In vitro fertilisation for unexplained subfertility

Abstract:
Background: In vitro fertilisation (IVF) is a widely accepted treatment for unexplained infertility (NICE 2004), which affects up to a third of all infertile couples. With estimated live birth rates (LBRs) per cycle varying from 33.1% in women aged under 35 years down to 12.5% in women aged between 40 and 42 years (HFEA 2011), its effectiveness has not been rigorously evaluated in comparison with other treatments. With increasing awareness of the role of expectant management, less-invasive procedures such as intrauterine insemination (IUI), and concerns about multiple pregnancies and costs associated with IVF, it is important to evaluate the effectiveness of IVF against other treatment options in couples with unexplained infertility.

Objectives: To evaluate the effectiveness and safety of IVF compared to expectant management, clomiphene citrate, IUI alone and intrauterine insemination plus controlled ovarian stimulation (IUI+SO). SEARCH

Methods: Cochrane Menstrual Disorders and Subfertility Group Trials Register (searched July 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, first quarter), MEDLINE (1970 to July 2011), EMBASE (1985 to July 2011) and reference lists of articles were searched. Relevant conference proceedings were handsearched. Authors were contacted.
Selection Criteria: Randomised controlled trials (RCTs) were included. LBR per woman was the primary outcome.
Data Collection and Analysis: Two review authors independently assessed eligibility and quality of trials.

MAIN Results: Six RCTs were included in the final analysis. LBR per woman was significantly higher with IVF (45.8%) than expectant management (3.7%) (odds ratio (OR) 22.00, 95% confidence interval (CI) 2.56 to 189.37, 1 RCT, 51 women). There were no comparative data for clomiphene citrate. There was no evidence of a significant difference in LBR between IVF and IUI alone (OR 1.96, 95% CI 0.88 to 4.36, 1 RCT, 113 women), 40.7% with IVF versus 25.9% with IUI. In studies comparing IVF versus IUI+SO, LBR per woman did not differ significantly between the groups among treatment-naive women (OR 1.09, 95% CI 0.74 to 1.59, 2 RCTs, 234 women) but was significantly higher in a large RCT of women pretreated with IUI + clomiphene citrate (OR 2.66, 95% CI 1.94 to 3.63, 1 RCT, 341 women). These three studies could not be pooled due to high heterogeneity (I(2) = 84%). There was no evidence of a significant difference in multiple pregnancy rate (MPR) or ovarian hyperstimulation syndrome (OHSS) between the two treatments (OR 0.64, 95% CI 0.31 to 1.29, 3 RCTs, 351 women; OR 1.53, 95% CI 0.25 to 9.49, 1 RCT, 118 women, respectively). AUTHORS'

Conclusions: IVF may be more effective than IUI+SO. Due to paucity of data from RCTs the effectiveness of IVF for unexplained infertility relative to expectant management, clomiphene citrate and IUI alone remains unproven. Adverse events and the costs associated with these interventions have not been adequately assessed.

The Cochrane Database of Systematic Reviews


Ovarian volume correlates strongly with the number of nongrowing follicles in the  human ovary

Abstract: A reliable indirect measure of ovarian reserve for the individual woman remains a challenge for reproductive specialists. Using descriptive statistics from a large-scale study of ovarian volumes, we have developed a normative model for healthy females for ages 25 through 85. For average values, this model has a strong and positive correlation (r = 0.89) with our recent model of nongrowing follicles (NGFs) in the human ovary for ages 25 through 51. When both models are log-adjusted, the correlation increases to r = 0.99, over the full range of ovarian volume. Furthermore we can deduce that an ovary of 3 cm(3) volume (or less) contains approximately 1000 NGF (or fewer). These strong correlations indicate that ovarian volume is a useful factor in the indirect estimation of human ovarian reserve for the individual woman.


Selective salpingography and tubal catheterization in infertile women

Abstract:
Background: Use of selective salpingography (SS) and fallopian tube catheterization (TC) has revolutionized the diagnosis and treatment of proximal tubal infertility.

Aim: To evaluate results of women treated for proximal tubal obstruction by selective salpingography and tubal catherization.

Methods: Selective salpingography was performed in women with proximal bilateral tubal obstructions. Follow-up ranged from 4 to 12 months.

Results: twelve patients had been shown to have bilateral proximal obstruction of the fallopian tube. After SS/TC, patency was achieved in 8 cases. Spontaneous conceptions occurred in 4 women.

Conclusion: SS and TC should be used more widely because it is simple and effective in case of proximal tubal blockage.


