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Background: in 2020, SARS-CoV-2 and the COVID-19 pandemic had a huge impact on the access to and provision of ART treatments. Gradually, knowledge of the virus and its transmission has become available, allowing ART activities to resume. Still, questions on the impact of the virus on human gametes and fertility remain. Onjective and rationale: This article summarizes published data, aiming to clarify the impact of SARS-CoV-2 and the COVID-19 disease on human fertility and assisted reproduction, as well as the impact of vaccination, and from this, provide answers to questions that are relevant for people contemplating pregnancy and for health care professionals. Search/methods: PUBMED/MEDLINE and the WHO COVID-19 database were searched from inception to 5 October 2022 with search terms focusing on 'SARS-CoV-2' and gametes, embryos, reproductive function, fertility and ART. Non-English studies and papers published prior to 2020 were excluded, as well as reviews and non-peer reviewed publications. Full papers were assessed for relevance and quality, where feasible. Outcomes: from the 148 papers included, the following observations were made. The SARS-CoV-2-binding proteins, angiotensin-converting enzyme 2 (ACE2) and type II transmembrane serine protease (TMPRSS2), are expressed in the testis, but co-expression remains to be proven. There is some evidence of SARS-CoV-2 RNA in the ejaculate of COVID-19 patients with severe disease, but not in those with mild/moderate disease. SARS-CoV-2 infection can impair spermatogenesis, but this seems to resolve after one spermatogenic cycle. Testosterone levels seem to be lower during and after COVID-19, but long-term data are lacking; disease severity may be associated with testosterone levels. COVID-19 cannot be considered a sexually transmitted disease. There is no co-expression of ACE2 and TMPRSS2 in the myometrium, uterus, ovaries or fallopian tubes. Oocytes seem to have the receptors and protease machinery to be susceptible to SARS-CoV-2 infection; however, viral RNA in oocytes has not been detected so far. Women contemplating pregnancy following COVID-19 may benefit from screening for thyroid dysfunction. There is a possible (transient) impact of COVID-19 on menstrual patterns. Embryos, and particularly late blastocysts, seem to have the machinery to be susceptible to SARS-CoV-2 infection. Most studies have not reported a significant impact of COVID-19 on ovarian reserve, ovarian function or follicular fluid parameters. Previous asymptomatic or mild SARS-CoV-2 infection in females does not seem to negatively affect laboratory and clinical outcomes of ART. There are no data on the minimum required interval, if any, between COVID-19 recovery and ART. There is no evidence of a negative effect of SARS-CoV-2 vaccination on semen parameters or spermatogenesis, ovarian function, ovarian reserve or folliculogenesis. A transient effect on the menstrual cycle has been documented. Despite concerns, cross reactivity between anti-SARS-CoV-2 spike protein antibodies and Syncytin-1, an essential protein in human implantation, is absent. There is no influence of mRNA SARS-CoV-2 vaccine on patients' performance during their immediate subsequent ART cycle. Pregnancy rates post-vaccination are similar to those in unvaccinated patients. Wider implication: this review highlights existing knowledge on the impact of SARS-CoV-2 infection or COVID-19 on fertility and assisted reproduction, but also identifies gaps and offers suggestions for future research. The knowledge presented should help to provide evidence-based advice for practitioners and couples contemplating pregnancy alike, facilitating informed decision-making in an environment of significant emotional turmoil., There was no funding for the current paper, apart from technical support from ESHRE.

Study question: what is the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on the outcome of a pregnancy after medically assisted reproduction (MAR)?. Summary answer: our results suggest that MAR pregnancies are not differentially affected by SARS-CoV-2 infection compared to spontaneous pregnancies. What is known already: information on the effects of coronavirus disease 2019 (COVID-19) on pregnancy after MAR is scarce when women get infected during MAR or early pregnancy, even though such information is vital for informing women seeking pregnancy. Study design, size, duration: data from SARS-CoV-2 affected MAR pregnancies were collected between May 2020 and June 2021 through a voluntary data collection, organised by the European Society of Human Reproduction and Embryology (ESHRE). Participants/materials, setting, methods: all ESHRE members were invited to participate to an online data collection for SARS-CoV-2-infected MAR pregnancies. Main results and the role of chance: the dataset includes 80 cases from 32 countries, including 67 live births, 10 miscarriages, 2 stillbirths and 1 maternal death. An additional 25pregnancies were ongoing at the time of writing. Limitations, reasons for caution: an international data registry based on voluntary contribution can be subject to selective reporting with possible risks of over- or under-estimation. Wider implications of the findings: the current data can be used to guide clinical decisions in the care of women pregnant after MAR, in the context of the COVID-19 pandemic., NA

STUDY QUESTIONIs the outcome of donor recruitment influenced by the country in which recruitment took place or the initial identity (ID)-release choice of applicants?SUMMARY ANSWERMore applicants are accepted as donors in Denmark than in the USA and those who choose ID release are more frequently accepted than those who do not.WHAT IS KNOWN ALREADYThe successful recruitment of sperm donors is essential to provide a range of medically assisted reproduction (MAR) procedures, which rely upon donor sperm. However, while much has been written about the medical screening and assessment of sperm donors from a safety perspective, relatively little has been written about the process of recruiting donors and how it works in practice. There are differences in demographic characteristics between donors who choose to allow their identity to be released to their donor offspring (ID release) compared to those who do not (non-ID release). These characteristics may also influence the likelihood of them being recruited.STUDY DESIGN, SIZE, DURATIONA total of 11 712 men applied to be sperm donors at a sperm bank in Denmark and the USA during 2018 and 2019.PARTICIPANTS/MATERIALS, SETTING, METHODSAnonymized records of all donor applicants were examined to assess the number passing through (or lost) at each stage of the recruitment process. Statistical analysis was carried out to examine differences between location (Denmark or USA) and/or donor type (ID release versus non-ID release).MAIN RESULTS AND THE ROLE OF CHANCEFew applicants (3.79%) were accepted as donors and had samples frozen and released for use; this was higher in Denmark (6.53%) than in the USA (1.03%) (χ2 = 243.2; 1 degree of freedom (df); z = 15.60; P 5 × 106 motile sperm/ml in their post-thaw samples (11.20%). At each stage, there were statistically significant differences between countries and the donor’s initial ID choice. During recruitment, some donors decided to change ID type. There were no country differences in the frequency in which this occurred (χ2 = 0.2852; 1 df; z = 0.5340; P = 0.5933), but it was more common for donors to change from non-ID release to ID release (27.19%) than the other way around (11.45%) (χ2 = 17.75; 1 df; z = 4.213; P LIMITATIONS, REASONS FOR CAUTIONNo information was available about the demographic characteristics of the applicants, which may also have influenced their chances of being accepted as a donor (e.g. ethnicity and age). Donor recruitment procedures may differ in other locations according to local laws or guidelines.WIDER IMPLICATIONS OF THE FINDINGSA better understanding of when and why candidate donors are lost in the recruitment process may help develop leaner and more efficient pathways for interested donors and sperm banks. This could ultimately increase the number of donors recruited (through enhanced information, support, and reassurance during the recruitment process) or it may reduce the financial cost to the recipients of donor sperm, thus making it more affordable to those who are ineligible for state-funded treatment.STUDY FUNDING/COMPETING INTEREST(S)The study received no funding from external sources. All authors are Cryos employees or members of the Cryos External Scientific Advisory Committee.TRIAL REGISTRATION NUMBERN/A.

