Weight loss remains one of the most important arms in obese patients with polycystic ovary syndrome (PCOS). Further studies are needed to identify the best treatment. To evaluate the effects of exenatide (EXE) on reproductive and metabolic function in overweight/obese (OW/OB) PCOS. This is a 24-week open-label prospective, randomized, clinical study. This study randomized 176 OW/OB women diagnosed with PCOS to receive either EXE 10 μg BID (n = 88) or metformin (MET) 1000 mg BID (n = 88) for the first 12 weeks. Then all patients were treated with MET alone during the second 12 weeks. We observed metabolic parameters at 0 and 12 weeks, and then tracked the rate of pregnancy during the second 12 weeks. After the first 12 weeks of intervention, compared with MET, subjects who received EXE had significantly decreased weight (4.29 ± 1.29 kg vs 2.28 ± 0.55 kg, P < .001) and total fat% (4.67 ± 0.09% vs 1.11 ± 0.32%, P < .001), improved the homeostasis model of assessment for insulin resistance (1.30 ± 0.58 vs 0.59 ± 0.12, P < .001) and increased the menstrual frequency ratio (0.62 ± 0.12 vs 0.37 ± 0.01, P < .001). During the second 12 weeks, the rate of natural pregnancy of EXE-treated patients was significantly higher than MET-treated patients (43.60% vs 18.70%, P < .05). Short-term EXE therapy was linked to significant weight loss and central adiposity reduction, which may further explain the improvements in insulin resistance, inflammatory marker and menstrual cycle, which may contribute to increasing pregnancy rates in OW/OB women with PCOS.
Cerqueira RO et al., 2017·Archives of women's mental health
The objective of this study was to evaluate whether Vitex agnus castus is a safe and effective treatment for PMS and premenstrual dysphoric disorder (PMDD) and to discuss the implications of these findings for clinical practice. A systematic review of literature was conducted using PubMed and Scielo databases. The inclusion criteria were randomized controlled trials (RCT) using V. agnus castus in individuals with PMS or PMDD that compared this intervention with placebo or an active comparator and included a description of blinding and dropouts/withdrawals. The search was conducted by two independent investigators who reached consensus on the included trials. A total of eight RCTs were included in this study. Most studies focused on PMS, and the diagnostic criteria of PMS and PMDD changed over the years. Three different preparations of V. agnus castus (VAC) were tested, and there was significant variability in the measurement of treatment outcomes between the studies. Nevertheless, all eight studies were positive for VAC in the treatment of PMS or PMDD and VAC was overall well tolerated. Main limitations were differences in definition of diagnostic criteria, the instruments used as main outcome measures, and different preparations of VAC extracts limit the comparison of results between studies. In conclusion, the RCTs using VAC for treatment of PMS/PMDD suggested that the VAC extract is a safe and efficacious alternative to be considered for the treatment of PMS/PMDD symptoms.
Fertility AwarenessSelf-Tracking App Ovulation AnalysisApp-Based Population DataMobile App Menstrual Cycle Protocols
Open Access
There are many mobile phone apps aimed at helping women map their ovulation and menstrual cycles and facilitating successful conception (or avoiding pregnancy). These apps usually ask users to input various biological features and have accumulated the menstrual cycle data of a vast number of women. The purpose of our study was to clarify how the data obtained from a self-tracking health app for female mobile phone users can be used to improve the accuracy of prediction of the date of next ovulation. Using the data of 7043 women who had reliable menstrual and ovulation records out of 8,000,000 users of a mobile phone app of a health care service, we analyzed the relationship between the menstrual cycle length, follicular phase length, and luteal phase length. Then we fitted a linear function to the relationship between the length of the menstrual cycle and timing of ovulation and compared it with the existing calendar-based methods. The correlation between the length of the menstrual cycle and the length of the follicular phase was stronger than the correlation between the length of the menstrual cycle and the length of the luteal phase, and there was a positive correlation between the lengths of past and future menstrual cycles. A strong positive correlation was also found between the mean length of past cycles and the length of the follicular phase. The correlation between the mean cycle length and the luteal phase length was also statistically significant. In most of the subjects, our method (ie, the calendar-based method based on the optimized function) outperformed the Ogino method of predicting the next ovulation date. Our method also outperformed the ovulation date prediction method that assumes the middle day of a mean menstrual cycle as the date of the next ovulation. The large number of subjects allowed us to capture the relationships between the lengths of the menstrual cycle, follicular phase, and luteal phase in more detail than previous studies. We then demonstrated how the present calendar methods could be improved by the better grouping of women. This study suggested that even without integrating various biological metrics, the dataset collected by a self-tracking app can be used to develop formulas that predict the ovulation day when the data are aggregated. Because the method that we developed requires data only on the first day of menstruation, it would be the best option for couples during the early stages of their attempt to have a baby or for those who want to avoid the cost associated with other methods. Moreover, the result will be the baseline for more advanced methods that integrate other biological metrics.
Fertility AwarenessWrist Wearable Temperature MonitoringContinuous Temperature TrackingOvulation Detection Validation
Open Access
Core and peripheral body temperatures are affected by changes in reproductive hormones during the menstrual cycle. Women worldwide use the basal body temperature (BBT) method to aid and prevent conception. However, prior research suggests that taking one's daily temperature can prove inconvenient and subject to environmental factors. We investigate whether a more automatic, non-invasive temperature measurement system can detect changes in temperature across the menstrual cycle. We examined how wrist skin temperature (WST), measured with wearable sensors, correlates with urinary tests of ovulation and may serve as a new method of fertility tracking. One hundred and thirty-six eumenorrheic, non-pregnant women participated in an observational study. Participants wore WST biosensors during sleep and reported their daily activities. An at-home luteinizing hormone (LH) test was used to confirm ovulation. WST was recorded across 437 cycles (mean cycles/participant = 3.21, S.D. = 2.25). We tested the relationship between the fertile window and WST temperature shifts, using the BBT three-over-six rule. A sustained 3-day temperature shift was observed in 357/437 cycles (82%), with the lowest cycle temperature occurring in the fertile window 41% of the time. Most temporal shifts (307/357, 86%) occurred on ovulation day (OV) or later. The average early-luteal phase temperature was 0.33°C higher than in the fertile window. Menstrual cycle changes in WST were impervious to lifestyle factors, like having sex, alcohol, or eating prior to bed, that, in prior work, have been shown to obfuscate BBT readings. Although currently costlier than BBT, the present study suggests that WST could be a promising, convenient parameter for future multiparameter fertility awareness methods.
The incidence of metabolic disorders like type 2 diabetes and obesity continues to increase. In addition to the well-known contributors to these disorders, such as food intake and sedentary lifestyle, recent research in the exposure science discipline provides evidence that exposure to endocrine-disrupting chemicals like bisphenol A and phthalates via multiple routes (e.g., food, drink, skin contact) also contribute to the increased risk of metabolic disorders. Endocrine-disrupting chemicals (EDCs) can disrupt any aspect of hormone action. It is becoming increasingly clear that EDCs not only affect endocrine function but also adversely affect immune system function. In this review, we focus on human, animal, and in vitro studies that demonstrate EDC exposure induces dysfunction of the immune system, which, in turn, has detrimental effects on metabolic health. These findings highlight how the immune system is emerging as a novel player by which EDCs may mediate their effects on metabolic health. We also discuss studies highlighting mechanisms by which EDCs affect the immune system. Finally, we consider that a better understanding of the immunomodulatory roles of EDCs will provide clues to enhance metabolic function and contribute toward the long-term goal of reducing the burden of environmentally induced diabetes and obesity.
The purpose of this study was to assess the relative risk of suicide attempt and suicide in users of hormonal contraception.
The authors assessed associations between hormonal contraceptive use and suicide attempt and suicide in a nationwide prospective cohort study of all women in Denmark who had no psychiatric diagnoses, antidepressant use, or hormonal contraceptive use before age 15 and who turned 15 during the study period, which extended from 1996 through 2013. Nationwide registers provided individually updated information about use of hormonal contraception, suicide attempt, suicide, and potential confounding variables. Psychiatric diagnoses or antidepressant use during the study period were considered potential mediators between hormonal contraceptive use and risk of suicide attempt. Adjusted hazard ratios for suicide attempt and suicide were estimated for users of hormonal contraception as compared with those who never used hormonal contraception. Among nearly half a million women followed on average for 8.3 years (3.9 million person-years) with a mean age of 21 years, 6,999 first suicide attempts and 71 suicides were identified. Compared with women who never used hormonal contraceptives, the relative risk among current and recent users was 1.97 (95% CI=1.85–2.10) for suicide attempt and 3.08 (95% CI=1.34–7.08) for suicide. Risk estimates for suicide attempt were 1.91 (95% CI=1.79–2.03) for oral combined products, 2.29 (95% CI=1.77–2.95) for oral progestin-only products, 2.58 (95% CI=2.06–3.22) for vaginal ring, and 3.28 (95% CI=2.08–5.16) for patch. The association between hormonal contraceptive use and a first suicide attempt peaked after 2 months of use. Use of hormonal contraception was positively associated with subsequent suicide attempt and suicide. Adolescent women experienced the highest relative risk.