Relationship satisfaction and outcome in women who meet their partner while using oral contraception

Abstract: Hormonal variation over the menstrual cycle alters women's preferences for phenotypic indicators of men's genetic or parental quality. Hormonal contraceptives suppress these shifts, inducing different mate preference patterns among users and non-users. This raises the possibility that women using oral contraception (OC) choose different partners than they would do otherwise but, to date, we know neither whether these laboratory-measured effects are sufficient to exert real-world consequences, nor what these consequences would be. Here, we test for differences in relationship quality and survival between women who were using or not using OC when they chose the partner who fathered their first child. Women who used OC scored lower on measures of sexual satisfaction and partner attraction, experienced increasing sexual dissatisfaction during the relationship, and were more likely to be the one to initiate an eventual separation if it occurred. However, the same women were more satisfied with their partner's paternal provision, and thus had longer relationships and were less likely to separate. These effects are congruent with evolutionary predictions based on cyclical preference shifts. Our results demonstrate that widespread use of hormonal contraception may contribute to relationship outcome, with implications for human reproductive behaviour, family cohesion and quality of life.


1,25-dihydroxyvitamin D3 treatment shrinks uterine leiomyoma tumors in the Eker rat model

Abstract: Uterine leiomyomas (fibroids) are the most common benign tumors in women of reproductive age. These tumors are three to four times more prevalent in African American women, who also have a 10 times higher incidence of hypovitaminosis D than white women. Recent studies have demonstrated the antitumor effects of 1,25-dihydroxyvitamin D3 on several cancers, but its effects on uterine leiomyomas are still unknown. To determine the antitumor and therapeutic effects of 1,25-dihydroxyvitamin D3 on uterine leiomyomas, female Eker rats (14-16 mo old) harboring uterine leiomyomas were randomized into control and experimental groups and were given vehicle versus 1,25-dihydroxyvitamin D3 (0.5 μg/kg per day) subcutaneously for 3 wk, respectively. At the end of the experiment, the rats were euthanized, and the leiomyoma tumors were analyzed. Treatment with 1,25-dihydroxyvitamin D3 significantly reduced leiomyoma tumor size in Eker rats. It also reduced leiomyoma size by suppressing cell growth and proliferation-related genes (Pcna, cyclin D1 [Ccnd1], Myc, Cdk1, Cdk2, and Cdk4), antiapoptotic genes (Bcl2 and Bcl2l1 [Bcl-x]), and estrogen and progesterone receptors. Additionally, immunohistochemistry revealed decreased expression of PCNA and MKI67 (a marker of proliferation) and increased expression of caspase 3 in 1,25-dihydroxyvitamin D3-treated Eker rat leiomyomas. Toxicity analyses using serum samples showed similar levels of SGOT, SGPT, calcium, and total bilirubin in 1,25-dihydroxyvitamin D3-treated and vehicle-treated control Eker rats. These results support that 1,25-dihydroxyvitamin D3 is an antitumor agent that may be a potential safe, nonsurgical therapeutic option for the treatment of uterine leiomyomas.


Migraine in women: the role of hormones and their impact on vascular diseases

Abstract: Migraine is a predominantly female disorder. Menarche, menstruation, pregnancy, and menopause, and also the use of hormonal contraceptives and hormone replacement treatment may influence migraine occurrence. Migraine usually starts after menarche, occurs more frequently in the days just before or during menstruation, and ameliorates during pregnancy and menopause. Those variations are mediated by fluctuation of estrogen levels through their influence on cellular excitability or cerebral vasculature. Moreover, administration of exogenous hormones may cause worsening of migraine as may expose migrainous women to an increased risk of vascular disease. In fact, migraine with aura represents a risk factor for stroke, cardiac disease, and vascular mortality. Studies have shown that administration of combined oral contraceptives to migraineurs may further increase the risk for ischemic stroke. Consequently, in women suffering from migraine with aura caution should be deserved when prescribing combined oral contraceptives.


Adverse Perinatal Events Associated with ART

Abstract: Since the advent of ART, much research has focused on the potential adverse for resultant harm. Prematurity, low birth-weight, PIH, congenital malformations, and CP are closely tied to multiple gestation. With the increase in elective single embryo transfer, there will be a reduction in adversity related to multiple birth. It is understood that underlying causes of infertility, including advanced maternal age, PCOS, thyroid disease, and uterine fibroids, predispose to adverse outcomes. However, imprinting abnormalities do not appear to stem from multiple births, and thus the need to consider the association between fertility treatment and methylation disorders remains essential. These, as well as risks of multi-fetal gestation, must be discussed with patients when considering using assisted reproduction.


