STUDY QUESTION: What (physiological) first-trimester fetal anatomic structures can be discerned by ultrasound (US) and can these structures be visualized using 3-dimensional (3D) US combined with virtual reality (VR) in a prospective clinical setting? SUMMARY ANSWER: 3D US combined with VR techniques has shown to be applicable for the assessment of fetal anatomy in the first trimester and may serve as a valuable tool for both professional training and patient counseling. WHAT IS KNOWN ALREADY: Due to technological developments, new imaging modalities are becoming available and the visualization of fetal anatomic structures continues to improve. Consequently, in recent years, the focus of antenatal US screening has progressively shifted toward the first trimester of pregnancy. To further assess the applicability of new imaging techniques in detecting anomalies it is essential first to demonstrate the visibility of physiological fetal anatomy. Until today, an extended overview of first-trimester physiological fetal structures discernable by US is missing and most knowledge on first-trimester fetal anatomy is still based on imaging modalities other than US evaluating ex vivo human subjects. STUDY DESIGN, SIZE, DURATION: A systematic literature search was performed by two independent reviewers in five electronic databases. All studies published between January 1946 and January 2024 in the English language, assessing ultrasonically discernible fetal structures in the first trimester of pregnancy were included. Subsequent, a literature-based checklist of ultrasonically discernible first-trimester fetal structures was developed. According to the constructed checklist, an offline VR assessment of 3D and 4-dimensional (4D) US datasets for discernable fetal structures was conducted. PARTICIPANTS/MATERIALS, SETTING, METHODS: In 55 high-risk pregnancies between a gestational age (GA) of 11+0-13+6 weeks 3D and 4D US datasets were collected prospectively and selected based on their quality. The US datasets were offline evaluated for discernable fetal structures as indicated on the predetermined checklist using VR by two trained observers. After offline VR assessment, visibility rates for all ultrasonically discernible structures were calculated as a proportion of the total number of US datasets. MAIN RESULTS AND THE ROLE OF CHANCE: A systematic literature search (N = 15 874 studies retrieved) resulted in the inclusion and quality assessment of 372 studies, from which 81 ultrasonically discernible fetal structures were identified and incorporated into the checklist. An offline VR assessment was performed in 3D and 4D US datasets of 55 pregnancies with a mean GA of 12 + 6 weeks (SD 0.4 days). The mean visibility rate of all fetal structures incorporated in the checklist was 82.2%. LIMITATIONS, REASONS FOR CAUTION: A key limitation of this study is the lack of targeted US examination during the acquisition of all 3D and 4D US datasets. A targeted approach could improve dataset quality and visibility rates in the offline evaluation of fetal anatomy using 3D US and VR. Additionally, the selection of high-quality 3D US datasets may introduce selection bias, which could impact the generalizability of the findings. Furthermore, since the study population was recruited from a tertiary referral center where US examinations were performed by experienced sonographers using a high-frequency transvaginal US transducer, there may be limitations in extrapolating these results to the broader general population, where access to such specialized expertise and equipment may be more limited. WIDER IMPLICATIONS OF THE FINDINGS: This is the first comprehensive literature-based overview of first-trimester physiological fetal structures discernable by US, which has been evaluated in a prospective clinical setting. Moreover, this study underlines the potential added value of the use of 3D US combined with VR, both as educational and reference resource for professionals and counseling in daily clinical practice. STUDY FUNDING/COMPETING INTEREST(S): No specific funding was used for the execution of this study. Departmental funds were utilized to support the authors throughout the study period and during manuscript preparation. These funds were provided by the Department of Obstetrics and Gynaecology at the Erasmus MC University Medical Center, Rotterdam, The Netherlands. The authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.