Sperm DNA fragmentation and recurrent pregnancy loss: a systematic review and  meta-analysis

Dana B McQueen

Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Northwestern University, Chicago, Illinois. Electronic address: dana.mcqueen@northwestern.edu.

Abstract:
Objective: To investigate the rate of sperm DNA fragmentation in male partners of women with recurrent pregnancy loss and fertile control women.
Design: Systematic review and meta-analysis.
Setting: Not applicable. PATIENT(S): A total of 579 male partners of women with recurrent pregnancy loss and 434 male partners fertile control women. INTERVENTION(S): Prospective studies were identified through a Pubmed search. Recurrent pregnancy loss was defined as two or more previous pregnancy losses. Fertile control women had a history of a live birth or ongoing pregnancy. MAIN OUTCOME MEASURE(S): The primary outcome was the rate of sperm DNA fragmentation. The summary measures were reported as mean difference with 95% confidence interval (CI). RESULT(S): Fifteen prospective studies were included in a qualitative review. Pooled data from 13 studies with sufficient data for meta-analysis suggest that male partners of women with a history of recurrent pregnancy loss have a significantly higher rate of sperm DNA fragmentation compared to the partners of fertile control women: mean difference 11.91, 95% CI 4.97-18.86. CONCLUSION(S): These findings support an association between sperm DNA fragmentation and recurrent pregnancy loss. However, given the significant heterogeneity between studies and lack of prospective pregnancy outcome data, further large prospective studies are needed.


Assisted reproductive technology and the risk of preeclampsia: an updated  systematic review and meta-analysis

Payam Amini

Ahvaz Jundishapur University of Medical Sciences

Amir Almasi-Hashiani

Department of Epidemiology, School of Health, Arak University of Medical Sciences, Arak, Iran.

Reza Omani-Samani

Department of Epidemiology and Reproductive Health, Reproductive Epidemiology Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran.

Abstract:
Background: The objective of this systematic review and meta-analyses was to assess the risk of preeclampsia among women who conceived with assisted reproductive technology (ART).

Methods: We searched the ISI Web of Knowledge, Medline/PubMed, Scopus, and Embase (from inception to May 2017) for English language articles using a list of key words. In addition, reference lists from identified studies and relevant review articles were also searched. Data extraction was performed by two authors, and the study quality was assessed using the Newcastle-Ottawa Scale. Random-effects model meta-analysis was applied to pool the relative risks (RR) across studies.

Results: A total of 48 studies (5 case-control studies and 43 cohort studies) were included in this meta-analysis. The Cochran Q test and I(2) statistics revealed substantial heterogeneity (Q = 26,313.92, d.f. = 47, p < 0.001 and I(2) = 99.8%). Meta-analysis showed a significant increase in preeclampsia in women who conceived by ART compared with those who conceived spontaneously (RR = 1.71, 95% CI = 1.11-2.62, p = 0.015).

Conclusions: The findings of this systematic review indicate that the use of ART treatment is associated with a 1.71-fold increase in preeclampsia.


Physiological and Pathological Androgen Actions in the Ovary

Abstract: Androgens, although traditionally thought to be male sex steroids, play important roles in female reproduction, both in healthy and pathological states. This mini-review focuses on recent advances in our knowledge of the role of androgens in the ovary. Androgen receptor (AR) is expressed in oocytes, granulosa cells, and theca cells, and is temporally regulated during follicular development. Mouse knockout studies have shown that AR expression in granulosa cells is critical for normal follicular development and subsequent ovulation. In addition, androgens are involved in regulating dynamic changes in ovarian steroidogenesis that are critical for normal cycling. Androgen effects on follicle development have been incorporated into clinical practice in women with diminished ovarian reserve, albeit with limited success in available literature. At the other extreme, androgen excess leads to disordered follicle development and anovulatory infertility known as polycystic ovary syndrome (PCOS), with studies suggesting that theca cell AR may mediate many of these negative effects. Finally, both prenatal and postnatal animal models of androgen excess have been developed and are being used to study the pathophysiology of PCOS both within the ovary and with regard to overall metabolic health. Taken together, current scientific consensus is that a careful balance of androgen activity in the ovary is necessary for reproductive health in women.


Effects of menstrual cycle phase on associations between the error-related negativity and checking symptoms in women

Abstract: The menstrual cycle is known to impact mood and cognitive function and has been shown to lead to variability in symptoms of obsessive-compulsive disorders and anxiety. Using a within-subject design, the present study examined ovarian hormones, the error-related negativity (ERN), and self-reported checking symptoms in both the mid-follicular and mid-luteal phases of the menstrual cycle. ERN amplitude and checking symptom severity did not vary between the follicular and luteal phases. However, a more negative ERN was associated with greater checking symptoms in the luteal phase of the menstrual cycle, even when controlling for ERN amplitude in the follicular phase. Moreover, changes in checking symptoms between phases were associated with phase-related changes in the ERN. Finally, a significant mediation model was found such that the ERN measured in the luteal phase mediated the association between progesterone in the luteal phase and checking symptoms in the luteal phase. Collectively, the present findings suggest that levels of progesterone in the luteal phase could impact checking symptoms by modulating response monitoring and sensitivity to errors, and that fluctuation in the ERN between menstrual cycle phases may play an important role in the expression of anxious and obsessive-compulsive symptoms.


Parity and lactation are not associated with incident fragility fractures or  radiographic vertebral fractures over 16 years of follow-up: Canadian Multicentre  Osteoporosis Study (CaMos)

William D Leslie

University of Manitoba, Winnipeg, MB, Canada

Linda Probyn

Department of Medical ImagingUniversity of TorontoTorontoONCanada

Jerilynn C Prior

Vancouver Hospital and Health Sciences Centre

Christopher S Kovacs

Memorial University of Newfoundland, St John’s, NL, Canada

Abstract:
Parity and lactation showed no associations with incident clinical fragility fractures or radiographic vertebral compression fractures in the 16-year CaMos prospective study. Parity was associated with slightly greater decline in femoral neck but not hip or spine areal bone mineral density (aBMD), while lactation showed no associations with aBMD change.
Purpose: Pregnancy and especially lactation cause loss of bone mass and microarchitectural changes, which temporarily increase fracture risk. After weaning, aBMD increases but skeletal microarchitecture may be incompletely restored. Most retrospective clinical studies found neutral or even protective associations of parity and lactation with fragility fractures, but prospective data are sparse. CaMos is a randomly selected observational cohort that includes ~ 6500 women followed prospectively for over 16 years.

Methods: We determined whether parity or lactation were related to incident clinical fragility fractures over 16 years, radiographic (morphometric and morphologic) vertebral fractures over 10 years, and aBMD change (spine, total hip, and femoral neck) over 10 years. Parity and lactation duration were analyzed as continuous variables in predicting these outcomes using univariate and multivariate regression analyses.

Results: Three thousand four hundred thirty-seven women completed 16 years of follow-up for incident clinical fractures, 3839 completed 10 years of morphometric vertebral fracture assessment, 3788 completed 10 years of morphologic vertebral fracture assessment, and 4464 completed 10 years of follow-up for change in aBMD. In the multivariate analyses, parity and lactation duration showed no associations with clinical fragility fractures, radiographic vertebral fractures, or change in aBMD, except that parity associated with a probable chance finding of a slightly greater decline in femoral neck aBMD.

Conclusions: Parity and lactation have no adverse associations with clinical fragility or radiographic vertebral fractures, or the rate of BMD decline over 10 years, in this prospective, multicenter study of a randomly selected, population-based cohort of women.


Risk assessment due to dermal exposure of trace elements and indigo dye in jeans: Migration to artificial sweat

Abstract: The concentration of a number of trace elements (Ag, Al, As, B, Ba, Be, Bi, Cd, Cr, Co, Cu, Fe, Mg, Mn, Mo, Ni, Pb, Sb, Sc, Se, Sm, Sr, Sn, Tl, Ti, V and Zn) were determined in 42 commercialized denim garments (jeans and shirts), being dermal exposure subsequently assessed. Migration experiments with artificial acid and basic sweat were also conducted to determine the release of these elements, as well as indigo dye. In a similar way than for the total content, Mg (124 and 99.4 µg/g) and Mn (27.1 and 7.20 µg/g) showed the highest concentrations in both artificial sweat, acid and basic, respectively. Indigo dye migrated at levels ranged from 3.22 to 7.76 mg/g, being higher in dark than in light blue fabrics. The levels of trace elements and indigo were analysed according to materials of fabric, colour, brand, and eco-labelling. Using total content and migrations rates, dermal exposure to trace elements for adult men, women and teenagers were calculated under the two sweat extractions. Non-carcinogenic and carcinogenic risks due to dermal exposure to the elements here analysed in cloths were assessed. Both risks were in the limits of safe to according to international regulations. However, the maximum exposure to Sb reached a hazard quotient (HQ) of 0.3 in clothes partially made of polyester. Despite some authors have established that indigo is an agonist of the aril receptor, health risks due to exposure to indigo dye were not calculated due the lack of toxicological data.


Clothing-Mediated Exposures to Chemicals and Particles

Abstract: A growing body of evidence identifies clothing as an important mediator of human exposure to chemicals and particles, which may have public health significance. This paper reviews and critically assesses the state of knowledge regarding how clothing, during wear, influences exposure to molecular chemicals, abiotic particles, and biotic particles, including microbes and allergens. The underlying processes that govern the acquisition, retention, and transmission of clothing-associated contaminants and the consequences of these for subsequent exposures are explored. Chemicals of concern have been identified in clothing, including byproducts of their manufacture and chemicals that adhere to clothing during use and care. Analogously, clothing acts as a reservoir for biotic and abiotic particles acquired from occupational and environmental sources. Evidence suggests that while clothing can be protective by acting as a physical or chemical barrier, clothing-mediated exposures can be substantial in certain circumstances and may have adverse health consequences. This complex process is influenced by the type and history of the clothing; the nature of the contaminant; and by wear, care, and storage practices. Future research efforts are warranted to better quantify, predict, and control clothing-related exposures.


Can Menopause Prediction Be Improved With Multiple AMH Measurements? Results From  the Prospective Doetinchem Cohort Study

Marinus J C Eijkemans

Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, CX Utrecht, Netherlands

W M Monique Verschuren

National Institute for Public Health and the Environment

Annelien C de Kat

Department of Reproductive Medicine and Gynecology, University Medical Center Utrecht, CX Utrecht, Netherlands.

Abstract:
Context: Anti-Müllerian hormone (AMH) levels are used worldwide as a screening tool for the duration of the female reproductive lifespan. Although AMH levels are associated with age at menopause, individual predictions of menopause with a single AMH measurement are unreliable.

