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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 countries. WIDER IMPLICATIONS OF THE FINDINGS A minimum data set should assist researchers in populating protocols, case report forms and other data collection tools. The generic reporting table should provide clear guidance to researchers and improve the reporting of their results within journal publications and conference presentations. Research funding bodies, the Standard Protocol Items: Recommendations for Interventional Trials statement, and over 80 specialty journals have committed to implementing this core outcome set. STUDY FUNDING/COMPETING INTEREST(S) This research was funded by the Catalyst Fund, Royal Society of New Zealand, Auckland Medical Research Fund and Maurice and Phyllis Paykel Trust. Siladitya Bhattacharya reports being the Editor-in-Chief of Human Reproduction Open and an editor of the Cochrane Gynaecology and Fertility Group. J.L.H.E. reports being the Editor Emeritus of Human Reproduction. R.S.L. reports consultancy fees from Abbvie, Bayer, Ferring, Fractyl, Insud Pharma and Kindex and research sponsorship from Guerbet and Hass Avocado Board. B.W.M. reports consultancy fees from Guerbet, iGenomix, Merck, Merck KGaA and ObsEva. C.N. reports being the Editor-in-Chief of Fertility and Sterility and Section Editor of the Journal of Urology, research sponsorship from Ferring, and a financial interest in NexHand. E.H.Y.N. reports research sponsorship from Merck. A.S. reports consultancy fees from Guerbet. J.W. reports being a statistical editor for the Cochrane Gynaecology and Fertility Group. A.V. reports that he is a Statistical Editor of the Cochrane Gynaecology & Fertility Review Group and of the journal Reproduction. His employing institution has received payment from Human Fertilisation and Embryology Authority for his advice on review of research evidence to inform their ‘traffic light’ system for infertility treatment ‘add-ons’. N.L.V. reports consultancy and conference fees from Ferring, Merck and Merck Sharp and Dohme. The remaining authors declare no competing interests in relation to the work presented. All authors have completed the disclosure form. TRIAL REGISTRATION NUMBER Core Outcome Measures in Effectiveness Trials Initiative: 1023.

BACKGROUND Ultrasound-guided embryo transfer (US-GET) is a widely performed procedure, but standards for the best practice are not available. OBJECTIVE AND RATIONALE This document aims to provide an overview of technical aspects of US-GET after considering the published data and including the preparation for the embryo transfer (ET) procedure, the actual procedure, the post-procedure care, associated pathologies, complications and risks, quality assurance and practitioners’ performance. SEARCH METHODS A literature search for evidence on key aspects of the ET procedure was carried out from database inception to November 2021. Selected papers (n = 359) relevant to the topic were analysed by the authors. The following key points were considered in the papers: whether ultrasound (US) practice standards were explained, to what extent the ET technique was described and whether complications or incidents and how to prevent such events were reported. In the end, 89 papers could be used to support the recommendations in this document, which focused on transabdominal US-GET. OUTCOMES The relevant papers found in the literature search were included in the current document and described according to the topic in three main sections: requirements and preparations prior to ET, the ET procedure and training and competence for ET. Recommendations are provided on preparations prior to ET, equipment and materials, ET technique, possible risks and complications, training and competence. Specific aspects of the laboratory procedures are covered, in particular the different loading techniques and their potential impact on the final outcomes. Potential future developments and research priorities regarding the ET technique are also outlined. LIMITATIONS, REASONS FOR CAUTION Many topics were not covered in the literature review and some recommendations were based on expert opinions and are not necessarily evidence based. WIDER IMPLICATIONS ET is the last procedural step in an ART treatment and is a crucial step towards achieving a pregnancy and live birth. The current paper set out to bring together the recent developments considering all aspects of ET, especially emphasizing US quality imaging. There are still many questions needing answers, and these can be subject of future research. STUDY FUNDING/COMPETING INTEREST(S) No funding. A.D.A. has received royalties from CRC Press and personal honorarium from Cook, Ferring and Cooper Surgical. The other co-authors have no conflicts of interest to declare that are relevant to the content of this article.

Study question What are the risks of oocyte donation? Which risks should be prioritised in policies aiming to improve the protection of third-party oocyte donors? Summary answer The risks for third-party oocyte donors are of a diverse nature, including physical risks, psychological risks, iatrogenic risks, and social risks. What is known already Oocyte donation involves ovarian stimulation and oocyte pick-up, which represent burdensome procedures for the donor. In a recent evaluation of the EU legislation on blood, tissue and cells, the European Commission highlighted that oocyte donors are currently not adequately protected. For effective oocyte donor protection measures to be developed and implemented, it is important to understand the risks that oocyte donors are exposed to. To date, there is no comprehensive overview of the existing knowledge on the physical and psychosocial risks of oocyte donation. Study design, size, duration A systematic literature review of the publications on PubMed, CINAHL, PsycINFO and the Notify Library was carried out. The search was conducted in May 2020. All empirical studies, including case reports, that reported or investigated negative experiences of oocyte donors and/or negative consequences of the donation on the donors’ physical health, mental health, or other aspects of their lives were included. No restriction was made with regard to the year of publication. Participants/materials, setting, methods In total, 88 empirical studies conducted in oocyte donors were reviewed. All reported information on oocyte donor risks was extracted and summarised. The identified risks were clustered into categories according to common themes and analysed with regard to their frequency of occurrence, severity, and imputability to the donation. A prioritisation of risks was carried out based on these three criteria, classifying each risk as a “priority risk” or a “non-priority risk”. Main results and the role of chance Nineteen priority risks were identified across the following six categories: short-term physical risks, long-term physical risks, short-term psychological risks, long-term psychological risks, iatrogenic risks, and social risks. The most frequently reported priority risks were moderate to severe Ovarian Hyperstimulation Syndrome (OHSS) and having lasting worries or concerns about the donation. While the findings confirmed the relevance of certain immediate physical risks for oocyte donors, no cases of death or permanent physical damage as a direct consequence of the donation could be detected. The results showed that donating oocytes can profoundly impact the donors’ psychological well-being in the short-term and in the long-term. Furthermore, the donation can have a strong effect on the donor’s social and family life, for instance, through the risk of unintended pregnancy. Moreover, it was found that oocyte donors are at risk of experiencing mistreatment or inadequate care during the donation procedure. Most studies included in the review reported on short-term risks of the donation. There is a high degree of uncertainty about the long-term health effects of oocyte donation. Due to the scarcity of large observational studies, the conclusions are mostly based on small studies and case reports, which limits the strength of any conclusion. Limitations, reasons for caution The literature search was limited to common databases for published data. Grey literature was not searched. Due to the heterogeneous nature of the relevant publications, it is possible that the search strategy was not able to detect all eligible articles. Wider implications of the findings: The findings emphasise the importance of implementing effective donor protection policies that address not only the physical, but also the psychological, social, and iatrogenic risks of oocyte donation. Moreover, the findings call for a systematic follow-up of oocyte donors to gain insight into the long-term consequences of the donation. Trial registration number Not applicable

