Background IVF add-ons are techniques, medicines or procedures used in addition to standard IVF with the aim of improving the chance of success. The United Kingdom’s IVF regulator, ( the Human Fertilisation Embryology Authority (HFEA) developed a traffic light system to categorise add-ons as either green, amber, or red, based on results of randomised controlled trials. Method Qualitative interviews were undertaken to explore understanding and views of the HFEA traffic light system among IVF clinicians, embryologists and IVF patients across Australia and the United Kingdom. Results A total of 73 interviews were conducted. Overall, participants were supportive of the intention of the traffic light system, however many limitations were raised. It was widely recognized that a simple traffic light system necessarily omits information which may be important to understanding the evidence base. In particular, the red category was used in scenarios that patients viewed as having different implications for their decision-making, including ‘no evidence’ and ‘evidence of harm’. Patients were surprised at the absence of any green add-ons and questioned the value of a traffic light system in this context. Many participants considered the website a helpful starting point, but desired more detail, including the contributing studies, results specific to patient demographics (e.g., <35 years and >35 years), and inclusion of more options (e.g. acupuncture). Overall, participants believed the website to be reliable and trustworthy, particularly due to the Government affiliation, and despite some concerns regarding transparency and an overly cautious regulator. Conclusion Participants identified many limitations with the current application of the traffic light system. These could be considered in any future updates to the HFEA website and for others developing similar decision support tools.

Study question Why do patients, clinicians and embryologists opt to use IVF add-ons in fertility treatment? Summary answer Add-ons offer options, hope and control in a desperate situation. The perceived drivers differ between patients and professionals; however, both feel add-ons offer bespoke care. What is known already Evidence that add-ons offer clinical advantages for the outcomes of IVF is lacking or insufficient. However, they remain popular in the UK and Australia, with over three-quarters of couples opting to use them. Professionals, clinical societies, and the media have latched onto the ethical aspects of offering non-evidence-based add-ons, often provided at an additional cost to vulnerable patients. Conversely, it has also been suggested that patients are driving add-on use. The VALUE study is the first large qualitative study to include both patients and professionals that explores the drivers behind their use, and how the existing evidence is weighed up. Study design, size, duration VALUE was a multinational semi-structured interview study in the UK and Australia. The interview schedule was reached through extensive patient and public involvement. Between January and May 2021, recruitment took place via social media advertisement, email invitation from professional societies, and snowballing. A purposive sampling strategy was planned; all eligible participants (25 patients, 25 embryologists, and 24 clinicians) were interviewed via recorded teleconference. Anonymised verbatim transcripts were analysed iteratively, and themes developed inductively. Participants/materials, setting, methods Patient and professional transcripts were coded separately using the software DedooseTM Two separate thematic analyses followed. An inductive approach to analysis was adopted, whereby themes emerged from the data, opposed to constructing a pre-conceived coding scheme. Codes were combined into broader themes, and sub-themes, which were discussed, debated, and named. The wider research team then commented upon and debated the themes and sub-themes, which were settled upon by consensus. Main results and the role of chance Thematic analysis of patient interviews identified five themes: ‘vulnerability’; ‘power of the trusted professional opinion’; ‘role of previous experience’; ‘acceptability of add-on’; and ‘the evidence doesn’t apply to me’. The professional interviews identified five themes: ‘Treating desperation’; ‘tensions within evidence-based practice’; ‘success, not profits’; ‘the patient shopper’; and ‘potential for harm’. Analysis identified that that people undergoing IVF are vulnerable and opting for non-evidence-based treatments at additional cost because of a sense of desperation following unsuccessful cycles. For patients, utilising add-ons lends hope and a sense of control, with considerations of safety and efficacy being ranked lower than hope. For professionals, add-ons are reasonable given the absence of anything else to add, and allows patients the opportunity to exhaust every avenue. At odds with one-another are the themes regarding who is driving add-on use. Patients describe the power of a professional recommendation, believing it to be in their best interest. For professionals, it’s the patients who research and request add-ons, and failing to offer them risks losing patients. The tension between evidence and bespoke care was evident across both analyses, with testimonies being particularly powerful for patients, and for professionals, a belief that add-ons are helpful in the right context. Limitations, reasons for caution The VALUE study has captured patients and professionals who have volunteered to talk about this particularly contentious area of medicine. Participants are likely to be a motivated group of individuals who may potentially represent those with strong views regarding add-ons. Wider implications of the findings The theme of desperation runs through VALUE’s analyses and whilst we did find that patients drive add-on use, professional opinion for or against add-ons was powerful. Patients want autonomy, but only in the context of informed consent. Trial registration number https://osf.io/he7tn/

