Fertility clinics have a duty of care towards patients who do not have children with treatment.

In medically assisted reproduction (MAR) success has mostly been measured in terms of achieving (healthy) livebirths. We argue this focus is too narrow and that success should be measured in terms of alleviating patient suffering caused by an unfulfilled child wish. The major implication is that clinics must better tailored care to effectively support patients who do not have child(ren) with treatment. First, we argue that clinics have a duty of care towards patients for whom MAR does not result in children because this is a common treatment outcome, because treatment is burdensome and creates new losses for patients, and because the field has the necessary expertise to provide support and it is part of patient-centred care. Then, we examine concerns about the adequacy of addressing the possibility that treatment may end without children, namely, that this may hinder patients' hope and put them off doing treatment, and that it may be perceived as a sign of clinical incompetence, as well as concerns about the required skill set. We end with a set of research-informed recommendations to promote healthy adjustment to ending fertility treatment without children. These focus on the need to reconceptualize 'success' and 'failure' in MAR, to promote open discussion about the possibility of treatment not resulting in children and encourage patients to develop 'plan(s) B', to support patients who end treatment without children, and to create the organizational structures needed to support clinics and healthcare professionals in this endeavour.

What is bad news in fertility care? A qualitative analysis of staff and patients' accounts of bad and challenging news in fertility care.

STUDY QUESTION: What do fertility staff and patients think is bad news in fertility care? SUMMARY ANSWER: Staff and patients agree bad news is any news that makes patients less likely to achieve parenthood spontaneously or access and do successful treatment, but their appraisals of how bad the news is are differently influenced by specific news features and the context of its delivery. WHAT IS KNOWN ALREADY: Bad news is common in fertility care, but staff feel unprepared to share it and four in 10 patients react to it with unanticipated emotional or physical reactions. Research has paid much attention to how bad news should be shared, but considerably less to what news is perceived as bad, despite the fact this may dictate elements of its delivery. STUDY DESIGN, SIZE, DURATION: Two cross-sectional, online, mixed-method surveys (active 7 January-16 July 2022) were distributed to fertility staff and patients across the UK and Europe. PARTICIPANTS/MATERIALS, SETTING, METHODS: Staff inclusion criteria were being a healthcare professional working in fertility care and having experience of sharing bad news at least once a month. Patients' inclusion criteria were being adults and having had a conversation in which staff shared or explained bad news concerning their fertility care within the last 2 months. Surveys were created in English using Qualtrics, reviewed by patients and healthcare professionals, and distributed via social media, Prolific, fertility organizations, and scientific societies. Patients were asked, regarding the last time bad news were shared with them, 'What was the bad news?' and 'What other news would you consider bad news in fertility care?'. Staff were asked to 'List the three most challenging topics of bad news you share with your patients'. Staff and patient data were separately thematically analysed to produce basic codes, organized into sub-themes and themes. Themes emerging from patients' and staff data were compared and synthesized into meta themes. MAIN RESULTS AND THE ROLE OF CHANCE: Three hundred thirty-four staff accessed the survey, 286 consented, and 217 completed (65% completion rate). Three hundred forty-four patients accessed the survey, 304 consented, and 222 completed (64% completion rate). Eighty-five percent of participants were women, 62% resided in Europe, and 59% were in private care. Average staff age was 45.2 (SD = 12.0), 44% were embryologists or lab technicians, 40% were clinicians (doctors, consultants, or physicians), and 8% nurses or midwifes. Average patient age was 32.2 (SD = 6.4) and 54% had children. Staff answers originated 100 codes, 19 sub-themes and six themes. Patients' answers produced 196 codes, 34 sub-themes, and 7 themes. Staff and patient themes were integrated into three meta-themes reflecting main topics of bad news. These were Diagnosis and negative treatment events and outcomes, Inability to do (more) treatment, and Care and patient factors disrupting communication. Staff and patients agreed that some news features (uncertain, disruptive, definitive) made news more challenging but disagreed in relation to other features (e.g. unexpected/expected). Patient factors made bad news more challenging to staff (e.g. difficult emotions) and care factors made bad news more challenging to patients (e.g. disorganized care). LIMITATIONS, REASONS FOR CAUTION: Participants were self-selected, and most were women from private European clinics. Questions differed for staff and patients, focused on subjective perceptions of news, and did not measure news impact. WIDER IMPLICATIONS OF THE FINDINGS: The badness of fertility news is not only a product of the extent to which the news compromises parenthood goals but also of its features (timing, nature, number) and the context in which the news is delivered. Guidance on sharing bad news in fertility care needs to go beyond easing the process for patients to also consider staff experiences. Guidance may need to be tailored to news features and context. STUDY FUNDING/COMPETING INTEREST(S): Cardiff University funded the research. S.G., J.B., O'.H., and A.D. report funding from the Higher Education Funding Council for Wales and the European Society for Human Reproduction and Embryology (ESHRE) to develop fertiShare: a sharing bad news eLearning course for fertility care. fertiShare will be distributed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International Licence (CC BY-NC-SA 4.0). No other conflicts are reported in relation to this work. TRIAL REGISTRATION NUMBER: N/A.

Discussing the possibility of fertility treatment being unsuccessful as part of routine care offered at clinics: patients' experiences, willingness, and preferences.

