To estimate the risk of congenital heart defects (CHD) associated with assisted reproductive technologies (ART).Methods and resultsWe used data from the Paris Registry of Congenital Malformations on 5493 cases of CHD and 3847 malformed controls for which no associations with ART were reported in the literature. Assisted reproductive technologies included inductors of ovulation only, in vitro fertilization, and intracytoplasmic sperm injection. Exposure to ART was higher for cases than controls (4.7 vs. 3.6%, P= 0.008) and was associated with a 40% increase in the maternal age, socioeconomic factors, and year of birth-adjusted odds of CHD without chromosomal abnormalities [adjusted odds ratio (OR) 1.4, 95% confidence interval (CI) 1.1-1.7]. Assisted reproductive technologies were specifically associated with significant increases in the odds of malformations of the outflow tracts and ventriculoarterial connections (adjusted OR 1.7, 95% CI 1.2-2.4) and of cardiac neural crest defects and double outlet right ventricle (adjusted OR 1.7, 95% CI 1.1-2.7). In general, we found specific associations between methods of ART and subcategories of CHD. Cases with CHD were more likely to have been conceived following ART when compared with malformed controls. This higher risk for CHD varied specifically according to the method of ART and the type of CHD and may be due to ART per se and/or the underlying infertility of couples.
Fathizadeh N et al., 2010·Iranian journal of nursing and midwifery research
Since premenstrual syndrome (PMS) can cause suicide, dissociation of familial relationships, abnormalities in the daily work and inter-personal relationships in the patients, and bring about direct and indirect economic burden for the society, it is important to resolve the problems of the patients. The objective of the current study is to determine the effect of magnesium (Mg), combination of vitamin B6 and Mg, and the placebo on the severity of PMS in the patients affected by the disease referred to the health centers of Isfahan University of Medical Sciences during 2009-2010. The participants were randomly assigned to two intervention groups and one control group. The study was carried out for four months in ten selected health centers in Isfahan. To confirm the PMS diagnosis in patients, they were asked to fill out the PMS daily symptom record form for two months and then, when the diagnosis was confirmed, the participants were randomly assigned to one of the three groups of the study (Mg, Mg plus vitamin B6, and placebo). Medical intervention was carried out in two menstrual cycles and the results of pre- and post-test were compared. After the intervention, the mean score of PMS significantly decreased in all the three groups (p < 0.05). The decrease was the greatest in the Mg plus vitamin B6 group, and was the least in the placebo group. The findings indicated that Mg plus vitamin B6 and placebo has the greatest and the least effect on the mean score of PMS, respectively.
Yogev Y et al., 2010·American journal of obstetrics and gynecology
The purpose of this study was to evaluate pregnancy outcome in women at extremely advanced maternal age (≥ 45 years). We compared the condition of women aged ≥ 45 years (n = 177) in a 10:1 ratio (20-29, 30-39, and 40-44 years.). Subgroup analysis compared the condition of women aged 45-49 years with those women aged ≥ 50 years. The rates of gestational diabetes mellitus and hypertensive complications were higher for the study group, compared with the whole group (17.0% vs 5.6% and 19.7% vs 4.5%, respectively; P < .001), as was the rate of preterm delivery at <37 and <34 weeks of gestation (odds ratio [OR], 2.1; 95% confidence interval [CI], 1.2-3.6 and OR, 3.5; 95% CI, 1.4-9.0, respectively). The rates of cesarean delivery (OR, 31.8; 95% CI, 18.0-56.1), placenta previa, postpartum hemorrhage, and adverse neonatal outcome were significantly higher among the study group. The risk for gestational diabetes mellitus, preeclampsia toxemia, preterm delivery, and neonatal intensive care unit admission was increased for women aged ≥ 50 years. Pregnancy at extreme advanced maternal age is associated with increased maternal and fetal risk.
Sakumoto T et al., 2010·Reproductive medicine and biology
Obesity, which disturbs lipid and glucose metabolism, is a recent medical concern. It threatens human health and also has adverse effects on reproductive functions by causing insulin resistance/hyperinsulinemia, especially in women with polycystic ovary syndrome (PCOS). For PCOS patients to prevent these adverse effects, it is important to take into account improving their lifestyles by exercise and proper diets. The relationship between insulin resistance/hyperinsulinemia and reproductive disorders should be understood as fully as possible in order to provide effective treatment. It is well known that insulin resistance and compensatory hyperinsulinemia can be triggered by obesity with visceral fat accumulation. Hyperinsulinemia affects granulosa cells in small follicles and theca cells. This condition induces early response to luteinizing hormones on granulosa cells of small follicles and causes premature differentiation of these cells, which eventually results in anovulation. For improvement of anovulation because of hyperinsulinemia, insulin-sensitizing agents (biguanide and thiazolidinedione derivatives) are useful. Hyperinsulinemia may adversely affect the endometrial functions and environment, and evoke implantation disturbance. Treatment with an insulin-sensitizing agent (metformin) improves the levels of glycodelin, insulin-like growth factor binding protein 1, and blood flow in spiral arteries during the peri-implantation period. It supports endometrial function, improves the endometrial environment, and facilitates embryo implantation. The rate of early pregnancy loss during the first trimester is 30-50% in women with PCOS, which is threefold higher than for normal women. Metformin treatment improves the levels of insulin, the homeostasis model assessment for insulin resistance, and plasminogen activator inhibitor activity, and decreases early pregnancy loss. It goes without saying that lifestyle change is fundamental for improving reproductive performance in addition to treatment with insulin-sensitizing agents.
Koren G et al., 2010·American journal of obstetrics and gynecology
To evaluate the effectiveness of Diclectin (doxylamine succinate 10 mg-pyridoxine hydrochloride 10 mg, delayed-release preparation) as compared with placebo for nausea and vomiting of pregnancy. A randomized, double-blind, multicenter placebo controlled trial studying pregnant women suffering from nausea and vomiting of pregnancy, analyzed by intention to treat. Women received Diclectin (n = 131) or placebo (n = 125) for 14 days. Nausea and vomiting of pregnancy symptoms were evaluated daily using the pregnancy unique quantification of emesis scale. Diclectin use resulted in a significantly larger improvement in symptoms of nausea and vomiting of pregnancy compared with placebo based on both the pregnancy unique quantification of emesis score (-4.8 ± 2.7 vs -3.9 ± 2.6; P = .006) and quality of life. After the trial, 64 (48.9%) women receiving Diclectin asked to continue compassionate use of their medication, as compared with 41 (32.8%) of placebo-treated women (P = .009). Diclectin delayed release formulation of doxylamine succinate and pyridoxine hydrochloride is effective and well tolerated in treating nausea and vomiting of pregnancy.
Yeung EH et al., 2010·The Journal of clinical endocrinology and metabolism
Conflicting findings have been reported regarding the effect of menstrual cycle phase and sex hormones on insulin sensitivity. The aim was to determine the pattern of insulin resistance over the menstrual cycle and whether variations in sex hormones explain these patterns. The BioCycle study is a longitudinal study that measured hormones at different phases of the menstrual cycle. Participants had up to eight visits per cycle; each visit was timed using fertility monitors to capture sensitive windows of hormonal changes. The study was conducted in the general community of the University at Buffalo (Buffalo, NY). A total of 257 healthy, premenopausal women (age, 27±8 yr; body mass index, 24±4 kg/m2) participated in the study. We measured fasting insulin, glucose, and insulin resistance by the homeostasis model of insulin resistance (HOMA-IR). Significant changes in HOMA-IR were observed over the menstrual cycle; from a midfollicular phase level of 1.35, levels rose to 1.59 during the early luteal phase and decreased to 1.55 in the late-luteal phase. HOMA-IR levels primarily reflected changes in insulin and not glucose. After adjustment for age, race, cycle, and other sex hormones, HOMA-IR was positively associated with estradiol (β=0.082; P<0.001) and progesterone (β=0.025; P<0.001), and inversely associated with FSH (adjusted β=-0.040; P<0.001) and SHBG (β=-0.085; P<0.001). LH was not associated with HOMA-IR. Further adjustment for BMI weakened the association with SHBG (β=-0.057; P=0.06) but did not affect other associations. Insulin exhibited minor menstrual cycle variability. Estradiol and progesterone were positively associated with insulin resistance and should be considered in studies of insulin resistance among premenopausal women.