Polycystic ovary syndrome (PCOS) is diagnosed by its characteristic reproductive features. However, PCOS is also associated with metabolic abnormalities, including insulin resistance and β-cell dysfunction. The severity of these abnormalities varies according to the reproductive phenotype, with the so-called NIH or classic phenotype conferring the greatest metabolic risk. The increased risk for type 2 diabetes (T2D) is well established among affected women with the NIH phenotype, but whether PCOS also confers an increased risk for cardiovascular events remains unknown. Recent studies in daughters of affected women have found evidence for pancreatic β-cell dysfunction prior to menarche. Further, genetic analyses have provided evidence that metabolic abnormalities such as obesity and insulin resistance contribute to the pathogenesis of PCOS. PCOS increases the risk for T2D. However, the risk for cardiovascular disease has not been quantified, and prospective, longitudinal studies are still critically needed.
InfertilityInternational Consensus Glossary 2017Reproductive Medicine DefinitionsFertility Care Terminology
Can a consensus and evidence-driven set of terms and definitions be generated to be used globally in order to ensure consistency when reporting on infertility issues and fertility care interventions, as well as to harmonize communication among the medical and scientific communities, policy-makers, and lay public including individuals and couples experiencing fertility problems? A set of 283 consensus-based and evidence-driven terminologies used in infertility and fertility care has been generated through an inclusive consensus-based process with multiple stakeholders. In 2006 the International Committee for Monitoring Assisted Reproductive Technologies (ICMART) published a first glossary of 53 terms and definitions. In 2009 ICMART together with WHO published a revised version expanded to 87 terms, which defined infertility as a disease of the reproductive system, and increased standardization of fertility treatment terminology. Since 2009, limitations were identified in several areas and enhancements were suggested for the glossary, especially concerning male factor, demography, epidemiology and public health issues. STUDY DESIGN, SIZE, Twenty-five professionals, from all parts of the world and representing their expertise in a variety of sub-specialties, were organized clinical definitions; outcome measurements; embryology laboratory; clinical and laboratory andrology; and epidemiology and public health. Assessment for revisions, as well as expansion on topics not covered by the previous glossary, were undertaken. A larger group of independent experts and representatives from collaborating organizations further discussed and assisted in refining all terms and definitions. PARTICIPANTS/MATERIALS, SETTING, Members of the working groups and glossary co-ordinators interacted through electronic mail and face-to-face in international/regional conferences. Two formal meetings were held in Geneva, Switzerland, with a final consensus meeting including independent experts as well as observers and representatives of international/regional scientific and patient organizations. MAIN A consensus-based and evidence-driven set of 283 terminologies used in infertility and fertility care was generated to harmonize communication among health professionals and scientists as well as the lay public, patients and policy makers. Definitions such as 'fertility care' and 'fertility awareness' together with terminologies used in embryology and andrology have been introduced in the glossary for the first time. Furthermore, the definition of 'infertility' has been expanded in order to cover a wider spectrum of conditions affecting the capacity of individuals and couples to reproduce. The definition of infertility remains as a disease characterized by the failure to establish a clinical pregnancy; however, it also acknowledges that the failure to become pregnant does not always result from a disease, and therefore introduces the concept of an impairment of function which can lead to a disability. Additionally, subfertility is now redundant, being replaced by the term infertility so as to standardize the definition and avoid confusion. LIMITATIONS, All stakeholders agreed to the vast majority of terminologies included in this glossary. In cases where disagreements were not resolved, the final decision was reached after a vote, defined before the meeting as consensus if passed with 75%. Over the following months, an external expert group, which included representatives from non-governmental organizations, reviewed and provided final feedback on the glossary. Some terminologies have different definitions, depending on the area of medicine, for example demographic or clinical as well as geographic differences. These differences were taken into account and this glossary represents a multinational effort to harmonize terminologies that should be used worldwide. None. N/A.
Down syndrome (trisomy 21) is a well-known cause of mental retardation. It can be diagnosed in early pregnancy. Scientists have made great strides in outlining the pathophysiologic mechanisms of mental retardation in Down syndrome. Much less has been published on human therapy. To our knowledge, these are the first published cases of fetal therapy for Down syndrome. Reports of three cases. In all cases, treatment was both biochemical (e.g. nutritional) and educational. In all cases, treatment was both before and after birth. All children lacked the characteristic faces usually seen in the children with Down syndrome. This suggests a treatment effect before birth. All children had better than expected development. Enhancement of development is proposed as a new therapeutic principle. Developing neurons exchange neurotrophic factors during development when they give or receive stimulation from other neurons. Neurons which receive neurotrophic stimulation survive, and those, which do not, are lost to apoptosis. The developmental therapeutic principle seeks to optimize brain development. Biochemical inputs (neurotransmitters, drugs, hormones, nutrients) and functional stimulation are integrated to optimize the growth and survival of neurons individually; other cells; subcellular organelles; and the brain as a whole. Treatment may be before and after birth, both biochemical and functional. These principles may be applied to Down syndrome, other conditions, and normal fetuses or children. Baggot PJ and Baggot RM (2014). Fetal Report of three cases and review of the literature. J Am Phys Surg 19(1):20-24.
Residents entering training in the specialty of Obstetrics and Gynecology (OB/GYN) often have misconceptions as to what medical interventions Roman Catholic healthcare institutions prohibit, and why certain restrictions are placed on the provision of reproductive health options that are otherwise legally available to women. The Ethical and Religious Directives for Catholic Healthcare Services, produced by the United States Conference of Catholic Bishops seeks to provide a stable framework upon which reproductive health decisions can be based. However, Catholic healthcare ethics may conflict with secular bioethical assertions that place a premium on autonomous patient choice. Residents training in part or whole at a Catholic institution may feel frustration at what they perceive to be a conflict with current secular ethics paradigms-such as access to abortion, contraception, sterilization, and assisted reproductive technologies. The recent adoption of Clinical Competencies by the Accreditation Council for Graduate Medical Education (ACGME), directs that residents shall be trained to function within the framework of their larger healthcare system ("Systems-based Practice"). This article will first, clarify areas of conflict and convergence between Catholic and secular reproductive ethics, which are unique to OB/GYN training. Next, using the ACGME's new Clinical Competency in Systems-Based practice as a model, a rationale for incorporating Catholic Healthcare ethics into an ethics curriculum for OB/GYN residents will be discussed. Finally, guidelines for faculty tackling the problem of how to teach Catholic Healthcare ethics will be described. Incorporating the rich tradition of Catholic healthcare ethics into the educational curriculum of OB/GYN residency fulfills training requirements while exposing young physicians to a rational decision-making framework in bioethics.
Fertility AwarenessComparison with Hormonal MethodsOral ContraceptivesSORT Criteria
Background and PurposePublished reports indicate that over 100 million women worldwide use the birth control pill (Oral Contraceptives, or OCPs).1,2 However, in a national study conducted by the Battelle Centers for Public Health Research and Evaluation, rates of discontinuation of some birth control methods were as high as 90%, and had averages between 40-61% (depending on marital status) for women who were followed over a two-year period.3 This suggests that women are searching for new methods, perhaps with fewer side effects or better effectiveness rates. Studies show up to 60% of women would be interested in using Fertility Awareness Based Methods (FABMs) if given information.4 Both FABMs and OCPs entail behavior modification on a daily basis, so the efficacy and side effects of FABMs and OCPs were chosen for comparison during this study.Most commonly reported unintended pregnancy rates for FABMs and OCPs are based on low quality retrospective surveys. A popularly cited review from J. R. Trussell and colleagues reports typical use failure rates of 24% for FABMs and 9% for OCPs.5 These numbers are based on estimates of the probability of pregnancy drawn from the 1995 and 2002 National Surveys of Family Growth.5'6 There are at least three major problems with these surveys. One is that these are lower quality retrospective surveys based primarily on patient recall, with the data collected via a series of phone surveys. Another major problem is that 86% of the purported FABM users surveyed identified the calendar method-a much older and less effective method-as their primary form of contraception. Then, the rates for all types of FABMs were pooled together, including some methods which are not even classified as FABMs by trained providers. This lumping together of all FABMs including rhythm masks important differences in effectiveness among the variety of modern methods; a fact acknowledged by Trussell, the author of this estimate.7'8'9 The third major issue with this review is that the rates of effectiveness were adjusted to account for the researchers' assumption of underreporting of abortion. As a result of the issues with these popularly cited statistics, we sought to design objective criteria with which to evaluate the primary literature available for FABMs and OCPs, in order to understand both the quality of the studies available as well as the true effectiveness rates. In total, three major search engines (Medline, PubMed, and EMBASE) were used with keyword searches to identify relevant articles. For FABMs, 30 articles from 1980 on were included in the study.6 For OCPs, 47 articles from 2000 on were included in the study. (The year 2000 was chosen in part because studies from earlier decades had used higher dose hormone formulations which were proven to be unsafe for women, and the trend in later years has been towards seeking lower dose hormonal formulations to provide the same efficacy with fewer side effects1). Strength of Recommendation Taxonomy (SORT) criteria10 were established first for the FABM review6 and then adapted for the OCP review (Adapted SORT). The adaptation was based on fundamental differences between FABMs and OCPs such as lack of a learning phase for OCPs. The purpose of the SORT and Adapted SORT criteria was to provide a framework to determine the level of evidence for individual studies.Two independent reviewers scored each of the identified articles for the FABMs and the OCPs reviewed. Major discrepancies in scores were resolved by sending the articles in question to a third reviewer for a tie-break score. For the FABMs reviewed, there were 56 maximum possible points with the SORT criteria. The scores ranged from 31-55 points, and 10 of the 30 articles (30%) were found to earn a SORT Level 1 status (qualified by earning a positive score in all of the critical criteria).6For the OCPs reviewed, there were 42 maximum possible points with the Adapted SORT criteria. …
EndometriosisMiscarriage RiskMild vs SevereEndometriosis-Related Pregnancy Loss
To investigate the prevalence of miscarriage in women with endometriosis (WwE) compared with disease-free control women (CW).