STUDY QUESTION Is it possible to define a set of performance indicators (PIs) for clinical work in ART, which can create competency profiles for clinicians and for specific clinical process steps? SUMMARY ANSWER The current paper recommends six PIs to be used for monitoring clinical work in ovarian stimulation for ART, embryo transfer, and pregnancy achievement: cycle cancellation rate (before oocyte pick-up (OPU)) (%CCR), rate of cycles with moderate/severe ovarian hyperstimulation syndrome (OHSS) (%mosOHSS), the proportion of mature (MII) oocytes at ICSI (%MII), complication rate after OPU (%CoOPU), clinical pregnancy rate (%CPR), and multiple pregnancy rate (%MPR). WHAT IS KNOWN ALREADY PIs are objective measures for evaluating critical healthcare domains. In 2017, ART laboratory key PIs (KPIs) were defined. STUDY DESIGN, SIZE, DURATION A list of possible indicators was defined by a working group. The value and limitations of each indicator were confirmed through assessing published data and acceptability was evaluated through an online survey among members of ESHRE, mostly clinicians, of the special interest group Reproductive Endocrinology. PARTICIPANTS/MATERIALS, SETTING, METHODS The online survey was open for 5 weeks and 222 replies were received. Statements (indicators, indicator definitions, or general statements) were considered accepted when ≥70% of the responders agreed (agreed or strongly agreed). There was only one round to seek levels of agreement between the stakeholders. Indicators that were accepted by the survey responders were included in the final list of indicators. Statements reaching less than 70% were not included in the final list but were discussed in the paper. MAIN RESULTS AND THE ROLE OF CHANCE Cycle cancellation rate (before OPU) and the rate of cycles with moderate/severe OHSS, calculated on the number of started cycles, were defined as relevant PIs for monitoring ovarian stimulation. For monitoring ovarian response, trigger and OPU, the proportion of MII oocytes at ICSI and complication rate after OPU were listed as PIs: the latter PI was defined as the number of complications (any) that require an (additional) medical intervention or hospital admission (apart from OHSS) over the number of OPUs performed. Finally, clinical pregnancy rate and multiple pregnancy rate were considered relevant PIs for embryo transfer and pregnancy. The defined PIs should be calculated every 6 months or per 100 cycles, whichever comes first. Clinical pregnancy rate and multiple pregnancy rate should be monitored more frequently (every 3 months or per 50 cycles). Live birth rate (LBR) is a generally accepted and an important parameter for measuring ART success. However, LBR is affected by many factors, even apart from ART, and it cannot be adequately used to monitor clinical practice. In addition to monitoring performance in general, PIs are essential for managing the performance of staff over time, and more specifically the gap between expected performance and actual performance measured. Individual clinics should determine which indicators are key to the success in their organisation based on their patient population, protocols, and procedures, and as such, which are their KPIs. LIMITATIONS, REASONS FOR CAUTION The consensus values are based on data found in the literature and suggestions of experts. When calculated and compared to the competence/benchmark limits, prudent interpretation is necessary taking into account the specific clinical practice of each individual centre. WIDER IMPLICATIONS OF THE FINDINGS The defined PIs complement the earlier defined indicators for the ART laboratory. Together, both sets of indicators aim to enhance the overall quality of the ART practice and are an essential part of the total quality management. PIs are important for education and can be applied during clinical subspecialty. STUDY FUNDING/COMPETING INTEREST(S) This paper was developed and funded by ESHRE, covering expenses associated with meetings, literature searches, and dissemination. The writing group members did not receive payment. Dr G.G. reports personal fees from Merck, MSD, Ferring, Theramex, Finox, Gedeon-Richter, Abbott, Biosilu, ReprodWissen, Obseva, PregLem, and Guerbet, outside the submitted work. Dr A.D. reports personal fees from Cook, outside the submitted work; Dr S.A. reports starting a new employment in May 2020 at Vitrolife. Previously, she has been part of the Nordic Embryology Academic Team, with meetings were sponsored by Gedeon Richter. The other authors have no conflicts of interest to declare. DISCLAIMER This document represents the views of ESHRE, which are the result of consensus between the relevant ESHRE stakeholders and where relevant based on the scientific evidence available at the time of preparation. The recommendations should be used for informational and educational purposes. They should not be interpreted as setting a standard of care, or be deemed inclusive of all proper methods of care nor exclusive of other methods of care reasonably directed to obtaining the same results. They do not replace the need for application of clinical judgment to each individual presentation, nor variations based on locality and facility type. Furthermore, ESHREs recommendations do not constitute or imply the endorsement, recommendation, or favouring of any of the included technologies by ESHRE.