Laparo-endoscopic single site (LESS) surgery has recently gained broader acceptance as a less-invasive approach to traditional multi-port laparoscopic procedures. LESS hysterectomy represents the gynecologic surgeon's progression toward this goal of performing minimally invasive hysterectomy procedures through increasingly fewer incisions. Although this procedure offers improved cosmesis and potentially decreased post-operative pain, there are also many challenges to adoption of this surgical procedure. LESS hysterectomy is associated with a steep learning curve and the need for the gynecologic surgeon to adopt new technologies and develop a new set of surgical skills. Following the basic principles of LESS surgery is essential for the gynecologic surgeon to safely and efficiently adopt this surgical procedure. Advances in surgical instrumentation will continue to allow surgeons to perform increasingly complex LESS surgical procedures in the future.
Previous research has shown that dietary patterns are related to the risk of several adverse health outcomes, but the relation of these patterns to skeletal fragility is not well understood. Our objective was to determine the relation between dietary patterns and incident fracture and possible mediation of this relation by body mass index, bone mineral density, or falls.
We performed a retrospective cohort study based on the Canadian Multicentre Osteoporosis Study-a randomly selected population-based cohort. We assessed dietary patterns by using self-administered food-frequency questionnaires in year 2 of the study (1997-1999). Our primary outcome was low-trauma fracture occurring before the 10th annual follow-up (2005-2007). We identified 2 dietary patterns by using factor analysis. The first factor (nutrient dense) was strongly associated with intake of fruit, vegetables, and whole grains. The second factor (energy dense) was strongly associated with intake of soft drinks, potato chips, French fries, meats, and desserts. The nutrient-dense factor was associated with a reduced risk of fracture per 1 SD in men overall [hazard ratio (HR): 0.83; 95% CI: 0.64, 1.08] and in women overall (HR: 0.86; 95% CI: 0.76, 0.98). An age trend (P = 0.03) was observed, which yielded an HR of 0.97 in younger women (age < 70 y) compared with an HR of 0.82 in older women (age ≥ 70 y). The associations were independent of body mass index, bone mineral density, falls, and demographic variables. The energy-dense pattern was not related to fracture. A diet high in vegetables, fruit, and whole grains may reduce the risk of low-trauma fracture, particularly in older women.
Gleicher N et al., 2010·Reproductive biology and endocrinology : RB&E
Dehydroepiandrosterone (DHEA) has been reported to improve pregnancy chances in women with diminished ovarian reserve (DOR), and to reduce miscarriage rates by 50-80%. Such an effect is mathematically inconceivable without beneficial effects on embryo ploidy. This study, therefore, assesses effects of DHEA on embryo aneuploidy. In a 1:2, matched case control study 22 consecutive women with DOR, supplemented with DHEA, underwent preimplantation genetic screening (PGS) of embryos during in vitro fertilization (IVF) cycles. Each was matched by patient age and time period of IVF with two control IVF cycles without DHEA supplementation (n = 44). PGS was performed for chromosomes X, Y, 13, 16, 18, 21 and 22, and involved determination of numbers and percentages of aneuploid embryos. DHEA supplementation to a significant degree reduced number (P = 0.029) and percentages (P < 0.001) of aneuploid embryos, adjusted for relevant covariates. Short term supplementation (4-12 weeks) resulted in greatest reduction in aneuploidy (21.6%, 95% CI -2.871-46.031). Beneficial DHEA effects on DOR patients, at least partially, are the likely consequence of lower embryo aneuploidy. DHEA supplementation also deserves investigation in older fertile women, attempting to conceive, where a similar effect, potentially, could positively affect public health.
Estradiol (E(2)) and progesterone (P(4)) collaborate within bone remodelling on resorption (E(2)) and formation (P(4)). We integrate evidence that P(4) may prevent and, with antiresorptives, treat women's osteoporosis. P(4) stimulates osteoblast differentiation in vitro. Menarche (E(2)) and onset of ovulation (P(4)) both contribute to peak BMD. Meta-analysis of 5 studies confirms that regularly cycling premenopausal women lose bone mineral density (BMD) related to subclinical ovulatory disturbances (SODs). Cyclic progestin prevents bone loss in healthy premenopausal women with amenorrhea or SOD. BMD loss is more rapid in perimenopause than postmenopause-decreased bone formation due to P(4) deficiency contributes. In 4 placebo-controlled RCTs, BMD loss is not prevented by P(4) in postmenopausal women with increased bone turnover. However, 5 studies of E(2)-MPA co-therapy show greater BMD increases versus E(2) alone. P(4) fracture data are lacking. P(4) prevents bone loss in preand possibly perimenopausal women; progesterone co-therapy with antiresorptives may increase bone formation and BMD.
To compare the risk of preterm delivery, low birth weight, and admission of the newborn to a neonatal intensive care unit (NICU) in women pregnant after fertility treatment and subfertile women with the risk in fertile women. Prospective follow-up study. Aarhus University Hospital, Skejby, Denmark, 1989-2006. PATIENT(S): A total of 20,080 liveborn singletons. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Preterm delivery, low birth weight, and admission of the newborn to a NICU. RESULT(S): After adjustment we found a statistically significantly increased risk of preterm delivery and very preterm delivery in women who conceived after in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) compared with fertile women. Compared with fertile women, the risk of preterm delivery and very preterm delivery was not statistically significantly different in women pregnant after non-IVF assisted reproductive treatment (non-IVF ART) or subfertile women. We found no association between IVF/ICSI and the risk of low birth weight at term or admittance to the NICU. CONCLUSION(S): The increased risk of preterm delivery after IVF/ICSI may be due to the fertility treatment or unknown characteristics in the couples who undergo IVF/ICSI.
A procedure for creating a simplified version of fracture risk assessment tool (FRAX®) is described. Calibration, fracture prediction, and concordance were compared with the full FRAX tool using two large, complementary Canadian datasets.
The Canadian Association of Radiologists and Osteoporosis Canada (CAROC) system for fracture risk assessment is based upon sex, age, bone mineral density (BMD), prior fragility fracture, and glucocorticoid use. CAROC does not require computer or web access, and categorizes 10-year major osteoporotic fracture risk as low (<10%), moderate (10-20%), or high (>20%). Basal CAROC fracture risk tables (by age, sex, and femoral neck BMD) were constructed from Canadian FRAX probabilities for major osteoporotic fractures (adjusted for prevalent clinical risk factors). We assessed categorization and fracture prediction with the updated CAROC system in the CaMos and Manitoba BMD cohorts. The new CAROC system demonstrated high concordance with the Canadian FRAX tool for risk category in both the CaMos and Manitoba cohorts (89% and 88%). Ten-year fracture outcomes in CaMos and Manitoba BMD cohorts showed good discrimination and calibration for both CAROC (6.1-6.5% in low-risk, 13.5-14.6% in moderate-risk, and 22.3-29.1% in high-risk individuals) and FRAX (6.1-6.6% in low-risk, 14.4-16.1% in moderate-risk, and 23.4-31.0% in high-risk individuals). Reclassification from the CAROC risk category to a different risk category under FRAX occurred in <5% for low-risk, 20-24% for moderate-risk, and 27-30% for high-risk individuals. Reclassified individuals had 10-year fracture outcomes that were still within or close to the original nominal-risk range.. The new CAROC system is well calibrated to the Canadian population and shows a high degree of concordance with the Canadian FRAX tool. The CAROC system provides s a simple alternative when it is not feasible to use the full Canadian FRAX tool.
