Evidence for an adverse effect of elevated serum estradiol concentrations on embryo implantation

Multiple follicular stimulation for IVF may be associated with greatly elevated serum E2 concentrations that are presumed to be antinidatory. This factor was analyzed in 825 consecutive embryo transfer cycles. The pregnancy rate decreased significantly after the transfer of one and two embryos in association with preovulatory E2 levels greater than the 90th percentile for the group (2320 pg/ml). The pregnancy rate did not vary with preovulatory E2 concentration following the transfer of three embryos. Highly significant correlations were noted between preovulatory E2 and early luteal phase concentrations of E2 and P. In a subgroup of 245 cycles, there were no significant relationships between implantation and early luteal phase levels of P or the ratio of E2/P. There was a small but nonsignificant tendency for the pregnancy rate to decrease in association with raised luteal E2. It is concluded that excessive E2 levels at the time of ovulation induction with hCG had an adverse effect on implantation when one or two embryos are transferred, but this may be overcome by the transfer of three embryos. The consequences for embryo transfer are discussed.