Dietary patterns and incident low-trauma fractures in postmenopausal women and  men aged ≥ 50 y: a population-based cohort study

Jerilynn C Prior

Vancouver Hospital and Health Sciences Centre

Abstract:
Background: 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.

Objective: 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.
Design: 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).

Results: 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.

Conclusion: A diet high in vegetables, fruit, and whole grains may reduce the risk of low-trauma fracture, particularly in older women.

The American Journal of Clinical Nutrition


Dehydroepiandrosterone (DHEA) reduces embryo aneuploidy: direct evidence from preimplantation genetic screening (PGS)

Abstract:
BACKGROUND: 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.

METHODS: 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.

RESULTS: 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).

DISCUSSION: 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.

Reproductive biology and endocrinology : RB&E


Progesterone and bone: actions promoting bone health in women

Abstract: 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.


In vitro fertilization and preterm delivery, low birth weight, and admission to the neonatal intensive care unit: a prospective follow-up study

Abstract:
OBJECTIVE: 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.

DESIGN: Prospective follow-up study.

SETTING: 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.


Construction and validation of a simplified fracture risk assessment tool for Canadian women and men: results from the CaMos and Manitoba cohorts

William D Leslie

University of Manitoba, Winnipeg, MB, Canada

Canadian Multicentre Osteoporosis Study (CaMos) Research Group

Jonathan D Adachi

McMaster University, Hamilton, ON, Canada

Christopher S Kovacs

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

Abstract:
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.
Introduction: 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%).

Methods: 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.

Results: 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..

Conclusion: 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.


Adding the Standard Days Method® to the contraceptive method mix in a  high-prevalence setting in Peru

Abstract:
Objective: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Revista Panamericana De Salud Publica = Pan American Journal of Public Health


Polycystic ovary syndrome in the pediatric population

Abstract: 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" hypothesis has been proposed: (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.

Metabolic Syndrome and Related Disorders


Types of ovarian activity in women and their significance: the continuum (a reinterpretation of early findings)

Abstract:
BACKGROUND: 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.

METHODS: 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.

RESULTS: 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.

CONCLUSIONS: 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.


Insulin and hyperandrogenism in women with polycystic ovary syndrome

Abstract: 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 to explain PCOS manifestations: (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.

The Journal of steroid biochemistry and molecular biology


Thyroid function and human reproductive health

K Poppe

Centre Hospitalier Universitaire Brugmann

D Glinoer

Centre Hospitalier Universitaire de Saint-Pierre

Abstract: 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.


Using the same bone density reference database for men and women provides a simpler estimation of fracture risk

Jerilynn C Prior

Vancouver Hospital and Health Sciences Centre

Abstract: 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.


Endometriosis fertility index: the new, validated endometriosis staging system

Abstract:
OBJECTIVE: To develop a clinical tool that predicts pregnancy rates (PRs) in patients with surgically documented endometriosis who attempt non-IVF conception.
DESIGN: 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.
SETTING: 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.


Efficacy of natural family planning methods

Abstract: 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.

The European journal of contraception & reproductive health care : the official journal of the European Society of Contraception


Circadian clocks in the ovary

Circadian clocks in the ovary

Abstract: 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.

Trends in endocrinology and metabolism: TEM


Determining whether women with osteopenic bone mineral density have low, moderate, or high clinical fracture risk

Christopher S Kovacs

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

Jonathan D Adachi

McMaster University, Hamilton, ON, Canada

Abstract:
Objective: 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.

Methods: 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.

Results: 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.

Conclusions: 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.


Peak bone mass from longitudinal data: implications for the prevalence, pathophysiology, and diagnosis of osteoporosis

Abstract: 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.


Oral contraceptive use and breast cancer: a prospective study of young women

Weixuan Chen

Ministry of Education of the People's Republic of China

Abstract:
Background: 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.

Methods: 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.

Results: 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 accounted for the excess risk: 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).

Conclusions: 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. IMPACT: Different oral contraceptive formulations might convey different risks of breast cancer; ongoing monitoring of these associations is necessary as oral contraceptive formulations change.

Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American  Association for Cancer Research, Cosponsored by the American Society of  Preventive Oncology


Natural family planning: physicians' knowledge, attitudes, and practice

Abstract:
OBJECTIVE: To assess physicians' knowledge, attitudes, and practice with respect to four evidence-based natural family planning (NFP)

methods: Standard Days, cervical mucus, basal body temperature, and the lactational amenorrhea method.

METHODS: 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.

RESULTS: 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.

CONCLUSION: 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.

Journal of Obstetrics and Gynaecology Canada : JOGC = Journal D'obstetrique Et  Gynecologie Du Canada : JOGC


Maca (L. meyenii) for improving sexual function: a systematic review

Abstract:
BACKGROUND: 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.