Cross-sectional analysis nested in a retrospective observational study (n = 940).
Hospitals and associated private practices. PATIENT(S): Previously pregnant women (n = 268) within reproductive age in matched pairs. INTERVENTION(S): Retrospective analysis of surgical reports and self-administered questionnaires. MAIN OUTCOME MEASURE(S): Rate of miscarriage, subanalysis for fertility status (≤12 vs. >12 months' time to conception), endometriosis stages (revised American Society of Reproductive Medicine classification [rASRM] I/II vs. III/IV) and phenotypic localizations (superficial peritoneal, ovarian, and deep infiltrating endometriosis). RESULT(S): The miscarriage rate was higher in WwE (35.8% [95% confidence interval 29.6%-42.0%]) compared with CW (22.0% [16.7%-27.0%]); adjusted incidence risk ratio of 1.97 (95% CI 1.41-2.75). This remained significant in subfertile WwE (50.0% [40.7%-59.4%]) vs. CW (25.8% [8.5%-41.2%]) but not in fertile WwE (24.5% [16.3%-31.6%]) vs. CW (21.5% [15.9%-26.8%]). The miscarriage rate was higher in women with milder forms (rASRM I/II 42.1% [32.6%-51.4%] vs. rASRM III/IV 30.8% [22.6%-38.7%], compared with 22.0% [16.7%-27.0%] in CW), and in women with superficial peritoneal endometriosis (42.0% [32.0%-53.9%]) compared with ovarian endometriosis (28.6% [17.7%-38.7%]) and deep infiltrating endometriosis (33.9% [21.2%-46.0%]) compared with CW (22.0% [16.7%-27.0%]). CONCLUSION(S): Mild endometriosis, as in superficial lesions, is related to a great extent of inflammatory disorder, possibly leading to defective folliculogenesis, fertilization, and/or implantation, presenting as increased risk of miscarriage. TRIAL NCT02511626.
Joseph DN et al., 2017·International journal of molecular sciences
An organism's reproductive fitness is sensitive to the environment, integrating cues of resource availability, ecological factors, and hazards within its habitat. Events that challenge the environment of an organism activate the central stress response system, which is primarily mediated by the hypothalamic-pituitary-adrenal (HPA) axis. The regulatory functions of the HPA axis govern the cardiovascular and metabolic system, immune functions, behavior, and reproduction. Activation of the HPA axis by various stressors primarily inhibits reproductive function and is able to alter fetal development, imparting a biological record of stress experienced in utero. Clinical studies and experimental data indicate that stress signaling can mediate these effects through direct actions in the brain, gonads, and embryonic tissues. This review focuses on the mechanisms by which stress activation of the HPA axis impacts fertility and fetal development.
Despite lack of evidence of their utility, biomarkers of ovarian reserve are being promoted as potential markers of reproductive potential. To determine the associations between biomarkers of ovarian reserve and reproductive potential among women of late reproductive age. DESIGN, SETTING, Prospective time-to-pregnancy cohort study (2008 to date of last follow-up in March 2016) of women (N = 981) aged 30 to 44 years without a history of infertility who had been trying to conceive for 3 months or less, recruited from the community in the Raleigh-Durham, North Carolina, area. Early-follicular-phase serum level of antimüllerian hormone (AMH), follicle-stimulating hormone (FSH), and inhibin B and urinary level of FSH. The primary outcomes were the cumulative probability of conception by 6 and 12 cycles of attempt and relative fecundability (probability of conception in a given menstrual cycle). Conception was defined as a positive pregnancy test result. A total of 750 women (mean age, 33.3 [SD, 3.2] years; 77% white; 36% overweight or obese) provided a blood and urine sample and were included in the analysis. After adjusting for age, body mass index, race, current smoking status, and recent hormonal contraceptive use, women with low AMH values (<0.7 ng/mL [n = 84]) did not have a significantly different predicted probability of conceiving by 6 cycles of attempt (65%; 95% CI, 50%-75%) compared with women (n = 579) with normal values (62%; 95% CI, 57%-66%) or by 12 cycles of attempt (84% [95% CI, 70%-91%] vs 75% [95% CI, 70%-79%], respectively). Women with high serum FSH values (>10 mIU/mL [n = 83]) did not have a significantly different predicted probability of conceiving after 6 cycles of attempt (63%; 95% CI, 50%-73%) compared with women (n = 654) with normal values (62%; 95% CI, 57%-66%) or after 12 cycles of attempt (82% [95% CI, 70%-89%] vs 75% [95% CI, 70%-78%], respectively). Women with high urinary FSH values (>11.5 mIU/mg creatinine [n = 69]) did not have a significantly different predicted probability of conceiving after 6 cycles of attempt (61%; 95% CI, 46%-74%) compared with women (n = 660) with normal values (62%; 95% CI, 58%-66%) or after 12 cycles of attempt (70% [95% CI, 54%-80%] vs 76% [95% CI, 72%-80%], respectively). Inhibin B levels (n = 737) were not associated with the probability of conceiving in a given cycle (hazard ratio per 1-pg/mL increase, 0.999; 95% CI, 0.997-1.001). Among women aged 30 to 44 years without a history of infertility who had been trying to conceive for 3 months or less, biomarkers indicating diminished ovarian reserve compared with normal ovarian reserve were not associated with reduced fertility. These findings do not support the use of urinary or blood follicle-stimulating hormone tests or antimüllerian hormone levels to assess natural fertility for women with these characteristics.
The US cesarean delivery rate remains 30%-32%. Increases in maternal age, obesity, and diabetes put upward pressure on this rate. Alternatives to cesarean delivery, vaginal birth after cesarean (VBAC), and operative vaginal delivery, are underutilized and there are substantial challenges to their resurgence. Practice guidelines offer promise, but demonstrate only minor reductions in cesarean delivery. We estimate that the overall rate in the US will remain 27%-30% for the immediate future. As more states move to recognize the independent practice of midwifery and more payers seek lower cost options for childbirth, we anticipate the overall rate will drop to 20% or 25%, but not for another 15 years or more.
InfertilityUterine and Upper Tract BacteriaFemale Reproductive Tract ContinuumMicrobiome Association
Open Access
Reports on bacteria detected in maternal fluids during pregnancy are typically associated with adverse consequences, and whether the female reproductive tract harbours distinct microbial communities beyond the vagina has been a matter of debate. Here we systematically sample the microbiota within the female reproductive tract in 110 women of reproductive age, and examine the nature of colonisation by 16S rRNA gene amplicon sequencing and cultivation. We find distinct microbial communities in cervical canal, uterus, fallopian tubes and peritoneal fluid, differing from that of the vagina. The results reflect a microbiota continuum along the female reproductive tract, indicative of a non-sterile environment. We also identify microbial taxa and potential functions that correlate with the menstrual cycle or are over-represented in subjects with adenomyosis or infertility due to endometriosis. The study provides insight into the nature of the vagino-uterine microbiome, and suggests that surveying the vaginal or cervical microbiota might be useful for detection of common diseases in the upper reproductive tract.Whether the female reproductive tract harbours distinct microbiomes beyond the vagina has been a matter of debate. Here, the authors show a subject-specific continuity in microbial communities at six sites along the female reproductive tract, indicative of a non-sterile environment.
DiagnosticsX-Ray Detector Material ScienceLead Oxide Characterization
Open Access
We investigated the electronic structure of Lead Oxide (PbO) - one of the most promising photoconductor materials for direct conversion x-ray imaging detectors, using soft x-ray emission and absorption spectroscopy. Two structural configurations of thin PbO layers, namely the polycrystalline and the amorphous phase, were studied, and compared to the properties of powdered α-PbO and β-PbO samples. In addition, we performed calculations within the framework of density functional theory and found an excellent agreement between the calculated and the measured absorption and emission spectra, which indicates high accuracy of our structural models. Our work provides strong evidence that the electronic structure of PbO layers, specifically the width of the band gap and the presence of additional interband and intraband states in both conduction and valence band, depend on the deposition conditions. We tested several model structures using DFT simulations to understand what the origin of these states is. The presence of O vacancies is the most plausible explanation for these additional electronic states. Several other plausible models were ruled out including interstitial O, dislocated O and the presence of significant lattice stress in PbO.
