Cytokines are a type of protein that play an important role in the immune response and can also affect many physiological processes in the body. Cytokine polymorphisms refer to genetic variations or mutations that occur within the genes that code for cytokines, which may affect the level of cytokine production and function. Some cytokine polymorphisms have been associated with an increased risk of developing certain diseases, while others may be protective or have no significant effect on health. In recent years, the role of cytokine polymorphisms in the development of recurrent pregnancy loss (RPL) has been studied. RPL or miscarriage is defined as the occurrence of two or more consecutive pregnancy losses before the 20th week of gestation. There are diverse causes leading to RPL, including genetic, anatomical, hormonal, and immunological factors. With regard to cytokine polymorphisms, a few of them have been found to be associated with an increased risk of RPL, for instance, variations in the genes that code for interleukin-6, tumor necrosis factor-alpha, and interleukin-10. The exact mechanisms by which cytokine polymorphisms affect the risk of recurrent miscarriage are still being studied, and further research is essential to fully understand this complex condition. This brief review aims to summarize the recent literature on the association between cytokine polymorphisms and RPL.

The number of females within the speciality of trauma and orthopaedics (T&O) is increasing. The aim of this study was to identify: 1) current attitudes and behaviours of UK female T&O surgeons towards pregnancy; 2) any barriers faced towards pregnancy with a career in T&O surgery; and 3) areas for improvement. This is a cross-sectional study using an anonymous 13-section web-based survey distributed to female-identifying T&O trainees, speciality and associate specialist surgeons (SASs) and locally employed doctors (LEDs), fellows, and consultants in the UK. Demographic data was collected as well as closed and open questions with adaptive answering relating to attitudes towards childbearing and experiences of fertility and complications associated with pregnancy. A descriptive data analysis was carried out. A total of 226 UK female T&O surgeons completed the survey. All regions of the UK were represented. Overall, 99/226 (44%) of respondents had at least one child, while 21/226 (9.3%) did not want children. Median age at first child was 33 years (interquartile range 32 to 36). Two-thirds (149/226; 66%) of respondents delayed childbearing due to a career in T&O and 140/226 (69%) of respondents had experienced bias from colleagues directed at female T&O surgeons having children during training. Nearly 24/121 (20%) of respondents required fertility assistance, 35/121 (28.9%) had experienced a miscarriage, and 53/121 (43.8%) had experienced obstetric complications. A large proportion of female T&O surgeons have and want children. T&O surgeons in the UK delay childbearing, have experienced bias and have high rates of infertility and obstetric complications. The information from this study will support female T&O surgeons with decision making and assist employers with workforce planning. Further steps are necessary in order to support female T&O surgeons having families.

Reciprocal IVF is a route to parenthood that, for the first time, allows cis two-mother families (and other couples in which both partners have a uterus and egg stores) to ‘share’ biological parenthood. This family form offers a valuable opportunity for researchers to examine experiences of gestational and genetic motherhood within the same family, and this article is the first to take a sociological approach to exploring kinship within this emerging family form. Drawing upon interview data with 14 two-mother families (28 mothers) who have conceived via reciprocal IVF, we show that mothers hold complex, creative and sometimes contradictory understandings of the ‘multiple motherhoods’ within their family (i.e. genetic, epigenetic and gestational motherhood). Overall, mothers took an active and strategic approach to constructing kinship within their family, and these findings have theoretical, empirical and clinical implications.

Irritable bowel syndrome (IBS) and endometriosis pose significant challenges to affected individuals. IBS, which is a functional gastrointestinal disorder, affects 5-10% of the population, while endometriosis affects 1 in 10 of those assigned female at birth. Despite distinct origins, symptom often overlap, which may lead to misdiagnosis. Diagnosing IBS and endometriosis requires a comprehensive approach. Nutritional management for IBS emphasises self-help strategies, nutritional changes and gut-brain axis modulation. The low FODMAP diet, which reduces the intake of foods containing specific types of carbohydrate, can be effective but requires the support of trained health professionals. For the management of endometriosis, a Mediterranean-style diet rich in antioxidants shows promise. Gastrointestinal symptoms are common with endometriosis and an individualised approach is recommended. Furthermore, vitamin D status assessment is advised. Collaboration between health professionals and dietitians is vital for tailored interventions, to enhance the wellbeing of individuals with IBS or endometriosis. A holistic approach holds promise in symptom management for both conditions.

