Randomized controlled study on the use of virtual reality for pain relief in oocyte retrieval under transvaginal ultrasound guidance using paracervical block and conscious sedation.

Oocyte retrieval, a fundamental surgical procedure during IVF, is performed under transvaginal ultrasound guidance and involves passing an aspiration needle through the vaginal wall into dominant follicles in the ovary. The pain experienced by women during the procedure is caused by puncture of vaginal wall and the ovarian capsule by the aspirating needle and manipulation of the needle within the ovary during the procedure ( Zelcer et al. , 1992 ). Different pain relief methods have been used including paracervical blocks ( Ng et al. , 1999 , 2000 ; Ng et al. , 2003 ), conscious sedation ( Kwan et al. , 2018 ; Lai et al. , 2020 ), spinal anaesthesia, and general anaesthesia ( Roest et al. , 2019 ). Due to the ambulatory setting in most assisted reproduction centres, spinal anaesthesia and general anaesthesia are not readily available in all settings. Conscious sedation remains a common pain relief method in oocyte retrieval ( Kwan et al. , 2018 ). A Cochrane review assessing the effectiveness and safety of different methods of conscious sedation and analgesia for pain relief in women undergoing oocyte retrieval concluded that the evidence did not support one particular method over another in pain relief during retrieval, but the concurrent use of more than one method of sedation and pain relief resulted in better pain relief than a single modality ( Kwan et al. , 2018 ). Oocyte retrieval performed under conscious sedation is still a painful procedure to some women. Therefore, it is important to optimize pain relief with conscious sedation. The pain relief method should be effective, safe and with minimal side effects. Recently, non-pharmacological management for both anxiety and pain, including the use of virtual reality (VR) has become an innovative intervention in healthcare. It leads to distraction of the patient from the acute pain during procedures and its effectiveness has been confirmed in meta-analyses ( Mallari et al. , 2019 ; Ahmad et al. , 2020 ). VR involves a computer-generated simulation, usually viewed via a headset. This provides the user with a realistic immersive virtual environment which can be interactive. Immersive VR technology offers effective pain control across various medical procedures as shown by a recent meta-analysis of 92 randomized controlled trials involving 7133 participants ( Teh et al. , 2024 ). VR is an effective technique for reducing anxiety, reducing pain, and increasing satisfaction during normal labour ( Baradwan et al. , 2022 ) and out-patient hysteroscopy ( Baradwan et al. , 2024 ). Its use in oocyte retrieval has not been studied before at the time of planning this study, although results from a preliminary study of 40 women highlights the potential of VR to alleviate stress and elevate satisfaction during oocyte retrieval ( Montjean, 2024 ). The aim of this randomized controlled study was to evaluate the effectiveness of VR in pain relief during oocyte retrieval using paracervical block and conscious sedation. We hypothesized that VR would significantly reduce pain levels during oocyte retrieval when compared to standard care.