STUDY QUESTION: Are patients willing to discuss the possibility of treatment being unsuccessful as part of routine care offered at clinics, and what are the factors associated with this willingness? SUMMARY ANSWER: Nine in every 10 patients are willing to discuss this possibility as part of routine care, with willingness being associated with higher perceived benefits, lower barriers, and stronger positive attitudes towards it. WHAT IS KNOWN ALREADY: Fifty-eight percent of patients who complete up to three cycles of IVF/ICSI in the UK do not achieve a live birth. Offering psychosocial care for unsuccessful fertility treatment (PCUFT), defined as assistance and guidance on the implications of treatment being unsuccessful, could reduce the psychosocial distress patients experience when it happens, and promote positive adjustment to this loss. Research shows 56% of patients are willing to plan for an unsuccessful cycle, but little is known about their willingness and preferences towards discussing the possibility of definitive unsuccessful treatment. STUDY DESIGN, SIZE, DURATION: The study was of cross-sectional design, comprising a theoretically driven and patient-centred bilingual (English, Portuguese) mixed-methods online survey. The survey was disseminated via social media (April 2021-January 2022). Eligibility criteria included being aged 18 or older, waiting to or undergoing an IVF/ICSI cycle, or having completed a cycle within the previous 6 months without achieving a pregnancy. Out of 651 people accessing the survey, 451 (69.3%) consented to participate. From these, 100 did not complete 50% of the survey questions, nine did not report on the primary outcome variable (willingness), and 342 completed the survey (completion rate 75.8%, 338 women). PARTICIPANTS/MATERIALS, SETTING, METHODS: The survey was informed by the Health Belief Model (HBM) and Theory of Planned Behaviour (TPB). Quantitative questions covered sociodemographic characteristics and treatment history. Quantitative and qualitative questions gathered data on past experiences, willingness, and preferences (with whom, what, how and when) to receive PCUFT, as well as theory-informed factors hypothesized to be associated with patients' willingness to receive it. Descriptive and inferential statistics were used on quantitative data about PCUFT experiences, willingness, and preferences, and thematic analysis was applied to textual data. Two logistic regressions were used to investigate the factors associated with patients' willingness. MAIN RESULTS AND THE ROLE OF CHANCE: Participants were, on average, 36 years old and most resided in Portugal (59.9%) and the UK (38.0%). The majority (97.1%) were in a relationship for around 10 years, and 86.3% were childless. Participants were undergoing treatment for, on average, 2 years [SD = 2.11, range: 0-12 years], with most (71.8%) having completed at least one IVF/ICSI cycle in the past, almost all (93.5%) without success. Around one-third (34.9%) reported having received PCUFT. Thematic analysis showed participants received it mainly from their consultant. The main topic discussed was patients' low prognosis, with the emphasis being put on achieving a positive outcome. Almost all participants (93.3%) would like to receive PCUFT. Reported preferences indicated that 78.6% wanted to receive it from a psychologist/psychiatrist/counsellor, mostly in case of a bad prognosis (79.4%), emotional distress (73.5%), or difficulties in accepting the possibility of treatment being unsuccessful (71.2%). The preferred time to receive PCUFT was before initiating the first cycle (73.3%), while the preferred format was in an individual (mean = 6.37, SD = 1.17; in 1-7 scale) or couple (mean = 6.34, SD = 1.24; in 1-7 scale) session. Thematic analysis showed participants would like PCUFT to provide an overview of treatment and all possible outcomes tailored to each patient's circumstances and to encompass psychosocial support, mainly focused on coping strategies to process loss and sustain hope towards the future. Willingness to receive PCUFT was associated with higher perceived benefit of building psychosocial resources and coping strategies (odds ratios (ORs) 3.40, 95% CI 1.23-9.38), lower perceived barrier of triggering negative emotions (OR 0.49, 95% CI 0.24-0.98), and stronger positive attitudes about PCUFT being beneficial and useful (OR 3.32, 95% CI 2.12-5.20). LIMITATIONS, REASONS FOR CAUTION: Self-selected sample, mainly composed of female patients who had not yet achieved their parenthood goals. The small number of participants unwilling to receive PCUFT reduced statistical power. The primary outcome variable was intentions, and research shows a moderate association between intentions and actual behaviour. WIDER IMPLICATIONS OF THE FINDINGS: Fertility clinics should provide patients with early opportunities to discuss the possibility of their treatment being unsuccessful as part of routine care. PCUFT should focus on minimizing suffering associated with grief and loss by reassuring patients they can cope with any treatment outcome, promoting coping resources, and signposting to additional support. STUDY FUNDING/COMPETING INTEREST(S): M.S.-L. holds a doctoral fellowship from the Portuguese Foundation for Science and Technology, I.P. [Fundação para a Ciência e a Tecnologia] (FCT; SFRH/BD/144429/2019). R.C. holds a post-doctoral fellowship supported by the European Social Fund (ESF) and FCT (SFRH/BPD/117597/2016). The EPIUnit, ITR and CIPsi (PSI/01662) are also financed by FCT through the Portuguese State Budget, in the scope of the projects UIDB/04750/2020, LA/P/0064/2020 and UIDB/PSI/01662/2020, respectively. Dr Gameiro reports consultancy fees from TMRW Life Sciences and Ferring Pharmaceuticals A/S, speaker fees from Access Fertility, SONA-Pharm LLC, Meridiano Congress International and Gedeon Richter, grants from Merck Serono Ltd, an affiliate of Merck KgaA, Darmstadt, Germany. TRIAL REGISTRATION NUMBER: N/A.

Qualitative evaluation of the acceptability and feasibility among healthcare professionals and patients of an ART multi-cycle treatment planning and continuation intervention prototype.

STUDY QUESTION: Is it possible to design an ART Treatment Planning and Continuation Intervention (TPCI) that is considered acceptable and feasible to patients and healthcare professionals (HCPs)? SUMMARY ANSWER: HCPs and patients responded positively to the TPCI prototype and perceived it as an acceptable intervention to support patients to stay engaged with planned treatment, but some concerns were raised about the feasibility of using it in practice. WHAT IS KNOWN ALREADY: People discontinue ART due to its psychological burden. Digital tools to support people undergoing ART are available but typically focus only on practical support rather than psychological support. Research about treatment continuation and multi-cycle planning indicates that cognitive factors (expectations, intentions, efficacy beliefs) should be targets of interventions designed to help patients engage with and continue treatment to meet their personal treatment plans and goals. However, it is not known whether this form of psychological support would be acceptable for HCPs and patients or feasible to implement in practice. STUDY DESIGN, SIZE, DURATION: Qualitative cognitive interviews with HCPs and patients (May 2021). Patients were eligible if they had had a consultation to start a first/repeat stimulated IVF/ICSI cycle in the 8 weeks prior to recruitment, were aged 18 or older (upper age limit of 42 years for women) and fluent in English. Eligible HCPs were those employed by a fertility clinic who were responsible for delivering treatment planning consultations to patients. PARTICIPANTS/MATERIALS, SETTING, METHODS: HCPs and patients were asked to think aloud while being exposed to and exploring the TPCI in one-to-one online cognitive interviews. The TPCI was designed to reduce treatment discontinuation via cognitive factors namely formation and maintenance of multi-cycle ART intentions and efficiency of decision-making during treatment, and continuation of treatment after an unsuccessful cycle (when recommended). To impact cognitive factors the TPCI comprised of two components: an expectation management and reasoning checklist for HCPs to use during planning consultations (TPCI Checklist) and a multi-feature cognitive support mobile application (TPCI App) for patients to use prior to and during treatment. After participants thought aloud while being exposed to the TPCI prototype (both components) they were asked open questions concerning their perceptions of the core components and activities on eight acceptability dimensions (e.g. acceptability, demand, integration). Interviews lasted between 40 and 90 min, were recorded, transcribed verbatim and analysed using thematic analysis. MAIN RESULTS AND THE ROLE OF CHANCE: Thirteen HCPs and 13 patients participated in 25 online interviews. Thematic analysis using inductive and deductive coding generated 180 codes, grouped into 22 categories and synthesized into 9 themes. The themes showed that HCPs and patients provided positive feedback about the TPCI, perceiving it as a needed, acceptable and potentially effective way to forewarn patients of the possible need for multiple cycles, to provide patients with a sense of patient-clinic collaboration and support, and to bolster treatment intentions, all of which were perceived to contribute to reduced treatment discontinuation. HCPs perceived implementation of the TPCI Checklist to be challenging in its current length due to time pressures and clinic workload. Suggestions for enhancing the TPCI Checklist and App were provided, but none required critical changes to its core components or activities. LIMITATIONS, REASONS FOR CAUTION: All patients were women recruited from social media websites, mainly associated with patient support groups, who may be highly committed to their fertility treatment. HCPs were predominantly from private fertility clinics. WIDER IMPLICATIONS OF THE FINDINGS: The findings suggest there is demand for digital support geared towards motivational aspects of undergoing ART. The TPCI is an acceptable support tool to meet that need according to HCPs responsible for delivering planning consultations and patients undergoing fertility treatment. Future research is needed to develop the prototype and examine the feasibility of implementation of the TPCI in clinics. STUDY FUNDING/COMPETING INTEREST(S): This research was financially supported by Merck Serono Ltd, an affiliate of Merck KGaA, Darmstadt, Germany. 'Merck KGaA, Darmstadt, Germany reviewed the manuscript for medical accuracy only before journal submission. The authors are fully responsible for the content of this manuscript, and the views and opinions described in the publication reflect solely those of the authors' J.B. reports personal fees from Merck KGaA, Darmstadt, Germany, Merck AB an affiliate of Merck KGaA, Darmstadt Germany, Theramex, Organon JJC, Ferring Pharmaceuticals A/S, research grant from Merck Serono Ltd, grants from ESHRE outside the submitted work and that she is co-developer of Fertility Quality of Life (FertiQoL) and MediEmo app. S.G. reports consultancy fees from TMRW Life Sciences and Ferring Pharmaceuticals A/S, speaker fees from Access Fertility, SONA-Pharm LLC, Meridiano Congress International and Gedeon Richter. C.H. declares no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Feasibility randomized controlled trial of a self-guided online intervention to promote psychosocial adjustment to unmet parenthood goals.

