RSS 1.0Gynaecology
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The paradox of poor cervical cancer screening uptake for kidney transplant recipientsKidney transplant recipients have an increased risk for developing and dying from cervical cancer compared with the general population due to their immunosuppressed state. As one of the cancers most amenable to an effective screening program, encouraging eligible women after transplantation to adhere to screening is critically important. Therefore, the observation that kidney transplant recipients may have a lower uptake of cervical cancer screening compared with the general population is concerning. The reasons for this should be studied so that any barriers can be identified and overcome. Kidney transplant recipients and recipients of other solid organ allografts must be encouraged and supported to adhere to recommended screening programs to mitigate the morbidity and mortality of posttransplantation cancer. See related article by Hsu et al., p. 1678.
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Serum luteal phase progesterone in women undergoing frozen embryo transfer in assisted conception: a systematic review and meta-analysis.Objective: To investigate the association between luteal serum progesterone levels and frozen embryo transfer (FET) outcomes. Design: Systematic review and meta-analysis. Setting: Not applicable. Patient(s): Women undergoing FET. Intervention(s): We conducted electronic searches of MEDLINE, PubMed, CINAHL, EMBASE, the Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Web of Science, ClinicalTrials.gov, and grey literature (not widely available) from inception to March 2021 to identify cohort studies in which the serum luteal progesterone level was measured around the time of FET. Main outcome measure(s): Ongoing pregnancy or live birth rate, clinical pregnancy rate, and miscarriage rate. Result(s): Among the studies analyzing serum progesterone level thresholds <10 ng/mL, a higher serum progesterone level was associated with increased rates of ongoing pregnancy or live birth (relative risk [RR] 1.47, 95% confidence interval [CI] 1.28 to 1.70), higher chance of clinical pregnancy (RR 1.31, 95% CI 1.16 to 1.49), and lower risk of miscarriage (RR 0.62, 95% CI 0.50 to 0.77) in cycles using exclusively vaginal progesterone and blastocyst embryos. There was uncertainty about whether progesterone thresholds ≥10 ng/mL were associated with FET outcomes in sensitivity analyses including all studies, owing to high interstudy heterogeneity and wide CIs. Conclusion(s): Our findings indicate that there may be a minimum clinically important luteal serum concentration of progesterone required to ensure an optimal endocrine milieu during embryo implantation and early pregnancy after FET treatment. Future clinical trials are required to assess whether administering higher-dose luteal phase support improves outcomes in women with a low serum progesterone level at the time of FET. Prospero number: CRD42019157071.
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Pregnancies in women with Turner syndrome: a retrospective multicentre UK studyObjective: To determine the characteristics and outcomes of pregnancy in women with Turner syndrome. Design: Retrospective 20-year cohort study (2000-20). Setting: Sixteen tertiary referral maternity units in the UK. Population or sample: A total of 81 women with Turner syndrome who became pregnant. Methods: Retrospective chart analysis. Main outcome measures: Mode of conception, pregnancy outcomes. Results: We obtained data on 127 pregnancies in 81 women with a Turner phenotype. All non-spontaneous pregnancies (54/127; 42.5%) were by egg donation. Only 9/31 (29%) pregnancies in women with karyotype 45,X were spontaneous, compared with 53/66 (80.3%) pregnancies in women with mosaic karyotype 45,X/46,XX (P < 0.0001). Women with mosaic karyotype 45,X/46,XX were younger at first pregnancy by 5.5-8.5 years compared with other Turner syndrome karyotype groups (P < 0.001), and more likely to have a spontaneous menarche (75.8% versus 50% or less, P = 0.008). There were 17 miscarriages, three terminations of pregnancy, two stillbirths and 105 live births. Two women had aortic dissection (2.5%); both were 45,X karyotype with bicuspid aortic valves and ovum donation pregnancies, one died. Another woman had an aortic root replacement within 6 months of delivery. Ten of 106 (9.4%) births with gestational age data were preterm and 22/96 (22.9%) singleton infants with birthweight/gestational age data weighed less than the tenth centile. The caesarean section rate was 72/107 (67.3%). In only 73/127 (57.4%) pregnancies was there documentation of cardiovascular imaging within the 24 months before conceiving. Conclusions: Pregnancy in women with Turner syndrome is associated with major maternal cardiovascular risks; these women deserve thorough cardiovascular assessment and counselling before assisted or spontaneous pregnancy managed by a specialist team.
