Endometriosis is associated with a range of pelvic-abdominal pain symptoms and infertility. It is a chronic disease that can have a significant impact on various aspects of women's lives, including their social and sexual relationships, work, and study. Despite several international guidelines on the management of endometriosis, there is a wide variety of clinical practice in the management of endometriosis, resulting in many women receiving delayed or suboptimal care. In this paper we discuss the possibilities and benefits of using electronic health records for clinical research in the field of endometriosis. The development of a wide range of clinical software for electronic patient records has made the registration of large datasets feasible and the integration of research files and clinical files possible. Integration of global standards on registration of endometriosis care in electronic health records could improve reporting of research data and facilitate the execution of large, multicentre randomized trials on the management of endometriosis. These highly needed trials could bring us the evidence needed for the optimisation of management of women with endometriosis.

Study question Does enhancing oxygen availability during dynamic in vitro culture of bovine ovarian cortical tissue (BOCT) improve follicle growth and health? Summary answer Enhancing oxygen availability during dynamic in vitro culture of BOCT in perifusion bioreactors (PB) does improve follicle health and yield to secondary follicles What is known already Oxygen availability has been demonstrated to represent a key factor in follicle health and growth during in vitro culture of bovine and human ovarian cortical tissue (HOCT) under static culture conditions. Disruption of solutes gradients and application of physiological fluid mechanical stress, through in vitro dynamic culture of HOCT in a newly designed perifusion bioreactor have been shown to further enhance follicle growth and health. As it shows striking similarities with human, bovine folliculogenesis is considered a valuable model to study follicle growth in vitro Study design, size, duration Bovine ovaries from animals aged 8-24 months were collected at slaughterhouse. In each experiment (n = 3), BOCT strips from the same ovary were cultured for 6 days in perifusion bioreactors (PB, dynamic culture) and conventional dishes (CD, static culture). Culture outcome in static culture was analysed and compared to two bioreactor configurations in which medium oxygenation was kept low by using a standard tube reservoir (StPB) or was enhanced by using a gas-permeable dish reservoir (PB+O2). Participants/materials, setting, methods Slices of BOCT 0.5mm thick were cut with a tissue slicer and chopped into 1x1mm strips. In each experiment, fresh (D0) and cultured tissue (groups of ten strips) were analyzed. Follicle stages and health were assessed by histology (hematoxylin-eosin staining). Follicle viability was estimated by labelling with live-dead far-red and propidium iodide followed by clearing before analysis at the confocal laser scanning microscope. Main results and the role of chance Overall, 2417 follicles were analyzed (histology, 1476; viability, 941). At day 0 most follicles were primordial (primordial, 88.7%; primary, 10.6%; secondary, 0.7%), and had good quality (grade 1-2, 92.2%; grade 3, 7.8%), and high viability (91.8%). At day 6, follicle growth and health in StPB was superior than in CD (StPB vs CD - staging: primordial, 6.8 vs 16.3, P < 0.01; primary, 70.7 vs 74.1, NS; secondary, 22.5 vs 9.6%, P < 0.01; grading: grade 1 + 2, 71.4 vs 44.8, P < 0.01; grade 3, 28.6 vs 55.2%, P < 0.01). Dynamic culture in StPB better-preserved follicle viability compared to static culture in CD (StPB vs CD: 77.75 vs 64.9%, P < 0.01). Enhancing oxygen availability during dynamic culture increased follicle progression and viability (PB+O2 vs StPB - staging: primordial, 5.1 vs 6.8, NS; primary, 65.4 vs 70.7, NS; secondary, 29.5 vs 22.5%, P < 0.05; viability - 92 vs 77.75, P < 0.01). Overall, the obtained results demonstrate that i) disruption of stagnant layers of medium and application of shear stress to BOCT through dynamic culture improves follicle activation, growth and health; ii) enhancing oxygen availability by means of a gas-permeable medium reservoir further increases follicle progression and viability. Limitations, reasons for caution Although the bovine is considered a reliable model for human folliculogenesis, the study should be validated on human ovarian tissue. Wider implications of the findings A limiting step in the in vitro production of mature oocytes starting from primordial follicles is the low yield of secondary follicles after organ culture. The adoption of a newly designed dynamic bioreactor and modulation of oxygen availability could represent a valuable tool for multistep in vitro folliculogenesis. Trial registration number none

