The effect of endometriosis on live birth rate and other reproductive outcomes in ART cycles: a cohort study

Study question: What is the effect of endometriosis compared to unexplained subfertility on live birth rate in women undergoing IVF and embryo transfer (ET)? Summary answer: Endometriosis decreases live birth rate in women undergoing IVF-ET treatment, particularly with increasing severity of the disease. What is known already: Endometriosis affects up to 50% of women seeking fertility treatment and is known to reduce fecundity. There remains a debate as to effects of endometriosis on the outcomes of IVF treatment, with live birth being a secondary outcome or not reported in most studies. Study design, size, duration: A retrospective cohort study analyzing data of IVF treatment cycles from January 2000 to December 2014 was carried out. Participants/materials, setting, methods: Women with endometriosis (n = 531) and women with unexplained subfertility (n = 737) undergoing a first cycle of IVF-ET in a tertiary fertility treatment center were included in the study. The primary outcome was live birth. Other outcome measures were response to ovarian stimulation, embryo development and implantation rate. Bivariate and multivariate logistic regression analysis was performed and differences compared using Chi squared test of Student’s t-test as appropriate. Main results and the role of chance: Women with endometriosis had 24% less likelihood of a live birth when compared to those with unexplained subfertility [odds ratio (OR) 0.76 (95% CI, 0.59–0.98) P = 0.035]. This effect became more apparent with increasing severity of endometriosis. Using multivariable logistic regression analysis, the trend for lower live birth rate remained but did not reach statistical significance [adjusted OR 0.76 (95% CI 0.56–1.03), P = 0.078]. Women with endometriosis were as likely as those with unexplained subfertility to have a singleton live birth when two embryos were transferred as opposed to a single ET [OR 1.38 (95% CI 0.73–2.62), P = 0.32 and OR 3.22 (95% CI 1.7–6.05), P = 0.0003, respectively]. Compared to women with unexplained subfertility, those with endometriosis had fewer oocytes retrieved [(10.54 (95% CI 10.13–0.95) and 9.15 (95% CI 8.69–9.6), respectively], lower blastocyst transfer [OR 0.24 (95% CI 0.12–0.5), P = 0.0001] and a significantly reduced implantation rate [OR 0.73 (0.58–0.92), P = 0.007]. Limitations reasons for caution: The study is limited by a retrospective design. By limiting the study to a single ET cycle, it was not possible to assess the cumulative outcome including use of all frozen embryos. Wider implications of the findings: Endometriosis has similar phenotypes among women in different populations and would be expected to have a similar effect on fertility. These results are therefore generalizable to other populations of women. Study funding/competing interest(s): None. Trial registration number: Not applicable

Comparison of the prevalence and characteristics of inpatient adverse events using medical records review and incident reporting

Background. Information on adverse events (AEs) in hospitalised patients in developing countries is scanty.Objective. To compare the magnitude and characteristics of inpatient AEs in a tertiary, not-for-profit healthcare facility in Kenya, using medical records review and incident reporting.Methods. Estimation of prevalence was done using incidents reported in 2010 from a random sample of medical records for hospital admissions. Nurse reviewers used 18 screening criteria, followed by physician reviewers to confirm occurrence. An AE was defined as an unexpected clinical event (UE) associated with death, disability or prolonged hospitalisation not explained by the disease condition. The kappa statistic was used to estimate inter-rater agreement, and analysis was done using logistic regression.Results. The study identified 53 UEs from 2 000 randomly selected medical records and 33 reported UEs from 23 026 admissions in the index year. The prevalences of AEs from medical records review and incident reports were 1.4% (95% confidence interval (CI) 0.9 - 2.0) and 0.03% (95% CI 0.012 - 0.063), respectively. Compared with incident reporting, review of medical records identified more disability (13.2% v. 0%; p=0.03) and prolonged hospital stays (43.4% v. 18.2%; p=0.02).Conclusions. Review of medical records is preferable to incident reporting in determining the prevalence of AEs in health facilities with limited inpatient quality improvement experience. Further research is needed to determine whether staff education and a positive culture change through promotion of non-punitive UE reporting or a combination of approaches would improve the comprehensiveness of AE reporting