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Placenta accreta spectrum disorders - detection rate and maternal outcomes following implementation of an institutional protocolPlacenta accreta spectrum (PAS) disorders have been on the rise in recent years with increasing caesarean rates. The purpose of this prospective observational study was to describe our detection rates and to review outcomes in PAS after the introduction of an institutional screening and management protocol. Twenty-one patients with suspected PAS over 5 years were identified. 20/21 patients had an accurate determination of placental invasion and positive correlation with surgical and histopathological examination. Early morbidity (massive haemorrhage) was found in 7/21 patients, whilst late morbidity (hospital readmission) was found in 5/21 patients. There were no maternal deaths and admissions to intensive therapy unit (ITU). In summary, our centre demonstrated a high antenatal detection rate for PAS using an evidence-based protocol. This has led to timely intervention by an experienced multidisciplinary team and excellent outcomes. Immediate and delayed postoperative counselling was effective for optimal patient understanding and experience.Impact StatementWhat is already known on this subject? With rising caesarean section rates, the incidence of placenta accreta spectrum (PAS) disorders is increasing. Despite this, most obstetricians have personally managed only a small number of patients with PAS. Moreover, there appears to be some debate over the optimal diagnostic and management strategy.What do the results of this study add? As the incidence increases, development of institutional screening and management protocol is a necessity for large units. Timely diagnosis, extensive pre and postoperative counselling and multidisciplinary teamwork ensure reduced early and late morbidity.What are the implications of these findings for clinical practice and/or further research? Evidence based screening protocols for PAS disorders reduce the likelihood of undiagnosed cases and should be developed in every unit. Consideration must also be given to standardisation of the diagnostic and management protocols, including contingency plan for emergencies.
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Why are women considering ovarian tissue cryopreservation to preserve reproductive and hormonal ovarian function? A qualitative study protocol.Introduction: Current fertility preservation options available to women are oocyte cryopreservation (egg freezing) or embryo cryopreservation. A newer procedure, ovarian tissue cryopreservation (OTC), has become available in some centres, which offers another option for women and girls considering fertility preservation. These procedures are commonly offered to women about to undergo treatments for cancer. OTC involves removing sections of ovarian tissue and cryopreserving it for future reimplantation, often several years later. OTC offers girls and women who may become infertile with optionality and the possibility of pregnancy. OTC has potential for other applications, including restoring ovarian endocrine function beyond biological menopause. This is not without controversy but has led to some women considering undergoing the procedure for purposes of ovarian hormonal preservation (conservation of ovarian endocrine function). OTC is invasive, involves two surgical procedures with concomitant risks and can be costly. Understanding why women may consider and ultimately undergo OTC is timely, so that evidence-based and women-centred care can be provided. Methods: A pragmatic narrative qualitative design will be used. A purposive sample of women aged 18-45 who are considering, or have sought, OTC will be recruited over 1-year period. Potential participants will be approached via a clinic that offers OTC on a private basis or via social media. Analysis: Participant interviews will be audio and, if consented, video recorded. These will be conducted face-to-face or virtually. The recordings will be transcribed verbatim and analysed using a thematic analysis approach supported by NVivo software. Ethics and dissemination: Ethical approval has been granted by the Institutional Ethical Review ERN_19-1578A. We expect to disseminate the findings of this study through journal articles, conference presentations and multimedia to public.
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The chromatin landscape of high-grade serous ovarian cancer metastasis identifies regulatory drivers in post-chemotherapy residual tumour cellsDisease recurrence following chemotherapy is a major clinical challenge in ovarian cancer (OC), but little is known regarding how the tumour epigenome regulates transcriptional programs underpinning chemoresistance. We determine the single cell chromatin accessibility landscape of omental OC metastasis from treatment-naïve and neoadjuvant chemotherapy-treated patients and define the chromatin accessibility profiles of epithelial, fibroblast, myeloid and lymphoid cells. Epithelial tumour cells display open chromatin regions enriched with motifs for the oncogenic transcription factors MEIS and PBX. Post chemotherapy microenvironments show profound tumour heterogeneity and selection for cells with accessible chromatin enriched for TP53, TP63, TWIST1 and resistance-pathway-activating transcription factor binding motifs. An OC chemoresistant tumour subpopulation known to be present prior to treatment, and characterised by stress-associated gene expression, is enriched post chemotherapy. Nuclear receptors RORa, NR2F6 and HNF4G are uncovered as candidate transcriptional drivers of these cells whilst closure of binding sites for E2F2 and E2F4 indicate post-treated tumour having low proliferative capacity. Delineation of the gene regulatory landscape of ovarian cancer cells surviving chemotherapy treatment therefore reveals potential core transcriptional regulators of chemoresistance, suggesting novel therapeutic targets for improving clinical outcome.
