ovulation induction (over 7 years) and the severity of ovarian dysplasia (‘time-effect’).

CONCLUSIONS: There is probably a relationship between ovarian epithelial dysplasia and either ovulation inducing drugs or infertility. By Fathalla’s incessant ovulation theory, ‘the dose effect and the time effect’ of ovarian stimulation may explain ovarian dysplasia formation.

Key words: female infertility/assisted reproduction/ovarian dysplasia/ovarian stimulation

Submitted on February 14, 2008; resubmitted on September 1, 2008; accepted on September 10, 2008.


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