Objective: This study investigated whether individual AMH decline patterns can improve the prediction of menopause compared with a single measurement.
Design: The study population comprised 2434 premenopausal women from the population-based Doetinchem Cohort Study. Participants were followed up every 5 years for a total of 20 years, and AMH was measured in 6699 plasma samples with the picoAMH assay. Longitudinal statistical modeling was combined with time varying Cox modeling, to integrate multiple AMH measurements per woman.

Results: The mean age at menopause was 50 years, and 7.4% of the women who reached menopause during follow-up did so before age 45 years. For a 25-year-old, the AMH decline rate between ages 20 and 25 years increased the C-statistic of menopause prediction from 0.64 to 0.69. Beyond that age, the AMH decline rate did not improve predictions of menopause or early menopause. For women younger than age 30 years, for whom menopause prediction is arguably most relevant, the models underestimated the risk of early menopause.

Conclusion: These results suggest that knowledge of the AMH decline rate does not improve the prediction of menopause. Based on the low discriminative ability and underestimation of the risk of early menopause, the use of AMH as a screening method for the timing of menopause cannot currently be advocated.

The Journal of Clinical Endocrinology and Metabolism


Wearable Sensors Reveal Menses-Driven Changes in Physiology and Enable Prediction  of the Fertile Window: Observational Study

Abstract:
Background: Previous research examining physiological changes across the menstrual cycle has considered biological responses to shifting hormones in isolation. Clinical studies, for example, have shown that women's nightly basal body temperature increases from 0.28 to 0.56 ˚C following postovulation progesterone production. Women's resting pulse rate, respiratory rate, and heart rate variability (HRV) are similarly elevated in the luteal phase, whereas skin perfusion decreases significantly following the fertile window's closing. Past research probed only 1 or 2 of these physiological features in a given study, requiring participants to come to a laboratory or hospital clinic multiple times throughout their cycle. Although initially designed for recreational purposes, wearable technology could enable more ambulatory studies of physiological changes across the menstrual cycle. Early research suggests that wearables can detect phase-based shifts in pulse rate and wrist skin temperature (WST). To date, previous work has studied these features separately, with the ability of wearables to accurately pinpoint the fertile window using multiple physiological parameters simultaneously yet unknown.

Objective: In this study, we probed what phase-based differences a wearable bracelet could detect in users' WST, heart rate, HRV, respiratory rate, and skin perfusion. Drawing on insight from artificial intelligence and machine learning, we then sought to develop an algorithm that could identify the fertile window in real time.

Methods: We conducted a prospective longitudinal study, recruiting 237 conception-seeking Swiss women. Participants wore the Ava bracelet (Ava AG) nightly while sleeping for up to a year or until they became pregnant. In addition to syncing the device to the corresponding smartphone app daily, women also completed an electronic diary about their activities in the past 24 hours. Finally, women took a urinary luteinizing hormone test at several points in a given cycle to determine the close of the fertile window. We assessed phase-based changes in physiological parameters using cross-classified mixed-effects models with random intercepts and random slopes. We then trained a machine learning algorithm to recognize the fertile window.

Results: We have demonstrated that wearable technology can detect significant, concurrent phase-based shifts in WST, heart rate, and respiratory rate (all P<.001). HRV and skin perfusion similarly varied across the menstrual cycle (all P<.05), although these effects only trended toward significance following a Bonferroni correction to maintain a family-wise alpha level. Our findings were robust to daily, individual, and cycle-level covariates. Furthermore, we developed a machine learning algorithm that can detect the fertile window with 90% accuracy (95% CI 0.89 to 0.92).

Conclusions: Our contributions highlight the impact of artificial intelligence and machine learning's integration into health care. By monitoring numerous physiological parameters simultaneously, wearable technology uniquely improves upon retrospective methods for fertility awareness and enables the first real-time predictive model of ovulation.


SUN-537 Progesterone Therapy and Serum Sclerostin Levels in Healthy Menopausal Women: A 3-month Randomized, Placebo Controlled Clinical Trial

Dharani Kalidasan

University of British Columbia, Vancouver, BC, Canada

Abstract: Sclerostin is an osteocyte-produced glycoprotein that inhibits the WNT/β-catenin pathway essential for bone formation. Sclerostin was postulated to relate to normal bone metabolism in 2001; we still have an incomplete understanding of its regulation. Estradiol, a bone antiresorptive ovarian steroid, inhibits sclerostin. Estrogen and progesterone act together in menstrual cycles and bone remodelling with progesterone exerting an anabolic effect. We hypothesized a relationship between progesterone and sclerostin because progesterone and estrogen are “partner” hormones in most tissues, and because progesterone and sclerostin modulate bone formation in opposite directions. Two observational menstrual cycle studies have reported sclerostin levels; neither documented changes across cycles nor in luteal phases during which progesterone levels are high(1)(,2). Some reports have also shown positive correlations between sclerostin and age and BMI. In this study, sclerostin was measured using an assay (MSD) of high sensitivity (LOD ± 1pg/mL), broad detection range (1-10 000 pg/mL), and intra/inter-assay precisions of 6% and 10% respectively(3). We collected fasting serum during a 3-month double blind randomized controlled trial (RCT) of 300 mg oral micronized progesterone vs placebo in symptomatic menopausal women; progesterone significantly decreased hot flushes/night sweats (vasomotor symptoms, VMS)(4). Statistical analysis showed sclerostin was not related to the 28-day baseline VMS Score (r=.18, p=.22). Pearson correlation coefficients were used to evaluate sclerostin vs baseline data and ANCOVA to analyze RCT results (alpha=0.05 significant, [SD]). The study’s purpose was to determine if sclerostin levels changed during a 3-month RCT of progesterone for VMS in healthy menopausal women(3). The primary outcome was sclerostin level in the 3(rd) month adjusted for baseline and randomization. Results showed the 52 participating women had a mean age of 55.2 (4.6) years, height 1.60 (0.07) m, weight 66.4 (8.6) kg, BMI 24.9 (2.9) kg/m(2) and were primarily Caucasian (91.2%). Baseline variables did not correlate with the baseline mean serum sclerostin level of 27.9 (10.2) pmol/L. Sclerostin had no statistically significant relationship with progesterone or placebo therapy during this RCT; mean changes were -1.07 and -2.60 pmol/L respectively. These data are the first evidence that progesterone neither increases nor decreases serum sclerostin levels. These data fit with the lack of menstrual cycle changes in sclerostin levels(1)(,2). That sclerostin did not correlate with age and BMI in this RCT is likely due to their low trial variance. A limitation of this study is the small sample size. However, it has considerable strength in its RCT design that can document causation. (1)Cidem M Gyn Obstetric Invest. 2012; (2)Liakou CG Endocrine 2016; (3)Van Lierop AH J Bone Miner Res 2011; (4)Hitchcock CL Menopause 2012.


MON-LB042 Health-Related Quality of Life in Women with Polycystic Ovary Syndrome/Anovulatory Androgen Excess versus Local Population-Based Control Women (from the British Columbia Canadian Multicentre Osteoporosis Study [BC CaMos])

Abstract: Polycystic Ovary Syndrome (PCOS) affects 5-20% of reproductive-aged women and is associated with lower Health-Related Quality of Life (HRQoL)1,2,3. HRQoL in PCOS, however, is often determined in small or clinical samples with no or convenience sample controls. Our aim was to cross-sectionally compare generic SF-36 HRQoL results in community dwelling, physician-diagnosed women with PCOS to randomly selected age-similar local women. Women with PCOS/AAE had enrolled in two local studies (n = 93)4, and were eligible if they were non-menopausal and had PCOS based on Androgen Excess/PCOS Society criteria. Eligibility in both groups required age ≤53 years and, for controls, menstruation in the last year. Control women were from both Adult and Youth BC CaMos cohorts (n = 56). All completed the interviewer-administered CaMos questionnaire5. Statistical analysis used descriptive, T-test and multiple regression to explore relationships among HRQoL domains/component scores versus demographic, anthropomorphic and comorbid condition variables, particularly body mass index (BMI), physical activity patterns and combined hormonal contraceptive (CHC) usage. We compared SF-36 data in pre/perimenopausal women mean aged 34.5±10.0 (SD) years, BMI 27.5±7.5. After controlling for BMI, education, comorbidities and past use of CHC, all HRQoL domain and component scores were significantly lower in women with PCOS then in controls. Domain score differences of 5 are clinically important; PCOS women scored -5.8 to -19.9 points lower (mean -11.6) with the greatest difference for Emotional Role. The Physical Component summary score was -2.2 and the Mental Component summary -7.2 lower in women with PCOS compared with population-based controls; score differences of 2-3 are considered clinically important. In both groups, participation in regular exercise was the strongest predictor of higher overall HRQoL. In both cohorts, comorbidity negatively predicted the physical component score (PCS) of HRQoL; PCOS status negatively predicted the mental component score of HRQoL. PCS group differences became less significant as BMI increased, but MCS remained significantly different. This first comparison of the validated, generic SF-36 in pre/perimenopausal population-based versus women with PCOS documented highly significantly lower scores in women with PCOS on all domains and both components. These data confirm evidence that participation in regular exercise is related to better overall HRQoL in PCOS. Also, obesity in women with PCOS, in contrast to controls, was not associated with the overall HRQoL. We also found that CHC was associated with general health, mental health and mental component scores in women with PCOS. Ref.1Prior JCEM 2014; 2Alvarez-Blasco Clin Endo 2010; 3Azziz Fertil Steril 2009; 4Kalyan Sci Reports 2017; 5Kreiger Can J. Aging 1999. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. Abstracts presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.


Prolactin concentration in various stages of endometriosis in infertile women

Abstract:
Objective: The relation between excessive prolactin and endometriosis-related infertility is debatable. Anovulation or defective luteal phase occurs frequently due to hyperprolactinemia in subfertile women. In this investigation, we evaluated the association between serum prolactin levels and the severity of endometriosis.

Methods: This retrospective cohort study carried out at the Babol Infertility Research Center looked into the baseline serum prolactin levels of 114 infertile women with endometriosis and compared them to the levels seen in 101 infertile women without endometriosis (controls). Statistical analysis included independent t-test, chi-square, Welch test and ROC curve analysis.

Results: Infertile women with endometriosis had significantly higher serum prolactin levels than infertile women without endometriosis (p=0.003). A significant difference was detected between controls and individuals with endometriosis stages III/IV (p-value=0.009). Prolactin was found to have diagnostic value to detect endometriosis stages III/IV vs. stages I/II in AUC=0.65, 95% CI (0.55, 0.76). Prolactin values with a cut off set at 20.08 ng/mL had a sensitivity of 0.74 and specificity of 0.54 in detecting disease stages III/IV vs. I/II. The prognostic capability of prolactin in detecting endometriosis in cases vs. controls by ROC curve analysis had an AUC=+0.67, 95% CI (0.60, 0.74). Prolactin values with a cut off set at 17.5 ng/mL had a sensitivity of 0.64 and specificity of 0.63 in segregating subjects with and without endometriosis.