Fertility AwarenessProgram IntegrationEffectivenessFertility Awareness Methods
Open Access
To determine what contribution the Standard Days Method® (SDM) makes to the contraceptive mix offered by regular health services in areas of Peru where contraceptive prevalence rates (CPR) are already high. SDM was added to the family planning methods offered by the Ministry of Health in two provinces in Peru in September 2002. Retrospective interviews were conducted in March-June 2004 with 1 200 women who had chosen SDM as their contraceptive method and had used it for 2-20 months. Data were also obtained from the databases of the participating health services. The evaluation covered SDM demand, whether or not clients were switching to SDM from other modern methods, and SDM continuation and effectiveness. Demand for SDM stabilized at 6% of all new family planning users. Most users had not been using any reliable contraception at the time they started using SDM. About 89% of those who began using SDM at least 6 months before the interview were still using it at 6 months. The 12-month typical use pregnancy rate was estimated to be around 10.0 per 100 women years. Adding SDM to a program's existing contraceptive method mix can increase coverage even in an already high-CPR setting. Most women who choose SDM do not switch from any other modern family planning method. Continuation compares well with other modern user-directed methods. SDM effectiveness, when offered in regular service delivery circumstances, compares well to efficacy trial findings.
Polycystic ovary syndrome (PCOS) is a common disorder characterized by hyperandrogenism and disordered gonadotropin secretion, often associated with insulin resistance. The syndrome, which modulates both hormonal and metabolic processes, is the most common endocrinopathy in reproductive-age women and increases a woman's risk of infertility, endometrial pathology, and cardiometabolic disease. As it is currently defined, PCOS most likely encompasses several distinct diseases with similar clinical phenotypes but different underlying pathophysiological processes. However, hyperandrogenism remains the syndrome's clinical hallmark. The clinical manifestations of PCOS often emerge during childhood or in the peripubertal years, suggesting that the syndrome is influenced by fetal programming and/or early postnatal events. However, given that the full clinical spectrum of PCOS does not typically appear until puberty, a "two-hit" (1) a girl develops hyperandrogenism via one or more of many different potential mechanisms; (2) the preexisting hyperandrogenism subsequently disturbs the hypothalamic–pituitary–ovarian axis, resulting in ovulatory dysfunction and sustained hyperandrogenism. No consensus guidelines exist regarding the diagnosis and management of PCOS in the pediatric population; however, because the syndrome is a diagnosis of exclusion, the clinical evaluation of girls suspected of having PCOS is aimed at excluding other causes of androgen excess and menstrual dysfunction. For the syndrome's management, emphasis is placed on lifestyle and symptom-directed treatment.
There are many types of ovarian activity that occur in women. This review provides information on the relationship between the hormone values and the degree of biological response to the hormones including the frequency and degree of uterine bleeding. The continuous process is termed the 'Continuum' and is thus similar to other processes in the body. This review draws on information already published from monitoring ovarian activity by urinary oestrogen and pregnanediol measurements using timed 24-h specimens of urine. Much of the rationalization was derived from 5 to 6 year studies of girls progressing from childhood to adulthood, women progressing through menopause, and the return of fertility post-partum. During these times, all the reported types of ovarian activity were encountered. All cycle types can be understood in terms of steps in the normal maturation of fertility at the beginning of reproductive life, its return post-partum and its demise at menopause. Each step merges into the next and therefore the sequence is termed the 'Continuum'. Unpredictable movement from fertile to infertile types and back can occur at any time during reproductive life. Stress is a major causative factor. Hormonal definitions for each step, the relevance of the various cycle types in determining fertility and in the initiation of uterine bleeding and the roles of the pituitary hormones in causing them, are presented. The findings explain the erratic fertility of women and why ovulation is not always associated with fertility. They provide an understanding of the various types of ovarian activity and their relation to pituitary function, fertility and uterine bleeding.
Baptiste CG et al., 2010·The Journal of steroid biochemistry and molecular biology
Polycystic ovary syndrome (PCOS) is a very common endocrine disorder characterized by chronic anovulation, clinical and/or biochemical hyperandrogenism, and/or polycystic ovaries. But most experts consider that hyperandrogenism is the main characteristic of PCOS. Several theories propose different mechanisms (1) a primary enzymatic default in the ovarian and/or adrenal steroidogenesis; (2) an impairment in gonadotropin releasing hormone (GnRH) secretion that promotes luteal hormone (LH) secretion; or (3) alterations in insulin actions that lead to insulin resistance with compensatory hyperinsulinemia. However, in the past 20 years there has been growing evidence supporting that defects in insulin actions or in the insulin signalling pathways are central in the pathogenesis of the syndrome. Indeed, most women with PCOS are metabolically insulin resistant, in part due to genetic predisposition and in part secondary to obesity. But some women with typical PCOS do not display insulin resistance, which supports the hypothesis of a genetic predisposition specific to PCOS that would be revealed by the development of insulin resistance and compensatory hyperinsulinemia in most, but not all, women with PCOS. However, these hypotheses are not yet appropriately confirmed, and more research is still needed to unravel the true pathogenesis underlying this syndrome. The present review thus aims at discussing new concepts and findings regarding insulin actions in PCOS women and how it is related to hyperandrogenemia.
Reproductive EndocrinologyThyroid and Reproductive FunctionThyroid Disease in PregnancyThyroid Dysfunction and Sperm Quality
Via its interaction in several pathways, normal thyroid function is important to maintain normal reproduction. In both genders, changes in SHBG and sex steroids are a consistent feature associated with hyper- and hypothyroidism and were already reported many years ago. Male reproduction is adversely affected by both thyrotoxicosis and hypothyroidism. Erectile abnormalities have been reported. Thyrotoxicosis induces abnormalities in sperm motility, whereas hypothyroidism is associated with abnormalities in sperm morphology; the latter normalize when euthyroidism is reached. In females, thyrotoxicosis and hypothyroidism can cause menstrual disturbances. Thyrotoxicosis is associated mainly with hypomenorrhea and polymenorrhea, whereas hypothyroidism is associated mainly with oligomenorrhea. Thyroid dysfunction has also been linked to reduced fertility. Controlled ovarian hyperstimulation leads to important increases in estradiol, which in turn may have an adverse effect on thyroid hormones and TSH. When autoimmune thyroid disease is present, the impact of controlled ovarian hyperstimulation may become more severe, depending on preexisting thyroid abnormalities. Autoimmune thyroid disease is present in 5-20% of unselected pregnant women. Isolated hypothyroxinemia has been described in approximately 2% of pregnancies, without serum TSH elevation and in the absence of thyroid autoantibodies. Overt hypothyroidism has been associated with increased rates of spontaneous abortion, premature delivery and/or low birth weight, fetal distress in labor, and perhaps gestation-induced hypertension and placental abruption. The links between such obstetrical complications and subclinical hypothyroidism are less evident. Thyrotoxicosis during pregnancy is due to Graves' disease and gestational transient thyrotoxicosis. All antithyroid drugs cross the placenta and may potentially affect fetal thyroid function.
Although low bone mineral density (BMD) predicts fractures, there are postulated sex differences in the fracture "threshold." Some studies demonstrate a higher mean BMD for men with fractures than for women, whereas others note similar absolute risk at the same level of BMD. Our objective was to test the preceding observations in the population-based Canadian Multicentre Osteoporosis Study (CaMOS). We included participants 50+ years of age at baseline. Mean BMD in men was higher than in women among both fracture cases and noncases. Three methods of BMD normalization were compared in age-adjusted Cox proportional hazards models. In a model using the same reference population mean and standard deviation (SD), there were strong effects of age and total-hip BMD for prediction of fractures but no significant effect of sex [hazard ratio (HR) = 0.97, 95% confidence interval (CI) 0.78-1.20] for men versus women. In a model using sex-specific reference means but a common SD, an apparent sex difference emerged (HR = 0.66, 95% CI 0.54-0.81) for men versus women. The sex term in the second model counterbalanced the higher risk introduced by the lower normalized BMD in men. A third model using sex-specific reference means and SDs gave nearly identical results. Parallel results for the three methods of normalization were seen when adjusting for clinical risk factors, excluding antiresorptive users and considering death as a competing risk. We conclude that no adjustment for sex is necessary when using common reference data for both men and women, whereas using sex-specific reference data requires a substantial secondary adjustment for sex.