Perinatal outcomes among children born by assisted reproductive techniques—a hospital-based case control study

Pratima Gupta

University Hospitals Birmingham NHS Foundation Trust


Oral micronized progesterone for vasomotor symptoms--a placebo-controlled  randomized trial in healthy postmenopausal women

Jerilynn C Prior

Vancouver Hospital and Health Sciences Centre

Christine L Hitchcock

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

Abstract:
Objective: The aim of this study was to compare oral micronized progesterone (progesterone) with placebo as therapy for postmenopausal hot flushes and night sweats (vasomotor symptoms [VMS]).

Methods: Healthy volunteer community women 1 to 10 years since final menstruation were recruited for a randomized double-blind placebo-controlled trial of progesterone (300 mg daily at bedtime) between 2003 and 2009 and were screened for clinical, physical, or laboratory evidence of cardiovascular risks (nonsmoking, moderate body mass index [<35 kg/m], normal lipids, electrocardiogram, nondiabetic). Women recorded daily frequency and severity (1-4) of VMS in the Daily Menopause Diary during run-in (4 wk) and intervention (12 wk). Average daily VMS score (day frequency × day severity + night frequency × night severity) during final 28 therapy days was the primary outcome, analyzed by therapy, with run-in score as covariate.

Results: Randomized participants were 133 healthy community women with VMS, ages 44 to 62 years, with a mean (SD) VMS score of 17.0 (10.4) at run-in (VMS frequency 6.8 [3.2] episodes/d). Women were randomized to progesterone (n = 75) or placebo (n = 58); analysis included all with VMS data at run-in and on therapy (n = 68 and 46, respectively). The VMS scores of women taking progesterone were better than placebo (mean adjusted difference, -4.3 (95% CI, -6.6 to -1.9), with mean reductions of 10.0 (95% CI, -12.0 to -8.1) and 4.4 (95% CI, -6.6 to -2.2) in the progesterone and placebo arms, respectively. Discontinuation with adverse events was 9% (progesterone, 8; placebo, 4), with no serious cases.

Conclusions: Oral micronized progesterone is effective for treatment of hot flushes and night sweats in healthy women early in postmenopause.


Body weight and composition in users of levonorgestrel-releasing intrauterine  system

Natalia Dal’Ava

Universidade Estadual de Campinas (UNICAMP)

Natália Dal'Ava

Human Reproduction Unit, Department of Obstetrics and Gynecology, School of Medical Sciences, University of Campinas (UNICAMP), and the National Institute of Hormones and Women's Health, 13084-971,...

Abstract:
Background: There is little information about body weight and body composition (BC) among users of the levonorgestrel-releasing intrauterine system (LNG-IUS). The aim of this study was to evaluate body weight and BC in LNG-IUS users compared to users of the TCu380A intrauterine device (IUD).

Study Design: A prospective study was done with 76 new users of both contraceptive methods. Women were paired by age (±2 years) and body mass index (BMI, kg/m², ±2). Body weight and BC (% lean mass and % fat mass) were evaluated by a trained professional at baseline and at 1 year of contraceptive use. The BC measurements were obtained using Lunar DXA equipment. Weight and BC were evaluated in each woman at baseline and at 12 months and analyzed as the mean change within each woman. Then, the changes in weight and BC for each woman were calculated and then compared between LNG-IUS and TCu380A IUD users (paired data for each woman). The central-to-peripheral fat ratio was calculated by dividing trunk fat by the upper and lower limb fat.

Results: There were no significant differences at time of IUD insertion between LNG-IUS and TCu380A IUD users regarding age (mean±SD) (34.4±7.5 vs. 33.9±8.0 years), BMI (25.3±4.1 vs. 25.9±4.1) and number of pregnancies (1.9±0.2 vs. 1.7±0.2), respectively. Mean body weight gain of 2.9 kg was observed among LNG-IUS users at 12 months (p=.0012), whereas the body weight of TCu380A IUD users only increased by 1.4 kg (p=.067). There was no significant difference in body weight change between the two groups of users at 12 months. The variation in the central-to-peripheral fat ratio was the same between the two groups (-1.6% vs. -0.2%; p=.364). LNG-IUS users showed a 2.5% gain in fat mass (p=.0009) and a 1.4% loss of lean mass, whereas TCu380A IUD users showed a loss of 1.3% of fat mass (p=.159) and gain of 1.0% of lean mass (p=.120). TCu380A IUD users gained more lean mass than LNG-IUS users (p=.0270), although there was no significant difference between the two groups after 12 months of use.

