A critical systematic review and meta-analyses of risk factors for fertility problems in a globalized world.

Globally, fertility awareness efforts include well-established risk factors for fertility problems. Risks disproportionately affecting women in the Global South, however, are neglected. To address this gap, we conducted a systematic review and meta-analyses of relevant risk factors to examine the association between risk factors and fertility problems. MEDLINE, Embase, Cochrane Library, regional databases and key organizational websites were used. Three authors screened and extracted data independently. Studies assessing exposure to risk (clinical, community-based samples) were included, and studies without control groups were excluded. Outcome of interest was fertility problems, e.g. inability to achieve pregnancy, live birth, neonatal death depending on study. The Newcastle-Ottawa Scale was used to assess study quality. A total of 3843 studies were identified, and 62 were included (58 in meta-analyses; n = 111,977). Results revealed the following: a ninefold risk of inability to become pregnant in genital tuberculosis (OR 8.91, 95% CI 1.89 to 42.12); an almost threefold risk in human immunodeficiency virus (OR 2.93, 95% CI 1.95 to 4.42) and bacterial vaginosis (OR 2.81, 95% CI 1.85 to 4.27); a twofold risk of tubal-factor infertility in female genital mutilation/cutting-Type II/III (OR 2.06, 95% CI 1.03 to 4.15); and postnatal mortality in consanguinity (stillbirth, OR 1.28, 95% CI 1.04 to 1.57; neonatal death, OR 1.57, 95% CI 1.22 to 2.02). It seems that risk factors affected reproductive processes through multiple pathways. Health promotion encompassing relevant health indicators could enhance prevention and early detection of fertility problems in the Global South and disproportionately affected populations. The multifactorial risk profile reinforces the need to place fertility within global health initiatives.

COVID-19-related uncertainty: fertility staff experiences of its sources, processing, responses, and consequences.

STUDY QUESTION: What are fertility staff experiences of managing COVID-19-related uncertainty after fertility clinics re-opened? SUMMARY ANSWER: Staff identified many COVID-19-related uncertainty sources, the main being the COVID-19 health threat, to which most clinics and staff responded effectively by implementing safety protocols and building strong collaborative environments that facilitated the acquisition and application of information to guide organizational responses during a rapidly changing situation, but with costs for staff and patients. WHAT IS KNOWN ALREADY: COVID-19 created significant disruption in fertility care delivery, including temporary clinic closure and treatment delay. Patients experienced significant distress, including concerns regarding the impact of COVID-19 and its vaccine on fertility and pregnancy. Multiple studies show that COVID-19-related uncertainty is a major threat and burden for healthcare staff, but this has not been investigated in reproductive medicine. STUDY DESIGN, SIZE, DURATION: A cross-sectional, online mixed-method bilingual (English, Spanish) survey (active 25 January-23 May 2021) was distributed to fertility staff across the UK, Latin America, and Africa. PARTICIPANTS/MATERIALS, SETTING, METHODS: Eligibility criteria were being a healthcare worker at a fertility clinic that had re-opened since its COVID-19-related closure, 18 years of age or older and ability to respond in English or Spanish. The survey was created in English, translated to Spanish, made available using Qualtrics, and consisted of four parts: (i) background and physical and mental wellbeing, (ii) open-ended questions regarding COVID-19 uncertainty, (iii) appraisal items regarding perceptions and impact of uncertainty, and (iv) changes in the workplace. The British Fertility Society and the African Network and Registry of Assisted Reproduction circulated the survey across the UK and Africa via email hyperlinks and social media platforms. The Argentinian Society of Reproductive Medicine and the Latin American Network of Assisted Reproduction distributed the survey across Latin America in the same manner. Thematic analysis was performed on responses from open-ended question to produce basic codes. Deductive coding grouped sub-themes across questions into themes related to the theory of uncertainty management. Descriptive statistics and repeated measures analysis of variance were used on the quantitative data. MAIN RESULTS AND THE ROLE OF CHANCE: In total, 382 staff consented to the survey, 107 did not complete (28% attrition), and 275 completed. Sixty-three percent were women, 69% were physicians, and 79% worked at private clinics. Thematic analysis produced 727 codes, organized in 92 sub-themes, and abstracted into 18 themes and one meta-theme reflecting that uncertainty is stressful but manageable. The types of uncertainties related to the threat of COVID-19 (20.6%), unpredictability of the future (19.5%), failure of communication (11.4%), and change in the workplace (8.4%). Staff appraisals of negative and positive impact of uncertainty were significantly lower (P < 0.001) than appraisals of stress, controllability, and having what it takes to cope with uncertainty. To process uncertainty, clinics focused on information dissemination (30.8%) and building a collaborative work environment (5.8%), while staff employed proactive coping (41.8%) and emotional and cognitive processing (9.6%). Main organizational responses consisted on work restructuring (41.3%, e.g. safety protocols), adapting to adversity (9.5%, e.g. supplies, preparation), and welfare support (13.8%), though staff perceived lack of support (17.5%). Negative consequences of uncertainty were worse self- and patient welfare (12.1%) and worse communication due to virtual medicine and use of mask (9.6%). Positive consequences were work improvements (8.3%), organizational adaptation (8.3%), improved relationships (5.6%), and individual adaptation (3.2%). Ninety-two percent of participants thought changes experienced in the workplace due to COVID-19 were negative, 9.1% nor negative nor positive, and 14.9% positive. Most staff thought that their physical (92.4%) and mental health (89.5%) were good to excellent. LIMITATIONS, REASONS FOR CAUTION: Participants were self-selected, and most were physicians and embryologists working at private clinics based in Latin America. The study did not account for how variability in national and regional COVID-19 policy shaped staff experiences of uncertainty. WIDER IMPLICATIONS OF THE FINDINGS: To address COVID-19 uncertainty, clinics need to promote collaborative (clinic, staff, patients) processing of uncertainty, clear team coordination and communication, organizational flexibility, and provision of support to staff and patients, with an emphasis on cognitive coping to decrease threat of and increase tolerance to uncertainty. Uncertainty management interventions bespoke to fertility care that integrate these components may increase clinics resilience to COVID-19-related and other types of uncertainty. STUDY FUNDING/COMPETING INTERESTS: Cardiff University funded this research. 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. F.Z.-H. reports speaker fees from Ferring Pharmaceuticals A/S and that he is a chair of the Latin American Registry of ART, Committee of Ethic and Public Policies, and Chilean Society of Obstetrics and Gynecology and a vice chair of the International Committee for monitoring ART. K.A., N.C., G.B., and J.B. report no conflict in relation to this work. TRIAL REGISTRATION NUMBER: N/A.

