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OBJECTIVES: In vitro fertilisation (IVF) add-ons are additional procedures offered alongside an IVF cycle with the aim of improving live birth rates. They are controversial because of the paucity of evidence to support their efficacy and safety, alongside the additional financial cost they often pose to patients. Despite this, they are popular. However, there is limited qualitative research regarding their use. The aims of the VALUE Study were to understand the decision-making process surrounding using or recommending add-ons; report sources of information for add-ons; and explore concerns for safety and effectiveness when considering their use. DESIGN: 'VALUE' is a qualitative semistructured interview study using inductive thematic analysis of anonymised transcriptions. SETTING: Participants were recruited from a broad geographical spread across the UK and Australia from public and private clinical settings. PARTICIPANTS: Patients (n=25) and health professionals (embryologists (n=25) and clinicians (n=24)) were interviewed. A purposive sampling strategy was undertaken. The sampling framework included people having state-subsidised and private cycles, professionals working in public and private sectors, geographical location and professionals of all grades. RESULTS: Patients often made decisions about add-ons based on hope, minimising considerations of safety, efficacy or cost, whereas professionals sought the best outcomes for their patients and wanted to avoid them wasting their money. The driving forces behind add-on use differed: for patients, a professional opinion was the most influential reason, whereas for professionals, it was seen as patient driven. For both groups, applying the available evidence to individual circumstances was very challenging, especially in the sphere of IVF medicine, where the stakes are high. CONCLUSIONS: There is scope to build on the quality of the discourse between patients and professionals. Patients describe valuing their autonom

STUDY QUESTION: We aim to develop, disseminate and implement a minimum data set, known as a core outcome set, for future male infertility research. WHAT IS KNOWN ALREADY: Research into male infertility can be challenging to design, conduct and report. Evidence from randomized trials can be difficult to interpret and of limited ability to inform clinical practice for numerous reasons. These may include complex issues, such as variation in outcome measures and outcome reporting bias, as well as failure to consider the perspectives of men and their partners with lived experience of fertility problems. Previously, the Core Outcome Measure for Infertility Trials (COMMIT) initiative, an international consortium of researchers, healthcare professionals and people with fertility problems, has developed a core outcome set for general infertility research. Now, a bespoke core outcome set for male infertility is required to address the unique challenges pertinent to male infertility research. STUDY DESIGN SIZE DURATION: Stakeholders, including healthcare professionals, allied healthcare professionals, scientists, researchers and people with fertility problems, will be invited to participate. Formal consensus science methods will be used, including the modified Delphi method, modified Nominal Group Technique and the National Institutes of Health's consensus development conference. PARTICIPANTS/MATERIALS SETTING METHODS: An international steering group, including the relevant stakeholders outlined above, has been established to guide the development of this core outcome set. Possible core outcomes will be identified by undertaking a systematic review of randomized controlled trials evaluating potential treatments for male factor infertility. These outcomes will be entered into a modified Delphi method. Repeated reflection and re-scoring should promote convergence towards consensus outcomes, which will be prioritized during a consensus development meeting to identify a final core

STUDY QUESTION: Can consensus definitions for the core outcome set for infertility be identified in order to recommend a standardized approach to reporting? SUMMARY ANSWER: Consensus definitions for individual core outcomes, contextual statements, and a standardized reporting table have been developed. WHAT IS KNOWN ALREADY: Different definitions exist for individual core outcomes for infertility. This variation increases the opportunities for researchers to engage with selective outcome reporting, which undermines secondary research and compromises clinical practice guideline development. STUDY DESIGN, SIZE, DURATION: Potential definitions were identified by a systematic review of definition development initiatives and clinical practice guidelines and by reviewing Cochrane Gynaecology and Fertility Group guidelines. These definitions were discussed in a face-to-face consensus development meeting, which agreed consensus definitions. A standardized approach to reporting was also developed as part of the process. PARTICIPANTS/MATERIALS, SETTING, METHODS: Healthcare professionals, researchers, and people with fertility problems were brought together in an open and transparent process using formal consensus development methods. MAIN RESULTS AND THE ROLE OF CHANCE: Forty-four potential definitions were inventoried across four definition development initiatives, including the Harbin Consensus Conference Workshop Group and International Committee for Monitoring Assisted Reproductive Technologies, 12 clinical practice guidelines, and Cochrane Gynaecology and Fertility Group guidelines. Twenty-seven participants, from 11 countries, contributed to the consensus development meeting. Consensus definitions were successfully developed for all core outcomes. Specific recommendations were made to improve reporting. LIMITATIONS, REASONS FOR CAUTION: We used consensus development methods, which have inherent limitations. There was limited representation from low- and middle-income co

