London Women's Clinic

Menstruation can negatively impact quality of life (QoL), particularly during adolescence. The stigma surrounding menstruation and lack of support and education, can have detrimental effects on physical, social, emotional and mental wellbeing. This study aims to (1) determine how adolescent girls from schools across England feel that periods affect their wellbeing, (2) understand the menstrual support and education that adolescents receive and (3) suggest improvements to menstrual health education and support in schools. Eight focus groups were carried out in four schools, two in each school, with year 10 girls. Four questions were asked in each focus group relating to the participants’ attitudes to having a period, how their period affected their wellbeing, the support they need and how could education be improved. A total of 49 girls participated, with most reporting negative attitudes about periods. Most stated that their periods negatively impacted their physical, emotional, and social QoL, affecting areas such as friendships, schoolwork, and socialising. They expressed a need for improved menstrual education and for boys to be included. They wanted improved menstrual support, especially at school, in the form of access to period products, days off school, and emotional support. This study highlights the negative impact that menstruation can have on the QoL of adolescent girls. It shows a need for improved support and education for all genders from an early age; which may help dissipate period stigma and increase QoL. We recommend improvements in education and support systems by providing training to teachers implementing menstrual policies, improving the curriculum and ensuring appropriate support systems are in place in schools.

Resolving the lineage history of human cells is fundamental to understanding ageing and cancer but remains hampered by a lack of native, high-resolution markers. Here, we identify the protocadherin (PCDH) gene cluster as a naturally occurring, highly diverse methylation barcode. While PCDH methylation creates neuronal diversity in the brain, we show that stochastic methylation patterns in this region are maintained as heritable, evolvable lineage markers across multiple non-neuronal tissues, including blood, kidney, prostate, and bladder. By tracking these barcodes in serial samples over a decade, we reveal clonal dynamics with high fidelity, quantitatively recapitulating genetic clone sizes. Crucially, PCDH barcodes identify “cryptic” clonal expansions invisible to standard driver-mutation sequencing and resolve subclonal architectures via continuous epimutation. This native barcoding system provides a scalable, driver-agnostic framework for reconstructing somatic evolution in humans.

To systematically review perinatally accessible body fluid biomarkers of gastroschisis and those associated with disease severity or postnatal morbidities. PubMed, Embase, Web of Science, Scopus, Cochrane CENTRAL, ClinicalTrials.gov, and the International Clinical Trials Registry Platform were searchedfor studies reporting body fluid biomarkers obtained from women carrying a fetus or neonates with gastroschisis. The primary aim was to identify biomarkers indicating gastroschisis; secondary aims included identifying biomarkers associated with disease severity (simple vs. complex) or postnatal morbidity. Twenty-two studies were included, showing substantial heterogeneity in sampling timing, fluid type, and biomarkers assessed. Among 13 studies reporting prenatal biomarkers, amniotic fluid total protein, IL-8, and ferritin differentiated fetuses with gastroschisis from normal fetuses. Total protein correlated with disease severity. Bile acid findings were inconsistent. Increased cord blood IL-8 at delivery was associated with the presence of gastroschisis and prolonged parenteral nutrition. Neonatal urinary intestinal fatty acid-binding protein indicated the presence and severity of gastroschisis. An individual patient datameta-analysis of three studies identified four inflammatory cord blood biomarkers (IL-8, CXCL10, IL-4, and CX3CL1) associated with prolonged parenteral nutrition. Several perinatally accessible biomarkers are associated with gastroschisis, and some further correlate with severity or postnatal morbidity.

