Use of virtual reality medical hypnosis for anxiolytic purposes during frozen embryo transfer: A prospective pilot study

According to the World Health Organization (WHO) [ 1 ], infertility rate is around 17.5% worldwide. In France, around 1 in 4 couples is affected. The use of Assisted Reproductive Techniques (ART) have become an unavoidable response for these couples and is constantly increasing [ 2 , 3 ]. This process is fraught with psychological challenges for patients [ 4 ]. It is often long and emotionally draining, exacerbating anxiety and stress levels [ 5 – 7 ]. Anxiety is particularly present at the time of embryo transfer [ 8 , 9 ], as this marks the end of the process and patients are concerns about possible discomfort during the procedure [ 10 ]. These factors have a direct impact on pregnancy rates [ 11 – 14 ]. Effective management of this anxiety is therefore essential to maximizing the chances of in vitro fertilization (IVF) success. Based on the “blunting” theory, which suggests the use of distractions to cope with anxiety-provoking situations, various non-medicated relaxation techniques have been developed [ 15 – 17 ], as the device of virtual reality hypnosis (VRH). By associating a sensory immersion with hypnotic suggestions, this device distracts patients from anxiety and pain [ 18 , 19 ]. Early studies have already demonstrated its potential to reduce anxiety in a variety of medical contexts, including painful and stressful procedures [ 19 – 21 ]. In addition safety of VRH is reassuring, with studies showing that adverse effects are rare and mild, mainly limited to motion sickness, with no serious events reported [ 22 , 23 ]. Despite these convincing data in terms of anxiolytic efficacy and safety, the VRH device is not yet offered to women during embryo transfer in ART. This may be due to organizational constraints, limited availability, or the lack of a clearly defined framework for use, as its application in this field remains unexplored . The aim of this study was to assess the feasibility of using a virtual reality medical hypnosis device for anxiolytic purposes during frozen embryo transfer (FET) and to observe its effect on subsequent pregnancy rate.