Study question How well informed are Australian women who undergo In Vitro Fertilisation (IVF) about their treatment and their chances of having a baby? Summary answer Only one in four women accurately estimated their individual chance of success with IVF and most women overestimated their chance. What is known already IVF is the cornerstone of infertility treatment, and high quality, transparent and reliable treatment information is essential for patient-centred care. A recent review into IVF practice in Victoria, Australia has highlighted deficiencies in information-provision. Similar findings have also been reported internationally. An assessment of women’s understanding of various aspects of the treatment is needed to identify information gaps that should be addressed by clinicians. While limited knowledge about infertility and infertility treatment in the general population is well-documented, little is known about the level of knowledge about infertility treatment among women undergoing IVF treatment. Study design, size, duration We conducted an anonymous online survey of women who had started IVF since 2018 in Australia. The survey aimed to assess how well-informed women feel about their treatment, and was advertised on social media, enabling women from across Australia to participate. Responses were collected from 3 to 21 June 2021. Participants/materials, setting, methods The survey included questions on demographic characteristics and IVF history. It also asked how well-informed participants felt about their treatment, what they thought their chance of having a baby from one IVF treatment cycle was, how they rated their knowledge about chance of success, and about their experience of receiving IVF-related information. Participants’ beliefs about chance of success were compared with their chance as calculated by the Society for Assisted Reproductive Technology’s (SART) online calculator. Main results and the role of chance The survey was completed by 225 women. Only about a quarter (25.8%) of participants accurately estimated their chance of success within 20% relative to their SART calculated chance, and more than half (52.4%) overestimated their chance. Among women who rated their understanding of their chance of success as ‘high’ (7-10/10), less than one third (31.6%) accurately estimated their chance of success. Older age and having undergone several cycles were associated with women being more likely to overestimate their chance of success (odds ratios of 3.2 and 2.5, respectively). Ninety percent of women indicated that their preferred source of treatment information was a consultation with their doctor, despite many women reporting that doctors only explained the probability of having a baby with IVF moderately well (mean 5.9/10). Women also reported that they wished they had been given more realistic information about IVF and their chance of success. It is difficult to determine to what extent women’s lack of understanding of what is possible with IVF is due to poor information-provision by clinicians and the clinic, and how much can be explained by optimism bias. Limitations, reasons for caution The dissemination method precludes calculation of response rate, and it is not possible to know if participants are representative of all women undergoing IVF. There is inherent imprecision in the way understanding of chance of success was estimated. The potential impact of recall bias could neither be quantified nor excluded. Wider implications of the findings The poor understanding of personal chance of success amongst women undergoing IVF in Australia, highlights the need for systematic and evidence-based improvement in the way clinics inform patients about the probability of having a baby with IVF. Further research into how information-provision in IVF can be improved is needed. Trial registration number Not applicable

Background: The Anti-Mullerian hormone (AMH) test is promoted to women as a way to find out how long they have left to have children. However, data consistently show the test is a poor predictor of natural fertility potential for an individual woman. As fertility clinic websites are often a primary source of information for reproductive information, it is essential the information provided is accurate and reflects the available evidence. Aim: To systematically record and categorise information about the AMH test found on Australian and New Zealand fertility clinic websites. Method: Data were extracted from accredited Australian and New Zealand fertility clinic websites between April and June 2020. Any webpage that mentioned the AMH test, including blogs specifically about the AMH test posted since 2015, were analysed and the content categorised. Results: 25 clinic websites included information about the AMH test. The available information embodied four overarching categories; 1) the utility of the AMH test, 2) who the test is suitable for, 3) possible actions in response to the test, and 4) caveats and limitations of the test. Eight specific statements about the utility of the test were identified, many of which are not supported by evidence (e.g. “a good snapshot of current fertility”). Whilst some websites were transparent regarding the test’s limitations, others mentioned no caveats or included persuasive statements actively promoting the test as empowering for a range of women in different circumstances (e.g. “women who would like to conceive in the future”). Conclusion: The quality of information about the AMH test varied considerably. Several websites had statements about the AMH test that are not supported by evidence. This highlights the need for higher standards for information provided on fertility clinic websites to prevent women being misled to believe the test can reliably predict their current or future fertility.