This randomized controlled trial was conducted in a single university-affiliated IVF clinic (Hadassah Hospital Mount Scopus, Jerusalem, Israel) from November 2023 to February 2024. The study was approved by the Hadassah research ethics board (0497–23-HMO REB) and was registered in ClinicalTrials.gov registry (NCT06280222) on December 07, 2023.

The primary outcome measure was the State Trait Anxiety Inventory (STAI) score, a validated tool to assess anxiety in a clinical setting [16, 17]. This questionnaire measures two types of anxiety—state anxiety and trait anxiety. STAI consists of two separate 20-item scales: one assessing state anxiety (S-STAI), referring to how a person is feeling at the very time of a perceived threat, and the other assessing trait anxiety (T-STAI) referring to a general perception. Each item is rated on a 4-point scale, ranging from “not at all” to “very much so” for state anxiety, and from “almost never” to “almost always” for trait anxiety. A score of up to 30 represents low anxiety, 31–45 indicates moderate anxiety, and a score > 45 is classified as high anxiety. This tool is frequently employed in both clinical and research settings to assess the psychological impact of medical procedures or stressors. Additional anxiety measures were the visual analog scale (VAS) for anxiety score [5], blood pressure (BP), and heart rate (HR): The VAS is a simple, self-report tool commonly used to assess subjective experiences, such as pain or anxiety, along a continuous line. The scale ranges from 0 (no anxiety) to 10 (extreme anxiety), and participants mark a point on the line that represents their current level of anxiety. This scale is effective in capturing changes in anxiety levels during and after interventions [18]. All data were collected at three time points: admission, pre-operative (after watching the VR video, before entering the procedure room), and before discharge (Fig. 1).

Eligible patients were offered to take part upon admission to the surgical outpatient clinic on the morning of oocyte retrieval. Only patients undergoing planned oocyte retrieval were approached. Patients were consented by a trained research nurse (surgical outpatient clinic), who was not involved in the prior clinical care, nor with the randomization process. The nurses were responsible for monitoring and documenting vital signs in the research file, as well as administering the questionnaires throughout the process. At each point of care, the patients were provided with the questionnaire to complete independently in the privacy of their bed.

Exclusion criteria were use of any medications for pain relief/anti-anxiety/anti-depressants, risk for seizures or previously diagnosed seizure disorder, sensitivity to flashing light/motion, a known predisposition to nausea/dizziness (vertigo, etc.), and any injury to the eyes/face/neck that would limit the use of the hardware, including blindness. In addition, patients undergoing fertility preservation for medical reasons or gender-affirming care were excluded.

In our institution, oocyte retrieval procedures are performed during the morning hours; all are conducted under anesthesia. Patients are asked to arrive at least 2 h before the surgical procedure. Patients wait in a private bed surrounded by curtains and are routinely monitored for blood pressure and pulse rate before the procedure. All patients are supervised routinely by nurses. One chaperon is allowed to accompany the patient until the procedure.

Upon signing the informed consent, patients were randomized into two groups: routine management (waiting for the procedure with no intervention) or exposure to a scenery video through a VR session. Staff members were not blinded to treatment allocation. The block randomization was performed in the gynecology outpatient clinic, removed from the IVF unit.

All patients in the intervention group watched three identical consecutive scenery movies (Virtual Nature 360°—Nature Meditation for VR Quest, Four Seasons. Winter Forest. Relax Flight. 360° and 360° VR—Morning Walk in Nature—4k Virtual Reality, Norwegian). Total session duration for the intervention group was 20 min.

The VR instrument utilized was an Oculus Quest 2 (Instructions for using the Oculus Quest 2 headset—VARWIN DOCS), which was donated to the Obstetrics and Gynecology department in Hadassah Medical Center. The VR was used as a viewer (Virtual Nature 360 for Oculus Quest). Each instrument was cleaned following use with special anti-septic wipes.

The intervention was immediately discontinued when a patient requested to discontinue watching, if discomfort or a side effect was reported, or when 20 min had elapsed.

The following demographic parameters were collected into an electronic database: age, AMH level, body mass index (BMI), cycle number, number of eggs retrieved, and whether lower than expected according to the last monitoring visit before retrieval, as well as whether accompanied by a relative/friend/parents or arrived alone. In addition, before discharge, each patient was asked to grade her general satisfaction with the procedure on a 1–10 scale, which was also recorded.

The sample size calculation was based on previous studies indicating high anxiety levels among fertility patients undergoing procedures such as oocyte retrieval (77.4 ± 16.6) or embryo transfer (76.5 ± 18) [5]. To demonstrate a 5-point reduction in the STAI score with 80% power and α = 0.05, a sample size of 12 patients was required in each group. The study aimed to recruit 30 patients to account for potential dropouts before reaching the necessary sample size.

Each stress score was compared for each patient using difference calculation between two assessment points, hence the change in each patient’s anxiety level between two assessment points. For example, “pre-procedure VAS minus baseline VAS,” “pre-discharge STAI score minus baseline STAI score.”

These difference scores were then used to obtain mean difference values for each group. To compare these mean difference values between the two independent groups (routine management vs. VR), appropriate statistical tests were applied based on data distribution:

A non-paired t-test was used for normally distributed variables, Mann–Whitney U test for non-parametric variables, and chi-squared for categorical variables.