Conclusion: Higher prolactin levels were observed in infertile women with more severe endometriosis when compared to infertile women without endometriosis. Prolactin levels act as a probable prognostic biomarker to detect endometriosis stages III/IV vs. I/II and segregate infertile women with endometriosis from subjects without endometriosis.


Systemic administration of low-dose naltrexone increases bone mass due to blockade of opioid growth factor receptor signaling in mice osteoblasts

Abstract:
AIMS: Opioid receptor blockers such as naloxone and naltrexone have been suggested to have a bone mass-increasing effect. However, the mechanisms at play have not been clarified. We examined the effects of naltrexone on osteoblasts and determined the expression of opioid growth factor receptor (OGFR) in osteoblasts. Naltrexone blocks the OGFR and other canonical opioid receptors. Thus, we designed experiments to clarify the effects of naltrexone on bone tissue by examining the physiological role of OGFR signaling in osteoblasts and the changes in bone structure after naltrexone systemic administration in mice.

MAIN

METHODS: We used mouse osteoblast-like cell line MC3T3-E1 for in vitro experiments. We cultured MC3T3-E1 cells in the presence of the OGFR agonist met-enkephalin (met-enk). Then, we measured cell proliferation activity and analyzed the expression levels of cell proliferation-related genes. For our in vivo experiments, we administered naltrexone intraperitoneally to mice daily for 28 days and administered the animals in the control group equivalent volumes of saline. After sacrificing the mice, we performed micro-computed tomography and bone morphology analyses.

KEY

FINDINGS: Met-enk suppressed cell proliferation in MC3T3-E1 cells. Moreover, Low dose naltrexone administration significantly increased their femoral bone mass, bone formation ratio, and osteoblast number/bone surface values when comparing the values for the same variables in the control group.

SIGNIFICANCE: Our results suggest that naltrexone increases bone mass due to osteoblast number increments caused by the OGFR signaling block. Opioid receptor blockers have potential as therapeutic agents for osteoporosis as well as opioid antagonists.


Clinical diagnosis of endometriosis: a call to action

Abstract: Endometriosis can have a profound impact on women's lives, including associated pain, infertility, decreased quality of life, and interference with daily life, relationships, and livelihood. The first step in alleviating these adverse sequelae is to diagnose the underlying condition. For many women, the journey to endometriosis diagnosis is long and fraught with barriers and misdiagnoses. Inherent challenges include a gold standard based on an invasive surgical procedure (laparoscopy) and diverse symptomatology, contributing to the well-established delay of 4-11 years from first symptom onset to surgical diagnosis. We believe that remedying the diagnostic delay requires increased patient education and timely referral to a women's healthcare provider and a shift in physician approach to the disorder. Endometriosis should be approached as a chronic, systemic, inflammatory, and heterogeneous disease that presents with symptoms of pelvic pain and/or infertility, rather than focusing primarily on surgical findings and pelvic lesions. Using this approach, symptoms, signs, and clinical findings of endometriosis are anticipated to become the main drivers of clinical diagnosis and earlier intervention. Combining these factors into a practical algorithm is expected to simplify endometriosis diagnosis and make the process accessible to more clinicians and patients, culminating in earlier effective management. The time has come to bridge disparities and to minimize delays in endometriosis diagnosis and treatment for the benefit of women worldwide.

American Journal of Obstetrics and Gynecology


The role of the midwife in the therapy of infertility in Poland in the opinion of patients

Abstract: Background. Infertility is a disease of the reproductive system manifesting with the inability to get pregnant within a minimum of 12 months. In diagnosing infertility and the therapeutic process, pharmacotherapy, surgery and assisted reproductive technology are used. In Poland, the NaProTechnology program is also available, which is a diagnostic and therapeutic method of reproductive health disorders without utilizing assisted reproduction. The midwife can play an important role in the care of the infertile couple.


Role of maternal age and pregnancy history in risk of miscarriage: prospective register based study

A J Wilcox

Epidemiology Branch, National Institute of Environmental Health Sciences, PO Box 12233, Research Triangle Park, NC 27709, USA

C R Weinberg

Abstract: OBJECTIVES: To estimate the burden of miscarriage in the Norwegian population and to evaluate the associations with maternal age and pregnancy history. DESIGN: Prospective register based study. SETTING: Medical Birth Register of Norway, the Norwegian Patient Register, and the induced abortion register. PARTICIPANTS: All Norwegian women that were pregnant between 2009-13. MAIN OUTCOME MEASURE: Risk of miscarriage according to the woman's age and pregnancy history estimated by logistic regression. RESULTS: There were 421,201 pregnancies during the study period. The risk of miscarriage was lowest in women aged 25-29 (10%), and rose rapidly after age 30, reaching 53% in women aged 45 and over. There was a strong recurrence risk of miscarriage, with age adjusted odds ratios of 1.54 (95% CI 1.48 to 1.60) after one miscarriage, 2.21 (2.03 to 2.41) after two, and 3.97 (3.29 to 4.78) after three consecutive miscarriages. The risk of miscarriage was modestly increased if the previous birth ended in a preterm delivery (aOR 1.22, 95% CI 1.12 to 1.29), stillbirth (1.30, 1.11 to 1.53), caesarean section (1.16, 1.12 to 1.21), or if the woman had gestational diabetes in the previous pregnancy (1.19, 1.05 to 1.36). The risk of miscarriage was slightly higher in women who themselves had been small for gestational age (1.08, 1.04 to 1.13). CONCLUSIONS: The risk of miscarriage varies greatly with maternal age, shows a strong pattern of recurrence, and is also increased after some adverse pregnancy outcomes. Miscarriage and other pregnancy complications might share underlying causes, which could be biological conditions or unmeasured common risk factors.


Developing and trialling a school-based ovulatory-menstrual health literacy programme for adolescent girls: a quasi-experimental mixed-method protocol

Abstract:
INTRODUCTION: A review of international and Australian school-based resources suggests that teaching of the ovulatory-menstrual (OM) cycle is predominantly couched in biology. A whole-person framework that integrates spiritual, intellectual, social and emotional dimensions with the physical changes of the OM cycle is needed to facilitate adolescent OM health literacy. This paper describes the protocol for a study that aims to develop and trial an intervention for adolescent girls aged 13-16 years that enhances positive attitudes towards OM health coupled with developing skills to monitor and self-report OM health. These skills aim to foster acceptance of the OM cycle as a 'vital sign' and facilitate confident communication of common OM disturbances (namely, dysmenorrhoea, abnormal uterine bleeding and premenstrual syndrome), which are known to impact school and social activities.

METHODS AND ANALYSIS: Phase I will comprise a Delphi panel of women's health specialists, public health professionals and curriculum consultants and focus groups with adolescent girls, teachers and school healthcare professionals. This will inform the development of an intervention to facilitate OM health literacy. The Delphi panel will also inform the development of a valid and reliable questionnaire to evaluate OM health literacy. Phase II will trial the intervention with a convenience sample of at least 175 adolescent girls from one single-sex school. The mixed-method evaluation of the intervention will include a pre-intervention and post-intervention questionnaire. One-on-one interviews with teachers and school healthcare professionals will expand the understanding of the barriers, enablers and suitability of implementation of the intervention in a school-based setting. Finally, focus groups with purposively selected trial participants will further refine the intervention.

ETHICS AND DISSEMINATION: The study findings will be disseminated through local community seminars, conferences, peer-review articles and media channels where appropriate. The Curtin University of Human Research Ethics Committee has approved this study (approval HRE2018-0101). This project is registered with the 'Australian and New Zealand Clinical Trials Registry'.

TRIAL REGISTRATION NUMBER: ACTRN12619000031167; Pre-results.


Perfect- and typical-use effectiveness of the Dot fertility app over 13 cycles:  results from a prospective contraceptive effectiveness trial

Jeff Spieler

Independent Consultant in Population and Reproductive Health, Bethesda, MD, USA

Abstract:
Objective: Dynamic Optimal Timing (Dot) is a smartphone application (app) that estimates the menstrual cycle fertile window based on the user's menstrual period start dates. Dot uses machine learning to adapt to cycles over time and informs users of 'low' and 'high' fertility days. We investigated Dot's effectiveness, calculating perfectand typical-use failure rates.

Methods: This prospective, 13 cycle observational study (ClinicalTrials.gov NCT02833922) followed 718 women who were using Dot to prevent pregnancy. Participants contributed 6616 cycles between February 2017 and October 2018, providing data on menstrual period start dates, daily sexual activity and prospective intent to prevent pregnancy. We determined pregnancy through participant-administered urine pregnancy tests and/or written or verbal confirmation. We calculated perfectand typical-use failure rates using multi-censoring, single-decrement life-table analysis, and conducted sensitivity, attrition and survival analyses.

Results: The perfect-use failure rate was calculated to be 1.0% (95% confidence interval [CI]: 0.9%, 2.9%) and the typical-use failure rate was 5.0% (95% CI: 3.4%, 6.6%) for women aged 18-39 (n = 718). Survival analyses identified no significant differences among age or racial/ethnic groups or women in different types of relationships. Attrition analyses revealed no significant sociodemographic differences, except in age, between women completing 13 cycles and those exiting the study earlier.

Conclusion: Dot's effectiveness is within the range of other user-initiated contraceptive methods.

The European Journal of Contraception & Reproductive Health Care : the Official  Journal of the European Society of Contraception


The role of lymphocytes in fetal development and recurrent pregnancy loss

Jan Modzelewski

Postgraduate School of Molecular Medicine

Abstract: Fetal survival and development is supported by the maternal immune system. Questions regarding those mechanisms have risen from development of transplantation medicine and observation of graft rejection. Initial theories of anatomic division, fetal immune immaturity and maternal immune system inertia were found incorrect. Rejection of fetal "semi-allograft" by maternal immune system could result in pregnancy loss. Two pregnancy losses of any etiology are considered recurrent and effort should be made to name the probable cause. Immune causes of pregnancy loss are probably multifactorial, thus difficult to research and implement findings in clinical practice. Although a full understating of pregnancy loss is not established, new therapies are being developed. This review summarizes the role of lymphocytes in pregnancy development, presents data from studies on recurrent pregnancy loss patients, evidence of new therapies and ESHRE guidelines regarding immunologic investigations.