Latif T et al., 2017·American journal of epidemiology
Semen quality has been suggested to be a biological marker of long-term morbidity and mortality; however, few studies have been conducted on this subject. We identified 5,370 men seen for infertility at Frederiksberg Hospital, Denmark, during 1977-2010, and 4,712 of these men were followed in the Danish National Patient Registry until first hospitalization, death, or the end of the study. We classified patients according to hospitalizations and the presence of cardiovascular disease, diabetes, testicular cancer, or prostate cancer. We found a clear association between sperm concentration below 15 million/mL and all-cause hospitalizations (hazard ratio = 1.5, 95% 1.4, 1.6) and cardiovascular disease (hazard ratio = 1.4, 95% 1.2, 1.6), compared with men with a concentration above 40 million/mL. The probabilities for hospitalizations were also higher with a low total sperm count and low motility. Men with a sperm concentration of 195-200 million/mL were, on average, hospitalized for the first time 7 years later than were men with a sperm concentration of 0-5 million/mL. Semen quality was associated with long-term morbidity, and a significantly higher risk of hospitalization was found, in particular for cardiovascular diseases and diabetes mellitus. Our study supports the suggestion that semen quality is a strong biomarker of general health.
An isthmocele appears as a fluid pouchlike defect in the anterior uterine wall at the site of a prior cesarean section and ranges in prevalence from 19% to 84%, a direct relation to the increase in cesarean sections performed worldwide. Many definitions have been suggested for the dehiscence resulting from cesarean sections, and we propose standardization with a single term for all cases-isthmocele. Patients are not always symptomatic, but symptoms typically include intermittent abnormal bleeding, pain, and infertility. Pregnancy complications that result from an isthmocele include ectopic pregnancy, low implantation, and uterine rupture. Magnetic resonance imaging and transvaginal ultrasound are the gold standard imaging techniques for diagnosis. Surgical treatment of an isthmocele is still a controversial issue but should be offered to symptomatic women or the asymptomatic patient who desires future pregnancy. When surgery is the treatment choice, laparoscopy guided by hysteroscopy, hysteroscopy alone, or vaginal repair are the best options depending on the isthmocele's characteristics and surgeon expertise.
Bone HealthPeak Bone Mass and Ovulation ProtectionBone Accrual ImpactProgesterone Bone Formation
Open Access
To evaluate the effect of endometriosis on pregnancy outcomes. Systematic review and meta-analysis. Not applicable. PATIENT(S): Women with or without endometriosis. INTERVENTION(S): Electronic databases searched from their inception until February 2017 with no limit for language and with all cohort studies reporting the incidence of obstetric complications in women with a diagnosis of endometriosis compared with a control group (women without a diagnosis of endometriosis) included. MEAN OUTCOME MEASURE(S): Primary outcome of incidence of preterm birth at <37 weeks with meta-analysis performed using the random effects model of DerSimonian and Laird to produce an odds ratio (OR) with 95% confidence interval (CI). RESULT(S): Twenty-four studies were analyzed comprising 1,924,114 women. In most of them, the diagnosis of endometriosis was made histologically after surgery. Women with endometriosis had a statistically significantly higher risk of preterm birth (OR 1.63; 95% CI, 1.32-2.01), miscarriage (OR 1.75; 95% CI, 1.29-2.37), placenta previa (OR 3.03; 95% CI, 1.50-6.13), small for gestational age (OR 1.27; 95% CI, 1.03-1.57), and cesarean delivery (OR 1.57; 95% CI, 1.39-1.78) compared with the healthy controls. No differences were found in the incidence of gestational hypertension and preeclampsia. CONCLUSION(S): Women with endometriosis have a statistically significantly higher risk of preterm birth, miscarriage, placenta previa, small for gestational age infants, and cesarean delivery.
Disorders of bone density are especially prevalent among athletic women. The severity of bone loss ranges from osteopenia to frank osteoporosis. In female athletes, a higher incidence of osteoporosis is due to a decreased rate of bone accretion in youth, often as a result of hormonal deficiency and/or excessive exercise. Low bone mass poses a particular challenge for athletes because it predisposes to stress-related bone injuries and increases the risk of osteoporosis and insufficiency fractures with aging. This article reviews the pathophysiology of bone thinning in premenopausal and postmenopausal women, the impact of exercise, and the treatment options presently available.
The Creighton Model FertilityCare(TM) System (CrM) is a standardized approach for educating women about the biomarkers of their fertility. Couples can use this information for timing intercourse during "fertile" or "infertile" days in order to try to conceive or to avoid pregnancy. The study of Creighton Model Effectiveness, Intentions, and Behaviors Assessment (CEIBA) was conducted to assess fertility motivations, intentions, fertility-related sexual behaviors, and their impact on effectiveness to avoid and to conceive among new users of the CrM. This paper reports enrollment baseline characteristics. We conducted this prospective cohort study at 17 CrM FertilityCare(TM) Centers; 16 in the USA and one in Toronto, Canada. Couples who were new or returning users of the CrM were eligible. Couples who were initially trying to conceive or had a history of subfertility were excluded. Couples were enrolled and followed prospectively by their CrM instructors and also by CEIBA study staff. They completed baseline questionnaires. 1,132 new couples were assessed; 1,090 (96%) couples were screened; 429 (39%) couples were eligible; 305 women (71%) and 290 (95%) male partners were enrolled. The majority of women was engaged (39%) or married (51%), college graduates (77%), Caucasian non-Hispanic (80%), and Roman Catholic (80%). The most common reasons for learning CrM (women) were to use a natural method for family planning (91%), for moral/ethical/religious reasons (70%), the lack of side effects (71%), or insight into the menstrual cycle and fertility (62%). Women and men intended to have a mean of three and two additional children, respectively. Of women, 21% intended to have a child within a year and 60% between 1 and 3 years. The mean positive childbearing motivation score was 3.3 for both women and men (range 1-4, with 4 being most positive). Couples beginning use of the CrM to avoid pregnancy have high levels of motivation, desire, and intention for future childbearing. The CEIBA study has prospective measures of desires, intentions, and sexual/fertility behaviors for up to 1 year. We will assess the impact of desires, intentions, and behaviors on the pregnancy rates among these couples.
PregnancyProbiotic Depression PreventionLactobacillus rhamnosus InterventionProbiotic Pregnancy Mental Health Trial
Open Access
Probiotics may help to prevent symptoms of anxiety and depression through several putative mechanisms. The aim of this study was to evaluate the effect of Lactobacillus rhamnosus HN001 (HN001) given in pregnancy and postpartum on symptoms of maternal depression and anxiety in the postpartum period. This was a secondary outcome, the primary outcome being eczema in the offspring at 12 months of age.
Design, Setting, A randomised, double-blind, placebo-controlled trial of the effect of HN001 on postnatal mood was conducted in 423 women in Auckland and Wellington, New Zealand. Women were recruited at 14–16 weeks gestation. Women were randomised to receive either placebo or HN001 daily from enrolment until 6 months postpartum if breastfeeding. Modified versions of the Edinburgh Postnatal Depression Scale and State Trait Anxiety Inventory were used to assess symptoms of depression and anxiety postpartum. Australia ACTRN12612000196842. 423 women were recruited between December 2012 and November 2014. 212 women were randomised to HN001 and 211 to placebo. 380 women (89.8%) completed the questionnaire on psychological outcomes, 193 (91.0%) in the treatment group and 187 (88.6%) in the placebo group. Mothers in the probiotic treatment group reported significantly lower depression scores (HN001 mean = 7·7 (SD = 5·4), placebo 9·0 (6·0); effect size -1·2, (95% CI -2·3, -0·1), p = 0·037) and anxiety scores (HN001 12·0 (4·0), placebo 13·0 (4·0); effect size -1·0 (-1·9, -0·2), p = 0·014) than those in the placebo group. Rates of clinically relevant anxiety on screening (score > 15) were significantly lower in the HN001 treated mothers (OR = 0·44 (0·26, 0·73), p = 0·002). Women who received HN001 had significantly lower depression and anxiety scores in the postpartum period. This probiotic may be useful for the prevention or treatment of symptoms of depression and anxiety postpartum.
