High performance of the DNA methylation-based WID-qEC test for detecting uterine cancers independent of sampling modalities.

Endometrial cancer (EC) is the most prevalent gynaecological cancer in high-income countries and its incidence is continuing to rise sharply. Simple and objective tools to reliably detect women with EC are urgently needed. We recently developed and validated the DNA methylation (DNAme)-based women's cancer risk identification-quantitative polymerase chain reaction test for endometrial cancer (WID-qEC) test that could address this need. Here, we demonstrate that the stability of the WID-qEC test remains consistent regardless of: (i) the cervicovaginal collection device and sample media used (Cervex brush and PreservCyt or FLOQSwab and eNAT), (ii) the collector of the specimen (gynaecologist- or patient-based), and (iii) the precise sampling site (cervical, cervicovaginal and vaginal). Furthermore, we demonstrate sample stability in eNAT medium for 7 days at room temperature, greatly facilitating the implementation of the test into diagnostic laboratory workflows. When applying FLOQSwabs (Copan) in combination with the eNAT (Copan) sample collection media, the sensitivity and specificity of the WID-qEC test to detect uterine (i.e., endometrial and cervical) cancers in gynaecologist-taken samples was 92.9% (95% confidence interval [CI] = 75.0%-98.8%) and 98.6% (95% CI = 91.7%-99.9%), respectively, whilst the sensitivity and specificity in patient collected self-samples was 75.0% (95% CI = 47.4%-91.7%) and 100.0% (95% CI = 93.9%-100.0%), respectively. Taken together these data confirm the robustness and clinical potential of the WID-qEC test.

Menopause depression: Under recognised and poorly treated.

Menopause is a biological process experienced by all people assigned female at birth. A significant number of women experience mental ill health related to the major brain gonadal hormone shifts that occur in their midlife. There is poor understanding and management of the complex mental ill health issues, with the biological brain hormone changes receiving little formal attention. The current treatment advice is to manage this special type of mental ill health in the same way that all mental ill health is managed. This leads to poor outcomes for women and their families. Many women leave the workforce earlier than expected due to menopause-related depression and anxiety, with subsequent loss of salary and superannuation. Others describe being unable to adequately parent or maintain meaningful relationships - all ending in a poor quality of life. We are a large and diverse group of national and international clinicians, lived experience and social community advocates, all working together to innovate the current approaches available for women with menopausal mental ill health. Above all, true innovation is only possible when the woman with lived experience of menopause is front and centre of this debate.

Endoscopic transabdominal cervical cerclage replacement after recurrent late miscarriage.

Transabdominal cerclage (TAC) is a recognised treatment for recurrent spontaneous late miscarriage or preterm birth due to cervical weakness. This can be performed via an open procedure before and during pregnancy, or a laparoscopic technique preconception. Complications include cerclage failure and suture migration. We present a case highlighting these complications where laparoscopic removal of an open TAC and replacement led to two successful term deliveries. A woman in her thirties with a fibroid uterus, adenomyosis and a history of three spontaneous mid-trimester losses, had an open TAC at 13 weeks of gestation. Preterm premature rupture of the membranes occurred shortly after and at 18 weeks of gestation she underwent surgical evacuation of the uterus. Subsequent hysteroscopy confirmed migration of the cerclage through the cervical canal. We demonstrate the application of endoscopic gynaecological surgery to remove and replace the TAC with two successful term births by Caesarean section in the ensuing pregnancies.

Preventive population genomics: The model of BRCA related cancers.

Preventive population genomics offers the prospect of population stratification for targeting screening and prevention and tailoring care to those at greatest risk. Within cancer, this approach is now within reach, given our expanding knowledge of its heritable components, improved ability to predict risk, and increasing availability of effective preventive strategies. Advances in technology and bioinformatics has made population-testing technically feasible. The BRCA model provides 30 years of insight and experience of how to conceive of and construct care and serves as an initial model for preventive population genomics. Population-based BRCA-testing in the Jewish population is feasible, acceptable, reduces anxiety, does not detrimentally affect psychological well-being or quality of life, is cost-effective and is now beginning to be implemented. Population-based BRCA-testing and multigene panel testing in the wider general population is cost-effective for numerous health systems and can save thousands more lives than the current clinical strategy. There is huge potential for using both genetic and non-genetic information in complex risk prediction algorithms to stratify populations for risk adapted screening and prevention. While numerous strides have been made in the last decade several issues need resolving for population genomics to fulfil its promise and potential for maximizing precision prevention. Healthcare systems need to overcome significant challenges associated with developing delivery pathways, infrastructure expansion including laboratory services, clinical workforce training, scaling of management pathways for screening and prevention. Large-scale real world population studies are needed to evaluate context specific population-testing implementation models for cancer risk prediction, screening and prevention.