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 survey completed by 317 respondents from 43 countries. The top 10 research priorities for each of the four categories male infertility, female and unexplained infertility (including age-related infertility, ovarian cysts, uterine cavity abnormalities and tubal factor infertility), medically assisted reproduction (including ovarian stimulation, IUI and IVF) and ethics, access and organization of care were identified during a consensus development meeting involving 41 participants from 11 countries. These research priorities were diverse and seek answers to questions regarding prevention, treatment and the longer-term impact of infertility. They highlight the importance of pursuing research which has often been overlooked, including addressing the emotional and psychological impact of infertility, improving access to fertility treatment, particularly in lower resource settings and securing appropriate regulation. Addressing these priorities will require diverse research methodologies, including laboratory-based science, qualitative and quantitative research and population science. LIMITATIONS, REASONS FOR CAUTION We used consensus development methods, which have inherent limitations, including the representativeness of the participant sample, methodological decisions informed by professional judgment and arbitrary consensus definitions. WIDER IMPLICATIONS OF THE FINDINGS We anticipate that identified research priorities, developed to specifically highlight the most pressing clinical needs as perceived by healthcare professionals, people with fertility problems and others, will help research funding organizations and researchers to develop their future research agenda. STUDY FUNDING/COMPETING INTEREST(S) The study was funded by the Auckland Medical Research Foundation, Catalyst Fund, Royal Society of New Zealand and Maurice and Phyllis Paykel Trust. G.D.A. reports research sponsorship from Abbott, personal fees from Abbott and LabCorp, a financial interest in Advanced Reproductive Care, committee membership of the FIGO Committee on Reproductive Medicine, International Committee for Monitoring Assisted Reproductive Technologies, International Federation of Fertility Societies and World Endometriosis Research Foundation, and research sponsorship of the International Committee for Monitoring Assisted Reproductive Technologies from Abbott and Ferring. Siladitya Bhattacharya reports being the Editor-in-Chief of Human Reproduction Open and editor for the Cochrane Gynaecology and Fertility Group. J.L.H.E. reports being the Editor Emeritus of Human Reproduction. A.W.H. reports research sponsorship from the Chief Scientist’s Office, Ferring, Medical Research Council, National Institute for Health Research and Wellbeing of Women and consultancy fees from AbbVie, Ferring, Nordic Pharma and Roche Diagnostics. M.L.H. reports grants from Merck, grants from Myovant, grants from Bayer, outside the submitted work and ownership in Embrace Fertility, a private fertility company. N.P.J. reports research sponsorship from AbbVie and Myovant Sciences and consultancy fees from Guerbet, Myovant Sciences, Roche Diagnostics and Vifor Pharma. J.M.L.K. reports research sponsorship from Ferring and Theramex. R.S.L. reports consultancy fees from AbbVie, Bayer, Ferring, Fractyl, Insud Pharma and Kindex and research sponsorship from Guerbet and Hass Avocado Board. B.W.M. reports consultancy fees from Guerbet, iGenomix, Merck, Merck KGaA and ObsEva. E.H.Y.N. reports research sponsorship from Merck. C.N. reports being the Co Editor-in-Chief of Fertility and Sterility and Section Editor of the Journal of Urology, research sponsorship from Ferring and retains a financial interest in NexHand. J.S. reports being employed by a National Health Service fertility clinic, consultancy fees from Merck for educational events, sponsorship to attend a fertility conference from Ferring and being a clinical subeditor of Human Fertility. A.S. reports consultancy fees from Guerbet. J.W. reports being a statistical editor for the Cochrane Gynaecology and Fertility Group. A.V. reports that he is a Statistical Editor of the Cochrane Gynaecology & Fertility Review Group and the journal Reproduction. His employing institution has received payment from Human Fertilisation and Embryology Authority for his advice on review of research evidence to inform their ‘traffic light’ system for infertility treatment ‘add-ons’. N.L.V. reports consultancy and conference fees from Ferring, Merck and Merck Sharp and Dohme. The remaining authors declare no competing interests in relation to the present work. All authors have completed the disclosure form. TRIAL REGISTRATION NUMBER N/A.

STUDY QUESTION To evaluate the implementation of the coding systems in medically assisted reproduction (MAR) centres in the European Union (EU). SUMMARY ANSWER Our data show that a significant number of MAR centres use the Single European Code (SEC), but it also shows certain limitations to the coding. WHAT IS KNOWN ALREADY Traceability and identification of tissue and cells used for clinical application are extremely important as it is one of the key aspects of quality and safety both for the donors and the recipients. Patients as well as tissues and cells move across the European continent and far beyond, hence a uniform coding system was very much needed. The coding of tissues and cells from human origin was already embedded in the EU directives 2004/23/EC. The use of the Single European Code (SEC) on tissues and cells was enforced in 2017 for tissues and cells distributed within the EU or exported from the EU. The SEC ensures standardization within the EU, allowing the integration of the two existing codes (ISBT-128 and Eurocode) within the SEC structure. Likewise, in the MAR field, the SEC was launched in order to ensure the traceability of reproductive tissues and cells. Gametes and embryos from partner donation as well as reproductive cells and tissues of allogeneic donation were excluded from the SEC as long as they remain in the centre of origin. STUDY DESIGN, SIZE, DURATION A cross-sectional survey aimed to gain insight into the use of SEC by MAR centres was conducted between 5 November and 15 December 2018. PARTICIPANTS/MATERIALS, SETTING, METHODS The online survey was distributed among the ESHRE members. MAIN RESULTS AND THE ROLE OF CHANCE The survey results highlight the strengths and weaknesses in the practical use of the SEC. The data from the survey showed that the SEC code is something that is known in the MAR field. Our data showed that over half of the respondents were using the SEC in their centre. On the other hand, there is also criticism about the use of SEC in MAR, especially that the added value for traceability and identification in ART is found to be rather limited. LIMITATIONS, REASONS FOR CAUTION The survey response rate was rather low (4.84%). The view of the use of SEC discussed in this paper still provides insight into the use of the SEC in several MAR centres. WIDER IMPLICATIONS OF THE FINDINGS The survey highlights some knowledge gaps concerning coding. This information can be used to develop tools to increase knowledge of the SEC. STUDY FUNDING/COMPETING INTEREST(S) There was no external funding for this study. The authors declare that they have no conflict of interest. TRIAL REGISTRATION NUMBER N/A.