METHODS: 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.

RESULTS: 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.

CONCLUSION: 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.

BMC complementary and alternative medicine


Thyroid and obesity: an intriguing relationship

Abstract: This population-based study suggests that use of DMPA is associated with a slightly increased risk of fractures.

The Journal of Clinical Endocrinology and Metabolism


Fragility fractures and the osteoporosis care gap in women: the Canadian Multicentre Osteoporosis Study

Jerilynn C Prior

Vancouver Hospital and Health Sciences Centre

Abstract:
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.
Introduction: 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.

Methods: 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.

Results: 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.

Conclusion: 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.


Risk of venous thromboembolism and the use of dienogest- and  drospirenone-containing oral contraceptives: results from a German case-control  study

Jürgen Dinger

Berlin Center for Epidemiology and Health Research

Abstract:
Objective: 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.

Methods: 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.

Results: 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).

The Journal of Family Planning and Reproductive Health Care


Effect of depot medroxyprogesterone acetate on postpartum depression

Abstract:
Background: 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.

Study Design: 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.

Results: 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).

Conclusion: Administration of DMPA in the immediate postpartum period does not appear to predispose women to PPD.


Oral contraceptive use and estrogen/progesterone receptor-negative breast cancer  among African American women

Lauren A Wise

Slone Epidemiology Center at Boston University, Boston, Massachusetts and 2Lombardi Comprehensive Cancer Center at Georgetown University Medical Center, Washington, District of Columbia

Julie R Palmer

Georgetown Lombardi Comprehensive Cancer Center

Abstract:
Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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. IMPACT: Mechanisms to explain the adverse influence of oral contraceptive use on ER(-) breast cancer need to be elucidated.


Evaluation of methods and costs associated with recruiting healthy women  volunteers to a study of ovulation

Abstract:
Objective: 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.

Methods: 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.

Results: 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.

Conclusions: 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.


Is it the patient or the IVF? Beckwith-Wiedemann syndrome in both spontaneous and assisted reproductive conceptions

Abstract:
Objective: 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.

Design: Case report.

Setting: 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 and infertility

Endometriosis and infertility

Maria Elisabetta Coccia

Department of Biomedical, Experimental and Clinical Sciences “Mario Serio”, University of Florence, 50134 Florence, Italy

Abstract: 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.

Journal of Assisted Reproduction and Genetics


Normative bone mineral density z-scores for Canadians aged 16 to 24 years: the  Canadian Multicenter Osteoporosis Study

Jonathan D Adachi

McMaster University, Hamilton, ON, Canada

Abstract: 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.

Journal of Clinical Densitometry : the Official Journal of the International  Society for Clinical Densitometry


Increased pregnancy loss rate in thyroid antibody negative women with TSH levels between 2.5 and 5.0 in the first trimester of pregnancy

Abstract:
CONTEXT: 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.

OBJECTIVE: 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.

DESIGN: 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 based on their initial TSH: 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.

SETTING: The study was conducted at two ambulatory clinics of community hospitals in southern Italy.

PATIENTS: A total of 4123 women were evaluated.

INTERVENTION: There was no intervention.

MAIN OUTCOME MEASURES: The incidence of pregnancy loss and preterm delivery in group A as compared with group B was measured.

RESULTS: 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.

CONCLUSIONS: 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 Journal of Clinical Endocrinology and Metabolism


Vaginal microbiome of reproductive-age women

Catherine C Davis

The Procter & Gamble Company, Cincinnati, OH 45224

Kevin Ault

Emory University School of Medicine, Atlanta, GA 30322;

Abstract: 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 clustered into five groups: 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.

Proceedings of the National Academy of Sciences of the United States of America


A systematic review of the effect of oral antioxidants on male infertility

Yacoub Khalaf

Guy's and St Thomas' NHS Foundation Trust

Arri Coomarasamy

Birmingham Women’s and Children’s NHS Foundation Trust

Tarek El-Toukhy

Assisted Conception Unit, Guy’s and St Thomas’ Hospital NHS Foundation Trust, London, UK

Abstract: 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.


Dignitas personae and the Adoption of Frozen Embryos: A New Chill Factor?

Abstract: 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.

The national Catholic bioethics quarterly


Insulin resistance, obesity, inflammation, and depression in polycystic ovary  syndrome: biobehavioral mechanisms and interventions

Abstract: Objective: 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.


Modulation of HIV-1 virulence via the host glucocorticoid receptor: towards  further understanding the molecular mechanisms of HIV-1 pathogenesis

Janet P Hapgood

Department of Molecular and Cell Biology University of Cape Town Rondebosch South Africa

Abstract: 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.


Implications of vitamin D deficiency in pregnancy and lactation

Abstract: 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.