STUDY QUESTION What is the recommended management for medically assisted reproduction (MAR) in patients with a viral infection or disease, based on the best available evidence in the literature? SUMMARY ANSWER The ESHRE guideline on MAR in patients with a viral infection/disease makes 78 recommendations on prevention of horizontal and vertical transmission before, during and after MAR, and the impact on its outcomes, and these also include recommendations regarding laboratory safety on the processing and storage of gametes and embryos testing positive for viral infections. WHAT IS KNOWN ALREADY The development of new and improved anti-viral medications has resulted in improved life expectancy and quality of life for patients with viral infections/diseases. Patients of reproductive age are increasingly exploring their options for family creation. STUDY DESIGN, SIZE, DURATION The guideline was developed according to the structured methodology for the development of ESHRE guidelines. After the formulation of nine key questions for six viruses (hepatitis B virus, hepatitis C virus, human immunodeficiency virus, human papilloma virus, human T-lymphotropic virus I/II and Zika virus) by a group of experts, literature searches and assessments were performed. Papers published up to 2 November 2020 and written in English were included in the review. Evidence was analyzed by female, male or couple testing positive for the virus. PARTICIPANTS/MATERIALS, SETTING, METHODS Based on the collected evidence, recommendations were formulated and discussed until consensus was reached within the guideline group. There were 61 key questions to be answered by the guideline development group (GDG), of which 12 were answered as narrative questions and 49 as PICO (Patient, Intervention, Comparison, Outcome) questions. A stakeholder review was organized after the finalization of the draft. The final version was approved by the GDG and the ESHRE Executive Committee. MAIN RESULTS AND THE ROLE OF CHANCE This guideline aims to help providers meet a growing demand for guidance on the management of patients with a viral infection/disease presenting in the fertility clinic. The guideline makes 78 recommendations on prevention of viral transmission before and during MAR, and interventions to reduce/avoid vertical transmission to the newborn. Preferred MAR treatments and interventions are described together with the effect of viral infections on outcomes. The GDG formulated 44 evidence-based recommendations—of which 37 were formulated as strong recommendations and 7 as weak—33 good practice points (GPP) and one research only recommendation. Of the evidence-based recommendations, none were supported by high-quality evidence, two by moderate-quality evidence, 15 by low-quality evidence and 27 by very low-quality evidence. To support future research in the field of MAR in patients with a viral infection/disease, a list of research recommendations is provided. LIMITATIONS, REASONS FOR CAUTION Most interventions included are not well-studied in patients with a viral infection/disease. For a large proportion of interventions, evidence was very limited and of very low quality. More evidence is required for these interventions, especially in the field of human papilloma virus (HPV). 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 MAR for patients with a viral infection/disease, based on the best evidence currently available. In addition, a list of research recommendations is provided to stimulate further studies in the field. 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 any financial incentives, all work was provided voluntarily. A.D. reports research fees from Ferring and Merck, consulting fees from Ferring, outside the submitted work. C.P. reports speakers fees from Merck and MSD outside the submitted work. K.T. reports speakers fees from Cooper Surgical and Ferring and consultancy fees as member of the advisory board BioTeam of Ferring, 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.)

Study question What is the opinion of gamete donors on extended carrier screening in Denmark and in US? Summary answer This study showed that the overwhelming majority of the donors were very positive towards genetic testing in general and the expanded carrier screening. What is known already There is a lack of empirical studies on the experiences of and attitudes of donors towards expanded carrier screening (ECS) (Amor et al. 2018). Oocyte donors in a Spanish clinic were surprised by the information on testing and the possibility of being carriers (Abuli et al., 2016). After adequate genetic counselling before and after the test, the results of testing did not seem to have a meaningful emotional or psychological impact on the donors. Study design, size, duration A questionnaire was emailed to all active sperm donors in a sperm bank in Denmark and in a sperm bank in US. Participants/materials, setting, methods A total of 393 donors received the email of which 233 donors completed the questionnaire, 196 in Denmark (response rate of 60.7%) and 37 in the United States (response rate of 52.9%). Main results and the role of chance We systematically compared the US and DK donors and ID-release versus non-ID-release donors for all characteristics and items. ID-release donors with a partner significantly more informed their partner about their donor status than non-ID-release donors (90.5% vs. 72.4%, p 0.027). ID-release donors significantly more intended to tell their own children (57.5% vs. 21.2%, p 0.001). ID-release donors significantly more thought about their potential donor children (56.2% vs. 35.0%; p 0.002) and significantly more likely to want information on whether a pregnancy occurred from their donation (70.6% vs. 55.0%, p 0.017). In addition, they also significantly more wished to obtain information about the children conceived with their sperm: the number of children (64.0% vs. 50.0%, p 0.048), their gender (40% vs. 26.2%, p 0.042), and their health (59.3% vs. 42.5%, p 0.018). The ID-release donors were much less likely than the other type not to want any information (19.3% vs. 32.5%, p 0.034). This general attitude is extended to the wish to be informed if a child with a hereditary disease is born after using their sperm. The ID-release donors were more likely to desire contact if their genetic child was diagnosed with a genetic disease (73.9% vs. 55.0%, p 0.003). Limitations, reasons for caution The main element that makes the study unique (i.e., the choice between ID-release and non-ID-release) also renders the generalization of the findings more difficult. Wider implications of the findings: A better understanding of the attitude among gamete doners will possibly guide future legislation and ensure the safety and welfare of the donors too. Trial registration number none

Background Polycystic ovary syndrome (PCOS) is complex with reproductive, metabolic and psychological features. Infertility is a prevalent presenting feature of PCOS with approximately 75% of these women suffering infertility due to anovulation, making PCOS by far the most common cause of anovulatory infertility. Previous guidelines either lacked rigorous evidence-based processes, did not engage consumer and international multidisciplinary perspectives, or were outdated. Aims This review paper aims to provide a brief update on the best available and most current research evidence supporting the treatment of PCOS which informed the recommendations in the assessment and treatment of infertility section of the international evidence-based guideline on PCOS 2018. Materials and methods International evidence-based guideline development engaged professional societies and consumer organisations with multidisciplinary experts and women with PCOS directly involved at all stages. Results Lifestyle change alone is considered the first-line treatment for the management of infertile anovulatory PCOS women who are overweight or obese. Letrozole should now be considered first-line pharmacological treatment for ovulation induction to improve fertility outcomes. Clomiphene citrate alone and metformin alone could also be used as first-line pharmacological therapy, although both are less effective than letrozole and metformin is less effective than clomiphene citrate in obese women. Gonadotrophins or laparoscopic ovarian surgery are usually second-line ovulation induction therapies. In the absence of an absolute indication for in vitro fertilisation (IVF) / intracytoplasmic sperm injection, women with PCOS and anovulatory infertility could be offered IVF as third-line therapy where first- or second-line ovulation induction therapies have failed. Conclusion This review provides the best available evidence informing recommendations (along with clinical expertise and consumer preference) which provide clinicians with clear advice on best practice for the management of infertile women with PCOS.

Research question What is sperm donors' attitude towards offspring, anonymity and extended genetic screening? Design An online questionnaire for sperm donors was administered at Cryos International in the USA and Denmark between 9 and 30 September 2020. A total of 233 donors (37 in the USA and 196 in Denmark) completed the questionnaire. This study is unique because it was performed in a setting that allows donors to choose to be either ID-release or non-ID-release donors. Results Most donors had two motives to donate: helping childless people and/or financial compensation. ID-release donors differed significantly from non-ID-release donors in numerous aspects of the donation, including relationships with the offspring, information sharing with others and wanting information about offspring. In general, donors had a very positive attitude towards genetic testing and extended genetic screening. Conclusions Offering the possibility for donors to be either ID-release or non-ID-release allows more donors to be recruited than if only one option were available. The multiple differences between the two donor types suggests that these are groups with profoundly different attitudes towards donation. The general attitude of donors towards genetic testing and expanded genetic screening is very positive but further studies on the attitude of candidate donors are needed.