A total of 214 women were approached between 1 December 2022 to 20 September 2023 and 54 women declined to participate in the study. A total of 160 women agreed to join and were randomly assigned into the VR group and the standard care group ( Fig. 1 ). All completed the retrieval procedure and filled in the pain level and postoperative side effects assessment. There was no loss to follow up. CONSORT flow diagram. Both groups were comparable in terms of age of the women, parity, body mass index, proportion with primary infertility, duration/causes of infertility, ovarian stimulation protocol, total amount of FSH used, duration of FSH injection, serum oestradiol level and endometrial thickness on the day of trigger, as well as the anxiety trait and state scores ( Table 1 ). However, significantly more women in the standard care group had no retrieval experience before joining this study ( P  = 0.0002). Demographic and ovarian stimulation characteristics. Continuous data are expressed in mean ± SD unless otherwise specified. Others included anovulation, coital problem, preimplantation genetic testing, and fertility preservation. Surgeon’s experience, duration of retrieval, amount of intravenous analgesics used, number of follicles aspirated, number of oocytes retrieved, proportion of women with follicular flushing and having the aspiration needle going through the cervix or uterus were similar for the two groups ( Table 2 ). Characteristics of the retrieval. Continuous data are expressed in mean ± SD unless otherwise specified. Women in both groups had similar pain levels during venepuncture, transvaginal ultrasound, insertion of intravenous cannula and anticipated pain levels during retrieval ( Table 3 ). No significant differences in the maximal and average pain levels during and after retrieval were demonstrated between the two groups. Further evaluation on the individual changes in the worst pain scores during and after oocyte retrieval between the two groups showed no statistically significant result (95% CI −4.06, 7.00; P  = 0.60). A subgroup analysis of pain levels in women without prior retrieval experience showed similar results and no statistical difference between the two groups ( Supplementary Table S1 ). The multivariate analysis examined factors that are influential to the worst pain score during oocyte retrieval. The duration of operation showed a statistically significant association with pain scores (B = 1.72, 95% CI 0.69, 2.75; P  = 0.001), revealing longer procedures were correlating with higher reported pain scores. Other variables including the use of VR, prior oocyte retrieval experience, number of follicles aspirated, number of oocytes retrieved, surgeon’s experience, application of follicular flushing, and whether the needle has passed through the cervix and uterus did not reach statistical significance ( Table 4 ). Pain levels. Continuous data are expressed in mean ± SD unless otherwise specified. Multivariate analysis considering the worst pain score during oocyte retrieval as the dependent variable. B, beta coefficient. There were minimal post-operative side effects reported in both groups. Two women in the VR group reported nausea, but none reported discomfort caused by the head-mount device. Two women in the standard care group similarly reported nausea after the retrieval, one had vomiting and two had dizziness, which could be due to the side effects of intravenous analgesics. The sedation level and patients’ satisfaction score were comparable in both groups. Only 24 women (15.0%) had either single embryo or blastocyst transferred in the fresh cycle. The clinical pregnancy rate per transfer in the VR group was 27.8% (5/18) and that in the standard care group was 33.3% (2/6). The ongoing pregnancy rate per transfer in the VR group was 22.2% (4/18) and 0% in the standard care group (0/6). No significant differences were found in clinical pregnancy and ongoing pregnancy rates between the two groups.

The study was a randomized controlled study conducted in the Centre of Assisted Reproduction and Embryology, The University of Hong Kong-Queen Mary Hospital, Hong Kong. Ethics approval was obtained from the Institutional Review Board of the University of Hong Kong/Hospital Authority Hong Kong West Cluster (reference number: UW 21-139). The study was registered in clinicaltrials.gov (identifier: NCT05218382 ). Women attending the Centre for IVF were recruited for the study. Inclusion criteria were those aged 18–43 years old, undergoing oocyte retrieval from bilateral ovaries, and capable of providing an informed consent and filling out pre- and post-procedure questionnaires in either Chinese or English. Those who have an allergic reaction towards pethidine, diazepam, or local anaesthetic agents, history of claustrophobia and easy motion sickness, and oocyte retrieval carried out on one ovary only were excluded. Eligible women were approached on the day of oocyte retrieval and informed consent was obtained