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Abstract STUDY QUESTION How should recurrent implantation failure (RIF) in patients undergoing ART be defined and managed? SUMMARY ANSWER This is the first ESHRE good practice recommendations paper providing a definition for RIF together with recommendations on how to investigate causes and contributing factors, and how to improve the chances of a pregnancy. WHAT IS KNOWN ALREADY RIF is a challenge in the ART clinic, with a multitude of investigations and interventions offered and applied in clinical practice, often without biological rationale or with unequivocal evidence of benefit. STUDY DESIGN, SIZE, DURATION This document was developed according to a predefined methodology for ESHRE good practice recommendations. Recommendations are supported by data from the literature, if available, and the results of a previously published survey on clinical practice in RIF and the expertise of the working group. A literature search was performed in PubMed and Cochrane focussing on ‘recurrent reproductive failure’, ‘recurrent implantation failure’, and ‘repeated implantation failure’. PARTICIPANTS/MATERIALS, SETTING, METHODS The ESHRE Working Group on Recurrent Implantation Failure included eight members representing the ESHRE Special Interest Groups for Implantation and Early Pregnancy, Reproductive Endocrinology, and Embryology, with an independent chair and an expert in statistics. The recommendations for clinical practice were formulated based on the expert opinion of the working group, while taking into consideration the published data and results of the survey on uptake in clinical practice. The draft document was then open to ESHRE members for online peer review and was revised in light of the comments received. MAIN RESULTS AND THE ROLE OF CHANCE The working group recommends considering RIF as a secondary phenomenon of ART, as it can only be observed in patients undergoing IVF, and that the following description of RIF be adopted: ‘RIF describes the scenario in which the transfer of embryos considered to be viable has failed to result in a positive pregnancy test sufficiently often in a specific patient to warrant consideration of further investigations and/or interventions'. It was agreed that the recommended threshold for the cumulative predicted chance of implantation to identify RIF for the purposes of initiating further investigation is 60%. When a couple have not had a successful implantation by a certain number of embryo transfers and the cumulative predicted chance of implantation associated with that number is greater than 60%, then they should be counselled on further investigation and/or treatment options. This term defines clinical RIF for which further actions should be considered. Nineteen recommendations were formulated on investigations when RIF is suspected, and 13 on interventions. Recommendations were colour-coded based on whether the investigations/interventions were recommended (green), to be considered (orange), or not recommended, i.e. not to be offered routinely (red). LIMITATIONS, REASONS FOR CAUTION While awaiting the results of further studies and trials, the ESHRE Working Group on Recurrent Implantation Failure recommends identifying RIF based on the chance of successful implantation for the individual patient or couple and to restrict investigations and treatments to those supported by a clear rationale and data indicating their likely benefit. WIDER IMPLICATIONS OF THE FINDINGS This article provides not only good practice advice but also highlights the investigations and interventions that need further research. This research, when well-conducted, will be key to making progress in the clinical management of RIF. STUDY FUNDING/COMPETING INTEREST(S) The meetings and technical support for this project were funded by ESHRE. N.M. declared consulting fees from ArtPRED (The Netherlands) and Freya Biosciences (Denmark); Honoraria for lectures from Gedeon Richter, Merck, Abbott, and IBSA; being co-founder of Verso Biosense. He is Co-Chief Editor of Reproductive Biomedicine Online (RBMO). D.C. declared being an Associate Editor of Human Reproduction Update, and declared honoraria for lectures from Merck, Organon, IBSA, and Fairtility; support for attending meetings from Cooper Surgical, Fujifilm Irvine Scientific. G.G. declared that he or his institution received financial or non-financial support for research, lectures, workshops, advisory roles, or travelling from Ferring, Merck, Gedeon-Richter, PregLem, Abbott, Vifor, Organon, MSD, Coopersurgical, ObsEVA, and ReprodWissen. He is an Editor of the journals Archives of Obstetrics and Gynecology and Reproductive Biomedicine Online, and Editor in Chief of Journal Gynäkologische Endokrinologie. He is involved in guideline developments and quality control on national and international level. G.L. declared he or his institution received honoraria for lectures from Merck, Ferring, Vianex/Organon, and MSD. He is an Associate Editor of Human Reproduction Update, immediate past Coordinator of Special Interest Group for Reproductive Endocrinology of ESHRE and has been involved in Guideline Development Groups of ESHRE and national fertility authorities. D.J.M. declared being an Associate Editor for Human Reproduction Open and statistical Advisor for Reproductive Biomedicine Online. B.T. declared being shareholder of Reprognostics and she or her institution received financial or non-financial support for research, clinical trials, lectures, workshops, advisory roles or travelling from support for attending meetings from Ferring, MSD, Exeltis, Merck Serono, Bayer, Teva, Theramex and Novartis, Astropharm, Ferring. The other authors had nothing to disclose. DISCLAIMER This Good Practice Recommendations (GPR) document represents the views of ESHRE, which are the result of consensus between the relevant ESHRE stakeholders and are based on the scientific evidence available at the time of preparation. ESHRE GPRs should be used for information and educational purposes. They should not be interpreted as setting a standard of care or be deemed inclusive of all proper methods of care, or be exclusive of other methods of care reasonably directed to obtaining the same results. They do not replace the need for application of clinical judgement to each individual presentation, or variations based on locality and facility type. Furthermore, ESHRE GPRs do not constitute or imply the endorsement, or favouring, of any of the included technologies by ESHRE.