Publisher Correction: Personalized early detection and prevention of breast cancer: ENVISION consensus statement.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Personalized early detection and prevention of breast cancer: ENVISION consensus statement.

The European Collaborative on Personalized Early Detection and Prevention of Breast Cancer (ENVISION) brings together several international research consortia working on different aspects of the personalized early detection and prevention of breast cancer. In a consensus conference held in 2019, the members of this network identified research areas requiring development to enable evidence-based personalized interventions that might improve the benefits and reduce the harms of existing breast cancer screening and prevention programmes. The priority areas identified were: 1) breast cancer subtype-specific risk assessment tools applicable to women of all ancestries; 2) intermediate surrogate markers of response to preventive measures; 3) novel non-surgical preventive measures to reduce the incidence of breast cancer of poor prognosis; and 4) hybrid effectiveness-implementation research combined with modelling studies to evaluate the long-term population outcomes of risk-based early detection strategies. The implementation of such programmes would require health-care systems to be open to learning and adapting, the engagement of a diverse range of stakeholders and tailoring to societal norms and values, while also addressing the ethical and legal issues. In this Consensus Statement, we discuss the current state of breast cancer risk prediction, risk-stratified prevention and early detection strategies, and their implementation. Throughout, we highlight priorities for advancing each of these areas.

Using an introduction website to start a family: implications for users and health practitioners.

Donor insemination treatment offered in licensed clinics protects the donor, recipient and offspring both medically and legally. The Internet has opened up novel, unregulated ways of donating sperm through 'introduction websites' and social media forums. Broadly, three categories of women use introduction websites: those who want to have a child with no further involvement of the donor; those who wish to know the identity of the donor from the start; and those who intend to electively co-parent, that is, to bring up the child together with the donor/father. Donors may choose to donate through introduction websites for altruistic reasons and/or in order to have greater involvement with the child. There are some donors who are motivated by the prospect of a sexual encounter, advertising their preference for 'natural insemination' - i.e. via sexual intercourse or partial intercourse. When people make their own arrangements online, they may do so in the absence of clear, accurate information. This article, sets out some of the issues that recipients and donors ought to consider before embarking on unregulated sperm donation.

The end of donor anonymity: how genetic testing is likely to drive anonymous gamete donation out of business.

Thousands of people worldwide have been conceived using donor gametes, but not all parents tell their children of their origin. Several countries now allow donor-conceived offspring to potentially know their genetic parent if they are informed of their donor-conceived status. At the same time, personal genetic testing is a rapidly expanding field. Over 3 million people have already used direct-to-consumer genetic testing to find information about their ancestry, and many are participating in international genetic genealogy databases that will match them with relatives. The increased prevalence of these technologies poses numerous challenges to the current practice of gamete donation. (i) Whether they are donating in a country that practices anonymous donation or not, donors should be informed that their anonymity is not guaranteed, as they may be traced if their DNA, or that of a relative, is added to a database. (ii) Donor-conceived adults who have not been informed of their status may find out that they are donor-conceived. (iii) Parents using donor conception need to be fully informed that their children's DNA will identify that they are not the biological parents and they should be encouraged to disclose the use of donor gametes to their children. Together, these concerns make urgent a wide-ranging societal conversation about how to best safeguard and promote the interests of donor-conceived offspring and protect the rights of donors. Specifically, there is a need to ensure that new genetic information is communicated in a way that promotes both the safety and the privacy rights of offspring and donors alike. All parties concerned must be aware that, in 2016, donor anonymity does not exist.

Long term health consequences of Female Genital Mutilation (FGM).

Female Genital Mutilation (FGM) comprises various procedures which remove or damage the external female genital organs for no medical reason. FGM has no health benefits and is recognised to cause severe short and long term damage to both physical and psychological health. Although FGM is primarily performed in Africa, Asia and the Middle East, migration of FGM practising communities means that the health complications of FGM will have a global impact. It is important that health professionals world wide are aware of the damage FGM causes to long term health. In some cases it may be possible to offer interventions that will alleviate or improve symptoms. However whilst there is some high quality research on FGM and pregnancy outcomes, little is known about the effects on gynaecological, psychological and sexual function. Research is hampered by the problems of data collection on such a sensitive topic as well as the practical difficulties of analysis of studies based mainly on retrospect recall. Well planned hospital based studies of the impact of FGM on physical and psychological health are urgently need but are currently absent from the medical literature. Such studies could generate robust evidence to allow clinicians to benchmark clinical effectiveness and high quality medical care for survivors of FGM.