McNulty KL et al., 2020·Sports medicine (Auckland, N.Z.)
Concentrations of endogenous sex hormones fluctuate across the menstrual cycle (MC), which could have implications for exercise performance in women. At present, data are conflicting, with no consensus on whether exercise performance is affected by MC phase. To determine the effects of the MC on exercise performance and provide evidence-based, practical, performance recommendations to eumenorrheic women. This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Four databases were searched for published experimental studies that investigated the effects of the MC on exercise performance, which included at least one outcome measure taken in two or more defined MC phases. All data were meta-analysed using multilevel models grounded in Bayesian principles. The initial meta-analysis pooled pairwise effect sizes comparing exercise performance during the early follicular phase with all other phases (late follicular, ovulation, early luteal, mid-luteal and late luteal) amalgamated. A more comprehensive analysis was then conducted, comparing exercise performance between all phases with direct and indirect pairwise effect sizes through a network meta-analysis. Results from the network meta-analysis were summarised by calculating the Surface Under the Cumulative Ranking curve (SUCRA). Study quality was assessed using a modified Downs and Black checklist and a strategy based on the recommendations of the Grading of Recommendations Assessment Development and Evaluation (GRADE) working group. Of the 78 included studies, data from 51 studies were eligible for inclusion in the initial pairwise meta-analysis. The three-level hierarchical model indicated a trivial effect for both endurance- and strength-based outcomes, with reduced exercise performance observed in the early follicular phase of the MC, based on the median pooled effect size (ES0.5 = - 0.06 [95% credible interval (CrI): - 0.16 to 0.04]). Seventy-three studies had enough data to be included in the network meta-analysis. The largest effect was identified between the early follicular and the late follicular phases of the MC (ES0.5 = - 0.14 [95% - 0.26 to - 0.03]). The lowest SUCRA value, which represents the likelihood that exercise performance is poor, or among the poorest, relative to other MC phases, was obtained for the early follicular phase (30%), with values for all other phases ranging between 53 and 55%. The quality of evidence for this review was classified as "low" (42%). The results from this systematic review and meta-analysis indicate that exercise performance might be trivially reduced during the early follicular phase of the MC, compared to all other phases. Due to the trivial effect size, the large between-study variation and the number of poor-quality studies included in this review, general guidelines on exercise performance across the MC cannot be formed; rather, it is recommended that a personalised approach should be taken based on each individual's response to exercise performance across the MC.
Skorseth P et al., 2020·Orthopaedic journal of sports medicine
Investigations of the female athlete triad (Triad) in high school athletes have found that 36% had low energy availability, 54% had menstrual abnormalities, and 16% had low bone mineral density (BMD). Limited data are available showing the prevalence of these risk factors in high school distance runners or regarding best practice on screening for the Triad in the adolescent population. To (1) evaluate the prevalence of Triad risk factors and iron supplementation in high school distance runners and (2) pilot a screening tool for Triad risk score. Descriptive epidemiology study. The study population included female high school athletes who participated in cross-country/track. Participants completed a survey including questions regarding dietary habits, menstrual history, and bone stress injury (BSI) history. They then underwent evaluation of 25-hydroxyvitamin D, free triiodothyronine (T3), and dual-energy x-ray absorptiometry scan to measure body fat and BMD through use of age-, sex-, and ethnicity-matched Z scores. Triad scores were calculated. Relationships were analyzed using Spearman correlation coefficient. There were 38 study participants (mean age, 16.9 years). Average body mass index was 19.8 kg/m2. Disordered eating or eating disorders were reported in 76.3% of runners; in addition, 23.7% reported delayed menarche, 45.9% had a history of amenorrhea or oligomenorrhea, 42.1% had low BMD (Z score < -1.0), and 15.8% reported prior BSI. Low free T3 was significantly associated with higher Triad risk scores (r S = -0.36; P = .028). More than 42% of athletes were supplementing iron. The prevalence of Triad risk factors in high school distance runners was high. Free T3 was inversely associated with Triad score, which may serve as an indicator of low energy availability. Nearly half of the athletes were using iron supplementation.
Cetin E et al., 2020·Current opinion in obstetrics & gynecology
Uterine fibroids are the most common benign neoplasms of the female reproductive tract and one of the major public health concerns. Although most women with uterine fibroids are asymptomatic, over 30% of them will present with varying symptoms. This review focuses on the role of non-hormonal mediators and pathways in uterine fibroid biology. Furthermore, it provides data regarding the most recent findings in the field of compounds, which use those non-hormonal pathways in the medical therapy of uterine fibroids. Complex signaling pathway alterations are crucial for uterine fibroid development. The topic of the pathophysiology of uterine fibroids focuses mostly on steroids and other hormones. However, other very important pathways exist, and some of them are independent of hormones. Some of the most important pathways, which are non-hormonal, but in some cases still hormone-depended, include growth factors, cytokines and inflammation, Smad proteins, wingless type/β-catenin and others. Much more is known about hormonal than about non-hormonal signaling in uterine fibroids. Growth factors, early life exposure and inflammation are key factors in uterine fibroid biology. Numerous agents depend on those pathways and may find their place in the current and future therapy of uterine fibroids.
We aim to describe the diagnosis and surgical management of urinary tract endometriosis (UTE). We detail current diagnostic tools, including advanced transvaginal ultrasound, magnetic resonance imaging, and surgical diagnostic tools such as cystourethroscopy. While discussing surgical treatment options, we emphasize the importance of an interdisciplinary team for complex cases that involve the urinary tract. While bladder deep endometriosis (DE) is more straightforward in its surgical treatment, ureteral DE requires a high level of surgical skill. Specialists should be aware of the important entity of UTE, due to the serious health implications for women. When UTE exists, it is important to work within an interdisciplinary radiological and surgical team.
AbstractObjectiveTo evaluate whether irregular or long menstrual cycles throughout the life course are associated with all cause and cause specific premature mortality (age <70 years). Prospective cohort study. Nurses’ Health Study II (1993-2017).Participants79 505 premenopausal women without a history of cardiovascular disease, cancer, or diabetes and who reported the usual length and regularity of their menstrual cycles at ages 14-17 years, 18-22 years, and 29-46 years. Hazard ratios and 95% confidence intervals for all cause and cause specific premature mortality (death before age 70 years) were estimated from multivariable Cox proportional hazards models. During 24 years of follow-up, 1975 premature deaths were documented, including 894 from cancer and 172 from cardiovascular disease. Women who reported always having irregular menstrual cycles experienced higher mortality rates during follow-up than women who reported very regular cycles in the same age ranges. The crude mortality rate per 1000 person years of follow-up for women reporting very regular cycles and women reporting always irregular cycles were 1.05 and 1.23 for cycle characteristics at ages 14-17 years, 1.00 and 1.37 for cycle characteristics at ages 18-22 years, and 1.00 and 1.68 for cycle characteristics at ages 29-46 years. The corresponding multivariable adjusted hazard ratios for premature death during follow-up were 1.18 (95% confidence interval 1.02 to 1.37), 1.37 (1.09 to 1.73), and 1.39 (1.14 to 1.70), respectively. Similarly, women who reported that their usual cycle length was 40 days or more at ages 18-22 years and 29-46 years were more likely to die prematurely than women who reported a usual cycle length of 26-31 days in the same age ranges (1.34, 1.06 to 1.69; and 1.40, 1.17 to 1.68, respectively). These relations were strongest for deaths related to cardiovascular disease. The higher mortality associated with long and irregular menstrual cycles was slightly stronger among current smokers. Irregular and long menstrual cycles in adolescence and adulthood are associated with a greater risk of premature mortality (age <70 years). This relation is slightly stronger among women who smoke.
DeVilbiss EA et al., 2020·Paediatr Perinat Epidemiol
Attaining pregnancy is conditional upon a series of complex processes, including adequately timed intercourse, ovulation, fertilisation, and implantation. Anovulation is a first-line treatment target for couples with difficulty conceiving and is frequently examined in studies of fecundability. To identify whether sporadic anovulation is an important determinant of cumulative pregnancy rates and time to pregnancy among fertile women with regular menstrual cycles. We simulated cumulative pregnancy rates and time to pregnancy for 12 consecutive menstrual cycles among 100 000 women based on data-driven probabilities of implantation, fertilisation, ovulation, and intercourse occurring in the fertile window. We assumed anovulation probabilities of 1%, 8%, or 14.5% and intercourse averaging once per week, every other day, or daily. The model incorporated reductions in implantation and fertilisation rates for successive cycles of non-pregnancy. After 12 cycles, a reduction in the per cycle incidence of anovulation from 14.5% to 1% resulted in a 4.0% higher cumulative pregnancy rate (86.7% vs 90.7%) and similar time to pregnancy (1-cycle median difference). In contrast, increasing mean unscheduled sexual intercourse frequency from weekly to every other day was associated with a 5-cycle median reduction in time to pregnancy (weekly: 7 cycles; 2 cycles) and a 28.9% increase in the cumulative pregnancy rate (weekly: 59.9%, 88.8%; 91.6%). In presumed fertile women with regular menstrual cycles, routine investigation of anovulation may not be an informative outcome in studies of fecundability, and routine testing to ensure ovulation and treatment of anovulation are unlikely to be medically necessary. While biomarkers or cervical fluid may help time intercourse to the fertile window, time to pregnancy can also be improved through increasing the frequency of unscheduled intercourse. These findings need corroboration in large preconception time to pregnancy studies.