To establish the role of periodontal pathobionts as a risk factor for myocardial infarction, we examined the contribution of five periodontal pathobionts and their virulence genes’ expressions to myocardial injury (Troponin-I) and coronary artery disease burden (SYNTAX-I scores) using hierarchical linear regression. Pathobiont loads in subgingival-plaques and intra-coronary-thrombi were compared. Troponin-I release increased with one 16S rRNA gene copy/ng DNA of Porphyromonas gingivalis (β = 6.8 × 10 –6 , 95% CI = 1.1 × 10 –7 –2.1 × 10 –5 ), one-fold increased expressions of fimA (β = 14.3, 95% CI = 1.5–27.1), bioF-3 (β = 7.8, 95% CI = 1.1–12.3), prtH (β = 1107.8, 95% CI = 235.6–2451.3),  prtP (β = 6772.8, 95% CI = 2418.7–11,126.9),  ltxA (β = 1811.8, 95% CI = 217.1–3840.8), cdtB (β = 568.3, 95% CI = 113.4–1250.1), all  p  < 0.05. SYNTAX-I score increased with one 16S rRNA gene copy/ng DNA of Porphyromonas gingivalis (β = 3.8 × 10 –9 , 95% CI = 3.6 × 10 –10 -1.8 × 10 –8 ), one-fold increased expressions of fimA (β = 1.2, 95% CI = 1.1–2.1), bioF-3 (β = 1.1, 95% CI = 1–5.2),  prtP (β = 3, 95% CI = 1.3–4.6),  ltxA (β = 1.5, 95% CI = 1.2–2.5), all  p  < 0.05. Within-subject Porphyromonas gingivalis  and  Tannerella forsythia from intra-coronary-thrombi and subgingival-plaques correlated (rho = 0.6,  p  < 0.05). Higher pathobiont load and/or upregulated virulence are risk factors for myocardial infarction. Trial registration: ClinicalTrials.gov Identifier: NCT04719026.

Objective To compare the effectiveness of elective single embryo transfer versus double embryo transfer on the outcomes of live birth, multiple live birth, miscarriage, preterm birth, term singleton birth, and low birth weight after fresh embryo transfer, and on the outcomes of cumulative live birth and multiple live birth after fresh and frozen embryo transfers.Design One stage meta-analysis of individual patient data.Data sources A systematic review of English and non-English articles from Medline, Embase, and the Cochrane Central Register of Controlled Trials (up to 2008). Additional studies were identified by contact with clinical experts and searches of bibliographies of all relevant primary articles. Search terms included embryo transfer, randomised controlled trial, controlled clinical trial, single embryo transfer, and double embryo transfer.Review methods Comparisons of the clinical effectiveness of cleavage stage (day 2 or 3) elective single versus double embryo transfer after fresh or frozen in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) treatments were included. Trials were included if the intervention differed only in terms of the intended number of embryos to be transferred. Trials that involved only blastocyst (day five) transfers were excluded.Results Individual patient data were received for every patient recruited to all eight eligible trials (n=1367). A total of 683 and 684 women randomised to the single and double embryo transfer arms, respectively, were included in the analysis. Baseline characteristics in the two groups were comparable. The overall live birth rate in a fresh IVF cycle was lower after single (181/683, 27%) than double embryo transfer (285/683, 42%) (adjusted odds ratio 0.50, 95% confidence interval 0.39 to 0.63), as was the multiple birth rate (3/181 (2%) v 84/285 (29%)) (0.04, 0.01 to 0.12). An additional frozen single embryo transfer, however, resulted in a cumulative live birth rate not significantly lower than the rate after one fresh double embryo transfer (132/350 (38%) v 149/353 (42%) (0.85, 0.62 to 1.15), with a minimal cumulative risk of multiple birth (1/132 (1%) v 47/149 (32%)). The odds of a term singleton birth (that is, over 37 weeks) after elective single embryo transfer was almost five times higher than the odds after double embryo transfer (4.93, 2.98 to 8.18).Conclusions Elective single embryo transfer results in a higher chance of delivering a term singleton live birth compared with double embryo transfer. Although this strategy yields a lower pregnancy rate than a double embryo transfer in a fresh IVF cycle, this difference is almost completely overcome by an additional frozen single embryo transfer cycle. The multiple pregnancy rate after elective single embryo transfer is comparable with that observed in spontaneous pregnancies.

