Sexual dysfunction among gynecologic cancer survivors in a population-based  cohort study

Chun-Pin Esther Chang

Department of Family and Preventive Medicine, Office of Cooperative Reproductive Health, Division of Public Health, Spencer Fox Eccles School of Medicine, University of Utah, Salt Lake City, United...

Chun-Pin Chang

Division of Public Health, Department of Family and Preventive Medicine, University of Utah School of Medicine, and Huntsman Cancer Institute, Salt Lake City, UT, United States of America.

Abstract: Treatment for gynecologic cancer is associated with sexual dysfunction, which may present during and/or after treatment. The aim of this study was to investigate the risk of sexual dysfunction among gynecologic cancer survivors compared to cancer-free women in a population-based cohort study. We identified a cohort of 4863 endometrial, ovarian, and cervical cancer survivors diagnosed between 1997 and 2012 in the Utah Cancer Registry. Up to five cancer-free women were matched to cancer survivors (N = 22,693). We used ICD-9 codes to identify sexual dysfunction. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for sexual dysfunction with adjustment for potential confounders. Approximately 6.6% of gynecologic cancer survivors had sexual dysfunction diagnoses 1-5 years after cancer diagnosis. Gynecologic cancer survivors had higher risks of overall sexual dysfunction (HR: 2.51, 95% CI: 2.16, 2.93), dyspareunia (HR: 3.27, 95% CI: 2.63, 4.06), and vaginal dryness (HR: 2.63, 95% CI: 2.21, 3.12) compared to a general population of women, 1-5 years after cancer diagnosis. Sexual dysfunction was associated with advance cancer stage (HR(Regional vs. Localized): 1.61, 95% CI: 1.19, 2.31), radiation therapy (HR: 1.73, 95% CI: 1.29, 2.31), and chemotherapy (HR: 1.80, 95% CI: 1.30, 2.50). This large cohort study confirms that there is an increased risk of sexual dysfunction among gynecologic cancer survivors when compared to the general population. Further investigation is needed to address the risk factors for sexual dysfunction and to improve patient-provider communication, diagnosis, documentation, and treatment of sexual dysfunction among gynecologic cancer survivors.

Supportive Care in Cancer : Official Journal of the Multinational Association of  Supportive Care in Cancer


Assisted Reproductive Technology and Natural Law: How Seven Years as an  Embryologist Revealed IVF's Disordered Approach to Patient Care

Craig Turczynski

RRM Diagnostics, Dallas, TX, USA; Duquesne University College of Osteopathic Medicine, Pittsburgh, PA, USA

Mary Anne Urlakis

Dignitas Personae Institute for Nascent Human Life, Inc., Colgate, WI, USA

Abstract: This article is a case study illuminating the experience of a cradle Catholic who pursued a career in the field of Assisted Reproductive Technology (ART) as a laboratory director and embryologist. Twenty years after leaving the field, the observations leading to the crisis of conscience are further amplified by the reports of social, legal, ethical, and medical consequences of the technology. These consequences are explored in detail and can serve as a mini-review of the published scientific literature describing the obstetrical complications, peri-natal outcomes, and the long-term health effects on the offspring. This paper provides the documented evidence that can be used by the religious and medical community for shepherding the flock. The disordered approach to patient care is evidenced by five serious consequences resulting from the use of the technology. These include multiple pregnancy and selective reduction, abandoned and discarded embryos, adverse health effects to the women and children, legal and ethical problems, and human experimentation. An explanation for the adverse consequences can be found by exploring and applying the principles of Natural Law. Natural Law, as embraced by the Catholic Church, can be used as a starting point for conversion of heart for many who struggle with the immorality of ART. Deterring use of the technology coupled with increased motivation by scientist and health professionals to pursue restorative approaches within a moral framework offer our best solution to the treatment of infertility. Natural Law and the consequences of violating it provide evidence that science and medicine should not be practiced in a vacuum void of ethical and moral boundaries grounded in divine Wisdom.


Diagnosis and treatment of tubal endometriosis in women undergoing laparoscopy: A  case series from a single hospital

Abstract:
Background: Tubal endometriosis (TEM) is a category of pelvic endometriosis (EM) that is characterized by ectopic endometrial glands and/or stroma within any part of the fallopian tube. The fallopian tubes may be a partial source of ovarian endometriosis (OEM). TEM is difficult to diagnose during surgery and is usually detected by pathology after surgery.

Aim: To provide a clinical basis for the diagnosis and treatment of TEM.

Methods: In this study, the data of 30 patients who underwent laparoscopic salpingectomy due to various gynecological diseases and had pathological confirmation of TEM at our hospital were retrospectively analyzed, and the clinical basis for the diagnosis and treatment of TEM was evaluated.

Results: Among 1982 surgical patients, 30 met the study criteria. Among those, 6 patients had a history of infertility, 12 patients had a history of artificial abortion, 13 patients had a history of cesarean section, 1 patient had a history of tubal ligation, 4 patients had an intrauterine device, and 22 patients had hydrosalpinx. Sixteen patients (53.33%) conceived naturally and gave birth to healthy babies. Pathology showed that only 2 patients had TEM without any other gynecological diseases, while the others all had simultaneous diseases, including 26 patients with EM at other pelvic sites.

Conclusion: The final diagnosis of TEM depends on pathological examination since there are no specific clinical characteristics. The rate of TEM combined with EM (especially OEM) was higher than that of other gynecological diseases, which indicates that TEM is related to OEM.


Does a short luteal phase correlate with an increased risk of miscarriage? A  cohort study

Abstract:
Background: Miscarriage is defined as spontaneous loss of pregnancy prior to 20 weeks gestation. With an estimated risk of 15% of clinically confirmed pregnancies ending in miscarriage, it is the most common adverse event in pregnancy. Woman's age is the primary risk factor for miscarriage, while medical conditions, including hormonal abnormalities, are also associated. Progesterone is essential for maintaining pregnancy. A short luteal phase may reflect inadequate levels of progesterone production, but it is unclear whether a short luteal phase correlates with an increase in the risk of miscarriage.

Methods: Using a cohort study design, we conducted a secondary data analysis from four cohorts of couples who used a standardized protocol to track biomarkers of the female cycles. A short luteal phase was defined as less than 10 days, with < 11, < 9, and < 8 days as alternate definitions in sensitivity analyses. We included women who experienced a pregnancy with a known outcome, identified the length of the luteal phase in up to 3 cycles prior to conception and assessed the relationship with miscarriage using a modified Poisson regression analysis, adjusting for demographic characteristics, smoking, alcohol use and previous pregnancy history.

Results: In our sample of 252 women; the overall miscarriage rate was 18.7%. The adjusted incident risk ratio of miscarriage in women who had at least one short luteal phase < 10 days, compared to those who had none, was 1.01 (95% CI: 0.57, 1.80) Similar null risk was found when assessing alternative lengths of short luteal phase. Women who had short luteal phases < 10 days in all 3 cycles prior to the conception cycle had an incident risk ratio of 2.14 (95% CI: 0.7, 6.55).

Conclusions: Our study found that a short luteal phase in the three cycles prior to conception was not associated with higher rates of miscarriage in an international cohort of women tracking their cycles, but our sample size was limited. Further research to determine if short luteal phases or luteal phase deficiency is associated with early pregnancy losses among preconception cohorts with daily tracking of cycle parameters, in addition to progesterone and human chorionic gonadotropin levels, is warranted. Additionally, future studies should include women with recurrent short luteal phases as a more likely risk factor than isolated short luteal phases.


Impact of Endocrine Disorders on IVF Outcomes: Results from a Large,  Single-Centre, Prospective Study

Vito Chiantera

Unit of Gynecologic Oncology, ARNAS “Civico-Di Cristina-Benfratelli”, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), University of Paler...

Abstract: Endocrine disorders negatively influence the ovarian function, and increasing incidence of endocrine diseases with age may have further negative effects on pregnancy rate. Prospective cohort study of 231 consecutively enrolled patients underwent IVF treatment. In patients with known endocrine disorders, the laboratory parameters were corrected before IVF treatment. One hundred sixty one patients (69.7%) had at least one known and treated endocrine disorder (study group), and 70 patients were endocrine negative (control group). Endocrine disorders diagnosed were thyroid disorders (32.5%), diminished ovarian reserve (23.8%), insulin resistance (22.5%), PCOS (15.2%), hyperprolactinaemia (13.4%), obesity (12.1%), hypogonadotropic hypogonadism (0.8%) and congenital adrenal hyperplasia (0.2%). Before the IVF treatment, systematic endocrine laboratory examinations were performed in all patients. Higher age, BMI and FSH were found in the study group, while AMH level was lower. There were no differences in LH, E2, prolactin, TSH, FT3, FT4, TT, DHEAS, androstendione, 17-OHP and SHBG level between the study and control groups. The study group had higher baseline glucose, baseline insulin, 120-min glucose and 120-min insulin level after oral glucose tolerance test. With no difference in the IVF cycles performed, pregnancy rate was lower in the study group (61.43% vs. 34.16%; p = 0.003), and this difference (p = 0.0151) remained in age-corrected rates, as well. The analyses were also performed in individual endocrinology groups. The prevalence of endocrine disorders is high in females participating in IVF programs, and they are often accompanying each other. Even after proper correction, the presence of the endocrine disorder negatively influences the pregnancy rate in IVF treatment.

Reproductive Sciences (Thousand Oaks, Calif.)


The longer-term effects of IVF on offspring from childhood to adolescence

Roger J Hart

School of Women's and Infants' Health; The University of Western Australia, King Edward Memorial Hospital and Fertility Specialists of Western Australia; Subiaco, Perth Australia

Abstract: It is well established that there are increased pregnancy-related complications  for a woman who conceives through assisted reproductive treatment (ART).  Furthermore, it is known that the risk to the child born is greater, believed to  be related to prematurity and growth restriction. Studies have also reported  epigenetic changes in the DNA of offspring conceived through ART. In addition,  it is believed that they have a greater risk of congenital malformations,  although some of these risks may relate to underlying infertility, rather than  the ART treatment per se. As a result, it may be expected that there is a  greater risk to the longer-term health of the child who is born from ART;  however, evidence about the long-term health of children conceived through ART  is reassuring. Even though, it is recognised that many of the studies in this  field come with limitations. Low numbers of participants is one of the major  limitations, which makes subgroup analyses for diverse types of ART, or diverse  types of infertility, not feasible. Furthermore, studies are often limited by  short follow-up periods because of the difficulty and costs involved in  longitudinal study designs. In addition, the rapid changes over time in ART  limit the generalisability and significance of long-term findings. Well-designed  studies investigating the long-term health outcomes of ART-conceived offspring  and the potential influences of various aspects of the ART procedure, as well as  studies of the potential underlying epigenetic mechanisms, are imperative.  Furthermore, conclusions from childhood hospitalisation data from the United  Kingdom, the long-term follow-up and quality of life study from researchers in  Melbourne, and the data published from the Western Australian Growing Up Healthy  Study will go a long way to help reassure current and prospective parents who  may require ART to conceive.