Bone HealthEthnic Differences in Bone DensityPopulation-Based StudiesMulticentre Observational
Fracture determinants differ between Canadians of Chinese and White descent, the former constituting the second largest visible minority group in Canada. The results of this study support the importance of characterizing bone health predictors in Canadians of different ethnicity to improve population-specific fracture prevention and treatment strategies.
We aimed to compare clinical risk factors, bone mineral density, prevalence of osteoporosis, and fractures between Chinese and White Canadians to identify ethnicity-specific risks. We studied 236 Chinese and 8945 White Canadians aged 25+ years from the Canadian Multicentre Osteoporosis Study (CaMos). The prevalence of osteoporosis using ethnicity-specific peak bone mass (PBM), and of prior and incident low trauma fractures were assessed and compared between groups. Linear regressions, adjusting for age and anthropometric measures, were used to examine the association between baseline and 5-year changes in BMD and ethnicity. Chinese participants had shorter stature, lower BMI, and lower rate of falls than White participants. Adjusted models showed no significant differences in baseline BMD between ethnic groups except in younger men where total hip BMD was 0.059 g/cm2 (0.009; 0.108) lower in Chinese. Adjusted 5-year BMD change at lumbar spine was higher in older Chinese women and men compared with Whites. When using Chinese-specific PBM, the prevalence of osteoporosis in Chinese women was 2-fold lower than when using that of White women The prevalence of fractures was higher in White women compared with Chinese with differences up to 14.5% (95% CI 9.2; 19.7) and 10.5% (95% CI 4.5-16.4) in older White men. Incident fractures were rare in young Chinese compared with White participants and not different in the older groups. Our results support the importance of characterizing bone strength predictors in Chinese Canadians and the development of ethnicity-specific fracture prediction and prevention strategies.
Breastfeeding has immediate and long-term benefits for both maternal and child health. This study examines the association between Baby-Friendly Hospital Initiative (BFHI) experiences and breastfeeding outcomes in the Mountain West region. A cross-sectional (retrospective secondary data analysis) was performed using the 2016 Pregnancy Risk Assessment Monitoring System (PRAMS) data. The participants were derived from a stratified random sample of 2,013 women living in Utah and Wyoming who recently had a live birth and who were surveyed on BFHI practices. The association between BFHI experiences and breastfeeding duration were assessed using crude and adjusted Poisson regression models, controlling for other BHFI experiences and maternal age, pre-pregnancy BMI, household income, smoking, alcohol, delivery method, and number of days spent in the hospital post delivery. 82.4% and 82.3% of women from Utah and Wyoming, respectively, reported breastfeeding for 2 months or longer. After controlling for other BFHI experiences and potential confounders, the one shared BFHI experience that was associated with breastfeeding for 2 months or longer vs less than 2 months was starting breastfeeding in the hospital (adjusted prevalence ratio [aPR]=1.49, 95% CI (1.12, 1.98) in Utah and aPR=2.03, 95% CI (1.13, 3.64) in Wyoming. Among women in Utah and Wyoming, only 5 of 7 BFHI steps were significant for breastfeeding duration in at least one state. There is substantial epidemiological support for health benefits to both mother and infant for exclusive breastfeeding to 6 months and prolonged breastfeeding until at least 1-year. Our findings suggest that women who initiate breastfeeding in the hospital may be more likely to breastfeed for a longer duration.
To investigate the association between pre-pregnancy body mass index (BMI) and subfertility within a population-based cohort, exploring Hispanic ethnicity as a potential effect modifier. We used cross-sectional study data from the Utah Pregnancy Risk Assessment Monitoring System from 2012-2015. Relationships between maternal pre-pregnancy BMI and subfertility were evaluated via Poisson regression models with robust error variance, accounting for the stratified survey sampling. Preconception BMI was analyzed continuously and categorically. Women's subfertility was defined 1) time trying to achieve pregnancy; and 2) report of using fertility-related drugs/medical procedures. The median age was 27.0; 18.8% were obese, and 15.9% were Hispanic. Women with preconception obesity (BMI>30kg/m(2)), compared to normal weight women (18.4kg/ m(2)<BMI<25kg/m(2)) had a 1.85 (95% CI 1.43, 2.38) higher adjusted prevalence ratio (aPR) for having subfertility defined by time trying and a 1.73 (95% CI 1.20, 2.32) higher aPR for receiving fertility-enhancing drugs/medical procedures. Continuous models indicated a linear relationship between BMI and subfertility (aPR 1.04, 95% CI 1.03, 1.06 for time trying; and 1.06, 95% CI 1.03, 1.10 for receiving fertility-enhancing drugs/medical procedures). Obese women, but not underweight or overweight women, reported higher subfertility than normal-weight women. Findings among this cohort of at-risk new mothers, oversampled on low education and birth weight and comprised of higher than the national average of Hispanics, indicated a dose-response relationship between obesity and subfertility.
Our findings highlight the importance of population-oriented obesity prevention for at-risk women with intentions to conceive.
To what extent does the use of mobile computing apps to track the menstrual cycle and the fertile window influence fecundability among women trying to conceive? After adjusting for potential confounders, use of any of several different apps was associated with increased fecundability ranging from 12% to 20% per cycle of attempt. Many women are using mobile computing apps to track their menstrual cycle and the fertile window, including while trying to conceive. STUDY DESIGN, SIZE, The Pregnancy Study Online (PRESTO) is a North American prospective internet-based cohort of women who are aged 21-45 years, trying to conceive and not using contraception or fertility treatment at baseline. PARTICIPANTS/MATERIALS, SETTING, We restricted the analysis to 8363 women trying to conceive for no more than 6 months at baseline; the women were recruited from June 2013 through May 2019. Women completed questionnaires at baseline and every 2 months for up to 1 year. The main outcome was fecundability, i.e. the per-cycle probability of conception, which we assessed using self-reported data on time to pregnancy (confirmed by positive home pregnancy test) in menstrual cycles. On the baseline and follow-up questionnaires, women reported whether they used mobile computing apps to track their menstrual cycles ('cycle apps') and, if so, which one(s). We estimated fecundability ratios (FRs) for the use of cycle apps, adjusted for female age, race/ethnicity, prior pregnancy, BMI, income, current smoking, education, partner education, caffeine intake, use of hormonal contraceptives as the last method of contraception, hours of sleep per night, cycle regularity, use of prenatal supplements, marital status, intercourse frequency and history of subfertility. We also examined the impact of concurrent basal body temperature, cervical fluid, cervix position and/or urine LH. MAIN Among 8363 women, 6077 (72.7%) were using one or more cycle apps at baseline. A total of 122 separate apps were reported by women. We designated five of these apps before analysis as more likely to be effective (Clue, Fertility Friend, Glow, Kindara, Ovia; hereafter referred to as 'selected apps'). The use of any app at baseline was associated with 20% increased fecundability, with little difference between selected apps versus other apps (selected apps FR (95% CI): 1.20 (1.13, 1.28); all other apps 1.21 (1.13, 1.30)). In time-varying analyses, cycle app use was associated with 12-15% increased fecundability (selected apps FR (95% CI): 1.12 (1.04, 1.21); all other apps 1.15 (1.07, 1.24)). When apps were used at baseline with one or more fertility indicators, there was higher fecundability than without fertility indicators (selected apps with indicators FR (95% CI): 1.23 (1.14, 1.34) versus without indicators 1.17 (1.05, 1.30); other apps with indicators 1.30 (1.19, 1.43) versus without indicators 1.16 (1.06, 1.27)). In time-varying analyses, results were similar when stratified by time trying at study entry (<3 vs. 3-6 cycles) or cycle regularity. For use of the selected apps, we observed higher fecundability among women FR 1.33 (1.05-1.67). LIMITATIONS, Neither regularity nor intensity of app use was ascertained. The prospective time-varying assessment of app use was based on questionnaires completed every 2 months, which would not capture more frequent changes. Intercourse frequency was also reported retrospectively and we do not have data on timing of intercourse relative to the fertile window. Although we controlled for a wide range of covariates, we cannot exclude the possibility of residual confounding (e.g. choosing to use an app in this observational study may be a marker for unmeasured health habits promoting fecundability). Half of the women in the study received a free premium subscription for one of the apps (Fertility Friend), which may have increased the overall prevalence of app use in the time-varying analyses, but would not affect app use at baseline. Most women in the study were college educated, which may limit application of results to other populations. Use of a cycle app, especially in combination with observation of one or more fertility indicators (basal body temperature, cervical fluid, cervix position and/or urine LH), may increase fecundability (per-cycle pregnancy probability) by about 12-20% for couples trying to conceive. We did not find consistent evidence of improved fecundability resulting from use of one specific app over another. STUDY FUNDING/COMPETING INTEREST(S): This research was supported by grants, R21HD072326 and R01HD086742, from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, USA. In the last 3 years, Dr L.A.W. has served as a fibroid consultant for AbbVie.com. Dr L.A.W. has also received in-kind donations from Sandstone Diagnostics, Swiss Precision Diagnostics, FertilityFriend.com and Kindara.com for primary data collection and participant incentives in the PRESTO cohort. Dr J.B.S. reports personal fees from Swiss Precision Diagnostics, outside the submitted work. The remaining authors have nothing to declare. N/A.