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Lactic acid gel versus metronidazole for recurrent bacterial vaginosis in women aged 16 years and over: the VITA RCT.Background: Bacterial vaginosis is a common and distressing condition associated with serious comorbidities. Antibiotic treatment is usually clinically effective in the short term, but recurrence is common and side effects can occur. Objectives: The objective is to assess whether or not intravaginal lactic acid gel is clinically effective and cost-effective for treating recurrent bacterial vaginosis compared with oral metronidazole (Flagyl, Sanofi). Design: This was an open-label, multicentre, parallel-arm, randomised (1 : 1) controlled trial. Setting: This took place in one general practice and 19 sexual health centres in the UK. Participants: Women aged ≥ 16 years with bacterial vaginosis symptoms and one or more episode(s) within the past 2 years took part. Interventions: The interventions were 5 ml of intravaginal lactic acid gel taken once daily for 7 days (intervention) or 400-mg oral metronidazole tablets taken twice daily for 7 days (control). Main outcome measures: The primary outcome was the resolution of bacterial vaginosis symptoms 14 days after randomisation. The secondary outcomes were time to first recurrence of symptoms; number of recurrences and treatment courses over 6 months; microbiological resolution on microscopy of vaginal smears at week 2; time to resolution of symptoms; tolerability, adherence and acceptability of the treatment; prevalence of concurrent sexually transmitted infections; quality of life; and cost-effectiveness. Results: Recruitment stopped prior to reaching the target of 1900 participants on recommendation from the Data Monitoring Committee and Trial Steering Committee after a planned review of the results indicated that the research question had been answered. Overall, 518 participants were randomised and primary outcome data were available for 409 participants (79%; 204 in the metronidazole arm, 205 in the lactic acid gel arm). Participant-reported symptom resolution at week 2 was higher with metronidazole (143/204; 70%) than with lactic acid gel (97/205; 47%) (adjusted risk difference -23.2%, 95% confidence interval -32.3% to -14.0%). Recurrence in 6 months in a subset of participants who had initial resolution and were available for follow-up was similar across arms (metronidazole arm: 51/72, 71%; lactic acid gel arm: 32/46, 70%). A higher incidence of some side effects was reported with metronidazole than with lactic acid gel (nausea 32% vs. 8%; taste changes 18% vs. 1%; diarrhoea 20% vs. 6%, respectively). At week 2, the average cost per participant with resolved symptoms was £86.94 (metronidazole), compared with £147.00 (lactic acid gel). Some participants preferred using lactic acid gel even if they perceived it to be less effective than metronidazole. Limitations: Loss to follow-up for collection of the primary outcome data was 21% and was similar in both arms. There is a risk of bias owing to missing outcome data at 3 and 6 months post treatment. Conclusions: A higher initial response was seen with metronidazole than with lactic acid gel, but subsequent treatment failure was common with both. Lactic acid gel was less cost-effective than metronidazole. In general, women disliked taking repeated courses of metronidazole and preferred lactic acid gel, even when they were aware that it was less likely to provide symptom resolution. In the absence of effective curative therapy, further evaluation of non-antibiotic treatments to control the symptoms of recurrent bacterial vaginosis is required to improve quality of life for these patients. Further microbiological analysis of vaginal samples would be useful to identify additional factors affecting response to treatment. Trial registration: Current Controlled Trials ISRCTN14161293. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 2. See the NIHR Journals Library website for further project information. Keywords: BACTERIAL VAGINOSIS; HEALTH ECONOMICS; LACTIC ACID GEL; METRONIDAZOLE; MICROSCOPY; QUALITATIVE RESEARCH; RANDOMISED CONTROLLED TRIAL; RECURRENCE; SEXUAL HEALTH. Plain language summary Bacterial vaginosis is a common cause of unpleasant vaginal discharge that is caused by an imbalance of vaginal bacteria. The usual treatment is an antibiotic called metronidazole (Flagyl, Sanofi). Although this generally works in the short term, symptoms often return, leading to the repeated use of antibiotics; this can cause side effects as well as increase the risk of antibiotic resistance. Lactic acid gel might be an alternative treatment, but previous studies have not confirmed how clinically effective it is. We wanted to find out if lactic acid gel was better than metronidazole for treating recurrent bacterial vaginosis. Women with typical symptoms and a history of bacterial vaginosis who were taking part in our trial were selected randomly to receive either 7 days of treatment with lactic acid gel inserted into the vagina once per day or 7 days of treatment with metronidazole tablets taken by mouth twice per day. Overall, 518 women took part in the trial. We originally intended to recruit 1900 women but the trial was stopped early because a planned review of the data showed which treatment was better. Most of the women took all of their treatment and 70% reported that symptoms had cleared 2 weeks after taking metronidazole, compared with 47% after using lactic acid gel. Less than half of the women stayed in the trial for the full 6 months; however, the data suggested that the majority of those whose symptoms cleared within 2 weeks with either treatment had symptoms return over the next 6 months. More side effects were reported for metronidazole than for lactic acid gel: nausea 32% compared with 8%, taste changes 18% compared with 1%, and diarrhoea 20% compared with 6%, respectively. Despite thinking that it was less effective, women preferred lactic acid gel because it avoided the need to take an antibiotic and had a soothing effect. The cost-effectiveness analysis found that lactic acid gel was less effective than metronidazole in clearing symptoms by 2 weeks and that the average costs for women whose symptoms resolved were higher (£86.94 with metronidazole vs. £147.00 with lactic acid gel).
