Hum. Reprod. Advance Access published online on September 11, 2007
Human Reproduction, doi:10.1093/humrep/dem269
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Mid-luteal endometrial intracrinology following controlled ovarian hyperstimulation involving use of a gonadotrophin releasing hormone antagonist
1 Reproductive and Developmental Sciences, Centre for Reproductive Biology, University of Edinburgh, Edinburgh EH16 4TJ, UK 2 Department of Pathology, University of Edinburgh, Royal Infirmary of Edinburgh, Edinburgh EH16 4SA 3 Edinburgh Assisted Conception Programme, Royal Infirmary of Edinburgh, Edinburgh EH16 4SA
4 Correspondence address. Tel: +44 (0) 131 242 6858; Fax: +44 (0) 131 242 6441; E-mail: hilary.critchley{at}ed.ac.uk
BACKGROUND: There are concerns of reduced pregnancy rates with the use of gonadotrophin-releasing hormone antagonists (GnRH antagonists) in IVF/ICSI cycles. Sex steroids and their metabolizing enzymes in the endometrium may play a vital role in embryo implantation. This study has evaluated the levels and localization of sex-steroid receptors and metabolizing enzymes, 3
-hydroxysteroid dehydrogenases (3HSD) and selected 17-HSD (17HSD), in mid-luteal endometrium of women treated with GnRH antagonist (Cetrorelix) and recombinant FSH (rFSH; Gonal-F) with luteal phase progesterone supplementation.
METHODS: Mid-luteal phase endometrial biopsies were obtained from oocyte donors undergoing ovarian stimulation and from control women with regular periods. Immunohistochemistry and real-time quantitative–polymerase chain reaction (QRT–PCR) were used to compare protein and mRNA expression of progesterone receptor (PR), estrogen receptor 
(ER), estrogen receptor (ER), androgen receptor (AR), 3HSD1, 3HSD2, 17HSD2 and 17HSD5.
RESULTS: Cetrorelix–rFSH treatment caused a mid-luteal suppression of PR protein expression in the endometrial stroma, surface epithelium and glands, although expression in the glands of control samples was variable. In contrast, the treatment caused an increase in PR staining in perivascular cells. No other significant differences in protein expression were observed between the two groups. mRNA levels of AR, ER, 3HSD1 and 17HSD2 were significantly reduced in the treatment group. PR mRNA levels were also reduced by GnRH antagonist–rFSH treatment, but the difference was not significant.
CONCLUSIONS: Changes in the expression of sex-steroid receptors and metabolizing enzymes may lead to alterations in the activity and intracellular availability of estrogens, progestogens and androgens in endometrium of women treated with Cetrorelix and rFSH. Their impact on embryo implantation merits further evaluation.
Key words: endometrium/GnRH antagonists/recombinant FSH/sex-steroid receptors/steroid metabolizing enzymes
Submitted on February 22, 2007; resubmitted on May 23, 2007; accepted on July 11, 2007.
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