Reliability of the European Society of Human Reproduction and Embryology/European Society for Gynaecological Endoscopy and American Society for Reproductive Medicine classification systems for congenital uterine anomalies detected using three-dimensional ultrasonography  Artur Ludwin, M.D., Ph.D., Inga Ludwin, M.D., Ph.D., Marek Kudla, M.D., Ph.D., Jan Kottner, Ph.D.  Fertility and Sterility  Volume 104, Issue 3, Pages 688-697.e8 (September 2015) DOI: 10.1016/j.fertnstert.2015.06.019 Copyright © 2015 American Society for Reproductive Medicine Terms and Conditions

Figure 1 Three-dimensional ultrasonography images. (A-1, B-1, C-1) Coronal views; HDlive surface rendering; (A-2, B-2, C-2) sagittal views obtained using computed tomography ultrasound imaging in the off-line analysis. The most common form of septate uterus (A-1, A-2) or normal uterus (B-1, B-2; C-1, C-2) by the European Society of Human Reproduction and Embryology/European Society for Gynaecological Endoscopy (ESHRE-ESGE) classification, and normal uterus (A-1; B-1; C-1) by the American Society for Reproductive Medicine (ASRM) classification with slight internal indentation (23). Small differences in the site of measurement of uterine wall thickness (A-2, B-2, C-2), or differences in the precision of the measurement of internal indentation (A-1, B-1, C-1) may have caused the intrarater (A-1, A-2; B-1, B-2) and inter-rater (A-1, A-2; C-1, C-2) diagnostic disagreements and insufficient reliability of the ESHRE-ESGE system. Fertility and Sterility 2015 104, 688-697.e8DOI: (10.1016/j.fertnstert.2015.06.019) Copyright © 2015 American Society for Reproductive Medicine Terms and Conditions

Figure 2 Three-dimensional ultrasonography images. (A, B, C) Coronal views; HDlive surface rendering; (D, E, F) sagittal views obtained using computed tomography ultrasound imaging in the off-line analysis. The common form of septate uterus by the American Society for Reproductive Medicine (ASRM) classification (A, B, C), with a large internal indentation, and a rare form of septate uterus according to the European Society of Human Reproduction and Embryology/European Society for Gynaecological Endoscopy (ESHRE-ESGE) (A/E, B/E, C/F) criteria (23). Differences in the site of measurement (D = left oblique-sagittal section of the uterus; E = sagittal section of the uterus; F = right oblique-sagittal section of the uterus). (A, B, C) The precision did not cause high inter-rater or intrarater disagreements in the diagnosis in these patients. Because the septate uterus, as diagnosed by the ESHRE-ESGE classification, presents most often with a small internal indentation, the reliability of the ESHRE-ESGE system is lower than the ASRM system for the diagnosis of septate uterus. Fertility and Sterility 2015 104, 688-697.e8DOI: (10.1016/j.fertnstert.2015.06.019) Copyright © 2015 American Society for Reproductive Medicine Terms and Conditions

Supplemental Figure 1 Main benchmarks for differentiating between common uterine malformations. Absolute measurements of (A) internal fundal indentation and (B) the external cleft used to supplement the American Society for Reproductive Medicine (ASRM) system (22, 23), relative to (C) measurements of uterine wall thickness used in the European Society of Human Reproduction and Embryology/European Society for Gynaecological Endoscopy (ESHRE-ESGE) system (23, 24). Fertility and Sterility 2015 104, 688-697.e8DOI: (10.1016/j.fertnstert.2015.06.019) Copyright © 2015 American Society for Reproductive Medicine Terms and Conditions

Supplemental Figure 2 Inter-rater agreement with regard to the measurement of the main benchmarks of uterine deformities. (A) Uterine wall thickness; (B) internal indentation; (C) external cleft; mean and SD. Fertility and Sterility 2015 104, 688-697.e8DOI: (10.1016/j.fertnstert.2015.06.019) Copyright © 2015 American Society for Reproductive Medicine Terms and Conditions

Supplemental Figure 3 Potential causes of insufficient reliability of the European Society of Human Reproduction and Embryology/European Society for Gynaecological Endoscopy (ESHRE-ESGE) systems in the diagnosis of septate uterus and differentiation between an anomalous and normal uteri; (i) 50% of the uterine wall thickness is a relative benchmark; (ii) exclusion of the arcuate uterus as a separate category provides two classes (ESHRE-ESGE: normal and septate) instead of three classes (American Society for Reproductive Medicine [ASRM]: normal, arcuate, and septate) for the same deformity (internal indentation); (iii) results, with a frequent need for differentiation between variations within the norm. In the ASRM classification, the differentiation is between relatively rarer transitional forms. Fertility and Sterility 2015 104, 688-697.e8DOI: (10.1016/j.fertnstert.2015.06.019) Copyright © 2015 American Society for Reproductive Medicine Terms and Conditions

Supplemental Figure 4 Transvaginal ultrasonography and sagittal view of the uterus. The main benchmark (uterine wall thickness) are used to differentiate between anomalies in the European Society of Human Reproduction and Embryology/European Society for Gynaecological Endoscopy (ESHRE-ESGE) system and borderline values for the recognition of septate uterus (50% of wall thickness) is highly variable for the same patient; (top row) the offline analysis depends on the site of measurements in (left to right) the same section (computed tomography ultrasound imaging); (bottom row) in real time, the reliability of the measurements is also dependent on additional sources of variability (e.g., left to right: various pressures applied on the ultrasound probe). Fertility and Sterility 2015 104, 688-697.e8DOI: (10.1016/j.fertnstert.2015.06.019) Copyright © 2015 American Society for Reproductive Medicine Terms and Conditions

Supplemental Figure 5 Three-dimensional ultrasonography. Local changes in the uterine muscle tension during real-time diagnosis. A uterus that is judged to be normal by the American Society for Reproductive Medicine (ASRM) system and (left scan) septate by the European Society of Human Reproduction and Embryology/European Society for Gynaecological Endoscopy (ESHRE-ESGE) system (middle scan) meets the criteria for normal after a few minutes according to the ESHRE-ESGE criteria (right scan; uterine wall thickness) as well. This undermines the recognition of small deformations (internal indentation <1 cm) as indications of congenital anomalies. Fertility and Sterility 2015 104, 688-697.e8DOI: (10.1016/j.fertnstert.2015.06.019) Copyright © 2015 American Society for Reproductive Medicine Terms and Conditions