Uterine scar rupture - Prediction, prevention, diagnosis, and management

Abstract: The increasing rate of elective and indicated caesarean sections worldwide has led to new pathologies and management challenges. The number of patients undergoing trial of labor after caesarean section (TOLAC) is also increasing. Three professional societies provide detailed guidelines based on scientific evidence for the management of patients attempting vaginal birth after caesarean section (VBAC). However, they do not provide any recommendations for the actual surgical steps to be followed to minimize the risks of uterine rupture (UR) during TOLAC. Uterine scar condition, intrapartum management and maternal health status correlate to uterine scar rupture risk and provide guidance for parturient TOLAC eligibility. TOLAC and vaginal delivery success rate as reported by the largest studies is between 60% and 77%. Uterine rupture is more prevalent in VBAC-2 patients (1.59%) in contrast to VBAC-1 (0.72%). Additionally, VBAC-2 patients have higher incidence of caesarean hysterectomy 0.56% vs. 0.19% for VBAC-1. The chances of successful VBAC increase when the interpregnancy/interdelivery interval is less than 6.3 years and less than 24 months, respectively. No difference was detected between the techniques of uterine incision closure of the previous CS and TOLAC results, although closure of the CS uterine incision in 2 layers seems to be practiced more widely. Niche or isthmocele presents another complication of CS. Secondary infertility due to niche, will eventually direct to hysteroscopic or laparoscopic repair, depending on the residual myometrial thickness (RMT) as measured by US scan. When RMT is below 3 mm or 2.5 mm surgery can be performed, to prevent any spontaneous UR in case of pregnancy. Monitoring by US scanning of hysterotomy scar after myomectomy can detect hematoma. In patients with severe postoperative pain but hemodynamically stable follow up by US scan examination can direct the management decision. In those patients with active bleeding and deterioration of hysterotomy scar edema will be an indication to surgery. There is no firm evidence regarding which type of thread, knotting or sequence of suturing is more favorable to reduce the risk of UR after VBAC or hysterotomy after myomectomy.

Best Practice & Research. Clinical Obstetrics & Gynaecology


Association of maternal prenatal acetaminophen use with the risk of attention deficit/hyperactivity disorder in offspring: A meta-analysis

Abstract:
BACKGROUND: Acetaminophen is a widely used medication for fever and pain management during pregnancy. However, recent studies have found a possible connection between maternal prenatal acetaminophen use and attention deficit/hyperactivity disorder in children.

OBJECTIVE: We aimed to explore the association between maternal acetaminophen use during pregnancy and the risk of attention deficit/hyperactivity disorder in offspring.

DATA SOURCES: PubMed, Embase, Web of Science and Cochrane Library were searched from their initial publications through November 2018 for studies.

STUDY SELECTION: We included all studies that examined the association between maternal acetaminophen use during pregnancy and the risk of attention deficit/hyperactivity disorder in offspring if the authors reported odds ratios, risk ratios, hazard ratios, regression coefficient, standard error and 95% confidence intervals.

DATA EXTRACTION AND SYNTHESIS: Two reviewers independently extracted data on the definition of exposure and outcome, exposed, non-exposed and total number of participants in the sample population, adjusted potential confounders and outcome parameters. Study quality was also assessed.

RESULTS: Eight cohort studies with a total of 244,940 participants were included. Maternal exposure to acetaminophen during pregnancy increased the risk of attention deficit/hyperactivity disorder in offspring with a pooled adjusted risk ratio of 1.25 (95% confidence interval = [1.17, 1.34]). Children exposed prenatally to acetaminophen in the third trimester seemed to have the greatest risk of developing attention deficit/hyperactivity disorder (risk ratio: 1.26; 95% confidence interval = [1.08, 1.47]). In addition, a longer duration of maternal acetaminophen use during pregnancy was correlated with a higher risk ratio. Children whose mothers used acetaminophen for 28 or more days during gestation had a higher risk of developing attention deficit/hyperactivity disorder (risk ratio: 1.63; 95% confidence interval = [1.23, 2.16]).

CONCLUSION: There is an association between maternal acetaminophen use during pregnancy and the risk of attention deficit/hyperactivity disorder in offspring. The timing and duration of acetaminophen use during pregnancy may have a major effect on the risk of attention deficit/hyperactivity disorder.

The Australian and New Zealand journal of psychiatry


Increased Preeclampsia Risk and Reduced Aortic Compliance With In Vitro Fertilization Cycles in the Absence of a Corpus Luteum

Abstract: In vitro fertilization involving frozen embryo transfer and donor oocytes increases preeclampsia risk. These in vitro fertilization protocols typically yield pregnancies without a corpus luteum (CL), which secretes vasoactive hormones. We investigated whether in vitro fertilization pregnancies without a CL disrupt maternal circulatory adaptations and increase preeclampsia risk. Women with 0 (n=26), 1 (n=23), or >1 (n=22) CL were serially evaluated before, during, and after pregnancy. Because increasing arterial compliance is a major physiological adaptation in pregnancy, we assessed carotid-femoral pulse wave velocity and transit time. In a parallel prospective cohort study, obstetric outcomes for singleton livebirths achieved with autologous oocytes were compared between groups by CL number (n=683). The expected decline in carotid-femoral pulse wave velocity and rise in carotid-femoral transit time during the first trimester were attenuated in the 0-CL compared with combined single/multiple-CL cohorts, which were similar (group-time interaction: P=0.06 and 0.03, respectively). The blunted changes of carotid-femoral pulse wave velocity and carotid-femoral transit time from prepregnancy in the 0-CL cohort were most striking at 10 to 12 weeks of gestation ( P=0.01 and 0.006, respectively, versus 1 and >1 CL). Zero CL was predictive of preeclampsia (adjusted odds ratio, 2.73; 95% CI, 1.14-6.49) and preeclampsia with severe features (6.45; 95% CI, 1.94-25.09) compared with 1 CL. Programmed frozen embryo transfer cycles (0 CL) were associated with higher rates of preeclampsia (12.8% versus 3.9%; P=0.02) and preeclampsia with severe features (9.6% versus 0.8%; P=0.002) compared with modified natural frozen embryo transfer cycles (1 CL). In common in vitro fertilization protocols, absence of the CL perturbed the maternal circulation in early pregnancy and increased the incidence of preeclampsia.


Anaemia and depletion of iron stores as risk factors for postpartum depression: a literature review

Abstract:
PURPOSE: Iron-deficiency and anaemia are common in pregnant and postpartum women because of increasing iron demand and blood loss. Many women also enter pregnancy with pre-depleted iron stores. We reviewed the evidence linking anaemia and/or iron-deficiency to postpartum depression (PPD).

METHODS: We identified seventeen studies in four databases including randomized-controlled trials (RCTs) and observational studies assessing the impact of anaemia, iron-deficiency and iron supplementation on the risk of PPD. We extracted data on sample size, geographical region, obstetrical complications, measures of depression, haemoglobin, iron levels and intake of iron supplementation and critically appraised the results from the studies.

RESULTS: Eight out of ten studies found higher risk for PPD (r - 0.19 to -0.43 and ORs 1.70-4.64) in anaemic women. Low ferritin in the postpartum period but not during pregnancy was associated with increased risk of PPD. Iron supplementation in the postpartum period decreased risk of PPD in four out of five studies, whereas it did not protect from PPD if given during pregnancy. Limitations include study heterogeneity, discrepancy of prevalence of PPD and usage of a screening tool for evaluation of PPD.

CONCLUSION: Anaemia and/or iron-deficiency may contribute to PPD in at-risk women. Further studies should elucidate the association between these entities.

Journal of psychosomatic obstetrics and gynaecology


Zinc status and polycystic ovarian syndrome: A systematic review and meta-analysis

Abstract: Several studies have investigated serum zinc levels in patients with polycystic ovarian syndrome (PCOS), but the results of these studies remain inconclusive. Therefore, to derive a more precise estimation, we conducted a meta-analysis to investigate serum zinc concentrations in women with PCOS in comparison with healthy subjects. Electronic search was performed in PubMed, Scopus, and Google scholar up to April; 4, 2018 without any restriction. Eligible studies that evaluated the levels of zinc status in subjects with PCOS were included. Weighted mean differences (WMDs) with corresponding 95% CIs in serum zinc levels were initially estimated using a random-effects model. Eight studies, measuring circulating zinc levels in 552 PCOS and 464 control subjects, were included. Pooled effect size suggested that serum zinc levels in women with PCOS were not statistically different than their controls (WMD = -4.43 mg/dL; 95% CI = [-10.30, 1.44]; P = 0.139). Exclusion of one study revealed that women with PCOS significantly have lower serum zinc levels compared to healthy controls (WMD: -6.60 mg/dL; 95% CI = [-12.43, -0.76], P = 0.027). Our study indicated that circulating zinc levels in women with PCOS were significantly lower than those in healthy controls when detailed analysis is conducted. Large scale studies are needed to elucidate clear relation between zinc status and etiology of PCOS.

Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS)


The Radiology of Osteoporotic Vertebral Fractures Revisited

Fjorda Koromani

Department of EpidemiologyUniversity Medical Center RotterdamErasmus MCRotterdamThe Netherlands

Ling Oei

Departments of Internal Medicine and Epidemiology, Erasmus MC, Rotterdam, The Netherlands.

Fernando Rivadeneira

Departments of Internal Medicine and EpidemiologyErasmus MCRotterdamThe Netherlands

William D Leslie

University of Manitoba, Winnipeg, MB, Canada

Linda Probyn

Department of Medical ImagingUniversity of TorontoTorontoONCanada

Jerilynn C Prior

Vancouver Hospital and Health Sciences Centre

Ian Hammond

Ottawa Hospital-General Campus, Ottawa, Ontario, Canada.

Angela M Cheung

Department of Medicine and Joint Department of Medical Imaging, Centre of Excellence in Skeletal Health Assessment, University Health NetworkUniversity of TorontoTorontoONCanada

on behalf of the Vertebral Fracture Research Groups of the CaMos, STOPP, and Rotterdam Studies

Abstract: Until recently there has been little evidence available to validate any method by which to make an accurate diagnosis of an osteoporotic vertebral fractures (OVFs) from plain radiographs. In part this reflects a lack of a completely satisfactory "gold standard," but primarily it relates to the absence of well-designed prospective studies in this context. Historically, OVFs were recognized by evidence of macroscopic structural failure in vertebrae using the criteria applied elsewhere in the skeleton. This comprised altered alignment, fragmentation, cortical disruptions, and breaks, among other changes. However, these morphological criteria were replaced by vertebral morphometry, referring to the use of quantitative or quasi-quantitative measurement tools for fracture diagnosis. Vertebral morphometry emerged as an understanding of and treatment for osteoporosis evolved, mainly in response to the need for expeditious assessments of large numbers of spine images for epidemiological and pharmaceutical purposes. Although most of the descriptions of such morphometric tools have stressed that they were not to be applied to clinical diagnosis with respect to individual patients, this constraint has been widely disregarded. Here we review the major attempts to develop a diagnostic strategy for OVF and describe their characteristics in adults and children. Recent evidence suggests that morphometric (quantitative; ie, based on measurement of dimensions and shape description) criteria are inferior to morphologic (qualitative; ie, based on structural integrity) vertebral damage assessment in identifying people with low bone density and at an increased risk of future fracture. Thus there is now an evidentiary basis for suggesting that morphological assessment is the preferred strategy for use in diagnosing OVF from radiographs.