With the increase in obesity prevalence among women of reproductive age globally, the risks of type 2 diabetes, gestational diabetes, pre-eclampsia, and other conditions are rising, with detrimental effects on maternal and newborn health. The period before pregnancy is increasingly recognized as crucial for addressing weight management and reducing malnutrition (both under- and overnutrition) in both parents to reduce the risk of noncommunicable diseases (NCDs) in the mother as well as the passage of risk to her offspring. Healthcare practitioners, including obstetricians, gynecologists, midwives, and general practitioners, have an important role to play in supporting women in planning a pregnancy and achieving healthy nutrition and weight before pregnancy. In this position paper, the FIGO Pregnancy Obesity and Nutrition Initiative provides an overview of the evidence for preconception clinical guidelines to reduce the risk of NCDs in mothers and their offspring. It encourages healthcare practitioners to initiate a dialogue on women's health, nutrition, and weight management before conception. While acknowledging the fundamental importance of the wider social and environmental determinants of health, this paper focuses on a simple set of recommendations for clinical practice that can be used even in short consultations. The recommendations can be contextualized based on local cultural and dietary practices as part of a system-wide public health approach to influence the wider determinants as well as individual factors influencing preconception health.

STUDY QUESTION How are ART and IUI regulated, funded and registered in European countries? SUMMARY ANSWER Of the 43 countries performing ART and IUI in Europe, and participating in the survey, specific legislation exists in only 39 countries, public funding (also available in the 39 countries) varies across and sometimes within countries and national registries are in place in 31 countries. WHAT IS KNOWN ALREADY Some information devoted to particular aspects of accessibility to ART and IUI is available, but most is fragmentary or out-dated. Annual reports from the European IVF-Monitoring (EIM) Consortium for ESHRE clearly mirror different approaches in European countries regarding accessibility to and efficacy of those techniques. STUDY DESIGN, SIZE, DURATION A survey was designed using the online SurveyMonkey tool consisting of 55 questions concerning three domains—legal, funding and registry. Answers refer to the countries’ situation on 31 December 2018. PARTICIPANTS/MATERIALS, SETTINGS, METHODS All members of EIM plus representatives of countries not yet members of the Consortium were invited to participate. Answers received were checked, and initial responders were asked to address unclear answers and to provide any additional information they considered important. Tables of individual countries resulting from the consolidated data were then sent to members of the Committee of National Representatives of ESHRE, asking for a second check. Conflicting information was clarified by direct contact. MAIN RESULTS AND THE ROLE OF CHANCE Information was received from 43 out of the 44 European countries where ART and IUI are performed. Thirty-nine countries reported specific legislation on ART, and artificial insemination was considered an ART technique in 35 of them. Accessibility is limited to infertile couples in 11 of the 43 countries. A total of 30 countries offer treatments to single women and 18 to female couples. In five countries ART and IUI are permitted for treatment of all patient groups, being infertile couples, single women and same sex couples, male and female. Use of donated sperm is allowed in 41 countries, egg donation in 38, the simultaneous donation of sperm and egg in 32 and embryo donation in 29. Preimplantation genetic testing (PGT) for monogenic disorders or structural rearrangements is not allowed in two countries, and PGT for aneuploidy is not allowed in 11; surrogacy is accepted in 16 countries. With the exception of marital/sexual situation, female age is the most frequently reported limiting criteria for legal access to ART—minimal age is usually set at 18 years and maximum ranging from 45 to 51 years with some countries not using numeric definition. Male maximum age is set in very few countries. Where permitted, age is frequently a limiting criterion for third-party donors (male maximum age 35 to 55 years; female maximum age 34 to 38 years). Other legal constraints in third-party donation are the number of children born from the same donor (in some countries, number of families with children from the same donor) and, in 10 countries, a maximum number of egg donations. How countries deal with the anonymity is diverse—strict anonymity, anonymity just for the recipients (not for children when reaching legal adulthood age), mixed system (anonymous and non-anonymous donations) and strict non-anonymity. Public funding systems are extremely variable. Four countries provide no financial assistance to patients. Limits to the provision of funding are defined in all the others i.e. age (female maximum age is the most used), existence of previous children, maximum number of treatments publicly supported and techniques not entitled for funding. In a few countries, reimbursement is linked to a clinical policy. The definition of the type of expenses covered within an IVF/ICSI cycle, up to what limit and the proportion of out-of-pocket costs for patients is also extremely dissimilar. National registries of ART and IUI are in place in 31 out of the 43 countries contributing to the survey, and a registry of donors exists in 18 of them. LIMITATIONS, REASONS FOR CAUTION The responses were provided by well-informed and committed individuals and submitted to double checking. Since no formal validation was in place, possible inaccuracies cannot be excluded. Also, results are a cross section in time and ART and IUI legislations within European countries undergo continuous evolution. Finally, several domains of ART activity were deliberately left out of the scope of this ESHRE survey. WIDER IMPLICATIONS OF THE FINDINGS Results of this survey offer a detailed view of the ART and IUI situation in European countries. It provides updated and extensive answers to many relevant questions related to ART usage at national level and could be used by institutions and policymakers in planning services at both national and European levels. Study funding/competing interest(s) The study has no external funding, and all costs were covered by ESHRE. There were no competing interests. ESHRE Pages are not externally peer reviewed. This article has been approved by the Executive Committee of ESHRE.