STUDY QUESTION What is the recommended management for women and transgender men with regards to fertility preservation (FP), based on the best available evidence in the literature? SUMMARY ANSWER The ESHRE Guideline on Female Fertility Preservation makes 78 recommendations on organization of care, information provision and support, pre-FP assessment, FP interventions and after treatment care. Ongoing developments in FP are also discussed. WHAT IS KNOWN ALREADY The field of FP has grown hugely in the last two decades, driven by the increasing recognition of the importance of potential loss of fertility as a significant effect of the treatment of cancer and other serious diseases, and the development of the enabling technologies of oocyte vitrification and ovarian tissue cryopreservation (OTC) for subsequent autografting. This has led to the widespread, though uneven, provision of FP for young women. STUDY DESIGN, SIZE, DURATION The guideline was developed according to the structured methodology for development of ESHRE guidelines. After formulation of key questions by a group of experts, literature searches and assessments were performed. Papers published up to 1 November 2019 and written in English were included in the review. PARTICIPANTS/MATERIALS, SETTING, METHODS Based on the collected evidence, recommendations were formulated and discussed until consensus was reached within the guideline group. A stakeholder review was organized after finalization of the draft. The final version was approved by the guideline group and the ESHRE Executive Committee. MAIN RESULTS AND THE ROLE OF CHANCE This guideline aims to help providers meet a growing demand for FP options by diverse groups of patients, including those diagnosed with cancer undergoing gonadotoxic treatments, with benign diseases undergoing gonadotoxic treatments or those with a genetic condition predisposing to premature ovarian insufficiency, transgender men (assigned female at birth), and women requesting oocyte cryopreservation for age-related fertility loss. The guideline makes 78 recommendations on information provision and support, pre-FP assessment, FP interventions and after treatment care, including 50 evidence-based recommendations—of which 31 were formulated as strong recommendations and 19 as weak—25 good practice points and 3 research only recommendations. Of the evidence-based recommendations, 1 was supported by high-quality evidence, 3 by moderate-quality evidence, 17 by low-quality evidence and 29 by very low-quality evidence. To support future research in the field of female FP, a list of research recommendations is provided. LIMITATIONS, REASONS FOR CAUTION Most interventions included are not well studied in FP patients. As some interventions, e.g. oocyte and embryo cryopreservation, are well established for treatment of infertility, technical aspects, feasibility and outcomes can be extrapolated. For other interventions, such as OTC and IVM, more evidence is required, specifically pregnancy outcomes after applying these techniques for FP patients. Such future studies may require the current recommendations to be revised. WIDER IMPLICATIONS OF THE FINDINGS The guideline provides clinicians with clear advice on best practice in female FP, based on the best evidence currently available. In addition, a list of research recommendations is provided to stimulate further studies in FP. STUDY FUNDING/COMPETING INTEREST(S) The guideline was developed and funded by ESHRE, covering expenses associated with the guideline meetings, with the literature searches and with the dissemination of the guideline. The guideline group members did not receive payment. R.A.A. reports personal fees and non-financial support from Roche Diagnostics, personal fees from Ferring Pharmaceuticals, IBSA and Merck Serono, outside the submitted work; D.B. reports grants from Merck Serono and Goodlife, outside the submitted work; I.D. reports consulting fees from Roche and speaker’s fees from Novartis; M.L. reports personal fees from Roche, Novartis, Pfizer, Lilly, Takeda, and Theramex, outside the submitted work. The other authors have no conflicts of interest to declare. DISCLAIMER This guideline represents the views of ESHRE, which were achieved after careful consideration of the scientific evidence available at the time of preparation. In the absence of scientific evidence on certain aspects, a consensus between the relevant ESHRE stakeholders has been obtained. Adherence to these clinical practice guidelines does not guarantee a successful or specific outcome, nor does it establish a standard of care. Clinical practice guidelines do not replace the need for application of clinical judgment to each individual presentation, nor variations based on locality and facility type. ESHRE makes no warranty, express or implied, regarding the clinical practice guidelines and specifically excludes any warranties of merchantability and fitness for a particular use or purpose. (Full disclaimer available at www.eshre.eu/guidelines.) †ESHRE Pages content is not externally peer reviewed. The manuscript has been approved by the Executive Committee of ESHRE.

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: Recommendations for Interventional Trials (SPIRIT) statement, and over 80 specialty journals, including the Cochrane Gynaecology and Fertility Group, Fertility and Sterility and Human Reproduction, have committed to implementing this core outcome set. STUDY FUNDING/COMPETING INTEREST(S) This research was funded by the Catalyst Fund, Royal Society of New Zealand, Auckland Medical Research Fund and Maurice and Phyllis Paykel Trust. The funder had no role in the design and conduct of the study, the collection, management, analysis or interpretation of data, or manuscript preparation. B.W.J.M. is supported by a National Health and Medical Research Council Practitioner Fellowship (GNT1082548). S.B. was supported by University of Auckland Foundation Seelye Travelling Fellowship. S.B. reports being the Editor-in-Chief of Human Reproduction Open and an editor of the Cochrane Gynaecology and Fertility group. J.L.H.E. reports being the Editor Emeritus of Human Reproduction. J.M.L.K. reports research sponsorship from Ferring and Theramex. R.S.L. reports consultancy fees from Abbvie, Bayer, Ferring, Fractyl, Insud Pharma and Kindex and research sponsorship from Guerbet and Hass Avocado Board. B.W.J.M. reports consultancy fees from Guerbet, iGenomix, Merck, Merck KGaA and ObsEva. C.N. reports being the Co Editor-in-Chief of Fertility and Sterility and Section Editor of the Journal of Urology, research sponsorship from Ferring, and retains a financial interest in NexHand. A.S. reports consultancy fees from Guerbet. E.H.Y.N. reports research sponsorship from Merck. N.L.V. reports consultancy and conference fees from Ferring, Merck and Merck Sharp and Dohme. The remaining authors declare no competing interests in relation to the work presented. All authors have completed the disclosure form. TRIAL REGISTRATION NUMBER Core Outcome Measures in Effectiveness Trials Initiative: 1023.

STUDY QUESTIONWhat is good practice in ultrasound (US), and more specifically during the different stages of transvaginal oocyte retrieval, based on evidence in the literature and expert opinion on US practice in ART?SUMMARY ANSWERThis document provides good practice recommendations covering technical aspects of US-guided transvaginal oocyte retrieval (oocyte pick up: OPU) formulated by a group of experts after considering the published data, and including the preparatory stage of OPU, the actual procedure and post-procedure care.WHAT IS KNOWN ALREADYUS-guided transvaginal OPU is a widely performed procedure, but standards for best practice are not available.STUDY DESIGN, SIZE, DURATIONA working group (WG) collaborated on writing recommendations on the practical aspects of transvaginal OPU. A literature search for evidence of the key aspects of the procedure was carried out. Selected papers (n = 190) relevant to the topic were analyzed by the WG.PARTICIPANTS/MATERIALS, SETTING, METHODSThe WG members considered the following key points in the papers: whether US practice standards were explained; to what extent the OPU technique was described and whether complications or incidents and how to prevent such events were reported. In the end, only 108 papers could be used to support the recommendations in this document, which focused on transvaginal OPU. Laparoscopic OPU, transabdominal OPU and OPU for IVM were outside the scope of the study.MAIN RESULTS AND THE ROLE OF CHANCEThere was a scarcity of studies on the actual procedural OPU technique. The document presents general recommendations for transvaginal OPU, and specific recommendations for its different stages, including prior to, during and after the procedure. Most evidence focussed on comparing different equipment (needles) and on complications and risks, including the risk of infection. For these topics, the recommendations were largely based on the results of the studies. Recommendations are provided on equipment and materials, possible risks and complications, audit and training. One of the major research gaps was training and competence. This paper has also outlined a list of research priorities (including clarification on the value or full blood count, antibiotic prophylaxis and flushing, and the need for training and proficiency).LIMITATIONS, REASONS FOR CAUTIONThe recommendations of this paper were mostly based on clinical expertise, as at present, only a few clinical trials have focused on the oocyte retrieval techniques, and almost all available data are observational. In addition, studies focusing on OPU were heterogeneous with significant difference in techniques used, which made drafting conclusions and recommendations based on these studies even more challenging.WIDER IMPLICATIONS OF THE FINDINGSThese recommendations complement previous guidelines on the management of good laboratory practice in ART. Some useful troubleshooting/checklist recommendations are given for easy implementation in clinical practice. These recommendations aim to contribute to the standardization of a rather common procedure that is still performed with great heterogeneity.STUDY FUNDING/COMPETING INTEREST(S)The meetings of the WG were funded by ESHRE. The other authors declare that they have no conflict of interest.TRIAL REGISTRATION NUMBERNA.ESHRE Pages content is not externally peer reviewed. The manuscript has been approved by the Executive Committee of ESHRE.