EndometriosisEndometriosis Fertility IndexFertility Outcomes After Surgical TreatmentPrognosis and Prediction Tools
To develop a clinical tool that predicts pregnancy rates (PRs) in patients with surgically documented endometriosis who attempt non-IVF conception.
Prospective data collection on 579 patients and comprehensive statistical analysis to derive a new staging system--the endometriosis fertility index (EFI)--from data rather than a priori assumptions, followed by testing the EFI prospectively on 222 additional patients for correlation of predicted and actual outcomes.
Private reproductive endocrinology practice.
PATIENT(S): A total of 801 consecutively diagnosed and treated infertile patients with endometriosis.
INTERVENTION(S): Surgical diagnosis and treatment followed by non-IVF fertility management.
MAIN OUTCOME MEASURE(S): The EFI and life table PRs.
RESULT(S): A statistically significant variable used to create the EFI was the least function score (i.e., the sum of those scores determined intraoperatively after surgical intervention that describe the function of the tube, fimbria, and ovary on both sides). Sensitivity analysis showed that the EFI varies little, even with variation in the assignment of functional scores, and predicted PRs.
CONCLUSION(S): The EFI is a simple, robust, and validated clinical tool that predicts PRs after endometriosis surgical staging. Its use provides reassurance to those patients with good prognoses and avoids wasted time and treatment for those with poor prognoses.
Fertility AwarenessMethod-Specific EffectivenessComparison of NFP ApproachesClassification of Natural Methods
Freundl G, 2010·Eur J Contracept Reprod Health Care
This letter to the editor discusses a review article commenting on the efficacy of contraceptive methods. It takes issue with section focused on natural family planning methods (Billings ovulation method calendar methods symptothermal method etc) and finds fault with the authors not differentiating between the various natural methods. It states that if the authors consider it appropriate to differentiate between the various hormonal contraceptives then differentiation between the natural methods is mandatory.
Sellix MT et al., 2010·Trends in endocrinology and metabolism: TEM
Clock gene expression has been observed in tissues of the hypothalamic-pituitary-gonadal (HPG) axis. Whereas the contribution of hypothalamic oscillators to the timing of reproductive biology is well known, the role of peripheral oscillators like those in the ovary is less clear. Circadian clocks in the ovary might play a role in the timing of ovulation. Disruption of the clock in ovarian cells or desynchrony between ovarian clocks and circadian oscillators elsewhere in the body may contribute to the onset and progression of various reproductive pathologies. In this paper, we review evidence for clock function in the ovary across a number of species and offer a novel perspective into the role of this clock in normal ovarian physiology and in diseases that negatively affect fertility.
Most low-trauma fractures occur among women with osteopenic bone mineral density (BMD), a population considered to have moderate absolute fracture risk. Our purpose was to refine the fracture risk prediction in women with osteopenic BMD to determine the subgroups at lowest and highest risk. We included 2,588 women aged 50 to 90 years with osteopenic BMD (femoral neck BMD between -1 and -2.5) participating in the Canadian Multicentre Osteoporosis Study, an ongoing prospective cohort study of randomly selected Canadians. Baseline variables, in addition to known risk factors, age, and BMD, were considered for inclusion in a model for the prediction of 5-year absolute risk of low-trauma fracture. Models were derived using logistic regression and assessed by the Bayesian Information Criterion. We found an increased fracture risk among those with lower BMD (odds ratio [OR], 1.53; 95% CI, 1.06-2.21) for each decrease in femoral neck T score (eg, from -1 to -2), those with prior low-trauma fracture (OR, 2.06; 95% CI, 1.46-2.92), those with self-reported worse general health (OR, 1.35; 95% CI, 1.15-1.59) for each lower category (categories: excellent, very good, good, fair, poor), and those with height loss (OR, 1.44; 95% CI, 1.16-1.90) for each 5-cm difference between current and maximal height. The new model had yielded a better risk stratification than did a model with World Health Organization risk factors. Including risk factors such as general health and height loss can be used to provide a highly effective assessment of fracture risk among women with osteopenic BMD.
We estimated peak bone mass (PBM) in 615 women and 527 men aged 16 to 40 years using longitudinal data from the Canadian Multicentre Osteoporosis Study (CaMos). Individual rates of change were averaged to find the mean rate of change for each baseline age. The age range for PBM was defined as the period during which bone mineral density (BMD) was stable. PBM was estimated via hierarchical models, weighted according to 2006 Canadian Census data. Lumbar spine PBM (1.046 ± 0.123 g/cm(2)) occurred at ages 33 to 40 years in women and at 19 to 33 years in men (1.066 ± 0.129 g/cm(2)). Total hip PBM (0.981 ± 0.122 g/cm(2)) occurred at ages 16 to 19 years in women and 19 to 21 years in men (1.093 ± 0.169 g/cm(2)). Analysis of Canadian geographic variation revealed that the levels of PBM and of mean BMD in those over age 65 sometimes were discordant, suggesting that PBM and subsequent rates of bone loss may be subject to different genetic and/or environmental influences. Based on our longitudinally estimated PBM values, the estimated Canadian prevalences of osteoporosis (T-score < -2.5) were 12.0% (L(1)-L(4)) and 9.1% (total hip) in women aged 50 years and older and 2.9% (L(1)-L(4)) and 0.9% (total hip) in men aged 50 years and older. These were higher than prevalences using cross-sectional PBM data. In summary, we found that the age at which PBM is achieved varies by sex and skeletal site, and different reference values for PBM lead to different estimates of the prevalence of osteoporosis. Furthermore, lack of concordance of PBM and BMD over age 65 suggests different determinants of PBM and subsequent bone loss.
Hunter DJ et al., 2010·Cancer Epidemiol Biomarkers Prev
Previous studies convincingly showed an increase in risk of breast cancer associated with current or recent use of oral contraceptives from the 1960s to 1980s. The relation of contemporary oral contraceptive formulations to breast cancer risk is less clear. We assessed lifetime oral contraceptive use and the specific formulations used among 116,608 female nurses ages 25 to 42 years at enrollment in 1989, and subsequently updated this information every 2 years. We related this information to risk of breast cancer up to June 1, 2001. During 1,246,967 person-years of follow-up, 1,344 cases of invasive breast cancer were diagnosed. Past use of any oral contraceptive was not related to breast cancer risk [multivariate relative risk (RR), 1.12; 95% confidence interval 0.95-1.33]. Current use of any oral contraceptive was related to a marginally significant higher risk (multivariate RR, 1.33; 95% CI, 1.03-1.73). One specific formulation substantially the RR for current use of triphasic preparations with levonorgestrel as the progestin was 3.05 (95% CI, 2.00-4.66; P < 0.0001). Current use of oral contraceptives carries an excess risk of breast cancer. Levonorgestrel used in triphasic preparations may account for much of this elevation in risk. Different oral contraceptive formulations might convey different risks of breast cancer; ongoing monitoring of these associations is necessary as oral contraceptive formulations change.
Fertility AwarenessPhysician Knowledge and AttitudesContraceptive Counseling PracticesCross-Sectional Physician Survey
To assess physicians' knowledge, attitudes, and practice with respect to four evidence-based natural family planning (NFP) Standard Days, cervical mucus, basal body temperature, and the lactational amenorrhea method. We undertook a cross-sectional survey of a random sample of family physicians and all gynaecologists in British Columbia (n = 460) who have women of reproductive age in their practice, as well as all affiliated residents (n = 239). Main outcome measures were (1) physicians' attitudes towards NFP and their perceptions of its effectiveness; (2) the relationship between physicians' demographic factors, their personal experience or beliefs, and their attitudes and knowledge; and (3) how these factors affect the counselling physicians offer their patients. The survey response rate was 44%. Only 3% to 6% of physicians had correct knowledge of the effectiveness in perfect use of the NFP methods cited in this study. Fifty percent of physicians who responded mention NFP to their patients as an option for contraception, and 77% of physicians mention NFP as an option to couples trying to conceive. Family physicians and residents were much more likely than gynaecologists or gynaecology residents to mention NFP during counselling. Older physicians were more likely to mention NFP than younger physicians and also had more personal experience with NFP. Most physicians in our study underestimated the effectiveness of NFP methods, and only a small proportion of physicians provide information about NFP during contraceptive counselling. Physicians need better understanding of modern methods of NFP to provide evidence-based contraceptive counselling to selected highly motivated patients who prefer NFP as a contraceptive choice.