American journal of obstetrics and gynecology


IVF and stillbirth: a prospective follow-up study

Abstract:
BACKGROUND: 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.

METHODS: 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.

RESULTS: 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.

CONCLUSIONS: 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.


A prospective exploration of cognitive dietary restraint, subclinical ovulatory  disturbances, cortisol, and change in bone density over two years in healthy  young women

Jerilynn C Prior

Vancouver Hospital and Health Sciences Centre

Abstract:
Context: Cross-sectional studies have found associations among elevated cognitive dietary restraint (CDR), increased ovulatory disturbances, and lower bone mass, possibly mediated by cortisol.

Objective: 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, AND

Participants: We conducted a 2-yr longitudinal study of 123 healthy, community-dwelling, nonobese, regularly menstruating women aged 19-35 yr.

MAIN OUTCOME MEASURES: 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.

Results: 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.

Conclusion: 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.

The Journal of Clinical Endocrinology and Metabolism


Cardiovascular and metabolic effects of medroxyprogesterone acetate versus  conjugated equine estrogen after premenopausal hysterectomy with bilateral  ovariectomy

Christine L Hitchcock

Centre for Menstrual Cycle and Ovulation Research, Division of Endocrinology, University of British Columbia, Vancouver, BC, Canada.

Abstract:
STUDY Objective: 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.
Design: Secondary analysis of a 12-month, double-blind, randomized, parallel-therapy trial.
Setting: Four teaching hospitals and one community hospital in Vancouver, Canada.

Participants: Thirty-three healthy women who underwent premenopausal hysterectomy with bilateral ovariectomy.

Intervention: 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. MEASUREMENTS AND

MAIN Results: 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.

Conclusion: 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.


"Relationships among cognitive dietary restraint, subclinical ovulation disturbances, cortisol and 2‐yr change in bone density in premenopausal women"

Abstract:
Cognitive dietary restraint (CDR) is the
perception
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.
Grant Funding Source
: Canadian Institute of Health Research


Can oral contraceptives cause vestibulodynia?

Abstract:
AIM: 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.

METHODS: A single case is presented including subjective reporting, laboratory evaluation, and quantitative sensory testing.

RESULTS: After topical hormonal therapy, the patient reported resolution of her dyspareunia and and her laboratory values normalized.


Celiac disease and its effect on human reproduction: a review

Abstract: 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.


Community pharmacists' therapeutic recommendations for heavy flow, androgen excess, fragility fractures and night sweats in menstruating women

Abstract:
Background: 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.

Objectives: To describe pharmacists' responses to vignette-based questions about the treatment of common clinical problems in menstruating women and review evidence-based therapies.

Methods: 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.

Results: 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.

Conclusions: 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.

Canadian Pharmacists Journal / Revue des Pharmaciens du Canada


Near Adhesion-Free Reconstructive Pelvic Surgery: Three Distinct Phases of Progress Over 23 Years

Abstract:
Background: 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.

Purpose: 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.

Materials and Methods: 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.

Results: 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.

Conclusions: 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)


Immunosuppression in Human Decidua Against Natural Killer Cells


Estrogen therapy and risk of breast cancer in postmenopausal women: a  case-control study and results of a multivariate analysis

Abstract:
Objective: Several randomized trials and observational studies show that the use of hormone therapy (HT) increases the risk of breast cancer (BC). The aim of this study was to assess the effects of exposure to both HT and oral contraceptives (OCs) on BC risk in postmenopausal women, all residing in the same metropolitan area.

Methods: Data regarding a series of 238 consecutive postmenopausal women with infiltrating ductal carcinoma (cases) and 255 randomly selected age-matched healthy women (controls) were reviewed. Odds ratios for no breast-feeding and HT and OC use were 1.82 (95% CI, 1.20-2.77), 2.49 (95% CI, 1.73-3.58), and 2.06 (95% CI 1.14-3.70), respectively.

Results: Four independent variables (years between menarche and menopause, breast-feeding, OC use, and HT use) were included in the final multivariate analysis using logistic regression. The cumulative odds ratio calculated from the observed versus predicted values, obtained using the logistic regression function, was 4.55 (95% CI, 2.13-9.71), whereas the cumulative risk of common exposure to both OCs and HT was 2.77 (95% CI, 1.44-5.32). The logistic model correctly classified 67.5% (95% CI, 63.2-71.5) of cases. The receiver operating characteristic (ROC) curve of the complete logistic function showed a fair area of accuracy (0.77; 95% CI, 0.72-0.81).

Conclusions: Our results show that the risk of common exposure to both OCs and HT increases in women with other risk factors. However, several parameters traditionally considered in epidemiological studies do not have the same weight in each local community, suggesting the need to create different models to correctly select the high-risk population.