To study the correlation between transperineal ultrasound (TPUS) findings immediately after birth and postpartum anal incontinence (AI) and constipation. This is a prospective cohort study in pregnant patients who delivered vaginally at term. Participants filled in questionnaires, including the St. Mark's Incontinence Score and the Patient Assessment of Constipation Symptoms, at inclusion and at 6-weeks postpartum follow-up. TPUS acquisitions were performed immediately after birth to detect anal sphincter and levator defects, the dimensions of the genital hiatus as well as the dimensions of rectovaginal septum defects. We report on the prevalence and severity of AI and constipation at the postpartum follow-up and ran regression models to quantify the association between the former and TPUS findings immediately after birth. We calculated that a minimum of 156 patients were required to detect potential predictors for AI (power = 80%; alpha = 0.05; f2 = 0.15). Of 182 consecutive participants, 109 (60%) reported AI and 78 (43%) constipation. There were 37 (20.3%) women with a levator avulsion, 83 (46%) with an external anal sphincter defect in one or more TUI-sections and 29 (16%) with a rectovaginal septum defect. On univariate regression, sphincter defects were associated with AI [OR = 1.94(1.28-2.94)]. On multivariate regression, levator avulsion was the only independent sonographic predictor of AI [aOR = 2.57(1.03-7.44)], whereas sphincter defects, dimensions of the genital hiatus or rectovaginal defects were not correlated with AI. We identified no factors associated with constipation. The presence of levator avulsion immediately after vaginal delivery predicts postpartum AI. Ultrasound appearance of the anal sphincter, genital hiatus and rectovaginal septum was not informative.

<h3>Introduction</h3> A successful pregnancy outcome depends on optimal physiological remodelling of the uteroplacental vasculature, a process driven by and regulated by blood flow, and characterised by vasodilatation and structural remodelling. This remodelling is key to ensuring that the developing placenta and fetus receive an adequate supply of nutrients and oxygen. When these processes go awry, pregnancies are afflicted by pre-eclampsia and fetal growth restriction (FGR), which can result in maternal and fetal complications, and an increased pre-disposition to heart and circulatory disorders in both the mother and the offspring. Despite extensive research over several years, our understanding of the molecular and cellular events that underpin pathophysiological uteroplacental remodelling is still very limited. Previous work from our lab has shown that the adaptor protein Shc plays a key role in flow-mediated collateral expansion and atherosclerosis. We now examine the importance of <i>Shc</i> in flow-mediated remodelling of the utero-placental vessels during pregnancy. <h3>Methods</h3> Conditional endothelial specific <i>Shc</i> knockout mice (<i>Shc</i>^ECKO mice) and littermate controls were time-mated, and fetuses harvested at embryonic day (E)18.5. Uterine artery and fetal morphometrics were measured along with placental weights. Structural remodelling of the uterine spiral arteries, as assayed by trophoblast invasion (Fig 1), was assessed by staining for cytokeratin-8. <i>In vitro</i> experiments involving application of shear stress and tensional force were performed on control and <i>SHC</i>-depleted human uterine endothelial cells (ECs) to elucidate the mechanistic role of <i>SHC</i> in flow-mediated remodelling. <h3>Results</h3> Uterine arteries from <i>Shc</i>^ECKO mice had significantly smaller lumen area and lumen circumference than controls. The extent of trophoblast invasion was attenuated in the uterine spiral arteries from <i>Shc</i>^ECKO mice, suggestive of diminished remodelling. Placentae and fetuses harvested from <i>Shc</i>^ECKO mice were also significantly lighter. Fetuses from <i>Shc</i>^ECKO mice demonstrated the adaptive response of preferential growth of the brain over the rest of the body (brain sparing), a hallmark of asymmetric FGR. Exposure of <i>SHC</i>-depleted uterine ECs to shear stress and tensional force resulted in reduced mechano-activation of key signalling mediators. <h3>Conclusion</h3> <i>Shc</i> is a key mechanotransducer that governs the flow-mediated remodelling of the uteroplacental vasculature in pregnancy.

Cancer during pregnancy is relatively rare. The incidence is underestimated due to the lack of international registries covering both high‐income and low‐ and middle‐income countries, and is expected to rise with increasing maternal age and increasing global adoption of cell‐free DNA testing for aneuploidy. Physiological changes during pregnancy often make the diagnosis challenging and delayed. Lack of experience and knowledge about this condition may also contribute to late diagnosis, suboptimal management, and occasionally inadvertent fetal and/or maternal harm. The principles of cancer management in pregnancy for most cancer types do not differ significantly from the non‐pregnant population. The impact of investigations for diagnosis and staging, risks of surgery, systemic chemotherapy, and/or radiotherapy on fetal well‐being and preterm birth need to be considered for treatment and management planning, in addition to maternal wishes. Working in a multidisciplinary setting, ideally with medical and radiation oncologists, surgeons, radiologists, cancer specialist nurses, geneticists, psychologists, teratologists, and clinical pharmacologists, obstetricians, obstetric physicians, neonatologists, and experienced nursing and midwifery staff helps provide optimal care for the woman. This best practice advice aims to provide recommendations on the diagnosis and management of cancer in pregnancy, which can be adopted in all resource settings.