Fertility AwarenessMobile ApplicationsFertile Window IdentificationDigital Tools
Open Access
To characterize mobile fertility tracking applications (apps) to determine the use of such apps for women trying to conceive by identifying the fertile window.
An exploratory cross-sectional audit study was conducted of fertility tracking applications. Ninety out of a possible total 200 apps were included for full review. The main outcome measures were the underlying app method for predicting ovulation, the fertile window, or both, price to download and use the app, disclaimers and cautions, information and features provided and tracked, and app marketing strategies.
All the apps except one monitored the women's menstrual cycle dates. Most apps only tracked menstrual cycle dates (n = 49 [54.4%]). The remainder tracked at least one fertility-based awareness method (basal body temperature, cervical mucus, LH) (n = 41 [45.6%]). Twenty-five apps measured dates, basal body temperature, LH and cervical mucus (27.8%). Seventy-six per cent of apps were free to download with free apps having more desirable features, tracking more measures and having more and better quality educational insights than paid apps. Seventy per cent of apps were classified as feminine apps, 41% of which were pink in colour. Mobile fertility tracking apps are heterogenous in their underlying methods of predicting fertile days, the price to obtain full app functionality, and in content and design. Unreliable calendar apps remain the most commonly available fertility apps on the market. The unregulated nature of fertility apps is a concern that could be addressed by app regulating bodies. The possible benefit of using fertility apps to reduce time to pregnancy needs to be evaluated.
Vidmar Golja M et al., 2020·Journal of clinical medicine
Adequate levels of folates are essential for homeostasis of the organism, prevention of congenital malformations, and the salvage of predisposed disease states. They depend on genetic predisposition, and therefore, a pharmacogenetic approach to individualized supplementation or therapeutic intervention is necessary for an optimal outcome. The role of folates in vital cell processes was investigated by translational pharmacogenetics employing lymphoblastoid cell lines (LCLs). Depriving cells of folates led to reversible S-phase arrest. Since 5,10-methylenetetrahydrofolate reductase (MTHFR) is the key enzyme in the biosynthesis of an active folate form, we evaluated the relevance of polymorphisms in the MTHFR gene on intracellular levels of bioactive metabolite, the 5-methyltetrahydrofolate (5-Me-THF). LCLs (n = 35) were divided into low- and normal-MTHFR activity groups based on their genotype. They were cultured in the presence of folic acid (FA) or 5-Me-THF. Based on the cells' metabolic activity and intracellular 5-Me-THF levels, we conclude supplementation of FA is sufficient to maintain adequate folate level in the normal MTHFR activity group, while low MTHFR activity cells require 5-Me-THF to overcome the metabolic defects caused by polymorphisms in their MTHFR genes. This finding was supported by the determination of intracellular levels of 5-Me-THF in cell lysates by LC-MS/MS. FA supplementation resulted in a 2.5-fold increase in 5-Me-THF in cells with normal MTHFR activity, but there was no increase after FA supplementation in low MTHFR activity cells. However, when LCLs were exposed to 5-Me-THF, a 10-fold increase in intracellular levels of this metabolite was determined. These findings indicate that patients undergoing folate supplementation to counteract anti-folate therapies, or patients with increased folate demand, would benefit from pharmacogenetics-based therapy choices.
Machado V et al., 2020·Reproduction (Cambridge, England)
Hormones and inflammatory mechanisms are implicated with female reproductive function, including follicle maturation, ovulation, embryo implantation, and pregnancy. Periodontitis is a chronic inflammatory disease due to a polymicrobial disruption of the homeostasis and may be considered as a potential risk factor that affect female fertility. The role of periodontitis is becoming meaningful, with significant associations with polycystic ovary syndrome, endometriosis and bacterial vaginosis. Further, periodontitis is linked with known risk factors towards female infertility, such as age, obesity, and chronic kidney disease. This review aims to summarize the available evidence on the association between periodontitis and female infertility-associated conditions, and to discuss warranting steps in future research.
Xu Y et al., 2020·American journal of reproductive immunology (New York, N.Y. : 1989)
Chronic endometritis (CE) is an unusual inflammatory condition characterized by endometrial plasmacyte infiltration. It has a high prevalence in women with reproductive failure. Because of its characteristic localization patterns and molecular functions, syndecan-1 has been identified as a biomarker of plasmacyte, and syndecan-1 immunohistochemistry (IHC) becomes the most dependable diagnostic method for CE. In this review, we discuss the association between CE and reproductive failure, the clinicopathological characterization of CE, the function and expression of syndecan-1, the progress of syndecan-1 IHC in the diagnosis of CE, and the prediction of reproductive outcome.
Raźnikiewicz A et al., 2020·Wideochirurgia i inne techniki maloinwazyjne = Videosurgery and other miniinvasive techniques
Paediatric and adolescent gynaecology is a narrow field of medicine dealing with the diagnosis of and treatment of gynaecological diseases from the neonatal period to sexual maturity. The current trend in surgical gynaecology in the paediatric population is to minimise the degree of invasiveness of diagnostic and therapeutic procedures. This contributes to reducing the number of complications and the risk of infertility. Laparoscopic procedures are a challenge for paediatric surgeons and gynaecologists, not only because of the age of treated patients, and anatomical and physiological differences between different age groups but also because of the complexity of the pathology, the differentiation of cancer tumours, and the presence of congenital developmental defects.
Creatine is an amino acid derivative synthesized from arginine, glycine and methionine. It serves as the substrate for the creatine kinase system, which is vital for maintaining ATP levels in tissues with high and fluctuating energy demand. There exists evidence that the creatine kinase system operates in both the endometrial and myometrial layers of the uterus. While use and regulation of this system in the uterus are not well understood, it is likely to be important given uterine tissues undergo phases of increased energy demand during certain stages of the female reproductive cycle, pregnancy, and parturition. This review discusses known adaptations of creatine metabolism in the uterus during the reproductive cycle (both estrous and menstrual), pregnancy and parturition, highlighting possible links to fertility and the existing knowledge gaps. Specifically, we discuss the adaptations and regulation of uterine creatine metabolite levels, cell creatine transport, de novo creatine synthesis, and creatine kinase expression in the various layers and cell types of the uterus. Finally, we discuss the effects of dietary creatine on uterine metabolism. In summary, there is growing evidence that creatine metabolism is up-regulated in uterine tissues during phases where energy demand is increased. While it remains unclear how important these adaptations are in the maintenance of healthy uterine function, furthering our understanding of uterine creatine metabolism may uncover strategies to combat poor embryo implantation and failure to conceive, as well as enhancing uterine contractile performance during labor.
Showell MG et al., 2020·Cochrane Database Syst Rev
M.G. Showell, R. Mackenzie‐Proctor, V. Jordan, and R.J. Hart, “Antioxidants for Female Subfertility,” Cochrane Database of Systematic Reviews, no. 8 (2020): CD007807, //doi.org/10.1002/14651858.CD007807.pub4 This Editorial Note is for the above article, published online on August 27, 2020, in Cochrane Library (cochranelibrary.com), and has been issued by the Publisher, John Wiley & Sons Ltd, in agreement with Cochrane. The Editorial note has been agreed due to concerns discovered by the Cochrane managing editor regarding the retraction of six studies in the Review (Badawy et al. 2006, 10.1016/j.fertnstert.2006.02.097; El Refaeey et al. 2014, 10.1016/j.rbmo.2014.03.011; El Sharkwy & Abd El Aziz 2019a, //doi.org/10.1002/ijgo.12902; Gerli et al. 2007, //doi.org/10.26355/eurrev_202309_33752, //europepmc.org/article/MED/18074942; Ismail et al. 2014, //dx.doi.org/10.1016/j.ejogrb.2014.06.008; Hashemi et al. 2017, //doi.org/10.1080/14767058.2017.1372413). In addition, expressions of concern have been published for two studies (Jamilian et al. 2018, //doi.org/10.1007/s12011-017-1236-3; Zadeh Modarres 2018, //doi.org/10.1007/s12011-017-1148-2). The retracted studies will be moved to the Excluded Studies table, and their impact on the review findings will be investigated and acted on accordingly in a future update. Initial checks indicate that removal of the six retracted studies did not make an appreciable difference to the results. Likewise, the studies for which Expressions of Concern were issued will be moved to the Awaiting classification table; they did not report any review outcomes, so removal will have no impact on the review findings.
A couple may be considered to have fertility problems if they have been trying to conceive for over a year with no success. This may affect up to a quarter of all couples planning a child. It is estimated that for 40% to 50% of couples, subfertility may result from factors affecting women. Antioxidants are thought to reduce the oxidative stress brought on by these conditions. Currently, limited evidence suggests that antioxidants improve fertility, and trials have explored this area with varied results. This review assesses the evidence for the effectiveness of different antioxidants in female subfertility. To determine whether supplementary oral antioxidants compared with placebo, no treatment/standard treatment or another antioxidant improve fertility outcomes for subfertile women. We searched the following databases (from their inception to September 2019), with no Cochrane Gynaecology and Fertility Group (CGFG) specialised register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL and AMED. We checked reference lists of relevant studies and searched the trial registers.
We included randomised controlled trials (RCTs) that compared any type, dose or combination of oral antioxidant supplement with placebo, no treatment or treatment with another antioxidant, among women attending a reproductive clinic. We excluded trials comparing antioxidants with fertility drugs alone and trials that only included fertile women attending a fertility clinic because of male partner infertility.
