Defining the "normal uterus" by ultrasound measurement of uterine lengths, thicknesses, and angles in a population of nulliparous women: the Normal UteRus asSEssment study

Abstract

Objective: The existing classifications of congenital uterine anomalies are inconsistent and subject to criticism for various reasons. Noteworthy, there is still no universally accepted definition of normal uterus (NU) based on ultrasound measurements, making it difficult to objectively distinguish the uterine anatomical variants within the population. The purpose of the Normal UteRus asSEssment study was to define the exact three-dimensional (3D) ultrasound measurements of an NU, in terms of uterine lengths, thicknesses, and angles.

Design: This multicenter, prospective cohort study was conducted between January 2021 and May 2024 at 15 European gynecology centers.

Subjects: Women aged 18 to 35 years, nulliparous, with regular menstrual cycles, with no previous attempts to conceive and no known diagnosis of uterine anomalies were considered eligible. Furthermore, they were referred to gynecology units either for routine gynecological evaluation or for gynecological complaints unrelated to fertility.

Exposures: All enrolled patients underwent two-dimensional and 3D transvaginal ultrasound during the proliferative phase of the menstrual cycle (days 11-14). Uterine measurements were obtained in two-dimensional on the mid-sagittal plane and in 3D on a standardized coronal plane, using the interstitial portions of the fallopian tubes as landmarks and ensuring optimal visualization of the uterine isthmus.

Main outcome measures: Multiple uterine lengths, thicknesses, and angles were evaluated, expressing their distribution in percentiles. Interrater and intrarater agreements were assessed using the Intraclass Correlation Coefficient.

Results: A total of 442 nulliparous women with a mean age of 25.7 (SD: 4.27) years were enrolled. Key measures obtained included a median fundal indentation of 1.7 mm, with a 90th percentile of 4.8 mm; a median interostial-to-outer-contour distance of 9.1 mm; and a median indentation angle of 161.8°. Collectively, the ultrasound measurements enabled the construction of a detailed model of the NU. Measurement values were consistent across all participating centers. Both interrater and intrarater analyses demonstrated high reproducibility of the measurements.

Conclusions: This study provides the first normative reference values for uterine lengths, thicknesses, and angles in a healthy population of nulliparous women, enabling the objective classification of a normal uterus based on measurable anatomical parameters rather than on arbitrarily established criteria. Further validation in larger and more heterogeneous cohorts is warranted to confirm these findings and to enhance their generalizability.

Keywords: 3D transvaginal ultrasound; Normal uterus; T-shaped uterus; congenital uterine anomalies; septate uterus.