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Investigating age and ethnicity as novel high-risk phenotypes in mucinous ovarian cancer : retrospective study in a multi-ethnic populationObjectives: Primary mucinous ovarian carcinoma represents 3% of ovarian cancers and is typically diagnosed early, yielding favorable outcomes. This study aims to identify risk factors, focussing on the impact of age and ethnicity on survival from primary mucinous ovarian cancer. Methods: A retrospective observational study of patients treated at Sandwell and West Birmingham Hospitals NHS Trust and University Hospital Coventry and Warwickshire. Patients included were women aged ≥16 years, with primary mucinous ovarian cancer confirmed by specialist gynecological histopathologist and tumor immunohistochemistry, including cytokeratin-7, cytokeratin-20, and CDX2. Statistical analyses were performed using R integrated development environment, with survival assessed by Cox proportional hazards models and Kaplan-Meier plots. Results: A total of 163 patients were analyzed; median age at diagnosis was 58 years (range 16-92), 145 (89%) were International Federation of Gynecology and Obstetrics stage I and 43 (26%) patients had infiltrative invasion. Women aged ≤45 years were more likely to have infiltrative invasion (RR=1.38, 95% CI 0.78 to 2.46), with increased risk of death associated with infiltrative invasion (HR=2.29, 95% CI 1.37 to 5.83). Compared with White counterparts, South Asian women were more likely to undergo fertility-sparing surgery (RR=3.52, 95% CI 1.48 to 8.32), and have infiltrative invasion (RR=1.25, 95% CI 0.60 to 2.58). South Asian women undergoing fertility-sparing surgery had worse prognosis than those undergoing traditional staging surgery (HR=2.20, 95% CI 0.39 to 13.14). In FIGO stage I disease, 59% South Asian and 37% White women received adjuvant chemotherapy (p=0.06). South Asian women exhibited a worse overall prognosis than White women (HR=2.07, 95% CI 0.86 to 4.36), particularly pronounced in those aged ≤45 years (HR=8.75, 95% CI 1.22 to 76.38). Conclusion: This study identified young age as a risk factor for diagnosis of infiltrative invasion. Fertility-sparing surgery in South Asian women is a risk factor for poorer prognosis. South Asian women exhibit poorer overall survival than their White counterparts.
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Conscious sedation for office hysteroscopy: a systematic review and meta-analysis.Objective: To evaluate the role of conscious sedation on pain control in office hysteroscopy. Methods: MEDLINE, EMBASE, CINAHL and CENTRAL were searched from inception to the 30th October 2020 in order to perform a systematic review and meta-analysis of all randomized controlled trials investigating women undergoing office hysteroscopic procedures, allocated to either conscious sedation or a suitable comparator, where the outcome was pain. Data regarding adverse events, feasibility and satisfaction/acceptability were also collected. The Risk of Bias 2 tool was used to assess study quality. Standard mean differences (SMD) or Odds Ratios (OR), and their 95% confidence intervals (CIs) were calculated for continuous (e.g. mean pain) and dichotomous (e.g. side-effects) outcomes, respectively. Results: The literature search returned 339 results, of which seven studies were included for systematic review, with five studies having data suitable for meta-analysis. Intravenous conscious sedation, when compared with local anesthesia, reduced pain during (SMD -0.26, 95% CI -0.51 to -0.01), but not after (SMD -0.18, 95% CI -0.43 to 0.07) office hysteroscopy. No significant difference in side-effects were noted (OR 15.58, 95% CI 0.08 to 2891.91). Intravenous conscious sedation, when compared to an oral analgesic and antispasmodic, was associated with increased pain, both during (SMD 1.03, 95% CI 0.56 to 1.49) and after (SMD 0.49, 95% CI 0.04 to 0.93) hysteroscopy and had significantly more side-effects (OR 134.33, 95% CI 16.14 to 1118.17). Inhalational conscious sedation (70% N2O/30% O2), when compared to oral analgesia and anxiolysis, showed the greatest reduction in pain during hysteroscopy (SMD -1.04, 95% CI -1.57 to -0.52), however side-effects were not reported. Whilst patients and hysteroscopists were more satisfied with deeper levels of sedation, resulting side-effects, such as delirium, increased the level of post-procedural attention required, leading to a significantly lower level of satisfaction amongst nursing staff. Conclusion: The routine use of conscious sedation in contemporary hysteroscopic practice should be avoided in the absence of any clear reduction in pain and a higher risk of side-effects.
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Folic acid supplementation in postmenopausal women with hot flushes: phase III randomised double-blind placebo-controlled trial.Objective: To assess whether folic acid supplementation ameliorates hot flushes. Design: Double-blind, placebo-controlled randomised trial. Setting: Nine hospitals in England. Population: Postmenopausal women experiencing ≥50 hot flushes weekly. Methods: Women (n = 164) were randomly assigned in a 1:1 ratio to receive folic acid 5 mg tablet or placebo daily for 12 weeks. Participants recorded frequency and severity of hot flushes in a Sloan Diary daily and completed Greene Climacteric and Utian Quality of Life (UQoL) Scales at 4-week intervals. Main outcome measures: The change in daily Hot Flush Score at week 12 from randomisation based on Sloan Diary Composite Score B calculation. Results: Data of 143 (87%) women were available for the primary outcome. The mean change (SD) in Hot Flush Score at week 12 was -6.98 (10.30) and -4.57 (9.46) for folic acid and placebo group, respectively. The difference between groups in the mean change was -2.41 (95% CI -5.68 to 0.87) (P = 0.149) and in the adjusted mean change -2.61 (95% CI -5.72 to 0.49) (P = 0.098). Analysis of secondary outcomes indicated an increased benefit in the folic acid group regarding changes in total and emotional UQoL scores at week 8 when compared with placebo. The difference in the mean change from baseline was 5.22 (95% CI 1.16-9.28) and 1.88 (95% CI 0.23-3.52) for total and emotional score, respectively. Conclusions: The study was not able to demonstrate that folic acid had a statistically significant greater benefit in reducing Hot Flush Score over 12 weeks in postmenopausal women when compared with placebo.