We used standard methodological procedures expected by Cochrane. The primary review outcome was live birth; secondary outcomes included clinical pregnancy rates and adverse events. We included 63 trials involving 7760 women. Investigators compared oral antioxidants, combinations of antioxidants, N-acetylcysteine, melatonin, L-arginine, myo-inositol, carnitine, selenium, vitamin E, vitamin B complex, vitamin C, vitamin D+calcium, CoQ10, and omega-3-polyunsaturated fatty acids versus placebo, no treatment/standard treatment or another antioxidant. Only 27 of the 63 included trials reported funding sources. Due to the very low-quality of the evidence we are uncertain whether antioxidants improve live birth rate compared with placebo or no treatment/standard treatment (odds ratio (OR) 1.81, 95% confidence interval (CI) 1.36 to 2.43; P < 0.001, I(2) = 29%; 13 RCTs, 1227 women). This suggests that among subfertile women with an expected live birth rate of 19%, the rate among women using antioxidants would be between 24% and 36%. Low-quality evidence suggests that antioxidants may improve clinical pregnancy rate compared with placebo or no treatment/standard treatment (OR 1.65, 95% CI 1.43 to 1.89; P < 0.001, I(2) = 63%; 35 RCTs, 5165 women). This suggests that among subfertile women with an expected clinical pregnancy rate of 19%, the rate among women using antioxidants would be between 25% and 30%. Heterogeneity was moderately high. Overall 28 trials reported on various adverse events in the meta-analysis. The evidence suggests that the use of antioxidants makes no difference between the groups in rates of miscarriage (OR 1.13, 95% CI 0.82 to 1.55; P = 0.46, I(2) = 0%; 24 RCTs, 3229 women; low-quality evidence). There was also no evidence of a difference between the groups in rates of multiple pregnancy (OR 1.00, 95% CI 0.63 to 1.56; P = 0.99, I(2) = 0%; 9 RCTs, 1886 women; low-quality evidence). There was also no evidence of a difference between the groups in rates of gastrointestinal disturbances (OR 1.55, 95% CI 0.47 to 5.10; P = 0.47, I(2) = 0%; 3 RCTs, 343 women; low-quality evidence). Low-quality evidence showed that there was also no difference between the groups in rates of ectopic pregnancy (OR 1.40, 95% CI 0.27 to 7.20; P = 0.69, I(2) = 0%; 4 RCTs, 404 women). In the antioxidant versus antioxidant comparison, low-quality evidence shows no difference in a lower dose of melatonin being associated with an increased live-birth rate compared with higher-dose melatonin (OR 0.94, 95% CI 0.41 to 2.15; P = 0.89, I(2) = 0%; 2 RCTs, 140 women). This suggests that among subfertile women with an expected live-birth rate of 24%, the rate among women using a lower dose of melatonin compared to a higher dose would be between 12% and 40%. Similarly with clinical pregnancy, there was no evidence of a difference between the groups in rates between a lower and a higher dose of melatonin (OR 0.94, 95% CI 0.41 to 2.15; P = 0.89, I(2) = 0%; 2 RCTs, 140 women). Three trials reported on miscarriage in the antioxidant versus antioxidant comparison (two used doses of melatonin and one compared N-acetylcysteine versus L-carnitine). There were no miscarriages in either melatonin trial. Multiple pregnancy and gastrointestinal disturbances were not reported, and ectopic pregnancy was reported by only one trial, with no events. The study comparing N-acetylcysteine with L-carnitine did not report live birth rate. Very low-quality evidence shows no evidence of a difference in clinical pregnancy (OR 0.81, 95% CI 0.33 to 2.00; 1 RCT, 164 women; low-quality evidence). Low quality evidence shows no difference in miscarriage (OR 1.54, 95% CI 0.42 to 5.67; 1 RCT, 164 women; low-quality evidence). The study did not report multiple pregnancy, gastrointestinal disturbances or ectopic pregnancy. The overall quality of evidence was limited by serious risk of bias associated with poor reporting of methods, imprecision and inconsistency. AUTHORS' In this review, there was lowto very low-quality evidence to show that taking an antioxidant may benefit subfertile women. Overall, there is no evidence of increased risk of miscarriage, multiple births, gastrointestinal effects or ectopic pregnancies, but evidence was of very low quality. At this time, there is limited evidence in support of supplemental oral antioxidants for subfertile women.
Compared to other genital cancers, cervical cancer is the most prevalent and the main cause of mortality in females in third-world countries, affected by different factors, including smoking, poor nutritional status, immune-deficiency, long-term use of contraceptives and so on. The present study was conducted to predict cervical cancer and identify its important predictors using machine learning classification algorithms. In a cross-sectional study, the data of 145 patients with 23 attributes, which referred to Shohada Hospital Tehran, Iran during 2017-2018, were analyzed by machine learning classification algorithms which included SVM, QUEST, C&R tree, MLP and RBF. The criteria measurement used to evaluate these algorithms included accuracy, sensitivity, specificity and area under the curve (AUC). The accuracy, sensitivity, specificity and AUC of Quest and C&R tree were, respectively 95.55, 90.48, 100, and 95.20, 95.55, 90.48, 100, and 95.20, those of RBF 95.45, 90.00, 100 and 91.50, those of SVM 93.33, 90.48, 95.83 and 95.80 and those of MLP 90.90, 90.00, 91.67 and 91.50 percentage. The important predictors in all the algorithms were found to comprise personal health level, marital status, social status, the dose of contraceptives used, level of education and number of caesarean deliveries. This investigation confirmed that ML can enhance the prediction of cervical cancer. The results of this study showed that Decision Tree algorithms can be applied to identify the most relevant predictors. Moreover, it seems that improving personal health and socio-cultural level of patients can be causing cervical cancer prevention.
Zinc is an essential microelement that plays many important functions in the body. It is crucial for the regulation of cell growth, hormone release, immunological response and reproduction. This review focuses on its importance in the reproductive system of women of reproductive and postmenopausal ages, not including its well described role in pregnancy. Only recently, attention has been drawn to the potential role of zinc in polycystic ovary syndrome (PCOS), dysmenorrhea, or endometriosis. This review is mainly based on 36 randomized, controlled studies on reproductive, pre- and post-menopausal populations of women and on research trying to explain the potential impact of zinc and its supplementation in the etiology of selected female reproductive system disorders. In women with PCOS, zinc supplementation has a positive effect on many parameters, especially those related to insulin resistance and lipid balance. In primary dysmenorrhea, zinc supplementation before and during each menstrual cycle seems to be an important factor reducing the intensity of menstrual pain. On the other hand, little is known of the role of zinc in endometriosis and in postmenopausal women. Therefore, further studies explaining the potential impact of zinc and its supplementation on female reproductive system would be highly advisable and valuable.
Does sexual intercourse in the implantation time window (5-9 days after ovulation) reduce fecundability? After adjustment for intercourse in the fecund window and clustering by couple, there was no association between intercourse in the implantation time window and fecundity. Previous research has suggested an association between intercourse in the peri-implantation time window (5-9 days after estimated ovulation) and reduced fecundability. STUDY DESIGN, SIZE, We used data from the FERTILI study, a prospective observational study conducted in five European countries, with data collected from 1992 to 1996. PARTICIPANTS/MATERIALS, SETTING, Women who were experienced in fertility awareness tracking kept a daily diary of cervical mucus observations, basal body temperature measurements, coitus and clinically identified pregnancy. We estimated the day of ovulation as cycle length minus 13 days. From 661 women, 2606 cycles had intercourse during the fecund window (from 5 days before to 3 days after the estimated day of ovulation), resulting in 418 pregnancies (conception cycles). An established Bayesian fecundability model was used to estimate the fecundability ratio (FR) of peri-implantation intercourse on fecundability, while adjusting for each partner's age, prior pregnancy, the couple's probability of conception and intercourse pattern(s). We conducted sensitivity analyses estimating ovulation as cycle length minus 12 days, or alternatively, as the peak day of estrogenic cervical mucus. MAIN There was no effect of peri-implantation adjusted FR for three or more acts of peri-implantation 1.00, 95% 0.76-1.13. Results were essentially the same with sensitivity analyses. There was an inverse relationship between frequency of intercourse in the fecund window and intercourse in the peri-implantation window. LIMITATIONS, Women with known subfertility were excluded from this study. Many couples in the study were avoiding pregnancy during much of the study, so 61% of otherwise eligible cycles in the database were not at meaningful risk of pregnancy and did not contribute to the analysis. Some couples may not have recorded all intercourse. We believe the current balance of evidence does not support a recommendation for avoiding intercourse in the peri-implantation period among couples trying to conceive. STUDY FUNDING/COMPETING INTEREST(S): No external funding. The authors have no potential competing interests. N/A.
