The influence of supraphysiologic estradiol levels on human nidation

OBJECTIVE: Exogenous estradiol (E2) has a well-recognized interceptive action when administered shortly after ovulation. The influence of extremely elevated levels of endogenous E2 on human oocyte fertilization and implantation are unclear. The purpose of this study was to evaluate a potential antinidatory role of extremely high endogenous E2 concentrations on implantation and pregnancy during in vitro fertilization-embryo transfer (IVF-ET). METHODS: Twenty-five patients receiving human menopausal gonadotropins (hMG) following midluteal GnRHa administration for IVF-ET, in which the maximal E2 concentration was > 5000 pg/ml (range 5358-16,344 pg/ml) were studied. Cycle parameters including oocyte and embryo characteristics, fertilization, cleavage, and implantation rates as well as pregnancy outcomes were compared to those of 25 patients treated contemporaneously whose treatment cycles had peak E2 values < 3500 pg/ml. Patients groups were matched for age, infertility diagnoses, duration of infertility and stimulation protocol. RESULTS: Cycles characterized by very high endogenous E2 levels resulted in significantly more oocytes per retrieval (21.4 +/- 1.7 versus 8.4 +/- 0.6; P < 0.0001), fewer postmature oocytes (1.6% +/- 1.0% versus 14% +/- 5.0%; P < 0.03), and a decreased fertilization rate (63% +/- 4.0% versus 73% +/- 3.0%; P < 0.04) compared to control cycles. There were no differences in the overall mean morphologic grade or cleavage rates between groups. However, high E2 cycles were associated with a significantly increased implantation rate (14% +/- 4.0% versus 8.0% +/- 4.0%; P < 0.01) and pregnancy rate per embryo transfer (62% +/- 16% versus 36% +/- 16%; P < 0.01) compared to controls. The incidence of spontaneous abortion did not differ between groups. CONCLUSIONS; Extremely high endogenous E2 levels do not appear to adversely affect implantation or overall cycle pregnancy rates in IVF-ET cycles. However, impaired fertilization rates in such cycles support a potential adverse effect on oocyte quality.