Impact of textile dyes on health and ecosystem: a review of structure, causes, and potential solutions

Abstract: The rapid growth of population and industrialization have intensified the problem of water pollution globally. To meet the challenge of industrialization, the use of synthetic dyes in the textile industry, dyeing and printing industry, tannery and paint industry, paper and pulp industry, cosmetic and food industry, dye manufacturing industry, and pharmaceutical industry has increased exponentially. Among these industries, the textile industry is prominent for the water pollution due to the hefty consumption of water and discharge of coloring materials in the effluent. The discharge of this effluent into the aquatic reservoir affects its biochemical oxygen demand (BOD), chemical oxygen demand (COD), total dissolved solids (TDS), total suspended solids (TSS), and pH. The release of the effluents without any remedial treatment will generate a gigantic peril to the aquatic ecosystem and human health. The ecological-friendly treatment of the dye-containing wastewater to minimize the detrimental effect on human health and the environment is the need of the hour. The purpose of this review is to evaluate the catastrophic effects of textile dyes on human health and the environment. This review provides a comprehensive insight into the dyes and chemicals used in the textile industry, focusing on the typical treatment processes for their removal from industrial wastewaters, including chemical, biological, physical, and hybrid techniques.

Environmental Science and Pollution Research


Elite female football players' perception of the impact of their menstrual cycle stages on their football performance. A semi-structured interview-based study

Abstract:
OBJECTIVES: This study assesses how female footballers perceive how their menstrual cycle impacts their physical and psychological performance, informing future research and intervention.

METHODS: Semi-structured interviews, developed using piloting and peer review took place with fifteen elite female footballers from two English WSL clubs (age: 25.2 [18-33]). Data was audio recorded, transcribed verbatim, and analysed thematically using NVivo.

RESULTS: All players (100%) perceive their menstrual cycle to negatively impact performance. Analysing 27,438 words of data revealed five themes: A) symptoms, B) preparation, C) performance, D) recovery, and E) management. Over half (53%) of players experienced decreased appetite and sleep quality prior to performance during menstruation. Competitive performance was perceived to be most negatively impacted during menses (54 references) following by the pre-menstrual stage (23 references). During menstruation, the most impacted physical performance indicators were power (93%) and fatigue (87%). Psychologically, confidence, focus, and reaction to criticism were commonly affected (66.7%). Players reported missing training (13.3%) and matches (13.3%) due to severity of impact. Recovery was affected during the pre-menstrual (26.7%) and menstrual (66.7) stages. Players self-manage symptoms using over the counter (66.7%) and prescription (26.7%) medication, some prophylactically prior to competition (46.7%).

CONCLUSIONS: This first attempt to ascertain player perception in football exposes a clear negative impact on performance. The complex interplay of biopsychosocial and logistical factors, lack of awareness and education highlight the need for further research. Intervention is necessary and immediate initiation would be prudent, starting with simple measures such as basic self-management advice, education, and provision of sanitary products.


Association of a Mediterranean Diet Pattern With Adverse Pregnancy Outcomes Among US Women

Abstract:
IMPORTANCE: The Mediterranean diet pattern is inversely associated with the leading causes of morbidity and mortality, including metabolic diseases and cardiovascular disease, but there are limited data on its association with adverse pregnancy outcomes (APOs) among US women.

OBJECTIVE: To evaluate whether concordance to a Mediterranean diet pattern around the time of conception is associated with lower risk of developing any APO and individual APOs.

DESIGN, SETTING, AND PARTICIPANTS: This prospective, multicenter, cohort study, the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be, enrolled 10 038 women between October 1, 2010, and September 30, 2013, with a final analytic sample of 7798 racially, ethnically, and geographically diverse women with singleton pregnancies who had complete diet data. Data analyses were completed between June 3, 2021, and April 7, 2022.

EXPOSURES: An Alternate Mediterranean Diet (aMed) score (range, 0-9; low, 0-3; moderate, 4-5; and high, 6-9) was computed from data on habitual diet in the 3 months around conception, assessed using a semiquantitative food frequency questionnaire.

MAIN OUTCOMES AND MEASURES: Adverse pregnancy outcomes were prospectively ascertained and defined as developing 1 or more of the following: preeclampsia or eclampsia, gestational hypertension, gestational diabetes, preterm birth, delivery of a small-for-gestational-age infant, or stillbirth.

RESULTS: Of 7798 participants (mean [SD] age, 27.4 [5.5] years), 754 (9.7%) were aged 35 years or older, 816 (10.5%) were non-Hispanic Black, 1294 (16.6%) were Hispanic, and 1522 (19.5%) had obesity at baseline. The mean (SD) aMed score was 4.3 (2.1), and the prevalence of high, moderate, and low concordance to a Mediterranean diet pattern around the time of conception was 30.6% (n=2388), 31.2% (n=2430), and 38.2% (n=2980), respectively. In multivariable models, a high vs low aMed score was associated with 21% lower odds of any APO (adjusted odds ratio [aOR], 0.79 [95% CI, 0.68-0.92]), 28% lower odds of preeclampsia or eclampsia (aOR, 0.72 [95% CI, 0.55-0.93]), and 37% lower odds of gestational diabetes (aOR, 0.63 [95% CI, 0.44-0.90]). There were no differences by race, ethnicity, and prepregnancy body mass index, but associations were stronger among women aged 35 years or older (aOR, 0.54 [95% CI, 0.34-0.84]; P = .02 for interaction). When aMed score quintiles were evaluated, similar associations were observed, with higher scores being inversely associated with the incidence of any APO.

CONCLUSIONS AND RELEVANCE: This cohort study suggests that greater adherence to a Mediterranean diet pattern is associated with lower risk of APOs, with evidence of a dose-response association. Intervention studies are needed to assess whether dietary modification around the time of conception can reduce risk of APOs and their downstream associations with future development of cardiovascular disease risk factors and overt disease.


The importance of estradiol for body weight regulation in women

Pilar Vigil

Pontificia Universidad Católica de Chile

Abstract: Obesity in women of reproductive age has a number of adverse metabolic effects, including Type II Diabetes (T2D), dyslipidemia, and cardiovascular disease. It is associated with increased menstrual irregularity, ovulatory dysfunction, development of insulin resistance and infertility. In women, estradiol is not only critical for reproductive function, but they also control food intake and energy expenditure. Food intake is known to change during the menstrual cycle in humans. This change in food intake is largely mediated by estradiol, which acts directly upon anorexigenic and orexigenic neurons, largely in the hypothalamus. Estradiol also acts indirectly with peripheral mediators such as glucagon like peptide-1 (GLP-1). Like estradiol, GLP-1 acts on receptors at the hypothalamus. This review describes the physiological and pathophysiological mechanisms governing the actions of estradiol during the menstrual cycle on food intake and energy expenditure and how estradiol acts with other weight-controlling molecules such as GLP-1. GLP-1 analogs have proven to be effective both to manage obesity and T2D in women. This review also highlights the relationship between steroid hormones and women's mental health. It explains how a decline or imbalance in estradiol levels affects insulin sensitivity in the brain. This can cause cerebral insulin resistance, which contributes to the development of conditions such as Parkinson's or Alzheimer's disease. The proper use of both estradiol and GLP-1 analogs can help to manage obesity and preserve an optimal mental health in women by reducing the mechanisms that trigger neurodegenerative disorders.


Prenatal Antidepressant Exposures and Autism Spectrum Disorder or Traits: A  Retrospective, Multi-Cohort Study

Brennan PA, Dunlop AL, Croen LA, Avalos LA, Salisbury AL, Hipwell AE, Nozadi SS, Sathyanarayana S, Crum RM, Musci R, Li M, Li X, Mansolf M, O'Connor TG, Elliott AJ, Ghildayal N, Lin PD, Sprowles JLN, Stanford JB, Bendixsen C, Ozonoff S, Lester BM, Shuster CL, Huddleston KC, Posner J, Paneth N

Abstract: Prenatal antidepressant exposure has been associated with increased risk for neurodevelopmental disorders in childhood, including autism spectrum disorder (ASD). The current study utilized multi-cohort data from the Environmental influences on Child Health Outcomes (ECHO) program (N = 3129) to test for this association, and determine whether the association remained after adjusting for maternal prenatal depression and other potential confounders. Antidepressants and a subset of selective serotonin reuptake inhibitors (SSRIs) were examined in relation to binary (e.g., diagnostic) and continuous measures of ASD and ASD related traits (e.g., social difficulties, behavior problems) in children 1.5 to 12 years of age. Child sex was tested as an effect modifier. While prenatal antidepressant exposure was associated with ASD related traits in univariate analyses, these associations were statistically non-significant in models that adjusted for prenatal maternal depression and other maternal and child characteristics. Sex assigned at birth was not an effect modifier for the prenatal antidepressant and child ASD relationship. Overall, we found no association between prenatal antidepressant exposures and ASD diagnoses or traits. Discontinuation of antidepressants in pregnancy does not appear to be warranted on the basis of increased risk for offspring ASD.

Research on Child and Adolescent Psychopathology


The Gut Microbiome and Female Health

The Gut Microbiome and Female Health

Abstract: The possession of two X chromosomes may come with the risk of various illnesses, females are more likely to be affected by osteoarthritis, heart disease, and anxiety. Given the reported correlations between gut microbiome dysbiosis and various illnesses, the female gut microbiome is worthy of exploration. Herein, we discuss the composition of the female gut microbiota and its dysbiosis in pathologies affecting the female population. Using PubMed, we performed a literature search, using key terms, namely: "gut microbiome", "estrogen", "menopause", "polycystic ovarian syndrome", "pregnancy", and "menstruation". In polycystic ovarian syndrome (PCOS), the abundance of Bacteroides vulgatus, Firmicutes, Streptococcus, and the ratio of Escherichia/Shigella was found to be increased while that of Tenericutes ML615J-28, Tenericutes 124-7, Akkermansia, Ruminococcaceae, and Bacteroidetes S24-7 was reduced. In breast cancer, the abundance of Clostridiales was enhanced, while in cervical cancer, Prevotella, Porphyromonas, and Dialister were enhanced but Bacteroides, Alistipes, and members of Lachnospiracea, were decreased. In ovarian cancer, Prevotella abundance was increased. Interestingly, the administration of Lactobacillus acidophilus, Bifidobacterium bifidum, Lactobacillus reuteri, and Lactobacillus fermentum ameliorated PCOS symptoms while that of a mix of Bifidobacterium lactis W51, Bifidobacterium bifidum W23, Lactobacillus brevis W63, Bifidobacterium lactis W52, Lactobacillus salivarius W24, Lactobacillus acidophilus W37, Lactococcus lactis W19, Lactobacillus casei W56, and Lactococcus lactis W58 alleviated vascular malfunction and arterial stiffness in obese postmenopausal women, and finally, while further research is needed, Prevotella maybe protective against postmenopausal bone mass loss. As several studies report the therapeutic potential of probiotics and since the gut microbiota of certain female pathological states has been relatively characterized, we speculate that the administration of certain bacterial species as probiotics is warranted, as novel independent or adjunct therapies for various female pathologies.