The aim of this review is to provide current knowledge on fertility preservation for non-medical reasons in women willing to postpone childbearing. The topic is highly debatable, starting from disagreement about its terminology, the number of eggs necessary to predict chances of success, and the safety and socio/ethical point of view. Cost analysis and discrepancies among countries' recommendations and regulations are described to confirm the controversies and unsolved issues around this very interesting topic. Finally, an overview on the returning rate of women among "egg bankers" and reasons behind their decisions are illustrated.

BACKGROUND: Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic and potentially life threatening condition resulting from excessive ovarian stimulation. Reported incidence of moderate to severe OHSS ranges from 0.6% to 5% of in vitro fertilization (IVF) cycles. The factors contributing to OHSS have not been completely explained. The release of vasoactive substances secreted by the ovaries under human chorionic gonadotrophin (hCG) stimulation may play a key role in triggering this syndrome. This condition is characterised by a massive shift of fluid from the intravascular compartment to the third space, resulting in profound intravascular depletion and haemoconcentration. OBJECTIVES: To assess the effect of withholding gonadotrophins (coasting) on the prevention of ovarian hyperstimulation syndrome in assisted reproduction cycles. SEARCH METHODS: For the update of this review, we searched the Cochrane Gynaecology and Fertility Group Trials Register, CENTRAL, MEDLINE (PubMed), CINHAL, PsycINFO, Embase, Google, and clinicaltrials.gov to 6 July 2016. SELECTION CRITERIA: We included only randomized controlled trials (RCTs) in which coasting was used to prevent OHSS. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials and extracted data. They resolved disagreements by discussion. They contacted study authors to request additional information or missing data. The intervention comparisons were coasting versus no coasting, coasting versus early unilateral follicular aspiration (EUFA), coasting versus gonadotrophin releasing hormone antagonist (antagonist), coasting versus follicle stimulating hormone administration at the time of hCG trigger (FSH co‐trigger), and coasting versus cabergoline. We performed statistical analysis in accordance with Cochrane guidelines. Our primary outcomes were moderate or severe OHSS and live birth. MAIN RESULTS: We included eight RCTs (702 women at high risk of developing OHSS). The quality of evidence was low or very low. The main limitations were failure to report live birth, risk of bias due to lack of information about study methods, and imprecision due to low event rates and lack of data. Four of the studies were published only as abstracts, and provided limited data. Coasting versus no coasting Rates of OHSS were lower in the coasting group (OR 0.11, 95% CI 0.05 to 0.24; I² = 0%, two RCTs; 207 women; low‐quality evidence), suggesting that if 45% of women developed moderate or severe OHSS without coasting, between 4% and 17% of women would develop it with coasting. There were too few data to determine whether there was a difference between the groups in rates of live birth (OR 0.48, 95% CI 0.14 to 1.62; one RCT; 68 women; very low‐quality evidence), clinical pregnancy (OR 0.82, 95% CI 0.46 to 1.44; I² = 0%; two RCTs; 207 women; low‐quality evidence), multiple pregnancy (OR 0.31, 95% CI 0.12 to 0.81; one RCT; 139 women; low‐quality evidence), or miscarriage (OR 0.85, 95% CI 0.25 to 2.86; I² = 0%; two RCTs; 207 women; very low‐quality evidence). Coasting versus EUFA There were too few data to determine whether there was a difference between the groups in rates of OHSS (OR 0.98, 95% CI 0.34 to 2.85; I² = 0%; 2 RCTs; 83 women; very low‐quality evidence), or clinical pregnancy (OR 0.67, 95% CI 0.25 to 1.79; I² = 0%; 2 RCTs; 83 women; very low‐quality evidence); no studies reported live birth, multiple pregnancy, or miscarriage. Coasting versus antagonist One RCT (190 women) reported this comparison, and no events of OHSS occurred in either arm. There were too few data to determine whether there was a difference between the groups in clinical pregnancy rates (OR 0.74, 95% CI 0.42 to 1.31; one RCT; 190 women; low‐quality evidence), or multiple pregnancy rates (OR 1.00, 95% CI 0.43 to 2.32; one RCT; 98 women; very low‐quality evidence); the study did not report live birth or miscarriage. Coasting versus FSH co‐trigger Rates of OHSS were higher in the coasting group (OR 43.74, 95% CI 2.54 to 754.58; one RCT; 102 women; very low‐quality evidence), with 15 events in the coasting arm and none in the FSH co‐trigger arm. There were too few data to determine whether there was a difference between the groups in clinical pregnancy rates (OR 0.92, 95% CI 0.43 to 2.10; one RCT; 102 women; low‐quality evidence). This study did not report data suitable for analysis on live birth, multiple pregnancy, or miscarriage, but stated that there was no significant difference between the groups. Coasting versus cabergoline There were too few data to determine whether there was a difference between the groups in rates of OHSS (OR 1.98, 95% CI 0.09 to 5.68; P = 0.20; I² = 72%; two RCTs; 120 women; very low‐quality evidence), with 11 events in the coasting arm and six in the cabergoline arm. The evidence suggested that coasting was associated with lower rates of clinical pregnancy (OR 0.38, 95% CI 0.16 to 0.88; P = 0.02; I² =0%; two RCTs; 120 women; very low‐quality evidence), but there were only 33 events altogether. These studies did not report data suitable for analysis on live birth, multiple pregnancy, or miscarriage. AUTHORS' CONCLUSIONS: There was low‐quality evidence to suggest that coasting reduced rates of moderate or severe OHSS more than no coasting. There was no evidence to suggest that coasting was more beneficial than other interventions, except that there was very low‐quality evidence from a single small study to suggest that using FSH co‐trigger at the time of HCG administration may be better at reducing the risk of OHSS than coasting. There were too few data to determine clearly whether there was a difference between the groups for any other outcomes.