INTRODUCTION: For couples undergoing assisted reproduction, a plethora of adjuncts are available; these are known as 'add-ons'. Most add-ons are not supported by good quality randomised trial evidence of efficacy, with some proven to be ineffective. However, estimates suggest that over 70% of fertility clinics provide at least one add-on, often at extra cost to the patient. This study has three aims. First, to undertake a survey of in vitro fertilisation (IVF) clinics in the UK to ascertain which add-ons are being offered and at what cost. Second, to undertake qualitative semi-structured interviews of patients, clinicians and embryologists, to explore their opinions and beliefs surrounding add-ons. Third, to review the interpretation of the Human Fertilisation and Embryology Authority traffic light system, to better understand the information required by IVF patients, clinicians and embryologists when making decisions about add-ons. METHODS AND ANALYSIS: All UK IVF clinics will be contacted by email and invited to complete an online survey. The survey will ask them which add-ons they offer, at what cost per cycle and how information is shared with patients. Semi-structured interviews will be conducted in the UK and Australia with three groups of participants: (i) fertility patients; (ii) clinicians and (iii) embryologists. Participants for the interviews will be recruited via social media channels, website adverts, email and snowball sampling. Up to 20 participants will be recruited for each group in each country. Following an online consent process, interviews will be conducted via video-conferencing software, transcribed verbatim and data subjected to inductive thematic analysis. ETHICS AND DISSEMINATION: Ethical approval has been granted by the Universities of Sheffield, Bath Spa and Melbourne. Findings will be published in a peer-reviewed journal and disseminated to regulatory bodies in the UK and Australia. A lay summary of findings will be shared via Fertility

Multiple embryo transfer (MET) is associated with both an increased risk of multiple pregnancy and of live birth. In recent years, MET has become standard practice for most surrogacy arrangements. There is limited review of the use of MET versus single embryo transfer (SET) in surrogacy practice. The present review systematically evaluated the pregnancy outcomes of surrogacy arrangements between MET versus SET among gestational carriers. A systematic search of five computerized databases without restriction to the English language or study type was conducted to evaluate the primary outcomes: (i) clinical pregnancy; (ii) live delivery; and (iii) multiple delivery rates. The search returned 97 articles, five of which met the inclusion criteria. The results showed that clinical pregnancy (RR = 1.21, 95% CI: 1.06-1.39, n = 5, I2 = 41%), live delivery (RR = 1.29, 95% CI: 1.10-1.51, n = 4, I2 = 35%) and multiple delivery rates (RR = 1.42, 95% CI: 6.58-69.73, n = 4, I2 = 54%) were statistically significantly different in MET compared to SET. Adverse events including miscarriage, preterm birth and low birthweight were found following MET. Our findings support the existing evidence that MET results in multiple pregnancy and subsequently more adverse outcomes compared to SET. From a public health perspective, SET should be advocated as the preferred treatment for gestational carriers.

Study Question: Can a core outcome set to standardize outcome selection, collection, and reporting across future infertility research be developed? Summary Answer: A minimum data set, known as a core outcome set, has been developed for randomized controlled trials (RCT) and systematic reviews evaluating potential treatments for infertility. What is Known Already: Complex issues, including a failure to consider the perspectives of people with fertility problems when selecting outcomes, variations in outcome definitions, and the selective reporting of outcomes on the basis of statistical analysis, make the results of infertility research difficult to interpret. Study Design, Size, Duration: A three-round Delphi survey (372 participants from 41 countries) and consensus development workshop (30 participants from 27 countries). Participants/Materials, Setting, Methods: Healthcare professionals, researchers, and people with fertility problems were brought together in an open and transparent process using formal consensus science methods. Main Results and the Role of Chance:The core outcome set consists of: viable intrauterine pregnancy confirmed by ultrasound (accounting for singleton, twin, and higher multiple pregnancy); pregnancy loss (accounting for ectopic pregnancy, miscarriage, stillbirth, and termination of pregnancy); live birth; gestational age at delivery; birthweight; neonatal mortality; and major congenital anomaly. Time to pregnancy leading to live birth should be reported when applicable. Limitations, Reasons for Caution: We used consensus development methods which have inherent limitations, including the representativeness of the participant sample, Delphi survey attrition, and an arbitrary consensus threshold. Wider Implications of the Findings: Embedding the core outcome set within RCTs and systematic reviews should ensure the comprehensive selection, collection, and reporting of core outcomes. Research funding bodies, the Standard Protocol Items: Recomm