InfertilityAffordability and AccessFertility TreatmentComparison with ART
What is the optimal endometrial preparation protocol for a frozen embryo transfer (FET)?Summary answerAlthough the optimal endometrial preparation protocol for FET needs further research and is yet to be determined, we propose a standardized timing strategy based on the current available evidence which could assist in the harmonization and comparability of clinic practice and future trials. Amid a continuous increase in the number of FET cycles, determining the optimal endometrial preparation protocol has become paramount to maximize ART success. In current daily practice, different FET preparation methods and timing strategies are used.Study design, size, durationThis is a review of the current literature on FET preparation methods, with special attention to the timing of the embryo transfer.Participants/materials, setting, methodsLiterature on the topic was retrieved in PubMed and references from relevant articles were investigated until June 2017.Main results and the role of chanceThe number of high quality randomized controlled trials (RCTs) is scarce and, hence, the evidence for the best protocol for FET is poor. Future research should compare both the pregnancy and neonatal outcomes between HRT and true natural cycle (NC) FET. In terms of embryo transfer timing, we propose to start progesterone intake on the theoretical day of oocyte retrieval in HRT and to perform blastocyst transfer at hCG + 7 or LH + 6 in modified or true NC, respectively.Limitations reasons for cautionAs only a few high quality RCTs on the optimal preparation for FET are available in the existing literature, no definitive conclusion for benefit of one protocol over the other can be drawn so far.Wider implications of the findingsCaution when using HRT for FET is warranted since the rate of early pregnancy loss is alarmingly high in some reports.Study funding/competing interest(s)S.M. is funded by the Research Fund of Flanders (FWO). H.T. and C.B. report grants from Merck, Goodlife, Besins and Abbott during the conduct of the study.Trial registration numberNot applicable.
Studies have demonstrated an association between hormonal contraception use with subsequent depression and antidepressant use. This association has not been assessed among postpartum women. This study is a secondary analysis of insurance records from 75,528 postpartum women enrolled in the US military medical system, who delivered between October 2012 and September 2014. Our analyses excluded women who used antidepressants or had a diagnosis of depression in the 24months prior to delivery. We assessed the relationship of hormonal contraception use with subsequent antidepressant use or diagnosis with depression in the first 12months postpartum using Cox proportional hazards regression, with a time dependent covariate measuring exposure to hormonal contraception. Antidepressants were prescribed to 7.8% of women and 5.0% were diagnosed with depression. In multivariable analysis adjusting for demographics, both antidepressant use and diagnosis with depression younger age, lower socioeconomic status, and a history of military service. Compared to women with no hormonal contraceptive use, use of etonogestrel containing contraception was associated with a higher risk of antidepressant use (Implant: 1.22(95%CI:1.06-1.41), p<0.001; 1.45(1.16-1.80), p=0.001). Use of norethindrone-only pills was associated with a lower risk of antidepressant use (0.58(0.52-0.64), p<0.001) and depression diagnosis (0.56(0.49-0.64), p<0.001). Use of a levonorgestrel intrauterine system was associated with a lower risk of depression diagnoses (0.65(0.52-0.82), p<0.001). The risk of major depression diagnosis and antidepressant use in the postpartum period varies with the type of hormonal contraception used. Further research is required to describe the mechanisms of these relationships.
Bone HealthProgesterone Bone Formation ContributionEstrogen-Progestin vs Estrogen-Only BMDHormone Therapy Bone Density
Prior JC et al., 2017·J Musculoskelet Neuronal Interact
To assess whether progesterone (P4) or osteoblast P4 receptor-acting progestin (P) contributed to estrogen (E) therapy-related increased areal bone mineral density (BMD) in randomized controlled trials (RCT) with direct randomization to estrogen (ET) or estrogen-progestin (EPT) therapy. Systematic literature searches in biomedical databases identified RCT with direct randomization and parallel estrogen doses that measured spinal BMD change/year. Cyclic P4/P was included in this random effects meta-analysis only if for ≥ half the number of E-days. Searches yielded 155 publications; five met inclusion criteria providing eight dose-parallel ET-EPT comparisons in 1058 women. Women averaged mid-50 years, ⟨five years into menopause and took conjugated equine E daily at 0.625 mg with/without 2.5 mg medroxyprogesterone acetate (MPA). The weighted mean EPT minus ET percentage difference in spinal BMD change was +0.68%/year (95% CI 0.38, 0.97%) (P=0.00001). This result was highly heterogeneous (I²=81%) but this may reflect the small number of studies. Estrogen with an osteoblast P4R-acting progestin (EPT) in these five published RCT provides Level 1 evidence that MPA caused significantly greater annual percent spinal BMD gains than the same dose of ET. These data have implications for management of vasomotor symptoms and potentially for osteoporosis treatment in menopausal women.
Khayat S et al., 2017·Journal of clinical and diagnostic research : JCDR
Micronutrients (include vitamins and minerals) are essential for normal function, growth and development. Minerals have important effects on the health of the mother and foetus. But biological mechanisms of minerals are not completely understood. Micronutrient deficiency during pregnancy can lead to anaemia, hypertension, obstetric complications and even maternal death and in foetus lead to a fail in growth and development. Mineral deficiency during pregnancy, particularly exist in developing countries. During pregnancy due to the increased demands caused by physiological changes, deficiency is exaggerated and as a result its complications occur. Thus, ensuring to receive enough macronutrients and micronutrients before and during pregnancy, is important. Nevertheless, there are controversies regarding administrating supplements. There are not enough studies about some of the minerals and the challenges remain. Regarding the importance of minerals in pregnancy and lactation, in this review we will analyze the role of them in pregnancy and lactation.
Low levels of gonadal circulating estrogen observed in post-menopausal women can adversely impact a diverse range of physiological factors, with clinical implications for brain cognition, gut health, the female reproductive tract and other aspects of women's health. One of the principal regulators of circulating estrogens is the gut microbiome. This review aims to shed light on the role of the gut microbiota in estrogen-modulated disease. The gut microbiota regulates estrogens through secretion of β-glucuronidase, an enzyme that deconjugates estrogens into their active forms. When this process is impaired through dysbiosis of gut microbiota, characterized by lower microbial diversity, the decrease in deconjugation results in a reduction of circulating estrogens. The alteration in circulating estrogens may contribute to the development obesity, metabolic syndrome, cancer, endometrial hyperplasia, endometriosis, polycystic ovary syndrome, fertility, cardiovascular disease (CVD) and cognitive function. The bi-directional relationship between the metabolic profile (including estrogen levels) and gut microbiota in estrogen-driven disease will also be discussed. Promising therapeutic interventions manipulating the gut microbiome and the metabolic profile of estrogen-driven disease, such as bariatric surgery and metformin, will be detailed. Modulation of the microbiome composition subsequently impacts the metabolic profile, and vice versa, and has been shown to alleviate many of the estrogen-modulated disease states. Last, we highlight promising research interventions in the field, such as dietary therapeutics, and discuss areas that provide exciting unexplored topics of study.
Su HW et al., 2017·Bioengineering & translational medicine
The ability to identify the precise time of ovulation is important for women who want to plan conception or practice contraception. Here, we review the current literature on various methods for detecting ovulation including a review of point-of-care device technology. We incorporate an examination of methods to detect ovulation that have been developed and practiced for decades and analyze the indications and limitations of each-transvaginal ultrasonography, urinary luteinizing hormone detection, serum progesterone and urinary pregnanediol 3-glucuronide detection, urinary follicular stimulating hormone detection, basal body temperature monitoring, and cervical mucus and salivary ferning analysis. Some point-of-care ovulation detection devices have been developed and commercialized based on these methods, however previous research was limited by small sample size and an inconsistent standard reference to true ovulation.
Frank-Herrmann P et al., 2017·Eur J Contracept Reprod Health Care
Sir,Currently, a variety of start-up companies are developing mobile phone apps to track the menstrual cycle and the fertile window, for the use of women who are trying to conceive or trying to avo...
InfertilityDietary Patterns and Fecundability ReviewSemen Quality and Dietary FactorsMediterranean Diet and Fertility
The literature on the relationship between diet and human fertility has greatly expanded over the last decade, resulting in the identification of a few clear patterns. Intake of supplemental folic acid, particularly at doses higher than those recommended for the prevention of neural tube defects, has been consistently related to lower frequency of infertility, lower risk of pregnancy loss, and greater success in infertility treatment. On the other hand and despite promising evidence from animal models, vitamin D does not appear to exert an important role in human fertility in the absence of deficiency. Antioxidant supplementation does not appear to offer any benefits to women undergoing infertility treatment, but it appears to be beneficial when it is the male partner who is supplemented. However, the available evidence does not allow discerning which specific antioxidants, or at which doses, are responsible for this benefit. Long-chain omega-3 fatty acids appear to improve female fertility, although it remains unclear to what extent contamination of shared food sources, such as fish with high levels of environmental toxicants, can dampen this benefit. Lastly, adherence to healthy diets favoring seafood, poultry, whole grains, fruits, and vegetables are related to better fertility in women and better semen quality in men. The cumulative evidence has also piled against popular hypotheses. Dairy and soy, once proposed as reproductive toxicants, have not been consistently related to poor fertility. In fact, soy and soy supplements appear to exert a beneficial effect among women undergoing infertility treatment. Similarly, because data from large, high-quality studies continue to accumulate, the evidence of a potentially deleterious effect of moderate alcohol and caffeine intake on the ability to become pregnant seems less solid than it once did. While a complete picture of the role of nutrition on fertility is far from complete, much progress has been made. The most salient gaps in the current evidence include jointly considering female and male diets and testing the most consistent findings in randomized trials.
