Management & prognosis of endometrial hyperplasia

This thesis investigates the management and prognosis of endometrial hyperplasia. The literature on conservative therapies for endometrial hyperplasia is systematically reviewed and a meta-analysis is performed to identify the most effective treatment. Further meta-analysis is performed for young women with severe endometrial hyperplasia or cancer to explore the effectiveness of fertility-sparing treatment. A national survey of Gynaecologists is performed to evaluate current and the need for further research. A large cohort study is included that defines the regression and relapse of endometrial hyperplasia with two popular conservative therapies, the Levonorgestrel-releasing intrauterine system (LNG-IUS) and oral progestogens. The LNG-IUS is found to induce regression more often with fewer events of relapse than oral progestogens. A prediction model based on clinical characteristics and biomarkers finds that morbid obesity is an independent predictor for relapse. This research has major implications for clinical practice and a national guideline in process is based on its findings

Effectiveness of strategies incorporating training and support of traditional birth attendants on perinatal and maternal mortality: meta-analysis

Objective To assess the effectiveness of strategies incorporating training and support of traditional birth attendants on the outcomes of perinatal, neonatal, and maternal death in developing countries

Individual, health facility and wider health system factors contributing to maternal deaths in Africa: a scoping review

The number of women dying during pregnancy and after childbirth remains unacceptably high, with African countries showing the slowest decline. The leading causes of maternal deaths in Africa are preventable direct obstetric causes such as haemorrhage, infection, hypertension, unsafe abortion, and obstructed labour. There is an information gap on factors contributing to maternal deaths in Africa. Our objective was to identify these contributing factors and assess the frequency of their reporting in published literature. We followed the Arksey and O’Malley methodological framework for scoping reviews. We searched six electronic bibliographic databases: MEDLINE, SCOPUS, African Index Medicus, African Journals Online (AJOL), French humanities and social sciences databases, and Web of Science. We included articles published between 1987 and 2021 without language restriction. Our conceptual framework was informed by a combination of the socio-ecological model, the three delays conceptual framework for analysing the determinants of maternal mortality and the signal functions of emergency obstetric care. We included 104 articles from 27 African countries. The most frequently reported contributory factors by level were: (1) Individual—level: Delay in deciding to seek help and in recognition of danger signs (37.5% of articles), (2) Health facility—level: Suboptimal service delivery relating to triage, monitoring, and referral (80.8% of articles) and (3) Wider health system—level: Transport to and between health facilities (84.6% of articles). Our findings indicate that health facility—level factors were the most frequently reported contributing factors to maternal deaths in Africa. There is a lack of data from some African countries, especially those countries with armed conflict currently or in the recent past. Information gaps exist in the following areas: Statistical significance of each contributing factor and whether contributing factors alone adequately explain the variations in maternal mortality ratios (MMR) seen between countries and at sub-national levels

Individual, health facility and wider health system factors contributing to maternal deaths in Africa: A scoping review

The number of women dying during pregnancy and after childbirth remains unacceptably high, with African countries showing the slowest decline. The leading causes of maternal deaths in Africa are preventable direct obstetric causes such as haemorrhage, infection, hypertension, unsafe abortion, and obstructed labour. There is an information gap on factors contributing to maternal deaths in Africa. Our objective was to identify these contributing factors and assess the frequency of their reporting in published literature. We followed the Arksey and O’Malley methodological framework for scoping reviews. We searched six electronic bibliographic databases: MEDLINE, SCOPUS, African Index Medicus, African Journals Online (AJOL), French humanities and social sciences databases, and Web of Science. We included articles published between 1987 and 2021 without language restriction. Our conceptual framework was informed by a combination of the socio-ecological model, the three delays conceptual framework for analysing the determinants of maternal mortality and the signal functions of emergency obstetric care. We included 104 articles from 27 African countries. The most frequently reported contributory factors by level were: (1) Individual—level: Delay in deciding to seek help and in recognition of danger signs (37.5% of articles), (2) Health facility—level: Suboptimal service delivery relating to triage, monitoring, and referral (80.8% of articles) and (3) Wider health system—level: Transport to and between health facilities (84.6% of articles). Our findings indicate that health facility—level factors were the most frequently reported contributing factors to maternal deaths in Africa. There is a lack of data from some African countries, especially those countries with armed conflict currently or in the recent past. Information gaps exist in the following areas: Statistical significance of each contributing factor and whether contributing factors alone adequately explain the variations in maternal mortality ratios (MMR) seen between countries and at sub-national levels