The global increase in frozen-thawed embryo transfer (FET) cycles has led to a critical evaluation of endometrial preparation methods. While various approaches such as natural or modified natural cycle FET, stimulated FET by use of letrozole (LTZ) and/or gonadotrophins, and artificial cycle (AC) FET, are currently in clinical use, the optimal regimen remains unclear, particularly for women with oligo-anovulation or polycystic ovarian syndrome (PCOS). This systematic review and meta-analysis compares LTZ FET with AC FET regarding reproductive, obstetric, and neonatal outcomes in these populations. The aim was to determine whether LTZ FET improves reproductive, obstetric, and neonatal outcomes compared to AC FET in women with ovulatory disorders and/or PCOS. A comprehensive search of MEDLINE, Cochrane, and ClinicalTrials.gov databases was conducted for studies until June 2024. Eligible studies included women with ovulatory disorders and/or PCOS, comparing LTZ FET to AC FET. Data extraction focused on the live birth rate (LBR), ongoing pregnancy rate, clinical pregnancy rate, pregnancy loss rate, hypertensive disorders of pregnancy (HDP), gestational diabetes mellitus (GDM), birth weight, small for gestational age (SGA), large for gestational age (LGA), and congenital malformations. The search identified 74 studies, and included 15 observational studies and two randomized controlled trials (RCTs) meeting the inclusion criteria; the studies encompassed a total of 8307 women treated with LTZ FET (±additional gonadotropin) and 16,940 women treated with AC FET. The meta-analysis comparing LTZ FET to AC FET demonstrated a modest yet statistically significant increase in the odds of LB (OR 1.37, 95% CI 1.21-1.56), corresponding to an 8% risk difference (95% CI 4%-11%). The one RCT that reported on LB yielded a similar LBR for LTZ FET and AC FET, thus did not support a better outcome after LTZ FET. Pregnancy losses, defined either as a loss following a positive serum hCG or following a clinical pregnancy, were compared between LTZ FET and AC FET. The meta-analysis indicated a reduction in the odds of PL with LTZ FET (OR 0.63, 95% CI 0.51-0.78). However, the two RCTs reporting this outcome exhibited high heterogeneity, introducing uncertainty of the result. LTZ FET was associated with lower risks of HDP (OR 0.70, 95% CI 0.58-0.84) and LGA (OR 0.75, 95% CI 0.67-0.85), but no significant differences were observed for GDM or SGA. For all outcomes, the certainty of evidence was low. LTZ FET may offer a modest improvement in reproductive outcomes and a lower risk of some obstetric complications compared to AC FET, particularly in women with oligo-anovulation. However, the quality of evidence remains low, and more well-designed RCTs are needed to confirm these findings. While awaiting further data, LTZ FET may be recommended as a viable alternative to AC FET for women with ovulatory disorders. PROSPERO-CRD42023395117.

SummaryIntroductionWomen undergoing induction of labour often utilise epidural analgesia. Obtaining consent for labour epidural presents a unique challenge for the obstetric anaesthetist, who must comply with the legal standards of consent. This study explores how women perceive the consent process for epidural analgesia during induction of labour.MethodsThis was a qualitative, single‐centre, interview‐based study. Fourteen women who received an epidural for labour analgesia were interviewed using a semi‐structured interview guide. Data were analysed using thematic analysis.ResultsFour themes described women's experience of the consent process. Understanding alternatives, risks and benefits; for example, time constraints hindering the effective communication of information around epidural analgesia, including alternative analgesic options. Timing of information; for example, the value of information was diminished by pain, fatigue and the imminence of the procedure. Timing of consent; for example, physiological and psychological demands of labour negatively impacted patients' ability to engage with the consent process. Anaesthetists' assessment of patient understanding; for example, confirmation of patient understanding by anaesthetists was lacking.DiscussionWomen's experiences of the consent process for induction of labour suggest that in the context of the pain and exhaustion of labour, inadequate and untimely information provision and dialogue between women and their anaesthetists can undermine the implementation of lawful consent.