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Journal of Obstetrics and Gynaecology ISSN: (Print) (Online) Journal homepage: https://www.tandfonline.com/loi/ijog20 Immersive virtual reality as tool to reduce anxiety during embryo transfer Federica Di Guardo & Marco Palumbo To cite this article: Federica Di Guardo & Marco Palumbo (2022) Immersive virtual reality as tool to reduce anxiety during embryo transfer, Journal of Obstetrics and Gynaecology, 42:5, 802-808, DOI: 10.1080/01443615.2021.1995855 To link to this article: https://doi.org/10.1080/01443615.2021.1995855 Published online: 05 Jan 2022 Submit your article to this journal Article views: 179 View related articles View Crossmark data Citing articles: View citing articles Full Terms & Conditions of access and use can be found at https://www.tandfonline.com/action/journalInformation?journalCode=ijog20 JOURNAL OF OBSTETRICS AND GYNAECOLOGY 2022, VOL 42, NO 5, 802–808 https://doi.org/10.1080/01443615.2021.1995855 REVIEW ARTICLE Immersive virtual reality as tool to reduce anxiety during embryo transfer Federica Di Guardo and Marco Palumbo Department of General Surgery and Medical Surgical Specialties, University of Catania, Catania, Italy KEYWORDS ABSTRACT The use of Virtual Reality (VR) has gained wide acceptance in several scientific fields It represents an innovative technological tool providing the experience to be immersed in a non-physical world putting on head-mounted displays that surround the users with images and sounds To date, VR has been mainly employed in the healthcare sector for educational aims, in order to provide the learners with a new method of delivering simulations However, its application to real clinical practice has recently generated beneficial effects for patients, especially for those who experience symptoms of psychological burden Infertile couples often struggle with anxiety and depression which have a strong impact on life quality Furthermore, the perspective to undergo long treatments with uncertain results and an history of failed attempts may contribute to enhance patients’ negative feelings during In Vitro Fertilization (IVF) cycles until Embryo Transfer (ET) The role of VR in reducing pain and anxiety during outpatient hysteroscopy, hysterosalpingography and oocytes retrieval, has been recently investigated with satisfactory results in terms of reducing pain and anxiety levels However, to date, inconclusive outcomes have been reported on pregnancy rate Our study would discuss the existent literature on VR applied to current medical practice and infertility, proposing its beneficial impact on women anxiety during IVF cycle with ET Introduction Infertility represents a real problem globally, affecting up to 16% of population in developed countries (Boivin et al 2007) The number of couples deciding to pursue Assisted Reproductive Techniques (ART) raises each year; this results in a constant increase in ART demand with progressive improvement in quality and efficacy of procedures and treatments (Boivin et al 2007) On the other hand, sub-fertile couples often struggle with psychological burden related to the diagnosis of infertility itself as well as to the perspective of potentially long-term treatments with uncertain results (Cousineau and Domar 2007) In this scenario, since the Embryo Transfer (ET) is the last and crucial step of In Vitro Fertilization (IVF) cycle, it frequently generates anxiety, especially in those couples having an history of previous failed ska et al 2017) attempts (Gdan Embryo implantation occurs only in 35% of ET (De Geyter et al 2018); given this, several efforts have been made to optimise ET technique which has been widely modified from its first description in order to achieve successful outcomes (Al-Shawaf et al 1993) In this context, the type of catheter used (van Weering et al 2002) the timing of catheter removal lu et al 2018) the period of patient rest (Gaikwad (Devranog et al 2013), procedures to minimise/avoid bleeding during the ET (Plowden et al 2017) as well as the possible beneficial effects of ultrasound guidance (Teixeira et al 2015) have been widely investigated and have changed several times CONTACT Federica Di Guardo Sofia, 78, Catania 95123, Italy fediguardo@gmail.com ß 2022 Informa UK Limited, trading as Taylor & Francis Group IVF treatment; assisted conception; embryo transfer during the last 20 years However, although the several technical variables added to ET with the aim to increase the success rate, psychological aspects remain an open issue for the treatment of infertile couples who experience symptoms of ska anxiety and depression of different intensity (Gdan et al 2017) Recent evidence suggests that immersive technologies, such as virtual reality (VR), when applied in a specific therapeutic context may represent an appropriate candidate to reduce symptoms of psychological burden Along this line, the role of VR in reducing anxiety in IVF cycles, specifically before oocytes retrieval, has been recently investigated in literature demonstrating satisfactory results in terms of lowering anxiety levels (Roelants 2017); however, inconclusive outcomes