Relationship of omega-3 and omega-6 fatty acids with semen characteristics, and anti-oxidant status of seminal plasma: a comparison between fertile and infertile men

Abstract:
BACKGROUND & AIMS: Fatty acid (FA) composition of the spermatozoa may be an important determinant of fertility. The aim was to evaluate polyunsaturated fatty acid (PUFA) composition of the blood plasma and spermatozoa in infertile men with idiopathic oligoasthenoteratozoospermia (OAT).

METHODS: Eighty-two infertile men with idiopathic OAT and seventy-eight fertile men defined according to semen concentration and proven fertility were enrolled in the study. The semen parameters were assessed according to World Health Organization criteria; three omega-3 fatty acids--alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and two omega-6 fatty acids--linoleic acid (LA) and arachidonic acid (AA) concentrations were measured in blood plasma and spermatozoa; and the seminal plasma enzymatic antioxidant levels of catalase, and superoxide dismutase (SOD) were also assessed.

RESULTS: Proven fertile men had higher blood and spermatozoa levels of omega-3 FAs compared with the infertile patients. The ratio of serum omega-6/omega-3 fatty acids was significantly higher in infertile (14.8+/-4.3) patients compared to fertile controls (6.3+/-2.2) (P=0.001). Additionally, levels of AA were higher and the omega-3 index (EPA+DHA) was lower in infertile subjects than in fertile controls (all P values<0.05). Infertile men had higher mean AA:DHA ratio and AA:EPA (6.4+/-2.9 and 12.0+/-4.9, respectively) than fertile men (3.3+/-1.8 and 6.7+/-2.6, respectively) (both P=0.001). A strong negative correlation was found between the AA:DHA and AA:EPA ratios and total sperm count (r=-0.62, P=0.001 and r=-0.64, P=0.001, respectively), sperm motility (r=-0.63, P=0.001 and r=-0.61, P=0.001, respectively), and sperm morphology (r=-0.61, P=0.001, and r=-0.59, P=0.002, respectively).

CONCLUSIONS: Infertile men had lower concentrations of omega-3 FAs in spermatozoa than fertile men. These results suggest that research should be performed to assess the potential benefits of omega-3 FA supplementation as a therapeutic approach in infertile men with idiopathic OAT.

Clinical nutrition (Edinburgh, Scotland)


Chronic endometritis is a frequent finding in women with recurrent implantation failure after in vitro fertilization

Abstract:
OBJECTIVE: To determine the role of endometrial sampling for identification and treatment of chronic endometritis (CE) in patients undergoing IVF-ET who repeatedly failed to conceive despite the transfer of good-quality embryos.

DESIGN: Retrospective chart review.

SETTING: University-based tertiary fertility center.

PATIENT(S): Thirty-three patients with recurrent implantation failure (RIF) who underwent endometrial sampling and subsequent ET were analyzed based on immunohistochemically confirmed CE: CE present on biopsy (group 1; n = 10) and CE absent on biopsy (group 2; n = 23). Patients with RIF undergoing IVF cycles during the same time period who did not have endometrial sampling were used as controls (group 3; n = 485).

INTERVENTION(S): Endometrial sampling for CE and subsequent antibiotic treatment in affected patients followed by another IVF-ET cycle.

RESULT(S): Chronic endometritis was identified in 30.3% of patients with RIF. Group 1 had lower implantation rates (11.5%) in the IVF cycle following treatment than did group 2 and group 3 (32.7% and 20.3%, respectively). Clinical pregnancy and ongoing pregnancy rates were similar across groups.

CONCLUSION(S): Recurrent implantation failure warrants investigation of CE as a contributing factor. Women demonstrating CE on endometrial sampling have lower implantation rates in a subsequent IVF-ET cycle; however, there were no differences in subsequent clinical pregnancy or ongoing pregnancy rates after successful antibiotic treatment.


Dietary patterns in Canadian men and women ages 25 and older: relationship to demographics, body mass index, and bone mineral density

Abstract:
Background: Previous research has shown that underlying dietary patterns are related to the risk of many different adverse health outcomes, but the relationship of these underlying patterns to skeletal fragility is not well understood. The objective of the study was to determine whether dietary patterns in men (ages 25-49, 50+) and women (pre-menopause, post-menopause) are related to femoral neck bone mineral density (BMD) independently of other lifestyle variables, and whether this relationship is mediated by body mass index.

Methods: We performed an analysis of 1928 men and 4611 women participants in the Canadian Multicentre Osteoporosis Study, a randomly selected population-based longitudinal cohort. We determined dietary patterns based on the self-administered food frequency questionnaires in year 2 of the study (1997-99). Our primary outcome was BMD as measured by dual x-ray absorptiometry in year 5 of the study (2000-02).