Paternal epigenetic influences on placental health and their impacts on offspring development and disease

Abstract: Our efforts to understand the developmental origins of birth defects and disease have primarily focused on maternal exposures and intrauterine stressors. Recently, research into non-genomic mechanisms of inheritance has led to the recognition that epigenetic factors carried in sperm also significantly impact the health of future generations. However, although researchers have described a range of potential epigenetic signals transmitted through sperm, we have yet to obtain a mechanistic understanding of how these paternally-inherited factors influence offspring development and modify life-long health. In this endeavor, the emerging influence of the paternal epigenetic program on placental development, patterning, and function may help explain how a diverse range of male exposures induce comparable intergenerational effects on offspring health. During pregnancy, the placenta serves as the dynamic interface between mother and fetus, regulating nutrient, oxygen, and waste exchange and coordinating fetal growth and maturation. Studies examining intrauterine maternal stressors routinely describe alterations in placental growth, histological organization, and glycogen content, which correlate with well-described influences on infant health and adult onset of disease. Significantly, the emergence of similar phenotypes in models examining preconception male exposures indicates that paternal stressors transmit an epigenetic memory to their offspring that also negatively impacts placental function. Like maternal models, paternally programmed placental dysfunction exerts life-long consequences on offspring health, particularly metabolic function. Here, focusing primarily on rodent models, we review the literature and discuss the influences of preconception male health and exposure history on placental growth and patterning. We emphasize the emergence of common placental phenotypes shared between models examining preconception male and intrauterine stressors but note that the direction of change frequently differs between maternal and paternal exposures. We posit that alterations in placental growth, histological organization, and glycogen content broadly serve as reliable markers of altered paternal developmental programming, predicting the emergence of structural and metabolic defects in the offspring. Finally, we suggest the existence of an unrecognized developmental axis between the male germline and the extraembryonic lineages that may have evolved to enhance fetal adaptation.


The association between endometriosis and risk of endometrial cancer and breast cancer: a meta-analysis

Abstract:
PURPOSE: Endometriosis (EMS) is confirmed pathophysiologically to be an estrogen-dependent disease, similar to endometrial hyperplasia/cancer and breast cancer. Epidemiological and biological data on endometriosis might explain links between endometriosis and these cancers. We sought to identify the differences in the risk of endometrial cancer and breast cancer between women with and women without endometriosis.

METHODS: We searched PubMed, EMBASE, the Cochrane Library, and four Chinese databases (CNKI, VIP, WanFang, CBM) to identify relevant studies published online between January 2011 and March 2021. In our meta-analysis, we used the Newcastle-Ottawa Scale (NOS) to evaluate the design and quality of all studies, and we calculated the pooled risk ratio (RR) using the random model. The Q test and I2 were used to evaluate the degree of heterogeneity of eligible studies. We used funnel plots and Begg's and Egger's tests to assess publication bias.

RESULTS: Of the 1369 articles, we finally included 14 cohort studies and seven case-control studies. Data from large cohort and case-control studies indicate that women with endometriosis had an increased risk of both endometrial cancer [RR, 1.662; 95% CI, (1.148-2.407)] and breast cancer [RR, 1.082; 95% CI, (1.001-1.169)].

CONCLUSION: Endometriosis can increase the risk of endometrial cancer and breast cancer, and women with endometriosis are recommended to receive routine screening in long-term management.


Contraceptives and cancer risks in BRCA1/2 pathogenic variant carriers: a  systematic review and meta-analysis

Majke H D van Bommel

Department of Obstetrics and Gynaecology, Radboud University Medical Center, Radboud Institute for Health Sciences , Nijmegen, the Netherlands

Abstract:
Background: Increasing numbers of BReast CAncer (BRCA) 1 or 2 pathogenic variant (PV) carriers, who have an inherited predisposition to breast and ovarian cancer, are being identified. Among these women, data regarding the effects of contraception on cancer risks are unclear and various guidelines provide various recommendations. OBJECTIVE AND

Rationale: We aim to optimize counselling regarding contraception for BRCA1/2-PV carriers. Therefore, we performed a systematic review and meta-analysis. We investigated the risk ratio for developing breast cancer or ovarian cancer in BRCA1/2-PV carriers who have used any form of contraception versus non-users. Second, we analysed breast and ovarian cancer risk among BRCA1/2-PV carriers as influenced by the duration of contraceptive use and by the time since last use. In addition, we provide an overview of all relevant international guidelines regarding contraceptive use for BRCA1/2-PV carriers. SEARCH

Methods: A systematic search in the Medline database and Cochrane library identified studies describing breast and/or ovarian cancer risk in BRCA1/2-PV carriers as modified by contraception until June 2021. The search included medical subject headings, keywords and synonyms related to BRCA and contraceptives (any kind). PRISMA guidance was followed. Risk Of Bias In Non-randomized Studies of Interventions and Grading of Recommendations, Assessment, Development and Evaluations assessments were performed. Random-effects meta-analyses were used to estimate pooled effects for breast and ovarian cancer risk separately. Subgroup analyses were conducted for BRCA1 versus BRCA2 and for the various contraceptive methods.

Outcomes: Results of the breast cancer risk with oral contraceptive pill (OCP) analysis depended on the outcome measure. Meta-analyses of seven studies with 7525 women revealed a hazard ratio (HR) of 1.55 (95% CI: 1.36-1.76) and of four studies including 9106 women resulted in an odds ratio (OR) of 1.06 (95% CI: 0.90-1.25), heterogeneity (I2) 0% and 52%, respectively. Breast cancer risk was still increased in ever-users compared with never-users >10 years after last OCP use. In contrast, ovarian cancer risk was decreased among OCP users: HR 0.62 (95% CI: 0.52-0.74) based on two studies including 10 981 women (I2: 0%), and OR 0.49 (95% CI: 0.38-0.63) based on eight studies including 10 390 women (I2: 64%). The protective effect vanished after cessation of use. Tubal ligation also protects against ovarian cancer: one study including 3319 women (I2: 0%): HR: 0.44 (95% CI: 0.26-0.74) and three studies with 7691 women (I2: 44%): OR: 0.74 (95% CI: 0.53-1.03). Data regarding other contraceptives were unavailable. No differences were observed between BRCA1 and BRCA2-PV carriers. The quality of evidence was either low or very low. WIDER Implications: The OCP potentially increases breast cancer risk, while ovarian cancer risk decreases with either the OCP and tubal ligation in BRCA1/2-PV carriers. Counselling of BRCA1/2-PV carriers should be personalized; the genetic and non-genetic factors (like prior risk-reducing surgeries, prior breast cancer and age) and patients' preferences (reversibility, ease of use, reliability and effect on menstrual cycle) should be balanced. To further optimize counselling for high-risk women, future research should focus on other (commonly used) contraceptive methods and cancer risks in this specific population, and on the potential impact of changing formulations over time.


Patient informed choice in the age of evidence-based medicine: IVF patients' approaches to biomedical evidence and fertility treatment add-ons

Abstract: With the increasing offer of fertility treatment by a largely privatised sector, which has involved the proliferation of treatment add-ons lacking evidence of effectiveness, In-Vitro Fertilisation (IVF) patients are expected to make informed choices on what to include in their treatment. Drawing on interviews with 51 individuals undergoing fertility treatment, this article explores patients' approaches to medical evidence interpretation and its role in their decisions to include add-ons. While most IVF patients share understandings of what counts as medical evidence, our findings show how their approaches also differ. Our analysis focuses on how patients negotiate the notion of medical evidence and its relation to other forms of experience or knowledge. We present four different approaches to evidence in IVF: (1) delegating evaluations of evidence to experts; (2) critically assessing available evidence; (3) acknowledging the process of making evidence; and (4) contextualising evidence in their lived experience of infertility. We suggest that patients' choice to include add-ons is not due to a lack of information on or understanding of evidence, but rather should be interpreted as part of the complexity of patients' experiences of infertility.


Adaptive, reversible, hypothalamic reproductive suppression: More than functional  hypothalamic amenorrhea

Jerilynn C Prior

Vancouver Hospital and Health Sciences Centre

Abstract: OPINION article Front. Endocrinol., 19 October 2022Sec. Reproduction Volume 13 - 2022 | https://doi.org/10.3389/fendo.2022.893889


Trends in copper versus hormonal intrauterine device breakage reporting within  the United States' Food and Drug Administration Adverse Event Reporting System

Kyle R Latack

Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI, United States. Electronic address: kyle.latack@gmail.com.

Abstract:
Objective: To examine trends in national reporting of broken intrauterine devices (IUDs).

Study Design: We enumerated IUD device "breakage" reports in the Food and Drug Administration Adverse Event Reporting System from inception (1998) until February 2022. We explored associations of breakage with IUD type (copper versus hormonal), year reported, reporter (consumer versus clinician), and patient characteristics (age and weight).

Results: We identified 4144 breakage reports for copper versus 2140 for hormonal IUDs. Among the 170,215 adverse events reported, breaks were disproportionately reported for copper (9.6%) versus hormonal (1.7%) IUDs.

Conclusion: National pharmacovigilance data suggests disproportionate breakage in copper versus hormonal IUDs though the true prevalence of breaks cannot be calculated from this dataset.


State of the Fertility Sector 2021/2022

State of the Fertility Sector 2021/2022

Abstract:
# State of the fertility sector 2021/22
Annual publication on HFEA licensed clinics
Published: October 2022
[Download the underlying dataset as .xlsx](https://www.hfea.gov.uk/media/lxkhzo04/state-of-the-fertility-sector-2021-2022-underlying-data.xlsx "State of the Fertility Sector 2021 - 2022 - underlying data")
## Table of contents
- [About this report](https://www.hfea.gov.uk/about-us/publications/research-and-data/state-of-the-fertility-sector-2021-2022/#section-1)
- [1\. Changes to interim inspection themes](https://www.hfea.gov.uk/about-us/publications/research-and-data/state-of-the-fertility-sector-2021-2022/#section-2)
- [2\. There were 105 inspections undertaken in 2021/22](https://www.hfea.gov.uk/about-us/publications/research-and-data/state-of-the-fertility-sector-2021-2022/#section-3)
- [3\. In 2021/22, 104 clinics were licensed by the HFEA to provide fertility treatment](https://www.hfea.gov.uk/about-us/publications/research-and-data/state-of-the-fertility-sector-2021-2022/#section-4)
- [4\. No Grade A incidents since 2020/21, and severe OHSS remained consistent with previous years](https://www.hfea.gov.uk/about-us/publications/research-and-data/state-of-the-fertility-sector-2021-2022/#section-5)
- [5\. Patient complaints decreased in 2021/22](https://www.hfea.gov.uk/about-us/publications/research-and-data/state-of-the-fertility-sector-2021-2022/#section-6)
- [About our data](https://www.hfea.gov.uk/about-us/publications/research-and-data/state-of-the-fertility-sector-2021-2022/#about-our-data)
## About this report
The Human Fertilisation and Embryology Authority (HFEA) is the independent regulator of fertility treatment and human embryo research in the United Kingdom (UK). We aim to ensure that everyone receives high quality care in a licenced fertility clinic. We do this by licensing, monitoring, and inspecting fertility clinics and providing free, clear and impartial information about fertility treatment, clinics, and egg, sperm, and embryo donation.
...