after detailed counselling. Randomization was then carried out in varying blocks of four to six by a computer generated randomization list generated by a research nurse not involved in clinical management of the women. Participants were randomly allocated to either the VR group or the standard care group. Blinding the of the participants and researchers were not feasible in view of the nature of the study, with the use of a headset in the VR group. Details of our treatment protocol have been previously described ( Li et al. , 2013 ). In the antagonist protocol, subcutaneous injection of cetrorelix 0.25 mg (Cetrotide ® ) (Merck Serono, Darmstadt, Germany) was commenced from the sixth day of gonadotrophin injection till the day of ovulation trigger. The progestin-primed ovarian stimulation protocol ( Chen et al. , 2024 ) was used in patients undergoing fertility preservation, oocyte donation, preimplantation genetic testing, or who were counselled to have elective freezing of all embryos for various reasons. Medroxyprogesterone acetate 10 mg daily (Provera ® ) (Pfizer Ltd, Ascoli Piceno, Italy) was started from the start of the ovarian stimulation till the trigger day and no GnRH antagonist was given. Menotrophin (Menopur ® ) (Ferring Pharmaceuticals, Kiel, Germany) or follitropin alfa (Gonal-F ® ) (Merck Serono, Modugno, Italy) was started at 225–300 IU per daily depending on the number of antral follicles in both ovaries. Choriogonadotropin alfa 0.25 mg (Ovidrel ® ) (Merck Serono, Modugno, Italy) or Triptorelin 0.3 mg (Decapeptyl ® ) (Ferring Pharmaceuticals, Kiel, Germany) was given as trigger for final oocyte maturation when at least three follicles reached >17 mm in diameter. Oocyte retrieval was carried out 34–36 hours after the trigger injection. After admission, an intravenous cannula was placed in the women’s forearm and antibiotics prophylaxis with 1 gram cefazolin (Zhuhai United Laboratories, Zhuhai, China) was injected intravenously 30 minutes before retrieval. Women who were randomized to the VR group had the VR headset put on upon arrival at the operating room before the administration of intravenous sedation. Immersive video content was delivered using a portable VR headset called Oculus Quest 2 with a head-mounted display with built-in audio drivers. The immersive video simulated a forest and a lake, which could be further explored using the headtracker, with a soundtrack simulating sounds originating from the nature. The video lasted 4 minutes and 20 seconds, and it was played and replayed for the entire duration of the procedure. The volume of the soundtrack could be tailored and adjusted by the women at the start of the procedure in order to achieve the immersive experience. The study research assistant was present in the operating room throughout the procedure to provide any technical support if required. The headset was cleansed with alcoholic wipes after each use. Those randomized to the standard care group was originally designed to have the VR headset put on but set to blank screen. A change in the protocol was required prior to recruitment as some women during the trial period reported discomfort with the mounted headset and were uncomfortable viewing an empty dark screen. Therefore, the standard care group eventually did not use the VR headset. Women were lying on the operative bed in the lithotomy position during the retrieval procedure. Pethidine 25 mg (Martindale Pharma, Buckinghamshire, UK) and diazepam 5 mg (Wockhardt Ltd, Mumbai, India) were given intravenously prior to the start of retrieval procedure by the scrub nurse assisting the procedure. Supplementary dose of the intravenous sedation can be administered by the assisting nurse upon the women’s request if the pain was still intolerable. The blood pressure and pulse of the women were checked before the drug administration and the oxygen saturation was monitored continuously throughout the retrieval procedure. Lignocaine 1% 10 ml was injected at 4 and 8 o’clock positions of the paracervical region by the surgeon with a 21-gauge needle after cleansing the vagina and cervix with chlorhexidine. Aspiration of follicles was performed under transvaginal ultrasound guidance using a 16-gauge ovum aspiration needle with a suction pressure of 120 mmHg. Follicular flushing with culture medium was not routinely performed. Data on the performing surgeon’s experience, duration of retrieval, amount of intravenous analgesics used, number of follicles aspirated, number of oocytes retrieved, the need of follicular flushing, and whether the aspiration needle had passed through the cervix or uterus were documented immediately after the procedure. After admission to the hospital prior to the procedure, women were asked to complete the state-trait anxiety inventory (STAI) questionnaire ( Shek, 1993 ) ( Supplementary Data File S1 ) and to rate the anticipated pain levels of retrieval by the 100 mm linear visual analogue scale (0—nil to 100—intolerable). They were