The effect of an educational animation on knowledge of testicular health and fertility of adolescents.

STUDY QUESTION: Does the provision of an educational animation, developed with young people, about testicular health and fertility impact the knowledge of these topics among adolescents? SUMMARY ANSWER: The development and provision of education on testicular health and fertility were welcomed by adolescents and associated with a significant increase in knowledge. WHAT IS KNOWN ALREADY: Young people may know less than they should about testicular health and male fertility topics. Lack of knowledge can have implications for health including late medical help-seeking for signs and symptoms of scrotal disorders, such as torsion, for which late presentation frequently results in testicular damage. STUDY DESIGN, SIZE, DURATION: A mixed methods experimental pre- and post-design was used with embedded qualitative data collection. High school students completed a pre-animation questionnaire, watched four animations on testicular health and fertility, and completed a post-animation questionnaire. Data were collected during Personal Social and Health Education lessons across a 2-week period. PARTICIPANTS/MATERIALS, SETTING, METHODS: Four animations on testicular health and fertility, informed by andrologists, academics, designers, boys, and young men, were developed. Eligible participants were boys and girls in the UK school years 8 and 9 (age 13-14 years). Participants completed a Time 1 (T1) survey (fertility knowledge, demographics) prior to watching the animations and a Time 2 (T2) survey (fertility knowledge, perceptions of the animations) immediately after the animations. Perceptions were rated on 10-point response scales (higher scores better). Participants additionally expressed in their own words positive and negative aspects of the animations. ANOVA was used to examine the effects of the animations using a 2 (time: T1, T2)×2 (gender: male, female) design on topic knowledge, perceived importance, usefulness, and style of the animations according to gender. Regression analysis examined the associations between gender, disability, class year, and knowledge at T2 while controlling for knowledge at T1. Qualitative data on perceptions of the animations were analyzed using inductive thematic analysis. MAIN RESULTS AND THE ROLE OF CHANCE: Results showed that the animations significantly increased testicular health and fertility-related knowledge from T1 (x̄=41.84 ± 24.72) to T2 (x̄=79.15, ±15.04). Boys had significantly higher levels of knowledge compared to girls at T1 (x̄=44.74, SD = 25.16 versus x̄=37.79 ± 23.49, respectively) and T2 (x̄=80.07, SD = 15.68 versus x̄=77.89 ± 14.30, respectively) but knowledge gain from T1 to T2 was not significantly different according to gender (P = 0.11) as shown by non-significant gender×time interaction. There were no significant gender differences in the perceived usefulness and importance of the animations or liking of the style of the animations, with both genders considering the animations as useful, important, and likable. Regression analysis showed only knowledge at T1 to be significantly associated with knowledge at T2. Qualitative data showed three main themes: accessibility of important and useful information; information engagement and help-seeking behaviour; and inclusivity of information. LIMITATIONS, REASONS FOR CAUTION: This was a pre- and post-study with a sample of young people from a selected educational institution without a control group. Only short-term effects of the animations were recorded. WIDER IMPLICATIONS OF THE FINDINGS: Adolescents are interested in and learn from the provision of engaging fertility-related information. Boys and men should be considered as being a relevant target population for fertility education, not just girls and women. STUDY FUNDING/COMPETING INTEREST(S): This research was carried out in partnership with the British Fertility Society, was financially supported by an Economic and Social Research Council Impact Acceleration Award (520792) and commercial sponsorship from iMediCare Ltd, Bayer AG, Merck Group, Cryos International given to the British Fertility Society, and a financial contribution from Orchid Cancer Appeal. The authors are fully responsible for the content of the animations and this manuscript, and the views and opinions described in the publication reflect solely those of the authors. J.B. reports a grant from Merck Serono Ltd outside the submitted work. C.H., G.G., A.D., E.B., U.G., M.L, B.W., and M.H. declare no conflict of interest. K.M. reports honoraria from Bayer and Merck. A.P. reports paid consultancy for Cryos International, Cytoswim Ltd, Exceed Health, and Merck Serono in the last 2 years, but all monies have been paid to the University of Sheffield. TRIAL REGISTRATION NUMBER: N/A.

Recommendations from the 2023 International Evidence-based Guideline for the Assessment and Management of Polycystic Ovary Syndrome†.