Item does not contain fulltext STUDY QUESTION: The precise delineation of the research phase is a recurrent subject of debate: When is the evidence base firm enough to decide that a new technology or treatment no longer needs to be regarded as 'experimental'? SUMMARY ANSWER: We propose a framework that distinguishes between three instead of two types of treatment and describes a continuum from experimental over innovative to established treatment, offering a tool meant to facilitate decision-making about the introduction of new technologies in the clinic. WHAT IS KNOWN ALREADY: Traditionally, guidelines from medical societies on the notion of 'experimental treatment' depart from a dichotomy between experimental and established treatment. However, in the field of reproductive medicine, there are several problems with a dichotomous framework. First, it does not offer an adequate account of the reality in the clinic. Secondly, this view may bring about several negative effects for the patient, such as techniques being considered established too early, holding risks unknown to patients. A further drawback of the dichotomy is that if a technique is no longer considered experimental, centres offering the technique may no longer consider it useful gathering and critically examining (follow-up) data. STUDY DESIGN, SIZE, DURATION: The framework and scoring tool were developed over several phases during which the authors operated as a consensus group of experts. PARTICIPANTS/MATERIALS, SETTING, METHODS: The scoring tool reflects the continuous progression of a new procedure from experimental through innovative to established. For this evolution, four criteria were considered relevant. The first (efficacy) is a categorical criterion (pass/fail). The other three criteria (safety, procedural reliability and transparency and effectiveness) are ordinal in nature. Thresholds have been introduced for all four criteria to avoid that a technology scoring high on procedure and effectiveness but extremely low on safety could move to the next level because of a sufficiently high overall score. MAIN RESULTS AND THE ROLE OF CHANCE: Only treatments that are rated above the thresholds for all four criteria could be considered at least innovative treatments. When they score 4 or higher on the last three criteria, they are considered established treatments. LIMITATIONS, REASONS FOR CAUTION: Knowledge about the procedures or techniques under discussion is essential in order to use the tool. WIDER IMPLICATIONS OF THE FINDINGS: The tool is designed to be used on a macro-level (e.g. by professional societies) although it could also be valuable in the local setting. Both the framework and the tool can bring more clarity on the notion of 'experimental treatment', especially with regard to how to decide when a specific technology or treatment falls in this category and when it can move into one of the other categories. STUDY FUNDING/COMPETING INTEREST(S): none. TRIAL REGISTRATION NUMBER: none.

Despite advances in understanding the molecular pathogenesis of multiple myeloma and promising new therapies, almost all patients eventually relapse with resistant disease. There is therefore a strong rationale for combining novel therapies that target intrinsic molecular pathways mediating multiple myeloma cell resistance. One such protein family is the heat shock proteins (HSP), especially the HSP90 family. Heat shock protein inhibitors have been identified as promising cancer treatments as, while they only inhibit a single biologic function, the chaperone–protein association, their effect is widespread as it results in the destruction of numerous client proteins. This article reviews the preclinical and clinical data, which support the testing of HSP90 inhibitors as cancer drugs and update the reader on the current status of the ongoing clinical trials of HSP90 inhibitors in multiple myeloma.

Objective To investigate the role of exogenous LH in controlled ovarian hyperstimulation for assisted reproductive technologies. Design Prospective randomized study. Setting SISMER fertility unit. Patient(s) Women showing a hyporesponsiveness to FSH under GnRH agoinst down-regulation were randomized into three groups: group A (n = 54) received an increased dosage of FSH; group B (n = 54) was administered recombinant LH in addition to the increased dose of FSH; group C (n = 22) was given additional FSH and LH using hMG as a combined drug. Fifty-four age-matched women with no need to increase the FSH dose were included as a control group (D). Intervention(s) None. Main outcome measure(s) Implantation and live birth rate per started cycles. Result(s) In group B, the pregnancy and implantation rates were statistically higher when compared with groups A and C and did not differ from the control group for normal response. The live birth rate was similar in groups B and D but was half as high in groups A and C. Conclusion(s) Hyporesponsiveness to FSH could be related to iatrogenic LH deficiency that, in turn, could affect oocyte competence. Addition of a small amount of recombinant LH is able to rescue oocyte competence to produce viable embryos.

A 51-year old female, treated for hyperthyroidism with methimazole, developed agranulocytosis in the third month of therapy. After discontinuing the drug, a broad spectrum antibiotic regimen plus recombinant human granulocyte colony-stimulating factor (G-CSF) were started. Her granulocyte count returned to normal with the 4(°) dose of G-CSF. We think that in patients with methimazole-induced agranulocytosis, G-CSF may reduce the risk and severity of infection and in some cases should be accepted as a part of the standard therapy.

Objective: To report a case of uneventful expulsion of huge fibroids after uterine artery embolization. Design: Case report. Setting: The Department of Obstetrics and Gynaecology of a university hospital. Patient(s): A 45-year-old woman who underwent uterine artery embolization for fibroids. Intervention(s): Transfemoral selective bilateral uterine artery catheterization and injection of 500–700 �m polyvinyl alcohol particles. Main Outcome Measure(s): Recovery of the patient. Result(s): The spontaneous expulsion of three fibroids on three different occasions over several months resulted in a significant reduction in menstrual loss and dysmenorrhea. Conclusion(s): Delivering fibroids or sections of fibroids may be a natural process after uterine artery embolization, therefore it is essential to warn women about the possible risk. Close follow-up is also essential. The size of the fibroids discharged did not require hysterectomy. Adequate antibiotic cover may be necessary to prevent sepsis.

1 Division of Hematology, University of Messina, Italy, 2 School and Division of Allergy and Clinical Immunology, Department of Human Pathology, University of Messina, Italy, 3 Institute of Biomedicine and Molecular Immunology “ A. Monroy ” (IBIM) – Consiglio Nazionale delle Ricerche (CNR), Palermo, Italy, 4 Department of Social and Environmental Medicine, University of Messina, Italy and 5 Institute of Hematology and Medical Oncology ‘ L. & A. Ser a gnoli ’ , University of Bologna, Italy