Bone HealthVertebral Fracture AssessmentVertebral Fracture ClassificationFracture Epidemiology
Study purposeMorphometric methods categorize potential osteoporotic vertebral fractures (OVF) on the basis of loss of vertebral height. A particular example is the widely used semiquantitative morphometric tool proposed by Genant (GSQ). A newer morphologic algorithm-based qualitative (mABQ) tool focuses on vertebral end-plate damage in recognizing OVF. We used data from both sexes in the Canadian Multicentre Osteoporosis Study (CaMos) to compare the 2 methods in identifying OVF at baseline and during 10 years of follow-up. We obtained lateral thoracic and lumbar spinal radiographs (T4-L4) 3 times, at 5-year intervals, in 828 participants of the population-based CaMos. Logistic regressions were used to study the association of 10-year changes in bone mineral density (BMD) with incident fractures. At baseline, 161 participants had grade 1 and 32 had grade 2 GSQ OVF; over the next 10 years, only 9 of these participants had sustained incident GSQ OVF. Contrastingly, 21 participants at baseline had grade 1 and 48 grade 2 mABQ events; over the next 10 years, 79 subjects experienced incident grade 1 or grade 2 mABQ events. Thus, incident grades 1 and 2 morphologic fractures were 8 times more common than morphometric deformities alone. Each 10-year decrease of 0.01 g/cm2 in total hip BMD was associated with a 4.1% (95% CI: 0.7-7.3) higher odds of having an incident vertebral fracture. This analysis further suggests that morphometric deformities and morphologic fractures constitute distinct entities; morphologic fractures conform more closely to the expected epidemiology of OVF.
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"ART in Europe, 2016: results generated from European registries by ESHRE"
source_file: "eshre-eim-2016-source.pdf"
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extracted_date: "2026-04-24"
figures_extracted: 3
tables_extracted: 5
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"Wyns C et al. ART in Europe, 2016: results generated from European registries by ESHRE. Hum Reprod Open. 2020;2020(3):hoaa032. 10.1093/hropen/hoaa032"
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DiagnosticsInsulin Resistance EstimationGlucose Tolerance TestingDiagnostic Software
Open Access
Sundström-Poromaa I et al., 2020·Front Neuroendocrinol
Estradiol is the "prototypic" sex hormone of women. Yet, women have another sex hormone, Progesterone. The goal of this article is to provide a comprehensive review on progesterone, and its metabolite allopregnanolone, biological properties, main functions, and effects on mood in women. Recent years of intensive research on progesterone and allopregnanolone have paved the way for new treatment of postpartum depression. However, treatment for premenstrual syndrome and premenstrual dysphoric disorder as well as contraception that women can use without risking mental health problems are still needed. As far as progesterone is concerned, we might be while its metabolite allopregnanolone has been proven useful for treatment of PPD, it may trigger negative symptoms in women with PMS and PMDD. Overall, our current knowledge on the beneficial and harmful effects of progesterone is limited and further research is imperative.
Bone HealthRisk Prediction ModelsFracture Risk AssessmentMultistate Prediction
Existing fracture risk assessment tools are not designed to predict fracture-associated consequences, possibly contributing to the current undermanagement of fragility fractures worldwide. We aimed to develop a risk assessment tool for predicting the conceptual risk of fragility fractures and its consequences. The study involved 8965 people aged ≥60 years from the Dubbo Osteoporosis Epidemiology Study and the Canadian Multicentre Osteoporosis Study. Incident fracture was identified from X-ray reports and questionnaires, and death was ascertained though contact with a family member or obituary review. We used a multistate model to quantify the effects of the predictors on the transition risks to an initial and subsequent incident fracture and mortality, accounting for their complex interrelationships, confounding effects, and death as a competing risk. There were 2364 initial fractures, 755 subsequent fractures, and 3300 deaths during a median follow-up of 13 years (interquartile range [IQR] 7-15). The prediction model included sex, age, bone mineral density, history of falls within 12 previous months, prior fracture after the age of 50 years, cardiovascular diseases, diabetes mellitus, chronic pulmonary diseases, hypertension, and cancer. The model accurately predicted fragility fractures up to 11 years of follow-up and post-fracture mortality up to 9 years, ranging from 7 years after hip fractures to 15 years after non-hip fractures. For example, a 70-year-old woman with a T-score of -1.5 and without other risk factors would have 10% chance of sustaining a fracture and an 8% risk of dying in 5 years. However, after an initial fracture, her risk of sustaining another fracture or dying doubles to 33%, ranging from 26% after a distal to 42% post hip fracture. A robust statistical technique was used to develop a prediction model for individualization of progression to fracture and its consequences, facilitating informed decision making about risk and thus treatment for individuals with different risk profiles.
Numerous evidences have alerted on the toxic effects of the exposure to glyphosate on living organisms. Glyphosate is the herbicide most used in crops such as maize and soybean worldwide, which implies that several non-target species are at a high risk of exposure. Although the Environmental Protection Agency (EPA-USA) has reaffirmed that glyphosate is safe for users, there are controversial studies that question this statement. Some of the reported effects are due to exposure to high doses; however, recent evidences have shown that exposure to low doses could also alter the development of the female reproductive tract, with consequences on fertility. Different animal models of exposure to glyphosate or glyphosate-based herbicides (GBHs) have shown that the effects on the female reproductive tract may be related to the potential and/or mechanisms of actions of an endocrine-disrupting compound. Studies have also demonstrated that the exposure to GBHs alters the development and differentiation of ovarian follicles and uterus, affecting fertility when animals are exposed before puberty. In addition, exposure to GBHs during gestation could alter the development of the offspring (F1 and F2). The main mechanism described associated with the endocrine-disrupting effect of GBHs is the modulation of estrogen receptors and molecules involved in the estrogenic pathways. This review summarizes the endocrine-disrupting effects of exposure to glyphosate and GBHs at low or "environmentally relevant" doses in the female reproductive tissues. Data suggesting that, at low doses, GBHs may have adverse effects on the female reproductive tract fertility are discussed.
Contraception/ComparisonGeneral OB/GYN
Open Access
It has been well documented that female sex is a significant risk factor for the development of various autoimmune diseases. While the reason for this has been debated, one well-regarded theory is that increased estrogen and decreased testosterone play a role in this predisposition. Interstitial cystitis (IC), also known as painful bladder syndrome (PBS), is an autoimmune disorder that affects over nine million women in the United States. It presents with pelvic and bladder pain and urinary symptoms, both of which significantly and negatively affect the quality of life. Even so, very few studies have examined the pathophysiologic relationship between autoimmune disorders and hormonal contraceptives. In this report, we present a case of IC likely precipitated by oral contraceptives (OCPs) in a premenopausal female. Shortly after beginning OCPs, this patient developed symptoms of severe pelvic pain and increased urinary frequency. Over the course of a year, the patient was diagnosed and treated for a variety of conditions, such as urinary tract infection (UTI), fungal vaginitis, and nephrolithiasis. After consultation with a gynecologist, a normal abdominal CT scan, and unsuccessful cystoscopy due to pain, she was finally diagnosed with IC. The patient independently learned of a potential link between hormonal contraceptive pills and IC and decided to discontinue this method of birth control. Following this, her symptoms completely resolved within several months. The timing of her initiation and discontinuation of OCPs, alongside her symptomatology, suggest a connection to the development of IC. A literature review was performed, which supports this association. We, therefore, highlight this case as an important example of IC precipitated by OCPs.
Yu O et al., 2020·American journal of obstetrics and gynecology
Adenomyosis symptoms are disabling. Population-based data on incidence and prevalence of adenomyosis are lacking that could guide future evidence-based treatments and clinical management. To evaluate the incidence, 10-year secular trends, and prevalence of adenomyosis diagnoses and to describe symptoms and treatment patterns in a large U.S. cohort. We performed a retrospective population-based cohort study of women aged 16-60 years in 2006-2015, enrolled in Kaiser Permanente Washington, a mixed-model health insurance and care delivery system. Adenomyosis diagnoses identified by ICD codes from the International Classification of Diseases 9th and 10th editions and potential covariates were extracted from computerized databases. Women with prior hysterectomy, and for incidence estimates women with prior adenomyosis diagnoses, were excluded. Linear trends in incidence rates over the 10-year study period were evaluated using Poisson regression. Rates and trend tests were examined for all women adjusting for age using direct standardization to the 2015 study population, by age groups, and by race/ethnicity. Chart reviews were performed to validate diagnostic accuracy of ICD codes in identifying adenomyosis incidence. Symptoms and treatment patterns at diagnosis and in the following 5 years were assessed. A total of 333,693 women contributed 1,185,855 woman-years (2006-2015) for incidence calculations. Associated symptom-related codes (menorrhagia or abnormal uterine bleeding, dysmenorrhea or pelvic pain, dyspareunia, and infertility) were observed in 90.8%; 18.0% had co-occurrent endometriosis codes and 47.6% had co-occurrent uterine fibroid codes. The overall adenomyosis incidence was 1.03% or 28.9 per 10,000 woman-years, with a high of 30.6 in 2007 and a low of 24.4 in 2014. Overall age-adjusted estimated incidence rates declined during the 10-year study interval (linear trend P < .05). Incidence was highest for women aged 41-45 years (69.1 per 10,000 woman-years in 2008) and was higher for black (highest 44.6 per 10,000 woman-years in 2011) vs white women (highest 27.9 per 10,000 woman-years in 2010). Overall prevalence in 2015 was 0.8% and was highest among women aged 41-45 years (1.5%). Among the 624 potential adenomyosis cases identified by diagnostic codes in 2012-2015 and with sufficient information in the medical record to determine true case status, 490 were confirmed as incident cases, yielding a 78.5% (95% confidence interval, 75.1%, 81.7%) positive predictive value of adenomyosis ICD-9/ICD-10 codes for identifying an incident adenomyosis case. Health 82.0% of women had hysterectomies, nearly 70% had imaging studies suggestive of adenomyosis, and 37.6% used chronic pain medications. Adenomyosis burden to the individual and the health care system is high. Incidence rates are disproportionately high among black women. These findings are of concern, as currently available long-term medical therapies remain limited beyond hysterectomy. Our data and methodologies are novel and could serve as a foundation to guide clinicians and health care systems to develop clinical management plans and track outcomes for women with adenomyosis.