Artificial intelligence as a medical device is increasingly being applied to healthcare for diagnosis, risk stratification and resource allocation. However, a growing body of evidence has highlighted the risk of algorithmic bias, which may perpetuate existing health inequity. This problem arises in part because of systemic inequalities in dataset curation, unequal opportunity to participate in research and inequalities of access. This study aims to explore existing standards, frameworks and best practices for ensuring adequate data diversity in health datasets. Exploring the body of existing literature and expert views is an important step towards the development of consensus-based guidelines. The study comprises two parts: a systematic review of existing standards, frameworks and best practices for healthcare datasets; and a survey and thematic analysis of stakeholder views of bias, health equity and best practices for artificial intelligence as a medical device. We found that the need for dataset diversity was well described in literature, and experts generally favored the development of a robust set of guidelines, but there were mixed views about how these could be implemented practically. The outputs of this study will be used to inform the development of standards for transparency of data diversity in health datasets (the STANDING Together initiative).

Analysis of cell-free DNA methylation (cfDNAme), alone or combined with CA125, could help to detect ovarian cancers earlier and may reduce mortality. We assessed cfDNAme in regions of ZNF154, C2CD4D and WNT6 via targeted bisulfite sequencing in diagnostic and early detection (preceding diagnosis) settings. Diagnostic samples were obtained via prospective blood collection in cell-free DNA tubes in a convenience series of patients with a pelvic mass. Early detection samples were matched case-control samples derived from the UK Familial Ovarian Cancer Screening Study (UKFOCSS). In the diagnostic set (ncases = 27, ncontrols = 41), the specificity of cfDNAme was 97.6% (95% CI: 87.1%-99.9%). High-risk cancers were detected with a sensitivity of 80% (56.3%-94.3%). Combination of cfDNAme and CA125 resulted in a sensitivity of 94.4% (72.7%-99.9%) for high-risk cancers. Despite technical issues in the early detection set (ncases = 29, ncontrols = 29), the specificity of cfDNAme was 100% (88.1%-100.0%). We detected 27.3% (6.0%-61.0%) of high-risk cases with relatively lower genomic DNA (gDNA) contamination. The sensitivity rose to 33.3% (7.5%-70.1%) in samples taken <1 year before diagnosis. We detected ovarian cancer in several patients up to 1 year before diagnosis despite technical limitations associated with archival samples (UKFOCSS). Combined cfDNAme and CA125 assessment may improve ovarian cancer screening in high-risk populations, but future large-scale prospective studies will be required to validate current findings.

A cyclical evolvement of the endometrium into a transient state of receptivity is crucial for acceptance of the semi-allogeneic foetus, conducive to pregnancy. Despite documentation of aberrances in this process within patients experiencing repeated embryo implantation failures and miscarriages, the endometrium is often overlooked in IVF clinics as the cause for failure. Focus instead is usually given to embryo-derived factors, such as aneuploidy. Nevertheless, failure of approximately 30 % of euploid embryos to implant demonstrates that other factors such as the endometrium require clinical exploration. Here, we review both traditional and novel methods used to assess endometrial receptivity such as identifying the WOI, endometrial immune profiling and transcriptomics panel testing. Where reported, we will also discuss their clinical application, as well as novel potential biomarkers within the pre-clinical research stages which show promise in their ability to assess endometrial receptivity.

BackgroundThe high incidence of aneuploidy in early human development, arising either from errors in meiosis or postzygotic mitosis, is the primary cause of pregnancy loss, miscarriage, and stillbirth following natural conception as well as in vitro fertilization (IVF). Preimplantation genetic testing for aneuploidy (PGT-A) has confirmed the prevalence of meiotic and mitotic aneuploidies among blastocyst-stage IVF embryos that are candidates for transfer. However, only about half of normally fertilized embryos develop to the blastocyst stage in vitro, while the others arrest at cleavage to late morula or early blastocyst stages.MethodsTo achieve a more complete view of the impacts of aneuploidy, we applied low-coverage sequencing-based PGT-A to a large series (n = 909) of arrested embryos and trophectoderm biopsies. We then correlated observed aneuploidies with abnormalities of the first two cleavage divisions using time-lapse imaging (n = 843).ResultsThe combined incidence of meiotic and mitotic aneuploidies was strongly associated with blastocyst morphological grading, with the proportion ranging from 20 to 90% for the highest to lowest grades, respectively. In contrast, the incidence of aneuploidy among arrested embryos was exceptionally high (94%), dominated by mitotic aneuploidies affecting multiple chromosomes. In turn, these mitotic aneuploidies were strongly associated with abnormal cleavage divisions, such that 51% of abnormally dividing embryos possessed mitotic aneuploidies compared to only 23% of normally dividing embryos.ConclusionsWe conclude that the combination of meiotic and mitotic aneuploidies drives arrest of human embryos in vitro, as development increasingly relies on embryonic gene expression at the blastocyst stage.