Introduction: Uterus transplantation has recently proved that infertility in women with uterine factor infertility can be cured. It is still an experimental procedure with numerous critical details remaining to be established, including tolerance to warm and cold ischemic insults. In preparation for human uterus transplantation trials, most teams use the sheep as a model system for research and team training, since the vasculature and the uterus is of similar size as in the human. We, therefore, aimed to develop an ex vivo sheep uterus reperfusion platform that mimics the reperfusion situation so that initial assessments and comparisons can be performed without the need for costly and labor-intensive in vivo transplantation experiments. Material and methods: Isolated sheep uteri were perfused with the preservation solution IGL-1 and were then exposed to cold ischemia for either 4 (n = 6) or 48 hours (n = 7). Uteri were then reperfused for 48 hours under normothermic conditions with an oxygenated recirculating perfusate containing growth factors and synthetic oxygen carriers. Histological and biochemical analysis of the perfusate was conducted to assess reperfusion injury. Results: Quantification of cell density indicated no significant edema in the myometrium or in the endometrium of uteri exposed to 4 hours cold ischemia and then a normothermic ex vivo reperfusion for 48 hours. Only the outer serosa layer and the inner columnar luminal epithelial cells were affected by the reperfusion. However, a much faster and severe reperfusion damage of all uterine layers were evident during the reperfusion experiment following 48 hours of cold ischemia. This was indicated by major accumulation of extracellular fluid, presence of apoptotic-labeled glandular epithelial layer and vascular endothelium. A significant accumulation of lactate was measured in the perfusate with a subsequent decrease in pH. Conclusions: We developed a novel ex vivo sheep uterus model for prolonged perfusion. This model proved to be able to distinguish reperfusion injury-related differences associated to organ preservation. The experimental setup is a platform that
Abbreviations: BMI, body mass index; CI, confidence interval; CI, Ncervical intraepithelial neoplasia; pPROM, preterm premature rupture of membranes; RR, relative risk; SG, Asmall-for-gestational-age. AbstractIntroduction: Increasing evidence suggests that cervical intraepithelial neoplasia, with or without subsequent treatment, is associated with preterm delivery. We aimed to explore the association between abnormal cervical cytology of different severity and the subsequent obstetric outcomes such as preterm delivery. Material and methods:The historical register-based cohort study comprised 19 822 women in the Western Region of Sweden who had at least one abnormal cervical cytology from 1978 to 2012 before the age of 45 and a subsequent singleton delivery. The reference group comprised 39 644 women with normal cervical cytology and a subsequent singleton delivery, matched by age and parity. Data were retrieved from the Swedish National Cervical Screening Registry, linked to the Swedish Medical Birth Register and Statistic Sweden. The study outcomes were spontaneous preterm delivery before 37 and 34 weeks, low birthweight (≤2500 g), small-for-gestationalage, preterm premature rupture of membranes and neonatal mortality. Multivariable log binominal regression analyses were applied.Results: Preterm delivery before 37 weeks was more common among women with abnormal cervical cytology compared with reference group: 6% vs 4.5%; adjusted relative risk 1.30 (95% confidence interval 1.21-1.39). High vs low-grade abnormal cervical cytology implied a higher risk: 7% vs 5.8% (P < 0.001). Early preterm delivery before 34 weeks, preterm premature rupture of membranes and low birthweight, but not small-for-gestational-age and neonatal mortality, were significantly more common in women with abnormal cervical cytology compared with the reference group.Conclusions: Abnormal cervical cytology may imply an increased risk of preterm delivery. Further studies are needed to investigate whether that risk is related to treatment. K E Y W O R D Sabnormal cervical cytology, cervical intraepithelial neoplasia, neonatal mortality, pregnancy outcome, preterm delivery, preterm premature rupture of membranes, small-for-gestationalage