have been reported so far on Clinical Pregnancy Rate (CPR) The presented study aims to discuss the existent literature on VR applied to current medical practice and infertility, proposing its potential beneficial impact on women anxiety during ET Material and methods Data sources A systematic review of the literature concerning the role of Immersive Virtual Reality in infertility was performed according to PRISMA guidelines (Liberati 2009) We searched MEDLINE (PubMed), EMBASE, Cochrane Central Register of Department of General Surgery and Medical Surgical Specialties, University of Catania, Via Santa JOURNAL OF OBSTETRICS AND GYNAECOLOGY Controlled Trials, IBECS, BIOSIS, Web of Science, SCOPUS, congress abstracts, and Grey literature (Google Scholar; British Library) from 2010 to 2020 The following keywords were used: ‘Virtual Reality’, ‘Immersive Virtual Reality’ These aforementioned terms were further combined with ‘Infertility’ and ‘Assisted Reproductive Technique’ This strategy yielded 42 hits, which we screened Screening of abstract for eligibility According to all Authors, the inclusion or exclusion of studies were established at first Two investigators (F.D.G and M.P.) screened abstracts and titles of the research Study selection and eligibility criteria The main criteria selection of the literature were original article and clinical trials conducted on human Only papers written in English were included Retrospective studies, case series/report and review of the literature were disregarded In 803 the event of overlapping studies, the most recent, comprehensive study, or both were selected Results A total of 30 citations were identified and selected in the initial screening Finally, 12 studies were included in the systematic review There were 18 citations excluded because they were review articles (n ¼ 10) or case series/report (n ¼ 8) The selection process of suitable studies is displayed in Figure Immersive virtual reality VR is defined as a computer-generated three-dimensional space in which the user is immersed Its purpose is to provide the users with the perception of being physically present in a non-physical world by using head-mounted displays (HMD) which surrounds them with images, sounds or other stimuli, creating the feeling of being immersed in the environment (Pottle 2019) (Figure 2) Schubert et al (2001), had Total number of citations obtained after on-line search (n=42) Citations excluded after reading abstracts and titles (n=12) Publication retrieved for detailed study (n=30) Articles excluded (n=18) Review articles=10 Case series=4 Case reports=4 Articles included in the systematic review (n=12) Figure Selection process for the inclusion of suitable studies for the systematic review 804 F DI GUARDO AND M PALUMBO Figure Possible scenarios used in Immersive Virtual Reality Images adapted from Blum et al (2019); Wang et al (2020) Figure VR headset and sticks used to interact with virtual environments produced Image adapted from Tibaldi et al (2020) commented on the feeling of ‘presence’, assessing it as the result of several factors including three main levels named immersion, interactivity, and attentional involvement The first concept refers to the quantity and quality of virtual stimuli provided to simulate features of physical environments (Sanchez-Vives and Slater 2005) Moreover, it involves also these stimuli abilities to create the illusion of being immersed in the VR, having left the real world However, the grade of immersion in VR depends on several factors related to the used technology (Slater et al 2009), such as the number of stimulated senses, the levels of interactions with the VR and the similarity of the artificial stimuli in reference to those found in the physical world Whereas presence is a psychological experience, immersion is mainly considered as a physical process in which body and senses are tricked into reacting and behaving as though the VR were real The interaction depends on the users’ ability to affect the VR content in which they are (Figure 3) Finally, with regards to attentional involvement, users are commonly not distracted by external interferences being attracted by the virtual objects’ characteristics, this process induces the feeling of presence (Witmer and Singer 1998; Schubert et al 2001) Recently, VR has gained wide acceptance in several fields, providing the scientist with novel navigation mechanisms in order to explore spaces in a full immersive way (Krokos et al 2019) Today, VR is becoming a prominent force in the healthcare sector, especially for educational aims (Vitale et al 2020) leading learners to simply access clinical experiences due to the creation of virtual models of human anatomy (Pottle 2019) Moreover, it represents a significant resource for the treatment of psychological/psychiatric illnesses (Park et al 2019) Intuitively, VR helps in relieving pain, stress, anxiety and depression symptoms in an imagined space, making possible to provide patients positive and pleasant feelings Psychological burden and infertility Psychological burden has an elevated impact on sub-fertile couples’ well-being, leading them to