Qiu Y et al., 2020·Archives of gynecology and obstetrics
No consensus exists on the relationship between vitamin D status and endometriosis. The chief aim of our study was to evaluate the association between serum vitamin D levels and endometriosis. We searched for MEDLINE, EMBASE, and China National Knowledge Infrastructure (CNKI) databases for studies elucidated the circulating vitamin D levels in endometriosis. The standardized mean differences (SMDs) or odds ratios (ORs) with their 95% confidence interval (CIs) were calculated to evaluate the association between vitamin D levels and endometriosis. Nine studies were included in this meta-analysis. The pooled results indicated that women with endometriosis had lower vitamin D status than that in controls (SMD - 0.97 ng/mL, 95% CI - 1.80 to - 0.14; p = 0.02), and vitamin D status had a negative correlation with the severity of the disease (stage SMD - 1.33 ng/mL, 95% CI - 2.54 to - 0.12; p = 0.03). Although it was not statistically significantly different, hypovitaminosis D had a tendency to be associated with endometriosis (OR 2.77, 95% CI 0.85-6.08, p = 0.10). Heterogeneity was high among included studies. Subgroup analyses revealed that women with no hormone use had lower vitamin D status when compared with controls (SMD - 1.38 ng/mL, 95% CI - 2.59 to - 0.18; p = 0.02). For studies which sample size < 100, serum vitamin D levels were significantly lower in patients than that in controls (SMD - 0.65 ng/mL, 95% CI - 1.19 to - 0.11; p = 0.02). Women with endometriosis had lower vitamin D status when compared with controls, and a negative relationship between vitamin D levels and severity of endometriosis was observed. In addition, hypovitaminosis D was a potential risk factor for endometriosis.
DeMayo FJ et al., 2020·Journal of molecular endocrinology
Progesterone's ability to maintain pregnancy in eutherian mammals highlighted this steroid as the 'hormone of pregnancy'. It was the unique 'pro-gestational' bioactivity of progesterone that enabled eventual purification of this ovarian steroid to crystalline form by Willard Myron Allen in the early 1930s. While a functional connection between normal progesterone responses ('progestational proliferation') of the uterus with the maintenance of pregnancy was quickly appreciated, an understanding of progesterone's involvement in the early stages of pregnancy establishment was comparatively less well understood. With the aforementioned as historical backdrop, this review focuses on a selection of key advances in our understanding of the molecular mechanisms by which progesterone, through its nuclear receptor (the progesterone receptor), drives the development of endometrial receptivity, a transient uterine state that allows for embryo implantation and the establishment of pregnancy. Highlighted in this review are the significant contributions of advanced mouse engineering and genome-wide transcriptomic and cistromic analytics which reveal the pivotal molecular mediators and modifiers that are essential to progesterone-dependent endometrial receptivity and decidualization. With a clearer understanding of the molecular landscape that underpins uterine responsiveness to progesterone during the periimplantation period, we predict that common gynecologic morbidities due to abnormal progesterone responsiveness will be more effectively diagnosed and/or treated in the future.
Kwiatkowski CF et al., 2020·Environmental Science & Technology Letters
This commentary presents a scientific basis for managing as one chemical class the thousands of chemicals known as PFAS (per- and polyfluoroalkyl substances). The class includes perfluoroalkyl acids, perfluoroalkylether acids, and their precursors; fluoropolymers and perfluoropolyethers; and other PFAS. The basis for the class approach is presented in relation to their physicochemical, environmental, and toxicological properties. Specifically, the high persistence, accumulation potential, and/or hazards (known and potential) of PFAS studied to date warrant treating all PFAS as a single class. Examples are provided of how some PFAS are being regulated and how some businesses are avoiding all PFAS in their products and purchasing decisions. We conclude with options for how governments and industry can apply the class-based approach, emphasizing the importance of eliminating non-essential uses of PFAS, and further developing safer alternatives and methods to remove existing PFAS from the environment.
Bone HealthAntiretroviral Therapy EffectsBone Mineral DensityHR-pQCT Assessment
With the advent of combined antiretroviral therapy (cART), life expectancy has increased among persons living with HIV, but so too has risk for comorbidities including osteoporosis and fragility fracture. To explore whether HIV status and cART influence three-dimensional measures of BMD, bone microarchitecture and strength we aimed to compare these outcomes between women living with HIV (WLWH; n = 50; 50.4 ± 1.2 years, 44% postmenopausal) and without HIV (controls; n = 50; 51.8 ± 1.2 years, 52% postmenopausal). Outcomes were lumbar spine, total hip and femoral neck areal BMD by DXA; distal radius and tibia trabecular BMD, thickness and number, and cortical BMD and area by HR-pQCT; and finite element analysis-derived bone strength (failure load). Multivariable regression analysis compared bone outcomes between groups adjusting for known osteoporosis risk factors. Within WLWH, we examined associations between bone outcomes and HIV-related factors including disease severity and cART duration. WLWH were diagnosed 20 ± 4 years ago, were on cART for 123 ± 37 months and 80% had HIV plasma viral load <40 copies/mL. For women ≥50 years (n = 61), total hip aBMD T-Score was lower among WLWH than controls. Adjusted distal radius trabecular BMD and thickness and distal tibia trabecular BMD and failure load were 8-19% lower in WLWH than controls (p < 0.05). Cortical BMD and area did not differ between groups at either site. Lifetime cART duration and current plasma viral load were not associated with bone outcomes in WLWH; however, previous treatment with tenofovir was negatively associated with distal radius trabecular BMD and trabecular number and LS aBMD T-score. WLWH have compromised BMD, bone microarchitecture and strength vs. controls of similar age and reproductive status. Treatment with tenofovir may contribute to bone deficits in WLWH.
Male infertility secondary to oligozoospermia is surprisingly common. Although a majority of cases are idiopathic, oligozoospermia can be caused by endocrine dysfunction, anatomic abnormalities, medications, or environmental exposures. The work-up includes excluding reversible factors such as hormonal deficiency, medication effects, and retrograde ejaculation and identifying any underlying genetic syndrome and treating reversible medical causes. If no reversible cause is found, appropriate referrals to urology and assisted reproductive technology should be initiated. Lastly, clinicians should be aware of and respond to the psychological and general health ramifications of a diagnosis of oligozoospermia as part of the comprehensive care of men and couples struggling with a diagnosis of infertility.
Grieger JA et al., 2020·Journal of medical Internet research
There is increasing information characterizing menstrual cycle length in women, but less information is available on the potential differences across lifestyle variables. This study aimed to describe differences in menstrual cycle length, variability, and menstrual phase across women of different ages and BMI among a global cohort of Flo app users. We have also reported on demographic and lifestyle characteristics across median cycle lengths. The analysis was run based on the aggregated anonymized dataset from a menstrual cycle tracker and ovulation calendar that covers all phases of the reproductive cycle. Self-reported information is documented, including demographics, menstrual flow and cycle length, ovulation information, and reproductive health and diseases. Data from women aged ≥18 years and who had logged at least three cycles (ie, 2 completed cycles and 1 current cycle) in the Flo app were included (1,579,819 women). Of the 1.5 million users, approximately half (638,683/1,579,819, 40.42%) were aged between 18 and 24 years. Just over half of those reporting BMIs were in the normal range (18.5-24.9 kg/m2; 202,420/356,598, 56.76%) and one-third were overweight or obese (>25 kg/m2; 120,983/356,598, 33.93%). A total of 16.32% (257,889/1,579,819) of women had a 28-day median cycle length. There was a higher percentage of women aged ≥40 years who had a 27-day median cycle length than those aged between 18 and 24 years (22,294/120,612, 18.48% vs 60,870/637,601, 9.55%), but a lower percentage with a 29-day median cycle length (10,572/120,612, 8.77% vs 79,626/637,601, 12.49%). There were a higher number of cycles with short luteal phases in younger women, whereas women aged ≥40 years had a higher number of cycles with longer luteal phases. Median menstrual cycle length and the length of the follicular and luteal phases were not remarkably different with increasing BMI, except for the heaviest women at a BMI of ≥50 kg/m2. On a global scale, we have provided extensive evidence on the characteristics of women and their menstrual cycle length and patterns across different age and BMI groups. This information is necessary to support updates of current clinical guidelines around menstrual cycle length and patterns for clinical use in fertility programs.
Perimenopause/MenopauseProgesteroneSclerostinPost Hoc Analysis
Sclerostin, a natural hormone made in bone, suppresses bone formation. Sclerostin is also decreased by estrogen. Progesterone, estrogen's menstrual partner, stimulates bone formation. It is unclear whether progesterone influences sclerostin. This study showed that progesterone did not change sclerostin using serum remaining from a randomized progesterone hot flush therapy trial.