STUDY QUESTION: Is it feasible to implement and evaluate an online self-guided psychosocial intervention for people with an unmet parenthood goal (UPG), aimed to improve well-being, in an online randomized controlled trial (RCT)? SUMMARY ANSWER: The evaluation of an online bilingual self-guided psychosocial intervention for people with a UPG is feasible, reflected by high demand, good acceptability, good adaptation and promise of efficacy, but minor adjustments to the intervention and study design of the RCT should be made to enhance practicality. WHAT IS KNOWN ALREADY: Self-identifying as having a UPG, defined as being unable to have children or as many as desired, is associated with impaired well-being and mental health. Practice guidelines and regulatory bodies have highlighted the need to address the lack of evidence-based support for this population. It is unknown if MyJourney (www.myjourney.pt), the first online self-guided intervention for people with UPGs, can be implemented and evaluated in an RCT. STUDY DESIGN, SIZE, DURATION: To evaluate the feasibility of MyJourney, we conducted a registered, two-arm, parallel group, non-blinded feasibility RCT, with a 1:1 computer-generated randomized allocation and embedded qualitative process evaluation. Participants were included between November 2020 and March 2021. Assessments were made before randomization (T1), 10 weeks (T2) and 6 months after (T3, intervention group only). Participants allocated to the intervention group received an email to access MyJourney immediately after randomization. Participants in the waitlist control group were given access to MyJourney after completing the 10-week assessment (T2). PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants were recruited via social media advertising of MyJourney and its feasibility study. People who self-identified as having a UPG could click on a link to participate, and of these 235 were randomized. Outcome measures related to demand, acceptability, implementation, practicality, adaptation and limited efficacy were assessed via online surveys. The primary outcome in limited efficacy testing was hedonic well-being, measured with the World Health Organisation Wellbeing Index (WHO-5). MAIN RESULTS AND THE ROLE OF CHANCE: Participation and retention rates were 58.3%, 31.7% (T2) and 45.2% (T3, intervention group only), respectively. Of participants invited to register with MyJourney, 91 (76.5%) set up an account, 51 (47.2%) completed the first Step of MyJourney, 12 (11.1%) completed six Steps (sufficient dose) and 6 (5.6%) completed all Steps within the 10-week recommended period. Acceptability ranged from 2.79 (successful at supporting) to 4.42 (easy to understand) on a 1 (not at all) to 5 (extremely acceptable) scale. Average time to complete sufficient dose was 15.6 h (SD = 18.15) and to complete all Steps was 12.4 h (SD = 18.15), with no differences found for participants using MyJourney in Portuguese and English. Modified intention-to-treat analysis showed a moderate increase in well-being from T1 to T2 in the intervention group (ηp2 = 0.156, mean difference (MD) = 9.300 (2.285, 16.315)) and no changes in the control group (ηp2 = 0.000, MD = 0.047 (-3.265, 3.358)). Participants in the process evaluation reported MyJourney was needed and answered their needs for support (reflecting high demand and acceptability), the recommended period to engage with MyJourney was short, and their engagement was influenced by multiple factors, including personal (e.g. lack of time) and MyJourney related (e.g. reminders). LIMITATIONS, REASONS FOR CAUTION: Participants were mostly white, well-educated, employed, childless women. Non-blinded allocation, use of self-reported questionnaire assessments and high attrition in the intervention group could have triggered bias favourable to positive evaluations of MyJourney and resulted in low power to detect T2 to T3 changes in limited efficacy outcomes. WIDER IMPLICATIONS OF THE FINDINGS: MyJourney can proceed to efficacy testing, but future work should eliminate barriers for engagement and explore strategies to maximize adherence. Entities wanting to support people with UPGs now have a freely accessible and promising resource that can be further tested and evaluated in different settings. STUDY FUNDING/COMPETING INTEREST(S): MyJourney's development was funded by the charity Portuguese Fertility Association, Cardiff University and University of Coimbra (CINEICC). Dr S.G. reports consultancy fees from Ferring Pharmaceuticals A/S, speaker fees from Access Fertility, SONA-Pharm LLC, Meridiano Congress International and Gedeon Richter and grants from Merck Serono Ltd. Bethan Rowbottom holds a PhD scholarship funded by the School of Psychology, Cardiff University. The other authors have no conflicts of interest. TRIAL REGISTRATION NUMBER: Clinical Trials.gov NCT04850482.

Talking about possible IVF/ICSI failure and need for multiple cycles in treatment planning: qualitative investigation of multi-cycle planning and its acceptability to patients and staff.