Interpregnancy interval and adverse pregnancy outcomes among pregnancies following miscarriages or induced abortions in Norway (2008-2016): A cohort study

Abstract:
BACKGROUND: The World Health Organization recommends to wait at least 6 months after miscarriage and induced abortion before becoming pregnant again to avoid complications in the next pregnancy, although the evidence-based underlying this recommendation is scarce. We aimed to investigate the risk of adverse pregnancy outcomes-preterm birth (PTB), spontaneous PTB, small for gestational age (SGA) birth, large for gestational age (LGA) birth, preeclampsia, and gestational diabetes mellitus (GDM)-by interpregnancy interval (IPI) for births following a previous miscarriage or induced abortion.

METHODS AND FINDINGS: We conducted a cohort study using a total of 49,058 births following a previous miscarriage and 23,707 births following a previous induced abortion in Norway between 2008 and 2016. We modeled the relationship between IPI and 6 adverse pregnancy outcomes separately for births after miscarriages and births after induced abortions. We used log-binomial regression to estimate unadjusted and adjusted relative risk (aRR) and 95% confidence intervals (CIs). In the adjusted model, we included maternal age, gravidity, and year of birth measured at the time of the index (after interval) births. In a sensitivity analysis, we further adjusted for smoking during pregnancy and prepregnancy body mass index. Compared to births with an IPI of 6 to 11 months after miscarriages (10.1%), there were lower risks of SGA births among births with an IPI of <3 months (8.6%) (aRR 0.85, 95% CI: 0.79, 0.92, p < 0.01) and 3 to 5 months (9.0%) (aRR 0.90, 95% CI: 0.83, 0.97, p = 0.01). An IPI of <3 months after a miscarriage (3.3%) was also associated with lower risk of GDM (aRR 0.84, 95% CI: 0.75, 0.96, p = 0.01) as compared to an IPI of 6 to 11 months (4.5%). For births following an induced abortion, an IPI <3 months (11.5%) was associated with a nonsignificant but increased risk of SGA (aRR 1.16, 95% CI: 0.99, 1.36, p = 0.07) as compared to an IPI of 6 to 11 months (10.0%), while the risk of LGA was lower among those with an IPI 3 to 5 months (8.0%) (aRR 0.84, 95% CI: 0.72, 0.98, p = 0.03) compared to an IPI of 6 to 11 months (9.4%). There was no observed association between adverse pregnancy outcomes with an IPI >12 months after either a miscarriage or induced abortion (p > 0.05), with the exception of an increased risk of GDM among women with an IPI of 12 to 17 months (5.8%) (aRR 1.20, 95% CI: 1.02, 1.40, p = 0.02), 18 to 23 months (6.2%) (aRR 1.24, 95% CI: 1.02, 1.50, p = 0.03), and ≥24 months (6.4%) (aRR 1.14, 95% CI: 0.97, 1.34, p = 0.10) compared to an IPI of 6 to 11 months (4.5%) after a miscarriage. Inherent to retrospective registry-based studies, we did not have information on potential confounders such as pregnancy intention and health-seeking bahaviour. Furthermore, we only had information on miscarriages that resulted in contact with the healthcare system.

CONCLUSIONS: Our study suggests that conceiving within 3 months after a miscarriage or an induced abortion is not associated with increased risks of adverse pregnancy outcomes. In combination with previous research, these results suggest that women could attempt pregnancy soon after a previous miscarriage or induced abortion without increasing perinatal health risks.


Metabolic dysregulation in patients with premature ovarian insufficiency revealed  by integrated transcriptomic, methylomic and metabolomic analyses

Abstract: Premature ovarian insufficiency (POI) is a disorder of ovarian function, which occurs in approximately 3.7% of women younger than 40 years of age.1 The aetiologies of most cases were unknown and usually manifest as isolated organ senescence at early stage of diagnosis, only with long-term consequences of increased risk of metabolic syndrome or disease.2 We tried to explore the essence of POI from multiple dimensions. First, we found that upregulated genes in POI patients' ovarian granulosa cells were mainly enriched in metabolic pathways. Then, we profiled metabolites in the patients' sera and identified some metabolites with changed levels, including fumarate, arachidonate and acetoacetate, and the combination of hyodeoxycholic acid (HDCA) and acetoacetate may be used as one of potential biomarkers for POI. In addition, we found genes with upregulated transcription levels and differential methylated levels were enriched in oxidative stress pathways, which can be also elucidated from abnormal metabolism.The transcriptomes of patient and control granulosa cells were profiled, and 3966 differentially expressed genes (DEGs) (fold change > 2, Padj < .05) were identified (Table S1). Gene ontology analyses found that downregulated DEGs were mainly related to extracellular matrix/structure organization and different types of junctions. The upregulated DEGs were enriched in various catabolic/metabolic/biosynthetic/processes (Figure 1A). KEGG (Kyoto Encyclopaedia of Genes and Genomes) analysis showed that cytokine–cytokine receptor interaction, PI3K-Akt-signalling pathway and MAPK-signalling pathway were enriched in the downregulated genes, whereas the metabolic pathway was the most enriched in the upregulated genes. Moreover, other pathways, such as amino acid degradation, synthesis, peroxisome and oxidative phosphorylation, were also enriched in upregulated DEGs (Figure 1B). Several previous studies present valuable information about metabolic features of POI, which mainly focus on total cholesterol, lipoprotein cholesterol and glucose metabolism.3-6 Elevated levels of free fatty acids in follicular fluid were also reported as a potential driver of human POI.7 However, many of these results were inconsistent and not so comprehensive, although they have been noteworthy. Therefore, we carried out metabolomic analyses on serum samples from POI patients and controls. The outlined demographic characteristics of all recruited patients and controls were shown (Table 1). Two cohorts were enrolled in the metabolomic analyses in this study (Figure 2A). In the discovery cohort, a total of 6 categories of 181 features were reliably detected. POI patients could be clearly distinguished from controls by conducting multivariate statistical analysis (Figure 2B). Sixty-two features with VIP (variable importance in projection) values greater than 1 were identified and considered as differential metabolites (DMets). Subsequently, 26 of the 63 DMets were found to be significantly different between POI patients and controls using univariate t test analysis (p < .05) (Figure 2C; Table S2). Next, 32 out of the 62 features were validated using the validation cohort (Table S3). The numbers of metabolites in the union and intersections of the DMets identified from the discovery and validation cohorts were 39 and 13, respectively. Pearson's correlation coefficient figure and heat map analysis of the 39 DMets are shown (Figure S1). Enrichment and pathway analysis of the 39 DMets are shown respectively (Figure 2D,E). Out of the 13 validated DMets, 5 (acetoacetate, glutamate, C22:1, arachidonate and succinate) and 4 (HDCA, C22:0, homocitrulline [Hcit] and fumarate) were increased and decreased in the sera of POI patients, respectively. In addition, ROS and LDH (lactic dehydrogenase) were increased, and NADH and ATP were decreased in patients (Figure 2F). Receiver-operating characteristic (ROC) analysis was performed and 8 metabolites had area under curve (AUCs) greater than .7. In addition, the top two combinations with the highest AUCs were NADH plus acetoacetate (.868) and HDCA plus acetoacetate (.955) (Figure 2G,H). Furthermore, we reanalysed the human granulosa cell whole-genome DNA methylation profiling data that we previously generated.7 A number of 536 genes were hypermethylated in their differentially methylated regions (DMRs), whereas 1583 genes with hypomethylated DMRs were identified (Table S4; Figure S2). Integrating our transcriptomic and methylomic data, we found that 240 differentially expressed and methylated genes (DEMGs) were mainly enriched in response to oxidative stress, response to chemical stress, reactive oxygen species and hydrogen peroxide (Table S5; Figure S3A,B). DNMT3, DNMT1, methylenetetrahydrofolate reductase) and 5-methyltetrahydrofolate–homocysteine methyltransferase reductase, involved in methionine cycle, were differently expressed in POI patients' granulosa cells (Figure S3C). We next conducted network analysis on these DEMGs and the metabolites we detected (Table S6; Figure S4). The top five DMets were ATP, arachidonate, serotonin, glutamate and citrate. Glutamine synthetase (GLUL) and FOS were revealed as the top two hub genes in terms of connectivity with metabolites. GLUL, which catalyses the ATP-dependent conversion of glutamate and ammonia to glutamine, is related to 9 metabolites and was significantly upregulated and hypomethylated in exonic regions and the 3′UTRs. In-line with this, metabolic profiling showed decreased ATP and increased glutamate in POI patients. FOS was related to 8 metabolites and significantly upregulated and hypomethylated in exonic and 3′UTR regions (Figure 3A). It was also recently reported as a hub gene in the gene regulatory network of antioxidant in aged monkeys and human ovaries.8 In addition, we searched the human metabolome database for the associated enzymes/proteins of the 39 DMets. Changes in the expression and methylation status of these genes were displayed using Cytoscape software (Table S7; Figure S4). Joint-pathway analysis of DEMGs and DMets showed pathways those were impacted (Figure 3B). All the previous analyses were summarized as a metabolic network composed of DMets and enzymes of DEMGs that may contribute to the aetiology of POI (Figure 3C). Genes for NMNAT, PAR3 and NAMPT, enzymes involved in the synthesis or consumption of nicotinamide adenine dinucleotide (NAD+), which were reported associated with POI or ovarian ageing,9, 10 were upregulated or downregulated DEGs. In summary, the integrated analyses of transcriptomic and methylomic data from granulosa cells of the human ovary and the metabolomic data from human sera have identified increased levels of acetoacetate and arachidonate and disturbances in the TCA (tricarboxylic acid) cycle, fatty acids, ketone bodies and antioxidative processes, all of which contribute to decreased levels of NADH and ATP, increased oxidative stress and eventually ovarian premature senescence. Our data not only yielded valuable fundamental insights into its pathological mechanism but also would aid in the development of new therapeutic targets for POI. The causal effect relationship between gene expression and metabolic changes warrants further investigation in the future. This work was supported by the National Natural Science Foundation of China (81971349 and 81300456 to Cuiling Lu) and National Key Research and Development Program of China (2018YFE0201100 to Chunsheng Han and 2016YFC1000302 to Xiumei Zhen). The authors declare that there is no conflict of interest. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.