experience symptoms of JOURNAL OF OBSTETRICS AND GYNAECOLOGY anxiety and depression during the whole IVF cycle until ET Major challenge in infertility consists in assessing the patients distress levels; indeed, it is possible that women who appear mentally healthy are less healthy than what they show Moreover, it seems that patients may progressively alternate a sense of increased optimism (prior to initiating the infertility treatments) to a hopeless feeling (Rooney and Domar 2016) Although, some recent studies concluded that women who struggle with fertility problems did not report significant differences in symptoms of anxiety and depression than women without difficulty in spontaneous conceiving, latest evidences showed a contrary tendency According to this, a recent study interviewed a total of 122 women prior to their first infertility consultation, reporting that 40% among them experienced anxiety, depression, or both (Chen et al 2004) Subsequent researches supported these findings A 31% prevalence of psychiatric symptoms, such as major depression was reported by Volgsten et al (2008) and a similar percentage of depression (35%) was reported by a large Danish study which screened women before undergoing ART treatment (Sejbaek et al 2013) Not surprisingly, Holley et al (2015) described that 39% of women eligible for infertility treatment met the criteria for major depressive disorder In addition, recent evidence concluded that infertile women significantly report more anxiety and depression symptoms than fertile counterpart (Lakatos et al 2017) The potential impact of psychological factors on reproductive outcomes is challenging to be demonstrated Although there are several papers supporting the notion that stress diminishes reproductive function, this theory has not yet gained a strong consensus However, recent studies focussed on the relationship between psychological symptoms during ART cycles and pregnancy rates, showed controversial results Some authors reported that the more stress level the women experienced prior and during the treatment, the lower will be the pregnancy rates (Klonoff-Cohen et al 2001; An et al 2013, Terzioglu et al 2016; Xu et al 2017) while other studies did not support the same results (Boivin et al 2011; Pasch et al 2012) Possible explanations for these discrepancies may be based on the different accuracy by which the individuals reported their distress level when completing psychological questionnaires According to this, selfreported symptoms of depression, anxiety and stress were not significantly associated with time to pregnancy in a study including 339 women trying to conceive in the United Kingdom (Lynch et al 2012) On the other hand, a study conducted on 501 women in the United States reported that levels of salivary a-amylase, which is a biomarker of stress, significantly correlated with time to pregnancy (Lynch et al 2014) Women who were in the highest quartile of a-amylase levels at baseline, had two-fold increased risk to subsequently experience infertility Finally, a recent study, after measuring cortisol through samplings of hair in 135 IVF patients, showed that cortisol levels were significantly correlated to pregnancy rates (P ¼ 017) (Massey et al 2016) These results support the fact that psychological symptoms have a negative impact on fertility (Rooney and Domar 2016) 805 Virtual reality uses in current practice VR distraction is an emerging tool used not only to reduce psychological symptoms of anxiety, but also as nonpharmacologic and non-invasive analgesic Whit regards to this last role; VR is commonly used for procedural-associated pain control reporting few minimal adverse effects Pain perception always requires attention (Eccleston and Crombez 1999; Eccleston 2001) The mechanism by which VR may work in pain control is based on the fact that almost the totality of patients’ attentional resources is interacting with VR According to this, during VR the patient has less attention available to process signals from pain receptors (Hoffman et al 2011) As results, patients start reporting less pain during VR, less attention and time focussing about pain when in VR and also having more fun during the procedures while in VR compared with no VR (Hoffman et al 2000; 2008) Moreover, several studies have recently explored the efficacy of VR for distraction from blunt force trauma (Hoffman et al 2009), hospital-based needle procedures (Chan et al 2019), dental/periodontal procedures (Furman et al 2009; Atzori et al 2018) and urological endoscopy patients (Wright et al 2005) showing satisfactory results in decreasing pain and adverse effects In the last two years, the use of VR has emerged as distracting tool during gynecological interventions According to this, a randomised controlled trial has been recently conducted to evaluate its efficacy in pain and anxiety control during outpatient hysteroscopy (Deo et al 2021) A total of 53 women were included in the study and were randomly allocated using sealed envelopes to either the VR intervention or standard care groups Primary outcome measurements were worst and average pain, based on numeric rating