STUDY QUESTION: What are patients' and fertility staff views of talking about possible IVF/ICSI failure and need for multiple cycles in treatment planning? SUMMARY ANSWER: Healthcare professionals (HCPs) typically plan treatment on a cycle-by-cycle basis but HCPs and patients see benefits in talking about possible IVF/ICSI failure and the consequent need for multiple cycles to better prepare patients for this possibility, to support them through treatment challenges and to foster a sense of collaboration with the clinic in achieving the shared goal of treatment success. WHAT IS KNOWN ALREADY: Many patients need more than one round of IVF/ICSI stimulation to achieve their parenthood goals. About 60% of patients are willing to plan for multiple cycles of treatment in advance of treatment engagement. However, it is not clear how patients are informed about the high possibility of failure and the subsequent need for multiple cycles during their treatment planning consultations, and how approaches could be optimized. STUDY DESIGN, SIZE, DURATION: Qualitative focus groups with HCPs working at fertility clinics, patient advocates employed by patient charities (April 2020) and patients (July and August 2020). Patients were eligible if they had had a consultation to start a first/repeat stimulated IVF/ICSI cycle in the 8 weeks prior to participation, were aged 18 or older (upper age limit of 42 years for women), in heterosexual relationships and fluent in English. Eligible HCPs and patient advocates were those employed at a fertility clinic or charity, respectively. PARTICIPANTS/MATERIALS, SETTINGS, METHOD: Focus group topic guides progressed from general questions about fertility consultations to if and how the possibility of treatment failure and need for multiple cycles was introduced and discussed in (attended/own) clinics. After, preferences regarding planning IVF/ICSI on a multi-cycle or cycle-by-cycle basis were explored. Focus groups were recorded, and recordings transcribed and analysed using framework analysis to identify shared, unique and incongruent themes across participant groups. MAIN RESULTS AND THE ROLE OF CHANCE: Twelve HCPs, 2 patient advocates and 10 patients participated in six semi-structured online focus group discussions. All patients were childless and had been trying to conceive for ∼3 years. Framework analysis generated four themes and one meta-theme across participant groups. The meta-theme showed planning IVF on a cycle-by-cycle basis is the norm at clinics and that this affects how treatment is planned and the acceptability of a shift towards planning for multiple cycles, which was perceived as beneficial despite some apprehension. The four themes were: (i) heterogeneity in information provision during treatment planning; (ii) the need for improved HCP-patient collaboration; (iii) the need to temper optimism about treatment success; and (iv) apprehension, benefits and preferences regarding multi-cycle planning. LIMITATIONS, REASONS FOR CAUTION: Most patients were women from private fertility clinics with no previous treatment experience recruited from social media websites, mainly associated with patient support groups. Similarly, most HCPs were women from private fertility clinics. WIDER IMPLICATIONS OF THE FINDINGS: The findings suggest that shifting from cycle-by-cycle to multi-cycle approaches in IVF planning is possible. Achieving this shift, like other shifts in IVF (e.g. single embryo transfer), is likely to require collaboration among all stakeholders (e.g. users, staff, policymakers, regulators) to ensure that costs and benefits are balanced through using appropriate benchmarks, avoiding deflating optimism, fostering a sense of collaboration and supporting patients through challenges of multi-cycle IVF. STUDY FUNDING/COMPETING INTEREST(S): This research is funded by an Investigator-Sponsor Noninterventional Study from Merck Serono Ltd (MS200059_0010), an affiliate of Merck KGaA, Darmstadt, Germany. 'Merck KGaA, Darmstadt, Germany reviewed the manuscript for medical accuracy only before journal submission. The Authors are fully responsible for the content of this manuscript, and the views and opinions described in the publication reflect solely those of the authors'. Prof. J.B. reports personal fees from Merck KGaA, Darmstadt, Germany, Merck AB an affiliate of Merck KGaA, Darmstadt Germany, Theramex, Ferring Pharmaceuticals A/S, grant from Merck Serono Ltd, outside the submitted work and that she is co-developer of Fertility Quality of Life (FertiQoL) and MediEmo app. Dr S.G. reports consultancy fees from Ferring Pharmaceuticals A/S, Access Fertility and SONA-Pharm LLC, and grants from Merck Serono Ltd, an affiliate of Merck KGaA, Darmstadt, Germany. Dr C.H. declares no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Patient willingness, preferences and decision-making about planning for three complete cycles of IVF/ICSI treatment.

STUDY QUESTION: What is willingness, preference and decision-making about planning for the possibility of needing multiple cycles of IVF/ICSI treatment among patients consulting for a first or repeat stimulated IVF/ICSI cycle? SUMMARY ANSWER: The majority of patients seem to value the opportunity to plan for multiple cycles of treatment while acknowledging both possible challenges and benefits of doing so and decisions that might need to be made in advance. WHAT IS KNOWN ALREADY: Patients have strong intentions to do treatment to achieve pregnancy and approximately 48-54% continue treatment when confronted with a failed cycle, undergoing at least three complete cycles of treatment. However, there is inconsistency between this apparent willingness to do multiple cycles of treatment and the way treatment is currently planned on a cycle-by-cycle basis with patients. STUDY DESIGN, SIZE, DURATION: The study was of cross-sectional design, comprising a mixed-methods English online survey posted between November 2019 and March 2020. Eligibility criteria were being a patient who had had a consultation to start a stimulated cycle of IVF/ICSI for the first time or for a repeat stimulated cycle after an unsuccessful cycle in the eight weeks prior to survey completion. Individuals were also required to be aged 18 or older (upper age limit of 42 years for women) and able to respond in English. In total 881 clicked on the survey link, 118 did not consent, 41 were excluded after data screening, 57 did not meet the inclusion criteria, 331 started the survey but did not complete it, 28 had missing data on critical variables (e.g., age) and 306 completed the survey (40.1% completion, 57 men, 249 women). PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants were allocated to either the willing or unwilling to plan for multiple cycles of treatment group based on their responses to three variables: willingness to plan for three complete cycles, whether they would choose to have another cycle of IVF and whether they would continue treatment after an unsuccessful cycle. Quantitative questions gathered data on preferences towards planning for multiple cycles (i.e., attitudes, subjective norms and perceived behavioural control), challenges, benefits of planning for multiple cycles, decisional conflict experienced and treatment decisions involved in planning for multiple cycles. Demographic, fertility and fertility treatment information were also collected. Qualitative questions gathered textual data on other perceived benefits and challenges of planning for multiple cycles and solutions to the challenges. Descriptive and inferential statistics were used on quantitative data. Thematic analysis (inductive coding) was performed on the textual data. MAIN RESULTS AND THE ROLE OF CHANCE: Overall, 73.2% (n = 224) of participants had had a consultation to start a first cycle of IVF/ICSI. Participants were on average 33 years of age and had been trying to conceive for three years. A total of 63.07% (n = 193) were university educated. A total of 56% (n = 172) of participants were willing to plan for multiple cycles of IVF/ICSI in advance of treatment. Repeated measures ANOVA, t-tests and chi-square analysis showed the willing group to be significantly more likely to have been in a relationship for longer (p<.05), have higher education (p<.05) and be resident in the United Kingdom (p<.05). The willing group had positive attitudes towards planning for multiple cycles (p<.001) and stronger agreement with subjective norms (p<.001), perceived behavioural control (p<.001), benefits of planning for multiple cycles (p<.01) and felt able and attached more importance to making treatment decisions in advance of treatment (p<.05). Data saturation was achieved for the thematic analysis of textual data which revealed a total of four other challenges (e.g., less decisional freedom) and six other benefits (e.g., having a realistic view of treatment) to planning for multiple cycles. Qualitative analysis also revealed that most patients could anticipate and provide solutions for the nine challenges of planning for multiple cycles (e.g., using flexible working for the negative effect of treatment on work). LIMITATIONS, REASONS FOR CAUTION: Limitations included the outcome measure being willingness to plan for multiple cycles rather than actual multi-cycle planning behaviour. The unwilling group represented a heterogeneous group with possibly unknown motivational coherence (e.g., definitely against planning, ambivalent about planning). Other limitations included the cross-sectional nature of the survey and the recruitment source. WIDER IMPLICATIONS OF THE FINDINGS: Treatment consultations about undergoing fertility treatment could re-frame treatment to be a multi-cycle process in line with patient's willingness, preference and decision-making. This multi-cycle approach could empower patients and clinicians to discuss treatment expectations realistically and formulate fully informed treatment plans that take account of the high likelihood of cycle failure in addition to the treatment decisions that may need to be made during treatment when a cycle fails. This multi-cycle approach could help us support patients in adhering to their treatment plans even when faced with challenges, and help ascertain the level of treatment engagement possible to achieve parenthood goals. STUDY FUNDING/COMPETING INTEREST(S): This project is funded by an Investigator-Sponsor Non-interventional Study from Merck Serono Ltd (MS200059_0010). Professor Boivin reports personal fees from Merck KGaA, Darmstadt, Germany, Merck AB an affiliate of Merck KGaA, Darmstadt Germany, Theramex, Ferring Pharmaceuticals A/S, grant from Merck Serono Ltd, outside the submitted work and that she is co-developer of Fertility Quality of Life (FertiQoL) and MediEmo app. Dr. Gameiro reports consultancy fees from Ferring Pharmaceuticals A/S, Access Fertility and SONA-Pharm LLC, and grants from Merck Serono Ltd. Dr. Harrison declares no conflicts of interest. TRIAL REGISTRATION NUMBER: n/a.