Impact of gender-affirming treatment on bone health in transgender and gender diverse youth

Abstract: Both in the United States and Europe, the number of minors who present at transgender healthcare services before the onset of puberty is rapidly expanding. Many of those who will have persistent gender dysphoria at the onset of puberty will pursue long-term puberty suppression before reaching the appropriate age to start using gender-affirming hormones. Exposure to pubertal sex steroids is thus significantly deferred in these individuals. Puberty is a critical period for bone development: increasing concentrations of estrogens and androgens (directly or after aromatization to estrogens) promote progressive bone growth and mineralization and induce sexually dimorphic skeletal changes. As a consequence, safety concerns regarding bone development and increased future fracture risk in transgender youth have been raised. We here review published data on bone development in transgender adolescents, focusing in particular on differences in age and pubertal stage at the start of puberty suppression, chosen strategy to block puberty progression, duration of puberty suppression, and the timing of re-evaluation after estradiol or testosterone administration. Results consistently indicate a negative impact of long-term puberty suppression on bone mineral density, especially at the lumbar spine, which is only partially restored after sex steroid administration. Trans girls are more vulnerable than trans boys for compromised bone health. Behavioral health measures that can promote bone mineralization, such as weight-bearing exercise and calcium and vitamin D supplementation, are strongly recommended in transgender youth, during the phase of puberty suppression and thereafter.


Association of Maternal Preeclampsia With Offspring Risks of Ischemic Heart Disease and Stroke in Nordic Countries

Abstract:
IMPORTANCE: An association between maternal preeclampsia and an increased risk of cardiovascular disease in the offspring is plausible, but evidence in this area is limited.

OBJECTIVE: To investigate (1) the association between maternal preeclampsia and risks of ischemic heart disease (IHD) and stroke in the offspring, (2) whether the association varies by severity or timing of onset of preeclampsia, and (3) the role of preterm birth and small for gestational age (SGA) birth, both of which are related to preeclampsia and cardiovascular diseases, in this association.

DESIGN, SETTING, AND PARTICIPANTS: This multinational population-based cohort study obtained data from Danish, Finnish, and Swedish national registries. Live singleton births from Denmark (1973-2016), Finland (1987-2014), and Sweden (1973-2014) were followed up until December 31, 2016, in Denmark and December 31, 2014, in Finland and Sweden. Data analyses were performed between September 2020 and September 2022.

EXPOSURES: Preeclampsia and its subtypes, including early onset (<34 gestational weeks) and late onset (≥34 gestational weeks), severe and mild or moderate, and with and without SGA birth.

MAIN OUTCOMES AND MEASURES: Diagnoses of IHD and stroke were extracted from patient and cause-of-death registers. Cox proportional hazards regression models and flexible parametric survival models were used to analyze the associations. Sibling analyses were conducted to control for unmeasured familial factors.

RESULTS: The cohort included of 8 475 819 births (2 668 697 [31.5%] from Denmark, 1 636 116 [19.3%] from Finland, and 4 171 006 [49.2%] from Sweden, comprising 4 350 546 boys [51.3%]). Of these offspring, 188 670 (2.2%) were exposed to maternal preeclampsia, 7446 (0.1%) were diagnosed with IHD, and 10 918 (0.1%) were diagnosed with stroke during the median (IQR) follow-up of 19.3 (9.0-28.1) years. Offspring of individuals with preeclampsia had increased risks of IHD (adjusted hazard ratio [HR], 1.33; 95% CI, 1.12-1.58) and stroke (adjusted HR, 1.34; 95% CI, 1.17-1.52). These associations were largely independent of preterm or SGA birth. Severe forms of preeclampsia were associated with a higher stroke risk than less severe forms (severe vs mild or moderate: adjusted HR, 1.81 [95% CI, 1.41-2.32] vs 1.22 [95% CI, 1.05-1.42]; early vs late onset: adjusted HR, 2.55 [95% CI, 1.97-3.28] vs 1.18 [95% CI, 1.01-1.39]; with vs without SGA birth: adjusted HR, 1.84 [95% CI, 1.44-2.34] vs 1.25 [95% CI, 1.07-1.48]). Sibling analyses suggested that the associations were partially explained by unmeasured familial factors.

CONCLUSIONS AND RELEVANCE: Results of this study suggest that offspring born to individuals with preeclampsia had increased IHD and stroke risk that were not fully explained by preterm or SGA birth, and that the associated risks for stroke were higher for severe forms of preeclampsia.


Time to Resumption of Menses, Spatial Distribution, and Predictors Among  Post-partum Period Women in Ethiopia, Evidence From Ethiopian Demographic and  Health Survey 2016 Data: Gompertz Inverse Gaussian Shared Frailty Model

Abstract:
Background: The timing of the resumption of post-partum menses is important for a woman who intends to avoid subsequent unintended pregnancy, and it has key implications on maternal, neonatal, and child health outcomes. Despite this, information is scant about the time to resumption of post-partum menses and predictors in Ethiopia. Therefore, this study aimed to determine the time it takes to start menses and spatial distribution among post-partum period women in Ethiopia and identify its predictors.

Methods: A secondary data analysis was conducted based on 2016 Ethiopian Demographic and Health Survey (EDHS). A total weighted sample of 6,489 post-partum women was included in the analysis. STATA 14 was used to weigh, clean, and analyze the data. The shared frailty model was applied since the EDHS data have a hierarchical nature. For checking the proportional hazard assumption, the Schenefold residual test, Log-Log plot, Kaplan-Meier, and predicted survival plot were applied. Akakie Information Criteria (AIC), Cox-Snell residual test, and deviance were used for checking model adequacy and for model comparison. Based on these, the Gompertz inverse Gaussian shared frailty model was the best-fitted model for this data. Variables with a p < 0.2 were considered for the multivariable Gompertz inverse Gaussian shared frailty model. Finally, the adjusted hazard ratio (AHR) with a 95% confidence interval (CI), and a p < 0.05 was reported to identify the significant predictors of time to the resumption of post-partum menses.

Results: The median survival time to post-partum menses resumption was 14.6 months. In this study, 51.90% [95% CI: 50.03, 53.76] of post-partum period women had resumed, and the risk of menses resumption was 1.17 times [AHR: 1.17; 95% CI: 1.03-1.33] higher among urban resident, 1.14 times [AHR: 1.14; 95% CI: 1.0-1.24] in women who had attended formal education, and 1.63 times [AHR: 1.63; 95% CI: 1.4-1.7] higher among women who used hormonal contraceptives. However, the risk of post-partum menses resumption was lower among 7-24 months breastfeeding women by 36% [AHR: 0.64; 95% CI: 0.5-0.76], women with child alive by 26% [AHR: 0.74; 95% CI: 0.6-0.85], and multiparous women by 27% [AHR: 0.73; 95% CI: 0.6-0.80].

Conclusion: Almost half of the participants had resumed post-partum menses, with the median survival timing of menses resumption at 14.5 months. Women residing in urban areas, who attended formal education, and using hormonal contraceptives have a shorter time to resume post-partum menses, whereas a woman with an alive child, breastfeeding practice, and multiple parity has a longer time to resume post-partum menses. Therefore, the healthcare providers and program managers should act on the resumption of post-partum menses through health education and promotion to cultivate the 14 months lag period identified by considering the significant factors.


Metabolic Disorders in Menopause

Metabolic Disorders in Menopause

Abstract: Menopause is an aging process and an important time equivalent to one-third of a woman's lifetime. Menopause significantly increases the risk of cardiometabolic diseases, such as obesity, type 2 diabetes, cardiovascular diseases, non-alcoholic liver disease (NAFLD)/metabolic associated fatty liver disease (MFFLD), and metabolic syndrome (MetS). Women experience a variety of symptoms in the perimenopausal period, and these symptoms are distressing for most women. Many factors worsen a woman's menopausal experience, and controlling these factors may be a strategy to improve postmenopausal women's health. This review aimed to confirm the association between menopause and metabolic diseases (especially MetS), including pathophysiology, definition, prevalence, diagnosis, management, and prevention.


The Effect of Menopause on Antipsychotic Response

Alexandre González-Rodríguez

Centro de Investigación Biomédica en Red de Salud Mental

Abstract:
Background: It has been hypothesized that, whenever estrogen levels decline, psychosis symptoms in women increase. At menopause, this can happen in two main ways: (a) the loss of estrogen (mainly estradiol) can directly affect central neurotransmission, leading to increase in schizophrenia-related symptoms, and (b) the loss of estrogen can decrease the synthesis of enzymes that metabolize antipsychotic drugs, thus weakening their efficacy. Aims and

Methods: The aim of this narrative review was to investigate the second possibility by searching PubMed and ClinicalTrials.gov for studies over the last two decades that investigated the metabolism of antipsychotics and their efficacy before and after menopause in women or that studied systemic and local estrogen level effects on the pharmacokinetics and pharmacodynamics of individual antipsychotic drugs.

Results: The evidence suggests that symptom level in women with schizophrenia rises after menopause for many reasons beyond hormones but, importantly, there is an estrogen-dependent loss of efficacy related to antipsychotic treatment.

Conclusion: Effective clinical intervention is challenging; nevertheless, several promising routes forward are suggested.


"It always gets pushed aside:" Qualitative perspectives on puberty and menstruation education in U.S.A. schools

Abstract: Adolescent girls in the U.S.A. often lack sufficient education on pubertal and menstrual health topics. This educational gap may be growing given the current decline in American elementary and middle schools' delivery of sexual health education. Furthermore, little is known about the actual scope and quality of existing menstruation and puberty education in U.S.A. schools. This paper provides insights into some of the challenges with the delivery of menstruation and puberty education in schools. Qualitative and participatory research methodologies were utilized with Black and Latina girls ages 15–19 and adults working with youth in three U.S.A. cities (Chicago, Los Angeles, and New York City), exploring experiences of menstruation within school and family contexts. Findings revealed tension between school responsibility and family authority in providing menstruation and puberty education in schools, school- and teacher-related delivery challenges, and inadequate and disengaging menstruation and puberty content. Further research is needed on the effectiveness and best practices for providing this education in schools, including improved understanding on student and parent preferences, delivery mediums and the scope of content.


Effect of the use of prediagnosis hormones on breast cancer prognosis: MCC-Spain  study

Alonso-Molero J, Gómez-Acebo I, Llorca J, Lope-Carvajal V, Amiano P, Guevara M, Martín V, Castaño-Vinyals G, Fernández-Ortiz M, Obón-Santacana M, Alguacil J, Fernandez-Tardon G, Molina-Barceló A, Marcos-Gragera R, Pérez-Gómez B, Aizpurua A, Ardanaz E, Molina AJ, Rodríguez-Cundín P, Moreno V, Rodríguez-Reinado C, Aragonés N, Kogevinas M, Pollán M, Dierssen-Sotos T

Abstract:
Objective: To extend knowledge about the long-term use of hormones in hormone therapy or oral contraception as prognostic factors in breast cancer.

Methods: The MCC-Spain project is a cohort of 1,685 women with incident breast cancer recruited in Spain. Recruitment was carried out between 2007 and 2010, and the follow-up finished in December 2017. The impact of hormone therapy or oral contraception on breast cancer prognosis was analyzed considering year of birth and menopausal status (1,095 women [65%] were postmenopausal). Hazard ratios (HRs) were estimated using Cox regression models. Death by any cause was considered as the event, and hormone therapy or oral contraception were analyzed as regressors.