STUDY QUESTION: What is the recommended assessment and management of women with polycystic ovary syndrome (PCOS), based on the best available evidence, clinical expertise and consumer preference?SUMMARY ANSWER: International evidence-based guidelines, including 166 recommendations and practice points, addressed prioritized questions to promote consistent, evidence-based care and improve the experience and health outcomes of women with PCOS.WHAT IS KNOWN ALREADY: Previous guidelines either lacked rigorous evidence-based processes, did not engage consumer and international multidisciplinary perspectives, or were outdated. Diagnosis of PCOS remains controversial, and assessment and management are inconsistent. The needs of women with PCOS are not being adequately met and evidence practice gaps persist.STUDY DESIGN, SIZE, DURATION: International evidence-based guideline development engaged professional societies and consumer organizations with multidisciplinary experts and women with PCOS directly involved at all stages. Appraisal of Guidelines for Research and Evaluation (AGREE) II-compliant processes were followed, with extensive evidence synthesis. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework was applied across evidence quality, feasibility, acceptability, cost, implementation and ultimately recommendation strength.PARTICIPANTS/MATERIALS, SETTING, METHODS: Governance included a six continent international advisory and a project board, five guideline development groups, and consumer and translation committees. Extensive health professional and consumer engagement informed guideline scope and priorities. Engaged international society-nominated panels included pediatrics, endocrinology, gynecology, primary care, reproductive endocrinology, obstetrics, psychiatry, psychology, dietetics, exercise physiology, public health and other experts, alongside consumers, project management, evidence synthesis and translation experts. In total, 37 societies and organizations covering 71 countries engaged in the process. Twenty face-to-face meetings over 15 months addressed 60 prioritized clinical questions involving 40 systematic and 20 narrative reviews. Evidence-based recommendations were developed and approved via consensus voting within the five guideline panels, modified based on international feedback and peer review, with final recommendations approved across all panels.MAIN RESULTS AND THE ROLE OF CHANCE: The evidence in the assessment and management of PCOS is generally of low to moderate quality. The guideline provides 31 evidence based recommendations, 59 clinical consensus recommendations and 76 clinical practice points all related to assessment and management of PCOS. Key changes in this guideline include: (i) considerable refinement of individual diagnostic criteria with a focus on improving accuracy of diagnosis; (ii) reducing unnecessary testing; (iii) increasing focus on education, lifestyle modification, emotional wellbeing and quality of life; and (iv) emphasizing evidence based medical therapy and cheaper and safer fertility management.LIMITATIONS, REASONS FOR CAUTION: Overall evidence is generally low to moderate quality, requiring significantly greater research in this neglected, yet common condition, especially around refining specific diagnostic features in PCOS. Regional health system variation is acknowledged and a process for guideline and translation resource adaptation is provided.WIDER IMPLICATIONS OF THE FINDINGS: The international guideline for the assessment and management of PCOS provides clinicians with clear advice on best practice based on the best available evidence, expert multidisciplinary input and consumer preferences. Research recommendations have been generated and a comprehensive multifaceted dissemination and translation program supports the guideline with an integrated evaluation program.STUDY FUNDING/COMPETING INTEREST(S): The guideline was primarily funded by the Australian National Health and Medical Research Council of Australia (NHMRC) supported by a partnership with ESHRE and the American Society for Reproductive Medicine. Guideline development group members did not receive payment. Travel expenses were covered by the sponsoring organizations. Disclosures of conflicts of interest were declared at the outset and updated throughout the guideline process, aligned with NHMRC guideline processes. Full details of conflicts declared across the guideline development groups are available at https://www.monash.edu/medicine/sphpm/mchri/pcos/guideline in the Register of disclosures of interest. Of named authors, Dr Costello has declared shares in Virtus Health and past sponsorship from Merck Serono for conference presentations. Prof. Laven declared grants from Ferring, Euroscreen and personal fees from Ferring, Euroscreen, Danone and Titus Healthcare. Prof. Norman has declared a minor shareholder interest in an IVF unit. The remaining authors have no conflicts of interest to declare. The guideline was peer reviewed by special interest groups across our partner and collaborating societies and consumer organizations, was independently assessed against AGREE-II criteria, and underwent methodological review. This guideline was approved by all members of the guideline development groups and was submitted for final approval by the NHMRC.

Study question: What are the European trends and developments in ART and IUI in 2014 as compared to previous years? Summary answer: The 18th ESHRE report on ART shows a continuing expansion of both treatment numbers in Europe and more variability in treatment modalities resulting in a rising contribution to the birth rates in most participating countries. What is known already: Since 1997, ART data generated by national registries have been collected, analysed by the European IVF-monitoring (EIM) Consortium and reported in 17 manuscripts published in Human Reproduction. Study design, size, duration: Continuous collection of European data by the EIM for ESHRE. The data for treatments performed in 2014 between 1 January and 31 December in 39 European countries were provided by national registries or on a voluntary basis by clinics or professional societies. Participants/materials, setting, methods: From 39 countries and 1279 institutions offering ART services, a total of 776 556 treatment cycles, involving 146 148 with IVF, 362 285 with ICSI, 192 027 with frozen embryo replacement (FER), 15 894 with PGT, 56 516 with egg donation (ED), 292 with IVM and 3404 with frozen oocyte replacement (FOR) were reported. European data on IUI using husband/partner's semen (IUI-H) and donor semen (IUI-D) were reported from 1364 institutions offering IUI in 26 countries and 21 countries, respectively. A total of 120 789 treatments with IUI-H and 49 163 treatments with IUI-D were included. Main results and the role of chance: In 14 countries (17 in 2013), where all institutions contributed to their respective national registers, a total of 291 235 treatment cycles were performed in a population of ~208 million inhabitants, corresponding to 1925 cycles per million inhabitants (range: 423-2978 per million inhabitants). After treatment with IVF the clinical pregnancy rates (PR) per aspiration and per transfer were marginally higher in 2014 than in 2013, at 29.9 and 35.8% versus 29.6 and 34.5%, respectively. After treatment with ICSI the PR per aspiration and per transfer were also higher than those achieved in 2013 (28.4 and 35.0% versus 27.8 and 32.9%, respectively). After FER with own embryos the PR continued to rise, from 27.0% in 2013 to 27.6% in 2014. After ED a similar trend was observed with PR reaching 50.3% per fresh transfer (49.8% in 2013) and 48.7% for FOR (46.4% in 2013). The delivery rates (DR) after IUI remained stable at 8.5% after IUI-H (8.6% in 2013) and at 11.6% after IUI-D (11.1% in 2013). In IVF and ICSI together, 1, 2, 3 and ≥4 embryos were transferred in 34.9, 54.5, 9.9 and in 0.7% of all treatments, respectively (corresponding to 31.4%, 56.3, 11.5% and 1% in 2013). This evolution in embryo transfer strategy in both IVF and ICSI resulted in a singleton, twin and triplet DR of 82.5, 17.0 and 0.5%, respectively (compared to 82.0, 17.5 and 0.5%, respectively, in 2013). Treatments with FER in 2014 resulted in a twin and triplet DR of 12.4 and 0.3%, respectively (versus 12.5 and 0.3% in 2013). Twin and triplet DR after IUI were 9.5 and 0.3%, respectively, after IUI-H (in 2013:9.5 and 0.6%) and 7.7 and 0.3% after IUI-D (in 2013: 7.5 and 0.3%). Limitation, reasons for caution: The method of data collection and reporting varies among European countries. The EIM receives aggregated data from various countries with variable levels of completeness. Registries from a number of countries have failed to provide adequate data about the number of initiated cycles and deliveries. As long as incomplete data are provided, the results should be interpreted with caution. Wider implications of the findings: The 18th ESHRE report on ART shows a continuing expansion of treatment numbers in Europe. The number of treatments reported, the variability in treatment modalities and the rising contribution to the birth rates in most participating countries point towards the increasing impact of ART on reproduction in Europe. Being the largest data collection on ART, the report gives detailed information about ongoing developments in the field. Study funding/competing interest(s): The study has no external funding and all costs are covered by ESHRE. There are no competing interests.