Progesterone and sclerostin are both endogenous hormones acting through osteoblast-origin cells and promote or suppress bone formation, respectively. Estradiol suppresses sclerostin, but progesterone, its menstrual cycle partner hormone, has unclear sclerostin relationships. We postulated that progesterone therapy would influence serum sclerostin levels. We obtained sclerostin levels for an ethics-approved post hoc analysis. Fasting sclerostin was measured in all remaining sera from a previous 12-week randomized controlled trial (RCT) of oral micronized progesterone (progesterone) for menopausal (> 1 year after last flow) vasomotor symptoms (VMS). Women in the RCT took 300 mg progesterone at bedtime or placebo (1:1) in a trial showing progesterone significantly decreased VMS. Participants were healthy menopausal, primarily Caucasian (91.2%) community-dwelling women (± SD), 55.2 ± 4.6 years old with BMI 24.9 ± 2.9 kg/m(2). The baseline sclerostin level in 60 women was 28.41 ± 10.47 pmol/L. Baseline sclerostin was not correlated with the run-in VMS score (r = 0.143, P = 0.294). Paired baseline and 12-week RCT data for 52 women showed serum sclerostin levels did not change related to experimental therapy (P = 0.504). Changes in final sclerostin values adjusted for baseline were progesterone (- 1.07 ± 7.96 pmol/L) and placebo (- 2.64 ± 8.70 pmol/L). In observational data (n = 60), baseline sclerostin levels correlated with the General Framingham Cardiovascular (CVD) Risk score (r = - 0.398, P = 0.003) and self-reported health by SF-36 quality of life instrument (QoL, r = - 0.331, P = 0.016). Physiological oral micronized progesterone did not stimulate nor suppress serum sclerostin levels based on post hoc analysis of RCT data. Exploratory results, however, showed sclerostin negatively correlated with CVD risk and QoL. ClinicalTrials.gov #NCT0146469.
Most Catholic physicians work with the comfortable assumption that we can practice our profession and our faith, fully assimilated into modern American culture and society. Increasingly, we have come to realize that to be a Catholic Christian is by nature to be countercultural. American culture, ordered by the founding fathers in concepts of liberty and freedom, has been profoundly affected by the introduction and reliance on a contraceptive pill. This has changed the mores and sexual behaviors of society in ways that are antithetical to Catholic values. The consequences of contraception have directly led to an acceptance of a broad number of behaviors and attitudes that society insists must be tolerated. This challenges the commitments of Catholic physicians both personally and professionally.
One aspect of the progressive secularization of biotechnology is the use of the by-products from abortion and the use of human embryos. These morally illicit cells and tissue create a significant moral and economic challenge for Catholics at different stages of their career. A practicing Catholic physician or scientific professional will face the dilemma of how to reconcile their Catholic identity with their profession. While the Catechism is clear on what actions Catholics should not pursue, there has been less religious guidance on what activities Catholics should proactively pursue in their professional life to advance the Catholic culture. This essay will examine these themes through the lens of a true story of the author's experience in starting Catholic for-profit and nonprofit biotechnology organizations.
Abortion and the destruction of human embryos create a moral dilemma for Catholics at different stages of a physician or scientist's career. A practicing Catholic physician or scientist must reconcile their Catholic identity with their profession. While there is little professional guidance on how to advance the culture, Jesus says that one must take up the cross and direct their God-given gifts towards His name. The only way to succeed and thrive in a secular healthcare environment is to emulate Jesus by putting aside their own self-interest; pray for courage against ridicule; accept risk; and pursue scientific and medical excellence.
General OB/GYNReproductive Endocrinology
Open Access
Autoimmune disorders are characterized as a condition in which the host's immune system mistakenly attacks itself. These disorders cause the immune system to cause a systemic reaction by attacking multiple organs or may be localized to attacking one specific organ, such as the skin. The exact mechanism of such autoimmune conditions is not well understood; however, the presumed mechanism tends to vary amongst the disorders. Autoimmune diseases present with a clear gender bias with a greater prevalence amongst women, occurring at a rate of 2 to 1. Many autoimmune disorders tend to affect women during periods of extensive stress, such as pregnancy, or during a great hormonal change. A far greater number of women are affected every year with autoimmune diseases, leading to researchers attempting to identify the underlying factors, which could be responsible for this disparity. Autoimmune disorders occur as a result of multiple factors as some disorders may be genetic, while others are sporadic. Throughout this review, various hypotheses are explored that provide insight into the increased susceptibility of autoimmune disorders within women.
Well-differentiated papillary mesothelioma (WDPM) is an uncommon mesothelial proliferation that is most commonly encountered as an incidental finding in the peritoneal cavity. There is controversy in the literature about whether WDPM is a neoplasm or a reactive process and, if neoplastic, whether it is a variant or precursor of epithelial malignant mesothelioma or is a different entity. Using whole exome sequencing of five WDPMs of the peritoneum, we have identified distinct mutations in EHD1, ATM, FBXO10, SH2D2A, CDH5, MAGED1, and TP73 shared by WDPM cases but not reported in malignant mesotheliomas. Furthermore, we show that WDPM is strongly enriched with C > A transversion substitution mutations, a pattern that is also not found in malignant mesotheliomas. The WDPMs lacked the alterations involving BAP1, SETD2, NF2, CDKN2A/B, LASTS1/2, PBRM1, and SMARCC1 that are frequently found in malignant mesotheliomas. We conclude that WDPMs are neoplasms that are genetically distinct from malignant mesotheliomas and, based on observed mutations, do not appear to be precursors of malignant mesotheliomas.
Interventions to prevent pregnancy complications have been largely unsuccessful. We suggest this is because the foundation for a healthy pregnancy is laid prior to the establishment of the pregnancy at the time of endometrial decidualization. Humans are one of only a few mammalian viviparous species in which decidualization begins during the latter half of each menstrual cycle and is therefore independent of the conceptus. Failure to adequately prepare (decidualize) the endometrium hormonally, biochemically, and immunologically in anticipation of the approaching blastocyst-including the downregulation of genes involved in the proinflammatory response and resisting tissue invasion along with the increased expression of genes that promote angiogenesis, foster immune tolerance, and facilitate tissue invasion-leads to abnormal implantation/placentation and ultimately to adverse pregnancy outcome. We hypothesize, therefore, that the primary driver of pregnancy health is the quality of the soil, not the seed.
Fiber release during domestic textile washing is a cause of marine microplastic pollution, but better understanding of the magnitude of the issue and role of fabric care products, appliances and washing cycles is needed. Soiled consumer wash loads from U.K. households were found to release a mean of 114 ± 66.8 ppm (mg microfiber per kg fabric) (n = 79) fibers during typical washing conditions and these were mainly composed of natural fibers. Microfiber release decreased with increasing wash load size and hence decreasing water to fabric ratio, with mean microfiber release from wash loads in the mass range 1.0-3.5 kg (n = 57) found to be 132.4 ± 68.6 ppm, significantly (p = 3.3 x 10-8) higher than the 66.3 ± 27.0 ppm of those in the 3.5-6.0 kg range (n = 22). In further tests with similar soiled consumer wash loads, moving to colder and quicker washing cycles (i.e. 15°C for 30 mins, as opposed to 40°C for 85 mins) significantly reduced microfiber generation by 30% (p = 0.036) and reduced whiteness loss by 42% (p = 0.000) through reduced dye transfer and soil re-deposition, compared to conventional 40°C cycles. In multicycle technical testing, detergent pods were selected for investigation and found to have no impact on microfiber release compared to washing in water alone. Fabric softeners were also found to have no direct impact on microfiber release in testing under both European and North American washing conditions. Extended testing of polyester fleece garments up to a 48-wash cycle history under European conditions found that microfiber release significantly reduced to a consistent low level of 28.7 ± 10.9 ppm from eight through 64 washes. Emerging North American High-Efficiency top-loading washing machines generated significantly lower microfiber release than traditional top-loading machines, likely due to their lower water fill volumes and hence lower water to fabric ratio, with a 69.7% reduction observed for polyester fleece (n = 32, p = 7.9 x 10-6) and 37.4% reduction for polyester T-shirt (n = 32, p = 0.0032). These results conclude that consumers can directly reduce the levels of microfibers generated per wash during domestic textile washing by using colder and quicker wash cycles, washing complete (but not overfilled) loads, and (in North America) converting to High-Efficiency washing machines. Moving to colder and quicker cycles will also indirectly reduce microfiber release by extending the lifetime of clothing, leading to fewer new garments being purchased and hence lower incidence of the high microfiber release occurring during the first few washes of a new item.
Dehydroepiandrosterone (DHEA) is a metabolic intermediate in the biosynthesis of estrogens and androgens with a past clouded in controversy and bold claims. It was once touted as a wonder drug, a fountain of youth that could cure all ailments. However, in the 1980s DHEA was banned by the FDA given a lack of documented health benefits and long-term use data. DHEA had a revival in 1994 when it was released for open market sale as a nutritional supplement under the Dietary Supplement Health and Safety Act. Since that time, there has been encouraging research on the hormone, including randomized controlled trials and subsequent meta-analyses on various conditions that DHEA may benefit. Bone health has been of particular interest, as many of the metabolites of DHEA are known to be involved in bone homeostasis, specifically estrogen and testosterone. Studies demonstrate a significant association between DHEA and increased bone mineral density, likely due to DHEA's ability to increase osteoblast activity and insulin like growth factor 1 (IGF-1) expression. Interestingly, IGF-1 is also known to improve fracture healing, though DHEA, a potent stimulator of IGF-1, has never been tested in this scenario. The aim of this review is to discuss the history and mechanisms of DHEA as they relate to the skeletal system, and to evaluate if DHEA has any role in treating fractures.