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Study question Which costs and effects must be considered in an economic evaluation of Medically Assisted Reproduction (MAR) and to which extent do published studies consider these? Summary answer Current economic evaluations of MAR focus on technical efficiency using narrow short-term perspectives and excluding relevant costs/effects, and hence, fail to provide adequate ‘value-for-money’ information. What is known already Due to limited budgets of health systems and patients, decision-makers need to understand which MAR interventions are cost-effective. However, it is complex to evaluate MAR from an economic perspective, as MAR treatment involves women, men, their relationship, and potential children born. Hence, it remains unclear which costs and effects related to these different stakeholders should be accounted for, and over which time horizon. In this study, we performed a systematic review of health economic studies in MAR and compared the results with a predefined value-framework providing 12 cost categories and 9 effect categories. Study design, size, duration A systematic review was performed of articles (published 2010-2021) in PubMed Central, Embase, Web of Science CC, CINAHL, Cochrane (CENTRAL), HTA and NHS EED. Using the PICO framework, full economic evaluations (cost-utility analysis (CUA), cost-benefit analysis (CBA), cost-minimization analysis (CMA) and cost-effectiveness analysis (CEA)) were selected and assessed. We identified 66 economic evaluations of MAR, including the analysis of 81 Incremental Cost-Effectiveness Ratios (ICER) as 15 studies presented more than one ICER. Participants/materials, setting, methods Our value-framework lists 12 cost-categories (infertility diagnosis, MAR, pregnancy, delivery, post-natal -care, basic/complicated childcare, care for involuntary childlessness, productivity losses (MAR/pregnancy/childcare), patient out-of-pocket expenses, broader long-term social costs) and 9 effect-categories (health child/parents short- and long-term, well-being child/parents short- and long-term, broader long-term social benefits) of MAR, indicating which costs/effects are relevant for different analytical methods (CEA/CUA/CBA), time-horizons (<1 year/1-5 years/>5 years) and perspectives (health system/patient/society). All ICERs were analysed based on their included costs/effects. Main results and the role of chance There is a large scope of costs and effects potentially relevant to understand the economic value of MAR. Of the 66 included studies, 88% performed a CEA whereas 2% performed a CUA. Most ICERs expressed cost-effectiveness as cost per live birth (52%) or cost per pregnancy (24%) whereas one study expressed the result as cost per QALY. 24% of all ICERs adopted the broader societal perspective, whereas 61% adopted the narrower health system perspective. Time horizons considered were very heterogeneous, with 68% not looking further than one year after treatment and 1% considering a time horizon of a lifetime. Only the direct costs of MAR and the short-term medical outcomes of born children were consistently accounted for in all ICERs. The following significant costs and effects were largely neglected: costs related to diagnostics, pregnancy and delivery (including complications), postnatal follow-up care and childcare; indirect costs (patient out-of-pocket expenses, productivity losses); indirect effects of infertility on the health of wish parents; longer term costs and effects of a live birth. These significant cost and effects were excluded due to the limited scope set by most studies, adopting short time horizons and narrow perspectives. Limitations, reasons for caution The systematic review relied on available databases of published scientific articles. Therefore, economic evaluations published in the grey literature (government reports, unpublished manuscripts, etc.) may have been missed. Only articles published in English were included. Wider implications of the findings As MAR has broad implications for many stakeholders, future studies should adopt more accurate costing-methods (using our value-framework) and focus on allocative efficiency. Hence, the debate about the value-for-money of MAR and about how large MAR budgets should be relative to those of other disease areas, will be better informed. Trial registration number Not applicable