Patient experiences of fertility clinic closure during the COVID-19 pandemic: appraisals, coping and emotions.

STUDY QUESTION: What are appraisals, coping strategies and emotional reactions of patients to coronavirus disease 2019 (COVID-19) fertility clinic closures? SUMMARY ANSWER: Clinic closure was appraised as stressful due to uncertainty and threat to the attainability of the parenthood goal but patients were able to cope using strategies that fit the uncertainty of the situation. WHAT IS KNOWN ALREADY: Psychological research on COVID-19 suggests that people are more anxious than historical norms and moderately to extremely upset about fertility treatment cancellation owing to COVID-19. STUDY DESIGN, SIZE, DURATION: The study was of cross-sectional design, comprising a mixed-methods, English language, anonymous, online survey posted from April 9 to 21 to social media. Eligibility criteria were being affected by COVID-19 fertility clinic closure, 18 years of age or older and able to complete the survey in English. In total, 946 people clicked on the survey link, 76 did not consent, 420 started but did not complete the survey and 450 completed (48% completion, 446 women, four men). PARTICIPANTS/MATERIALS, SETTING, METHODS: Overall 74.7% (n = 336) of respondents were residents in the UK with an average age of 33.6 years (SD = 4.4) and average years trying to conceive, 3.5 years (SD = 2.22). The survey comprised quantitative questions about the intensity of cognitive appraisals and emotions about clinic closure, and ability to cope with clinic closure. Open-text questions covered their understanding of COVID-19 and its effect on reproductive health and fertility plans, concerns and perceived benefits of clinic closure, and knowledge about closure. Sociodemographic information was collected. Descriptive and inferential statistics were used on quantitative data. Thematic qualitative analysis (inductive coding) was performed on the textual data from each question. Deductive coding grouped themes from each question into meta-themes related to cognitive stress and coping theory. MAIN RESULTS AND THE ROLE OF CHANCE: Most patients (81.6%, n = 367) had tests or treatments postponed, with these being self (41.3%, n = 186) or publicly (46.4%, n = 209) funded. Patients appraised fertility clinic closure as having potential for a more negative than positive impact on their lives, and to be very or extremely uncontrollable and stressful (P ≤ 0.001). Most reported a slight to moderate ability to cope with closure. Data saturation was achieved with all open-text questions, with 33 broad themes identified and four meta-themes linked to components of the cognitive stress and coping theory. First, participants understood clinic closure was precautionary due to unknown effects of COVID-19 but some felt clinic closure was unfair relative to advice about getting pregnant given to the public. Second, closure was appraised as a threat to attainability of the parenthood goal largely due to uncertainty of the situation (e.g. re-opening, effect of delay) and intensification of pre-existing hardships of fertility problems (e.g. long time waiting for treatment, history of failed treatment). Third, closure taxed personal coping resources but most were able to cope using thought-management (e.g. distraction, focusing on positives), getting mentally and physically fit for next treatments, strengthening their social network, and keeping up-to-date. Finally, participants reported more negative than positive emotions (P ≤ 0.001) and, almost all participants reported stress, worry and frustration at the situation, while some expressed anger and resentment at the unfairness of the situation. Overall, 11.8% were not at all able to cope, with reports of intense feelings of hopelessness and deteriorating well-being and mental health. LIMITATIONS, REASONS FOR CAUTION: The survey captures patient reactions at a specific point in time, during lockdown and before clinics announced re-opening. Participants were self-selected (e.g. UK residents, women, 48% starting but not completing the survey), which may affect generalisability. WIDER IMPLICATIONS OF THE FINDINGS: Fertility stakeholders (e.g. clinics, patient support groups, regulators, professional societies) need to work together to address the great uncertainty from COVID-19. This goal can be met proactively by setting up transparent processes for COVID-19 eventualities and signposting to information and coping resources. Future psychological research priorities should be on identifying patients at risk of distress with standardised measures and developing digital technologies appropriate for the realities of fertility care under COVID-19. STUDY FUNDING/COMPETING INTEREST(S): University funded research. Outside of the submitted work, Prof. J.B. reports personal fees from Merck KGaA, Merck AB, Theramex, Ferring Pharmaceuticals A/S; grants from Merck Serono Ltd; and that she is co-developer of the Fertility Quality of Life (FertiQoL) and MediEmo apps. Outside of the submitted work, Dr R.M. reports personal or consultancy fees from Manchester Fertility, Gedeon Richter, Ferring and Merck. Outside of the submitted work, Dr S.G. reports consultancy fees from Ferring Pharmaceuticals A/S, Access Fertility and SONA-Pharm LLC, and grants from Merck Serono Ltd. The other authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Dissemination, implementation and impact of the ESHRE evidence-based guidelines.

