The global pandemic and changes in women's reproductive health : an observational study

Altres ajuts: Valley Electronics AG, Zurich, Switzerland.Objective: The COVID-19 global pandemic has led to the death of millions around the world and impacted the overall health of many people. In this article we aim to compare reproductive health indicators in the first 6 months of 2020 to the prior year, as well as explore stress and quality of life during this time. Methods: This retrospective observational study examined the menstrual cycles of 1159 women who were using a fertility tracking device to record their menstrual cycle and BBT data. We utilised a supplemental mobile application to administer a supplemental survey to collect data on stress and quality of life. Descriptive analyses were conducted with t-tests for two-group comparisons. Results: Study participants from 15 countries contributed to a total of 13,194 cycles. 23.1% (268/1159) responded to the survey focussed on assessing psychosocial distress. 44.4% (119/268) of the study participants reported that they had noticed a change in their menstrual cycle, temperature curve, or menstruation in the past 12 months. Cycle analysis found the average cycle length and pre-ovulation phase length was longer in the first 6 months of 2019, while the average days of menstruation was slightly longer in 2020. Discussion: Our findings indicate that menstrual cycle indicators changed only slightly in the first 6 months of 2020 but were still statistically significant. We were also able to understand that these study participants had some level of awareness of changes to their menstrual health

Comparison of two doses and two routes of administration of misoprostol after pre-treatment with mifepristone for early pregnancy termination

<p>Abstract</p> <p>Background</p> <p>It is not known whether a 400 μg dose of misoprostol has a similar efficacy as an 800 μg dose when administered sublingually or vaginally 24 hours after 200 mg mifepristone.</p> <p>Methods</p> <p>It is proposed to undertake a placebo-controlled, randomized, non-inferiority trial (3% margin of equivalence) of the two misoprostol doses when administered sublingually or vaginally using factorial design. A total of 3008 pregnant women (< 63 days of gestational age) who request legal termination of pregnancy will be recruited for the trial at 16 clinics in ten countries providing abortion services. Eligible women willing to join the study will be allocated randomly to one of the four treatment groups within each centre. Women in all treatment groups will first receive 200 mg mifepristone, followed 24 hours later by either 400 μg or 800 μg misoprostol, administered either sublingually or vaginally. The dose and route of administration of misoprostol will be blinded to women, each woman receiving four tablets vaginally and four tablets sublingually, two or four of which are 200 μg tablets of misoprostol and the rest are placebo tablets.</p> <p>The four treatment regimens will be compared in terms of: (i) their efficacy to induce complete abortion; (ii) induction-to-abortion interval when possible; (iii) the frequency of side effects; and (iv) women's perceptions. The initial judgment of the outcome of treatment is made at the follow-up visit on day 15 of the study and the final assessment four weeks later. It is estimated that the clinical phase will require 12–14 months for data collection.</p> <p>To compare the two routes and two doses, relative risks (RR) of failure to achieve a complete abortion and failure to terminate pregnancy and the two-sided 95% CIs will be calculated by standard methods, as well as risk differences and two-sided 95% CIs. The latter will be used to test the non-inferiority hypotheses (at 2.5% level of significance) for achieving complete abortion. The factorial structure will be taken into account in the analysis after testing the interaction.</p> <p>Trial registration</p> <p>ISRCTN87811512</p

Characterization of molecular changes in endometrium associated with chronic use of progesterone receptor modulators: ulipristal acetate vs. mifepristone

Ulipristal acetate (UPA) is a selective progesterone receptor modulator (PRM), which is used as an emergency contraceptive in women. Recent studies demonstrated the efficacy of an UPA contraceptive vaginal ring (UPA-CVR) as a blocker of ovulation. However, the endometrium of women exposed to UPA over a 6-month period display glandular changes, termed PRM-associated endometrial changes (PAECs). We, therefore, investigated whether UPA-induced PAECs are associated with altered expression of the transcription factor heart- and neural crest derivatives-expressed protein 2 (HAND2) whose downregulation is observed in endometrial epithelial hyperplasia and cancer. Our results showed that while exposure to mifepristone, a well-known PRM, leads to suppression of endometrial HAND2 expression, long-term exposure to UPA-CVR did not cause downregulation of this marker. Further studies, using human primary endometrial stromal cells, confirmed that whereas mifepristone-mediated suppression of HAND2 elevated the levels of its downstream target fibroblast growth factor 18, UPA did not significantly alter the expression of this growth factor. A rationale for the differential regulation of HAND2 by these PRMs was provided by our observation that mifepristone-bound progesterone receptors turn over at a faster rate than those bound to UPA. Collectively, these results support the selective effects of different PRMs and indicate that chronic exposure to UPA does not alter the HAND2 pathway whose dysregulation is linked to complex atypical endometrial hyperplasia and cancer. The results from this study involving a limited number of clinical samples should pave the way for a larger study to determine the safety of UPA for long-term use

