A critical analysis of the accuracy, reproducibility, and clinical utility of histologic endometrial dating in fertile women  Michael J. Murray, M.D., William R. Meyer, M.D., Richard J. Zaino, M.D., Bruce A. Lessey, M.D., Ph.D., Debra B. Novotny, M.D., Karen Ireland, M.D., Donglin Zeng, Ph.D., Marc A. Fritz, M.D.  Fertility and Sterility  Volume 81, Issue 5, Pages 1333-1343 (May 2004) DOI: 10.1016/j.fertnstert.2003.11.030

FIGURE 1 Comparison of the fitted polynomial curves generated from scoring data with the traditional curves drawn by Noyes et al. (1). The curves on the left represent the predicted mean and 95% confidence intervals calculated from the scores assigned by three pathologists masked to the luteal day. The curves on the right are copied from the original drawings in the Noyes study. Murray. Endometrial dating revisited. Fertil Steril 2004. Fertility and Sterility 2004 81, 1333-1343DOI: (10.1016/j.fertnstert.2003.11.030)

FIGURE 2 Endometrial specimens obtained from two different proven fertile women on luteal day 8. (A) In one tissue specimen, subnuclear vacuoles (arrow) are abundant; (B) in the other specimen, subnuclear vacuoles are altogether absent. If judged according to traditional histologic criteria (1), maturation is abnormally delayed in specimen A and normal in specimen B. Murray. Endometrial dating revisited. Fertil Steril 2004. Fertility and Sterility 2004 81, 1333-1343DOI: (10.1016/j.fertnstert.2003.11.030)

FIGURE 3 Interobserver and between subject variation in histologic dating using the traditional criteria of Noyes et al. (1). The three plots illustrate the extent of interobserver variability. Individual points (•, ■, and ▴) represent the mean histologic dates (postovulatory day) assigned by the three different pathologists for all tissue specimens obtained on the same luteal day. Between-subject variation is represented by the shaded area and corresponds to the standard deviation around the mean assigned histologic date among the three pathologists. The mean assigned date was calculated from the individual results for all specimens obtained on each luteal day, thereby eliminating interobserver variation from calculation of the standard deviation. Murray. Endometrial dating revisited. Fertil Steril 2004. Fertility and Sterility 2004 81, 1333-1343DOI: (10.1016/j.fertnstert.2003.11.030)

FIGURE 4 The proportion (%) of endometrial specimens obtained in the periovulatory (luteal days [LD] 0 to 2), early (LD 3 to 5), middle (LD 6 to 10), and late (LD 11 to 13) luteal phase in which the histologic date (postovulatory day) assigned by two or three pathologists was delayed by more than 2 days from the actual LD, using traditional criteria (1). Murray. Endometrial dating revisited. Fertil Steril 2004. Fertility and Sterility 2004 81, 1333-1343DOI: (10.1016/j.fertnstert.2003.11.030)

FIGURE 5 Between-cycle variation (%) in the periovulatory (luteal day [LD] 0 to 2), early (LD 3 to 5), mid (LD 6 to 10) and late (LD 11 to 13) luteal phase as determined in 49 women. A second endometrial biopsy was obtained from each woman in a subsequent menstrual cycle on the same LD as in the first study cycle. Using traditional criteria (1), each tissue specimen was designated with a postovulatory date (POD), calculated by averaging the dates assigned by each of the three pathologists. Between-cycle variation was considered present when the mean POD for the woman's two tissue specimens differed by more than 2 days. Using the average POD of the three pathologists eliminates interobserver variability in this comparison. Murray. Endometrial dating revisited. Fertil Steril 2004. Fertility and Sterility 2004 81, 1333-1343DOI: (10.1016/j.fertnstert.2003.11.030)