STUDY QUESTION: What is the recommended assessment and management of those with polycystic ovary syndrome (PCOS), based on the best available evidence, clinical expertise, and consumer preference? SUMMARY ANSWER: International evidence-based guidelines address prioritized questions and outcomes and include 254 recommendations and practice points, to promote consistent, evidence-based care and improve the experience and health outcomes in PCOS. WHAT IS KNOWN ALREADY: The 2018 International PCOS Guideline was independently evaluated as high quality and integrated multidisciplinary and consumer perspectives from six continents; it is now used in 196 countries and is widely cited. It was based on best available, but generally very low to low quality, evidence. It applied robust methodological processes and addressed shared priorities. The guideline transitioned from consensus based to evidence-based diagnostic criteria and enhanced accuracy of diagnosis, whilst promoting consistency of care. However, diagnosis is still delayed, the needs of those with PCOS are not being adequately met, evidence quality was low and evidence-practice gaps persist. STUDY DESIGN, SIZE, DURATION: The 2023 International Evidence-based Guideline update reengaged the 2018 network across professional societies and consumer organizations, with multidisciplinary experts and women with PCOS directly involved at all stages. Extensive evidence synthesis was completed. Appraisal of Guidelines for Research and Evaluation-II (AGREEII)-compliant processes were followed. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework was applied across evidence quality, feasibility, acceptability, cost, implementation and ultimately recommendation strength and diversity and inclusion were considered throughout. PARTICIPANTS/MATERIALS, SETTING, METHODS: This summary should be read in conjunction with the full Guideline for detailed participants and methods. Governance included a six-continent international advisory and management committee, five guideline development groups, and paediatric, consumer, and translation committees. Extensive consumer engagement and guideline experts informed the update scope and priorities. Engaged international society-nominated panels included paediatrics, endocrinology, gynaecology, primary care, reproductive endocrinology, obstetrics, psychiatry, psychology, dietetics, exercise physiology, obesity care, public health and other experts, alongside consumers, project management, evidence synthesis, statisticians and translation experts. Thirty-nine professional and consumer organizations covering 71 countries engaged in the process. Twenty meetings and five face-to-face forums over 12 months addressed 58 prioritized clinical questions involving 52 systematic and 3 narrative reviews. Evidence-based recommendations were developed and approved via consensus across five guideline panels, modified based on international feedback and peer review, independently reviewed for methodological rigour, and approved by the Australian Government National Health and Medical Research Council (NHMRC). MAIN RESULTS AND THE ROLE OF CHANCE: The evidence in the assessment and management of PCOS has generally improved in the past five years, but remains of low to moderate quality. The technical evidence report and analyses (∼6000 pages) underpins 77 evidence-based and 54 consensus recommendations, with 123 practice points. Key updates include: i) further refinement of individual diagnostic criteria, a simplified diagnostic algorithm and inclusion of anti-Müllerian hormone (AMH) levels as an alternative to ultrasound in adults only; ii) strengthening recognition of broader features of PCOS including metabolic risk factors, cardiovascular disease, sleep apnea, very high prevalence of psychological features, and high risk status for adverse outcomes during pregnancy; iii) emphasizing the poorly recognized, diverse burden of disease and the need for greater healthcare professional education, evidence-based patient information, improved models of care and shared decision making to improve patient experience, alongside greater research; iv) maintained emphasis on healthy lifestyle, emotional wellbeing and quality of life, with awareness and consideration of weight stigma; and v) emphasizing evidence-based medical therapy and cheaper and safer fertility management. LIMITATIONS, REASONS FOR CAUTION: Overall, recommendations are strengthened and evidence is improved, but remains generally low to moderate quality. Significantly greater research is now needed in this neglected, yet common condition. Regional health system variation was considered and acknowledged, with a further process for guideline and translation resource adaptation provided. WIDER IMPLICATIONS OF THE FINDINGS: The 2023 International Guideline for the Assessment and Management of PCOS provides clinicians and patients with clear advice on best practice, based on the best available evidence, expert multidisciplinary input and consumer preferences. Research recommendations have been generated and a comprehensive multifaceted dissemination and translation program supports the Guideline with an integrated evaluation program. STUDY FUNDING/COMPETING INTEREST(S): This effort was primarily funded by the Australian Government via the National Health Medical Research Council (NHMRC) (APP1171592), supported by a partnership with American Society for Reproductive Medicine, Endocrine Society, European Society for Human Reproduction and Embryology, and European Society for Endocrinology. The Commonwealth Government of Australia also supported Guideline translation through the Medical Research Future Fund (MRFCRI000266). HJT and AM are funded by NHMRC fellowships. JT is funded by a Royal Australasian College of Physicians (RACP) fellowship. Guideline development group members were volunteers. Travel expenses were covered by the partnering organizations. Disclosures of interest were strictly managed according to NHMRC policy and are available with the full guideline, technical evidence report, peer review and responses (www.monash.edu/medicine/mchri/pcos). Of named authors HJT, CTT, AD, LM, LR, JBoyle, AM have no conflicts of interest to declare. JL declares grant from Ferring and Merck; consulting fees from Ferring and Titus Health Care; speaker's fees from Ferring; unpaid consultancy for Ferring, Roche Diagnostics and Ansh Labs; and sits on advisory boards for Ferring, Roche Diagnostics, Ansh Labs, and Gedeon Richter. TP declares a grant from Roche; consulting fees from Gedeon Richter and Organon; speaker's fees from Gedeon Richter and Exeltis; travel support from Gedeon Richter and Exeltis; unpaid consultancy for Roche Diagnostics; and sits on advisory boards for Roche Diagnostics. MC declares travels support from Merck; and sits on an advisory board for Merck. JBoivin declares grants from Merck Serono Ltd.; consulting fees from Ferring B.V; speaker's fees from Ferring Arzneimittell GmbH; travel support from Organon; and sits on an advisory board for the Office of Health Economics. RJN has received speaker's fees from Merck and sits on an advisory board for Ferring. AJoham has received speaker's fees from Novo Nordisk and Boehringer Ingelheim. The guideline was peer reviewed by special interest groups across our 39 partner and collaborating organizations, was independently methodologically assessed against AGREEII criteria and was approved by all members of the guideline development groups and by the NHMRC.