Shin BC et al., 2010·BMC complementary and alternative medicine
Maca (Lepidium meyenii) is an Andean plant of the brassica (mustard) family. Preparations from maca root have been reported to improve sexual function. The aim of this review was to assess the clinical evidence for or against the effectiveness of the maca plant as a treatment for sexual dysfunction. We searched 17 databases from their inception to April 2010 and included all randomised clinical trials (RCTs) of any type of maca compared to a placebo for the treatment of healthy people or human patients with sexual dysfunction. The risk of bias for each study was assessed using Cochrane criteria, and statistical pooling of data was performed where possible. The selection of studies, data extraction, and validations were performed independently by two authors. Discrepancies were resolved through discussion by the two authors. Four RCTs met all the inclusion criteria. Two RCTs suggested a significant positive effect of maca on sexual dysfunction or sexual desire in healthy menopausal women or healthy adult men, respectively, while the other RCT failed to show any effects in healthy cyclists. The further RCT assessed the effects of maca in patients with erectile dysfunction using the International Index of Erectile Dysfunction-5 and showed significant effects. The results of our systematic review provide limited evidence for the effectiveness of maca in improving sexual function. However, the total number of trials, the total sample size, and the average methodological quality of the primary studies were too limited to draw firm conclusions. More rigorous studies are warranted.
Reproductive EndocrinologyThyroid and ObesityDMPA and Bone Health
Canadian women over 50 years old were studied over a 10-year period to see if those who sustained a fracture (caused by minimal trauma) were receiving the recommended osteoporosis therapy. We found that approximately half of these women were not being treated, indicating a significant care gap in osteoporosis treatment.
Prevalent fragility fracture strongly predicts future fracture. Previous studies have indicated that women with fragility fractures are not receiving the indicated treatment. We aimed to describe post fracture care in Canadian women using a large, population-based prospective cohort that began in 1995-1997. We followed 5,566 women over 50 years of age from across Canada over a period of 10 years in the Canadian Multicentre Osteoporosis Study. Information on medication use and incident clinical fragility fractures was obtained during a yearly questionnaire or interview and fractures were confirmed by radiographic/medical reports. Over the 10-year study period, 42-56% of women with yearly incident clinical fragility fractures were not treated with an osteoporosis medication. During year 1 of the study, 22% of the women who had experienced a fragility fracture were on treatment with a bisphosphonate and 26% were on hormone therapy (HT). We were not able to differentiate HT use for menopause symptoms vs osteoporosis. Use of bisphosphonate therapy increased over time; odds ratio (OR) for use at year 10 compared to use at year 1 was 3.65 (95% confidence interval (CI) 1.83-7.26). In contrast, HT use declined, with an OR of 0.07 (95%CI 0.02-0.24) at year 10 compared to year 1 of the study. In a large population-based cohort study, we found a therapeutic care gap in women with osteoporosis and fragility fractures. Although bisphosphonate therapy usage improved over time, a substantial gap remains.
Contraception/ComparisonVenous Thromboembolism RiskProgestin Type Safety ComparisonContraceptive Safety
Dinger J et al., 2010·J Fam Plann Reprod Health Care
The primary objective of the study was to clarify whether the use of the oral contraceptive 2 mg dienogest/30 microg ethinylestradiol (DNG/EE) is associated with a higher risk of venous thromboembolism (VTE) than the use of other combined oral low-dose contraceptives (i.e. containing < or =30 microg EE), particularly oral contraceptives containing levonorgestrel (LNG). The secondary objective was to investigate the VTE risk associated with drospirenone/ethinylestradiol (DRSP/EE) in comparison to low-dose LNG/EE. This German community-based, case-control study recruited VTE cases from the primary care sector. Eligible cases were women aged 15-49 years with a VTE between January 2002 and February 2008. Four controls (women without a confirmed or potential VTE before the index date) were matched by age and region to each case. Medical information relevant for the assessment of VTE was abstracted from patient charts. Data on personal characteristics of the patients were collected via self-administered questionnaires. At the end of the study a blinded adjudication of the reported VTE was conducted. Conditional logistic regression techniques were used, adjusting for nine potential confounders, including personal history of VTE, family history of VTE, body mass index, duration of current combined oral contraceptive (COC) use and smoking. A total of 680 VTE cases and 2720 corresponding controls were analysed. The mean age of cases and controls was - as a result of matching - almost identical (36.1 years).
PregnancyPostpartum Depression and Hormonal ContraceptionDMPA and Mood DisordersDepression Screening and Risk Factors
Depot medroxyprogesterone acetate (DMPA) is commonly prescribed to women immediately postpartum due to its efficacy, convenience and lack of estrogen. It is unclear whether administering a progestin injection can affect the course of postpartum depression (PPD), which some suspect to be influenced by hormonal changes. In this retrospective study, the objective was to determine whether DMPA administered immediately postpartum influences the development of PPD. A retrospective review of a total of 404 charts was conducted of clinic patients who were scheduled for 6-week postpartum visits at a major medical center, where all patients are routinely asked to complete the Edinburgh Postnatal Depression Scale (EPDS). The average scores on the EPDS at these visits were compared between patients who had received DMPA prior to postpartum discharge from the hospital and patients who had not received any hormonal contraception by using an unpaired t test. In addition, the proportions of women diagnosed with PPD via the scale were compared via contingency tables. Fifty-five women who had received immediate DMPA were compared with 192 women with no hormonal contraception after delivery. The groups were similar in parity, race, mode of delivery and weight, but women receiving DMPA were significantly younger (24.2 vs. 26.2 years, p=.03). Mean EPDS scores at 6 weeks postpartum were not statistically significant between the groups (5.02 vs. 6.17, p=.16). Six patients (10.9%) who received immediate DMPA were diagnosed with PPD based on EPDS scores greater than or equal to 13, while 27 (14.1%) in the comparison group had PPD (p=.88). Administration of DMPA in the immediate postpartum period does not appear to predispose women to PPD.
Rosenberg L et al., 2010·Cancer Epidemiol Biomarkers Prev
Oral contraceptive formulations have changed over time, making it relevant to assess the effect of more recent formulations on breast cancer risk. In addition, some studies have found stronger positive associations of oral contraceptive use with estrogen receptor-negative (ER(-)) than with ER-positive (ER(+)) breast cancer. We carried out the first assessment of the effect of oral contraceptive use on the incidence of breast cancer classified by receptor status among African American women, a group disproportionately affected by ER(-) cancer. We followed 53,848 Black Women's Health Study participants from 1995 to 2007 through biennial health questionnaires, in which participants reported information about incident breast cancer, oral contraceptive use, and breast cancer risk factors. Pathology information was obtained on receptor status for 789 incident cases. Incidence rate ratios (IRR) with 95% confidence intervals (95% CI) were derived from Cox regression models with control for confounding factors. Ever use of oral contraceptives was more strongly associated with ER(-)PR(-) breast cancer (279 cases; IRR, 1.65; 95% CI, 1.19-2.30) than with ER(+)PR(+) cancer (386 cases; IRR, 1.11; 95% CI, 0.86-1.42). The risk of ER(-)PR(-) breast cancer increased with increasing duration of use among recent users. These results indicate that the oral contraceptive formulations used in recent decades increase breast cancer risk in African American women, with a greater effect for ER(-) than ER(+) cancer. Mechanisms to explain the adverse influence of oral contraceptive use on ER(-) breast cancer need to be elucidated.