Techniques for embryo transfer (ET) are being developed, optimized, and standardized to provide the best outcomes.This includes methods to reduce the risk of embryo loss following ET.To systematically locate, analyse, and review the best available evidence regarding the effectiveness of post-ET techniques for women undergoing in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI).We searched electronic databases; reference lists of primary studies, review articles, and relevant publications; and conference abstracts. No language restrictions were applied.Screening and selection of 2436 possible trial citations were performed independently by two review authors. Four prospective, truly randomised trials met the inclusion criteria. The trials compared two competing post ET interventions or an intervention versus no treatment in women undergoing IVF and ICSI.Two review authors independently collected data and assessed risk of bias using a standardized data extraction form. Individual outcome data were extracted to support an intention-to-treat analysis.The primary outcome, live birth rate, was not reported in any of the included trials. The ongoing pregnancy rate was only available for one trial that compared immediate ambulation with 30 minute bed rest, with no evidence of an effect with bed rest (OR 1.00; 95% CI 0.54 to 1.85).Secondary outcomes were sporadically reported with the exception of clinical pregnancy rate, which was reported in all of the included trials. There was no significant difference between less bed rest and more rest (OR 1.13; 95% CI 0.77 to 1.67). Nor was there any significant difference between the use of a fibrin sealant and control (OR 0.98; 95% CI 0.54 to 1.78). Even so, there was a significantly higher probability of pregnancy following mechanical closure of the cervix compared with no intervention (OR 1.92; 95% CI 1.40 to 2.63).The risk of bias of the included studies was variable. The reporting of a proper method of randomisation and allocation concealment was demonstrated in the majority of trials, while only one trial was reported to be blinded.There is insufficient evidence to support a certain amount of time for women to remain recumbent following ET, or to support the use of fibrin sealants. Finally, there is limited evidence to support the use of mechanical closure of the cervical canal following ET. Further well-designed and powered studies are required to determine the true effect, if any, of these and other post ET techniques for women undergoing IVF and ICSI.

Tubal sterilisation is the most popular contraceptive method in the world. Approximately 138 million women of reproductive age have had tubal sterilisation and there is evidence that increasingly younger women are being sterilized. With such large numbers of women choosing this option of birth control it is clear that even if a small percentage of women later regret the decision large numbers of women will seek counselling regarding reversal from their physicians. The objectives were to compare the efficacy of surgical tubal reanastomosis and in vitro fertilisation in terms of live birth rates. The morbidity and cost-effectiveness of both techniques were also to be compared. The following databases were searched: Cochrane Menstrual Disorders and Subfertility Review Group Specialised Register MEDLINE (1966 to 2005) EMBASE (1980 to 2005) and other electronic databases. We hand-searched the reference lists of trials reviews and relevant textbooks; searched abstracts from relevant conferences and personally communicated with experts in the field. Randomised and quasi-randomised trials comparing surgical reversal of tubal sterilisation with in vitro fertilisation (IVF). The method of allocation will be assessed and results subgrouped according to whether the trials were randomised or quasi-randomised. No trials were found that met the selection criteria. No data exist on which to report. There is a need for well-designed controlled clinical trials to compare the efficacy and safety of surgical reversal of tubal sterilisation and IVF in restoring fertility in women seeking pregnancy following tubal sterilisation. (authors)

To evaluate the influence of inner myometrium fibroids (myomas) on the outcome of IVF cycles, a retrospective agematched controlled study was performed at SISMeR Reproductive Medicine Unit. The study group included 129 IVF/intracytoplasmic sperm injection cycles in 75 patients with one or more intramural and/or submucosal fibroids, while the control group consisted of 129 cycles in 127 patients without fibroids. The two groups were similar for mean oestradiol concentration at human chorionic gonadotrophin administration (1205.16 +/- 874 versus 1395 +/- 821 pg/ml), mean number of transferred embryos (2.02 +/- 0.4 versus 2.14 +/- 0.6) and clinical pregnancy rate (34.9 versus 41.1%). Conversely, the implantation rate was significantly lower in the study group (18.0%) than in the control group (26.5%; chi(2) = 4.81, P < 0.05), whereas the rate of spontaneous abortion demonstrated an opposite trend (40 versus 18.9%; chi(2) = 4.34, P < 0.05). Further research should be aimed at classifying fibroids on the basis of their location, especially when they are positioned in the junctional zone of the myometrium. Whether this classification will be superior in predicting the impact of fibroids on the reproductive outcome should be elaborated in a large multicentric study.

Objective To assess the value of different serum E 2 cut-off levels for predicting women at risk for ovarian hyperstimulation syndrome (OHSS). Design Retrospective case-control study of a cohort of women undergoing assisted reproduction treatment (ART) over 12 months. Setting Tertiary university hospital. Patient(s) The study group included women with OHSS who fulfilled the endocrine inclusion criteria (n = 40). The control group was a random sample (n = 40) from the cohort of women undergoing ART. Intervention(s) None. Main outcome measure(s) To evaluate the sensitivity and specificity of different serum E 2 cut-off levels on day 11 of ovarian stimulation in preventing the establishment of OHSS. Result(s) Three hundred ninety-nine cycles (IVF and intracytoplasmic sperm injection) were undertaken between June 2000 and May 2001. The study group (n = 40) was compared with the control group (n = 40) undergoing ART during the same period of time. On day 8 of ovarian stimulation, the mean (SD) E 2 level in the study group was 8,517(5.3) pmol/L (2,320 pg/mL), and in the control group it was 2,540 (2.6) pmol/L (691 pg/mL). On day 11 of stimulation the mean (SD) E 2 level was 15,662 (4.2) pmol/L (4,266 pg/mL) and 5,804 (4.5) pmol/L (1,581 pg/mL), respectively. Twenty-four (60%) women who developed OHSS had E 2 levels >6,000 pmol/L (1,634 pg/mL) on day 8 and above 11,000 pmol/L (2,996 pg/mL) on day 11. Sixteen (40%) had E 2 levels Conclusion(s) A serum E 2 level of 12,315 pmol/L (3,354 pg/mL) on day 11 of ovarian stimulation gives a sensitivity and specificity of 85% for the detection of women at risk for OHSS.

This paper is based on a Cochrane review published in The Cochrane Library, issue 3, 2002 (see www.CochraneLibrary.net for information) with permission from The Cochrane Collaboration and Update Software. Cochrane reviews are regularly updated as new evidence emerges and in response to comments and criticisms, and The Cochrane Library should be consulted for the most recent version of the review.Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic condition resulting from an excessive ovarian response to superovulation medication. The objective of this review was to evaluate the effectiveness of cryopreservation (embryo freezing) when compared with human i.v. albumin infusion and with fresh embryo transfer for the prevention of OHSS.This was based on a Cochrane Review. Randomized controlled trials in which either human i.v. albumin or cryopreservation of all embryos was used as a therapeutic approach to OHSS were included. The participants were women down-regulated by GnRH agonist, undergoing superovulation in IVF/ICSI cycles. The interventions compared were cryopreservation versus i.v. human albumin administration and elective cryopreservation of all embryos versus fresh embryo transfer. The primary outcomes were: incidence of moderate and severe OHSS versus nil/mild OHSS, and clinical pregnancies/woman. Statistical analysis was performed in accordance with the Cochrane Menstrual Disorders and Subfertility Group guidelines.Seventeen studies were identified, two of which met our inclusion criteria. One study was included where cryopreservation was compared with i.v. human albumin administration and another where elective cryopreservation of all embryos was compared with fresh embryo transfer. In both interventions no difference was found in all the outcomes examined between the two groups.This review has shown that there is insufficient evidence to support routine cryopreservation and insufficient evidence for the relative merits of i.v. albumin versus cryopreservation.

Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic potentially life threatening condition resulting from an excessive ovarian stimulation. Its reported incidence varies from 1% to 10% of in vitro fertilization (IVF) cycles. The factors leading to this syndrome have not been completely explained. It seems likely that the release of vasoactive substances, secreted by the ovaries under human chorionic gonadotropin (hCG) stimulation plays a key role in triggering this syndrome. The hallmark of this condition, is a massive shift of fluid from the intra-vascular compartment to the third space resulting in profound intra-vascular depletion and hemoconcentration.To evaluate (i) the effectiveness of cryopreservation (embryo freezing) for the prevention of OHSS when compared with human intra-venous albumin infusion and (ii) the effectiveness of the elective cryopreservation (embryo freezing ) of all embryos for the prevention of OHSS when compared with fresh embryo transfer.Publications in the literature that describe or may describe randomised controlled trials of both human intra-venous albumin and freezing of all embryos in the management of OHSS as consequence of the superovulation in assisted reproduction techniques (ART) cycles were searched. The Cochrane Menstrual Disorders and Subfertility Review Group specialised register of controlled trials was searched. In addition, MEDLINE (PUBMED 1985 to 2001), EMBASE (1985 to 2001), CINHAL (1985 to 2001) and the National Research Register were searchedRandomised controlled trials (RCTs) in which either human intra-venous albumin or cryopreservation of all embryos were used as a therapeutic approach to OHSS were included. The participants were women of reproductive age who were down regulated by gonadotrophin-releasing hormone-analogue (GnRH-a), undergoing superovulation in in vitro fertilization/intra-cytoplasmic sperm injection (IVF/ICSI) cycles.Two reviewers, Mr N.N. Amso (NNA) and Dr A. D'Angelo (ADA) scanned the titles and the abstracts of the reports identified by electronic searching in order to find relevant papers. One reviewer (ADA) obtained copies of the full text articles and made copies for the other reviewer (NNA) in which details of authors, institution, results and discussion were removed in order to assess their eligibility for inclusion. Then, both reviewers extracted data independently using forms designed according to Cochrane guidelines. Disagreements were resolved by discussion. Additional information on the trial methodology or data were requested by writing to the corresponding authors directly. The interventions compared were cryopreservation (embryo freezing) versus intra-venous human albumin administration and elective cryopreservation of all embryos versus fresh embryo transfer. The primary outcomes were: incidence of moderate and severe OHSS versus nil/mild OHSS, clinical pregnancies/woman. The secondary outcomes were: number of oocytes retrieved, number of oocytes fertilized, number of embryos transferred, number of embryos frozen, multiple pregnancy rate, live birth rate, number of women admitted to the hospital as inpatient or outpatient and time to the next menstrual period (resolution time). Statistical analysis was performed in accordance with the Cochrane Menstrual Disorders and Subfertility Group guidelines.Seventeen studies were identified, two of which met our inclusion criteria. One study was included where cryopreservation (embryo freezing) was compared with intra-venous human albumin administration (Shaker 1996) and one study was included where elective cryopreservation of all embryos was compared with fresh embryo transfer (Ferraretti 1999). When cryopreservation was compared with intra-venous human albumin administration no difference was found in all the outcomes examined between the two groups. When elective cryopreservation of all embryos was compared with fresh embryo transfer no difference was found in all the outcomes examined between the two groups.This review has showed that there is insufficient evidence to support routine cryopreservation and insufficient evidence for the relative merits of intra-venous albumin versus cryopreservation.

Objective: To test a new software package (Color Quantifier, Kinetic Imaging, Liverpool, United Kingdom) that quantifies power Doppler energy and to determine its reproducibility. Design: Intraobserver and interobserver reproducibility study. Setting: University tertiary referral center. Patient(s): Transvaginal power Doppler ultrasound images were recorded from women taking part in a study evaluating the physiological vascular changes in the uterus and ovaries during the normal menstrual cycle. Intervention(s): Nineteen consecutive frames of regions of interest in the uterus, ovary, and follicle, respectively, were analyzed by each of four observers on 10 occasions. Main Outcome Measure(s): Analysis of variance to determine the image and observer effect as well as the intraobserver and interobserver coefficients of variation. Result(s): Significant image and observer effects were found. However, the image effect was by far the largest component of the total variation. The large image-to-image variability was expected because the cardiac cycle was included within the 19 frames (images) analyzed. The combined intraobserver and interobserver variation, expressed as the coefficients of variation, was found to be small for the above indices (as low as 1.9%), particularly for total ovary and endometrium. Conclusion(s): The indices obtained with this color quantification software are reproducible in an in vitro setting using prerecorded images. Its applicability as a useful assay in the clinical setting requires further evaluation.

Anemia is a frequent complication in myelodysplastic syndrome (MDS). Treatment with recombinant human epoetin, though effective in up to 40% of patients, is generally limited by financial constraints. On the other hand, anemia has been associated with increased cardiac morbidity and mortality. The main hemodynamic factor is the increased cardiac output mediated by lower afterload, higher preload and positive inotropic and chronotropic effects, leading to gradual cardiac enlargement and left ventricular hypertrophy (LVH). The important relationship between anemia and cardiac morbidity has never been investigated in MDS. We evaluated this association, together with quality of life (QOL) dimensions, in a cross-sectional study in 34 MDS patients. Mean age was 70 (range 41–88) years. QOL measures were obtained by applying the MDS-specific questionnaire QOL-E©. Echocardiographic measurements were carried out according to the recommendations of the American Society of Echocardiography by an external investigator who was blind to the biochemical results. Since 11 patients were transfusion-dependent and 23 were transfusion-free with mean Hb concentration of 10.9 (SD ± 2) g/dL, two groups of patients were formed initially. The groups were comparable for body mass index (BMI), weight, age, blood pressure and heart rate. Echocardiography detected significant cardiac remodeling in 10 out of 11 transfusion-dependent vs 11 out of 23 transfusion-free patients (p=0.01), associated with lower mean Hb levels (8.7±1.5 g/dL versus 11.5±2.4 g/dL, p