Emotional reactions to infertility diagnosis: thematic and natural language processing analyses of the 1000 Dreams survey.

RESEARCH QUESTION: What are the emotional effects of infertility on patients, partners, or both, and how can qualitative thematic analyses and natural language processing (NLP) help evaluate textual data? DESIGN: A cross-sectional, multi-country survey conducted between March 2019 and May 2019. A total of 1944 patients, partners, or both, from nine countries responded to the open-ended question asking about their initial feelings related to an infertility diagnosis. A mixed-method approach that integrated NLP topic modelling and thematic analyses was used to analyse responses. Sentiment polarity was quantified for each response. Linear regression evaluated the association between patient characteristics and sentiment negativity. RESULTS: Common emotional reactions to infertility diagnoses were sadness, depression, stress, disappointment, anxiety, frustration, confusion and loss of self-confidence. NLP topic modelling found additional reactions, i.e. shared feelings with partners, recollections about causes of infertility and treatment experience. Responses to the open-ended question were brief (median: three words) with 71.8% conveying negative sentiments. Some respondent characteristics showed small but significant associations with sentiment negativity, i.e. country (Spain, China and France were more negative than the USA, P < 0.001, P < 0.003 and P < 0.009 respectively), treatment engagement (no treatment was more negative than one or more treatment, P = 0.027) and marital status (missing/other was more negative than divorced, P = 0.003). CONCLUSION: Infertility diagnoses create an emotional burden for patients and partners. The mixed-method approach provides a compelling synergy in support of the validity of these findings and shows potential for these techniques in future research.

Tailored support may reduce mental and relational impact of infertility on infertile patients and partners.

RESEARCH QUESTION: What is the psychological impact of infertility on infertile patients and partners of infertile patients? DESIGN: This online, international, quantitative survey assessed the impact of infertility on mental health, relationships and daily activities for 1944 respondents. Respondents were male or female infertile patients (n = 1037) or partners to infertile patients (n = 907; not necessarily partners of the patient sample) and were recruited at different stages of the treatment journey. RESULTS: The most common emotions were 'sadness' at infertility diagnosis and 'anxiety' during treatment. Emotions differed in nature and intensity throughout the journey. Envy of others who achieved pregnancy was frequently reported by women. More than half of respondents (60.4%; n = 1174) perceived the infertility journey to have impacted their mental health, and 44.1% (n = 857) of respondents sought mental health support. More patients reported mental health impacts (70.1%, n = 727) than partners (49.3%, n = 447). One in three respondents indicated that their relationship had suffered due to the infertility diagnosis. Of these respondents, 55.0% (n = 409) strongly agreed that infertility caused an emotional strain. Patients more often than partners reported a detrimental impact on daily activities. Respondents most commonly agreed with statements regarding an 'effect on work-life balance'. CONCLUSION: Treatment journey stages are defined by their impact profile, which differs between infertile patients and partners of infertile patients. Negative impacts are diverse (mental health, relational, daily activities). There was disparity between the number of respondents reporting mental health issues and the number seeking mental health support. This indicates the need for support services tailored to different treatment stages.

The impact of pharaonic female genital mutilation on sexuality: Two cases from Sudan highlighting the need for widespread dissemination of sexual and reproductive health education in Africa.

It is well documented that female genital mutilation (FGM) can have numerous physical and psychosocial consequences. The increased awareness about FGM and its impact on female health over the past few decades has led to a ban on FGM in many countries, however, this has yet to translate into measurable changes in prevalence. Efforts to enforce legislation have been unsuccessful in part because the general public lacks information about the negative consequences of FGM. In this report we present two cases of sexual difficulties as a result of FGM from Sudan, where the most severe form of FGM is still being practiced. During an interview about infertility, these two women volunteered information about how FGM has affected their sexuality. The lack of information about the impact of FGM on sexuality reflected in these cases, highlighted the significant need for widespread dissemination of sexual and reproductive health education in Africa.

Barriers and factors associated with significant delays to initial consultation and treatment for infertile patients and partners of infertile patients.

RESEARCH QUESTION: What are the key drivers and barriers for infertile patients and their partners to see an infertility specialist and initiate treatment? DESIGN: An online, international, 30-minute quantitative survey collected data from 1944 respondents from nine countries. Respondents were infertile patients (n = 1037) or partners of infertile patients (n = 907; but not necessarily partners of the patient sample), at different stages of the treatment journey. RESULTS: The overall average times were 3.2 years to receiving a medical infertility diagnosis, 2.0 years attempting to achieve pregnancy without assistance before treatment, and 1.6 years of treatment before successful respondents achieved pregnancy. The most common driver for considering treatment after a consultation (n = 1025) was an equal desire within the couple to have a child (40.8%). Of the partners (n = 356), 29.8% reported that transparency of information from healthcare professionals about treatment expectations was important. A significantly higher proportion of respondents seeking treatment reported that healthcare professionals offered supportive services (61.2%) and mental health services (62.0%), than of the 207 respondents who did not seek treatment (32.4% and 36.7%, respectively; P < 0.001). Perceived cost was the most commonly reported barrier for respondents not seeking a consultation (37.5% of n = 352) or treatment (42.0% of n = 207). Of the 95 respondents who discontinued treatment, 34.7% discontinued due to the financial impact. CONCLUSIONS: Respondents reported significant delays to seeking treatment, probably negatively impacting the chances of achieving pregnancy. Motivational coherence within couples was a key driver and cost of treatment was the main barrier. Reported supportive service offerings by healthcare professionals were significantly associated with continuation of the treatment journey.