Research MethodologyCost-Effective Participant EnrollmentObservational Study DesignWomen's Health Research Methods
Battistella E et al., 2010·J Womens Health (Larchmt)
We address the crucial and challenging task of anticipating the resources needed to recruit eligible participants for research. We provide our analysis of various recruitment strategies and their cost-effectiveness in our experience in enrolling 610 women for an observational study on ovulation. We assess the cost-effectiveness and success of multiple recruitment strategies we employed and provide the estimated cost of labor and materials for each. At enrollment, all participants were asked an open-ended question about how they learned about the study. No financial compensation was provided, but participants received personal hormonal analysis results on completion. Of the 610 enrolled women, 552 provided information on how they learned about the study. The total cost of recruitment was $7645.11, which includes 183 staff hours. The average recruitment cost per participant was $12.53 (ranging from $0 to $118.63). The two methods with the lowest total costs resulted in enrollment of 48% of the recruitment goal using only 0.3% of the budget. In contrast, the two methods with the highest total costs produced 13% of the participants needed but consumed over 72% of the budget. Low-cost methods are a viable, practical source for attracting healthy women for observational research. Investigators are encouraged to track sources of recruitment and analyze their data at regular intervals during the recruitment phase. Sharing comprehensive recruitment data will assist other researchers to better estimate the resources needed to meet their enrollment goal, leading to more efficient use of time and funding.
To describe two children diagnosed with Beckwith-Wiedemann Syndrome (BWS) arising from a spontaneous conception and an assisted reproductive technology (ART) cycle from one patient with a long-standing history of subfertility. Case report. Academic medical center.Patient(s)Two children with the morphologic features of BWS as a result of a spontaneous conception and an ART cycle from the same patient.Intervention(s)Assisted reproductive technology.Main outcome measure(s)Neonatal and pediatric morphologic evaluation by geneticists.Result(s)Two children with the morphologic features consistent with the criteria for the diagnosis of BWS.Conclusion(s)Patients with subfertility may be carriers for genetic disorders that can be passed to a child with or without the use of assisted reproductive technologies (ART). The use of ART may bypass natural selection mechanisms.
Endometriosis is a debilitating condition characterized by high recurrence rates. The etiology and pathogenesis remain unclear. Typically, endometriosis causes pain and infertility, although 20-25% of patients are asymptomatic. The principal aims of therapy include relief of symptoms, resolution of existing endometriotic implants, and prevention of new foci of ectopic endometrial tissue. Current therapeutic approaches are far from being curative; they focus on managing the clinical symptoms of the disease rather than fighting the disease. Specific combinations of medical, surgical, and psychological treatments can ameliorate the quality of life of women with endometriosis. The benefits of these treatments have not been entirely demonstrated, particularly in terms of expectations that women hold for their own lives. Although theoretically advantageous, there is no evidence that a combination medical-surgical treatment significantly enhances fertility, and it may unnecessarily delay further fertility therapy. Randomized controlled trials are required to demonstrate the efficacy of different treatments.
The objectives of the study were to develop bone mineral density (BMD) reference norms and BMD Z-scores at various skeletal sites, to determine whether prior fracture and/or asthma were related to BMD, and to assess possible geographic variation of BMD among Canadian youth aged 16-24 yr. Z-Scores were defined as the number of standard deviations from the mean BMD of a healthy population of the same age, race, and sex. Z-Scores were calculated using the reference sample defined as Canadian Caucasian participants without asthma or prior fracture. Reference standards were created for lumbar spine (L1-L4), femoral neck, total hip, and greater trochanter, by each year of age (16-24 yr), and by sex. The Z-score norms were developed for groups noted earlier. Mean Z-scores between the asthma or fracture subgroups compared with the mean Z-scores in the reference sample were not different. There were minor differences in mean BMD across different Canadian geographic regions. This study provides age, sex, and skeletal site-specific Caucasian reference norms and formulae for the calculation of BMD Z-scores for Canadian youth aged 16-24 yr. This information will be valuable to help to identify individuals with clinically meaningful low BMD.
PregnancyThyroid Dysfunction and Pregnancy LossTSH Reference Ranges in PregnancyFirst Trimester TSH Thresholds
The definition of what constitutes a normal TSH during pregnancy is in flux. Recent studies suggested that the first trimester upper limit of normal for TSH should be 2.5 mIU/liter. The objective of the study was to evaluate the pregnancy loss and preterm delivery rate in first-trimester thyroid peroxidase antibody-negative women with TSH values between 2.5 and 5.0 mIU/liter. The present study is a component of a recently published large-scale prospective trial that evaluated the impact of levothyroxine treatment on maternal and neonatal complications in thyroid peroxidase-positive women with TSH levels above 2.5 mIU/liter. The present study evaluated 4123 thyroid peroxidase antibody-negative women with TSH levels at or below 5.0 mIU/liter. Women were divided into two groups group A, TSH level below 2.5 mIU/liter, excluding hyperthyroid women defined as an undetectable TSH with an elevated free T(4), and group B, TSH level between 2.5 and 5.0 mIU/liter. The study was conducted at two ambulatory clinics of community hospitals in southern Italy. A total of 4123 women were evaluated. There was no intervention. The incidence of pregnancy loss and preterm delivery in group A as compared with group B was measured. The rate of pregnancy loss was significantly higher in group B as compared with group A (6.1 vs. 3.6% respectively, P = 0.006). There was no difference in the rate of preterm delivery between the two groups. The increased incidence of pregnancy loss in pregnant women with TSH levels between 2.5 and 5.0 mIU/liter provides strong physiological evidence to support redefining the TSH upper limit of normal in the first trimester to 2.5 mIU/liter.
The means by which vaginal microbiomes help prevent urogenital diseases in women and maintain health are poorly understood. To gain insight into this, the vaginal bacterial communities of 396 asymptomatic North American women who represented four ethnic groups (white, black, Hispanic, and Asian) were sampled and the species composition characterized by pyrosequencing of barcoded 16S rRNA genes. The communities four were dominated by Lactobacillus iners, L. crispatus, L. gasseri, or L. jensenii, whereas the fifth had lower proportions of lactic acid bacteria and higher proportions of strictly anaerobic organisms, indicating that a potential key ecological function, the production of lactic acid, seems to be conserved in all communities. The proportions of each community group varied among the four ethnic groups, and these differences were statistically significant [χ(2)(10) = 36.8, P < 0.0001]. Moreover, the vaginal pH of women in different ethnic groups also differed and was higher in Hispanic (pH 5.0 ± 0.59) and black (pH 4.7 ± 1.04) women as compared with Asian (pH 4.4 ± 0.59) and white (pH 4.2 ± 0.3) women. Phylotypes with correlated relative abundances were found in all communities, and these patterns were associated with either high or low Nugent scores, which are used as a factor for the diagnosis of bacterial vaginosis. The inherent differences within and between women in different ethnic groups strongly argues for a more refined definition of the kinds of bacterial communities normally found in healthy women and the need to appreciate differences between individuals so they can be taken into account in risk assessment and disease diagnosis.
Ross C et al., 2010·Reproductive biomedicine online
The use of antioxidants in treatment of infertile men has been suggested, although the evidence base for this practice is unclear. A systematic review of randomized studies was conducted to evaluate the effects of oral antioxidants (vitamins C and E, zinc, selenium, folate, carnitine and carotenoids) on sperm quality and pregnancy rate in infertile men. MEDLINE, EMBASE, Cochrane Library and CINAHL were searched for relevant trials published from respective database inception dates to May 2009. Study selection, quality appraisal and data extraction were performed independently and in duplicate. Seventeen randomized trials, including a total of 1665 men, were identified, which differed in the populations studied and type, dosage and duration of antioxidants used. Only two-thirds of the studies (11/17) reported using allocation concealment and three studies (18%) used intention-to-treat analysis. Despite the methodological and clinical heterogeneity, 14 of the 17 (82%) trials showed an improvement in either sperm quality or pregnancy rate after antioxidant therapy. Ten trials examined pregnancy rate and six showed a significant improvement after antioxidant therapy. The use of oral antioxidants in infertile men could improve sperm quality and pregnancy rates. Adequately powered robust trials of individual and combinations of antioxidants are needed to guide clinical practice.