Results: We identified two underlying dietary patterns using factor analysis and then derived factor scores. The first factor (nutrient dense) was most strongly associated with intake of fruits, vegetables, and whole grains. The second factor (energy dense) was most strongly associated with intake of soft drinks, potato chips and French fries, certain meats (hamburger, hot dog, lunch meat, bacon, and sausage), and certain desserts (doughnuts, chocolate, ice cream). The energy dense factor was associated with higher body mass index independent of other demographic and lifestyle factors, and body mass index was a strong independent predictor of BMD. Surprisingly, we did not find a similar positive association between diet and BMD. In fact, when adjusted for body mass index, each standard deviation increase in the energy dense score was associated with a BMD decrease of 0.009 (95% CI: 0.002, 0.016) g/cm(2) for men 50+ years old and 0.004 (95% CI: 0.000, 0.008) g/cm(2) for postmenopausal women. In contrast, for men 25-49 years old, each standard deviation increase in the nutrient dense score, adjusted for body mass index, was associated with a BMD increase of 0.012 (95% CI: 0.002, 0.022) g/cm(2).

Conclusions: In summary, we found no consistent relationship between diet and BMD despite finding a positive association between a diet high in energy dense foods and higher body mass index and a strong correlation between body mass index and BMD. Our data suggest that some factor related to the energy dense dietary pattern may partially offset the advantages of higher body mass index with regard to bone health.


Variations in body mass index of users of depot-medroxyprogesterone acetate as a  contraceptive

Luis Bahamondes

Universidade Estadual de Campinas (UNICAMP)

Abstract:
Background: Weight gain is a frequent reason for discontinuing the contraceptive with depot-medroxyprogesterone acetate (DMPA).

Study Design: This 3-year retrospective cohort study assessed body mass index (BMI; kg/m(2)) variations in 379 current or past DMPA users compared to TCu380A intrauterine device (IUD) users matched for age and BMI, categorized into G1 (normal weight), G2 (overweight) or G3 (obese) according to baseline BMI. Variations in weight and BMI were evaluated using analysis of variance.

Results: BMI increased progressively in all groups but significantly more in G1 and G2 DMPA users compared to nonusers and according to duration of use. In the G3 subgroup, weight trends were similar in the DMPA and IUD users.

Conclusions: Normal and overweight women increased BMI with DMPA use; however, obese women did not increase weight. Weight increase in DMPA users could be associated with metabolic alterations related to duration of use in normal and overweight women and to alterations already present in obese women. Prospective studies are required to determine triggering factors. DMPA use or=30.


Progesterone function in human endometrium: clinical perspectives

Steven L Young

University of North Carolina at Chapel Hill

Abstract: Progesterone is essential for endometrial receptivity and successful establishment of pregnancy. Either an insufficient progesterone concentration or an insufficient response to progesterone, therefore can lead to infertility and pregnancy loss. Assessment of the role that either progesterone insufficiency or inadequate progesterone response plays in human reproductive failure has been difficult to assess because serum progesterone concentrations fluctuate markedly, limiting the ability to characterize sufficiency of progesterone, and there are no highly reliable markers of endometrial function available. Recent evidence demonstrates exquisite sensitivity of normal endometrium to very low levels of progesterone stimulation, suggesting that progesterone insufficiency should not be a common cause of reproductive failure. Further evidence suggests that women with endometriosis, and possibly polycystic ovarian syndrome, have an altered progesterone response, which may explain some of the clinical features of these disorders and supports the hypothesis that progesterone resistance underlies some cases of human reproductive failure.


Use of oral contraceptives in pregnancy and major structural birth defects in offspring

Dorothy Kim Waller

The University of Texas Health Science Center at Houston

Tunu Ramadhani

Texas Department of State Health Services

Sonia Hernández-Diaz

Department of Epidemiology, Harvard T.H. Chan School of Public Health , Boston, MA,

Abstract:
BACKGROUND: Oral contraceptives (OCs) are the most commonly used reversible contraceptive method among US women. Although the majority of previous studies have reported no association between OC use during pregnancy and birth defects, some studies have reported increased occurrence of neural tube defects, limb reduction defects, and urinary tract anomalies.

METHODS: We assessed OC use among mothers who participated in the multisite, case-control, National Birth Defects Prevention Study. Mothers of 9986 infants with 32 types of birth defects and 4000 infants without birth defects were included.

RESULTS: Maternal OC use during the first 3 months of pregnancy was associated with an increased odds ratio for 2 of 32 birth defects: hypoplastic left heart syndrome (adjusted odds ratio = 2.3 [95% confidence interval = 1.3-4.3) and gastroschisis (1.8 [1.3-2.7]).