STUDY QUESTION Are there any changes in the treatments involving ART and IUI initiated in Europe during 2013 compared with previous years? SUMMARY ANSWER An increase in the overall number of ART cycles resulting from a higher number of countries reporting data was evident, the pregnancy rates (PRs) in 2013 remained stable compared with those reported in 2012, the number of transfers with multiple embryos (3+) was lower than ever before yet the multiple delivery rates (DRs) remained unchanged, and IUI activity and success rates were similar to those of last years. WHAT IS KNOWN ALREADY Since 1997, ART data in Europe have been collected and reported in 16 manuscripts, published in Human Reproduction. STUDY DESIGN, SIZE, DURATION Retrospective data collection of European ART data by the European IVF-monitoring Consortium for ESHRE. Data for cycles between 1 January and 31 December 2013 were collected from National Registers, when existing, or on a voluntary basis by personal information. PARTICIPANTS/MATERIALS, SETTINGS, METHODS From 38 countries (+4 compared with 2012), 1169 clinics reported 686 271 treatment cycles including 144 299 of IVF, 330 367 of ICSI, 154 712 of frozen embryo replacement (FER), 40 244 of egg donation (ED), 247 of IVM, 9791 of PGD/PGS and 6611 of frozen oocyte replacements. European data on intrauterine insemination using husband/partner's semen (IUI-H) and donor semen (IUI-D) were reported from 1095 IUI labs in 22 countries. A total of 175 467 IUI-H and 43 785 IUI-D cycles were included. MAIN RESULTS AND THE ROLE OF CHANCE In 17 countries where all clinics reported to their ART register, a total of 374 177 ART cycles were performed in a population of around 310 million inhabitants, corresponding to 1175 cycles per million inhabitants (range, 235-2703 cycles per million inhabitants). For all IVF cycles, the clinical PRs per aspiration and per transfer were stable with 29.6% (29.4% in 2012) and 34.5% (33.8% in 2012), respectively. For ICSI, the corresponding rates also were stable with 27.8% (27.8% in 2012) and 32.9% (32.3% in 2012). In FER-cycles, the PR per thawing/warming increased to 27.0% (23.1% in 2012). In ED cycles, the PR per fresh transfer increased to 49.8% (48.4% in 2012), to 38.5% (35.9% in 2012) per thawed transfer, and to 46.4% for transfers after FOR (45.1% in 2012). The DRs after IUI remained stable at 8.6% (8.5% in 2012) after IUI-H and was slightly lower after IUI-D (11.1% versus 12.0% in 2012). In IVF and ICSI cycles, 1, 2, 3 and 4+ embryos were transferred in 31.4, 56.3, 11.5, and 1.0% of the cycles, respectively (corresponding numbers were 30.2, 55.4, 13.3 and 1.1% in 2012). The proportions of singleton, twin and triplet deliveries after IVF and ICSI (added together) were 82., 17.5 and 0.5%, respectively, resulting in a total multiple DR of 18.0% compared to 17.9% in 2012. In FER-cycles, the multiple DR was 12.8% (12.5% twins and 0.3% triplets), nearly the same as in 2012 (12.5, 12.2 and 0.3% respectively). Twin and triplet DRs associated with IUI cycles were 9.5%/0.6% and 7.5%/0.3%, following treatment with husband/donor semen, respectively. LIMITATIONS, REASONS FOR CAUTION The method of reporting varies among countries, and registers from a number of countries have been unable to provide some of the relevant data such as initiated cycles and deliveries. As long as data are incomplete and generated through different methods of collection, the results should be interpreted with caution. WIDER IMPLICATIONS OF THE FINDINGS The 17th ESHRE report on ART shows a continuing expansion of the number of treatment cycles in Europe, with more than 685 000 cycles reported in 2013 and an increasing contribution to birth rate in many countries. However, the need to improve and standardize the national registries, and to establish validation methodologies, remains manifest. STUDY FUNDING/COMPETING INTEREST(S) The study has no external funding; all costs are covered by ESHRE. There are no competing interests.

Ovarian hyperstimulation syndrome (OHSS) is a rare, but serious iatrogenic complication of In Vitro Fertilization treatments. Since 1943, when the first cases of OHSS were reported, strategies to prevent it have not been very successful. At present, the most used strategy to prevent OHSS is the “freeze-all strategy”, which consists in the utilization of a gonadotropin releasing hormone (GnRH) agonist trigger for oocytes maturation in a GnRH antagonist protocol, followed by cryopreservation of all embryos. In this paper, we present a case of a young woman who developed OHSS after GnRH agonist trigger followed by rhCG luteal rescue protocol. By reporting this case, we want to highlight the importance of OHSS prevention and patients’ selection for hCG luteal rescue protocol.

In clomiphene-citrate-resistant anovulatory women with polycystic ovary syndrome (PCOS) and no other infertility factors, either metformin combined with clomiphene citrate or gonadotrophins could be used as a second-line pharmacological therapy, although gonadotrophins are more effective. Gonadotrophins could also be used as a second-line pharmacological therapy in anovulatory women with PCOS and clomiphene-citrate-failure. Laparoscopic ovarian surgery can also be used as a second-line therapy for ovulation induction in anovulatory women with clomiphene-citrate-resistant PCOS and no other infertility factors. The usefulness of letrozole as a second-line pharmacological treatment for ovulation induction in clomiphene-citrate-resistant women with PCOS requires further research. In terms of improving fertility, both pharmacological anti-obesity agents and bariatric surgery should be considered an experimental therapy in anovulatory women with PCOS and no other infertility factors. Where first- or second-line ovulation induction therapies have failed, in vitro fertilization (IVF)/ intracytoplasmic sperm injection (ICSI) could be offered as a third-line therapy in women with PCOS in the absence of an absolute indication for IVF/ICSI. For women with PCOS undergoing IVF/ICSI treatment, the gonadotropin-releasing hormone (GnRH) antagonist protocol is preferred and an elective frozen embryo transfer strategy could be considered. In assisted conception units with sufficient expertise, in-vitro maturation (IVM) of oocytes could be offered to women with PCOS.

Objective To compare the ovarian reserves between female patients with cancer and patients experiencing infertility. Methods A retrospective age-matched observational study was performed at Rotunda Hospital, Dublin. The study group included data from all female oncology patients attending for oocyte or embryo cryopreservation between January 1, 2009 and December 31, 2013. Anti-Mullerian hormone (AMH) levels were recorded at patients' initial visits before beginning chemotherapy or radiotherapy. The control group included patients without cancer who had their AMH levels recorded to investigate fertility or as a baseline level prior to beginning assisted reproductive treatment. Results The records of 118 oncology and 5231 control patients from the study period were identified. There was no difference in AMH levels between patients in the oncology and control groups aged 30–38 years; however, significantly lower AMH levels were observed in patients in the oncology group aged 29 years and younger (17.89 pmol/L vs 23.35 pmol/L; P = 0.015), or at least 39 years (2.65 pmol/L vs 5.87 pmol/L; P = 0.028). Conclusion Before commencing chemotherapy or radiotherapy, patients in the oncology group at the margins of reproductive age had a diminished ovarian reserve compared with the control group. This should be considered when planning optimal doses of follicular stimulating hormone as part of controlled ovarian-stimulation regimes performed for embryo or oocyte cryopreservation prior to chemotherapy or radiotherapy.

Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility in women of reproductive age. Lifestyle change is considered the first line treatment for the management of infertile anovulatory women with PCOS, and weight loss for those who are overweight or obese. First line medical ovulation induction therapy to improve fertility outcomes is letrozole, whilst other less efficacious ovulation induction agents, such as clomiphene citrate, metformin, and metformin combined with clomiphene citrate, may also be considered. Metformin combined with clomiphene citrate is more effective than clomiphene citrate alone. In obese women with PCOS, clomiphene citrate could be used in preference to metformin alone whilst clomiphene citrate could be added to metformin alone in order to improve reproductive outcome in all women with PCOS. Gonadotrophins, which are more effective than clomiphene citrate in therapy naïve women with PCOS, can be considered a first line therapy in the presence of ultrasound monitoring, following counselling on the cost and the potential risk of multiple pregnancy.

Existing evidence suggests that administration of intravenous fluids has been shown to improve outcomes including pain in gynecological laparoscopic surgery but the optimum fluid dose has not been determined. To determine the effect of administration of intravenous fluids on post-operative pain and pulmonary function after gynecological laparoscopy. In a prospective randomized double-blinded study 100 ASA 1 and 2 elective patients undergoing gynecological laparoscopy were randomized to receive intravenous compound sodium lactate 10 ml kg−1 (CSL10-restrictive) or 30 ml kg−1 (CSL30-liberal) administered intra-operatively. The primary outcome measure was the post-operative pain score at 24, 48 and 72 h, assessed by 0–10 verbal rating scale (VRS). Pulmonary function (FEV1, FVC, PEFR) and oxygen saturation were also measured. Patients who received CSL 30 had lower post-operative pain scores than CSL 10 (ANCOVA—mean difference = 0.47, 95 % CI 0.11–0.83, P = 0.01). Post-operative pain VRS was lower in CSL30 than CSL10 at 48 h (mean difference 0.56, 95 % CI 0.04–1.09, P = 0.036). Patients in CSL30 reported shoulder tip pain less frequently than those in CSL10 (30.4 vs. 43.9 % of assessments, P = 0.03, OR 0.58) but reported wound pain more frequently 39.0 vs. 24.2 %, P = 0.01, OR 2.0). Indices of pulmonary function did not differ between groups at any time. Liberal compared to restrictive administration of i.v. crystalloid is associated with a clinical modest reduction in pain. Pulmonary dysfunction was not increased with liberal fluid administration.