Ethics/PhilosophyEmbryo Adoption and Moral StatusDignitas Personae and Reproductive TechnologyFertility Industry Cooperation and Scandal
The Congregation of the Doctrine of the Faith’s Dignitas personae doesnotofferadefinitiverejectionofthepracticeofhumanembryoadoptionas intrinsicallyevil,butneitherdoesitsimplyleavethematteran“openquestion.” The document does indeed oppose the practice, but its reasons for doing so are notclearlystatedandseemtobeintensionwithitsownaffirmationsofthe personal dignity of embryos and the goodness of adoption. The Congregation’s opposition is therefore best read as a prudential judgment that embryo adoption cannotbejustifiedinthepresentcircumstancesduetothepotentialforscandal and the cooperation with the fertility industry which it involves. National Catholic Bioethics Quarterly 10.2(Summer2010):307–328.
To summarize physiological and psychological characteristics that are common among women diagnosed with polycystic ovary syndrome (PCOS) and provide evidence suggesting that addressing psychological disturbances can reduce or alleviate physical symptoms of PCOS through behavioral pathways and physiological pathways. METHOD(S): Empirical studies and expert consensuses pertaining to physiological, psychological, and medical management aspects of PCOS were identified and presented in this review. Articles were identified by searching Pubmed, PsycInfo, Medline ISI, CINAHL, or a Web browser (i.e., Google) using numerous combinations of terms pertaining to physiological, psychological, and medical management aspects of PCOS. An article was chosen to be included in this review if it reported findings and/or provided information that related to and helped support the main purpose(s) of this review article. RESULT(S): Available literature on the physiological (i.e., hyperandrogenism, central obesity, inflammation, insulin resistance) and psychological (i.e., depression, anxiety, eating disorders) factors among women with PCOS provides evidence that these various aspects of PCOS are strongly interrelated. CONCLUSION(S): The existence of these relationships among physiological and psychological factors strongly suggests that medical management of PCOS would greatly benefit from inclusion of psychological and behavioral approaches.
Contraception/ComparisonProgestins and HIV RiskGlucocorticoid Receptor Mechanisms
The glucocorticoid receptor (GR) is a steroid receptor that regulates diverse functions, which include the immune response. In humans, the GR acts via binding to cortisol, resulting in the transcriptional modulation of key host genes. Several lines of evidence suggest that the host GR could be a key protein exploited by HIV at multiple levels to ensure its pathogenic success. Endogenous and therapeutic glucocorticoids play important roles in patients with HIV due to their well-established effects on immune function. AIDS patients develop glucocorticoid hypersensitivity, consistent with a mechanism involving an HIV-1-induced increase in expression or activity of the GR. Both the HIV-1 accessory protein Vpr and the host GR affect transcription of viral proteins from the long terminal repeat (LTR) region of the HIV-1 promoter. In addition, Vpr modulates host GR function to affect transcription of host genes, most likely via direct interaction with the GR. Vpr appears to regulate GR function by acting as a co-activator for the GR. Since both the GR and Vpr are involved in apoptosis in T cells and dendritic cells, crosstalk between these proteins may also regulate apoptosis in these and other cells. Given that cortisol is not the only ligand that activates the GR, other endogenous as well as synthetic GR ligands such as progestins may also modulate HIV pathogenesis, in particular in the cervicovaginal environment. Investigating the molecular determinants, ligand-selectivity and role in HIV pathogenesis of the GR-Vpr interaction may lead to new strategies for development of anti-HIV drugs.
Mulligan ML et al., 2010·American journal of obstetrics and gynecology
Vitamin D is an essential fat soluble vitamin and a key modulator of calcium metabolism in children and adults. Because calcium demands increase in the third trimester of pregnancy, vitamin D status becomes crucial for maternal health, fetal skeletal growth, and optimal maternal and fetal outcomes. Vitamin D deficiency is common in pregnant women (5-50%) and in breastfed infants (10-56%), despite the widespread use of prenatal vitamins, because these are inadequate to maintain normal vitamin D levels (>or=32 ng/mL). Adverse health outcomes such as preeclampsia, low birthweight, neonatal hypocalcemia, poor postnatal growth, bone fragility, and increased incidence of autoimmune diseases have been linked to low vitamin D levels during pregnancy and infancy. Studies are underway to establish the recommended daily doses of vitamin D in pregnant women. This review discusses vitamin D metabolism and the implications of vitamin D deficiency in pregnancy and lactation.
Wisborg K et al., 2010·Human reproduction (Oxford, England)
Previous studies have indicated that the risk of stillbirth is increased in singleton pregnancies achieved after assisted reproduction technology (ART). However, no previous study fully accounted for factors with potential influence on the risk of stillbirth. Further, whether fertility treatment, the possible reproductive pathology of the infertile couples or other characteristics related to being subfertile may explain a possible association with stillbirth remains unclear. This study compares the risk of stillbirth in women pregnant after fertility treatment (IVF/ICSI and non-IVF ART) and subfertile women with that in fertile women. We used prospectively collected data from the Aarhus Birth Cohort, Denmark and included information about 20 166 singleton pregnancies (1989-2006). Outcome measure was stillbirth. The risk of stillbirth in women who conceived after IVF/ICSI was 16.2 per thousand ( per thousand) and in women who conceived after non-IVF ART 2.3 per thousand. In fertile and subfertile women, the risk of stillbirth was 3.7 per thousand and 5.4 per thousand, respectively. Compared with fertile women, women who conceived after IVF/ICSI had more than four times the risk of stillbirth [odds ratio (OR): 4.44, 95% confidence interval (CI): 2.38-8.28], and adjustments for maternal age, BMI, education, smoking habits and alcohol and coffee intake during pregnancy had only minor impact on the findings (OR: 4.08; 95% CI: 2.11-7.93). The risk of stillbirth in women who conceived after non-IVF ART and in women who conceived spontaneously with a waiting time to pregnancy of a year or more was not significantly different from the risk in women with a shorter time to pregnancy. Compared with fertile women, women who conceived by IVF/ICSI had an increased risk of stillbirth that was not explained by confounding. Our results indicate that the increased risk of stillbirth seen after fertility treatment is a result of the fertility treatment or unknown factors pertaining to couples who undergo IVF/ICSI.
Menstrual CycleSubclinical AnovulationOvulatory Disturbance EffectsStress and Ovulation
Cross-sectional studies have found associations among elevated cognitive dietary restraint (CDR), increased ovulatory disturbances, and lower bone mass, possibly mediated by cortisol. To determine whether healthy young women with higher CDR have more menstrual cycles with subclinical ovulatory disturbances (SOD), elevated 24-h urinary free cortisol (UFC), and less positive 2-yr areal bone mineral density change (Delta-aBMD). DESIGN, SETTING, We conducted a 2-yr longitudinal study of 123 healthy, community-dwelling, nonobese, regularly menstruating women aged 19-35 yr. Key variables were Three Factor Eating Questionnaire Restraint score, percent of cycles with anvoluation and/or luteal phase length <10 d (%SOD), UFC, and Delta-aBMD at the lumbar spine (L1-L4), total hip, and whole body. Anthropometrics, general stress, physical activity, and energy intake were measured. Adjusting for potential confounders, differences were examined by general linear modeling using median split of CDR score and %SOD. Women with higher CDR had higher %SOD (56 vs. 34%, P < 0.001) and higher UFC (28.0 vs. 24.0 microg/d, P = 0.021). Delta-aBMD did not differ by CDR. Women with higher %SOD had less positive Delta-aBMD at L1-L4 (0.7 vs. 1.9%, P = 0.034) and hip (-0.6 vs. 0.9%, P = 0.001), and higher CDR score (8.7 vs. 7.1, P = 0.04). Physical activity, general stress, body mass index, and energy intake did not explain differences by CDR or %SOD. UFC was not associated with %SOD or Delta-aBMD. Women with more frequent SOD reported higher CDR and experienced less positive Delta-aBMD. Although women with higher CDR had higher UFC, the mechanism linking CDR, SOD, and aBMD is not clear.