CONCLUSION: Previous reports of associations between OC use and specific types of anomalies were not corroborated. Given that associations were assessed for 32 types of birth defects, our findings of 2 increased associations between OC use and gastroschisis and hypoplastic left heart syndrome should be interpreted as hypotheses until they can be evaluated further. Overall, our findings are consistent with the majority of previous studies that found women who use OCs during early pregnancy have no increased risk for most types of major congenital malformations.


Use of four biomarkers to evaluate the risk of breast cancer subtypes in the  women's contraceptive and reproductive experiences study

Giske Ursin

Division of Cancer Etiology, Department of Population Sciences, City of Hope Medical Center, Duarte, California; Departments of 2Preventive Medicine and 3Pathology, Keck School of Medicine, Univers...

Leslie Bernstein

Centers for Disease Control and Prevention

Abstract: Epidemiologic studies suggest that some hormone-related risk factors in breast cancer differentially influence risk for disease subtypes classified by the status of the estrogen and progesterone receptors (ER/PR). However, it remains unclear whether human epidermal growth factor receptor 2 (HER2) or p53 expression status further differentiates these exposure-risk group associations. We evaluated the associations of oral contraceptive (OC) use and reproductive factors with incident invasive breast cancer subtypes among 1,197 population-based cases and 2,015 controls from the Los Angeles County or Detroit components of the Women's Contraceptive and Reproductive Experiences Study. Case-control comparisons by ER/PR/HER2/p53 status were conducted by multivariable polychotomous unconditional logistic regression methods. We found that OC use was not associated with any breast cancer subtype as defined by ER/PR/HER2/p53 status, except for a 2.9-fold increased risk of so-called triple-negative tumors (ER(-)/PR(-)/HER2(-)) among women of 45 to 64 years of age who started OC use before age 18. Parity was associated with a decreased risk of luminal A (ER(+) or PR(+), HER2(-)), luminal B (ER(+) or PR(+)/HER2(+)), and ER(-)/PR(-)/HER2(+) tumors. Age at first full-term pregnancy was positively associated with luminal A tumors among older women. Neither of these reproductive factors was associated with triple-negative tumors. Long duration of breast-feeding lowered the risk of triple-negative and luminal A tumors. p53 status did not define further differential risk patterns. Our findings offer evidence of differences in the hormone-related risk factors between triple-negative cancers and other ER/PR/HER2-defined subtypes of breast cancer.


[Retrospective studies of pregnancies after assisted medical reproduction from 2001-2009 and Central Hospital in Luxembourg (part 2)]

Abstract: The first chapter analyses the ART methods of the Centre Hospitalier of Luxembourg, in the department of reproductive medicine between 2001 and 2009. The second chapter examines the techniques individually, their influence on pregnancy outcomes, the complications on offsprings and their health. The results coincide with literature in that risks are acceptable as long as good medical and biological conditions are maintained. Multiple pregnancies remain the most frequent complication, particularly once out of IVF. These are analysed separately as well as the pregnancies after egg and semen donation.

Bulletin de la Societe des sciences medicales du Grand-Duche de Luxembourg


Effects of oral, vaginal, and transdermal hormonal contraception on serum levels of coenzyme q(10), vitamin e, and total antioxidant activity

Abstract: The use of the transdermal contraceptive patch is associated with greater bioavailability of ethinyl estradiol (EE) compared with contraceptive vaginal ring or oral contraceptives (OC). We compared the influences of three contraceptive methods (OC, vaginal ring, and transdermal patch) on serum levels of coenzyme Q(10), alpha-tocopherol, gamma-tocopherol and total antioxidant capacity in premenopausal women. Blood samples from 30 premenopausal women who used hormonal contraception for at least 4 months were collected. Forty subjects who did not use any contraception were studied as control. Serum levels of coenzyme Q(10), alpha-tocopherol and gamma-tocopherol were measured by high-pressure liquid chromatography. Serum samples were also assayed for total antioxidant capacity (TAOC). Serum levels of coenzyme Q(10) and alpha-tocopherol were found to be significantly lower (P < .05) in all three contraceptive users compared with controls. Contraceptive patch users had the lowest levels of coenzyme Q(10) levels compared with normal subjects. Serum TAOC levels were significantly lower (P < .05) among the contraceptive user groups. Alterations in coenzyme Q(10) and alpha-tocopherol induced by hormonal contraception and the potential effect(s) of exogenous ovarian hormones should be taken into consideration in future antioxidant research.