Demographic and lifestyle determinants of time spent in physical activity among  Malaysian adolescents

Hock Kuang Lim

Institute for Medical Research, Jalan Pahang, 50588 Kuala Lumpur, Malaysia.

Abstract:
BACKGROUND AND Objectives: The objective of the present study is to examine factors affecting time spent in physical activity among adolescents in Malaysia. PATIENTS AND

Methods: A nationally representative data of adolescents that consists of 25399 respondents is used. The demographic (age, gender, education) and lifestyle (fruits and vegetables consumption, carbonated soft drink consumption, cigarette smoking, alcohol drinking, sex behaviour, participation in physical education class, obesity) determinants of physical activity are assessed using binomial regression.

Results: The results show that age is negatively associated with time spent in physical activity. However, being male and education levels are positively related to time spent in physical activity. Having unhealthy lifestyle and being obese are associated with low levels of physical activity. Physical education seems to promote participation in physical activity.

Conclusion: In conclusion, demographic and lifestyle factors play an important role in determining levels of physical activity among adolescents. In order to reduce the prevalence of physically inactive adolescents, policy makers should focus primarily on late adolescents, females, adolescents who engage in unhealthy lifestyle and seldom attend physical education classes, as well as obese adolescents.

International Journal of Pediatrics & Adolescent Medicine


Hemoperitoneum after Ovulation in Systemic Lupus Erythematosus and Autoimmune  Thrombocytopenia

Cara Buskmiller

Department of Obstetrics, Gynecology, and Women’s Health, St. Louis University, St. Louis, MO, USA

Henri Rosenberg

Department of Obstetrics and Gynecology, Icahn School of Medicine at Mount Sinai, New York, NY, USA

Abstract:
Background: Three prior cases of hemoperitoneum associated with immune thrombocytopenia (ITP) have been reported in adolescents. This reports a case of hemoperitoneum after ovulation in an adult. CASE: A 34-year-old nulligravida presented with abdominal pain after a heavy period and rebound tenderness. Urine beta-hCG was negative, hemoglobin was 5.4, and platelet count was zero. CT revealed hemoperitoneum and contrast blush surrounding the left ovary. She was treated for newly diagnosed systemic lupus erythematosus and steroid-refractory ITP. Her platelet count and symptoms improved.

Conclusion: Hemoperitoneum after ovulation in ITP is rare; this represents the first adult case in the literature and reviews differential diagnosis of thrombocytopenia. The obstetrician/gynecologist is part of a multidisciplinary team caring for patients with bleeding of gynecological origin and should withhold surgical intervention for hemoperitoneum when medical therapy is warranted.

Case Reports in Obstetrics and Gynecology


Naltrexone: A History and Future Directions

Abstract: Trying to kick drug addiction without medicines is said to be like relying on willpower to overcome diabetes or asthma. Enter naltrexone, which has been around since 1984 and reduces the cravings for drugs and alcohol by fine-tuning the brain's chemical reward system. Why has it recently increased in popularity? How does it compare to similar strategies? Has it made a difference? Our authors, who have long studied addiction and the brain, confront a drug and alcohol addiction problem that today kills more Americans each day than gun violence or car accidents.

Cerebrum : the Dana Forum on Brain Science


Textile Contact Dermatitis: How Fabrics Can Induce Dermatitis

Abstract: Purpose of the review: Textile dermatitis can sometimes be difficult to diagnose due to the fact that it is difficult to clinically suspect, and when allergic, patch test correctly and advice the patient as to what garments to avoid. Recent findings: The textile fibres as such are rarely the causative agent. Allergic contact dermatitis due to textiles is primarily caused by substances that are used to give the material certain qualities or performances. The textile dye mix, now in the baseline series, has proven to be a useful tool in diagnosing allergic contact dermatitis but additional patch testing with own material is advocated. Future research will hopefully facilitate the diagnostic procedure. Summary: This review is a short update on textile dermatitis, both irritant and allergic, the present recommendations regarding patch testing when suspecting contact allergy and the advice to give to those allergic that will hopefully help the clinician in daily work.


Incident Fragility Fractures Have a Long-Term Negative Impact on Health-Related Quality of Life of Older People: The Canadian Multicentre Osteoporosis Study

Sayem Borhan

Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Canada.

Olga Gajic-Veljanoski

Hamilton Health Sciences–Geriatric Education and Research in Aging Sciences (GERAS) CentreHamiltonONCanada

Christopher S Kovacs

Memorial University of Newfoundland, St John’s, NL, Canada

Jerilynn C Prior

Vancouver Hospital and Health Sciences Centre

Angela M Cheung

Department of Medicine and Joint Department of Medical Imaging, Centre of Excellence in Skeletal Health Assessment, University Health NetworkUniversity of TorontoTorontoONCanada

Jonathan D Adachi

McMaster University, Hamilton, ON, Canada

Abstract: Although the short-term impact of incident fragility fractures on health-related quality of life (HRQL) of older people has been confirmed, we lack long-term evidence. We explored the impact of incident fragility fractures on HRQL, among people aged 50 years and older, using 10-year prospective data from the Canadian Multicentre Osteoporosis Study (CaMos). This study was based on data from 7753 (2187 men and 5566 women) participants of CaMos. The HRQL, measured through the Health Utility Index (HUI), was captured at baseline and year 10. The incident fragility fractures were recorded over 10 years of follow-up at spine, hip, rib, shoulder, pelvis, or forearm. Multivariable regression analysis was conducted to measure the mean difference, termed as deficit, in the HUI scores for participants with and without fractures. We examined the effects of single or multiple fragility fractures, time (fractures that occurred between year 1 to 5 and 6 to 10) and recovery to the prefracture level. Incident spine and hip fractures were associated with significant deficits (varied from -0.19 to -0.07) on the HUI scores. Hip and spine fractures were associated with negative impact on mobility, self-care, and ambulation. Fractures that occurred closer to the follow-up assessment were associated with significant impact on HRQL compared to fractures occurring a long time before it, except for hip fracture (deficits lasted 5 years or longer). Similarly, multiple hip (-0.14), spine (-0.16), and rib (-0.21) fractures significantly impacted the HRQL of women. Women with a hip fracture never recovered to their prefracture level score (OR = 0.41; 95% confidence interval [CI], 0.19 to 0.98). Our analysis suggests that single and multiple hip fractures as well as multiple spine and rib fractures strongly impact the HRQL of older people over a prolonged period of time.


Comparison of body weight among hormonal and non-hormonal users in a Malaysian cohort

Abstract:
OBJECTIVES: Weight gain remains an issue for contraceptive users due to the high prevalence of obesity. This retrospective study compares the weight gain between hormonal and non-hormonal contraceptive users in government health clinics in Kota Bharu, Kelantan, Malaysia.

METHODS: A total of 380 women who had used the same contraceptive method for at least twelve months were recruited in this study. Covariance analysis was done to compare the weight gain between hormonal and non-hormonal contraceptive users, while studying the same confounders [age, household income, number of pregnancies, and baseline body mass index (BMI)].

RESULTS: Hormonal methods were more commonly used. The mean weight gain among hormonal users (adjusted mean 2.85, 95% CI 2.45, 3.24) was significantly higher than non-hormonal users (adjusted mean 0.46, 95% CI -0.73, 1.65; p-value <0.001), after controlling for age, household income, number of pregnancies, and baseline BMI.

CONCLUSION: The possibility of weight gain following the use of hormonal methods should be investigated and non-hormonal methods should be considered to prevent weight gain.

أهداف البحث: لا تزال زيادة الوزن قضية، لمستخدمات وسائل منع الحمل بسبب زيادة الوزن وانتشار معدل السمنة. تهدف هذه الدراسة المرجعية لمقارنة زيادة الوزن بين موانع الحمل الهرمونية وغير الهرمونية في عيادات الصحة الحكومية في مدينة بهارو، كلنتان، ماليزيا.

طرق البحث: تم مشاركة ما مجموعه ٣٨٠ سيدة من اللواتي استخدمن نفس وسيلة منع الحمل لمدة ١٢ شهرا في هذه الدراسة. تم عمل تحليل التباين لمقارنة زيادة الوزن بين مستخدمات موانع الحمل الهرمونية وغير الهرمونية، أثناء دراسة نفس العوامل (العمر، ودخل الأسرة، وعدد مرات الحمل ومؤشر كتلة الجسم الأساسي).

النتائج: كانت الطرق الهرمونية هي الأكثر شيوعا. متوسط زيادة الوزن بين مستخدمات الهرمون (المتوسط المعدل ٢.٨، فاصل الثقة ٩٥٪ ٢.٤٥، ٣.٢٤) أعلى بكثير من مستخدمات الطرق غير الهرمونية (المتوسط المعدل ٠.٤٦، فاصل الثقة ٠.٧٣-، ١.٦٥) بعد التحكم في العمر، ودخل الأسرة، وعدد مرات الحمل ومؤشر كتلة الجسم الأساسي.

الاستنتاجات: ينبغي التحقق من إمكانية زيادة الوزن بعد استخدام الطرق الهرمونية وينبغي النظر في خيارات أخرى من الطرق غير الهرمونية للحد من زيادة الوزن.

Journal of Taibah University Medical Sciences


A Quantitative Self-Assessment of Seminarians' Response to a Curriculum Addition  on Marriage, Sexuality, FertilityCare, and Naprotechnology: The Kenrick-Glennon  Experience (2006-2015)

Edward Richárd

Our Lady of Prompt Succor, Sulphur, LA, USA.

Abstract: A special course on Marriage, the Family and Human Sexuality was established at Kenrick-Glennon Seminary in St. Louis so as to assist the seminarians in their better understanding of the Church's teaching relative to natural methods of family planning and women's health care. This article compares the response at the beginning of this three-credit semester course to the same seven-item questionnaire given at the conclusion of the course. The preand postcourse scores were calculated for each of the questions. The scores obtained after the course were all significantly higher than they were before the course with p values ranging from 0.01 to <0.0001. Four of the items showed marked improvement including an understanding of the church's teaching related to natural methods, current methods of natural family planning, the impact of a natural method on a couple's marriage, and also the impact of a natural method on family life. Statistically significant improvement was also seen in their understanding of the topic of natural family planning and the Creighton Model System and its relevance toward the seminarian's vocation, the use of the methods to either achieve or avoid pregnancy, and how contraception and abortion are linked. In these last three items, the level of statistical significance was quite high, although not as high as the other four items. There were 104 seminarians over an eight-year period of time, who provided answers to these questions, both before and after the course. This course was modeled after a course that was initiated at the Pope Paul VI Institute for the Study of Human Reproduction, which was for priests, seminarians, and Catholic leaders, titled Love & Life Unlimited. NONTECHNICAL Summary: This is an evaluation of a ten-point, seven-question questionnaire that was utilized at the beginning of a course at Kenrick Seminary in Marriage, Sexuality, Creighton Model and NaProTECHNOLOGY. The same questionnaire was given to the students at the beginning of the course and then two to three months later at the conclusion of the three-credit course. The results show that there is a significant improvement in the seminarians' knowledge and general attitude about natural methods of family planning and suggests that such courses would be beneficial to establish in seminaries throughout the country.