Results: Oral contraception use for less than 5 years shows an HR of 1.10 (95% CI, 0.75 to 1.62), whereas use for 5 or more years shows an HR of 1.46 (95% CI, 0.95 to 2.25), with a P trend of 0.01, showing a dose-dependent response. Regarding hormone therapy and restricting the analysis to postmenopausal women born between1940 and 1959, where most hormone therapy (consumption) is concentrated, the results did not show any trend.

Conclusion: Concerning oral contraception use, our results demonstrate that their use is related to poor prognosis in breast cancer. However, research in this field is limited and controversial, indicating the need for more research in this area. Regarding hormone therapy consumption, our results indicate no association with better prognosis, which contradicts what has previously been published.


The Impact of IT-Based Healthcare Communication on Mammography Screening  Utilization among Women in the United States: National Health Interview Survey  (2011-2018)

Noof Alabdullatif

Department of Health Policy and Management, FIU Robert Stempel College of Public Health and Social Work, Miami, FL 33199, USA

Lucie Dlugasch

Dr. Herbert & Nicole Wertheim Family Foundation

Abstract: Effective patient-provider communication improves mammography utilization. Using information technology (IT) promotes health outcomes. However, there are disparities in access to IT that could contribute to disparities in mammography utilization. This study aims to assess the association between IT-based health care communication and mammography utilization and to evaluate if this effect is modified by race/ethnicity and age. To this end, this study was conducted using the National Health Interview Survey from 2011 to 2018. A total of 94,290 women aged 40 years and older were included. Multiple logistic regression models were used, and odds ratios were reported. The study found that all IT-based healthcare communication strategies were significantly associated with mammography utilization in all years from 2011 to 2018. In 2018, women who looked up health information on the internet, scheduled a medical appointment on the internet, and communicated with providers by email had a significantly higher chance to use mammography (p ≤ 0.005 for all strategies across all years). White women and women aged 50 years and older benefited the most from IT-based healthcare communication. In conclusion, facilitating access to IT may help increase mammography utilization, which may contribute to eliminating disparities in breast cancer mortality.

International Journal of Environmental Research and Public Health


Characteristics of menstrual cycles with or without intercourse in women with no known subfertility

Abstract:
STUDY QUESTION: Does sexual intercourse enhance the cycle fecundability in women without known subfertility?

SUMMARY ANSWER: Sexual intercourse (regardless of timing during the cycle) was associated with cycle characteristics suggesting higher fecundability, including longer luteal phase, less premenstrual spotting and more than 2 days of cervical fluid with estrogen-stimulated qualities.

WHAT IS KNOWN ALREADY: Human females are spontaneous ovulators, experiencing an LH surge and ovulation cyclically, independent of copulation. Natural conception requires intercourse to occur during the fertile window of a woman's menstrual cycle, i.e. the 6-day interval ending on the day of ovulation. However, most women with normal fecundity do not ovulate on Day 14, thus the timing of the hypothetical fertile window varies within and between women. This variability is influenced by age and parity and other known or unknown elements. While the impact of sexual intercourse around the time of implantation on the probability of achieving a pregnancy has been discussed by some researchers, there are limited data regarding how sexual intercourse may influence ovulation occurrence and menstrual cycle characteristics in humans.

STUDY DESIGN SIZE DURATION: This study is a pooled analysis of three cohorts of women, enrolled at Creighton Model FertilityCare centers in the USA and Canada: 'Creighton Model MultiCenter Fecundability Study' (CMFS: retrospective cohort, 1990-1996), 'Time to Pregnancy in Normal Fertility' (TTP: randomized trial, 2003-2006) and 'Creighton Model Effectiveness, Intentions, and Behaviors Assessment' (CEIBA: prospective cohort, 2009-2013). We evaluated cycle phase lengths, bleeding and cervical mucus patterns and estimated the fertile window in 2564 cycles of 530 women, followed for up to 1 year.

PARTICIPANTS/MATERIALS SETTING

METHODS: Participants were US or Canadian women aged 18-40 and not pregnant, who were heterosexually active, without known subfertility and not taking exogenous hormones. Most of the women were intending to avoid pregnancy at the start of follow-up. Women recorded daily vaginal bleeding, mucus discharge and sexual intercourse using a standardized protocol and recording system for up to 1 year, yielding 2564 cycles available for analysis. The peak day of mucus discharge (generally the last day of cervical fluid with estrogen-stimulated qualities of being clear, stretchy or slippery) was used to identify the estimated day of ovulation, which we considered the last day of the follicular phase in ovulatory cycles. We used linear mixed models to assess continuous cycle parameters including cycle, menses and cycle phase lengths, and generalized linear models using Poisson regression with robust variance to assess dichotomous outcomes such as ovulatory function, short luteal phases and presence or absence of follicular or luteal bleeding. Cycles were stratified by the presence or absence of any sexual intercourse, while adjusting for women's parity, age, recent oral contraceptive use and breast feeding.

MAIN RESULTS AND THE ROLE OF CHANCE: Most women were <30 years of age (75.5%; median 27, interquartile range 24-29), non-Hispanic white (88.1%), with high socioeconomic indicators and nulliparous (70.9%). Cycles with no sexual intercourse compared to cycles with at least 1 day of sexual intercourse were shorter (29.1 days (95% CI 27.6, 30.7) versus 30.1 days (95% CI 28.7, 31.4)), had shorter luteal phases (10.8 days (95% CI 10.2, 11.5) versus 11.4 days (95% CI 10.9, 12.0)), had a higher probability of luteal phase deficiency (<10 days; adjusted probability ratio (PR) 1.31 (95% CI 1.00, 1.71)), had a higher probability of 2 days of premenstrual spotting (adjusted PR 2.15 (95% CI 1.09, 4.24)) and a higher probability of having two or fewer days of peak-type (estrogenic) cervical fluid (adjusted PR 1.49 (95% CI 1.03, 2.15)).

LIMITATIONS REASONS FOR CAUTION: Our study participants were geographically dispersed but relatively homogeneous in regard to race, ethnicity, income and educational levels, and all had male partners, which may limit the generalizability of the findings. We cannot exclude the possibility of undetected subfertility or related gynecologic disorders among some of the women, such as undetected endometriosis or polycystic ovary syndrome, which would impact the generalizability of our findings. Acute illness or stressful events might have reduced the likelihood of any intercourse during a cycle, while also altering cycle characteristics. Some cycles in the no intercourse group may have actually had undocumented intercourse or other sexual activity, but this would bias our results toward the null. The Creighton Model FertilityCare System (CrM) discourages use of barrier methods, so we believe that most instances of intercourse involved exposure to semen; however, condoms may have been used in some cycles. Our dataset lacks any information about the occurrence of female orgasm, precluding our ability to evaluate the independent or combined impact of female orgasm on cycle characteristics.

WIDER IMPLICATIONS OF THE FINDINGS: Sexual activity may change reproductive hormonal patterns, and/or levels of reproductive hormones may influence the likelihood of sexual activity. Future work may help with understanding the extent to which exposure to seminal fluid, and/or female orgasm and/or timing of intercourse could impact menstrual cycle function. In theory, large data sets from women using menstrual and fertility tracking apps could be informative if women can be appropriately incentivized to record intercourse completely. It is also of interest to understand how cycle characteristics may differ in women with gynecological problems or subfertility.

STUDY FUNDING/COMPETING INTERESTS: Funding for the research on the three cohorts analyzed in this study was provided by the Robert Wood Johnson Foundation #029258 (Creighton Model MultiCenter Fecundability Study), the Eunice Kennedy Shriver National Institute of Child Health and Human Development 1K23 HD0147901-01A1 (Time to Pregnancy in Normal Fertility) and the Office of Family Planning, Office of Population Affairs, Health and Human Services 1FPRPA006035 (Creighton Model Effectiveness, Intentions, and Behaviors Assessment). The authors declare that they have no conflict of interest.

TRIAL REGISTRATION NUMBER: N/A.


Fluoroscopically-Guided Hysteroscopic Tubal Cannulation: A Procedure for Proximal Tubal Obstruction

Abstract:
OBJECTIVES: To evaluate the cannulation success rate, cumulative pregnancy, and time to intrauterine pregnancy rate following fluoroscopically-guided hysteroscopic tubal cannulation (FHTC) for infertile subjects with proximal tubal obstruction.

METHODS: This retrospective study evaluated subjects with unilateral or bilateral proximal tubal obstruction on hysterosalpingography, who failed concomitant selective salpingography and subsequently underwent FHTC at the time of a hysteroscopy performed for findings seen on sonohysterography. FHTC employed a Novy Catheter (CooperSurgical, Inc, Trumbull, CT.) with or without the 3 French inner catheter and guidewire, to cannulate the occluded fallopian tube(s), followed by the injection of HypaqueTM (Amersham Health, Inc, Princeton, NJ.) contrast under C-arm imaging. Technical success rates, complications, post-procedure pregnancies, and average time from surgery to pregnancy were evaluated.

RESULTS: Thirty-two women between January 1, 2017 and December 31, 2019 met the entry criteria and underwent FHTC. Of those women with bilateral obstruction, 6/6 (100%) of subjects achieved at least unilateral patency, while patency was achieved in 23/26 (88.5%) subjects with unilateral obstruction. Twenty-nine of 32 (90.6%) subjects had at least one tube successfully cannulated with 34/38 (89.5%) of proximally obstructed tubes opened. Asymptomatic tubal perforation occurred in 1/38 tubes (2.6%). Ten subjects (34.5%) achieved intrauterine pregnancies without in vitro fertilization in an average of 64.9 days from the procedure. There were no multiple pregnancies and one ectopic pregnancy.

CONCLUSIONS: FHTC is a safe, effective, incision free procedure that results in 90% of tubes successfully cannulated, and an observed short time to intrauterine pregnancy.

JSLS : Journal of the Society of Laparoendoscopic Surgeons


A Bayesian network for complex pain-related features of endometriosis


Hormone-based models for comparing menstrual cycle and hormonal contraceptive effects on human resting-state functional connectivity

Abstract: Oral contraceptives (OCs) are widely used yet understudied given their potential for public health consequences. Emerging investigations scaling from single-subject, dense-sampling neuroimaging studies to population-level metrics have linked OCs to altered brain structure and function. Modeling the hypogonadal, hypergonadal, or mixed state effects of OCs in terms of their impact on hormone action in the brain is a valuable approach to synthesizing results across neuroimaging studies and comparing OC effects to companion findings from research on menstrual cycle phase effects on brain anatomy and function. Resting-state functional connectivity studies provide a powerful tool to evaluate the role of OCs on the intrinsic network connectivity that underlies multiple behavioral domains. The preponderance (but not consensus) of the current literature indicates that (1) as the menstrual cycle proceeds from a low to high progesterone state, prefrontal connectivity increases and parietal connectivity decreases; (2) OCs tend to mimic this connectivity pattern; therefore (3) OCs may produce a hyperprogestogenic state in the brain, in spite of overall reductions in endogenous steroid hormone levels. Alternative models are also considered.