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Neratinib could be effective as monotherapy or in combination with trastuzumab in HER2-low breast cancer cells and organoid models.Background: Previous studies have suggested that patients with HER2-low breast cancers do not benefit from trastuzumab treatment although the reasons remain unclear. Methods: We investigated the effect of trastuzumab monotherapy and its combination with different HER2 targeting treatments in a panel of breast cancer cell lines and patient-derived organoids (PDOs) using biochemical methods and cell viability assays. Results: Compared to sensitive HER2 over-expressing (IHC3 + ) breast cancer cells, increasing doses of trastuzumab could not achieve IC50 in MDA-MB-361 (IHC 2 + FISH + ) and MDA-MB-453 (IHC 2 + FISH-) cells which showed an intermediate response to trastuzumab. Trastuzumab treatment induced upregulation of HER ligand release, resulting in the activation of HER receptors in these cells, which could account for their trastuzumab insensitivity. Adding a dual ADAM10/17 inhibitor to inhibit the shedding of HER ligands in combination with trastuzumab only showed a modest decrease in the cell viability of HER2-low breast cancer cells and PDOs. However, the panHER inhibitor neratinib was an effective monotherapy in HER2-low breast cancer cells and PDOs, and showed additive effects when combined with trastuzumab. Conclusion: This study demonstrates that neratinib in combination with trastuzumab may be effective in a subset of HER2-low breast cancers although further validation is required in a larger panel of PDOs and in future clinical studies.
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Atypia detected during breast screening and subsequent development of cancer: observational analysis of the Sloane atypia prospective cohort in England.There was a fourfold increase in detection of atypia after the introduction of digital mammography between 2010 (n=119) and 2015 (n=502). During 19 088 person years of follow-up after atypia diagnosis (until December 2018), 141 women developed breast cancer. Cumulative incidence of cancer per 1000 women with atypia was 0.95 (95% confidence interval 0.28 to 2.69), 14.2 (10.3 to 19.1), and 45.0 (36.3 to 55.1) at one, three, and six years after atypia diagnosis, respectively. Women with atypia detected more recently have lower rates of subsequent cancers detected within three years (6.0 invasive cancers per 1000 women (95% confidence interval 3.1 to 10.9) in 2013-18 v 24.3 (13.7 to 40.1) in 2003-07, and 24.6 (14.9 to 38.3) in 2008-12). Grade, size, and nodal involvement of subsequent invasive cancers were similar to those of cancers detected in the general screening population, with equal numbers of ipsilateral and contralateral cancers.
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Evidence-informed recommendations on managing breast screening atypia: perspectives from an expert panel consensus meeting reviewing results from the Sloane atypia project.Evidence-based clinical guidelines are essential to maximize patient benefit and to reduce clinical uncertainty and inconsistency in clinical practice. Gaps in the evidence base can be addressed by data acquired in routine practice. At present, there is no international consensus on management of women diagnosed with atypical lesions in breast screening programmes. Here, we describe how routine NHS breast screening data collected by the Sloane atypia project was used to inform a management pathway that maximizes early detection of cancer and minimizes over-investigation of lesions with uncertain malignant potential. A half-day consensus meeting with 11 clinical experts, 1 representative from Independent Cancer Patients' Voice, 6 representatives from NHS England (NHSE) including from Commissioning, and 2 researchers was held to facilitate discussions of findings from an analysis of the Sloane atypia project. Key considerations of the expert group in terms of the management of women with screen detected atypia were: (1) frequency and purpose of follow-up; (2) communication to patients; (3) generalizability of study results; and (4) workforce challenges. The group concurred that the new evidence does not support annual surveillance mammography for women with atypia, irrespective of type of lesion, or woman's age. Continued data collection is paramount to monitor and audit the change in recommendations.