Perimenopause/MenopauseProgestin vs Estrogen TherapyCardiovascular and Metabolic OutcomesMedroxyprogesterone Acetate Effects
To compare the cardiovascular and metabolic effects of medroxyprogesterone acetate (MPA) with those of conjugated equine estrogen (CEE) as single-hormone therapies in women who underwent hysterectomy with bilateral ovariectomy.
Secondary analysis of a 12-month, double-blind, randomized, parallel-therapy trial.
Four teaching hospitals and one community hospital in Vancouver, Canada. Thirty-three healthy women who underwent premenopausal hysterectomy with bilateral ovariectomy. Subjects received either MPA 10 mg/day (18 women) or CEE 0.6 mg/day (15 women) for 12 months, started immediately after hysterectomy with bilateral ovariectomy. MAIN Lipid profiles (high-density lipoprotein cholesterol [HDL], total cholesterol, apolipoprotein B, and triglyceride levels), homeostatic measures (hemoglobin A(1c) and fasting blood glucose level), hormone levels (free and bioavailable testosterone, cortisol, sex hormone-binding globulin [SHBG], and dehydroepiandrosterone sulfate), inflammatory markers (C-reactive protein [CRP] and serum albumin levels), and anthropometric measures (body mass index [BMI], truncal fat, and total body fat) were assessed over the 12-month period. After 12 months, the women assigned to MPA had lesser increases in BMI (p=0.04), triglyceride (p=0.003), HDL (p<0.0005), SHBG (p<0.0005), total testosterone (p=0.003), and CRP values (p=0.01) and higher serum albumin levels (p<0.0005) compared with the women receiving CEE. Therapy with CEE, but not MPA, after surgical menopause appears to predispose healthy women to low-grade inflammation, as evidenced by its independent associations with elevated CRP and reduced albumin levels. In women treated with MPA, the favorable levels of inflammatory markers, BMI, and triglyceride levels need to be confirmed in larger controlled trials, as progesterone therapy may provide a safe and effective alternative to estrogen for vasomotor symptoms in women with surgical menopause.
Menstrual CycleSubclinical AnovulationOvulatory Disturbance EffectsBasal Body Temperature
Cognitive dietary restraint (CDR) of limiting food intake to achieve/maintain a perceived ideal body weight. The objective of this 2‐yr prospective study was to determine if women with higher CDR have more subclinical ovulation disturbances (SOD; anovulation or luteal phase <10 d), elevated cortisol excretion and less positive changes in areal bone mineral density over two years (ΔaBMD). Participants were 123 healthy, non‐obese, regularly menstruating women aged 19–35. Annually participants completed questionnaires (Three Factor Eating Questionnaire, physical activity, general stress, dietary intake), anthropometrics and 24‐hr urine collections for measurement of 24‐hr urinary free cortisol (UFC). At baseline and final follow‐up, dual energy x‐ray absorptiometry scans measured ΔaBMD at the lumbar spine (L1‐4), hip and total body. Quantitative waking temperature was used to determine SOD frequency. SOD correlated positively with CDR and inversely with hip ΔaBMD but not with UFC. CDR and UFC were not associated with each other or ΔaBMD. Women with higher CDR had more SOD. Women with more SOD had less positive ΔaBMD and higher CDR. Physical activity, general stress, body mass and energy intake did not explain differences by CDR or SOD. In conclusion, CDR was the only study variable associated with SOD which was associated with less positive ΔaBMD. Canadian Institutes of Health Research 79563.
: Canadian Institute of Health Research
Goldstein A et al., 2010·The journal of sexual medicine
To describe the clinical course of a young woman who developed vestibulodynia with introital dyspareunia while on oral contraceptive (OCs) and to provide a possible explanation for the etiology of her symptoms as well as her recovery after treatment. A single case is presented including subjective reporting, laboratory evaluation, and quantitative sensory testing. After topical hormonal therapy, the patient reported resolution of her dyspareunia and and her laboratory values normalized.
InfertilityAutoimmune and Systemic DiseasesCeliac Disease and ReproductionSecondary Amenorrhea
Celiac disease is an intestinal inflammatory disease that is triggered by gluten in the diet. Patients present with a wide array of symptoms due to malabsorption that include diarrhea, abdominal pain, bloating and weight loss. In women, this disease may have implications on menstrual and reproductive health. The symptom complex includes delayed menarche, early menopause, secondary amenorrhea, infertility, recurrent miscarriages and intrauterine growth restriction. These women benefit from early diagnosis and treatment. Therefore, celiac disease should be considered and screening tests performed on women presenting with menstrual and reproductive problems and treated accordingly. The objective of this article is to review the current literature on celiac disease and its association with the above-mentioned disorders.
Physicians and menstruating women often ask pharmacists for recommendations about menstrual cycle–related problems. Progesterone and medroxyprogesterone may provide physiology-based treatment, but official indications in menstruating women in Canada are minimal. To describe pharmacists' responses to vignette-based questions about the treatment of common clinical problems in menstruating women and review evidence-based therapies. A pharmacist interviewer administered an 11-item questionnaire to a random sample of community pharmacists. Questions were based on clinical vignettes in adolescent, preand perimenopausal women and related to heavy flow, polycystic ovary syndrome, premenopausal osteoporosis, perimenopausal night sweats and side effects/contraindications for estrogens and progesterone/progestins. The participation rate was 58%, including equal numbers of male and female pharmacists. Seventy-two percent indicated that they would treat menorrhagia in an anemic 13-year-old with oral contraceptives — 21% would recommend ibuprofen and 86% iron. Half recommended that a 35-year-old smoker with heavy flow and acne stop oral contraceptives, but the other 50% recommended a switch to an oral contraceptive with cyproterone. For premenopausal osteoporosis, the majority recommended calcium and vitamin D, but 53% endorsed oral contraceptives — only 7% suggested cyclic medroxyprogesterone. For night sweats, the majority recommended progesterone/progestin in a regularly menstruating 42-year-old woman. Estrogens are contraindicated with past thrombosis and/or breast cancer family history, and they could cause nausea; 50% of pharmacists also attributed these adverse effects to progesterone/progestins. Community pharmacists vary widely in their treatment choices for common preand perimenopausal women's menstrual cycle–related problems. The evidence in support of most recommendations is minimal or lacking.
A somewhat pessimistic view on the prevention of postsurgical adhesions has developed over the years because rigorous surgical approaches may still result in the formation of postsurgical adhesions. In addition, postsurgical adhesion formation is associated with a significant degree of long-term morbidity. In this article, a surgical technique is presented which allows patients with the most extensive form of pelvic adhesions to undergo reconstructive pelvic surgery with a near–adhesion-free postoperative outcome. This study was undertaken to assess the effectiveness of a comprehensive, well-defined set of surgical techniques, with well-defined additions and subtractions in surgical technique over a period of 23 years and three distinct phases of implementation. This work was a systematic comparison of three case-series evaluated sequentially over time. The three surgical protocols were each completely standardized. This was a systematic comparison of three distinct case series of patients who had extensive pelvic adhesions. Three distinct and standardized surgical protocols were prospectively introduced and adhesion scores before and after surgical treatment were assessed and statistically compared for each of the three case series. Ninety-five (95) patients with extensive pelvic adhesive disease due to endometriosis or pelvic inflammatory disease participated in this assessment. They were chosen because of the extensive nature of their pelvic and adnexal adhesions. There were 26 patients in phase I (1987–1993), 44 patients in phase II (1994–2005), and 25 patients in phase III (2006–2009). Using the American Fertility Society scoring system for adnexal adhesions, the total adhesion score decreased from 33.8 to 18.1 in phase I, from 33.3 to 6.0 in phase II, and from 33.2 to 2.5 in phase III. Each decrease was statistically significant within each phase (P < 0.001). Further, a statistically significant decrease in subsequent adhesion scores (P < 0.01) was observed at the time of second-look laparoscopy, when comparing phases I to II, II to III, and I to III, with the lowest scores obtained with the phase III surgical techniques. With the use of a comprehensive, well-defined set of surgical antiadhesion techniques, it is possible to perform adhesion-free or near adhesion-free reconstructive pelvic surgery. (J GYNECOL SURG 26:31)