STUDY QUESTION: Can a core outcome set to standardize outcome selection, collection and reporting across future infertility research be developed? SUMMARY ANSWER: A minimum data set, known as a core outcome set, has been developed for randomized controlled trials (RCTs) and systematic reviews evaluating potential treatments for infertility. WHAT IS KNOWN ALREADY: Complex issues, including a failure to consider the perspectives of people with fertility problems when selecting outcomes, variations in outcome definitions and the selective reporting of outcomes on the basis of statistical analysis, make the results of infertility research difficult to interpret. STUDY DESIGN, SIZE, DURATION: A three-round Delphi survey (372 participants from 41 countries) and consensus development workshop (30 participants from 27 countries). PARTICIPANTS/MATERIALS, SETTING, METHODS: Healthcare professionals, researchers and people with fertility problems were brought together in an open and transparent process using formal consensus science methods. MAIN RESULTS AND THE ROLE OF CHANCE: The core outcome set consists of: viable intrauterine pregnancy confirmed by ultrasound (accounting for singleton, twin and higher multiple pregnancy); pregnancy loss (accounting for ectopic pregnancy, miscarriage, stillbirth and termination of pregnancy); live birth; gestational age at delivery; birthweight; neonatal mortality; and major congenital anomaly. Time to pregnancy leading to live birth should be reported when applicable. LIMITATIONS, REASONS FOR CAUTION: We used consensus development methods which have inherent limitations, including the representativeness of the participant sample, Delphi survey attrition and an arbitrary consensus threshold. WIDER IMPLICATIONS OF THE FINDINGS: Embedding the core outcome set within RCTs and systematic reviews should ensure the comprehensive selection, collection and reporting of core outcomes. Research funding bodies, the Standard Protocol Items: Recommendat

STUDY QUESTIONS: In couples with unexplained infertility and a poor prognosis of natural conception, are four cycles of IUI with ovarian stimulation (IUI-OS) non-inferior to one completed cycle of IVF for the outcome of cumulative live birth? Are four cycles of IUI-OS associated with a lower cost per live birth compared to one completed cycle of IVF? Will four cycles of IUI-OS followed by one complete cycle of IVF result in as many live births at lower cost per live birth, than two complete cycles of IVF? Will four cycles of IUI-OS followed by two complete cycles of IVF result in more live births at lower cost per live birth, than two complete cycles of IVF alone? WHAT IS KNOWN ALREADY: IUI is widely used in the USA, the UK and Europe as a low cost, less invasive alternative to IVF for couples with unexplained infertility. Although three to six cycles of IUI were comparable to IVF in the three major studies carried out to date, gonadotrophin ovarian stimulation was used in the majority of cases, and this also resulted in a high multiple pregnancy rate in some studies. Ovarian stimulation with clomiphene citrate is known to have lower multiple pregnancy rates. STUDY DESIGN SIZE DURATION: The FIIX study is a multicentre, open label, parallel, pragmatic non-inferiority randomized controlled trial of 580 couples with unexplained infertility comparing four cycles of IUI-OS with clomiphene citrate and one completed cycle of IVF. Variable block randomization stratified by age and clinic with electronic allocation will be used. PARTICIPANTS/MATERIALS SETTING METHODS: Couples with poor prognosis for natural conception and who are eligible for publicly funded fertility treatment in six fertility clinics in New Zealand. STUDY FUNDING/COMPETING INTERESTS: Auckland Medical Research Fund (3718892/1119003), A+ Trust, Auckland District Health Board (A + 8479), Maurice and Phyllis Paykel Trust (3718514). No competing interests. TRIAL REGISTRATION NUMBER: ACTRN12619001003167. TRIAL R