Study Question The 16th European IVF-monitoring (EIM) report presents the data of the treatments involving assisted reproductive technology (ART) and intrauterine insemination (IUI) initiated in Europe during 2012: are there any changes compared with previous years? Summary Answer Despite some fluctuations in the number of countries reporting data, the overall number of ART cycles has continued to increase year by year, the pregnancy rates (PRs) in 2012 remained stable compared with those reported in 2011, and the number of transfers with multiple embryos (3+) and the multiple delivery rates were lower than ever before. What is Known Already Since 1997, ART data in Europe have been collected and re-ported in 15 manuscripts, published in Human Reproduction. Study Design, Size, Duration Retrospective data collection of European ART data by the EIM Consortium for the European Society of Human Reproduction and Embryology (ESHRE). Data for cycles between 1 January and 31 December 2012 were collected from National Registers, when existing, or on a voluntary basis by personal information. Participants/Materials, Setting, Methods From 34 countries (+1 compared with 2011), 1111 clinics reported 640 144 treatment cycles including 139 978 of IVF, 312 600 of ICSI, 139 558 of frozen embryo replacement (FER), 33 605 of egg donation (ED), 421 of in vitro maturation, 8433 of preimplantation genetic diagnosis/preimplantation genetic screening and 5549 of frozen oocyte replacements (FOR). European data on intrauterine insemination using husband/partner's semen (IUI-H) and donor semen (IUI-D) were reported from 1126 IUI labs in 24 countries. A total of 175 028 IUI-H and 43 497 IUI-D cycles were included. Main Results and the Role of Chance In 18 countries where all clinics reported to their ART register, a total of 369 081 ART cycles were performed in a population of around 295 million inhabitants, corresponding to 1252 cycles per million inhabitants (range 325-2732 cycles per million inhabitants). For all IVF cycles, the clinical PRs per aspiration and per transfer were stable with 29.4 (29.1% in 2011) and 33.8% (33.2% in 2011), respectively. For ICSI, the corresponding rates also were stable with 27.8 (27.9% in 2011) and 32.3% (31.8% in 2011). In FER cycles, the PR per thawing/warming increased to 23.1% (21.3% in 2011). In ED cycles, the PR per fresh transfer increased to 48.4% (45.8% in 2011) and to 35.9% (33.6% in 2011) per thawed transfer, while it was 45.1% for transfers after FOR. The delivery rate after IUI remained stable, at 8.5% (8.3% in 2011) after IUI-H and 12.0% (12.2% in 2011) after IUI-D. In IVF and ICSI cycles, 1, 2, 3 and 4+ embryos were transferred in 30.2, 55.4, 13.3 and 1.1% of the cycles, respectively. The proportions of singleton, twin and triplet deliveries after IVF and ICSI (added together) were 82.1, 17.3 and 0.6%, respectively, resulting in a total multiple delivery rate of 17.9% compared with 19.2% in 2011 and 20.6% in 2010. In FER cycles, the multiple delivery rate was 12.5% (12.2% twins and 0.3% triplets). Twin and triplet delivery rates associated with IUI cycles were 9.0%/0.4% and 7.2%/0.5%, following treatment with husband and donor semen, respectively. LIMITATIONS, REASONS FOR CAUTION The method of reporting varies among countries, and registers from a number of countries have been unable to provide some of the relevant data such as initiated cycles and deliveries. As long as data are incomplete and generated through different methods of collection, results should be interpreted with caution. Wider Implications of the Findings The 16th ESHRE report on ART shows a continuing expansion of the number of treatment cycles in Europe, with more than 640 000 cycles reported in 2012 with an increasing contribution to birthrate in many countries. However, the need to improve and standardize the national registries, and to establish validation methodologies remains manifest. STUDY FUNDING/COMPETING INTERESTS The study has no external funding; all costs are covered by ESHRE. There are no competing interests.

Ovarian stimulation is an essential part of assisted reproduction treatments. Research on whether the duration of stimulation alters the success in assisted reproduction has not been conclusive. The purpose of the study was to establish whether the duration of ovarian stimulation alters the success in assisted reproduction treatments. All fresh (non-donor) stimulation cycles performed in an academic tertiary referral ART centre over a period of 18 years, between 1st January 1997 and 31st December 2014, were identified. Data were prospectively and electronically collected. IVF and ICSI cycles were analysed independently. Each category was then subdivided into assisted reproduction cycles where the antagonist, long (down regulation) and flare protocol were used. Clinical pregnancy was the main outcome measured. A total of 10,478 stimulation cycles (6011 fresh IVF and 4467 fresh ICSI) reaching egg collection were included. We showed no significant difference in CP rates in IVF cycles for the long (p = 0.082), antagonist (p = 0.217) or flare (p = 0.741) protocol cycles or in ICSI cycles with the long (p = 0.223), antagonist (p = 0.766) or the flare (p = 0.690) protocol with regards the duration of stimulation. The duration of stimulation does not alter the CP rate in ICSI or IVF cycles using the long, antagonist or flare stimulation protocol.

In assisted reproductive technology (ART), quality control necessitates the collection of outcome data and occurring complications. Traditional quality assurance is based on data derived from single ART centres and more recently from national registries, both recording outcome parameters during well-defined observation periods. Nowadays, ART is moving towards much more diverse approaches, with sequential activities including short- or long-term freezing of gametes, gonadal tissues and embryos, and cross-border reproductive care. Hence, long-term cumulative treatment rates and an international approach are becoming a necessity. We suggest the initiation of an easy access European Reproductive Coding System, through which each ART recipient is allocated a unique reproductive care code. This code would identify individuals (and reproductive material) during case to case data reporting to national ART data collecting institutions and to a central European ART monitoring agency. For confidentiality reasons, the identity of the individuals should remain with the local ART provider. This way, cumulative and fully reliable reproductive outcome data can be constructed with follow-up over prolonged time periods.

background: The frequency for virology testing for couples undergoing assisted reproductive treatment (ART) in Europe is currently under debate, with little scientific data available to support the time-frame imposed by EU legislation. The aim of this study was to determine the incidence of blood-borne viruses (BBV) in this population and to assess the likelihood of seroconversion after an initial negative screen and the possible cost saving to couples. methods: We identified all cases where a BBV screen was performed on patients attending our tertiary referral unit for ART. We calculated the incidence of Hepatitis B surface antigen, Hepatitis C antibody and HIV infection in this population and the incidence of seroconversion in follow-up screening (which included Hepatitis B core antibody) following the implementation of the EU legislation. In all cases identified, we sought to assess the risk of seroconversion after an initial negative screen. results: Between 1998 and 2009, we identified a total of 79 291 tests performed in over 12 500 patients. The incidence in this population of Hepatitis B surface antigen was 0.28% (37/12 797), Hepatitis B core antibody 3.32% (96/2891), Hepatitis C antibody 0.33% (43/12 762) and HIV 0.007% (1/12 819). We were able to show that for over 6500 individuals who were tested and re-tested for all three viruses, no seroconversions were reported. conclusions: Based on the above measured negligible risk of seroconversion after an initial negative screen in co-habitating couples participating in an ART programme, current legislation requiring screening of couples at each procurement of cells in the assisted reproductive setting is not clinically justified.