Conclusions: Although an increase in mean fat mass among LNG-IUS users at 12 months of use was observed, it should be noted that an increase of body weight was also observed in both groups after 1 year of insertion of the device. However, a study with a larger number of women and long-term evaluation is necessary to evaluate these body changes.


Eggs, ethics and exploitation? Investigating women’s experiences of an egg sharing scheme

Abstract: AbstractThere is a growing global demand for human eggs for the treatment of sub‐fertile women and for stem cell‐related research. This demand provokes concerns for the women providing the eggs, including their possible exploitation, whether they should be paid, whether they can give properly informed consent and whether their eggs and bodies are becoming commodified. However, few of the debates have benefitted from insights from the women themselves. We address this gap in knowledge by reporting on a study investigating women’s views and experiences of a scheme in which they can volunteer, in their capacity as fertility patients, to ‘share’ their eggs with researchers and receive a reduction in in vitro fertilisation fees. We focus our discussion on the question of exploitation, a concept central to many sociological and ethical interests. In brief, our analysis suggests that while interviewees acknowledge the potential of this scheme to be exploitative, they argue that this is not the case, emphasising their ability to act autonomously in deciding to volunteer. Nonetheless, these freely made decisions do not necessarily take place under circumstances of their choosing. We discuss the implications of this for egg provision in general and for understandings of exploitation.


Persistent lipophilic environmental chemicals and endometriosis: the ENDO Study

Germaine M Buck Louis

Eunice Kennedy Shriver National Institute of Child Health and Human Development

Patrick J Parsons

University at Albany, State University of New York

Abstract:
BACKGROUND: An equivocal literature exists regarding the relation between persistent organochlorine pollutants (POPs) and endometriosis in women, with differences attributed to methodologies.

OBJECTIVES: We assessed the association between POPs and the odds of an endometriosis diagnosis and the consistency of findings by biological medium and study cohort.

METHODS: Using a matched cohort design, we assembled an operative cohort of women 18-44 years of age undergoing laparoscopy or laparotomy at 14 participating clinical centers from 2007 to 2009 and a population-based cohort matched on age and residence within a 50-mile catchment area of the clinical centers. Endometriosis was defined as visualized disease in the operative cohort and as diagnosed by magnetic resonance imaging in the population cohort. Logistic regression analysis was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for each POP in relation to an endometriosis diagnosis, with separate models run for each medium (omental fat in the operative cohort, serum in both cohorts) and cohort. Adjusted models included age, body mass index, breast-feeding conditional on parity, cotinine, and lipids.

RESULTS: Concentrations were higher in omental fat than in serum for all POPs. In the operative cohort, γ-hexachlorocyclohexane (γ-HCH) was the only POP with a significant positive association with endometriosis [per 1-SD increase in log-transformed γ-HCH: adjusted OR (AOR) = 1.27; 95% CI: 1.01, 1.59]; β-HCH was the only significant predictor in the population cohort (per 1-SD increase in log-transformed β-HCH: AOR = 1.72; 95% CI: 1.09, 2.72).

CONCLUSIONS: Using a matched cohort design, we found that cohort-specific and biological-medium-specific POPs were associated with endometriosis, underscoring the importance of methodological considerations when interpreting findings.


Hysteroscopic treatment of the cesarean-induced isthmocele in restoring  infertility

Abstract:
PURPOSE OF Review: To review the treatments of the cesarean-induced isthmocele in restoring infertility, associated techniques, and the risks of complications associated with their use.
Recent Findings: Isthmocele is a reservoir-like pouch defect on the anterior wall of the uterine isthmus located at the site of a previous cesarean delivery scar. The flow of menstrual blood through the cervix may be slowed by the presence of isthmocele, as the blood may accumulate in the niche because of the presence of fibrotic tissue, causing pelvic pain in the suprapubic area. Moreover, persistence of the menstrual blood after menstruation in the cervix may negatively influence the mucus quality and sperm quality, obstruct sperm transport through the cervical canal, interfere with embryo implantation, leading to secondary infertility. The removal of the local inflamed tissue may be performed by laparoscopic, combined laparoscopic-vaginal, or vaginal surgery, and operative hysteroscopy, a minimally invasive approach to improve symptoms and restore fertility.
Summary: Isthmocele occurs after cesarean section, a common method of delivery and one of the most frequent surgical procedures, so that its upward incidence appears likely to continue in the near future. Because of its minimal invasiveness, resectoscopy may be the better choice for treatment, yielding good therapeutic results.