ESHRE guideline: endometriosis

Main results and the role of chance: This guideline aims to help clinicians to apply best care for women with endometriosis. Although studies mostly focus on women of reproductive age, the guideline also addresses endometriosis in adolescents and postmenopausal women. The guideline outlines the diagnostic process for endometriosis, which challenges laparoscopy and histology as gold standard diagnostic tests. The options for treatment of endometriosis-associated pain symptoms include analgesics, medical treatments and surgery. Non-pharmacological treatments are also discussed. For management of endometriosis-associated infertility, surgical treatment and/or medically assisted reproduction are feasible. While most of the more recent studies confirm previous ESHRE recommendations, there are five topics in which significant changes to recommendations were required and changes in clinical practice are to be expected. Limitations reasons for caution: The guideline describes different management options but, based on existing evidence, no firm recommendations could be formulated on the most appropriate treatments. Also, for specific clinical issues, such as asymptomatic endometriosis or extrapelvic endometriosis, the evidence is too scarce to make evidence-based recommendations. Wider implications of the findings: The guideline provides clinicians with clear advice on best practice in endometriosis care, based on the best evidence currently available. In addition, a list of research recommendations is provided to stimulate further studies in endometriosis.Study question: How should endometriosis be diagnosed and managed based on the best available evidence from published literature? Summary answer: The current guideline provides 109 recommendations on diagnosis, treatments for pain and infertility, management of disease recurrence, asymptomatic or extrapelvic disease, endometriosis in adolescents and postmenopausal women, prevention and the association with cancer. What is known already: Endometriosis is a chronic condition with a plethora of presentations in terms of not only the occurrence of lesions, but also the presence of signs and symptoms. The most important symptoms include pain and infertility. Study design size duration: The guideline was developed according to the structured methodology for development of ESHRE guidelines. After formulation of key questions by a group of experts, literature searches and assessments were performed. Papers published up to 1 December 2020 and written in English were included in the literature review. Participants/materials setting methods: Based on the collected evidence, recommendations were formulated and discussed within specialist subgroups and then presented to the core guideline development group (GDG) until consensus was reached. A stakeholder review was organized after finalization of the draft. The final version was approved by the GDG and the ESHRE Executive Committee. Summary answer: The current guideline provides 109 recommendations on diagnosis, treatments for pain and infertility, management of disease recurrence, asymptomatic or extrapelvic disease, endometriosis in adolescents and postmenopausal women, prevention and the association with cancer. What is known already: Endometriosis is a chronic condition with a plethora of presentations in terms of not only the occurrence of lesions, but also the presence of signs and symptoms. The most important symptoms include pain and infertility. Study design size duration: The guideline was developed according to the structured methodology for development of ESHRE guidelines. After formulation of key questions by a group of experts, literature searches and assessments were performed. Papers published up to 1 December 2020 and written in English were included in the literature review. Participants/materials setting methods: Based on the collected evidence, recommendations were formulated and discussed within specialist subgroups and then presented to the core guideline development group (GDG) until consensus was reached. A stakeholder review was organized after 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 clinicians to apply best care for women with endometriosis. Although studies mostly focus on women of reproductive age, the guideline also addresses endometriosis in adolescents and postmenopausal women. The guideline outlines the diagnostic process for endometriosis, which challenges laparoscopy and histology as gold standard diagnostic tests. The options for treatment of endometriosis-associated pain symptoms include analgesics, medical treatments and surgery. Non-pharmacological treatments are also discussed. For management of endometriosis-associated infertility, surgical treatment and/or medically assisted reproduction are feasible. While most of the more recent studies confirm previous ESHRE recommendations, there are five topics in which significant changes to recommendations were required and changes in clinical practice are to be expected. Limitations reasons for caution: The guideline describes different management options but, based on existing evidence, no firm recommendations could be formulated on the most appropriate treatments. Also, for specific clinical issues, such as asymptomatic endometriosis or extrapelvic endometriosis, the evidence is too scarce to make evidence-based recommendations. Wider implications of the findings: The guideline provides clinicians with clear advice on best practice in endometriosis care, based on the best evidence currently available. In addition, a list of research recommendations is provided to stimulate further studies in endometriosis. Study funding/competing interests: 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 payments. C.M.B. reports grants from Bayer Healthcare and the European Commission; Participation on a Data Safety Monitoring Board or Advisory Board with ObsEva (Data Safety Monitoring Group) and Myovant (Scientific Advisory Group). A.B. reports grants from FEMaLE executive board member and European Commission Horizon 2020 grant; consulting fees from Ethicon Endo Surgery, Medtronic; honoraria for lectures from Ethicon; and support for meeting attendance from Gedeon Richter; A.H. reports grants from MRC, NIHR, CSO, Roche Diagnostics, Astra Zeneca, Ferring; Consulting fees from Roche Diagnostics, Nordic Pharma, Chugai and Benevolent Al Bio Limited all paid to the institution; a pending patent on Serum endometriosis biomarker; he is also Chair of TSC for STOP-OHSS and CERM trials. O.H. reports consulting fees and speaker's fees from Gedeon Richter and Bayer AG; support for attending meetings from Gedeon-Richter, and leadership roles at the Finnish Society for Obstetrics and Gynecology and the Nordic federation of the societies of obstetrics and gynecology. L.K. reports consulting fees from Gedeon Richter, AstraZeneca, Novartis, Dr KADE/Besins, Palleos Healthcare, Roche, Mithra; honoraria for lectures from Gedeon Richter, AstraZeneca, Novartis, Dr KADE/Besins, Palleos Healthcare, Roche, Mithra; support for attending meetings from Gedeon Richter, AstraZeneca, Novartis, Dr KADE/Besins, Palleos Healthcare, Roche, Mithra; he also has a leadership role in the German Society of Gynecological Endocrinology (DGGEF). M.K. reports grants from French Foundation for Medical Research (FRM), Australian Ministry of Health, Medical Research Future Fund and French National Cancer Institute; support for meeting attendance from European Society for Gynaecological Endoscopy (ESGE), European Congress on Endometriosis (EEC) and ESHRE; She is an advisory Board Member, FEMaLe Project (Finding Endometriosis Using Machine Learning), Scientific Committee Chair for the French Foundation for Research on Endometriosis and Scientific Committee Chair for the ComPaRe-Endometriosis cohort. A.N. reports grants from Merck SA and Ferring; speaker fees from Merck SA and Ferring; support for meeting attendance from Merck SA; Participation on a Data Safety Monitoring Board or Advisory Board with Nordic Pharma and Merck SA; she also is a board member of medical advisory board, Endometriosis Society, the Netherlands (patients advocacy group) and an executive board member of the World Endometriosis Society. E.S. reports grants from National Institute for Health Research UK, Rosetrees Trust, Barts and the London Charity; Royalties from De Gruyter (book editor); consulting fees from Hologic; speakers fees from Hologic, Johnson & Johnson, Medtronic, Intuitive, Olympus and Karl Storz; Participation in the Medicines for Women's Health Expert Advisory Group with Medicines and Healthcare Products Regulatory Agency (MHRA); he is also Ambassador for the World Endometriosis Society. C.T. reports grants from Merck SA; Consulting fees from Gedeon Richter, Nordic Pharma and Merck SA; speaker fees from Merck SA, all paid to the institution; and support for meeting attendance from Ferring, Gedeon Richter and Merck SA. The other authors have no conflicts of interest to declar