STUDY QUESTION: What are the perceptions of ESHRE members about the dissemination, implementation and impact of the first four ESHRE evidence-based guidelines to be published? SUMMARY ANSWER: Around 30% of ESHRE members know and use the ESHRE evidence-based guidelines in their routine practice and this is perceived to result in better treatment, better screening/evaluation/diagnosis and better psychosocial and patient-centred care, with on average three in each four members who make changes perceiving that their patients benefit from it. WHAT IS KNOWN ALREADY: ESHRE has been developing and disseminating evidence-based guidelines, aiming to improve the quality of fertility care across Europe. However, evidence has shown that guidelines dissemination is not enough to change practice at clinics, with implementation strategies that address local barriers to implementation being recommended. STUDY DESIGN SIZE DURATION: A cross-sectional study based on an online survey was sent by email to all ESHRE members (n = 7664) and advertised on ESHRE social media (20 February-3 April 2018). The survey was carried out to evaluate their perceptions about the dissemination, implementation and impact of the Management of Endometriosis (ENDO), Routine Psychosocial Care (RPC), Premature Ovarian Insufficiency (POI) and Recurrent Pregnancy Loss (RPL) ESHRE guidelines. PARTICIPANTS/MATERIALS SETTING METHODS: The survey was advertised via the ESHRE website, social media and email to all ESHRE members. It assessed the dissemination (knowledge the guidelines were published, downloaded), implementation (using guidelines in daily practice, changed practice) and impact (perceived patient benefit, referred patients to the guidelines) of the guidelines, as well as their perceived implementability. Open questions assessed perceived changes in practice, barriers to and desired support for implementation. MAIN RESULTS AND THE ROLE OF CHANCE: The final sample consisted of 658 participants (not possible to calculate response rate), with the majority being embryologists, biologists or geneticists (n = 268, 40.7%), followed by clinicians (n = 260, 39.5%), scientists (n = 48, 7.3%), nurses or midwives (n = 30, 4.6%), psychologists, counsellors or social workers (n = 28, 4.3%) and others (e.g. medical student, lab manager, marketing, ethicist; n = 24, 3.6%). The majority knew that ESHRE published the guidelines (82.1% ENDO, 54.6% RPC, 56.6% POI, 59.4% RPL). From these, the majority downloaded it (65.9% ENDO, 52.4% RPC, 54.2% POI, 56.8% RPL), around one-third used it in their routine practice (41.7% ENDO, 29.5% RPC, 33.7% POI) and around one quarter made changes to their practice (30.7% ENDO, 18.9% RPC, 21.5% POI). Overall, <20% of members think that patients benefited from the guideline (19.4% ENDO, 16.3% RPC, 16.1% POI) and very few referred them to it (ENDO 8.9%, 12.8% RPC, 16.1% POI). However, on average every three in every four people who made changes to practice perceived that their patients benefited from it (ENDO 62%, RPC 80%, POI 75%). The main reported changes in practice were better treatment, better screening/evaluation/diagnosis and better psychosocial and patient-centred care. Main perceived barriers to implementation were lack of translation to other languages, guidelines being long and difficult to understand and lack of supporting evidence. Financial constraints and lack of staff expertise were also reported. Participants desired clear support for implementation in the form of step-by-step instructions, more training and support materials for staff and patients and translation to other languages. Results for the clinicians only showed that, despite less knowledge about the RPC guideline, they were more likely to download all the guidelines, to follow them, make changes in their daily practice and refer them to their patients. LIMITATIONS REASONS FOR CAUTION: Respondents were ESHRE members and these are not representative of all European reproductive health professionals. The response rate could not be calculated as ESHRE social media reaches more than just the members. The guidelines are mainly written for clinicians and in this sample the clinicians were under-represented. In addition, missing values increased as participants progressed through each guideline's questions, with the open-ended questions being answered by only 74-97 participants. The survey assessed perceptions instead of actual practice. Overall, the results may convey a too optimistic picture of the impact of the guidelines. WIDER IMPLICATIONS OF THE FINDINGS: ESHRE's policy of investing in implementation and dissemination is important but insufficient to ensure the guidelines are implemented at clinics across Europe. ESHRE can address perceived barriers that are directly related to the guidelines, in particular lack of translation, as well as provide further support for implementation. This support should be clear and concise, focusing on how to implement the guidelines rather than on what to do. STUDY FUNDING/COMPETING INTERESTS: None.

Quality of life, anxiety and depression of German, Italian and French couples undergoing cross-border oocyte donation in Spain.

STUDY QUESTION: What is the quality of life (QoL) and mental health of infertile heterosexual couples from different nations (Italy, Germany and France) undergoing cross-border oocyte donation (OD) in Spain? SUMMARY ANSWER: Women have lower QoL and more anxiety than their male partners; overall French couples have lower QoL than their Italian and German counterparts. WHAT IS KNOWN ALREADY: In Europe, thousands of couples move across national borders annually to seek ARTs, primarily OD, driven mainly by legal restrictions in their countries of origin. Most research shows that infertility and ARTs affect patients' mental health and QoL. The decision to undergo reproductive care abroad might add further emotional and practical complexity. Reliable information on how this experience affects the mental health and QoL of cross-border reproductive care (CBRC) patients is lacking. Moreover, most research has focused on women, and further research on male partners and intercultural differences is needed. STUDY DESIGN, SIZE, DURATION: Cross-sectional study including 548 heterosexual individuals (347 women, 201 men) from Italy, Germany and France seeking IVF with donated oocytes in Barcelona, Spain between March and November 2013. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 432 couples were invited to participate and handed a questionnaire set. Questionnaires were answered separately and anonymously by each member of the couple on the day of embryo transfer. The questionnaire set included the Fertility Quality of Life (FertiQoL) instrument, the generic Hospital Anxiety and Depression Scale (HADS) instrument and three close-ended questions assessing perceived usefulness, desire, and use of psychological support. The overall response rate was 63.4%. MAIN RESULTS AND THE ROLE OF CHANCE: Men reported significantly higher scores than women in the emotional (+13.74; P < 0.001), mind-body (+13.39; P < 0.001) and social (+4.11; P < 0.01) FertiQoL domains, at multilevel analysis controlled for confounder factors. Intercultural differences in QoL of couples were seen. French individuals had significantly lower emotional (-6.44; P < 0.01), mind-body (-7.41; P < 0.001) and relational scores (-6.41; P < 0.001) compared to Italians. Germans showed higher social scores (+6.41; P < 0.001) but lower relational scores (-8.94; P < 0.002) than Italians. Men reported significantly lower anxiety scores for the HADS than their partners (-1.38; P < 0.001), and German couples reported lower anxiety (-1.70; P = 0.003) and depression than their Italian counterparts (-1.56; P < 0.001). French patients were more likely to have required support by a mental health professional due to fertility problems in the past (+0.19; P < 0.001). LIMITATIONS, REASONS FOR CAUTION: The scope of this study is limited to heterosexual couples undergoing cross-border OD. Caution on the interpretation of the results in men is advised, mainly because only three men for every five women completed the questionnaire. WIDER IMPLICATIONS OF THE FINDINGS: These findings call for further work to identify the true nature of the differences in QoL and mental health observed. STUDY FUNDING/COMPETING INTEREST(S): None.

ESHRE guideline: routine psychosocial care in infertility and medically assisted reproduction-a guide for fertility staff.