Current Opinion in Obstetrics & Gynecology


Low-dose lisinopril in normotensive men with idiopathic oligospermia and infertility: a 5-year randomized, controlled, crossover pilot study

Abstract: The outcomes of drug treatment for male infertility remain conjectural, with controversial study results. Our pilot study employed a randomized, placebo-controlled, crossover methodology with intention-to-treat analysis. Thirty-three men with idiopathic oligospermia were randomized to start either daily oral lisinopril 2.5 mg (n = 17) or daily oral placebo (n = 16). Lisinopril was found to cause a normalization of seminal parameters in 53.6% of the participants. Although the mean ejaculate volume was unchanged (P ≥ 0.093), the total sperm cell count and the percentage of motile sperm cells increased (P ≤ 0.03 and P < 0.001, respectively), whereas the percentage of sperm cells with abnormal morphology decreased (P ≤ 0.04). The pregnancy rate was 48.5%, and there was no serious adverse drug event. It is concluded, albeit cautiously, that prolonged treatment with 2.5 mg/day of oral lisinopril may be well tolerated in normotensive men with idiopathic oligospermia, may improve sperm quantity and quality, and may enhance fertility in approximately half of those treated.


Effect of depo-medroxyprogesterone acetate on breast cancer risk among women 20  to 44 years of age

Abstract: Depo-medroxyprogesterone acetate (DMPA) is an injectable contraceptive that contains the same progestin as the menopausal hormone therapy regimen found to increase breast cancer risk among postmenopausal women in the Women's Health Initiative clinical trial. However, few studies have evaluated the relationship between DMPA use and breast cancer risk. Here, we conducted a population-based case-control study among 1,028 women ages 20 to 44 years to assess the association between DMPA use and breast cancer risk. Detailed information on DMPA use and other relevant covariates was obtained through structured interviewer-administered in-person questionnaires, and unconditional logistic regression was used to evaluate associations between various aspects of DMPA use and breast cancer risk. We found that recent DMPA use for 12 months or longer was associated with a 2.2-fold [95% confidence interval (CI), 1.2-4.2] increased risk of invasive breast cancer. This risk did not vary appreciably by tumor stage, size, hormone receptor expression, or histologic subtype. Although breast cancer is rare among young women and the elevated risk of breast cancer associated with DMPA appears to dissipate after discontinuation of use, our findings emphasize the importance of identifying the potential risks associated with specific forms of contraceptives given the number of available alternatives.


Medical management of metabolic dysfunction in PCOS

Abstract: Polycystic ovary syndrome (PCOS) is associated with metabolic derangements including insulin resistance, dyslipidemia, systemic inflammation and endothelial dysfunction. There is a growing need to develop pharmacologic interventions to improve metabolic function in women with PCOS. Medications that have been tested in patients with PCOS include metformin, thiazolidinediones, acarbose, naltrexone, orlistat, vitamin D and statins. Metformin decreases hepatic gluconeogenesis and free fatty acid oxidation while increasing peripheral glucose uptake. Early studies in PCOS suggested that metformin indirectly reduces insulin level, dyslipidemia and systemic inflammation; however, recent placebo-controlled trials failed to demonstrate significant metabolic benefit. Thiazolidinediones act primarily by increasing peripheral glucose uptake. Most studies in PCOS have demonstrated that thiazolidinediones reduce insulin resistance; however, effects on dyslipidemia were disappointing. Use of thiazolidinediones is associated with weight gain and major complications. Acarbose reduces digestion of polysaccharides. Studies in PCOS yielded inconsistent effects of acarbose on insulin sensitivity and no significant improvement of dyslipidemia. Naltrexone reduces appetite and modulates insulin release; its use in PCOS may reduce hyperinsulinemia. Orlistat decreases absorption of dietary fats; studies in PCOS suggest beneficial effects on insulin sensitivity. Vitamin D may improve insulin sensitivity but mixed results on lipid profile in PCOS have been reported. Statins are competitive inhibitors of the key enzyme regulating the mevalonate pathway; their effects are related to reduced cholesterol production as well as anti-inflammatory and anti-oxidant properties. In women with PCOS, statins reduce hyperandrogenism, improve lipid profile and reduce systemic inflammation while the effects on insulin sensitivity are variable. Use of statins is contraindicated in pregnancy.