We estimated prevalence and incidence of liver condition outcomes, and costs to the health service of diagnosed hepatitis B virus (HBV) in Tayside, UK. HBV patients were identified from electronic virology data between 1989 and 2003. The health resource costs of HBV for surface antigen-positive (HBsAg+) patients and HBV (HBsAg+ or immune, i.e. recovered) patients were calculated. A total of 633 patients had HBV (275 HBsAg+), and were more likely to be male (62% vs. 48%), older (mean age 42·6 vs. 39·2 years) and deprived than the general population. The prevalence of immune individuals increased steadily. Post-HBV diagnosis, 24% of immune and 13% of HBsAg+ patients were diagnosed with a liver condition. The median cost per immune patient (£3023) was greater than per HBsAg+ patient (£1498) (P = 0·02). While increasing prevalence of immune HBV patients highlights an increase in screening and treatment, the costs associated with this group are high.

Summary Concern about calcium supplements, and mainly minor side effects (e.g. constipation) impacting on compliance, means that assessing dietary calcium intake is important. There is no suitable biomarker. Compared to food diaries, a short questionnaire was an efficient way of confirming that patients had adequate calcium intakes (>700 or >1,000 mg) Introduction Calcium is usually given alongside treatments for osteoporosis, but recent concerns about potential side effects have led to questioning whether supplements are always necessary. It is difficult to assess calcium intake in a clinical setting and be certain that the patient is getting enough calcium. The aim of this study was to determine whether a short questionnaire for estimating dietary calcium intakes in a clinical setting was fit for purpose. Methods We assessed dietary calcium intakes using a short questionnaire (CaQ) in patients attending an osteoporosis clinic ( n  = 117) and compared them with calcium intakes obtained from a 7-day food diary ( n  = 72) and a food frequency questionnaire (FFQ) ( n  = 33). Results Mean (SD) daily calcium intakes from the CaQ were 836 (348) mg; from the diaries, 949 (384) mg; and from the FFQ, 1,141 (387) mg. The positive predictive value (PPV) was >80 % for calcium cut-offs > 700 mg and 70 % for cut-offs > 1,000 mg. The calcium intakes for the false positives results were not far below the cut-off. For 1,200 mg, the PPV was 67 % or less. Conclusion The CaQ is an adequate tool for assessing whether a patient has daily calcium intakes above 700 or 1,000 mg; if below these cut-offs, it is possible that the patient still has enough calcium in the diet, which could be clarified by questioning the patient further. As there were few patients with calcium intakes above 1,200 mg a day, the CaQ cannot be recommended as a tool for confirming higher dietary calcium intakes.