scores, and anxiety, recorded prior to the procedure and during the procedure Results showed that VR is feasible, effective and acceptable in a clinical setting as a distractive method to control pain and anxiety in patients undergoing outpatient hysteroscopy Indeed, the group receiving VR intervention, experienced significantly less pain and anxiety than the control group This study has demonstrated a robust effect for VR technology in this application within a relatively small-scale trial VR can also be a valuable resource to be applied to infertility-related procedure According to this, the possibility to use VR as distractive method to control discomfort during Hysterosalpingography (HSG) has been recently proposed by Wang et al (2020) in an ongoing study Authors’ intention was to realise a singlecenter, parallel-group, randomised controlled trial including 200 participants scheduled for HSG The participants were randomised (1:1) into two groups: a VR group and a blank control group The VR group received routine care and immersive VR intervention (Figure 4) and the blank control group received routine care only The primary outcome will be the worst pain score during HSG by a visual analog scale (VAS) Secondary endpoints will include anxiety experienced during the procedure, affective and cognitive pain, worst pain after 15 minutes from HSG, woman satisfaction/acceptance with management of pain, physiological parameters, adverse effects, HSG results and immersion perception score of the VR system Outcomes will be monitored at baseline, 806 F DI GUARDO AND M PALUMBO Figure A patient undergoing Hysterosalpingography with Virtual Reality applied to diminish anxiety and control the related-procedure pain Image adapted from Wang et al (2020) immediately after HSG and 15 minutes after HSG for each group Recent use of virtual reality in IVF cycle Anxiety in relation to infertility occurs frequently and over time, causing psychological burden in sub-fertile patients and reducing their quality of life Furthermore, latest evidences suggested that high level of stress may influence the outcomes of the infertility treatment (Rooney and Domar 2016) According to this, a prospective randomised double-blinded trial has recently investigated the role of VR in reducing anxiety during IVF cycles The study compared two groups named distraction group (n ¼ 56) and hypnosis group (n ¼ 44) who received two different VR session before oocytes retrieval with the aim to evaluate the impact of reducing anxiety levels on CPR following an IVF cycle Preliminary results showed a consistent lowering of the anxiety score in both groups, however outcomes on CPR are still inconclusive, due to the small number of patients included in this first phase of the study (Roelants 2017) Virtual reality future applications Immersive VR is an innovative technological tool which has recently emerged in the healthcare sector Although the multiple uses already explored in the medical field, the presented study would comment on the potential beneficial role of VR when applied to ET Indeed, VR would offer a valuable option in order to contrast anxiety in women undergoing this procedure: lowering anxiety levels may help patients to face stress and negative feelings potentially promoting a greater chance of pregnancy Additionally, VR might be useful not only to reduce psychological burden symptoms and anxiety, but it can also help to easier perform ET in difficult patients such as those affected by vaginismus (De Souza Maria Carmo et al 2018) In this last case, psychological support as well as interventions to reduce anxiety may help these women lowering stress levels and thus relax the pelvic floor (Pacik 2014), performing the ET with minimal patients’ discomfort Conclusions Although, to date, VR had been mainly used for educational aims (Pottle 2019), its application to real clinical practice has recently produced several beneficial effects for patients In this context, immersive VR has recently been proposed as method to relief pain and symptoms of psychological burden prior and during HSG, outpatient hysteroscopy and oocytes retrieval with promising results in pain control and lowering anxiety levels of infertile patients (Roelants 2017; Wang et al 2020; Deo et al 2021) In view of this, we propose and auspicate the use of VR during ET not only to reduce women anxiety during the procedure, but also to provide a way to minimise discomfort in selected categories of patients (Pacik 2014; De Souza Maria Carmo et al 2018; Di Guardo and Palumbo 2020; Genovese et al 2020) Finally, the impact of VR on CPR in IVF cycles has still to be clearly defined Further larger prospective randomised studied are warranted to validate our hypothesis JOURNAL OF OBSTETRICS AND GYNAECOLOGY Disclosure statement The authors declare no conflict of interest in relation to this article Funding This work was not supported by any grant or other form of funding References Al-Shawaf T, Dave R, Harper J, Linehan D, Riley P, Craft I 1993 Transfer of embryos into the uterus: how much technical factors affect pregnancy rates? 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