Ultrastructural interaction between spermatozoon and human oviductal cells in  vitro

Pilar Vigil

Pontificia Universidad Católica de Chile

Abstract: The oviduct is an important organ for successful mammalian reproduction. In this work, human oviducts were inseminated and their explants analyzed using scanning electron microscopy in order to study, at a finer ultrastructual level, the interaction between spermatozoon and oviduct in vitro. Results show unequivocally a spermatozoon tightly attached through the acrosomal region of its head to several cilia of the human tubal epithelial cells. This finding proves that spermatozoa do indeed adhere to the endosalpinx, a fact of utmost relevance for the physiology of the reproductive process, since it supports the idea of a spermatozoa reservoir being formed in the oviduct, which is also briefly discussed.


Menstrual bleeding patterns among regularly menstruating women

Jean Wactawski-Wende

Department of Epidemiology and Environmental Health, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY.

Abstract: Menstrual bleeding patterns are considered relevant indicators of reproductive health, though few studies have evaluated patterns among regularly menstruating premenopausal women. The authors evaluated self-reported bleeding patterns, incidence of spotting, and associations with reproductive hormones among 201 women in the BioCycle Study (2005-2007) with 2 consecutive cycles. Bleeding patterns were assessed by using daily questionnaires and pictograms. Marginal structural models were used to evaluate associations between endogenous hormone concentrations and subsequent total reported blood loss and bleeding length by weighted linear mixed-effects models and weighted parametric survival analysis models. Women bled for a median of 5 days (standard deviation: 1.5) during menstruation, with heavier bleeding during the first 3 days. Only 4.8% of women experienced midcycle bleeding. Increased levels of follicle-stimulating hormone (β = 0.20, 95% confidence interval: 0.13, 0.27) and progesterone (β = 0.06, 95% confidence interval: 0.03, 0.09) throughout the cycle were associated with heavier menstrual bleeding, and higher follicle-stimulating hormone levels were associated with longer menses. Bleeding duration and volume were reduced after anovulatory compared with ovulatory cycles (geometric mean blood loss: 29.6 vs. 47.2 mL; P = 0.07). Study findings suggest that detailed characterizations of bleeding patterns may provide more insight than previously thought as noninvasive markers for endocrine status in a given cycle.


Direct Abortion or Legitimate Medical Procedure Double Effect?

Abstract: The distinction between direct abortion and legitimate medical procedures deemed necessary to save the life of the mother but resulting in the death of the unborn child challenge all clinicians and persons of faith. A careful analysis of the principle of double effect and a recent statement by the Committee on Doctrine of the United States Conference of Catholic Bishops offer some clarity to this difficult conflict. Two case examples offer illustration for the analysis.


Significant Risks of Oral Contraceptives (OCPs): Why This Drug Class Should Not  Be Included in a Preventive Care Mandate

Abstract: Pregnancy is not a disease. But more fundamentally, neither is human fertility. They are normal physiologic processes of the sexually mature person. By classifying pregnancy and fertility as disease states, certain entities are able to position contraception as "the cure." Currently, these same organizations want to include oral contraceptive counseling and medications in the new national health-care plan under a preventive care mandate. But it is the physician's role to counsel patients on preventive care measures. We understand that these evidenced-based screenings help to change risky behaviors and catch disease in its earliest stages, thereby reducing patients' overall morbidity and mortality. However, we believe that patients incur substantial health risks when choosing oral contraceptives (OCPs). This paper reviews the major risks of OCPs. The authors presume that the prevailing widespread acceptance and promotion of OCPs indicates general agreement within the medical community that OCPs are good for the patient (or at least not significantly harmful). Therefore, this paper concentrates on the studies which show increased harm and risk to the patient choosing to use OCPs. We have concentrated our efforts on three major areas: increased rates of cardiovascular disease, breast cancer, and human papillomavirus (HPV) or cervical cancer. If fertility and pregnancy are not disease states, and are, in fact, normal conditions associated with healthy individuals, OCPs fail the most important test of preventive medicine: they increase risk of disease instead of decreasing it. Patients should not be misled or confused into believing that what they are taking is "good for them" and is of the same beneficial effect as other preventive measures.


Sexual Behavior and Oral Contraception: A Pilot Study

Abstract:
ABSTRACT

Introduction
Oral contraceptives (OCs) induce mood and libido changes.

Aim
The aim of this study was to evaluate in young, eumenorrheic, healthy women the sexual behavior and the genital vascular effects of an OC containing 30 µg ethinylestradiol (EE) and 3 mg drospirenone (DRSP).

Main Outcome Measures
The main outcome measures are McCoy Female Sexuality Questionnaire (MFSQ), the labia minora thickness and vaginal introitus area, the pulsatility index (PI) of clitoral and labia minora arteries, and hormonal and biochemical assays.