The WID-BC-index identifies women with primary poor prognostic breast cancer based on DNA methylation in cervical samples

Genetic and non-genetic factors contribute to breast cancer development. An epigenome-based signature capturing these components in easily accessible samples could identify women at risk. Here, we analyse the DNA methylome in 2,818 cervical, 357 and 227 matched buccal and blood samples respectively, and 42 breast tissue samples from women with and without breast cancer. Utilising cervical liquid-based cytology samples, we develop the DNA methylation-based Women’s risk IDentification for Breast Cancer index (WID-BC-index) that identifies women with breast cancer with an AUROC (Area Under the Receiver Operator Characteristic) of 0.84 (95% CI: 0.80–0.88) and 0.81 (95% CI: 0.76–0.86) in internal and external validation sets, respectively. CpGs at progesterone receptor binding sites hypomethylated in normal breast tissue of women with breast cancer or in BRCA mutation carriers are also hypomethylated in cervical samples of women with poor prognostic breast cancer. Our data indicate that a systemic epigenetic programming defect is highly prevalent in women who develop breast cancer. Further studies validating the WID-BC-index may enable clinical implementation for monitoring breast cancer risk.publishedVersio

Adrenalectomy-Produced Facilitation of Pavlovian Conditioned Cardiodecelerations in Immobilized Rats

Previous evidence has suggested that both hormonal and behavioral aspects of adrenal stress activation may contribute to heart rate (HR) conditioning during physical/pharmacological immobilization. Accordingly, four studies were conducted to determine if bilateral adrenalectomy facilitates stimulus-control over Pavlovian conditioned cardiodecelerations in rats immobilized either through physical restraint or neuromuscular paralysis. Plasma corticosterone assays were used as an index of the effectiveness of adrenal removal. The results showed that adrenalectomy facilitated both simple and discriminated Pavlovian conditioned cardiodecelerations in rats paralyzed with d-tubocurarine chloride (dTC) without significantly altering the characteristics of EMG recovery from paralysis. Similarly, adrenalectomy facilitated simple Pavlovian HR conditioning in physically restrained rats. The results suggest that adrenal activation may disrupt the parasympathetically-mediated Pavlovian conditioned cardiodeceleration in the physically-and dTC-immobilized rat. However, the specific nature of neuroendocrine mechanisms underlying cardiovascular conditioning during immobilization remains problematical.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75069/1/j.1469-8986.1977.tb03371.x.pd

Simultaneous prevention of unintended pregnancy and STIs: A challenging compromise

Background: Unintended pregnancy and sexually transmitted infections (STIs) are the major negative consequences of unsafe sex. Both are common and have long-term social and health consequences. Barrier methods of contraception can prevent both, but unfortunately they are much less effective than the more modern methods at pregnancy prevention. Modern effective contraceptives, however, do not protect against STIs and some may increase the risk of acquisition of infection. This comprehensive review discusses the magnitude of burden of reproductive ill-health, focussing on data from the European region, and explores the relationship between contraceptive use and STIs. methods: Searches were performed by using Medline, Popline, EMBASE, Cochrane Library and the Social Sciences Citation Index databases for relevant English language publications from 1995 to 2012. Summaries were discussed by the European Society of Human Reproduction and Embryology (ESHRE)Workshop Group. results: An understanding of patterns of sexual behaviour helps to understand the epidemiology of unintended pregnancy and STIs and gives pointers towards their prevention, but survey methodologies differ and results are hard to compare. Contraceptive prevalence and method mix vary widely between countries, and the use of the dual method of protection is very infrequent. Abortion rates have fallen in many European countries, particularly Eastern Europe, and contraceptive prevalence increased but unsafe abortion still accounts for 11% of maternal mortality in Eastern Europe. STIs are common but reporting systems are often rudimentary or non-existent and robust data are scarce. Providers still worry about the effect of intrauterine contraception on reproductive tract infections despite reassuring evidence to the contrary. New data on HIV acquisition and hormonal contraception are causing concern in settings where HIV infection is common. Newdevelopments in multipurpose technologies aimed at producing a single device/drug, which prevents infection and pregnancy simultaneously, are in early stages. While the benefits of national screening programmes for STIs remain uncertain, human papilloma virus (HPV) vaccination is clearly reducing HPV infection rates and gives hope for the public health benefits of other STI vaccines. conclusions: The consequences of unsafe sex-unintended pregnancy and STI-continue to present major public health problems worldwide even in countries where the prevalence of use of modern contraception is high. Robust systems for routine data collection are sorely needed in most countries and systematic attempts to compare patterns of sexual behaviour across men and women of all ages would be welcome