IntroductionAlthough considered an essential service by the WHO, there are indications that access to induced abortion care has been restricted during the COVID-19 pandemic.ObjectivesTo investigate if the number of induced abortions and ongoing pregnancies changed during the first pandemic wave of COVID-19 in 2020 compared with recent years prior to the pandemic and explore possible reasons for the findings.DesignConvergent parallel mixed-methods design. Collection of quantitative data from the Swedish National Board of Health and Welfare and the Swedish Pregnancy Register, and qualitative data from interviews.Setting and time periodNational data on abortions (January 2018–June 2020) and births (January 2018–March 2021). Interviews performed at the main abortion clinic, Gothenburg, Sweden, in June 2020.ParticipantsAll women aged 15–44 years living in Sweden 2018–2020, approximately 1.9 million. 15 women who sought abortion were interviewed.Primary and secondary outcome measuresNumber of abortions and births/1000 women aged 15–44 years. Themes and subthemes identified from interviews.ResultsThe number of abortions and ongoing pregnancies did not change significantly during the study period compared with before the pandemic started. Interview themes identified were the following: meeting with abortion care during the COVID-19 pandemic (availability, and fear of being infected and infecting others); and the impact of the COVID-19 pandemic on the abortion decision (to catch COVID-19 during pregnancy, feelings of loneliness and isolation, and social aspects).ConclusionsThis study shows that the number of abortions and ongoing pregnancies remained unchanged during the first wave of the COVID-19 pandemic in 2020 in Sweden compared with before the start of the pandemic. Abortion-seeking women did not hesitate to proceed with the abortion. The women expressed a number of fears concerning both availability of care and their health, which could have been properly addressed by the authorities.
Study question To develop an alternative fertility preservation method for young female cancer patients based on an ex vivo perfusion of whole ovaries serving as a platform for future ovarian stimulation studies. Summary answer It is possible to maintain viable follicles and to retrieve oocytes after ex vivo perfusion of ewe ovaries for up to 7 days. What is known already Some progress has been made in terms of follicular growth and the isolation of mature oocytes in vitro. However, full development, from early follicular stages to a viable offspring, has only been described in rodent models. The complex events controlling follicular expansion and the long time required for folliculogenesis and oocyte maturity in large mammalian species creating challenges and limitations for in vitro studies. Ex vivo perfusion of a whole ovary could potentially be a solution by exploiting the intact ovarian architecture to support folliculogenesis and oocyte maturation. Study design, size, duration Thirty-one ewe ovaries were divided into 4 groups and ex vivo perfused in a bioreactor. Group 1 (n = 14) perfusion for 48 hours with no hormone supplementation; Group 2 (n = 4) perfusion 96–101 hours with follicle stimulating hormone (FSH); Group 3 (n = 3) perfusion 120–168 hours with human menopausal gonadotropin (hMG); Group 4 (n = 10) perfusion 72–144 hours with hMG. Participants/materials, setting, methods Ewe ovaries from sexually mature ewes were ex vivo perfused in a bioreactor under normothermic conditions for up to 7 days (max total 168 hours). Histomorphological, immunohistochemical, hormonal and biochemical analyses were performed to assess ovarian structure and viability after cold ischemia and after perfusion which was subsequently compared to control ovaries. Main results and the role of chance The perfused ovaries in group 2 and 3 showed no significant differences in follicular density, viability and oocyte quality after ischemia and perfusion compared to control ovaries. Estradiol and progesterone levels did not increase during the perfusion. The perfused ovaries in group 1 and 4 showed a significant decrease in the ovarian reserve and oocyte quality. In total, 16 GV-MI oocytes were retrieved from groups 3 and 4. Limitations, reasons for caution 1. Ovaries were retrieved from ewes of unknown cycle and reproductive history. 2. The perfusion medium was changed after 24 hours from perfusion start to remove detrimental metabolites and this could affect the measured concentrations of hormones and metabolites in the perfusion medium. Wider implications of the findings: These results pave the way to propose ex vivo perfusion as a good platform for fertility preservation studies on whole mammalian and human ovaries to retrieve fully mature oocytes. Trial registration number Not applicable
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