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Views of female genital mutilation survivors, men and health-care professionals on timing of deinfibulation surgery and NHS service provision: qualitative FGM Sister Study.Background: Female genital mutilation is an important UK health-care challenge. There are no health benefits of female genital mutilation, and it is associated with lifelong physical, psychological and sexual impacts. The annual cost to the NHS to care for survivors is £100M. Deinfibulation may improve the health and well-being of some women, but there is no consensus on the optimal timing of surgery for type 3 survivors. UK care provision is reportedly suboptimal. Objectives: We aimed to explore the views of survivors, men and health-care professionals on the timing of deinfibulation surgery and NHS service provision. Methods: This was a qualitative study informed by the Sound of Silence framework. This framework is useful for researching sensitive issues and the health-care needs of marginalised populations. A total of 101 interviews with 44 survivors, 13 men and 44 health-care professionals were conducted, supplemented by two workshops with affected communities (participants, n = 10) and one workshop with stakeholders (participants, n = 30). Data were analysed using a hybrid framework method. Results: There was no clear consensus between groups on the optimal timing of deinfibulation. However, within groups, survivors expressed a preference for deinfibulation pre pregnancy; health-care professionals preferred antenatal deinfibulation, with the caveat that it should be the survivor's choice. There was no consensus among men. There was agreement that deinfibulation should take place in a hospital setting and be undertaken by a suitable health-care professional. Decision-making around deinfibulation was complex. Deficiencies in professionals' awareness, knowledge and understanding resulted in impacts on the provision of appropriate care. Although there were examples of good practice and positive care interactions, in general, service provision was opaque and remains suboptimal, with deficiencies most notable in mental health. Deinfibulation reportedly helps to mitigate some of the impacts of female genital mutilation. Interactions between survivors and health-care professionals were disproportionately framed around the law. The way in which services are planned and provided often silences the perspectives and preferences of survivors and their families. Limitations: Only a minority of the interviews were conducted in a language other than English, and the recruitment of survivors was predominantly through maternity settings, which meant that some voices may not have been heard. The sample of men was relatively small, limiting interpretation. Conclusions: In general, service provision remains suboptimal and can silence the perspectives and preferences of survivors. Deinfibulation services need to be widely advertised and information should highlight that the procedure will be carried out in hospital by suitable health-care professionals and that a range of time points will be offered to facilitate choice. Future services should be developed with survivors to ensure that they are clinically and culturally appropriate. Guidelines should be updated to better reflect the needs of survivors and to ensure consistency in service provision. Future work: Research is needed to (1) map female genital mutilation service provision; (2) develop and test effective education to address deficits in awareness and knowledge for affected communities and health-care professionals; and (3) develop, monitor and evaluate clinically and culturally competent female genital mutilation services. Trial registration: Current Controlled Trials ISRCTN14710507. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment Programme and will be published in full in Health Technology Assessment; Vol. 27, No. 3. See the NIHR Journals Library website for further project information. K
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Co-morbid Polycystic Ovarian Syndrome with Idiopathic Intracranial HypertensionThe link between polycystic ovarian syndrome (PCOS) and idiopathic intracranial hypertension (IIH) has long been debated. Historically, there is a wide range of reported occurrence of both conditions, being between 15% and 64%. Both conditions share a common phenotype. The awareness that in a new large data study that there is a 1.5-fold increased prevalence of diagnosed PCOS in participants with IIH as compared to the controls is important. Assessment for the potential of co-morbid PCOS in women with IIH is important as this may enable optimisation of weight and fertility management.
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The DEVA trial: protocol for a randomised controlled trial of dequalinium chloride versus usual care antibiotics for the treatment of bacterial vaginosis.Background: Bacterial vaginosis (BV) is the most common cause of vaginal discharge in women of reproductive age, and it is estimated that up to a third of women will experience it at some point in their lives. BV produces an offensive vaginal odour and it is associated with serious sequelae. The most frequently prescribed treatment for BV in the UK is 7-day oral metronidazole but recurrences are common following it. Dequalinium chloride (Fluomizin©) is an anti-infective, antiseptic agent administered as a vaginal tablet. Small studies have shown this to be an effective alternative to antibiotics as a BV treatment. This trial aims to investigate whether dequalinium is as effective as current antibiotic treatments for the treatment of BV 1 month after treatment start. Methods: DEVA is a multi-centre, randomised, open-label, parallel group, non-inferiority trial of dequalinium chloride versus usual care antibiotics for the treatment of BV. Recruitment will take place in 15 GUM clinics in the UK with Leeds Sexual Health also managing remote recruitment via the trial website. Women will be randomised 1:1 to receive dequalinium or usual care antibiotics. The primary outcome is to determine if the proportion of women reporting resolution of BV symptoms 4 weeks after treatment (without the need for additional treatment) is not worse in women treated with dequalinium chloride compared to usual care antibiotics. Questionnaire follow-up will take place 4 and 12 weeks after starting treatment, and remotely recruited patients will also provide a week 4 BV vaginal smear. The sample size is 904. Discussion: This trial will provide high-quality evidence on the use of dequalinium chloride as a BV treatment, which could result in patients reducing the number of antibiotics they take. Trial registration: ISRCTN ISRCTN91800263. Prospectively registered on 20 January 2020.