Time as an outcome measure in fertility-related clinical studies: long-awaited.

Time taken to achieve a live birth is an important consideration that is central to managing patient expectations during infertility treatment. However, time-related endpoints are not reported as standard in the majority of fertility-related clinical studies and there is no internationally recognized consensus definition for such endpoints. There is, therefore, a need for meaningful discussions around the selection of appropriate time-related treatment outcome measures for studies evaluating fertility treatments that will be relevant to diverse stakeholders (e.g. patients, healthcare professionals, clinical scientists, authorities and industry). Here, we provide a proposal for the evaluation of time-related outcome measures in fertility-related clinical studies, alongside associated definitions.

Promoting fertility awareness and preconception health using a chatbot: a randomized controlled trial.

RESEARCH QUESTION: What are the effects of using a fertility education chatbot, i.e. automatic conversation programme, on knowledge, intentions to improve preconception behaviour and anxiety? DESIGN: A three-armed, randomized controlled trial was conducted using an online social research panel. Participants included 927 women aged 20-34 years who were randomly allocated to one of three groups: a fertility education chatbot (intervention group), a document about fertility and preconception health (control group 1) or a document about an irrelevant topic (control group 2). Participants' scores on the Cardiff Fertility Knowledge Scale and the State-Trait Anxiety Inventory, their intentions to optimize preconception behaviours, e.g. taking folic acid, and the free-text feedback provided by chatbot users were assessed. RESULTS: A repeated-measures analysis of variance showed significant fertility knowledge gains after the intervention in the intervention group (+9.1 points) and control group 1 (+14.9 points) but no significant change in control group 2 (+1.1 points). Post-test increases in the intentions to optimize behaviours were significantly higher in the intervention group than in control group 2, and were similar to those in control group 1. Post-test state anxiety scores were significantly lower in the intervention group than in control group 1 and control group 2. User feedbacks about the chatbot suggested technical limitations, e.g. low comprehension of users' words, and pros and cons of using the chatbot, e.g. convenient versus coldness. CONCLUSIONS: Providing fertility education using a chatbot improved fertility knowledge and intentions to optimize preconception behaviour without increasing anxiety, but the improvement in knowledge was small. Further technical development and exploration of personal affinity for technology is required.

Effective support following recurrent pregnancy loss: a randomized controlled feasibility and acceptability study.

RESEARCH QUESTION: Is it feasible to perform a future definitive trial to determine the effectiveness of the positive reappraisal coping intervention (PRCI) in improving the psychological well-being of women with recurrent pregnancy loss (RPL) during the early stages of a new pregnancy? DESIGN: This mixed method study aimed to establish the feasibility of conducting a multicentre randomized controlled trial (RCT) to definitively test the effects of the PRCI on the psychological well-being of women with RPL. Participants (n = 75) were recruited to the study and at the point of a positive pregnancy test, 47 were randomized into two study groups. The intervention group received the PRCI and weekly questionnaire assessment (Hospital Anxiety and Depression Scale and Weekly Record Keeping Form [WRK]) to monitor psychological well-being; the control group received the same questionnaires. Nested within the RCT was a qualitative process evaluation (QPE) exploring participants' subjective experience of study methods and the intervention. The study was conducted over a two-year period between 2014 and 2016. RESULTS: This study successfully gathered knowledge about the feasibility aspects of conducting a future multicentre definitive study to determine the effects of the PRCI on the psychological well-being of women with RPL. Participants were receptive to its use and the intervention appeared to convey benefits with no apparent downside. CONCLUSIONS: The study concluded that a definitive RCT of the PRCI is possible and that the model of care already has the potential to be made more widely available as a safe, low-cost, convenient and easily deliverable intervention to provide much-needed support to a vulnerable patient population.

A rapid scoping review of fear of infertility in Africa.

BACKGROUND: Fear of infertility (FOI) is often reported in studies about reproductive health but this literature not yet mapped. The aim of this rapid scoping review of qualitative studies was to describe the nature of FOI in Africa. METHODS: Eligibility criteria were qualitative data from Africa reporting views of women and men of any age. MEDLINE and CINAHL databases were searched for English language citations to February 2019 using keywords related to fear, infertility and Africa. Two independent reviewers screened texts for inclusion. RESULTS: Of 248 citations identified, 38 qualitative and six review papers were included. FOI was reported in diverse groups (e.g., men, women, fertile, infertile, married, unmarried, teachers, religious leaders). Two types of fears were identified: (1) fear of triggering infertility due to specific reproductive choices and (2) fear of the dire future consequences of infertility. Choices were perceived to affect fertility via internal accumulation and blockage (e.g., of menstrual blood), structural damage (e.g., burnt eggs), internal movement of contraceptive material, deliberate toxicity preventing population growth and behavioral effects impeding sexual activity. Diverse feared consequences of infertility were reported (e.g., polygamy, economic hardships). Fears were reported to affect reproductive behaviour (e.g., stopping contraception), help-seeking and social behaviour. CONCLUSION: FOI is a phenomenon that should be studied in its own right. Fears could originate from genuine threats, incorrect knowledge, distortions of truths, or dissemination of false information. Rigorous studies are needed to better understand FOI and integrate it in health education, client counselling and family planning service provision.

Claims of causality in health news: a randomised trial.