also asked to rate the pain levels upon venepuncture, intravenous cannula insertion, and transvaginal scanning. The women were asked to rate the average and worst pain levels during vaginal puncture and oocyte collection within 5 minutes after the retrieval, then the average and worst vaginal and abdominal pain levels four hours after the retrieval. Postoperative side effects including nausea, vomiting, dizziness, and any discomfort caused by the head-mount device were documented. They also completed a satisfaction questionnaire before discharge ( Supplementary Data File S2 ). The surgeon performing oocyte retrieval scored the sedation level of the women according to the Ramsay Sedation Scale ( Ramsay et al. , 1974 ) at the end of the retrieval. Level 1: Awake, agitated or restless, or both; Level 2: Awake, cooperative, oriented, and tranquil; Level 3: Awake but responds to commands only; Level 4: Asleep, brisk response to light glabellar tap or loud auditory stimulus; Level 5: Asleep, sluggish response to light glabellar tap or loud auditory stimulus; Level 6: Asleep, no response to glabellar tap or loud auditory stimulus. The primary outcome was the worst pain level during the retrieval. Secondary outcomes included average pain level during and after the retrieval, postoperative side effects, sedation level, satisfaction level, and clinical/ongoing pregnancy rates for those women who had fresh embryos transfer. Subgroup analysis focusing on the level of pain in women without prior experience of oocyte retrieval was also performed. Based on our previous study, the mean pain score was 47.8 ± 22.3 on a 100-point visual analogue scale (unpublished data). Taking a significance of 0.05 and power of 0.9, with an anticipated 25% reduction in pain levels, 71 women were required in each group. A total of 160 women were recruited with 80 women in each group, assuming a 10% dropout rate. Statistical analysis was conducted using IBM SPSS Statistics (macOS version 29, IBM Corp, New York, USA) by an investigator who was blinded to the coding representing the two randomization groups before completion of the analyses. Results of continuous variables were expressed as mean ± standard deviation (SD). The differences in categorical variables between the two groups were calculated using chi-squared tests and Fisher exact tests. Student t-test was used with mean differences and 95% confidence intervals to compare continuous variables between groups. Multivariate analysis was performed to examine the relationship of multiple independent variables on the primary outcome. The P -value of <0.05 was considered statistically significant.

We did not find any difference in pain levels at vaginal puncture and during the retrieval between women using VR and those in the standard care. The use of VR was well tolerated with no serious side effects. Two randomized trials ( Malard et al. , 2024 ; Pirard et al. , 2025 ) were published on the use of virtual reality in egg retrieval. Both randomized studies did not have the sample size calculation. Malard et al. (2024) assessed the effectiveness of a VR headset as an adjunct to local anaesthesia in managing nociception during oocyte retrieval and did not find any significant difference on the pain score measured by the visual analogue scale between the VR group and the usual care group. Pirard et al. (2025) evaluate the effect of VR session with and without hypnosis before sedation for oocyte retrieval on anxiety levels and on pregnancy rate. They showed a reduction in the preoperative anxiety and no difference in the ongoing pregnancy rate at 12 weeks. However, pain was not measured as an outcome in that study. Many women used the progestin-primed ovarian stimulation because of the unstable supply of antagonist during the study period and therefore did not have fresh embryo transfer. This study was not powered to show any difference in pregnancy outcomes. Currently, there is still controversy in the optimal method of analgesia in egg retrieval. Finding the optimal method of pain relief during oocyte retrieval remains an ongoing challenge with a lack of consensus. Increased procedural anxiety can lead to increased pain perception ( del Valle et al. , 2016 ), with negative impact on patients’ satisfaction ( Gupta et al. , 2004 ). A recently published systematic review and meta-analysis, consisted of 6 randomized controlled trials, involving a total of 457 patients showed that VR is effective in reducing pain and anxiety during outpatient hysteroscopy ( Baradwan et al. , 2024 ). Several factors could have attributed to the failure in demonstrating pain relief from the use of VR in the present study. The nature of pain and nerve innervation experienced by women between outpatient hysteroscopy and oocyte retrieval are different. Women undergoing outpatient hysteroscopy experienced pain during placement of the tenaculum if required, passage of the hysteroscope via the cervical canal and distension of the uterine