Frailty and Risk of Fractures in Patients With Type 2 Diabetes

William D Leslie

University of Manitoba, Winnipeg, MB, Canada

Mitchell Levine

Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada.

Abstract:
Objective: We aimed to explore whether frailty was associated with fracture risk and whether frailty could modify the propensity of type 2 diabetes toward increased risk of fractures.Research design and methodsData were from a prospective cohort study. Our primary outcome was time to the first incident clinical fragility fracture; secondary outcomes included time to hip fracture and to clinical spine fracture. Frailty status was measured by a Frailty Index (FI) of deficit accumulation. The Cox model incorporating an interaction term (frailty × diabetes) was used for analyses.

Results: The analysis included 3,149 (70% women) participants; 138 (60% women) had diabetes. Higher bone mineral density and FI were observed in participants with diabetes compared with control subjects. A significant relationship between the FI and the risk of incident fragility fractures was found, with a hazard ratio (HR) of 1.02 (95% CI 1.01-1.03) and 1.19 (95% CI 1.10-1.33) for per-0.01 and per-0.10 FI increase, respectively. The interaction was also statistically significant (P = 0.018). The HR for per-0.1 increase in the FI was 1.33 for participants with diabetes and 1.19 for those without diabetes if combining the estimate for the FI itself with the estimate from the interaction term. No evidence of interaction between frailty and diabetes was found for risk of hip and clinical spine fractures.

Conclusions: Participants with type 2 diabetes were significantly frailer than individuals without diabetes. Frailty increases the risk of fragility fracture and enhances the effect of diabetes on fragility fractures. Particular attention should be paid to diabetes as a risk factor for fragility fractures in those who are frail.


ACOG Practice Bulletin No. 206: Use of Hormonal Contraception in Women With Coexisting Medical Conditions

Abstract: Although numerous studies have addressed the safety and effectiveness of hormonal contraceptive use in healthy women, data regarding women with underlying medical conditions or other special circumstances are limited. The U.S. Medical Eligibility Criteria (USMEC) for Contraceptive Use, 2016 (), which has been endorsed by the American College of Obstetricians and Gynecologists, is a published guideline based on the best available evidence and expert opinion to help health care providers better care for women with chronic medical problems who need contraception. The goal of this Practice Bulletin is to explain how to use the USMEC rating system in clinical practice and to specifically discuss the rationale behind the ratings for various medical conditions. Contraception for women with human immunodeficiency virus (HIV) (); the use of emergency contraception in women with medical coexisting medical conditions, including obesity, (); and the effect of depot medroxyprogesterone acetate (DMPA) on bone health () are addressed in other documents from the American College of Obstetricians and Gynecologists.


Oral contraceptive use and depression among adolescents

Abstract:
Purpose: Depression is a prevalent health problem affecting U.S. women. Oral contraceptive pills (OCPs) are commonly used for pregnancy prevention, and evidence is mixed regarding any increased risk for incident depression among users, particularly adolescents.

Methods: We examined the relationship between OCP use and depressive disorders among female adolescents using validated, structured interview assessments in a general population sample of adolescents in the National Comorbidity Survey-Adolescent Supplement. Respondents were 4765 female adolescents with no history of pregnancy who reported current OCP use, lifetime OCP use, and age of OCP initiation. Lifetime and current depressive disorders, including major depressive disorder and depressive episodes, were assessed by lay interviewers.

Results: In logistic regression models adjusted for a range of confounders, there was no relationship between ever using OCPs and lifetime depressive disorder (OR 1.10, 95% CI 0.88-1.37), nor current use of OCPs and current depressive disorder (OR 0.82, 95% CI 0.50-1.35). Using survival analysis for age-of-onset data, we found that OCP use is not associated with an increased risk of depressive disorders.

Conclusions: In sum, use of OCPs in a general population sample of adolescents did not increase the risk of depressive disorders.


Isthmocele: From Risk Factors to Management

Pantaleo Greco

Department of Translational and for Romagna Medicine, University of Ferrara, 44121 Ferrara, Italy

Abstract:
Objective: The aim of the present study was to perform a comprehensive review of the literature to provide a complete and clear picture of isthmocele-a hypoechoic area within the myometrium at the site of the uterine scar of a previous cesarean section-by exploring in depth every aspect of this condition.

Methods: A comprehensive review of the literature was performed to identify the most relevant studies about this topic.

Results: Every aspect of isthmocele has been studied and described: pathophysiology, clinical symptoms, classification, and diagnosis. Its treatment, both medical and surgical, has also been reported according to the actual literature data.

Conclusion: Cesarean section is the most common surgical procedure performed worldwide, and one of the consequences of this technique is isthmocele. A single and systematic classification of isthmocele is needed to improve its diagnosis and management. Further studies should be performed to better understand its pathogenesis.

Revista Brasileira De Ginecologia E Obstetricia : Revista Da Federacao Brasileira  Das Sociedades De Ginecologia E Obstetricia


Effect of progesterone administration on the prognosis of patients with severe traumatic brain injury: a meta-analysis of randomized clinical trials

Abstract: PURPOSE: The aim of this study was to assess the neuroprotective effect of progesterone administration on severe traumatic brain injury (TBI) for different follow-up periods and administration route by completing a meta-analysis of randomized clinical trials (RCTs). METHODS: A systematic literature search of PubMed, Embase, and Cochrane databases and the Web of Science (from establishment of each to September 1, 2018) was performed to identify original RCTs that evaluated the associations between progesterone treatment and the prognosis of patients with severe TBI. RESULTS: Eight RCTs enrolling 2,251 patients with severe TBI were included. Within 3 months post-injury, patients with progesterone administration had a lower mortality (risk ratio [RR] =0.59; 95% CI [0.42-0.81], P=0.001) and better neurologic outcomes (RR =1.51; 95% CI [1.12-2.02], P=0.007) than those who received placebo. However, these differences did not persist at 6 months post-injury for mortality (RR =0.96; 95% CI [0.65-1.41], P=0.83) or neurologic outcomes (RR =1.09; 95% CI [0.93-1.27], P=0.31). The analysis stratified by administration route showed that beneficial effects were only observed in patients who received progesterone intramuscularly (RR =1.61, 95% CI [1.19-2.18], P=0.002); no benefit was observed with intravenous administration (RR =0.99, 95% CI [0.91-1.07], P=0.75). CONCLUSION: Progesterone administration improved the clinical outcomes of severe TBI patients within 3 months but may not have significant long-term benefits 6 months post-injury.


Adolescent use of combined hormonal contraception and peak bone mineral density  accrual: A meta-analysis of international prospective controlled studies

Abbey B. Berenson

The University of Texas Medical Branch at Galveston

Tatjana S Brajic

Centre for Menstrual Cycle and Ovulation Research, Medicine/Endocrinology, University of British Columbia, Vancouver, B.C., Canada.

Jerilynn C Prior

Vancouver Hospital and Health Sciences Centre

Delia Scholes

Kaiser Permanente Washington Health Research Institute

Abstract:
Objective: Many women use combined hormonal contraceptives (CHC) during adolescence during which they are accruing peak areal bone mineral density (BMD) that relates to lifetime fracture risk. To build BMD requires formation with which CHC-related exogenous oestrogen may interfere. We compared peak BMD accrual in adolescents using and not using CHC. DESIGN/

Participants: We performed literature searches for prospective published peer-reviewed articles providing 12to 24-month BMD change in adolescent (12to 19-year-old) women using CHC vs CHC-unexposed control women.

Methods: Meta-analyses used random-effects models to assess BMD change rate at lumbar spine (LS) and other sites in adolescent CHC users vs CHC nonusers.

Results: Literature searches yielded 84 publications of which nine were eligible. Adolescent-only data were sought from cohorts with wider age inclusions. The 12-month LS meta-analysis with eight paired comparisons in 1535 adolescents showed a weighted mean BMD difference of -0.02 (95% confidence interval [CI]: -0.05 to 0.00) g/cm(2) in CHC-exposed adolescents (P = 0.04). The 24-month LS meta-analysis with five paired comparisons in 885 adolescents showed a highly significant weighted mean BMD difference of -0.02 (95% CI: -0.03 to -0.01) g/cm(2) in CHC-exposed adolescents (P = 0.0006). Heterogeneities by I(2) were 96% and 85%, respectively. Insufficient data for other bone sites precluded quantitative analysis.

Conclusion: Given that adolescent exposure to CHC appears to be increasing, this evidence for potential impairment of peak spinal BMD accrual is of concern and suggests a potential public health problem. Randomized controlled trial data are needed to determine CHC effects on adolescent bone health.


Progesterone Is Important for Transgender Women's Therapy-Applying Evidence for  the Benefits of Progesterone in Ciswomen

Abstract:
Background: Although the 2017 Endocrine Society Guidelines for gender dysphoria stipulated that cross-sex hormone therapy (CHT) achieve gonadal steroid levels equivalent to those of a cisperson of the chosen sex, for transgender women (male-to-female gender dysphoria), current gonadal therapy is usually estradiol. Accumulated evidence indicates that normally ovulatory menstrual cycles are necessary for ciswomen's current fertility, as well as for later-life bone and cardiovascular health and the prevention of breast and endometrial cancers.
Evidence Acquisition: Extensive past clinical experience with transgender women's CHT using estradiol/estrogen combined with progesterone/medroxyprogesterone and pioneering the addition of spironolactone. Comprehensive progesterone physiology research plus a brief review of transgender women's literature to assess current therapy and clinical outcomes, including morbidity and mortality.

Purpose: To emphasize that both ovarian hormones, progesterone as well as estradiol, are theoretically and clinically important for optimal transgender women's CHT.
Evidence Synthesis: It is important to add progesterone to estradiol and an antiandrogen in transgender women's CHT. Progesterone may add the following: (i) more rapid feminization, (ii) decreased endogenous testosterone production, (iii) optimal breast maturation to Tanner stages 4/5, (iv) increased bone formation, (v) improved sleep and vasomotor symptom control, and (vi) cardiovascular health benefits.