STUDY QUESTION: Can the priorities for future research in infertility be identified? SUMMARY ANSWER: The top 10 research priorities for the four areas of male infertility, female and unexplained infertility, medically assisted reproduction and ethics, access and organization of care for people with fertility problems were identified. WHAT IS KNOWN ALREADY: Many fundamental questions regarding the prevention, management and consequences of infertility remain unanswered. This is a barrier to improving the care received by those people with fertility problems. STUDY DESIGN, SIZE, DURATION: Potential research questions were collated from an initial international survey, a systematic review of clinical practice guidelines and Cochrane systematic reviews. A rationalized list of confirmed research uncertainties was prioritized in an interim international survey. Prioritized research uncertainties were discussed during a consensus development meeting. Using a formal consensus development method, the modified nominal group technique, diverse stakeholders identified the top 10 research priorities for each of the categories male infertility, female and unexplained infertility, medically assisted reproduction and ethics, access and organization of care. PARTICIPANTS/MATERIALS, SETTING, METHODS: Healthcare professionals, people with fertility problems and others (healthcare funders, healthcare providers, healthcare regulators, research funding bodies and researchers) were brought together in an open and transparent process using formal consensus methods advocated by the James Lind Alliance. MAIN RESULTS AND THE ROLE OF CHANCE: The initial survey was completed by 388 participants from 40 countries, and 423 potential research questions were submitted. Fourteen clinical practice guidelines and 162 Cochrane systematic reviews identified a further 236 potential research questions. A rationalized list of 231 confirmed research uncertainties was entered into an interim prioritization s

STUDY QUESTION: Can consensus definitions for the core outcome set for infertility be identified in order to recommend a standardized approach to reporting? SUMMARY ANSWER: Consensus definitions for individual core outcomes, contextual statements and a standardized reporting table have been developed. WHAT IS KNOWN ALREADY: Different definitions exist for individual core outcomes for infertility. This variation increases the opportunities for researchers to engage with selective outcome reporting, which undermines secondary research and compromises clinical practice guideline development. STUDY DESIGN, SIZE, DURATION: Potential definitions were identified by a systematic review of definition development initiatives and clinical practice guidelines and by reviewing Cochrane Gynaecology and Fertility Group guidelines. These definitions were discussed in a face-to-face consensus development meeting, which agreed consensus definitions. A standardized approach to reporting was also developed as part of the process. PARTICIPANTS/MATERIALS, SETTING, METHODS: Healthcare professionals, researchers and people with fertility problems were brought together in an open and transparent process using formal consensus development methods. MAIN RESULTS AND THE ROLE OF CHANCE: Forty-four potential definitions were inventoried across four definition development initiatives, including the Harbin Consensus Conference Workshop Group and International Committee for Monitoring Assisted Reproductive Technologies, 12 clinical practice guidelines and Cochrane Gynaecology and Fertility Group guidelines. Twenty-seven participants, from 11 countries, contributed to the consensus development meeting. Consensus definitions were successfully developed for all core outcomes. Specific recommendations were made to improve reporting. LIMITATIONS, REASONS FOR CAUTION: We used consensus development methods, which have inherent limitations. There was limited representation from low- and middle-income count

© 2019 Author(s). Introduction Social egg freezing is storing egg for the purpose of preserving fertility and delayed childbearing. Currently, little is known about the utilisation and effectiveness of this approach. This review aims to determine (1) the proportion of women who used their stored eggs, and (2) the egg survival rate through vitrification, and the clinical pregnancy rate and live birth rate per 100 women partaking in the procedure, and among women who stored their eggs for medical reasons. Methods and analyses This systematic review will be done according to the items listed in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. PubMed, Embase, Scopus, The Cumulative Index to Nursing and Allied Health Literature (CINAHL) and the Cochrane Library and Health Technology Assessment databases will be searched to identify eligible studies published since 2012. Two reviewers will independently appraise the eligibility and quality of the studies based on preset checklists and extract the data using a data extraction template. Outcomes of interest are proportion of women who used their stored eggs, egg survival rate, pregnancy rate and live birth rates. We will determine the presence heterogeneity among studies using the Cochrane's Q test. The percentage of total variation across studies, which is due to statistical heterogeneity, will be calculated using the I 2 statistics. Outcomes of interest will be pooled together using metaprop programme STATA V.14. Ethics and dissemination For this review, ethical committee approval is not required. We will use publically available data from previously published studies. The final report of the review will be disseminated through publication on national or international journal, and it will be presented on different scientific conferences.