Occurrence and health implications of heavy metals in preschool children’s clothing manufactured in four Asian regions

Abstract: Clothing may be a potential contributor to body metal burden in children. However, available information on heavy metals in children's clothing is extremely limited and the associated health risks remain poorly understood. This study investigated the concentrations of Pb, Cd, Co, Zn, Cr, As, Cu and Ni in new preschool children's clothing manufactured in four Asian regions. The children's clothing had higher levels of Ni and Cr but lower levels of Pb and Cd in comparison to the concentrations reported in other textile products. The concentrations of Cd were higher in the black clothing than those in the white and color samples. The non-cotton samples contained higher Co concentrations. The Pb concentrations in the samples manufactured in China were significantly higher than those in the other three regions. We estimated the dermal exposure doses for these metals and calculated the associated risks. The results indicated that the health risks from exposure to these metals in the children's clothing were acceptable. However, more research is required to investigate heavy metals and the associated risks in child clothing due to the increasing complexity of their materials and manufacturing processes.


Laparoscopically Confirmed Endometriosis and Risk of Incident Stroke: A Prospective Cohort Study

Leslie V Farland

Department of Epidemiology and Biostatistics, Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, Arizona; Department of Obstetrics and Gynecology, College of Medicine -...

Abstract:
BACKGROUND: Prior research suggests that women with endometriosis are at greater risk of coronary heart disease. Therefore, our objective was to prospectively investigate the association between laparoscopically confirmed endometriosis and risk of incident stroke during 28 years of follow-up.

METHODS: Participants in the NHSII cohort study (Nurses' Health Study II) were followed from 1989 when they were between the ages of 25 to 42 until 2017 for development of incident stroke (ischemic and hemorrhagic). Cox proportional hazard models were used to calculate hazard ratios and 95% CI, with adjustment for potential confounding variables (alcohol intake, body mass index at age 18, current body mass index, age at menarche, menstrual cycle pattern in adolescence, current menstrual cycle pattern, parity, oral contraceptive use history, smoking history, diet quality, physical activity, NSAID use, aspirin use, race/ethnicity, and income). We estimated the proportion of the total association mediated by history of hypertension, hypercholesterolemia, hysterectomy/oophorectomy, and hormone therapy. We also tested for effect modification by age (<50, ≥50 years), infertility history, body mass index (<25, ≥25 kg/m2), and menopausal status.

RESULTS: We documented 893 incident cases of stroke during 2 770 152 person-years of follow-up. Women with laparoscopically confirmed endometriosis had a 34% greater risk of stroke in multivariable-adjusted models (hazard ratio, 1.34 [95% CI, 1.10-1.62]), compared to those without a history of endometriosis. Of the total association of endometriosis with risk of stroke, the largest proportion was attributed to hysterectomy/oophorectomy (39% mediated [95% CI, 14%-71%]) and hormone therapy (16% mediated [95% CI, 5%-40%]). We observed no differences in the relationship between endometriosis and stroke by age, infertility history, body mass index, or menopausal status.

CONCLUSIONS: We observed that women with endometriosis were at elevated risk of stroke. Women and their health care providers should be aware of endometriosis history, maximize primary cardiovascular prevention, and discuss signs and symptoms of cardiovascular disease.


The effect of sex, menstrual cycle phase and oral contraceptive use on intestinal permeability and ex-vivo monocyte TNFα release following treatment with lipopolysaccharide and hyperthermia

Abstract:
PURPOSE: Investigate the impact of sex, menstrual cycle phase and oral contraceptive use on intestinal permeability and ex-vivo tumour necrosis factor alpha (TNFα) release following treatment with lipopolysaccharide (LPS) and hyperthermia.

METHODS: Twenty-seven participants (9 men, 9 eumenorrheic women (MC) and 9 women taking an oral contraceptive pill (OC)) completed three trials. Men were tested on 3 occasions over 6 weeks; MC during early-follicular, ovulation, and mid-luteal phases; OC during the pill and pill-free phase. Intestinal permeability was assessed following a 4-hour dual sugar absorption test (lactulose: rhamnose). Venous blood was collected each trial and stimulated with 100 μg·mL-1 LPS before incubation at 37 °C and 40 °C and analysed for TNFα via ELISA.

RESULTS: L:R ratio was higher in OC than MC (+0.003, p = 0.061) and men (+0.005, p = 0.007). Men had higher TNFα responses than both MC (+53 %, p = 0.004) and OC (+61 %, p = 0.003). TNFα release was greater at 40 °C than 37 °C (+23 %, p < 0.001).

CONCLUSIONS: Men present with lower resting intestinal barrier permeability relative to women regardless of OC use and displayed greater monocyte TNFα release following whole blood treatment with LPS and hyperthermia. Oral contraceptive users had highest intestinal permeability however, neither permeability or TNFα release were impacted by the pill cycle. Although no statistical effect was seen in the menstrual cycle, intestinal permeability and TNFα release were more variable across the phases.


The FIGO Ovulatory Disorders Classification System

Malcolm G Munro

Kaiser Permanente West Los Angeles Medical Center

Abstract: Ovulatory disorders are common causes of amenorrhea, abnormal uterine bleeding and infertility and are frequent manifestations of polycystic ovary syndrome (PCOS). There are many potential causes and contributors to ovulatory dysfunction that challenge clinicians, trainees, educators, and those who perform basic, translational, clinical and epidemiological research. Similarly, therapeutic approaches to ovulatory dysfunction potentially involve a spectrum of lifestyle, psychological, medical and procedural interventions. Collaborative research, effective education and consistent clinical care remain challenged by the absence of a consensus comprehensive system for classification of these disorders. The existing and complex system, attributed to the World Health Organization (WHO), was developed more than three decades ago and did not consider more than 30 years of research into these disorders in addition to technical advances in imaging and endocrinology. This article describes the development of a new classification of ovulatory disorders performed under the aegis of the International Federation of Gynecology and Obstetrics (FIGO) and conducted using a rigorously applied Delphi process. The stakeholder organizations and individuals who participated in this process comprised specialty journals, experts at large, national, specialty obstetrical and gynecological societies, and informed lay representatives. After two face-to-face meetings and five Delphi rounds, the result is a three-level multi-tiered system. The system is applied after a preliminary assessment identifies the presence of an ovulatory disorder. The primary level of the system is based on an anatomic model (Hypothalamus, Pituitary, Ovary) that is completed with a separate category for PCOS. This core component of the system is easily remembered using the acronym HyPO-P. Each anatomic category is stratified in the second layer of the system to provide granularity for investigators, clinicians and trainees using the GAIN-FIT-PIE mnemonic (Genetic, Autoimmune, Iatrogenic, Neoplasm; Functional, Infectious and Inflammatory, Trauma and Vascular; Physiological, Idiopathic, Endocrine). The tertiary level allows for specific diagnostic entities. It is anticipated that, if widely adopted, this system will facilitate education, clinical care and the design and interpretation of research in a fashion that better informs progress in this field. Integral to the deployment of this system is a periodic process of reevaluation and appropriate revision, reflecting an improved understanding of this collection of disorders.


Chronic Endometritis in Infertile Women: Impact of Untreated Disease, Plasma Cell  Count and Antibiotic Therapy on IVF Outcome-A Systematic Review and  Meta-Analysis

Dominique De Ziegler

Université de Versailles Saint-Quentin-en-Yvelines

Vito Chiantera

Unit of Gynecologic Oncology, ARNAS “Civico-Di Cristina-Benfratelli”, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), University of Paler...

Ettore Cicinelli

Unit of Obstetrics and Gynecology, Department of Biomedical and Human Oncologic Science, University of Bari, 70124 Bari, Italy

Abstract: This systematic review and meta-analysis aims to evaluate the impact of chronic endometritis (CE) and its therapy on in vitro fertilization (IVF) outcome. Additionally, we aim to investigate whether various degrees of CE severity may exert a different effect on IVF outcome. Ongoing-pregnancy rate/live-birth-rate (OPR/LBR), clinical-pregnancy rate (CPR), and miscarriage rate (MR) were calculated. A total number of 4145 patients (from ten studies) were included. Women with CE had lower OPR/LBR (OR 1.97, p = 0.02) and CPR (OR 2.28, p = 0.002) compared to those without CE. CE cure increased OPR/LBR (OR 5.33, p < 0.0001) and CPR (OR 3.64, p = 0.0001). IVF outcome was comparable between women with cured CE and those without CE (OPR/LBR, CPR and MR: p = ns). Women with severe CE had lower OPR/LBR (OR 0.43, p = 0.003) and CPR (OR 0.40, p = 0.0007) compared to those mild CE. Mild CE showed no influence on the IVF outcome as compared to women without CE (OPR/LBR, CPR and MR: p = ns). Based on this data analysis, CE significantly reduces OPR/LBR and CPR in women undergoing IVF. Importantly, CE resolution after antibiotic therapy may improves IVF outcome, leading to similar OPR/LBR and CPR as compared to unaffected patients. The negative effects of CE on IVF outcome may be restricted to severe disease, whereas mild CE may have no influence on IVF success.


Incidence and survival of neuroendocrine neoplasia in England 1995-2018: A retrospective, population-based study

Abstract: BACKGROUND: Neuroendocrine neoplasia (NEN) incidence is rising internationally.  We aimed to evaluate the epidemiology of NEN in England and examine changes in  survival over time. METHODS: A retrospective, population-based study using nationally representative  data between 1995 and 2018 from the National Cancer Registry and Analysis  Service (NCRAS) in England was conducted on 63,949 tumours. Age-standardized  incidence was calculated using Office for National Statistics (ONS) data.  Overall survival (OS) was calculated using the Kaplan-Meier estimator.  Multivariable analysis was performed using an accelerated failure time model. FINDINGS: Of 63,949 cases, 50.5% (32,309) were female. Age-adjusted incidence  increased 3.7-fold between 1995 and 2018 from 2.35 to 8.61 per 100,000. In 2018,  highest incidence occurred in lung (1.47 per 100,000), small intestine (1.46 per  100,000), pancreas (1.00 per 100,000) and appendix (0.95 per 100,000). In  multivariable analysis, age, sex, morphology, stage, site and deprivation were  independent predictors of survival (p < 0.001). Survival of the entire cohort,  and by primary site, is improving over time. INTERPRETATION: NEN incidence continues to rise in England with survival  improving over time. Relatively high survival compared to other cancers is an  issue for long-term outcomes and funding of care. FUNDING: Data were extracted and transferred using a grant from Neuroendocrine  cancer UK.