Author Correction:A comprehensive analysis of chromosomal polymorphic variants on reproductive outcomes after intracytoplasmic sperm injection treatment

Correction to: Scientific Reports https://doi.org/10.1038/s41598-023-28552-w, published online 24 January 202

Methods for managing miscarriage:a network meta-analysis

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:The objectives of this review are:• to estimate the relative effectiveness and safety profiles for methods of management of miscarriage;• to provide a ranking of the available methods according to their effectiveness and safety profile

Uterotonic Drugs for the Prevention of Postpartum Haemorrhage: A Cost-Effectiveness Analysis.

ObjectiveThe objective of this study was to estimate the relative cost effectiveness for the full range of uterotonic drugs available for preventing postpartum haemorrhage (PPH).MethodsA model-based economic evaluation was constructed using effectiveness data from a network meta-analysis, and supplemented by the literature. A UK National Health Service (NHS) perspective was adopted for the analysis, which is based on UK costs from published sources. The primary outcome measure is cost per case of PPH avoided (≥ 500 mL blood loss), with secondary outcome measures of cost per case of severe PPH avoided (≥ 1000 mL) and cost per major outcome (surgery) averted also being analysed.ResultsCarbetocin is shown to be the most effective strategy. Excluding adverse events, 'ergometrine plus oxytocin' was shown to be the least costly strategy. The incremental cost-effectiveness ratio for prevention of PPH with carbetocin compared with prevention with 'ergometrine plus oxytocin' was £1889 per case of PPH ≥ 500 mL avoided; £30,013 per case of PPH ≥ 1000 mL avoided; and £1,172,378 per major outcome averted. Including adverse events in the analysis showed oxytocin to be the least costly strategy. The incremental cost-effectiveness ratio for prevention of PPH with carbetocin compared with prevention with oxytocin was £928 per case of PPH ≥ 500 mL avoided; £22,900 per case of PPH ≥ 1000 mL avoided; and £894,514 per major outcome averted.ConclusionThe results suggest carbetocin, oxytocin and 'ergometrine plus oxytocin' could all be favourable options for being the most cost-effective strategy for preventing PPH. Carbetocin could be the preferred choice, especially if the price of carbetocin decreased. Mixed findings mean a clear-cut conclusion cannot be made as to which uterotonic is the most cost effective. Future research should focus on collecting more robust evidence on the probability of having adverse events from the uterotonic drugs, and on adapting the model for low- and middle-income countries

Miscarriage syndrome : linking early pregnancy loss to obstetric and age-related disorders

Upon embryo implantation, the uterine mucosa - the endometrium - transforms into a robust decidual matrix that accommodates the fetal placenta throughout pregnancy. This transition is driven by the differentiation of endometrial fibroblasts into specialised decidual cells. A synchronised influx of circulating natural killer (NK) cells and bone marrow-derived mesenchymal stem/progenitor cells (BM-MSC) is pivotal for decidual homeostasis and expansion in early pregnancy. We hypothesise that pathological signals interfering with the recruitment or activity of extrauterine cells at the maternal-fetal interface link miscarriage to subsequent adverse pregnancy outcomes, including further pregnancy losses and preterm labour. NK cells and BM-MSC are key homeostatic regulators in multiple tissues, pointing towards a shared aetiology between recurrent miscarriage and age-related disorders, including cardiometabolic disease. We propose the term ‘miscarriage syndrome’ to capture the health risks associated with miscarriage and discuss how this paradigm can inform clinical practice and accelerate the development of preventative strategies