PCOSMyo-Inositol and D-Chiro-Inositol SupplementationInositol TherapyNon-Pharmaceutical Ovulation Restoration
Open Access
Polycystic ovary syndrome (PCOS)’s rate is about 6% to10% among the reproductive aged women; it is characterized by menstrual cycle irregularity with oligo-anovulation, hyperandrogenism, insulin resistance, and compensatory hyperinsulinemia. Despite the fact that the last two elements are present in a large percentage of PCOS women, they are not mandatory for the diagnosis; in order to explain the pathogenesis in these patients, it was supposed that ovarian theca cells got higher insulin sensitivity probably related to the mechanism of intracellular signalling transduction (1). Corroborating this view, it was previously demonstrated that diazoxid, which has the well-known effect of decreasing insulin levels, reduced hyperandrogenism in lean women affected by PCOS, even in the cases of normal insulin level and insulin sensitivity (2). Based on the detrimental role of insulin resistance, several insulin sensitizer drugs have been used to ameliorate PCOS symptoms and signs. Although metformin has represented the landmark of PCOS therapy in the recent past, to date several studies have tested the efficacy of Inositols, a carbocyclic polyols. Two stereoisomers, in particular Myo-inositol (MI) and D-Dhiro-inositol (DCI) showed a clinical efficacy and safety during PCOS. MI is converted in DCI by epimerase, an enzyme regulated also by insulin action. In the form of inositol-phosphoglycans (IPGs), they are involved in a non-classical insulin receptor is coupled by G-protein which can activate phospholipase, allowing the release of second messengers (DCI-glycan), which is able to stimulate pyruvate dehydrogenase and glycogen synthase activities, the enzyme involved in the oxidative and the non-oxidative glucose metabolism (3). On one hand, MI-IPG is able to inhibit cyclic adenosine monophosphate (cAMP) kinase and adenylyl cyclase, both involved in free fatty acid metabolism. On the other hand, DCI-IPG play a pivotal role during the binding of insulin to its receptor on cell membrane where it stimulates IPG release and starts signalling cascade. In addition, Inositols are incorporated in membrane phospholipids as phosphoinositides. Phosphatidylinositol 4, 5 bisphosphate (PtdIns-4, 5P) and phosphatidylinositol 4P (PtdIns-4P), in particular, are involved in the regulation of the cytoskeleton structure and in the regulation of cellular motility, which account also the beneficial effects of Inositol administration on sperm parameters. PtdIns-4, 5P plays a key role in controlling calcium-mediated intracellular signalling which is mandatory to address the oocytes maturation and fecundation (4).
PCOSCurcumin Anti-Inflammatory EffectsCurcumin InterventionPCOS Hepatic Inflammation Study
Curcumin protects the liver against injury and fibrosis through suppressing hepatic inflammation, attenuating hepatic oxidative stress (OS), and inhibiting hepatic stellate cells (HSCs) activation. Non-alcoholic fatty liver disease (NAFLD) and polycystic ovary syndrome (PCOS) are considered as common metabolic disorders. Low-grade chronic inflammation with different markers, such as elevated C-reactive protein (CRP) and interleukin-6 (IL-6) levels, play a crucial role in PCOS. This study aimed to evaluate the therapeutic effects of curcumin on IL-6 and CRP levels as well as insulin resistance (IR) index on liver function in PCOS rats. In this experimental study, 90 adult Wistar rats were divided into control (n=18), sham (n=18), PCOS (n=18) and curcumin-treated PCOS groups (n=36). PCOS group was injected subcutaneously with 2 mg estradio-valerate (E2V). After 60 days, PCOS group was treated with curcumin [100 and 300 mg/kg body weight (BW)] for 14 days and anesthetized by chloroform. Blood and liver samples were collected for histological and serological analyses. Data were analyzed using In-Stat 3 via one-way analysis of variance (ANOVA). Histological and serological analyses showed a reduction in number of necrotic cells, IR index, as well as IL-6 and CRP levels in PCOS rats that were treated with various concentrations of curcumin. In this study, curcumin decreased liver inflammation by induction of insulin sensitivity and reduction of hepatic necrosis. Therefore, curcumin may be considered as protective factor against inflammatory state of PCOS.
Reproductive EndocrinologyDisease Mechanism ReviewROS in Health and DiseaseGamete Quality and Reproductive Impact
Open Access
Oxidative stress is a phenomenon caused by an imbalance between production and accumulation of oxygen reactive species (ROS) in cells and tissues and the ability of a biological system to detoxify these reactive products. ROS can play, and in fact they do it, several physiological roles (i.e., cell signaling), and they are normally generated as by-products of oxygen metabolism; despite this, environmental stressors (i.e., UV, ionizing radiations, pollutants, and heavy metals) and xenobiotics (i.e., antiblastic drugs) contribute to greatly increase ROS production, therefore causing the imbalance that leads to cell and tissue damage (oxidative stress). Several antioxidants have been exploited in recent years for their actual or supposed beneficial effect against oxidative stress, such as vitamin E, flavonoids, and polyphenols. While we tend to describe oxidative stress just as harmful for human body, it is true as well that it is exploited as a therapeutic approach to treat clinical conditions such as cancer, with a certain degree of clinical success. In this review, we will describe the most recent findings in the oxidative stress field, highlighting both its bad and good sides for human health.
PostpartumBreast Cancer Risk ReductionBlack Mothers Breastfeeding and CancerProtective Health Effects of Breastfeeding
Breast cancer is the most commonly diagnosed cancer and a leading cause of death from cancer among U.S. women. Studies have suggested that breastfeeding reduces breast cancer risk among parous women, and there is mounting evidence that this association may differ by subtype such that breastfeeding may be more protective of some invasive breast cancer types. The purpose of this review is to discuss breast cancer disparities in the context of breastfeeding and the implications for black mothers. Black women in the U.S. have lower rates of breastfeeding and nearly twice the rates of triple-negative breast cancer (an aggressive subtype) compared with white women. In addition to individual challenges to breastfeeding, black women may also differentially face contextual barriers such as a lack of social and cultural acceptance in their communities, inadequate support from the healthcare community, and unsupportive work environments. More work is needed to improve the social factors and policies that influence breastfeeding rates at a population level. Such efforts should give special consideration to the needs of black mothers to adequately address disparities in breastfeeding among this group and possibly help reduce breast cancer risk. Interventions such as peer counseling, hospital policy changes, breastfeeding-specific clinic appointments, group prenatal education, and enhanced breastfeeding programs have been shown to be effective in communities of color. A comprehensive approach that integrates interventions across multiple levels and settings may be most successful in helping mothers reach their breastfeeding goals and reducing disparities in breastfeeding and potentially breast cancer incidence.
PregnancyInositol Prevention StrategyInositol Supplementation in PregnancyGDM Prevention with Inositol
The aim of the present study was to demonstrate that the use of inositol and folic acid from the first trimester of pregnancy, counteracts the onset of gestational diabetes mellitus (GDM) in women at risk, preserving the infants from macrosomia, hypoglycemia and preterm delivery. The authors collected data from the pregnant women at the laboratory (Unit of Cytogenic and Molecular Genetics), from January 2014 to April 2016, all with first trimester fasting plasma glucose (FPG) >92 mg/dl. A total of 40 women were treated with 250 mg/day D-chiro-inositol, 1.75 g/day D-myo-inositol, 12.5 mg/day zinc, 10 mg/day methylsulfonylmethane, 400 µg/day 5-methyltetrahydrofolic acid. The other 43 women (control group) were treated with only 400 µg/day folic acid. The primary outcome measure was the incidence of maternal GDM. The secondary outcome measures were the incidence of fetal macrosomia, preterm delivery and neonatal hypoglycemia. At the 24th week of pregnancy, the incidence of maternal GDM was recorded in 18 women in the control group and in 5 women in the treated group [relative risk (RR)=3.35; 95% confidence interval (CI)=1.37-8.17; P=0.0028). A significant difference was observed between treated and control groups in terms of risk of macrosomia. A total of seven infants in the control group, and two in the treated group, weighed >4,000 g (RR=5,12; 95% CI=1.21-21.68; P=0.0099). No significant difference was identified between two groups, regarding the other two secondary outcomes, neonatal hypoglycemia (RR=4.650; 95% CI=0.57-38.11; P=0.1086) and preterm delivery (RR=1.74; 95% CI=0.83-3.66; P=0.1301). The current study demonstrated the potential benefit of supplementation with the association of D-chiro-inositol and D-myo-inositol in pregnant 'at risk' women, with first trimester FPG >92 mg/dl, in preventing the onset of maternal GDM and macrosomia in newborns.