The immune system in pregnancy: a unique complexity

Abstract: Placental immune response and its tropism for specific viruses and pathogens affect the outcome of the pregnant woman's susceptibility to and severity of certain infectious diseases. The generalization of pregnancy as a condition of immune suppression or increased risk is misleading and prevents the determination of adequate guidelines for treating pregnant women during pandemics. There is a need to evaluate the interaction of each specific pathogen with the fetal/placental unit and its responses to design the adequate prophylaxis or therapy. The complexity of the immunology of pregnancy and the focus, for many years, on the concept of immunology of pregnancy as an organ transplantation have complicated the field and delayed the development of new guidelines with clinical implications that could help to answer these and other relevant questions. Our challenge as scientists and clinicians interested in the field of reproductive immunology is to evaluate many of the 'classical concepts' to define new approaches for a better understanding of the immunology of pregnancy that will benefit mothers and fetuses in different clinical scenarios.

American journal of reproductive immunology (New York, N.Y. : 1989)


Altered gene expression profiling in endometrium: evidence for progesterone resistance

Abstract: Progesterone plays an important role in regulating multiple events in the uterus. It controls endometrial proliferation and differentiation, which are important for uterine function. Dysregulation of progesterone signaling leads to impaired physiological functions. Indeed, aberrant expression of progesterone-regulated genes in the endometrium has been implicated in several gynecologic disorders, including endometriosis, polycystic ovarian syndrome (PCOS), and endometrial hyperplasia. Although several investigators have analyzed eutopic endometrial expression of progesterone-target genes, the genesis and consequences of progesterone resistance remain unclear. We review evidence for progesterone resistance in endometrium of women with endometriosis, PCOS, and endometrial hyperplasia, and we identify possible mechanisms associated with reduced progesterone activity in endometrium of (some) women with these gynecologic disorders that have a significant impact on women's health and well-being.


Abstract:
1. Int J Pharm Compd. 2010 Mar-Apr;14(2):171-3.

Low dose naltrexone: side effects and efficacy in gastrointestinal disorders.

Ploesser J(1), Weinstock LB, Thomas E.

Author information:
(1)St. Louis College of Pharmacy, St. Louis, Missouri.

Use of low dose naltrexone has been advocated for a variety of medical problems.
Only a few articles published in peer review journals have documented side
effects of low dose naltrexone. The purpose of this study was to determine the
frequency of adverse effects of low dose naltrexone in patients who have been
treated for a variety of gastrointestinal disorders. The secondary purpose was
to determine global efficacy in a retrospective survey. Patients (206) form a
single gastroenterologist's clinical practice who had been prescribed naltrexone
were mailed a survey to evaluate the side effects and efficacy of naltrexone.
Patients had either irritable bowel syndrome without evidence for small
intestinal bacterial overgrowth, chronic idiopathic constipation, or
inflammatory bowel disease. Patients with diarrhea were given 2.5 mg daily,
constipation 2.5 mg twice daily, and inflammatory bowel disease 4.5 mg daily. In
the patients who returned the survey, 47/121 (38.8%) had no side effects. Of the
74/121 (61.2%) patients who had side effects, 58 had one or more neurological
complaints, and 32 had one or more gastrointestinal side effects. In the
patients with side effects, 24/74 (32.4%) had short lived symptoms. Low dose
naltrexone was terminated owing to side effects in 20/74 patients (27.0%). In 13
patients with idiopathic irritable bowel syndrome, 2 were markedly worse. In 85
patients with irritable bowel syndrome-small intestinal bacterial overgrowth, 15
were markedly improved, 32 were moderately worse, and 1 was markedly worse. In
12 patients with chronic constipation, 7 were markedly improved, 1 was
moderately improved, 1 was mildly improved, and 4 were unchanged. Low dose
naltrexone frequently has side effects but in most is tolerable. It appears to
be helpful for a member of patients with gastrointestinal disorders.

PMID: 23965429

International journal of pharmaceutical compounding


DIR Jahrbuch 2009 (Deutsches IVF-Register Annual Report 2009)

Abstract: Annual report (Jahrbuch) of the Deutsches IVF-Register (DIR) for treatment year 2009. DIR is the German national IVF/ICSI registry, founded 1982 — the oldest continuously operating ART registry. Voluntary professional-society database with high de-facto coverage of German fertility centres. Reports cycles, transfers, pregnancies and clinical outcomes by treatment type (IVF, ICSI, frozen embryo transfer, donor). German-language registry document. Used as a Phase B historical-archive source for the ART Registry Comparison study (cross-registry classification by reporting completeness on 7 framework dimensions).


Does Therapy for Minimal/Mild Endometriosis Enhance Conception?

Kim AH

Eidgenossische Technische Hochschule Zurich Institute of Pharmaceutical Sciences


CARTR 2010 Annual Report - 2009 Results from the Canadian ART Register

Abstract: Canadian ART Register (CARTR) annual report for 2009. A total of 16,315 cycles was reported to CARTR. Voluntary professional society database operated by the Canadian Fertility and Andrology Society.


