Comparison of transdermal versus oral estradiol on endometrial receptivity

Objective: To compare the effects of oral micronized E₂ with transdermal E₂ on endometrial receptivity in women undergoing oocyte donation. Design: Prospective, randomized, crossover trial, Serum E₂ and P concentrations were measured on cycle days 14 and 22 (luteal day +8). Endometrial biopsies were obtained on day 22 and read in a blinded fashion for histology and β-3- integrin expression. Setting: University-based donor oocyte program. Patients: Twenty-seven patients presenting for donor oocytes. Main Outcome Measures: Endometrial histology and β-3-integrin expression. Results: The endometrial glandular histology in women given oral micronized E₂ was delayed by a mean of 1.6 days in comparison to that of women given transdermal E₂. Seventy percent of women given oral E₂ displayed a lag ≥4 days whereas 29.6% given transdermal E₂ displayed a similar lag. Serum E₂ levels were 1,194 ± 108.8 pg/mL (mean ± SEM; conversion factor to SI unit, 3.671) in women on oral micronized E₂ and 117.4 ± 14.0 pg/mL in those on transdermal E₂. Conclusion: The supraphysiologic serum E₂ levels associated with oral micronized E₂ may have a deleterious impact on endometrial receptivity. The development of more physiologic hormone replacement protocols may enhance endometrial receptivity and lead to improved clinical pregnancy rates.