Mid-luteal endometrial intracrinology following controlled ovarian hyperstimulation involving use of a gonadotrophin releasing hormone antagonist

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 beta-hydroxysteroid dehydrogenases (3 beta HSD) and selected 17 beta-HSD (17 beta HSD), 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 alpha (ER alpha), estrogen receptor beta (ER beta), androgen receptor (AR), 3 beta HSD1, 3 beta HSD2, 17 beta HSD2 and 17 beta HSD5. 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 alpha, 3 beta HSD1 and 17 beta HSD2 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.