Retrospective Review: Outcomes from All Couples with 3 or More Recurrent Miscarriages Receiving Treatment from NaPro Fertility Clinic, Ireland 2010

Phil C Boyle

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

Abstract: Couples presenting with 3 or more miscarriages fit the definition of recurrent miscarriage which affects 1% of those trying to conceive. Clinics based in Dublin and Galway use a multifactorial approach with NaProTechnology to evaluate and treat such couples. 355 couples with subfertility attended for 2+ consultations during 2010. 50 (14%) had 3+ miscarriages. Of 36 who conceived, 29 (80.6%) had live births, 4 (11.1%) miscarried, 2 (5.6%) had ectopic pregnancies. Average female age 37.5 years. Expected miscarriage rate for this population would be above 30-40%. A total miscarriage and ectopic rate of 16.7% per couple is encouraging. Women with recurrent miscarriage appear to have better than expected outcomes following a multifactorial NaPro treatment approach.


Veerle Goossens

Abstract: 22. Assisted reproductive technology in Europe, 2006: results generated from European registers by ESHRE. de Mouzon J(1), Goossens V, Bhattacharya S, Castilla JA, Ferraretti AP, Korsak V, Kupka M, Nygren KG, Nyboe Andersen A; European IVF-monitoring (EIM) Consortium, for the European Society of Human Reproduction and Embryology (ESHRE). Collaborators: Glozheni O, Strohmer H, Bogaerts K, Kyurkchiev S, Pelekanos M, Rezabek K, Erb K, Gissler M, de Mouzon J, Shojaei T, Buhler K, Tarlatzis B, Kosztolanyi G, Bjorgvinsson H, Mocanu E, Scaravelli G, Lejins V, Gudleviciene Z, Lazarevski S, Simic TM, Lambalk C, Hazekamp JT, Kuczynski W, Calhaz-Jorge C. (1)ESHRE Central Office, Meerstraat 60, B-1852 Grimbergen, Belgium. jacques.demouzon@inserm.fr BACKGROUND: In this 10th European IVF-monitoring (EIM) report, the results of assisted reproductive techniques from treatments initiated in Europe during 2006 are presented. Data were mainly collected from existing national registers. METHODS: From 32 countries, 998 clinics reported 458 759 treatment cycles including: IVF (117 318), ICSI (232 844), frozen embryo replacement (FER, 86 059), egg donation (ED, 12 685), preimplantation genetic diagnosis/screening (6561), in vitro maturation (247) and frozen oocytes replacements (3498). Overall this represents a 9.7% increase in activity since 2005, which is partly due to an increase in registers (seven more countries with complete coverage). European data on intrauterine insemination using husband/partner's (IUI-H) and donor (IUI-D) semen were reported from 22 countries. A total of 134 261 IUI-H and 24 339 IUI-D cycles were included. RESULTS: In 20 countries, where all clinics reported to the IVF register, a total of 359 110 assisted reproductive technology (ART) cycles were performed in a population of 422.5 million, corresponding to 850 cycles per million inhabitants. For IVF, the clinical pregnancy rates per aspiration and per transfer were 29.0 and 32.4%, respectively. For ICSI, the corresponding rates were 29.9 and 33.0%. After IUI-H the delivery rate was 9.2% in women below 40. After IVF and ICSI the distribution of transfer of one, two, three and four or more embryos was 22.1, 57.3, 19.0 and 1.6%, respectively. Compared with 2005, fewer embryos were replaced per transfer, but significant national differences in practice were apparent. The proportion of singleton, twin and triplet deliveries after IVF and ICSI combined was 79.2, 19.9 and 0.9%, respectively. This gives a total multiple delivery rates of 20.8% compared with 21.8% in 2005 and 22.7% in 2004. IUI-H in women below 40 years of age resulted in 10.6% twin and 0.6% triplet pregnancies. CONCLUSIONS: Compared with previous years, the reported number of ART cycles in Europe has increased, pregnancy rates have increased marginally, even though fewer embryos were transferred and the multiple delivery rates have declined.


ACOG Practice Bulletin No. 110: noncontraceptive uses of hormonal contraceptives

Abstract:
Patients are often unaware of the non-contraceptive benefits of hormonal contraception. and this represents an opportunity for counseling (2). A brief list of some common non-contraceptive benefits is provided in Box I.
Most hormonal contraceptives combine progestin for its contraceptive effects and an estrogen to stabilize the endometrium and reduce unwanted spocane. Users progestin-only hormonal contraceptives avoid the sile citects associated with the use of contraceptives containing estrogen. Progestin-only contraceptives often can be used in women when estrogen is contraindicated; however, unpredictable spotting may be problematic for some patients. Over time, this unwanted bleeding generally subsides and progestin-only methods may provide highly effective long-term contraception.
Since oral contraceptives containing 150 micrograms or mestranol were introduced in ryo0, the dose of estrogen per pill has been reduced: current bills may. . .