A critical analysis of the accuracy, reproducibility, and clinical utility of histologic endometrial dating in fertile women

Objective: To refine or redefine the traditional histologic criteria used to date the secretory phase endometrium. Design: Randomized, observational study. Setting: Academic clinical research center. Patient(s): One hundred and thirty healthy, regularly cycling, fertile volunteers, aged 18 to 35 years. Intervention(s): Patients were randomized to undergo endometrial sampling and measurement of serum estradiol and progesterone I to 14 days after the midcycle urinary luteinizing hormone surge. Three gynecologic histopathologists objectively scored each tissue specimen for 32 distinct histologic features and dated the endometrium using traditional histologic criteria. Main Outcome Measure(s): The 32 features were evaluated for [1] temporally dependent variation, [2] the amplitude of variations in score observed across the secretory phase, and [3] interobserver variability. Additionally, traditional dating criteria were analyzed. Result(s): The traditional endometrial histologic dating criteria are much less temporally distinct and discriminating than originally described, due to considerable intersubject, intrasubject, and interobserver variability. Neither traditional dating criteria nor any combination of the best performing histologic features identified by our objective and systematic analyses could reliably distinguish any specific cycle day or narrow interval of days. Conclusion(s): Histologic endometrial dating does not have the accuracy or the precision necessary to provide a valid method for the diagnosis of luteal phase deficiency or to otherwise guide the clinical management of women with reproductive failure.