cavity with distension medium; while women undergoing oocyte retrieval experience pain during puncture of vaginal mucosa and ovarian capsule by the aspiration needle. The software and hardware used in this intervention may also have affected the result as the degree of interaction with the video is likely to affect the effectiveness of pain relief ( Hoffman et al. , 2011 ). The video and audio were both standardized aiming to minimize the variability and experience amongst women. The interruption when the video was replayed may disrupt the immersive experience of the patients. The video played was also commented to be blurry by some women which may have affected the effect of VR. There was limitation in obtaining an objective measurement regarding the level of immersion while using VR. With further advancement in technology, it may be probable to create a more immersive environment, hence providing an increase in potential of VR in the medical field. The VR scenario and audio can also be a limitation in our study. As we standardized one VR scenario to all the patients, this provided less flexibility in personalization of the experience, which may hinder the immersion and sense of relaxation during the procedure. Pirard et al. (2025) incorporated an audio narrative with a calming voice and mediative instructions to the immersive visuals. A randomized study has shown distraction techniques with use of music to be effective in reducing pain in outpatient hysteroscopy ( Law et al. , 2021 ). Another study offering music therapy as an adjuvant for pain relief in women undergoing oocyte retrieval under conscious sedation found a significant reduction in pain and improvement in the level of satisfaction about pain control ( Cheung et al. , 2018 ). As music is an integral part of VR sessions, the beneficial effects of music may help reducing the anxiety, consequently lowering the pain perception during the procedure ( Angioli et al. , 2014 ). Sewell et al. (2023) showed that VR during outpatient hysteroscopy significantly reduced the patients’ anxiety but not pain level. Similar findings were demonstrated in a randomized trial ( Fouks et al. , 2022 ). Our study did not address the effect of anxiety during the procedure and further studies in assessing the anxiety level during the retrieval can be considered. Additionally, further documentation including the pulse rate and respiratory rate may also provide objective measures of pain and anxiety level. The small sample size was one of the limitations of our study. The maximal pain level experienced by the women in this study was found to be higher compared to our previous study, which could have impact on the initial calculation of sample size. Another limitation of the intervention was the video showed on the VR headset was designed to be viewed from a standing rather than a prone perspective. Therefore, the field of vision cannot be fully explored during the procedure as it required the patient to be lying still and supine, the degree of immersion will also be constricted. Such limitation was similarly reported in a previous study involving VR ( Deo et al. , 2021 ). The visual analogue scale is an easy method and a known validated tool in quantifying pain. The intraoperative pain score was recorded within 5 minutes after the retrieval to minimize recall bias. However, due to the nature of the intervention, both the women and the surgeons could not be blinded, a placebo effect in the patient reported pain score may have influenced the results. Malard et al. (2024) showed the relative parasympathetic tone, as measured by the Analgesia Nociception Index (ANI) of patients was significantly lower in the VR group during oocyte retrieval under local anaesthesia, indicating the patients experienced less pain; however, there was similarly no significant effect on the pain score measured by the visual analogue scale in that study. Although the use of ANI may provide an objective measurement of pain by employing the heart rate variability, the discrepancy in results between the self-reported pain score may require further investigations and explanation. The study also found no significant reduction in the anxiety level before and after the operation. A number of randomized trials investigating on the use of VR in pain relief during egg retrieval are being carried out in different centres around the globe. In view of the conflicting results amongst previous published study, further research is necessary to address various fields, including the auditory and visual input of the VR, use of adjuncts including music and hypnosis, objective measurements of pain and anxiety levels before generalization and implementation of the intervention. In conclusion, we failed to demonstrate that use of VR significantly reduced pain levels during oocyte retrieval under transvaginal ultrasound guidance using conscious sedation and paracervical block, although its use is well tolerated with no serious side effects.