Per- and Polyfluoroalkyl Substances in North American School Uniforms

Zhaoyi Wang

Guangdong Province Women and Children Hospital

Abstract: We analyzed 72 children's textile products marketed as stain-resistant from US and Canadian stores, particularly school uniforms, to assess if clothing represents a significant route of exposure to per- and polyfluoroalkyl substances (PFAS). Products were first screened for total fluorine (total F) using particle-induced γ-ray emission (PIGE) spectroscopy (n = 72), followed by targeted analysis of 49 neutral and ionic PFAS (n = 57). PFAS were detected in all products from both markets, with the most abundant compound being 6:2 fluorotelomer alcohol (6:2 FTOH). Total targeted PFAS concentrations for all products collected from both countries ranged from 0.250 to 153 000 ng/g with a median of 117 ng/g (0.0281-38 100 μg/m2, median: 24.0 μg/m2). Total targeted PFAS levels in school uniforms were significantly higher than in other items such as bibs, hats, stroller covers, and swimsuits, but comparable to outdoor wear. Higher total targeted PFAS concentrations were found in school uniforms made of 100% cotton than synthetic blends. Perfluoroalkyl acids (PFAAs) precursors were abundant in school uniforms based on the results of hydrolysis and total oxidizable precursor assay. The estimated median potential children's exposure to PFAS via dermal exposure through school uniforms was 1.03 ng/kg bw/day. Substance flow analysis estimated that ∼3 tonnes/year (ranging from 0.05 to 33 tonnes/year) of PFAS are used in US children's uniforms, mostly of polymeric PFAS but with ∼0.1 tonne/year of mobile, nonpolymeric PFAS.


Anti-Inflammatory Diets in Fertility: An Evidence Review

Abstract: Infertility is a global health concern affecting 48 million couples and 186 million individuals worldwide. Infertility creates a significant economic and social burden for couples who wish to conceive and has been associated with suboptimal lifestyle factors, including poor diet and physical inactivity. Modifying preconception nutrition to better adhere with Food-Based Dietary Guidelines (FBDGs) is a non-invasive and potentially effective means for improving fertility outcomes. While several dietary patterns have been associated with fertility outcomes, the mechanistic links between diet and infertility remain unclear. A key mechanism outlined in the literature relates to the adverse effects of inflammation on fertility, potentially contributing to irregular menstrual cyclicity, implantation failure, and other negative reproductive sequelae. Therefore, dietary interventions which act to reduce inflammation may improve fertility outcomes. This review consistently shows that adherence to anti-inflammatory diets such as the Mediterranean diet (specifically, increased intake of monounsaturated and n-3 polyunsaturated fatty acids, flavonoids, and reduced intake of red and processed meat) improves fertility, assisted reproductive technology (ART) success, and sperm quality in men. Therefore, integration of anti-inflammatory dietary patterns as low-risk adjunctive fertility treatments may improve fertility partially or fully and reduce the need for prolonged or intensive pharmacological or surgical interventions.


"Effect of birth ball abdominal core training on pregnancy fatigue, waist pain and delivery outcomes"

Ruiting Zhang

Women's Hospital, School of Medicine, Zhejiang University

Wei Wei

Second Affiliated Hospital of Zhejiang University

Abstract:
Objective: To evaluate the effect of birth ball abdominal core training on fatigue, waist pain, and delivery outcomes in middle and late pregnancy.

Methods: A prospective study of 209 primipara in total with 24–27 weeks of gestation were recruited and divided into the training group (109 cases) and the control group (100 cases). The control group received routine prenatal exercise. On the basis of routine prenatal exercise, pregnant women in the training group were given birth ball exercises based on abdominal core training. The difference in pregnancy fatigue, waist discomfort, and delivery outcomes between the two groups were compared.

Results: The waist pain and fatigue ratings of women were significantly lower and the vaginal delivery rate (74.3%) was significantly higher (62%) (P < 0.001) in the training group. There were no significant differences in the total stage of labor, postpartum hemorrhage, neonatal weight and 1‐min neonatal Apgar score between the two groups. The rate of episiotomy in the training group (14.7%) was significantly lower than that in the control group (25.0%) (P < 0.05).

Conclusion: Birth ball exercises can relieve fatigue and waist pain in middle and late 2021 pregnancy, reduce the rate of episiotomy, and promote spontaneous vaginal delivery.

International Journal of Gynecology & Obstetrics


Cancer in children born after frozen-thawed embryo transfer: A cohort study

Abstract:
BACKGROUND: The aim was to investigate whether children born after assisted reproduction technology (ART), particularly after frozen-thawed embryo transfer (FET), are at higher risk of childhood cancer than children born after fresh embryo transfer and spontaneous conception.

METHODS AND FINDINGS: We performed a registry-based cohort study using data from the 4 Nordic countries: Denmark, Finland, Norway, and Sweden. The study included 7,944,248 children, out of whom 171,774 children were born after use of ART (2.2%) and 7,772,474 children were born after spontaneous conception, representing all children born between the years 1994 to 2014 in Denmark, 1990 to 2014 in Finland, 1984 to 2015 in Norway, and 1985 to 2015 in Sweden. Rates for any cancer and specific cancer groups in children born after each conception method were determined by cross-linking national ART registry data with national cancer and health data registries and population registries. We used Cox proportional hazards models to estimate the risk of any cancer, with age as the time scale. After a mean follow-up of 9.9 and 12.5 years, the incidence rate (IR) of cancer before age 18 years was 19.3/100,000 person-years for children born after ART (329 cases) and 16.7/100,000 person-years for children born after spontaneous conception (16,184 cases). Adjusted hazard ratio (aHR) was 1.08, 95% confidence interval (CI) 0.96 to 1.21, p = 0.18. Adjustment was performed for sex, plurality, year of birth, country of birth, maternal age at birth, and parity. Children born after FET had a higher risk of cancer (48 cases; IR 30.1/100,000 person-years) compared to both fresh embryo transfer (IR 18.8/100,000 person-years), aHR 1.59, 95% CI 1.15 to 2.20, p = 0.005, and spontaneous conception, aHR 1.65, 95% CI 1.24 to 2.19, p = 0.001. Adjustment either for macrosomia, birth weight, or major birth defects attenuated the association marginally. Higher risks of epithelial tumors and melanoma after any assisted reproductive method and of leukemia after FET were observed. The main limitation of this study is the small number of children with cancer in the FET group.

CONCLUSIONS: Children born after FET had a higher risk of childhood cancer than children born after fresh embryo transfer and spontaneous conception. The results should be interpreted cautiously based on the small number of children with cancer, but the findings raise concerns considering the increasing use of FET, in particular freeze-all strategies without clear medical indications.

TRIAL REGISTRATION: Trial registration number: ISRCTN 11780826.


Allergies caused by textiles: control, research and future perspective in the medical field

Abstract: Textile production forms one of the most polluting industries worldwide. However, other than damaging environmental effects, chemical waste products, such as formaldehyde or thiazolinone, are problematic for human health, as allergic potential is present in these compounds. Mostly, contact dermatitis occurs when human skin is exposed to textiles. Moreover, non-eczemous variants are mainly associated to textiles. In order to diagnose the possible allergy of the patient towards these compounds, in vivo and in vitro methods ca be performed, such as patch testing or cytokine detection assays, respectively. Newest research focuses on medical textiles such as garments or sutures to help in diagnosis, therapy and recovery of the patients. Sutures and dressings with antimicrobial properties, with the release of oxygen and growth factors offer greater properties. In this review, state of the art in the field as well as future perspectives will be discussed, which are based on the smart textiles that are going to become more important and probably widespread after the current limits exceeded.


Associations Between Prenatal Urinary Biomarkers of Phthalate Exposure and Preterm Birth: A Pooled Study of 16 US Cohorts

Welch BM, Keil AP, Buckley JP, Calafat AM, Christenbury KE, Engel SM, O'Brien KM, Rosen EM, James-Todd T, Zota AR, Ferguson KK, Pooled Phthalate Exposure and Preterm Birth Study Group, Alshawabkeh AN, Cordero JF, Meeker JD, Barrett ES, Bush NR, Nguyen RHN, Sathyanarayana S, Swan SH, Cantonwine DE, McElrath TF, Aalborg J, Dabelea D, Starling AP, Hauser R, Messerlian C, Zhang Y, Bradman A, Eskenazi B, Harley KG, Holland N, Bloom MS, Newman RB, Wenzel AG, Braun JM, Lanphear BP, Yolton K, Factor-Litvak P, Herbstman JB, Rauh VA, Drobnis EZ, Sparks AE, Redmon JB, Wang C, Binder AM, Michels KB, Baird DD, Jukic AMZ, Weinberg CR, Wilcox AJ, Rich DQ, Weinberger B, Padmanabhan V, Watkins DJ, Hertz-Picciotto I, Schmidt RJ

Abstract:
IMPORTANCE: Phthalate exposure is widespread among pregnant women and may be a risk factor for preterm birth.

OBJECTIVE: To investigate the prospective association between urinary biomarkers of phthalates in pregnancy and preterm birth among individuals living in the US.

DESIGN, SETTING, AND PARTICIPANTS: Individual-level data were pooled from 16 preconception and pregnancy studies conducted in the US. Pregnant individuals who delivered between 1983 and 2018 and provided 1 or more urine samples during pregnancy were included.

EXPOSURES: Urinary phthalate metabolites were quantified as biomarkers of phthalate exposure. Concentrations of 11 phthalate metabolites were standardized for urine dilution and mean repeated measurements across pregnancy were calculated.

MAIN OUTCOMES AND MEASURES: Logistic regression models were used to examine the association between each phthalate metabolite with the odds of preterm birth, defined as less than 37 weeks of gestation at delivery (n = 539). Models pooled data using fixed effects and adjusted for maternal age, race and ethnicity, education, and prepregnancy body mass index. The association between the overall mixture of phthalate metabolites and preterm birth was also examined with logistic regression. G-computation, which requires certain assumptions to be considered causal, was used to estimate the association with hypothetical interventions to reduce the mixture concentrations on preterm birth.

RESULTS: The final analytic sample included 6045 participants (mean [SD] age, 29.1 [6.1] years). Overall, 802 individuals (13.3%) were Black, 2323 (38.4%) were Hispanic/Latina, 2576 (42.6%) were White, and 328 (5.4%) had other race and ethnicity (including American Indian/Alaskan Native, Native Hawaiian, >1 racial identity, or reported as other). Most phthalate metabolites were detected in more than 96% of participants. Higher odds of preterm birth, ranging from 12% to 16%, were observed in association with an interquartile range increase in urinary concentrations of mono-n-butyl phthalate (odds ratio [OR], 1.12 [95% CI, 0.98-1.27]), mono-isobutyl phthalate (OR, 1.16 [95% CI, 1.00-1.34]), mono(2-ethyl-5-carboxypentyl) phthalate (OR, 1.16 [95% CI, 1.00-1.34]), and mono(3-carboxypropyl) phthalate (OR, 1.14 [95% CI, 1.01-1.29]). Among approximately 90 preterm births per 1000 live births in this study population, hypothetical interventions to reduce the mixture of phthalate metabolite levels by 10%, 30%, and 50% were estimated to prevent 1.8 (95% CI, 0.5-3.1), 5.9 (95% CI, 1.7-9.9), and 11.1 (95% CI, 3.6-18.3) preterm births, respectively.

CONCLUSIONS AND RELEVANCE: Results from this large US study population suggest that phthalate exposure during pregnancy may be a preventable risk factor for preterm delivery.