STUDY QUESTION: Based on the best available evidence in the literature, what is the optimal management of routine psychosocial care at infertility and medically assisted reproduction (MAR) clinics? SUMMARY ANSWER: Using the structured methodology of the Manual for the European Society of Human Reproduction and Embryology (ESHRE) Guideline Development, 120 recommendations were formulated that answered the 12 key questions on optimal management of routine psychosocial care by all fertility staff. WHAT IS ALREADY KNOWN: The 2002 ESHRE Guidelines for counselling in infertility has been a reference point for best psychosocial care in infertility for years, but this guideline needed updating and did not focus on routine psychosocial care that can be delivered by all fertility staff. STUDY, DESIGN, SIZE, DURATION: This guideline was produced by a group of experts in the field according to the 12-step process described in the ESHRE Manual for Guideline Development. After scoping the guideline and listing a set of 12 key questions in PICO (Patient, Intervention, Comparison and Outcome) format, thorough systematic searches of the literature were conducted; evidence from papers published until April 2014 was collected, evaluated for quality and analysed. A summary of evidence was written in a reply to each of the key questions and used as the basis for recommendations, which were defined by consensus within the guideline development group (GDG). Patient and additional clinical input was collected during the scoping and the review phase of the guideline development. PARTICIPANTS/MATERIALS, SETTING, METHODS: The guideline group, comprising psychologists, two medical doctors, a midwife, a patient representative and a methodological expert, met three times to discuss evidence and reach consensus on the recommendations. MAIN RESULTS AND THE ROLE OF CHANCE THE GUIDELINE PROVIDES: 120 recommendations that aim at guiding fertility clinic staff in providing optimal evidence-based routine psychosocial care to patients dealing with infertility and MAR. The guideline is written in two sections. The first section describes patients' preferences regarding the psychosocial care they would like to receive at clinics and how this care is associated with their well-being. The second section of the guideline provides information about the psychosocial needs patients experience across their treatment pathway (before, during and after treatment) and how fertility clinic staff can detect and address these. Needs refer to conditions assumed necessary for patients to have a healthy experience of the fertility treatment. Needs can be behavioural (lifestyle, exercise, nutrition and compliance), relational (relationship with partner if there is one, family friends and larger network, and work), emotional (well-being, e.g. anxiety, depression and quality of life) and cognitive (treatment concerns and knowledge). LIMITATIONS, REASONS FOR CAUTION: We identified many areas in care for which robust evidence was lacking. Gaps in evidence were addressed by formulating good practice points, based on the expert opinion of the GDG, but it is critical for such recommendations to be empirically validated. WIDER IMPLICATIONS OF THE FINDINGS: The evidence presented in this guideline shows that providing routine psychosocial care is associated with or has potential to reduce stress and concerns about medical procedures and improve lifestyle outcomes, fertility-related knowledge, patient well-being and compliance with treatment. As only 45 (36.0%) of the 125 recommendations were based on high-quality evidence, the guideline group formulated recommendations to guide future research with the aim of increasing the body of evidence.

Expanding the use of monoclonal antibody therapy of cancer by using ionising radiation to upregulate antibody targets.

BACKGROUND: Monoclonal antibody (mAb) therapy for the treatment of solid and haematologic malignancies has shown poor response rates as a monotherapy. Furthermore, its use is limited to tumours expressing certain molecular targets. It has been shown that single-dose radiation can induce immunogenic modulation that is characterised by cell-surface phenotypic changes leading to augmented tumour cell/cytotoxic T-cell interaction. METHODS: We examined radiation's ability to upregulate mAb therapy targets. We also used radiation to sensitise tumour cells to antibody-dependent cell-mediated cytotoxicity (ADCC). RESULTS: Radiation significantly increased cell-surface and total protein expression of mAb targets HER2, EGFR, and CD20. Focusing on HER2, targeted by trastuzumab, we observed significant upregulation of HER2 following radiation of 3 out of 3 breast cancer cell lines, one of which was triple negative, as well as in residential stem-cell populations. HER2 upregulation was sustained up to 96 h following radiation exposure and was largely dependent on intracellular reactive oxygen species. Improved ADCC and sensitisation to the antiproliferative effects of trastuzumab demonstrated the functional significance of radiation-induced HER2 upregulation. CONCLUSIONS: We show that single-dose radiation enhances mAb therapy. These findings highlight a mechanism for combining radiation with immunotherapy and expand the patient population that can be treated with targeted therapy.

Are patients at risk for psychological maladjustment during fertility treatment less willing to comply with treatment? Results from the Portuguese validation of the SCREENIVF.

STUDY QUESTION: Do patients at risk for psychological maladjustment during fertility treatment present lower intentions to comply with recommended treatment than patients not at risk? SUMMARY ANSWER: Patients at risk of psychological maladjustment present similar high intentions to comply with recommended fertility treatment to those not at risk but their intentions are conditioned by the degree of control they perceive over their fertility and its treatment and their capacity to accept a future without biological children. WHAT IS KNOWN ALREADY: Infertile couples refer to the psychological burden of treatment as one of the most important reasons for withdrawal from recommended treatment. The SCREENIVF can be used before treatment to screen patients at risk for psychological maladjustment by assessing five risk factors: anxiety, depression, helplessness and lack of acceptance cognitions and social support. STUDY DESIGN, SIZE, DURATION: Cross-sectional study. First, we investigated the psychometric properties of the Portuguese version of the SCREENIVF. Secondly, we investigated associations between risk for psychological maladjustment and intentions to comply with treatment. PARTICIPANTS/ MATERIALS, SETTING, METHODS: Two hundred and ninety-one women and 92 men undergoing any stage of fertility treatment at Portuguese infertility clinics were recruited online or in the clinical setting (55% response rate). Participants completed questionnaires that assessed their emotional adjustment, quality of life and compliance intentions. MAIN RESULTS AND ROLE OF CHANCE: The confirmatory factor analysis for the SCREENIVF indicated good fit [χ(2) = 188.50, P < 0.001; comparative fit index = 0.97; root-mean-square error of approximation = 0.06 (90% CI 0.05-0.07)] and all dimensions were reliable (α ≥ 0.70, except depression for men: α = 0.66). Fifty-two percent of women and 30% of men were at risk for maladjustment. Women and men at risk and not at risk for maladjustment reported similar intentions to comply with treatment (P > 0.05). Cognitive risk factors moderated negative associations found between distress and compliance intentions. Higher anxiety was associated with lower compliance intentions for patients with lower helplessness cognitions (ß = -0.45, P = 0.01) and men with higher acceptance cognitions (ß = -0.60; P = 0.03), but not for patients with higher helplessness cognitions (ß = 0.25, P = 0.13) and men with lower acceptance cognitions (ß = 0.38; P = 0.21). Higher depression was associated with lower compliance intentions for patients with higher helplessness cognitions (ß = -0.33, P = 0.02), but not for patients with lower helplessness cognitions (ß = 0.19, P = 0.30). LIMITATIONS, REASONS FOR CAUTION: Few men participated and thus only medium-to-large effect sizes could be detected for them. Forty-eight percent of participants were recruited online and this could have resulted in higher rates of patients at risk. WIDER IMPLICATIONS OF THE FINDINGS: The SCREENIVF is not useful to identify patients at risk for non-compliance. However, the clinic staff should be aware that patients who score high on helplessness cognitions and low on acceptance may need additional decisional aid to make autonomous and satisfying decisions about uptake of treatment. The Portuguese version of the SCREENIVF is valid and reliable and can be used with women undergoing any type of fertility treatment. STUDY FUNDING/ COMPETING INTEREST(S): S.G. received a postdoctoral fellowship from the Portuguese Foundation for Science and Technology (FCT-SFRH/BPD/63063/2009). There are no conflicts of interest to declare.

Cassandra's prophecy: a psychological perspective. Why we need to do more than just tell women.