Between December 2023 and April 2024, 50 women were enrolled. The mean age was 33.0 years (±3.6), ranging from 27 to 40 years. The majority of them (n = 40, 80%) had experienced at least one previous pregnancy (with or without ART), including 25 women who had given birth to at least one child ( Table 1 ). The mean duration of infertility was 69.6 months (± 3.0). A total of 78% had primary infertility, 6% had secondary infertility, and 16% had primary-secondary infertility (i.e., conception without live birth) ( S1 Fig ). Approximately one-third of the causes of infertility were female, one-third were male, and one-third were mixed, with the majority being endometriosis among women and oligoasthenoteratozoospermia (OAT) among men ( S1 Fig ). For infertility markers, the median antral follicle count was 21.0, and the median AMH was 2.8 ng/ml. AMH: Anti-Müllerian Hormone; PCOS: Polycystic Ovary Syndrome; POI: Primary Ovarian Insufficiency; DOR: Diminished Ovarian Reserve; OAT: Oligoasthenoteratozoospermia In this study, 80% of FET were derived from intracytoplasmic sperm injection (ICSI), with the majority using fresh spousal sperm (74%). The antagonist protocol was the most commonly used (58%), either triggered by a gonadotropin-releasing hormone (GnRH) agonist or by a double trigger (GnRH agonist and recombinant HCG). Half of the women had at least 14 oocytes at ovarian puncture and obtained at least 3 blastocysts after fertilization ( Table 2 ). For 22% of women this was their first embryo transfer within the current IVF cycle. Endometrial preparation for FET was performed in a programmed cycle in 90% women, with a majority of transdermal estradiol patches used (n = 35). One embryo was transferred in 40 FET, while two embryos were transferred in 10 FET. Majority of the embryos were ‘day-5’ embryos, and over 80% were graded as either AA or AB ( Table 2 ). ART: Assisted Reproductive Treatment; c-IVF: Conventional In Vitro Fertilization; DET: Double Embryo Transfer; GnRH: Gonadotropin-Releasing Hormone; ICSI: Intracytoplasmic Sperm Injection; IMSI: Intracytoplasmic Morphologically selected Sperm Injection; FET: Frozen Embryo Transfer; NK: Not Known; r-HCG: recombinant Human Chorionic Gonadotropin; SET: Single Embryo Transfer The procedure was deemed feasible with a 96% success rate and 100% acceptability (i.e., no adverse effects reported). Two transfers could not be performed optimally due to a disconnection between the headset and the driving tablet; however, this did not interrupt the ongoing scenario or disrupt the women’s immersion. On average, the device was used for 12.3 minutes (±1.3) ( Table 3 ). * Several attempts were required Women satisfaction was reported at 98%, with 39 women being very satisfied, 10 satisfied, and only one expressing no opinion ( S2 Fig ). VRH was considered beneficial by 42 women during the transfer procedure, 20 of whom also considered it necessary before and after the transfer ( S2 Fig ). Most women (n = 42, 84%) reported enjoying both the audio and visual experiences ( S2 Fig ). Women freewrites are reported in S1 Table . Satisfaction among caregivers reached 100%, and they had favorable opinions about using the device in routine practice. The mean anxiety score after the procedure was 28.8 out of 80, compared to 39.3 out of 80 before the device was fitted, as measured by the STAI-Y1 self-report questionnaire. A statistically significant difference was observed between these two measures (p < 0.001) ( Fig 1 ), with a large effect size (r = 0.799). Only two women reported a higher anxiety score after the procedure. One woman's score increased from 32 to 51; she found the initial relaxation exercise helpful, but experienced discomfort during speculum insertion. The other woman's score increased slightly from 25 to 29, despite feeling generally more relaxed, particularly during the uterine transfer. Regarding pregnancy outcomes, considered as exploratory endpoints, 50% of women had a positive HCG test result ten days after the FET, with 20 women (40%) had HCG levels greater than 100 IU/L ( Table 3 ). Among them, 19 were subsequently confirmed by ultrasound. During the study period, 321 women underwent FET without the VRH headset within the department. The pregnancy rate in this group was 37.1%, which was lower than that observed in our study. Of these 321 women, only 49 could be matched with women of the concurrent non-exposed cohort due to missing data from one participant who underwent a FET with an embryo imported from another center. The results of the data used for the propensity score before and after matching are shown in S2 Table . After matching and conducting a marginal comparison of the odds ratios for pregnancy rates, a positive trend was observed with a pregnancy rate of 40.8% in the VRH headset group compared to 38.8% in the concurrent non-exposed cohort. This difference was not statistically significant (OR 1.18, 95% CI 0.65–2.14; p = 0.583).

This pilot study demonstrated the feasibility and safety of using a virtual reality hypnosis device in current practice during frozen embryo transfer. Both women and caregiver satisfaction was high, reflecting broad acceptance of the device. The anxiolytic effect was observed, with a significant reduction in the STAI-Y1 score. Therefore, this device may be a useful non-medical tool for improving the overall patient experience and personalizing care pathways in assisted reproduction. Although a positive trend in pregnancy rates was observed, this outcome was exploratory and did not reach statistical significance. Further large-scale and controlled studies are warranted to confirm these encouraging findings and to more thoroughly assess the potential impact of the device on pregnancy outcomes.