Ovarian hyperstimulation syndrome (OHSS) is a potentially life-threatening complication of Assisted Reproductive Technology (ART) treatment. The objective of this study was to assess the odds of OHSS hospital admission in relation to oestradiol levels on day of hCG administration and number of oocytes collected.We performed a 24 months retrospective analysis of a cohort of patients receiving ART treatment in a University teaching hospital including all patients requiring admission due to OHSS. Main outcome measures were oestradiol levels, number of oocytes collected and incidence of admission with OHSS.OHSS requiring admission to hospital occurred in 1.8% of cases. While no patients with an oestradiol level at hCG/=15,000 pmol/L developed OHSS, those with oestradiol levels/=15,000 pmol/L had different risks of admission according to the number of oocytes collected: those with30 oocytes were 6.7 times more likely to be admitted that those with20 oocytes.This study identifies an oestradiol level (/=15,000 pmol/L) and number of oocytes (/=20) above which the odds of being admitted with OHSS increases significantly. Although OHSS cannot always be prevented, these measurable parameters should be used to allow appropriate counselling and subsequent safe management of ART patients.

The aim of the present study is to investigate the effect of embryonic blastomere loss, following cryopreservation and thaw of Day 2 embryos in an assisted reproductive technology (ART) setting, on pregnancy outcome and fetal development.This is a retrospective analysis performed on 3553 slow frozen-thawed Day 2 embryos, of all IVF/ICSI thawing cycles carried out during the 11 year study period. Of these thawed embryos, 628 underwent SET on Day 3 of embryo development. We measured the influence of several laboratory parameters on blastomere loss after thaw including: cell stage at cryopreservation, blastomere loss post-thaw, ability to resume mitosis and the rate of overnight cleavage.There is an association between cell number on day of freeze and embryonic survival post-thaw; 3 cell (77.4%), 4 cell (92.1%), 5 cell (81.4%) and 6 cell (86.5%) embryos (p0.05). We found a significant association between the rate of overnight cleavage and positive hCG and implantation rate (p-value0.05), while there is no association with live birth rate (p-value 0.242). Embryos with 100% blastomere survival have significantly higher cleavage rates, positive hCG, implantation and live birth rates than embryos which experienced blastomere loss (p0.05). However, blastomere survival has no impact on miscarriage rate or the observed newborn birth weight (3.85 ± 0.77 kg).In the present study we demonstrate, for the first time, that although it is optimal to select an embryo with 100% blastomere survival, transfer of an embryo with ≥ 50% blastomeres intact post-thaw does not influence the development of the baby, as indicated by weight at birth.

A 32-year-old patient with primary infertility received in vitro fertilisation (IVF) therapy. Four weeks later she developed intermittent left iliac fossa pain. Transvaginal ultrasound showed an empty uterus and an adnexal mass adjacent to the right ovary. Serum β-human chronic gonadotropin was 33 492 IU/L. At laparoscopy a mass attached to right ovary, suggestive of a right ovarian ectopic pregnancy, was excised. Histological examination confirmed an ovarian ectopic gestation, but noted enlarged chorionic villi and trophoblastic atypia, which raised the suspicion of molar pregnancy. Subsequent p57 immunohistochemistry and DNA ploidy studies excluded a mole, however. Cases of suspected molar disease in ectopic pregnancy present a diagnostic challenge for both clinicians and histopathologists, and establishing a definitive diagnosis may be difficult.

Tamoxifen, a nonsteroidal synthetic anti-oestrogen is the most widely used selective estrogen receptor modulator (SERM). Designed as a contraceptive it is most frequently used in prevention and treatment of breast cancer. Its role in gynaecology is limited to ovulation induction. Although it has a favourable effect on lipid profiles and increases bone density in postmenopausal women its use for these indications is not warranted. The practising gynaecologist will most likely be faced with the risks associated with long-term tamoxifen use: endometrial polyps, endometrial hyperplasia and endometrial cancer; venous thromboembolism, ovarian cysts and endometrioid ovarian cancers. Further insight into the oestrogen receptor (ER) tamoxifen induced changes could potentially identify new therapeutic opportunities.

We assessed the frequency of CFTR mutations in groups with varying degrees of sub-fertility and compared these groups to a fertile male group with proven paternity. Screening for CFTR mutations should be routine for all azoospermic males, irrespective of obstructive or non-obstructive etiology, prior to proposing ICSI treatment. CFTR testing has no value in the investigation of non-azoospermic infertile males.

There has been much interest in the use of anti-Mullerian hormone (AMH) as a biomarker in the assessment of ovarian reserve, and debate on its use as a predictor of assisted reproductive technology (ART) outcomes. Normal levels have not been well defined, and age-based reference ranges may have a role in counselling patients. To determine AMH levels in females attending with subfertility, identify age-specific centiles and the age-related decline, to create population normograms to be used in patient counselling prior to ART. Retrospective study in a tertiary academic Assisted Conception Centre analysing AMH levels in female patients attending for investigation of subfertility between January 2009 and December 2011 (n = 3,058). Few patients have AMH levels within external laboratory pre-defined “normal fertility potential” ranges. Only 8.1 % had “optimal fertility” and 18.6 % “satisfactory”, with 54.6 % “low” fertility and 15.9 % in the “very low/undetectable” group. By age 32, over 50 % of women have AMH levels categorised as “low fertility” (AMH ≤19.5 pmol/L), increasing to 75 % by age 39. Based on a regression model a decrease in mean AMH of 1.72 pmol/L/year was measured. We recommend that each ART centre defines their “own” normograms for accurate advice for and treatment of their patients. External laboratory-defined “normal” and “abnormal” AMH levels should be filtered and adapted to the reality of each population. These findings need to be considered when counselling patients and planning treatments as age-specific population normograms can provide a tailored approach.

Objectives: To analyse by parity the obstetric and neonatal outcome of babies delivered weighing more than 4.5 kg. Methods: All deliveries resulting in a baby weighing more than 4.5 kg, in the 5 years from 1991 to 1995, were identified using a computerised database. The following variables confined to singleton, cephalic pregnancies were recorded: mode of delivery, duration of labour, incidence of shoulder dystocia and admission to the neonatal centre. Outcome measures in primigravidae and multigravidae were compared using the Epi Info package (WHO, Version 6.0b January 1997). Results: There were 32,834 deliveries over the study period and 828 (2.5%) weighed more than 4.5 kg. Birthweight more than 4.5 kg occurred in 1.6% (n=198) of primigravidae and 3.1% (n=630) of multigravidae (P