Conclusions: Evidence has accrued that normal progesterone (and ovulation), as well as physiological estradiol levels, is necessary during ciswomen's premenopausal menstrual cycles for current fertility and long-term health; transgender women deserve progesterone therapy and similar potential physiological benefits.

The Journal of Clinical Endocrinology and Metabolism


Hypothalamic-Pituitary-Ovarian Axis Disorders Impacting Female Fertility

Abstract: The hypothalamic-pituitary-ovarian (HPO) axis is a tightly regulated system controlling female reproduction. HPO axis dysfunction leading to ovulation disorders can be classified into three categories defined by the World Health Organization (WHO). Group I ovulation disorders involve hypothalamic failure characterized as hypogonadotropic hypogonadism. Group II disorders display a eugonadal state commonly associated with a wide range of endocrinopathies. Finally, group III constitutes hypergonadotropic hypogonadism secondary to depleted ovarian function. Optimal evaluation and management of these disorders is based on a careful analysis tailored to each patient. This article reviews ovulation disorders based on pathophysiologic mechanisms, evaluation principles, and currently available management options.


Mortality risk reduction differs according to bisphosphonate class: a 15-year observational study

Tineke van Geel

Department of Family MedicineResearch School Care and Public Health Research Institute (CAPHRI)Maastricht UniversityMaastrichtThe Netherlands

Jonathan D Adachi

McMaster University, Hamilton, ON, Canada

Joop van den Bergh

Department of Internal MedicineVieCuri Medical Centre of Noord-LimburgVenloThe Netherlands

Christopher S Kovacs

Memorial University of Newfoundland, St John’s, NL, Canada

Jacqueline R Center

Faculty of MedicineUniversity of New South WalesSydneyAustralia

Abstract:
In this prospective cohort of 6120 participants aged 50+, nitrogen-bisphosphonates but not non-nitrogen bisphosphonates were associated with a significant 34% mortality risk reduction compared to non-treated propensity score matched controls. These findings open new avenues for research into mechanistic pathways.
Introduction: Emerging evidence suggests that bisphosphonates (BP), first-line treatment of osteoporosis, are associated with reduced risks for all-cause mortality. This study aimed to determine the association between different BP types and mortality risk in participants with or without a fracture.

Methods: A prospective cohort study of users of different BPs matched to non-users by propensity score (age, gender, co-morbidities, fragility fracture status) and time to starting the BP medication from the population-based Canadian Multicentre Osteoporosis Study from nine Canadian centres followed from 1995 to 2013. Mortality risk for bisphosphonate users vs matched non-users was assessed using pairwise multivariable Cox proportional hazards models.

Results: There were 2048 women and 308 men on BP and 1970 women and 1794 men who did not receive medication for osteoporosis. The relationship between BP and mortality risk was explored in three separate 1:1 propensity score-matched cohorts of BP users and no treatment (etidronate, n = 599, alendronate, n = 498, and risedronate n = 213). Nitrogen BP (n-BP) (alendronate and risedronate) was associated with lower mortality risks [pairwise HR, 0.66 (95% CI, 0.48-0.91)] while the less potent non-n-BP, etidronate, was not [pairwise HR: 0.89 (95% CI, 0.66-1.20)]. A direct comparison between n-BP and etidronate (n = 340 pairs) also suggested a better survival for n-BP [paired HR, 0.47 (95%CI, (95% CI, 031-0.70)] for n-BP vs. etidronate].

Conclusion: Compared to no treatment, nitrogen but not non-nitrogen bisphosphonates appear to be associated with better survival.


DIR Jahrbuch 2018 (Deutsches IVF-Register Annual Report 2018)

Abstract: Annual report (Jahrbuch) of the Deutsches IVF-Register (DIR) for treatment year 2018. DIR is the German national IVF/ICSI registry, founded 1982 — the oldest continuously operating ART registry. Voluntary professional-society database with high de-facto coverage of German fertility centres. Reports cycles, transfers, pregnancies and clinical outcomes by treatment type (IVF, ICSI, frozen embryo transfer, donor). German-language registry document. Used as a Phase B historical-archive source for the ART Registry Comparison study (cross-registry classification by reporting completeness on 7 framework dimensions).


CARTR Plus 2019 Annual Report (2018 Data) - Canadian Assisted Reproductive Technologies Register Plus

Canadian Fertility and Andrology Society; BORN Ontario

Abstract: CARTR Plus annual report containing final treatment cycle and pregnancy outcome data for 2016 and preliminary treatment cycle data for 2017. Presented at the Canadian Fertility and Andrology Society Annual Meeting (Montreal, September 2018). The Canadian Assisted Reproductive Technologies Register Plus (CARTR Plus) is a voluntary professional society database operated by CFAS in collaboration with BORN Ontario, capturing IVF/ART cycle outcomes from Canadian fertility clinics.


Hirsutism: Options for Treating the Whole Patient


Fertility Treatment Options for Women With Polycystic Ovary Syndrome

Abstract: Polycystic ovary syndrome is the most common endocrinological disorder in women of reproductive age. It is commonly associated with anovulatory subfertility, for which there are a range of treatment options available to help them conceive. These options are given in a step-wise manner with an appropriate selection of patients to maximise success rates with minimal complications. This review discusses the importance and involvement of multidisciplinary care when offering treatment to women with subfertility. Multidisciplinary care gives an excellent opportunity to identify, assess risk, and potentially prevent future morbidities and complications while treating women for fertility issues. We have also summarised the various options available for fertility treatment: pharmacological treatments, nonpharmacological intervention, and assisted reproductive technology.

Clinical medicine insights. Reproductive health


Mitochondrial function in oocytes and early embryos


Yuhua Li

Third Affiliated Hospital of Guangzhou Medical University

Abstract:
1. Aging (Albany NY). 2019 Jan 23;11(2):817-832. doi: 10.18632/aging.101784.

Can ovarian aging be delayed by pharmacological strategies?

Zhang J(1), Chen Q(1), Du D(1), Wu T(1), Wen J(1), Wu M(1), Zhang Y(1), Yan
W(1), Zhou S(1), Li Y(1), Jin Y(1), Luo A(1), Wang S(1).

Author information:
(1)Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical
College, Huazhong University of Science and Technology, Wuhan, Hubei, China.

Aging has been regarded as a treatable condition, and delaying aging could
prevent some diseases. Ovarian aging, a special type of organ senescence, is the
earliest-aging organ, as ovaries exhibit an accelerated rate of aging with
characteristics of gradual declines in ovarian follicle quantity and quality
since birth, compared to other organs. Ovarian aging is considered as the
pacemaker of female body aging, which drives the aging of multiple organs of the
body. Hence, anti-ovarian aging has become a research topic broadly interesting
to both biomedical scientists and pharmaceutical industry. A marked progress has
been made in exploration of possible anti-ovarian agents or approaches, such as
calorie restriction mimetics, antioxidants, autophagy inducers etc., over the
past years. This review is attempted to discuss recent advances in the area of
anti-ovarian aging pharmacology and to offer new insights into our better
understanding of molecular mechanisms underlying ovarian aging, which might be
informative for future prevention and treatment of ovarian aging and its related
diseases.

DOI: 10.18632/aging.101784
PMCID: PMC6366956
PMID: 30674710 [Indexed for MEDLINE]

Conflict of interest statement: CONFLICTS OF INTEREST: The authors have no
conflicts of interest.


Assisted reproductive technology in Japan: A summary report for 2016 by the Ethics Committee of the Japan Society of Obstetrics and Gynecology

Abstract: Annual summary report on assisted reproductive technology (ART) cycles performed in Japan during 2016, published by the Ethics Committee of the Japan Society of Obstetrics and Gynecology (JSOG).


Human health risks due to exposure to inorganic and organic chemicals from textiles: A review

Abstract: It is well known that a number of substances used in the textile industry can mean not only environmental, but also health problems. The scientific literature regarding potential adverse health effects of chemical substances in that industry is mainly related with human exposure during textile production. However, information about exposure of consumers is much more limited. Although most research on the health effects of chemicals in textiles concern allergic skin reactions, contact allergy is not the only potential human health problem. In this paper, we have reviewed the current scientific information regarding human exposure to chemicals through skin-contact clothes. The review has been focused mainly on those chemicals whose probabilities of being detected in clothes were rather higher. Thus, we have revised the presence of flame retardants, trace elements, aromatic amines, quinoline, bisphenols, benzothiazoles/benzotriazoles, phthalates, formaldehyde, and also metal nanoparticles. Human dermal exposure to potentially toxic chemicals through skin-contact textiles/clothes shows a non-negligible presence in some textiles, which might lead to potential systemic risks. Under specific circumstances of exposure, the presence of some chemicals might mean non-assumable cancer risks for the consumers.


Low Dose Naltrexone in Pregnancy

Low Dose Naltrexone in Pregnancy

Phil C Boyle

NeoFertility Clinic, Suite 7, 1st Floor, Beacon Mall, Sandyford, Dublin 18, Ireland. Phil.Boyle@NeoFertility.ie.

Abstract: Presentation examining the safety and potential benefits of low-dose naltrexone (LDN) use during pregnancy. Reports on a patient survey of 237 successful pregnancies comparing outcomes between LDN users and non-users. Addresses three key questions: safety of LDN in pregnancy, additional benefits to mother and baby, and optimal duration of treatment. Findings suggest LDN is safe during pregnancy with trends toward improved outcomes (reduced prematurity, fewer SCBU admissions, fewer complications) for those continuing LDN beyond 26 weeks, though results did not achieve statistical significance. Also discusses potential epigenetic benefits of LDN for reducing endometriosis expression in the next generation and possible reduction of autism risk through immune modification.


Ultrasound in reproductive medicine: is it safe?

Abstract: Ultrasound is a form of energy with effects in tissues it traverses (bioeffects). The major bioeffects are a rise in temperature (thermal effects) and some effects secondary to the alternating positive and negative pressures of the ultrasound wave (nonthermal or mechanical effects). Two on-screen indices, the thermal index (TI) and the mechanical index (MI), give the end user an indication of possible thermal and nonthermal changes occurring in real time during the ultrasound scan. No harmful effects have been described in epidemiological studies in humans, but some deleterious results have been demonstrated in animals. While intensities produced by B-mode, gray-scale ultrasound are, most likely, safe, the use of Doppler involves much higher levels of energy. In addition, the very early fetus is known to be very vulnerable to external influences or insults. Information on susceptibility of the ovum, preor postfertilization, is virtually inexistent. In addition, knowledge regarding bioeffects and safety of ultrasound by clinical end users is grossly inadequate. In vivo exposure to ultrasound at spatial average intensities below 1 W/cm2, which is, arguably, almost always the case in ART as well as early gestation, does not adversely affect oocytes/embryos/fetuses. It is advocated to utilize ultrasound only when medically indicated, for the shortest time and at the lowest intensity compatible with accurate diagnosis. The TI and MI should be kept below 1. Further prospective studies on ultrasound safety in ART and pregnancy are highly recommended, as is education of the end users.