Menstrual CycleFolate Homocysteine and Ovulatory FunctionOvarian Cycle EffectsB-Vitamin Status and Anovulation
How are concentrations of plasma homocysteine and serum folate associated with reproductive hormones and anovulation in regularly menstruating women? Higher homocysteine was associated with sporadic anovulation and hormonal changes that may be indicative of impaired ovulatory function, but higher serum folate was associated only with higher luteal phase progesterone. Higher folate levels as well as some variants in genes relevant to one-carbon metabolism, are associated with improved reproductive outcomes and responses to fertility treatment, but only a few small studies have explored the relationship between markers of one-carbon metabolism and menstrual cycle characteristics. STUDY DESIGN, SIZE, The BioCycle Study (2005-2007) is a prospective, longitudinal cohort of 259 regularly menstruating women not using hormonal contraceptives or dietary supplements who were followed for up to two menstrual cycles. PARTICIPANTS/MATERIALS, SETTING, Serum folate and reproductive hormones were measured up to eight times per cycle and plasma homocysteine up to three times. Linear mixed models were used to estimate associations between serum folate or plasma homocysteine and log-transformed reproductive hormone levels while accounting for multiple observations and cycles per woman. Generalized estimating equations were used to examine risk of sporadic anovulation. All models were adjusted for age, race, body mass index, cigarette and alcohol use, and energy and fiber intake. Main Higher plasma homocysteine concentrations were associated with lower total estradiol across the cycle (adjusted percent change per unit increase in homocysteine [aPC] -2.3%, 95% CI: -4.2, -0.03), higher follicle stimulating hormone around the time of expected ovulation (aPC 2.4%, 95% CI: 0.2, 4.7) and lower luteal phase progesterone (aPC -6.5%, 95% CI: -11.1, -1.8). Higher serum folate concentrations were associated with higher luteal phase progesterone (aPC per unit increase in folate 1.0%, 95% CI: 0.4, 1.6). Higher homocysteine concentrations at expected ovulation were associated with a 33% increased risk of sporadic anovulation. We observed no risk associated with decreased folate concentrations, but a higher ratio of folate to homocysteine at ovulation was associated with a 10% decreased risk of anovulation. LIMITATIONS, Our results are generalizable to healthy women with adequate serum folate levels. The independent influence of homocysteine should be confirmed in larger cohorts and among women with folate deficiency or increased risks of anovulation. If these findings are confirmed, it is possible that lowering homocysteine with B-vitamins through diet or supplementation could improve ovulatory function in some women. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health (Contract HHSN275200403394C, HHSN275201100002I and Task one HHSN27500001). None of the authors has any conflicts of interest to disclose.
To evaluate the association between endometriosis end chronic endometritis (CE) diagnosed by hysteroscopy, conventional histology, and immunohistochemistry. Case-control study. University hospital. PATIENT(S): Women with and without endometriosis who have undergone hysterectomy. INTERVENTION(S): Retrospective evaluation of 78 women who have undergone hysterectomy and were affected by endometriosis and 78 women without endometriosis. MAIN OUTCOME MEASURE(S): CE diagnosed based on conventional histology and immunohistochemistry with anti-syndecan-1 antibodies to identify CD138 cells. RESULT(S): The prevalence of CE was statistically significantly higher in the women with endometriosis as compared with the women who did not have endometriosis (33 of 78, 42.3% vs. 12 of 78, 15.4% according to hysteroscopy; and 30 of 78, 38.5% vs. 11 of 78, 14.1% according to histology). The women were divided into two groups, 115 patients without CE and 41 patients with CE. With univariate analysis, parity was associated with a lower risk for CE, and endometriosis was associated with a statistically significantly elevated risk of CE. Using multivariate analysis, parity continued to be associated with a lower incidence of CE, whereas endometriosis was associated with a 2.7 fold higher risk. CONCLUSION(S): The diagnosis of CE is more frequent in women with endometriosis. Although no etiologic relationships between CE and endometriosis can be established, this study suggests that CE should be considered and if necessary ruled out in women with endometriosis, particularly if they have abnormal uterine bleeding. Identification and appropriate treatment of CE may avoid unnecessary surgery.
Bone HealthVertebral Fracture AssessmentSex DifferencesRadiological Assessment
We compared two methods for osteoporotic vertebral fracture (VF) assessment on lateral spine radiographs, the Genant semiquantitative (GSQ) technique and a modified algorithm-based qualitative (mABQ) approach. We evaluated 4465 women and 1771 men aged ≥50 years from the Canadian Multicentre Osteoporosis Study with available X-ray images at baseline. Observer agreement was lowest for grade 1 VFs determined by GSQ. Among physician readers, agreement was greater for VFs diagnosed by mABQ (ranging from 0.62 [95% confidence interval (CI) 0.00-1.00] to 0.88 [0.76-1.00]) than by GSQ (ranging from 0.38 [0.17-0.60] to 0.69 [0.54-0.85]). GSQ VF prevalence (16.4% [95% CI 15.4-17.4]) and incidence (10.2/1000 person-years [9.2; 11.2]) were higher than with the mABQ method (prevalence 6.7% [6.1-7.4] and incidence 6.3/1000 person-years [5.5-7.1]). Women had more prevalent and incident VFs relative to men as defined by mABQ but not as defined by GSQ. Prevalent GSQ VFs were predominantly found in the mid-thoracic spine, whereas prevalent mABQ and incident VFs by both methods co-localized to the junction of the thoracic and lumbar spine. Prevalent mABQ VFs compared with GSQ VFs were more highly associated with reduced adjusted L(1) to L(4) bone mineral density (BMD) (-0.065 g/cm(2) [-0.087 to -0.042]), femoral neck BMD (-0.051 g/cm(2) [-0.065 to -0.036]), and total hip BMD (-0.059 g/cm(2) [-0.076 to -0.041]). Prevalent mABQ VFs compared with prevalent GSQ were also more highly associated with incident VF by GSQ (odds ratio [OR] = 3.3 [2.2-5.0]), incident VF by mABQ (9.0 [5.3-15.3]), and incident non-vertebral major osteoporotic fractures (1.9 [1.2-3.0]). Grade 1 mABQ VFs, but not grade 1 GSQ VFs, were associated with incident non-vertebral major osteoporotic fractures (OR = 3.0 [1.4-6.5]). We conclude that defining VF by mABQ is preferred to the use of GSQ for clinical assessments.
Glazer CH et al., 2017·Human reproduction (Oxford, England)
Is male factor infertility associated with an increased risk of developing diabetes? The study provides evidence that male factor infertility may predict later occurrence of diabetes mellitus with the risk being related to the severity of the underlying fertility problem. Previous cross-sectional studies have shown an increased prevalence of comorbidities among infertile men when compared to controls. STUDY DESIGN, SIZE, In this prospective cohort study, 39 516 men who had since 1994 undergone fertility treatment with their female partner were identified from the Danish national IVF register, which includes data on assumed cause of couple infertility (male/female factor, mixed and unexplained infertility) and type of fertility treatment. With a median follow-up time of 5.6 years, each man was followed for diabetes occurrence from enrollment until 31 December 2012 using the National Diabetes Register (NDR). Men with a history of diabetes prior to their fertility diagnosis were excluded. Hazard ratios (HR) were estimated by Cox proportional hazard models with age as the underlying time scale. In addition to analyzing the data for the entire IVF registration period (1994-2012), separate analyses were performed for men identified from the first (1994-2005) and second (2006-2012) IVF registration period owing to heterogeneity in the reporting of male factor infertility in these two time periods, because the reason for male factor infertility was not available from the first register. PARTICIPANTS/MATERIALS, SETTING, Male factor infertility was identified from the variable 'yes' or 'no' from the first IVF register and through a diagnosis code (e.g. oligospermia, azoospermia) from the second IVF register. The reference group was men with male factor infertility (='no') and those with normal semen quality or sterilized men. Of the included men, 18 499 (46.8%) had male factor infertility and 21 017 (53.2%) made up the reference group. MAIN A total of 651 (1.6%) diabetes cases were identified during the follow-up period. The adjusted HR's for diabetes risk among men with male factor infertility when compared to the reference group were HR = 1.08 (95% CI: 0.89, 1.31) and HR = 1.45 (95% CI: 1.06, 1.97) for the first and second IVF registration period, respectively. When assessing the effects of individual causes of male factor infertility, the adjusted HR's for men with oligospermia, azoospermia and aspermia were HR = 1.44 (95% CI: 1.01, 2.06), HR = 2.10 (95% 1.25, 3.56) and HR = 3.20 (95% CI 1.00, 10.31), respectively. LIMITATIONS, We found no increased risk among men identified from the first IVF register, which may be related to exposure misclassification as the reason for male factor infertility was not available from this time period. The NDR does not distinguish between type 1 and type 2 diabetes. These findings support previous studies that a man's reproductive and somatic health are closely intertwined and highlight the importance for further monitoring of these men. Further, implementation of diabetes screening may be especially relevant among aspermic and azoospermic men. This article is part of the ReproUnion collaborative study, co-financed by the European Union, Intereg V Öresund-Kattegat-Skagerrak. None of the authors declare any conflict of interest. None.