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Appraising Unmet Needs and Misinformation Spread About Polycystic Ovary Syndrome in 85,872 YouTube Comments Over 12 Years: Big Data Infodemiology StudyBackground: Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women, resulting in substantial burden related to metabolic, reproductive, and psychological complications. While attempts have been made to understand the themes and sentiments of the public regarding PCOS at the local and regional levels, no study has explored worldwide views, mainly due to financial and logistical limitations. YouTube is one of the largest sources of health-related information, where many visitors share their views as questions or comments. These can be used as a surrogate to understand the public's perceptions. Objective: We analyzed the comments of all videos related to PCOS published on YouTube from May 2011 to April 2023 and identified trends over time in the comments, their context, associated themes, gender-based differences, and underlying sentiments. Methods: After extracting all the comments using the YouTube application programming interface, we contextually studied the keywords and analyzed gender differences using the Benjamini-Hochberg procedure. We applied a multidimensional approach to analyzing the content via association mining using Mozdeh. We performed network analysis to study associated themes using the Fruchterman-Reingold algorithm and then manually screened the comments for content analysis. The sentiments associated with YouTube comments were analyzed using SentiStrength. Results: A total of 85,872 comments from 940 PCOS videos on YouTube were extracted. We identified a specific gender for 13,106 comments. Of these, 1506 were matched to male users (11.5%), and 11,601 comments to female users (88.5%). Keywords including diagnosing PCOS, symptoms of PCOS, pills for PCOS (medication), and pregnancy were significantly associated with female users. Keywords such as herbal treatment, natural treatment, curing PCOS, and online searches were significantly associated with male users. The key themes associated with female users were symptoms of PCOS, positive personal experiences (themes such as helpful and love), negative personal experiences (fatigue and pain), motherhood (infertility and trying to conceive), self-diagnosis, and use of professional terminology detailing their journey. The key themes associated with male users were misinformation regarding the "cure" for PCOS, using natural and herbal remedies to cure PCOS, fake testimonies from spammers selling their courses and consultations, finding treatment for PCOS, and sharing perspectives of female family members. The overall average positive sentiment was 1.6651 (95% CI 1.6593-1.6709), and the average negative sentiment was 1.4742 (95% CI 1.4683-1.4802) with a net positive difference of 0.1909. Conclusions: There may be a disparity in views on PCOS between women and men, with the latter associated with non-evidence-based approaches and misinformation. The improving sentiment noticed with YouTube comments may reflect better health care services. Prioritizing and promoting evidence-based care and disseminating pragmatic online coverage is warranted to improve public sentiment and limit misinformation spread. Keywords: PCOS; YouTube; big data; comments; contextualization; endocrinopathy; fatigue; gender; global equity; global health; infodemiology; misinformation; motherhood; network analysis; online trends; pain; polycystic ovary syndrome; public; sentiment; treatment; users; women; word association.
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Menopausal status, ultrasound and biomarker tests in combination for the diagnosis of ovarian cancer in symptomatic womenBackground: Ovarian cancer (OC) has the highest case fatality rate of all gynaecological cancers. Diagnostic delays are caused by non-specific symptoms. Existing systematic reviews have not comprehensively covered tests in current practice, not estimated accuracy separately in pre- and postmenopausal women, or used inappropriate meta-analytic methods. Objectives: To establish the accuracy of combinations of menopausal status, ultrasound scan (USS) and biomarkers for the diagnosis of ovarian cancer in pre- and postmenopausal women and compare the accuracy of different test combinations. Search methods: We searched CENTRAL, MEDLINE (Ovid), Embase (Ovid), five other databases and three trial registries from 1991 to 2015 and MEDLINE (Ovid) and Embase (Ovid) form June 2015 to June 2019. We also searched conference proceedings from the European Society of Gynaecological Oncology, International Gynecologic Cancer Society, American Society of Clinical Oncology and Society of Gynecologic Oncology, ZETOC and Conference Proceedings Citation Index (Web of Knowledge). We searched reference lists of included studies and published systematic reviews. Selection criteria: We included cross-sectional diagnostic test accuracy studies evaluating single tests or comparing two or more tests, randomised trials comparing two or more tests, and studies validating multivariable models for the diagnosis of OC investigating test combinations, compared with a reference standard of histological confirmation or clinical follow-up in women with a pelvic mass (detected clinically or through USS) suspicious for OC. Data collection and analysis: Two review authors independently extracted data and assessed quality using QUADAS-2. We used the bivariate hierarchical model to indirectly compare tests at commonly reported thresholds in pre- and postmenopausal women separately. We indirectly compared tests across all thresholds and estimated sensitivity at fixed specificities of 80% and 90% by fitting hierarchical summary receiver operating