The most salient psychological issue in the article 'Cassandra's prophecy' is the lack of fertility knowledge. This lack of knowledge exhibited by both Jane and the medical professionals resulted in a delay in trying to get pregnant and in seeking and receiving appropriate care, ultimately resulting in inadvertent childlessness. We identify five educational initiatives to increase fertility knowledge and personal awareness in order to promote informed decision-making about fertility health issues. These initiatives cover: (i) better sexual education for children; (ii) family planning for young adults that involves value and preference clarification about future parenthood goals; (iii) public health campaigns to increase awareness of the risk factors associated with reduced fertility; (iv) investigation of adherence to fertility guidelines within the medical profession; and (v) clearer information about the benefits and limitations of available fertility treatment. The future of fertility health care must be centred on providing people with information leading to informed choice about all aspects of their own fertility health. Empowerment may mean that people can better optimize their fertility health and be more likely to reach their parenthood goals.

Why we should talk about compliance with assisted reproductive technologies (ART): a systematic review and meta-analysis of ART compliance rates.

BACKGROUND: The goal of this systematic review and meta-analysis was to estimate the rate of compliance with assisted reproductive technologies (ART) and examine its relationship with treatment success rates. METHODS: Six databases were systematically searched from 1978 to December 2011. Studies were included if they reported data on patient progression through three consecutive standard ART cycles. Compliance was estimated for the first three ART cycles (typical ART Regimen Compliance, TARC) and after the first and the second failed cycles (CAF1, CAF2). Treatment success rates for all patients who started ART and for those who fully complied with the three ART cycles were estimated. RESULTS: Ten studies with data for 14 810 patients were included. TARC was 78.2% [95% confidence interval (CI) 68.8-85.3%], CAF1 was 81.8% (73.3-88.1%) and CAF2 was 75.3% (68.2-81.2%). The overall success rate was 42.7% (32.6-53.6%) for all patients starting ART and 57.9% (49.4-65.9%) for those who complied with three ART cycles. Compliance rates did not vary according to study quality, but TARC was higher for studies that reported data on doctor-censored patients versus those that did not (84.2% 95% CI 75.5-90.2 versus 70.6% 95% CI 58.3-80.5, P = 0.043). Analysis of funnel plots and the Egger test indicated publication bias for CAF1. CONCLUSIONS: Findings from this meta-analysis should reassure clinics and patients that most patients are able to comply with three cycles of ART. Compliers could increase their chances of success by as much as 15%. A more detailed assessment of compliance requires monitoring long-term treatment trajectories through the creation of national registries.

Why do patients discontinue fertility treatment? A systematic review of reasons and predictors of discontinuation in fertility treatment.

BACKGROUND Chances of achieving parenthood are high for couples who undergo fertility treatment. However, many choose to discontinue before conceiving. A systematic review was conducted to investigate patients' stated reasons for and predictors of discontinuation at five fertility treatment stages. METHODS Six databases were systematically searched. Search-terms referred to fertility treatment and discontinuation. Studies reporting on patients' stated reasons for or predictors of treatment discontinuation were included. A list of all reasons for discontinuation presented in each study was made, different categories of reasons were defined and the percentage of selections of each category was calculated. For each predictor, it was noted how many studies investigated it and how many found a positive and/or negative association with discontinuation. RESULTS The review included 22 studies that sampled 21 453 patients from eight countries. The most selected reasons for discontinuation were: postponement of treatment (39.18%, postponement of treatment or unknown 19.17%), physical and psychological burden (19.07%, psychological burden 14%, physical burden 6.32%), relational and personal problems (16.67%, personal reasons 9.27%, relational problems 8.83%), treatment rejection (13.23%) and organizational (11.68%) and clinic (7.71%) problems. Some reasons were common across stages (e.g. psychological burden). Others were stage-specific (e.g. treatment rejection during workup). None of the predictors reported were consistently associated with discontinuation. CONCLUSIONS Much longitudinal and theory led research is required to explain discontinuation. Meanwhile, treatment burden should be addressed by better care organization and support for patients. Patients should be well informed, have the opportunity to discuss values and worries about treatment and receive advice to decide about continuing treatment.

Assessing infertility stress: re-examining the factor structure of the Fertility Problem Inventory.

BACKGROUND: Research has documented that fertility problems can negatively affect the life of infertile patients, by imposing an obstacle to one important life goal: the achievement of parenthood. The Fertility Problem Inventory (FPI) proposes a comprehensive approach in assessing infertility stress, by measuring the impact on social, marital and sexual life dimensions and the importance of parenthood in infertile patients' life. This study examined the factor structure of the FPI, testing two alternative models using confirmatory factor analysis. METHODS: A sample of 209 infertile patients was recruited in two public hospital departments of assisted reproduction technology. Measures included the FPI, the Brief Symptom Inventory and the ENRICH Marital Inventory. RESULTS: Results confirmed the original measurement model of the instrument but suggested that the inclusion of an intermediate conceptual level resulted in a better fit to the model (χ²84= 147.89, P< 0.001) i.e. the instrument assesses infertility stress by assessing two main conceptual domains: the impact of infertility in infertile patients' life and representations about the importance of parenthood. The instrument revealed measurement and structure invariance and construct validity by correlating with other measures assessing similar constructs. CONCLUSIONS: This approach to the FPI has important contributions for research and clinical practice by distinguishing between the impact of infertility on different dimensions of a couple's' life and representations about the importance of parenthood, therefore extending the utility of the FPI in research and clinical practice.

The indirect effect of contextual factors on the emotional distress of infertile couples.

Few studies were dedicated to study the role of contextual factors, such as the socioeconomic status and urban or rural residence in emotional distress of infertile couples. This study aimed to explore the impact of contextual factors on emotional distress, either directly or by affecting the importance of parenthood in one's life, which in turn affects emotional distress. In this cross-sectional study, 70 couples recruited during hormonal stimulation phase prior to in vitro fertilisation completed clinical and sociodemographic forms and self-report questionnaires assessing representations about the importance of parenthood and emotional distress. Path analysis using structural equation modelling was used to examine direct and indirect effects among variables. Results indicated that socioeconomic status and place of residence had an impact in emotional distress by affecting the representations about the importance of parenthood in one's life. Gender differences were found regarding model paths, suggesting that the social context may have a stronger influence on women's emotional distress than on their partners' distress. When delineating psychological interventions, health care providers should consider that cultural values about children and parenthood contribute to shape the infertility experience.

Parental investment in couples who conceived spontaneously or with assisted reproductive techniques.

BACKGROUND: It has been suggested that couples who conceive with assisted reproductive technologies (ART) invest more in their child than those who conceive spontaneously. This study examined how parental investment in the child (PIC) varied as a function of method-of-conception, gender and other contextual variables, i.e. prenatal depression, social support and satisfaction with the marital relationship. METHODS: A total of 39 couples who conceived with ART and 34 couples who conceived spontaneously completed self-report questionnaires about depression, marital satisfaction and social support at their 24th pregnancy week and about PIC 4 months after the partum. Data were analysed with multilevel regression analyses. RESULTS: Results showed that method-of-conception and gender did not predict parental investment. There was a strong association between spouses on parental investment and investment was associated with couples' satisfaction with their marital relationship and the amount of support they perceived from their network. CONCLUSIONS: Investment in children depends on the marital relationship and support perceived from family members and friends and not on how the child was conceived nor on the gender of the parents.