BACKGROUND: Misleading news claims can be detrimental to public health. We aimed to improve the alignment between causal claims and evidence, without losing news interest (counter to assumptions that news is not interested in communicating caution). METHODS: We tested two interventions in press releases, which are the main sources for science and health news: (a) aligning the headlines and main causal claims with the underlying evidence (strong for experimental, cautious for correlational) and (b) inserting explicit statements/caveats about inferring causality. The 'participants' were press releases on health-related topics (N = 312; control = 89, claim alignment = 64, causality statement = 79, both = 80) from nine press offices (journals, universities, funders). Outcomes were news content (headlines, causal claims, caveats) in English-language international and national media (newspapers, websites, broadcast; N = 2257), news uptake (% press releases gaining news coverage) and feasibility (% press releases implementing cautious statements). RESULTS: News headlines showed better alignment to evidence when press releases were aligned (intention-to-treat analysis (ITT) 56% vs 52%, OR = 1.2 to 1.9; as-treated analysis (AT) 60% vs 32%, OR = 1.3 to 4.4). News claims also followed press releases, significant only for AT (ITT 62% vs 60%, OR = 0.7 to 1.6; AT, 67% vs 39%, OR = 1.4 to 5.7). The same was true for causality statements/caveats (ITT 15% vs 10%, OR = 0.9 to 2.6; AT 20% vs 0%, OR 16 to 156). There was no evidence of lost news uptake for press releases with aligned headlines and claims (ITT 55% vs 55%, OR = 0.7 to 1.3, AT 58% vs 60%, OR = 0.7 to 1.7), or causality statements/caveats (ITT 53% vs 56%, OR = 0.8 to 1.0, AT 66% vs 52%, OR = 1.3 to 2.7). Feasibility was demonstrated by a spontaneous increase in cautious headlines, claims and caveats in press releases compared to the pre-trial period (OR = 1.01 to 2.6, 1.3 to 3.4, 1.1 to 26, respectively). CONCLUSIONS: News claims-even headlines-can become better aligned with evidence. Cautious claims and explicit caveats about correlational findings may penetrate into news without harming news interest. Findings from AT analysis are correlational and may not imply cause, although here the linking mechanism between press releases and news is known. ITT analysis was insensitive due to spontaneous adoption of interventions across conditions. TRIAL REGISTRATION: ISRCTN10492618 (20 August 2015).

How does stress, depression and anxiety affect patients undergoing treatment?

PURPOSE OF REVIEW: To review latest findings about the impact of fertility care on emotional distress and effect of distress on treatment outcome. RECENT FINDINGS: Treatment failure and long agonist protocols are associated with increased emotional distress during treatment. Screening tools can be used to identify men and women at risk of emotional maladjustment at the start of fertility treatment and people unlikely to need emotional support during or after treatment. There are inconclusive results about the association between emotional distress and outcome of fertility treatment. Systematic review of studies evaluating the effect of psychological and educational interventions on anxiety, depression and live birth (or ongoing pregnancy) are uninformative because of clinical heterogeneity and risk of bias. SUMMARY: ART is emotionally demanding, patients that adapt more poorly can be identified in advance. Fertility staff should follow good practice guidelines to provide patients with support during treatment.

Cross-Cultural Adaptation of the Cardiff Fertility Knowledge Scale and the Fertility Status Awareness Tool for the French-Canadian Population.

OBJECTIVE: The Cardiff Fertility Knowledge Scale (CFKS) and the Fertility Status Awareness Tool (FertiSTAT) are validated tools allowing the evaluation of fertility knowledge and raising awareness about risk indicators for reduced fertility. Their use by health care professionals practicing in the field of reproductive health might optimize fertility of the Canadian population. However, there currently is no version of these questionnaires for the French-Canadian population. The objective of this study was to translate and culturally adapt the CFKS and FertiSTAT to the French-Canadian population. METHODS: The translation and adaptation of the questionnaires was completed following a four-stage approach: (1) forward translation, (2) synthesis, (3) expert committee review, and (4) testing of the prefinal version of the questionnaires. The testing stage was conducted with a sample of 30 women and 10 men. RESULTS: During the translation process, linguistic difficulties were met for some items of both questionnaires but were resolved by consensus of the expert committee. Thirty women and 10 men tested the prefinal version of the CFKS-F and FertiSTAT-F. On a 5-point Likert scale, the global comprehension was 4.8 ± 0.5 and 4.6 ± 0.6, respectively. Based on the comments of the participants, the expert committee made minor modifications in the final version of the questionnaires to clarify the formulation of questions and adapt to one medical term. CONCLUSION: Tools to assess fertility knowledge and the presence of risk indicators for reduced fertility are now available for health care professionals practicing in the field of reproductive health.

Two-year follow-up of a randomized controlled trial: knowledge and reproductive outcome after online fertility education.