Study question The 13th European in vitro fertilization (IVF)-monitoring (EIM) report presents the results of treatments involving assisted reproductive technology (ART) initiated in Europe during 2009: are there any changes in the trends compared with previous years? Summary answer Despite some fluctuations in the number of countries reporting data, the overall number of ART cycles has continued to increase year by year and, while pregnancy rates in 2009 remained similar to those reported in 2008, the number of transfers with multiple embryos (3+) and the multiple delivery rates declined. What is known already Since 1997, ART data in Europe have been collected and reported in 12 manuscripts, published in Human Reproduction. Study design, size, duration Retrospective data collection of European ART data by the EIM Consortium for the European Society of Human Reproduction and Embryology (ESHRE); cycles started between 1st January and 31st December are collected on a yearly basis; the data are collected by the National Registers, when existing, or on a voluntary basis. Participants/materials setting, methods From 34 countries (-2 compared with 2008), 1005 clinics reported 537 463 treatment cycles including: IVF (135 621), intracytoplasmic sperm injection (ICSI, 266 084), frozen embryo replacement (FER, 104 153), egg donation (ED, 21 604), in vitro maturation (IVM, 1334), preimplantation genetic diagnosis/screening (PGD/PGS, 4389) and frozen oocyte replacements (FOR, 4278). European data on intrauterine insemination using husband/partner's semen (IUI-H) and donor (IUI-D) semen were reported from 21 and 18 countries, respectively. A total of 162 843 IUI-H (+12.7%) and 29 235 IUI-D (+17.3%) cycles were included. Data available from each country are presented in the tables; total values (as numbers and percentages) refer to those countries where all data have been reported. Main results and the role of chance In 21 countries where all clinics reported to the ART register, a total of 399 020 ART cycles were performed in a population of 373.8 million, corresponding to 1067 cycles per million inhabitants. For IVF, the clinical pregnancy rates per aspiration and per transfer were 28.9 and 32.9%, respectively and for ICSI, the corresponding rates were 28.7 and 32.0%. In FER cycles, the pregnancy rate per thawing was 20.9%; in ED cycles, the pregnancy rate per transfer was 42.3%. The delivery rate after IUI-H was 8.3 and 13.4% after IUI-D. In IVF and ICSI cycles, 1, 2, 3 and 4+ embryos were transferred in 24.2, 57.7, 16.9 and 1.2%, respectively. The proportions of singleton, twin and triplet deliveries after IVF and ICSI (combined) were 79.8, 19.4 and 0.8%, respectively, resulting in a total multiple delivery rate of 20.2%, compared with 21.7% in 2008, 22.3% in 2007, 20.8% in 2006 and 21.8% in 2005. In FER cycles, the multiple delivery rate was 13.0% (12.7% twins and 0.3% triplets). Twin and triplet delivery rates associated with IUI cycles were 10.4/0.7% and 10.3/0.5%, following treatment with husband and donor semen, respectively. Limitations, reasons for caution The method of reporting varies among countries, and registers from a number of countries have been unable to provide some of the relevant data such as initiated cycles and deliveries. As long as data are incomplete and generated through different methods of collection, results should be interpreted with caution. Wider implications of the findings The 13th ESHRE report on ART shows a continuing expansion of the number of treatment cycles in Europe, with more than half a million of cycles reported in 2009. The use of ICSI has reached a plateau. Pregnancy and delivery rates after IVF and ICSI remained relatively stable compared with 2008 and 2007. The number of multiple embryo transfers (3+ embryos) and the multiple delivery rate have shown a clear decline.

Background Intravenous fluid is recommended in international guidelines to improve patient post-operative symptoms, particularly nausea and vomiting. The optimum fluid regimen has not been established. This prospective, randomized, blinded study was designed to determine if administration of equivolumes of a colloid (hydroxyethyl starch 130/0.4) reduced post operative nausea and vomiting in healthy volunteers undergoing ambulatory gynecologic laparoscopy surgery compared to a crystalloid solution (Hartmann’s Solution). Methods 120 patients were randomized to receive intravenous colloid (N = 60) or crystalloid (N = 60) intra-operatively. The volume of fluid administered was calculated at 1.5 ml.kg-1 per hour of fasting. Patients were interviewed to assess nausea, vomiting, anti-emetic use, dizziness, sore throat, headache and subjective general well being at 30 minutes and 2, 24 and 48 hours post operatively. Pulmonary function testing was performed on a subgroup. Results At 2 hours the proportion of patients experiencing nausea (38.2 % vs 17.9%, P = 0.03) and the mean nausea score were increased in the colloid compared to crystalloid group respectively (1.49 ± 0.3 vs 0.68 ± 0.2, P = 0.028). The incidence of vomiting and anti-emetic usage was low and did not differ between the groups. Sore throat, dizziness, headache and general well being were not different between the groups. A comparable reduction on post-operative FVC and FEV-1 and PEFR was observed in both groups. Conclusions Intra-operative administration of colloid increased the incidence of early postoperative nausea and has no advantage over crystalloid for symptom control after gynaecological laparoscopic surgery.

Background Male infertility is a common cause of reproductive failure in humans. In mice, targeted deletions of the genes coding for FKBP6 or FKBP52, members of the FK506 binding protein family, can result in male infertility. In the case of FKBP52, this reflects an important role in potentiating Androgen Receptor (AR) signalling in the prostate and accessory glands, but not the testis. In infertile men, no mutations of FKBP52 or FKBP6 have been found so far, but the gene for FKBP-like (FKBPL) maps to chromosome 6p21.3, an area linked to azoospermia in a group of Japanese patients. Methods To determine whether mutations in FKBPL could contribute to the azoospermic phenotype, we examined expression in mouse and human tissues by RNA array blot, RT-PCR and immunohistochemistry and sequenced the complete gene from two azoospermic patient cohorts and matching control groups. FKBPL-AR interaction was assayed using reporter constructs in vitro. Results FKBPL is strongly expressed in mouse testis, with expression upregulated at puberty. The protein is expressed in human testis in a pattern similar to FKBP52 and also enhanced AR transcriptional activity in reporter assays. We examined sixty patients from the Japanese patient group and found one inactivating mutation and one coding change, as well as a number of non-coding changes, all absent in fifty-six controls. A second, Irish patient cohort of thirty showed another two coding changes not present in thirty proven fertile controls. Conclusions Our results describe the first alterations in the gene for FKBPL in azoospermic patients and indicate a potential role in AR-mediated signalling in the testis.

Usage of herbal and complimentary medicines by patients presenting for procedures that require the use of anaesthetic agents is common. To determine the prevalence of herbal medication usage among female patients attending for assisted reproduction procedures involving the use of sedative or hypnotic agents. Questionnaire-based survey carried out over a 6-month period from January to July 2007. Forty-six percent of patients admitted regular use of herbal medications, with 38% of patients having taken herbal preparations in the 3-month period prior to their attendance for treatment. No patient taking herbal preparations had discussed the use of these products with the attending anaesthetist or fertility specialist prior to attending for the procedure. The usage of herbal medications with potential for serious adverse effects is high in this unique patient population. Education of both healthcare providers and patients is indicated.

During in vitro fertilization (IVF), the prevention of a premature LH surge was traditionally achieved using a gonadotrophin releasing hormone agonist (GnRH-a), and more recently, a GnRH antagonist.We report a case of a 37 year old treated using the GnRH antagonist in a second completed cycle of IVF.IVF was performed for primary infertility of 5-year duration due to frozen pelvis secondary to endometriosis.Following controlled ovarian hyperstimulation, oocyte recovery and fertilization, cleavage and transfer of two zygotes, a pregnancy established. A twin gestation was diagnosed at 7-weeks scan and pregnancy ended with the delivery of twin girls by emergency caesarean section.This is a first report of a delivery following IVF using the antagonist protocol in Ireland. Such therapy is patient friendly and its use should be introduced on a larger scale in clinical practice.

Zygote transfer is a significant limiting factor in pregnancy rates after Assisted Reproductive Technology (ART) treatment. Adequate technique appraisal should be a high priority task for any medical facility that offers this treatment. Although many clinicians have extensive personal experience, it is difficult for trainees to understand the anatomical and mechanical process of safe and adequate placing of zygotes in the uterine cavity. Ultimately, even with ultrasound help, it is a “blind procedure”. The experimental module described here allows for direct visualisation of the mechanical passage of a catheter through the cervix and final placement of the tip in relation to the intravaginal visible part of the catheter. It has worldwide practical applicability for trainees and experienced clinicians accompanying the theory and allowing adequate training and retraining of all staff performing zygote transfers.