STUDY QUESTIONS: We aim to produce, disseminate and implement a core outcome set for future infertility research. WHAT IS KNOWN ALREADY: Randomized controlled trials (RCTs) evaluating infertility treatments have reported many different outcomes, which are often defined and measured in different ways. Such variation contributes to an inability to compare, contrast and combine results of individual RCTs. The development of a core outcome set will ensure outcomes important to key stakeholders are consistently collected and reported across future infertility research. STUDY DESIGN SIZE DURATION: This is a consensus study using the modified Delphi method. All stakeholders, including healthcare professionals, allied healthcare professionals, researchers and people with lived experience of infertility will be invited to participate. PARTICIPANTS/MATERIALS SETTING METHODS: An international steering group, including people with lived experience of infertility, healthcare professionals, allied healthcare professionals and researchers, has been formed to guide the development of this core outcome set. Potential core outcomes have been identified through a comprehensive literature review of RCTs evaluating treatments for infertility and will be entered into a modified Delphi method. Participants will be asked to score potential core outcomes on a nine-point Likert scale anchored between one (not important) and nine (critical). Repeated reflection and rescoring should promote convergence towards consensus 'core' outcomes. We will establish standardized definitions and recommend high-quality measurement instruments for individual core outcomes. STUDY FUNDING/COMPETING INTERESTS: This project is funded by the Royal Society of New Zealand Catalyst Fund (3712235). BWM reports consultancy fees from Guerbet, Merck, and ObsEva. R.S.L. reports consultancy fees from Abbvie, Bayer, Fractyl and Ogeda and research sponsorship from Ferring. S.B. is the Editor-in-Chief of Human Reproduction O

Background: There is a need to have uniformed reporting of perinatal mortality for births following assisted reproductive technology (ART) treatment to enable international comparison and benchmarking of ART practice.Methods: The Australian and New Zealand Assisted Reproduction Database was used in this study. Births of ≥ 20 weeks gestation and/or ≥ 400 grams of birth weight following embryos transfer cycles in Australia and New Zealand during the period 2004 to 2008 were included. Differences in the mortality rates by different perinatal periods from a gestational age cutoff of ≥ 20, ≥ 22, ≥ 24, or ≥ 28 weeks (wks) to a neonatal period cutoff of either < 7 or < 28 days after birth were assessed. Crude and specific (number of embryos transferred and plurality) rates of perinatal mortality were calculated for selected gestational and neonatal periods.Results: When the perinatal period is defined as ≥ 20 wks gestation to < 28 days after birth, the perinatal mortality rate (PMR) was 16.1 per 1000 births (n = 630). A progressive contraction of the gestational age groups resulted in marked reductions in the PMR for deaths at < 28 days (22 wks 11.0; 24 wks 7.7; 28 wks 5.6); and similarly for deaths at < 7 days (20 wks 15.6, 22 wks 10.5; 24 wks 7.3; 28 wks 5.3). In contrast, a contraction of the perinatal period from < 28 to < 7 days after birth only marginally reduced the PMR from 16.2 to 15.6 per 1000 births which was consistent across all gestational ages.The PMR for single embryo transfer (SET) births (≥ 20 weeks gestation to < 7 days post-birth) was significantly lower (12.8 per 1000 SET births) compared to double embryo transfer (DET) births (PMR 18.3 per 1000 DET births; p < 0.001, Fisher's Exact Test). Similarly, the PMR for SET births (≥ 22 weeks gestation to < 7 days post-birth) was significantly lower (8.8 per 1000 SET births, p < 0.001, Fisher's Exact Test) when compared to DET births (12.2 per 1000 DET births). The highest PMR (50.5 per 1000 SET births, 95% CI