STUDY QUESTION: What are the long-term effects of fertility education on knowledge and reproductive outcome? SUMMARY ANSWER: Participants in the intervention group retained some knowledge after 2 years and the partnered women had a new child more quickly than the comparison group. WHAT IS KNOWN ALREADY: Fertility education improves knowledge, at least in the short-term. Attitudes toward childbearing and its timing can change after exposure to educational materials. STUDY DESIGN, SIZE, DURATION: Participants were recruited via an online social research panel. In the original randomized controlled trial (RCT), knowledge of reproductive-aged participants was assessed before (T1) and immediately after (T2) receiving one of three information brochures: fertility (intervention group), healthy pre-pregnancy (focused on intake of folic acid during pregnancy, control group 1), or family policies in Japan (childcare provision, control group 2). The present follow-up study was conducted 2 years later in January 2017 (T3) with the same participants. PARTICIPANTS/MATERIALS, SETTING, METHODS: Of the T1 participants (n = 1455), 383 men and 360 women (51%) responded to the T3 survey. Fertility knowledge measured with the Japanese version of the Cardiff Fertility Knowledge Scale (CFKS-J) and fertility status (e.g. new births, new medical consultations, and the timing of new birth) was assessed. MAIN RESULTS AND THE ROLE OF CHANCE: Baseline (T1) characteristics of the T3 participants were well balanced between groups, but T3 participants were older, married, and more educated compared to those lost to follow-up. A repeated-measures analysis of variance showed significant knowledge gains among the intervention group from T1 to T3 (11.2% and 7.0% among men and women, respectively) but no significant change over time for the control groups. There were no differences between groups in the incidence of new births or new medical consultations. However, subgroup analysis showed that timing of new births was accelerated for partnered individuals in the intervention group. Specifically, the proportion of partnered participants at T1 who had a new birth in the first year subsequent to presentation of information was higher in the intervention group versus control group 1 (folic acid): 8.8% versus 1.4% (P = 0.09) among men and 10.6% versus 2.3% (P = 0.03) among women, respectively. The odds ratios (adjusted for age) were 7.8 (95% CI: 0.86-70.7) and 5.2 (95% CI: 1.09-25.0) among men and women, respectively. The timing of births and the proportion of new births during the 2-year follow-up period in the intervention group were similar to that of control group 2 (family policy). The incidence of new medical consultation was higher in the male intervention group (12.0%) than in male control group 2 (family policy, 1.5%, P = 0.04) but similar among women in all groups. LIMITATIONS REASONS FOR CAUTION: First, the high attrition rate may limit the generalizability of these findings for longer-term acquisition of fertility knowledge, especially when applied to younger people who were more likely to be lost to follow-up. Second, this is a 2-year follow-up study and the results may change in the longer-term. Finally, we relied on self-reported questionnaire data and there is a possibility that some women were unknowingly pregnant at T1 but this risk should be distributed equally in the three groups through randomization. WIDER IMPLICATIONS OF THE FINDINGS: Effects of one-time education were limited but retained beyond baseline levels. Importantly, education was found to potentially accelerate decision-making about achieving births in partnered subgroups compared to receiving healthy pre-pregnancy information. However, this finding should be confirmed in future stratified RCTs designed to evaluate effects in these subgroups. Follow-up 'booster' education sessions might help people retain knowledge and facilitate reproductive decisions for longer. In view of the high attrition rate, especially among young populations, novel educational strategies to retain young people in fertility education cohorts should be explored. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by National Center for Child Health and Development, the Daiwa Anglo-Japanese Foundation, Pfizer Health Research Foundation, and the Japan Society for the Promotion of Science. E.M. reports joint research funds from a public interest incorporated foundation '1 more Baby Ohendan.'

Perceived challenges of working in a fertility clinic: a qualitative analysis of work stressors and difficulties working with patients.

STUDY QUESTION: What are some of the challenges of working in a fertility clinic? SUMMARY ANSWER: The most frequently mentioned challenges were workload (e.g. high time pressure) and patient-related sources (e.g. unrealistic expectations). WHAT IS KNOWN ALREADY: One study showed a too high workload, worry about handling human material and low success rates were main stressors in fertility clinics. STUDY DESIGN, SIZE, DURATION: An online open-ended survey inviting participants to respond to seven questions was distributed to 5902 members of the European Society for Human Reproduction and Embryology (ESHRE, October 2010). Questions asked participants to describe the top three factors that made (i) their work stressful (hereafter 'Work stressors') and (ii) working with patients difficult (hereafter 'Perceived sources of difficulties'), and (iii) to choose from these factors which top three issues they would be willing to attend a workshop to resolve (hereafter 'Workshops'). A qualitative content analysis using inductive coding for each question was used to extract meaningful themes from the text replies, at three levels of increasing abstraction (lower and higher categories, general themes). PARTICIPANTS/MATERIALS, SETTING, METHODS: The final sample comprised 526 respondents (8.9% participation rate). Respondents were predominantly clinicians (41.3%, n = 216) or embryologists (35.5%, n = 186) from European countries (73.0%, n = 386). MAIN RESULTS AND THE ROLE OF CHANCE: The number of text replies generated for each question was 1421, 1208 and 907 for the 'Work Stressors', 'Perceived sources of difficulties' and 'Workshop' questions, respectively. The most often reported higher-order categories of Work Stressors were 'Time and Workload' (61.6%, e.g. time pressure), 'Organisation, Team and management issues' (60.4%, e.g. team conflicts) and 'Job content and work environment' (50.3%, e.g. burdensome administration). For 'Perceived sources of difficulties' these were 'Patient-related sources' (66.7%, e.g. unrealistic expectations), 'Communication and Counselling with patients' (33.7%, e.g. strained information giving) and 'Misinformation and lack of knowledge' (27.8%, e.g. Dr Google). Finally, the topics participants would be willing to address in Workshops were 'Communicating and Counselling with Patients' (24.9%), 'Dealing with Patient-related sources' (19.6%) and 'Clinical topics' (19.6%). Three general themes emerged. First, a theme of 'time and time trade-offs' expressed the oft-mentioned need to trade-off time spent on one activity (e.g. managing patient demands) against another activity (e.g. clinical workload, administration) with stress level dependent on the efficacy of trading-off. Second, the theme of 'multifactorial causes' of challenging patient interactions that embodied the many sources of difficulties working with patients. What staff would be willing to address in workshops was indicated by the final general theme of 'a little of everything', which linked to the need for multiple workshops addressing the multifactorial nature of challenges in fertility clinics. LIMITATIONS, REASONS FOR CAUTION: Only about 10% of members receiving the survey participated. The work was limited to the stressful and difficult aspects of working in fertility clinics, which may give a more negative impression than if questions about the rewards and benefits had also been included. WIDER IMPLICATIONS OF THE FINDINGS: The nature of stressors and difficulties of working in a fertility clinic are consistent with models of occupational stress and patient complexity. Specialized psychologists, management consultants and other occupational experts could assist fertility teams in overcoming many of the challenges. More research is required on the effect of encountered work stressors and perceived sources of difficulties in working with patients on staff and patient outcomes. STUDY FUNDING/COMPETING INTERESTS: None declared.