characteristic (HSROC) models in pre- and postmenopausal women separately. Main results: We included 59 studies (32,059 women, 9545 cases of OC). Two tests evaluated the accuracy of a combination of menopausal status and USS findings (IOTA Logistic Regression Model 2 (LR2) and the Assessment of Different NEoplasias in the adneXa model (ADNEX)); one test evaluated the accuracy of a combination of menopausal status, USS findings and serum biomarker CA125 (Risk of Malignancy Index (RMI)); and one test evaluated the accuracy of a combination of menopausal status and two serum biomarkers (CA125 and HE4) (Risk of Ovarian Malignancy Algorithm (ROMA)). Most studies were at high or unclear risk of bias in participant, reference standard, and flow and timing domains. All studies were in hospital settings. Prevalence was 16% (RMI, ROMA), 22% (LR2) and 27% (ADNEX) in premenopausal women and 38% (RMI), 45% (ROMA), 52% (LR2) and 55% (ADNEX) in postmenopausal women. The prevalence of OC in the studies was considerably higher than would be expected in symptomatic women presenting in community-based settings, or in women referred from the community to hospital with a suspicion of OC. Studies were at high or unclear applicability because presenting features were not reported, or USS was performed by experienced ultrasonographers for RMI, LR2 and ADNEX. The higher sensitivity and lower specificity observed in postmenopausal compared to premenopausal women across all index tests and at all thresholds may reflect highly selected patient cohorts in the included studies. In premenopausal women, ROMA at a threshold of 13.1 (± 2), LR2 at a threshold to achieve a post-test probability of OC of 10% and ADNEX (post-test probability 10%) demonstrated a higher sensitivity (ROMA: 77.4%, 95% CI 72.7% to 81.5%; LR2: 83.3%, 95% CI 74.7% to 89.5%; ADNEX: 95.5%, 95% CI 91.0% to 97.8%) compared to RMI (57.2%, 95% CI 50.3% to 63.8%). The specificity of ROMA and ADNEX were lower in premenopausal women (ROMA: 84.3%, 95% CI 81.2% to 87.0%; ADNEX: 77.8%, 95% CI 67.4% to 85.5%) compared to RMI 92.5% (95% CI 90.3% to 94.2%). The specificity of LR2 was comparable to RMI (90.4%, 95% CI 84.6% to 94.1%). In postmenopausal women, ROMA at a threshold of 27.7 (± 2), LR2 (post-test probability 10%) and ADNEX (post-test probability 10%) demonstrated a higher sensitivity (ROMA: 90.3%, 95% CI 87.5% to 92.6%; LR2: 94.8%, 95% CI 92.3% to 96.6%; ADNEX: 97.6%, 95% CI 95.6% to 98.7%) compared to RMI (78.4%, 95% CI 74.6% to 81.7%). Specificity of ROMA at a threshold of 27.7 (± 2) (81.5, 95% CI 76.5% to 85.5%) was comparable to RMI (85.4%, 95% CI 82.0% to 88.2%), whereas for LR2 (post-test probability 10%) and ADNEX (post-test probability 10%) specificity was lower (LR2: 60.6%, 95% CI 50.5% to 69.9%; ADNEX: 55.0%, 95% CI 42.8% to 66.6%). Authors' conclusions: In specialist healthcare settings in both premenopausal and postmenopausal women, RMI has poor sensitivity. In premenopausal women, ROMA, LR2 and ADNEX offer better sensitivity (fewer missed cancers), but for ROMA and ADNEX this is off-set by a decrease in specificity and increase in false positives. In postmenopausal women, ROMA demonstrates a higher sensitivity and comparable specificity to RMI. ADNEX has the highest sensitivity in postmenopausal women, but reduced specificity. The prevalence of OC in included studies is representative of a highly selected referred population, rather than a population in whom referral is being considered. The comparative accuracy of tests observed here may not be transferable to non-specialist settings. Ultimately health systems need to balance accuracy and resource implications to identify the most suitable test.
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Emotional and psychosexual well-being is influenced by ethnicity and birthplace in women and individuals with polycystic ovary syndrome in the UK and India.Abstract Objective: To assess the association of ethnicity and birthplace on emotional and psychosexual well-being in women with polycystic ovary syndrome (PCOS). Design: Cross-sectional study. Setting: Community recruitment via social media campaigns. Population: Women with PCOS completing an online questionnaire in September-October 2020 (UK) and May-June 2021 (India). Methods: The survey has five components, with a baseline information and sociodemographic section followed by four validated questionnaires: Hospital Anxiety and Depression Scale (HADS); Body Image Concern Inventory (BICI); Beliefs About Obese Persons Scale (BAOP); and Female Sexual Function Index (FSFI). Main outcome measures: We used adjusted linear and logistic regression models, adjusting for age, education, marital status and parity, to evaluate the impact of ethnicity and birthplace on questionnaire scores and outcomes (anxiety and/or depression, HADS ≥ 11; body dysmorphic disorder (BDD), BICI ≥ 72). Results: A total of 1008 women with PCOS were included. Women of non-white ethnicity (613/1008) reported higher rates of depression (OR 1.96, 95% CI 1.41-2.73) and lower BDD (OR 0.57, 95% CI 0.41-0.79) than white women (395/1008). Women born in India (453/1008) had higher anxiety (OR 1.57, 95% CI 1.00-2.46) and depression (OR 2.20, 95% CI 1.52-3.18) but lower BDD rates (OR 0.42, 95% CI 0.29-0.61) than women born in the UK (437/1008). All sexual domains, excluding desire, scored lower for non-white women and women born in India. Conclusions: Non-white women and women born in India reported higher emotional and sexual dysfunction, whereas white women and women born in the UK reported higher body image concerns and weight stigma. Ethnicity and birthplace need to be considered for tailored, multidisciplinary care. Keywords: anxiety; body image; depression; obesity; polycystic ovarian syndrome; sexual function; weight stigma.