Minebois H et al., 2017·Gynécologie Obstétrique Fertilité & Sénologie
In spontaneous pregnancies, endometriosis appears to be a risk factor of miscarriage. The aim of this study is to evaluate the association between endometriosis and miscarriage in spontaneous pregnancy. We searched the Cochrane Library, Medline of eligible studies from inception to December 2016, without any restriction. We selected studies that compared endometriosis-affected pregnant women to disease-free pregnant women. To ensure the quality of the methodology, the PRISMA criteria have been met at all stages of the development of this meta-analysis. The primary adverse pregnancy outcomes studied was miscarriage. Three reviewers independently extracted the studies' characteristics and outcome data. Of 225 identified abstracts, 4 primary studies met our inclusion criteria by comparing spontaneous pregnant patients with endometriosis to disease-free women. Miscarriage rate was higher in the endometriosis group (OR 1.77 [CI 95% 1.13-2.78]). In spontaneous pregnancies, endometriosis appears to be a risk factor of miscarriages (almost 80% increased risk). Further prospective studies are needed to confirm these results in order to establish the exact impact of endometriosis on spontaneous pregnancy course.
Herzberg SD et al., 2017·Orthopaedic journal of sports medicine
Women are at substantially greater risk for anterior cruciate ligament (ACL) injuries than are men. To conduct a systematic review and meta-analysis of the literature to clarify the effect of the menstrual cycle and contraceptives on the laxity of and noncontact injuries to the ACL. Systematic review; Level of evidence, 4. Searches were conducted using MEDLINE (1946-August 2016), the Cochrane Library Database, clinical trial registries, and related reference lists. Search terms included athletic injuries, knee injuries, ligaments, joint instability, menstrual cycle, ovulation, hormones, and contraceptives. Investigators independently dually abstracted and reviewed study details and quality using predefined criteria and evaluated overall strength of evidence using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) criteria. Twenty-one studies totaling 68,758 5 on the menstrual cycle and ACL injury, 7 on hormonal contraceptives and ACL injury, as well as 13 on menstrual cycle and ligament laxity. Four of 5 studies of women not using hormonal contraception indicated that the luteal phase was the least associated with ACL injuries. The 2 largest and highest quality studies on hormonal contraceptives suggested that hormonal contraceptives may be protective against ACL injury. Six of 12 studies on ACL laxity provided quantitative data for meta-analysis, finding significantly increased laxity during the ovulatory phase compared with the follicular phase. The literature suggests an association between hormonal fluctuations and ACL injury. Recent studies have suggested that oral contraceptives may offer up to a 20% reduction in risk of injury. The literature on ACL injuries and the menstrual cycle has more than doubled over the past decade, permitting quantitative analysis for the first time. However, the overall strength of this evidence is low. Promising potential directions for future research include long-term observational studies with ongoing hormonal assays and large interventional trials of follicular suppression, including newer hormonal methods.
Malaria is prevalent in Nigeria, and artemether + lumefantrine (artemisinin-based combination therapy [ACT]) is drug of choice in treatment of uncomplicated cases. ACT is contraindicated in early pregnancy. They release-free radicals that can compromise female fertility. Infertility and its associated complications such as miscarriages, abnormal gestation, and unstable marriages seem to be on the increase. This study aims at evaluating the effect of ACT on female fertility. The significance of this research is to draw the attention of fertility care givers to this possible cause of infertility and fertility challenges. Creighton Model FertilityCare System and NaProTECHNOLOGY are simply technologies that can be used to assess female fertility. They are used in this study to assess the effect of ACT administered at different stages of menstrual cycles of three selected fertile adult females. The results are interpreted on the background of standard Creighton model chart. This study has shown that ACT has a significant fertility deteriorating effect on the women. It caused ovulation defect and diagnosed as partial rupture syndrome in the very cycle of use and in the first cycle after use. It also significantly reduced cervical mucus production and significantly reduced luteal phase progesterone production with an associated significant increase of luteal phase estrogen production. ACT use as antimalarial may be a possible cause of infertility and fertility challenges in women.
NaProTECHNOLOGYCulture of LifeResponsible ParenthoodCreighton Model System
Open Access
NaProTECHNOLOGY is a new field of medicine specializing in the promotion of human procreation. Its foundation is a teaching system called the Creighton Model Fertility Care System. It is based on the ability to observe and record biological biomarkers, enabling spouses to recognize and understand the naturally occurring cycle of fertility and infertility. The spouses can use their acquired knowledge both for achiving pregnancy and avoiding pregnancy. The system also enables them to broaden their knowledge to better understand sexuality and deepen their mutual love. It also plays an important role in diagnosing and treating reproductive health according to the natural cycle of women. NaProTECHNOLOGY is involved in building a "new culture of life" through integral concern for human fertility by restoring natural procreation and respecting the principles of responsible parenthood.
InfertilityContaminant Exposure and FertilityBPA Phthalate Pesticide EffectsSemen Quality and Chemical Exposure
This review article summarizes the epidemiological findings published between 2011 and 2016 concerning bisphenol A (BPA), phthalates, dioxins, pesticides, air pollution, fracking chemicals, triclosan, and parabens and fertility parameters in men (i.e., semen volume, sperm concentration, sperm motility, and sperm morphology) as well as fertility parameters in women (i.e., cyclicity, fertility treatment outcomes), pregnancy outcomes (i.e., preterm birth,miscarriage), and reproductive disorders (i.e., polycystic ovary syndrome, endometriosis, and uterine fibroids). Overall, this review indicates that several environmental toxicants are significantly associated with reduced fertility parameters in men and women as well as several reproductive disorders in women. Although many studies reported that the selected exposures are associated with adverse fertility outcomes, several studies reported null associations. Thus, future studies are still needed to better elucidate the associations and potential mechanisms between these environmental chemicals and fertility outcomes in men and women.
Preterm preeclampsia is an important cause of maternal and perinatal death and complications. It is uncertain whether the intake of low-dose aspirin during pregnancy reduces the risk of preterm preeclampsia. In this multicenter, double-blind, placebo-controlled trial, we randomly assigned 1776 women with singleton pregnancies who were at high risk for preterm preeclampsia to receive aspirin, at a dose of 150 mg per day, or placebo from 11 to 14 weeks of gestation until 36 weeks of gestation. The primary outcome was delivery with preeclampsia before 37 weeks of gestation. The analysis was performed according to the intention-to-treat principle. A total of 152 women withdrew consent during the trial, and 4 were lost to follow up, which left 798 participants in the aspirin group and 822 in the placebo group. Preterm preeclampsia occurred in 13 participants (1.6%) in the aspirin group, as compared with 35 (4.3%) in the placebo group (odds ratio in the aspirin group, 0.38; 95% confidence interval, 0.20 to 0.74; P=0.004). Results were materially unchanged in a sensitivity analysis that took into account participants who had withdrawn or were lost to follow-up. Adherence was good, with a reported intake of 85% or more of the required number of tablets in 79.9% of the participants. There were no significant between-group differences in the incidence of neonatal adverse outcomes or other adverse events. Treatment with low-dose aspirin in women at high risk for preterm preeclampsia resulted in a lower incidence of this diagnosis than placebo. (Funded by the European Union Seventh Framework Program and the Fetal Medicine Foundation; EudraCT number, 2013-003778-29 ; Current Controlled Trials number, ISRCTN13633058 .).
Fertility AwarenessMedical Student FABM Knowledge AssessmentFABM Curriculum GapPhysician Training in Natural Family Planning
Open Access
Traditional medical school curricula have not addressed fertility awareness-based methods (FABMs) of family planning. The objective of this study was to assess (1) 3-year medical students' knowledge of FABMs of family planning, (2) their confidence in utilizing that knowledge in patient care, and (3) to implement focused education on FABMs to improve knowledge and confidence. Third-year medical students at one institution in the United States were given a 10-question assessment at the beginning of their OB-GYN rotation. Two lectures about FABMs and their clinical applications were given during the rotation. Students were given the same questions at the end of the rotation. Each questionnaire consisted of eight questions to assess a student's knowledge of FABMs and two questions to assess the student's confidence in sharing and utilizing that information in a clinical setting. McNemar's test was used to analyze the data. Two hundred seventy-seven students completed a pretest questionnaire and 196 students completed the posttest questionnaire. Medical knowledge improved from an initial test score of 38.99% to final test score of 53.57% (p < 0.05). Confidence in sharing FABM information with patients (0 = very uncomfortable; 5 = very comfortable) improved from 1.51 to 3.00 (p < 0.05). Confidence in utilizing FABM to diagnose and treat gynecologic/reproductive problems (0 = not very confident and 5 = very confident) improved from 1.01 to 3.15 (p < 0.05). Medical schools may not include FABMs in OB-GYN curriculum; however, to patients, these methods remain a sought after and valid form of family planning. This study shows that brief, focused education can increase medical students' knowledge of and confidence with FABMs of family planning.