This was a prospective, single-center, non-comparative feasibility study conducted in a French public reproductive center at the ‘Femme, Mère, Enfant’ hospital (HFME). Eligible women were identified during consultations dedicated to the FET prescription. Women scheduled to undergo a FET protocol between December 2023 and May 2024 were invited to participate in the trial. Eligibility criteria were women aged 18–45 years, undergoing IVF in the center, with a scheduled FET, and whose partner was willing to be present. The presence of the partner (or a third party) was required on the day of the procedure for identity verification and ethical considerations. Exclusion criteria included uncontrolled epilepsy, documented psychiatric disorders, visual or auditory impairments, claustrophobia, first embryo transfer, and fresh embryo transfer (due to organizational constraints). All participants provided an informed consent and agreed to the use of their survey data. The VRH headset was used during the FET procedure. The device consisted of a virtual reality headset and noise-reducing headphones. A tablet was also used to control the sessions. Although sessions with a programmed duration were available, the free duration mode was used for the study. The caregiver set up the equipment and then asked the patients to select their preferred auditory scenario (male or female voice) and visual scenario (one of 6 virtual worlds) using the tablet. The auditory scenario was a pre-recorded medical hypnosis session categorized as anxiety, while the visual scenario was a 3D world whose animations adapted to head movements thanks to special lenses and motion sensors. The session was launched using the tablet, which was connected to the headsets via Bluetooth. The device was applied five minutes before the transfer to allow sufficient immersion time in the virtual environment [ 24 ]. It remained active throughout the transfer. Once the transfer was complete, the caregiver ended the session after five minutes using a specific gradual shutdown mode. Demographic variables, data related to IVF and FET were obtained from patients’ electronic medical records. Feasibility of using VRH was assessed based on three criteria completed by the caregiver performing the FET: device availability, caregiver provision, and incident-free use. Feasibility required all the criteria to be approved. Acceptability of the procedure was assessed by recording any potential adverse effects reported by the women after the procedure. Women and caregiver satisfaction was measured using self-administered Likert scales at the end of the procedure. Secondary exploratory endpoints included the anxiolytic effects and the pregnancy rates. The anxiolytic effect was evaluated using the standardized State-Trait Anxiety Inventory (STAI) self-report scale, which measures anxiety in response to a particular situation [ 25 ]. This was administered to women both before and after the procedure. Consisted of 20 questions, it used a four-point Likert-type scale, with 10 items being reverse-scored. The final score could range from 0 to 80, with a higher score indicating greater anxiety. The rate of pregnancies were determined based on the human chorionic gonadotropin (HCG) blood test, which is systematically performed ten days after the FET. A pregnancy was considered to have occurred when the HCG level was greater than 100 IU/L. An HCG level below this threshold was classified as a biochemical pregnancy. Those confirmed by ultrasound were subsequently categorized as clinical pregnancy, following the definitions of the international glossary in fertility [ 26 ]. As the primary endpoint was device feasibility rather than clinical efficacy, and no prior data were available to estimate expected parameters, no formal sample size calculation was performed. A pragmatic sample size of 50 women over a six-month period was considered appropriate to evaluate the feasibility of the intervention, its acceptability, and to explore anxiolytic effects. Qualitative variables were described using numbers and percentages for each category. Quantitative variables were described using the mean and standard deviation or the median and interquartile range, as appropriate. A two-sided Wilcoxon signed-rank test with a significance level of 5% was used to determine whether there was a significant difference in mean anxiety scores before and after the procedure. Effect sizes were calculated using r, derived from the test. To analyze pregnancy rates, a comparison was made with a concurrent non-exposed cohort from the same department and inclusion period. Causal inference method was used. Each woman of the prospective interventional cohort (FET with VRH headset) was matched with a women of a concurrent non-exposed cohort (FET without VRH headset) using a propensity score (PS) constructed with logistic regression. The variables included in the PS were: female age and body mass index, AMH level, type of ART, total quantity of gonadotropin, treatment duration, sperm type, number of oocytes retrieved, number of embryos obtained and frozen, FET rank, number of embryos transferred, and stage of embryo transfer. Data processing was conducted using R software (v 4.4.0) and the ‘Matchit’ package was used for PS matching [ 27 ]. This matching was performed using the nearest neighbor method, with a 1:1 ratio, and a caliper equal to zero. After matching, a marginal comparison of the odds ratio for pregnancy with VRH was performed using the ‘Marginaleffects’ package. Only variables with no missing data were used for causal inference. A p-value < 0.05 was considered statistically significant. This clinical investigation falls under category 4.2 of the medical device regulations, according to the European Regulation 2017/745. The Clinical Research and Innovation Department of HCL (Hospices Civils de Lyon) provided support for this research. The study received validation from the French National Agency for the Safety of Medicines and Health Products (ANSM) on 4th of August 2023 and approved by the Regional Committee for Personal Protection (CPP) on 4th of September 2023 (ref: 2023-A01273-42).

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