Methods
Twenty-two adult, eumenorrheic, healthy women were administered the two-factor Italian MFSQ. The labia minora thickness was studied by two-dimensional ultrasonographic, and the clitoral and labia minora arteries were evaluated by color Doppler; three-dimensional static volumes of the vulvar area were calculated. Hormonal (estradiol, androstenedione, and testosterone) and biohumoral (sex hormone binding globulin) parameters were assayed. Subjects were studied in baseline conditions and after 3 months of therapy with an OC (Yasmin®, Bayer-Schering Italia, Milan, Italy; −30 µg EE + 3 mg DRSP).

Results
After 3-month treatment, the labia minora thickness and the vaginal introitus area significantly decreased in comparison with the baseline values, whereas the PI of the dorsal clitoral artery and the posterior labial artery significantly increased. The OC use induced a significant decrease of the two-factor Italian MFSQ score, a reduction of the number of intercourse/week, and a reduction of the frequency of orgasm during intercourse. The item 18 (pain during intercourse) worsened after OC.

Conclusions
The treatment with Yasmin® (Bayer-Schering Italia) is associated with increased pain during intercourse, with decreased libido and spontaneous arousability, and with diminished frequency of sexual intercourse and orgasm.


The effects of injectable hormonal contraceptives on HIV seroconversion and on sexually transmitted infections

Abstract:
Objectives: To investigate the association between hormonal contraceptives and risk of HIV-1 seroconversion and prevalence of other sexually transmitted infections.
Design: Prospective cohort.

Methods: The study population was 2,236 HIV-negative women who were screened in a biomedical intervention trial in Durban, South Africa. The association between the use of hormonal contraceptives and risk of HIV-1 seroconversion was modeled using Cox proportional hazards regression analysis. Prevalence of Chlamydia trachomatis and Neisseria gonorrhoeae infections were assessed using logistic regression models.

Results: Hormonal injectables were the most common method of contraceptives (46.47%) followed by condom use (28.04%). Overall, compared with women who reported using condoms or other methods as their preferred form of contraceptive, those who reported using hormonal contraceptives (injectables and oral pills) were less likely to use condoms in their last sexual act. Using hormonal injectables during the study was significantly associated with increased risk for HIV-1 infection [adjusted hazard ratio 1.72, 95% confidence interval (CI) 1.19-2.49, P = 0.005]; hormonal injectables were also significantly associated with higher prevalent of C. trachomatis infections (adjusted odds ratio 2.46, 95% CI 1.52-3.97, P < 0.001).

Conclusion: Hormonal injectables are highly effective and well tolerated family planning methods and have played an important role in reducing unplanned pregnancies and maternal and infant mortality. However, they do not protect against HIV-1 and other sexually transmitted infections. This study reinforces the importance of comprehensive contraceptive counseling to women about the importance of dual protection, such as male condoms and hormonal contraceptives use.


Clinician perceptions of providing natural family planning methods in Title X funded clinics

Abstract:
INTRODUCTION: Natural family planning (NFP) methods are effective for contraception with proper and consistent use. However, only 1% of patients at federally funded Title X family planning clinics select NFP as a contraceptive method. The goal of this study was to understand from clinicians' perspectives the barriers and facilitators to providing NFP methods.

METHODS: Six telephone focus groups were conducted with 29 clinicians from Title X clinics across the United States and Puerto Rico. A hermeneutic method was used to analyze data for related themes.

RESULTS: The overarching theme from the study was that participants had a strong desire to teach their patients how their bodies work and to empower them to learn to control fertility. Four subthemes emerged: patient misinformation and misunderstanding about fertility; provider ideas about ideal types of candidates for NFP; inconsistent patient teaching strategies; and lack of time to teach NFP methods.

DISCUSSION: There is a need for increased NFP training for providers and efficient NFP patient teaching strategies to meet the needs of patients with limited knowledge about fertility.


Relationship between antithyroid antibody and pregnancy outcome following in  vitro fertilization and embryo transfer

Yi-ping Zhong

The First Affiliated Hospital, Sun Yat-sen University

Abstract:
Objective: To investigate the impact of antithyroid antibody on pregnancy outcome following the in vitro fertilization and embryo transfer (IVF-ET).

Methods: A total of 90 patients (156 cycles) positive for antithyroid antibody (ATA+ group) and 676 infertile women (1062 cycles) negative for antithyroid antibody (ATAgroup) undergoing IVF/ICSI from August 2009 to August 2010 were retrospectively analyzed.