Influences on anticipated time to ovarian cancer symptom presentation in women at increased risk compared to population risk of ovarian cancer.

BACKGROUND: In the absence of routine ovarian cancer screening, promoting help-seeking in response to ovarian symptoms is a potential route to early diagnosis. The factors influencing women's anticipated time to presentation with potential ovarian cancer symptoms were examined. METHODS: Cross-sectional questionnaires were completed by a sample of women at increased familial risk (n = 283) and population risk (n = 1043) for ovarian cancer. Measures included demographic characteristics, symptom knowledge, anticipated time to symptom presentation, and health beliefs (perceived susceptibility, worry, perceived threat, confidence in symptom detection, benefits and barriers to presentation). Structural equation modelling was used to identify determinants of anticipated time to symptomatic presentation in both groups. RESULTS: Associations between health beliefs and anticipated symptom presentation differed according to risk group. In increased risk women, high perceived susceptibility (r = .35***), ovarian cancer worry (r = .98**), perceived threat (r = -.18**), confidence (r = .16**) and perceiving more benefits than barriers to presentation (r = -.34**), were statistically significant in determining earlier anticipated presentation. The pattern was the same for population risk women, except ovarian cancer worry (r = .36) and perceived threat (r = -.03) were not statistically significant determinants. CONCLUSIONS: Associations between underlying health beliefs and anticipated presentation differed according to risk group. Women at population risk had higher symptom knowledge and anticipated presenting in shorter time frames than the increased risk sample. The cancer worry component of perceived threat was a unique predictor in the increased risk group. In increased risk women, the worry component of perceived threat may be more influential than susceptibility aspects in influencing early presentation behaviour, highlighting the need for ovarian symptom awareness interventions with tailored content to minimise cancer-related worry in this population.

Women's intentions to use fertility preservation to prevent age-related fertility decline.

The optimal age to cryopreserve oocytes for later use is before 36 years. Current users are on average 38 years old. In this cross-sectional study an online survey was constructed about the factors associated with the intentions of childless women aged 28-35 years to use fertility preservation (FP). Questions were derived from the Theory of Planned Behaviour (attitudes and subjective norms regarding FP and perceived behaviour control to do FP) and the Health Belief Model (perceived susceptibility of infertility, perceived severity of childlessness, barriers and benefits of FP and cue to use FP). Also addressed were parenthood goals, fertility knowledge and intentions to use FP within 2 years. The data were analysed using structural equation modelling. The Health Belief Model showed a good fit to the data (χ(2) [14, n = 257] = 13.63, P = 0.477; CFI = 1.000: RMSEA = 00, 90% CI [0.00-0.06]). Higher intentions to use FP were associated with feeling susceptible to infertility, considering FP useful to achieve parenthood, perceiving the implications of infertility as severe, expecting to have children at a later age and having fewer ethical concerns. This suggests an increase of fertility awareness is necessary for the optimal use of FP.

A cross sectional study on fertility knowledge in Japan, measured with the Japanese version of Cardiff Fertility Knowledge Scale (CFKS-J).

BACKGROUND: A recent survey of 79 countries showed that fertility knowledge was lower in Japan than in any other developed country. Given the fertility decline in Japan and the importance of fertility knowledge, we conducted an online survey to examine fertility knowledge and the related factors for effective public education. METHODS: We studied people aged 18-59 years old, n = 4,328 (the "General" group), and also people who had been trying to conceive for at least six months, 18-50 years old, n = 618 (the "Triers" group). Fertility knowledge was assessed using the Japanese version of the 13-item Cardiff Fertility Knowledge Scale (CFKS-J). All participants provided socio-demographic and fertility information. Participants also completed a 14-item health literacy scale and an 11-item health numeracy scale. We asked participants who were aware of age-related decline in fertility when and where they first acquired that knowledge. RESULTS: The average percentages of CFKS-J items answered correctly were 53.1% in the Triers group and 44.4% in the General group (p < 0.001). Multivariate linear regression models showed in the Triers group greater fertility knowledge was associated with greater health literacy and prior medical consultation regarding their fertility. In the General group greater fertility knowledge was associated with being female, younger, university educated, currently trying to conceive, non-smoking, having higher household income, having higher health literacy and having higher health numeracy. Of those who were aware of the age-related decline in fertility, around 3% first learned the fact "at school", and around 65% first learned it "through mass media" or "via the Internet". More than 30% of the respondents first learned it "less than 5 years before" the survey. CONCLUSIONS: Although fertility knowledge had improved since a previous study, possibly due to recent media coverage of age-related infertility, it was still low. Educational interventions, both in schools and in the community, may be needed to increase fertility knowledge in the general population because most people obtain fertility knowledge from mass media, which has been shown to often present distorted and inaccurate fertility information.