Ultrasound Imaging in Reproductive Medicine


Complementary and Alternative Medicine for Menopause

Abstract: Menopause is associated with problematic symptoms, including hot flashes, sleep problems, mood disorders, sexual dysfunction, weight gain, and declines in cognitive functioning. Many women seek complementary and alternative medicine (CAM) for symptom management. This article critically reviews the existing literature on CAM treatments most commonly used for menopausal symptoms. Electronic searches were conducted to identify relevant, English-language literature published through March 2017. Results indicate that mind and body practices may be of benefit in reducing stress and bothersomeness of some menopausal symptoms. In particular, hypnosis is a mind-body intervention that has consistently shown to have a clinically significant effect on reducing hot flashes. Evidence is mixed in regard to the efficacy of natural products and there are some safety concerns. Health care providers should consider the evidence on CAM in providing an integrative health approach to menopausal symptom management.

Journal of evidence-based integrative medicine


Thoracic Endometriosis Syndrome: A Review of Diagnosis and Management

Abstract:
BACKGROUND: Endometriosis is characterized by the presence of endometrial-like glands and stroma outside the uterine cavity and is believed to affect 6%-10% of reproductive-age women. Endometriosis within the lung parenchyma or on the diaphragm and pleural surfaces produces a range of clinical and radiological manifestations. This includes catamenial pneumothorax, hemothorax, hemoptysis, and pulmonary nodules, resulting in an entity known as thoracic endometriosis syndrome (TES).

DATABASE: Computerized searches of MEDLINE and PubMed were conducted using the key words "thoracic endometriosis," "catamenial pneumothorax," "catamenial hemothorax," and "catamenial hemoptysis." References from identified sources were manually searched to allow for a thorough review.

CONCLUSION: TES can produce incapacitating symptoms for some patients. Symptoms of TES are nonspecific, so a high degree of clinical suspicion is warranted. Medical management represents the first-line treatment approach. When this fails or is contraindicated, definitive surgical treatment for cases of suspected TES uses a combined video laparoscopy performed by a gynecologic surgeon and video-assisted thoracoscopic surgery performed by a thoracic surgeon. Postoperative hormonal suppression may further reduce disease recurrence.

JSLS : Journal of the Society of Laparoendoscopic Surgeons


Risk of stillbirth in low-risk singleton term pregnancies following fertility treatment: a national cohort study

Abstract:
OBJECTIVE: To assess the risk of stillbirth in low-risk in vitro fertilisation (IVF) pregnancies.

DESIGN: Register-based national cohort study.

SETTING: Denmark 2003-2013.

POPULATION: Cohort of 425 732 singleton pregnancies including 10 235 conceived following IVF/intracytoplasmic sperm injection (ICSI), 4521 conceived following intrauterine insemination (IUI), and 410 976 spontaneously conceived.

METHODS: Information on pregnancy, obstetrical risk factors, stillbirth, and fertility treatment was obtained from the Danish national health registers for all pregnancies after gestational week 21+6 . We estimated the overall and gestational age-specific risk of stillbirth in low-risk term pregnancies following IVF, ICSI, and IUI. Further, we estimated the association between stillbirth and IVF and ICSI respectively as well as fresh or frozen-thawed embryo transfer.

MAIN OUTCOME MEASURES: Risk of stillbirth.

RESULTS: The number of stillbirths in spontaneously conceived and IVF/ICSI low-risk term pregnancies was 525 (0.1%) and 35 (0.3%), respectively. In multivariate analysis, the risk of stillbirth in pregnancies following IVF/ICSI was increased (odds ratio 2.1, 95% CI 1.4-3.1). The risk of stillbirth was correspondingly increased in time-to-event analyses taking risk time for each fetus into account from gestational week 37 and onwards (hazard ratio 2.4, 95% CI 1.6-3.6). In sub-analyses, the risk of stillbirth was increased for pregnancies following ICSI (odds ratio 2.2, 95% CI 1.2-3.1), but not IVF (odds ratio 1.7, 95% CI 0.9-3.1).

CONCLUSION: We found a systematically increased risk of stillbirth in low-risk term pregnancies following IVF/ICSI. Whether the risk was related to the treatment or to underlying subfertility is uncertain. The results may indicate a need for obstetrical surveillance for these pregnancies when reaching term.

TWEETABLE ABSTRACT: Increased risk of stillbirth in low-risk term pregnancies following fresh cycle IVF/ICSI.

BJOG : an international journal of obstetrics and gynaecology


Endometriosis as a Comorbid Condition in Chronic Fatigue Syndrome (CFS): Secondary Analysis of Data From a CFS Case-Control Study

Robert N Taylor

Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility (Drs. Peterson and Taylor), University of Utah, Salt Lake City, Utah.

Abstract: Background: Endometriosis (EM) is a recognized co-morbid condition in women with chronic fatigue syndrome (CFS). This analysis evaluates the impact of EM on the health of women with CFS by comparing selected health characteristics and laboratory parameters in women with CFS with and without EM (CFS+EM and CFS-only). Methods: This secondary analysis included all 36 women with CFS from a cross-sectional study of CFS in Wichita, KS, conducted between 2002 and 2003. The health characteristics and laboratory parameters of interest included functioning, fatigue, CFS-related symptoms, gynecologic history, routine laboratory parameters, inflammatory markers, cortisol levels, allostatic load, and sleep parameters (overnight polysomnography). We used parametric or non-parametric tests to compare group differences in the selected health characteristics and laboratory parameters. For examining the association between EM and variables of interest, logistic regression models were performed and odds ratios (OR) with 95% confidence intervals (CI) were reported for the magnitude of associations. Statistical significance was set at 0.05 (two-sided). Results: The mean age of this study sample was 50.9 years. Of women with CFS, 36.1% reported having EM. Age and body mass index (BMI) did not differ between CFS+EM and CFS-only groups. When examining the impact of EM, compared to women with CFS-only, women with both CFS and EM were more likely to report chronic pelvic pain [OR = 9.00 (95% CI, 1.47-55.25)] and hysterectomy [OR = 10.3 (1.82-58.39)], had more CFS symptoms (6.8 ± 0.3 vs. 5.5 ± 0.3, p = 0.02), younger mean age at menopause onset (36.4 ± 3.0 vs. 47.0 ± 2.7 years, p = 0.03), higher mean number of obstructive apnea episodes per hour (20.3 vs. 4.4, p = 0.05) and reported more negative life events (15.8 vs. 4.4, p = 0.05). Other parameters did not differ significantly between the two groups. Conclusions: We found more than a third of women with CFS reported endometriosis as a comorbid condition. The endometriosis comorbidity was associated with chronic pelvic pain, earlier menopause, hysterectomy, and more CFS-related symptoms. However, endometriosis in women with CFS did not appear to further impact functioning, fatigue, inflammatory markers, or other laboratory parameters. Further investigations including younger women are warranted.


Binge eating in patients with polycystic ovary syndrome: prevalence, causes, and management strategies

Abstract: Emerging evidence suggests that disordered eating, particularly binge-eating symptomatology, is overrepresented within Polycystic Ovary Syndrome (PCOS) populations. This comorbidity presents a clinical dilemma as current treatment approaches for PCOS emphasize the importance of weight management, diet, exercise, and the potential for harm of such treatment approaches in PCOS patients with comorbid disordered eating. However, limited research has assessed the occurrence of binge eating and disordered eating in PCOS patients. Consequently, little is known about the prevalence of binge eating in PCOS, and the possible etiological processes to explain this comorbidity remain poorly understood. Given the paucity of research on this topic, the aims of this narrative review are fourfold: 1) to outline the main symptoms of PCOS and binge eating; 2) to provide an overview of the prevalence of binge eating in PCOS; 3) to outline possible etiological factors for the comorbidity between PCOS and binge eating; and 4) to provide an overview of management strategies of binge eating in PCOS.


Postpartum depression and vitamin D: A systematic review

Abstract: Postpartum depression (PPD) is a prevalent mood disorder estimated to affect 20%-40% of women worldwide after childbirth. In recent studies, the effect of vitamin D on prevention of mood disorders and depression has been investigated, but it is still unclear how vitamin D may affect PPD. The evidence on the relevance between vitamin D deficiency and PPD is inconsistent, and assessment of the recent literature has not previously been carried out. Moreover, there are few clinical studies on PPD and vitamin D supplementation. Five studies have so far assessed the relationship between the levels of vitamin D and PPD. Findings from cohort studies suggest that vitamin-D deficiency is related to the incidence of PPD and vitamin D may play a significant role in the recovery of women with PPD, but it is uncertain whether these actions are the effect of vitamin D on the function of hypothalamic-pituitary-adrenal (HPA) axis, the levels of estradiol, serotonin, pro-inflammatory cytokines, and/or of other mechanisms involved in PPD.

Critical reviews in food science and nutrition


Coat-A-Count Progesterone Radioimmunoassay

Johan O Nöthling

Department of Production Animal Studies, Section of Reproduction, Faculty of Veterinary Science, Onderstepoort. johan.nothling@up.ac.za.


Recent advances in understanding and managing adenomyosis

Abstract: Adenomyosis is a benign uterine disorder in which endometrial glands and stroma are pathologically demonstrated in the uterine myometrium and it is considered a specific entity in the PALM-COEIN FIGO (polyp; adenomyosis; leiomyoma; malignancy and hyperplasia; coagulopathy; ovulatory dysfunction; endometrial; iatrogenic; and not yet classified - International Federation of Gynecology and Obstetrics) classification of causes of abnormal uterine bleeding (AUB). Although it has always been considered the classic condition of multiparous women over 40 years old who have pain and heavy menstrual bleeding, diagnosed at hysterectomy, the epidemiological scenario has completely changed. Adenomyosis is increasingly identified in young women with pain, AUB, infertility, or no symptoms by using imaging techniques such as transvaginal ultrasound and magnetic resonance. However, there is no agreement on the definition and classification of adenomyotic lesions from both the histopathology and the imaging point of view, and the diagnosis remains difficult and unclear. A uniform and shared reporting system needs to be implemented in order to improve our understanding on imaging features, their relationship with pathogenic theories, and their importance in terms of clinical symptoms and response to treatment. In fact, adenomyosis pathogenesis remains elusive and not a single theory can explain all of the different phenotypes of the disease. Furthermore, adenomyosis often coexists with other gynecological conditions, such as endometriosis and uterine fibroids, increasing the heterogeneity of available data. Treatment requires a lifelong management plan as the disease has a negative impact on quality of life in terms of menstrual symptoms, fertility, and pregnancy outcome and has a high risk of miscarriage and obstetric complications.