IntroductionNew patients’ attendance rates at the specialist clinic for hepatitis C virus (HCV) management in Grampian are around 45% and a significant proportion of those attending fail to remain under follow-up for a variety of reasons. In an attempt to increase the number of HCV positive individuals attending specialist care, an appointment with a Hepatology Nurse Specialist at their General Practice surgery or community hospital was offered to all those previously referred, still alive and living in our Health Board area.Aim(1). Describe the demography of those previously referred, still alive and living in the area but no longer attending specialist care; (2). Evaluate different strategies for re-engagement with Hepatitis C services; (3). Compare the demographic features of those accepting and declining offer of re-engagement.MethodSubjects were identified from the Grampian HCV database and the re-engagement exercise was conducted using three methods depending on the preference and resources of General Practice Surgeries: (1). Appointments coincided with provision of existing Methadone prescriptions; (2). Patients were telephoned and chose the time of their appointment. If patients were uncontactable by telephone, appointments were sent by post; (3). Appointments were allocated and time communicated by letter. Only one surgery linked appointments with current Methadone prescriptions. Data were analysed using PASW Statistics V.18. Characteristics of individuals under follow-up were compared to individuals requiring appointments using the Continuity corrected χ2 test for categorical data and the non-parametric Mann–Whitney test for skewed continuous data. A logistic regression model was fitted to investigate whether gender, age and Carstair's deprivation category could influence loss to follow-up. The same statistical tests were used to compare characteristics of individuals who re-engaged with those who failed to attend clinic appointments. Associations between clinic attendance and method of re-engagement were examined using the Continuity corrected χ2 test for categorical data.ResultsWe identified 276 patients requiring follow-up. Those lost to follow-up were significantly younger than patients under continued follow-up (median (IQR) age 34 (30–40) vs 39 (32–49)) (p<0.001). Patients under continued follow-up were more likely to live in deprivation category 1 (OR 2.50 (CI 1.07 to 5.85)) (p=0.035) and 2 (OR 2.43 (CI 1.27 to 4.62)) (p=0.007) than those lost to follow-up, although the gender distribution was similar in both groups. All 276 patients not under follow-up were offered appointments: 96 (35%) attended and 11 declined. Gender, age and deprivation category had no significant effect on re-engagement. Linking appointments with Methadone prescriptions resulted in 89% (31/35) attendance, significantly higher than arranging appointments by prior telephone discussion 43% (24/56) (p=0.009) or allocating appointments with communication by letter 24% (41/174) (p<0.001).ConclusionLinking appointments with Methadone prescriptions was associated with significantly higher attendance than other methods although this was only possible in 13% of cases. Allocation and communication by letter resulted in very disappointing attendance rates. This study has demonstrated that a change in the traditional method of service delivery may be required for the successful re-engagement of those with hepatitis C infection and effort should be directed in linking appointments for management of Hepatitis C with their Methadone appointment in appropriate individuals.

ObjectiveTo ascertain the chance of a second pregnancy resulting in live birth following pregnancy loss.MethodsScottish data on all women whose first pregnancy occurred between 1981 and 2000 were linked to records of a subsequent pregnancy. The exposed cohorts comprised women with a first ectopic pregnancy, miscarriage, stillbirth or termination. The unexposed cohort comprised women who had an initial live birth. Kaplan–Meier curves of time to second pregnancy outcome and live birth from the date of first pregnancy were constructed. Cox's proportional hazards models were used to calculate the HR with 95% CI of any second pregnancy and live birth. The reference category was women whose first pregnancy ended in a live birth.ResultsThere were 667 144 women with an initial live birth, 39 530 with a miscarriage, 2969 with an ectopic first pregnancy, 3094 with a stillbirth and 78 493 with termination of their first pregnancy. After adjusting for maternal age at first delivery, socioeconomic status and year of first pregnancy event, the HR (95% CI) of any second pregnancy was 1.35 (1.28 to 1.42), 2.24 (2.21 to 2.27), 2.44 (2.35 to 2.54), 0.66 (0.65 to 0.67) following ectopic, miscarriage, stillbirth and termination respectively. The adjusted hazards of a live birth following ectopic, miscarriage, stillbirth and termination were 0.71 (0.64 to 0.79); 0.92 (0.90 to 0.95), 1.17 (1.06 to 1.29), 0.62 (0.60 to 0.63) respectively.ConclusionCompared to an initial live birth, pregnancy loss increased the chance of another pregnancy (except in case of termination) but decreased the chance of a live birth (except stillbirth), emphasising the role of voluntary contraception in fertility patterns.

A recent improvement in superimposed training for channel estimation, where the training sequence is actually added to the information data, is called data-dependent superimposed training (DDST). Here we show (theoretically and via simulations) that the performance of DDST (both for channel estimation and equalisation) may suffer minimal degradation when implemented without the use of a cyclic prefix (which carries only redundant information).