Neonatal mortality in Kenyan hospitals: a multisite, retrospective, cohort study

Background Most of the deaths among neonates in low-income and middle-income countries (LMICs) can be prevented through universal access to basic high-quality health services including essential facility-based inpatient care. However, poor routine data undermines data-informed efforts to monitor and promote improvements in the quality of newborn care across hospitals.Methods Continuously collected routine patients’ data from structured paper record forms for all admissions to newborn units (NBUs) from 16 purposively selected Kenyan public hospitals that are part of a clinical information network were analysed together with data from all paediatric admissions ages 0–13 years from 14 of these hospitals. Data are used to show the proportion of all admissions and deaths in the neonatal age group and examine morbidity and mortality patterns, stratified by birth weight, and their variation across hospitals.Findings During the 354 hospital months study period, 90 222 patients were admitted to the 14 hospitals contributing NBU and general paediatric ward data. 46% of all the admissions were neonates (aged 0–28 days), but they accounted for 66% of the deaths in the age group 0–13 years. 41 657 inborn neonates were admitted in the NBUs across the 16 hospitals during the study period. 4266/41 657 died giving a crude mortality rate of 10.2% (95% CI 9.97% to 10.55%), with 60% of these deaths occurring on the first-day of admission. Intrapartum-related complications was the single most common diagnosis among the neonates with birth weight of 2000 g or more who died. A threefold variation in mortality across hospitals was observed for birth weight categories 1000–1499 g and 1500–1999 g.Interpretation The high proportion of neonatal deaths in hospitals may reflect changing patterns of childhood mortality. Majority of newborns died of preventable causes (>95%). Despite availability of high-impact low-cost interventions, hospitals have high and very variable mortality proportions after stratification by birth weight