Human Fertilisation and Embryology Authority, 2020
# Fertility treatment 2018: **UK statistics for IVF and DI treatment, storage, and donation**
30 June 2020
Fertility trends is our annual statistical release. The key findings are published on this page with a statistical appendix available for download.
[**Download the underlying data set in .xlsx (151kb)**](https://www.hfea.gov.uk/media/3293/underlying-data-tables-fertility-trends-2018.xlsx "download the data as .xlsx").
[**Download a PDF version of this report (1.04mb)**](https://www.hfea.gov.uk/media/3158/fertility-treatment-2018-trends-and-figures.pdf "Fertility treatment 2018: trends and figures").
## - [Main points](https://www.hfea.gov.uk/about-us/publications/research-and-data/fertility-treatment-2018-trends-and-figures/#mainpoints)
- [Section 1. IVF birth rates have increased for patients under 43 years](https://www.hfea.gov.uk/about-us/publications/research-and-data/fertility-treatment-2018-trends-and-figures/#birthrates)
- [Section 2. Birth rates were above 20% per embryo transferred on average in the first three cycles](https://www.hfea.gov.uk/about-us/publications/research-and-data/fertility-treatment-2018-trends-and-figures/#birthrates2)
- [Section 3. Using donor eggs can result in high birth rates for older patients, but they are not widely used](https://www.hfea.gov.uk/about-us/publications/research-and-data/fertility-treatment-2018-trends-and-figures/#donoreggs)
- [Section 4. The multiple birth rate decreased further to 8% in 2018](https://www.hfea.gov.uk/about-us/publications/research-and-data/fertility-treatment-2018-trends-and-figures/#multiplebirths)
- [Section 5. Transferring more than one embryo could result in a multiple birth rate over 30%](https://www.hfea.gov.uk/about-us/publications/research-and-data/fertility-treatment-2018-trends-and-figures/#multiplebirths2)
- [Section 6. Embryo and egg storage have increased as freezing becomes more common](https://www.hfea...
Breastfeeding has been associated with a reduced risk of epithelial ovarian cancer in multiple studies, but others showed no association. Whether risk reduction extends beyond that provided by pregnancy alone or differs by histotype is unclear. Furthermore, the observed associations between duration and timing of breastfeeding with ovarian cancer risk have been inconsistent. To determine the association between breastfeeding (ie, ever/never, duration, timing) and ovarian cancer risk overall and by histotype. DESIGN, SETTING, A pooled analysis of parous women with ovarian cancer and controls from 13 case-control studies participating in the Ovarian Cancer Association Consortium was performed. Odds ratios (ORs) and 95% CIs of the overall association were calculated using multivariable logistic regression and polytomous logistic regression for histotype-specific associations. All data were collected from individual sites from November 1989 to December 2009, and analysis took place from September 2017 to July 2019. Data on breastfeeding history, including duration per child breastfed, age at first and last breastfeeding, and years since last breastfeeding were collected by questionnaire or interview and was harmonized across studies. Diagnosis of epithelial ovarian cancer. A total of 9973 women with ovarian cancer (mean [SD] age, 57.4 [11.1] years) and 13 843 controls (mean [SD] age, 56.4 [11.7] years) were included. Breastfeeding was associated with a 24% lower risk of invasive ovarian cancer (odds ratio [OR], 0.76; 95% CI, 0.71-0.80). Independent of parity, ever having breastfed was associated with reduction in risk of all invasive ovarian cancers, particularly high-grade serous and endometrioid cancers. For a single breastfeeding episode, mean breastfeeding duration of 1 to 3 months was associated with 18% lower risk (OR, 0.82; 95% CI, 0.76-0.88), and breastfeeding for 12 or more months was associated with a 34% lower risk (OR, 0.66; 95% CI, 0.58-0.75). More recent breastfeeding was associated with a reduction in risk (OR, 0.56; 95% CI, 0.47-0.66 for <10 years) that persisted for decades (OR, 0.83; 95% CI, 0.77-0.90 for ≥30 years; P for trend = .02). Breastfeeding is associated with a significant decrease in risk of ovarian cancer overall and for the high-grade serous subtype, the most lethal type of ovarian cancer. The findings suggest that breastfeeding is a potentially modifiable factor that may lower risk of ovarian cancer independent of pregnancy alone.
This review sought to evaluate the evidence for embryo formation during intrauterine device (IUD) use, to articulate how often embryo loss occurs in well-designed studies, and to comment on other bodies of literature suggestive of postfertilization mechanisms of action of IUDs. The MEDLINE, EMBASE, and Ovid databases were searched for English-language studies of markers of pregnancy in IUD users in May 2018. Studies of human chorionic gonadotropin (hCG) were subjected to quality assessment based on the US Preventive Services Task Force quality tool. Bias of studies assessing pregnancy in other ways was assessed on a study-to-study basis. In all, 1,073 studies were identified and 138 were read in detail. Twenty-three studies of β-hCG, 4 studies of direct observation of embryos in fallopian tubes, 2 studies of pregnancy-specific binding globulin (PSBG), and 1 study of heat-shock protein 10 (Hsp10) or chaperonin 10 were included. In all studies considered together, 7.3 percent of IUD users had evidence of fertilization and pregnancy failure. In good-quality studies, 4.5 percent had evidence of fertilization and pregnancy failure. There are no randomized trials of embryo formation and loss in IUD users compared with noncontracepting controls. Studies of β-hCG span a large spectrum of quality, but several good-quality studies exist, which support embryo formation and loss in IUD users. Evidence of embryos found in tubes is moderate and evidence of PSBG and Hsp10 elaboration was limited, but these are also concerning for embryo formation and loss. There is good-quality evidence of embryo formation and loss in IUD users. Studies are inconsistent, and the stated conclusions of several papers inaccurately diminish postfertilization evidence of embryo formation. To better assess the rate of embryo loss in IUD users compared with non-users, future research should include well-designed prospective trials and less subjective assessments of embryos in fallopian tubes. A systematic review was carried out examining the English-language literature in the MEDLINE, EMBASE, and Ovid databases for evidence of embryo formation and loss during IUD use. In all, 1,073 studies were identified and 138 were read. There are no randomized trials and evidence ranges in quality, but evidence for the embryo formation and loss in 4.5 percent of IUD users exists in good-quality research. Further research is needed to compare embryo loss in IUD users to loss in controls.
This study explores differences in the use of CycleProGo™ (CPG), a fertility-tracking app developed by Couple to Couple League (CCL), between those exposed to it as a part of natural family planning (NFP) instruction versus those who find it on their own. An anonymous data set of 17,543 CPG accounts opened between April 2013 and June 2016 was used for analysis. Nonmember users opened the most accounts (58 percent, n = 10,134), CCL members represented 38 percent (n = 6,758) of new accounts, and 207 CCL teachers (4 percent) were using CPG for personal charting. Significantly more nonmember accounts had zero days of use after the initial opening compared to CCL member accounts (61 percent vs. 23 percent, respectively, χ(2) = 2,405.9, p < .001). Conversely, significantly more CCL member accounts were used for ninety days or longer than nonmember accounts (47 percent vs. 13 percent, respectively, χ(2) = 2,404.2, p < .001). CCL students-those who began using the app as part of a formal NFP teaching curriculum-were more likely to use the app for > six cycles compared to nonmembers. In accounts with at least one complete cycle, CCL students were the most diligent at daily recording (95 percent of cycle days with observation recorded) followed by CCL members (88 percent) and nonmembers (76 percent). CCL teachers had the lowest frequency of cycle days with a recorded observation (73 percent). Within each cohort, accounts with > six recorded cycles had a lower proportion of cycle days with an observation recorded, likely reflecting increasing knowledge of their personal fertility patterns. Long-term users who had no known formal training in NFP still had the lowest proportion cycle days with a fertility observation. We conclude formal NFP instruction increases the probability of long-term app use, and regardless of training, long-term users will likely record observations on about 70 percent of cycle days.
"CycleProGo™ users with NFP training were more persistent and diligent about daily data input than those without training."
This study reports on 632 cycles from 105 women who were using the CREIGHTON MODEL FertilityCare™ System to avoid pregnancy and had either a serious reason to avoid pregnancy or some degree of a lack of confidence. A progesterone level was drawn on the third day after the Peak Day as they were charting, and if the progesterone level was 2.3 ng/mL or greater, then ovulation was determined to have passed. If the level was greater than 3.0 ng/mL, this indicated that an absolute period of infertility had begun. In these cases, no pregnancies were observed. In the 27 cycles in which a specific follow-up relative to pregnancy could not be definitively determined, the progesterone levels in all cases were 2.3 ng/mL or greater with 23 of the 27 cycles being 3.1 ng/mL or greater. It is highly unlikely that any of those became pregnant as well. These cycles were collected over thirteen years (2004-2016). Two case presentations are also a part of this article of two families in which the couples had very serious reasons to avoid pregnancy. In these two couples, each of the women was multi-gravid and had no evidence of subfertility or infertility. They used the family planning progesterone level (the Peak Day +3 progesterone level) for a total of 167 cycles over a number of years successfully without a subsequent pregnancy.
This article presents a thirteen-year effort to evaluate the serum progesterone level on the third day after the Peak Day as observed by women charting the CREIGHTON MODEL FertilityCare™ System. It is known that the Peak Day is associated with ovulation, and if the progesterone reaches a certain level, then an absolute period of infertility should follow. In fact, this is what this study reflects.