Results: There was no significant difference in the days of ovarian stimulation, total gonadotropin dose, serum E2 level of HCG day and number of oocytes retrieved between the two groups. The fertilization rate, implantation rate and pregnancy rate following IVF-ET were significantly lower in women with antithyroid antibody than in control group (64.3% vs 74.6%, 17.8% vs 27.1% and 33.3% vs 46.7%, respectively), but the abortion rate was significantly higher in patients with antithyroid antibody (26.9% vs 11.8%).

Conclusion: Patients with antithyroid antibody showed significantly lower fertilization rate, implantation rate and pregnancy rate and higher risk for abortion following IVF-ET when compared with those without antithyroid antibody. Thus, the presence of antithyroid antibody is detrimental for the pregnancy outcome following IVF-ET.

International Journal of Medical Sciences


DIR Jahrbuch 2011 (Deutsches IVF-Register Annual Report 2011)

Abstract: Annual report (Jahrbuch) of the Deutsches IVF-Register (DIR) for treatment year 2011. 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).


Reducing uterine and ovarian mortality risks of religious sisters

Renee Mirkes

Pontifical John Paul II Institute for Studies on Marriage and Family

Abstract: Consecrated women religious have been shown to be at increased risk for uterine and ovarian cancers. The authors critique a proposal by Kara Britt and Roger Short advocating the distribution of a combined oral contraceptive to women religious as a way of reducing this risk. The authors argue that the proposal is seriously flawed: the data it references attenuate its conclusion, the execution protocol is incomplete, and the proposal fails to address the serious health risks of combined oral contraceptives. As a counterproposal, the authors recommend that women religious be taught to monitor their gynecologic health by charting their menstrual and ovulatory cycles. National Catholic Bioethics Quarterly 12.2 (Summer 2012): 235–239.

The national Catholic bioethics quarterly


Diagnosis and management of catamenial seizures: a review

Abstract: Catamenial epilepsy is defined as a pattern of seizures that changes in severity during particular phases of the menstrual cycle, wherein estrogens are proconvulsant, increasing the neuronal excitability; and progesterone is anticonvulsant, enhancing GABA-mediated inhibition. Thus, changes in serum estradiol/progesterone ratio throughout a normal reproductive cycle bring about an increased or decreased risk of seizure occurrence. To date, there are no specific drug treatments for catamenial epilepsy however, non-hormonal and hormonal therapies have been proposed. The aim of this review is to report preclinical and clinical evidences about the relationship between female reproductive steroids and epileptic seizures, and to describe treatment approaches for catamenial epilepsy.


Circulating unmetabolized folic Acid: relationship to folate status and effect of supplementation

Abstract: There are increasing concerns that exposure to unmetabolized folic acid, which results from folic acid intakes that overwhelm the liver's metabolic capacity, may be associated with adverse effects. In this paper, we examined the folic acid status of women of reproductive age in relation to dietary intake and the effect of folic acid supplementation (1.1 mg or 5 mg). Plasma unmetabolized folic acid was not significantly correlated with folate intake estimated by food frequency questionnaire or biomarkers. The proportion of women with detectable levels of unmetabolized folic acid increased from 65% to 100% after twelve weeks of supplementation (P < 0.05); however, the increase in concentrations did not reach statistical significance and the effect was not sustained. Moreover, there were no significant differences between the two doses. This suggests that there are mechanisms by which the body adapts to high folic acid intakes to limit exposure to unmetabolized folic acid.


The pathophysiology of uterine adenomyosis: an update


Assessing the effect of introducing a new method into family planning programs in India, Peru, and Rwanda

Abstract: Background: Introducing a new method into family planning programs requires careful attention to ensure it meets an actual need and has a positive effect on program goals. The Standard Days Method® is a fertility awareness-based method of family planning that is being introduced into family planning programs in countries around the world. It is different from other methods offered by programs, and may bring new couples into family planning, and increase contraceptive prevalence. The study assesses the effect on contraceptive use and prevalence of Introducing Standard Days Method into existing family planning services in whole regions of India, Peru, and Rwanda. Methods: In collaboration with the Ministry of Health, health providers were given a contraceptive update on all methods, then trained in counseling on Standard Days Method. Efforts were made to promote demand in the context of informed choice. Routine monthly service statistics in control and intervention areas were used to assess the effect of Standard Days Method introduction at the clinic level; baseline and endline household-based surveys were undertaken to obtain results at the community level (n > 3400 women at endline). Results: Demand for the method is evident in countries with different levels of contraceptive prevalence. The method attracts couples new to family planning, and introducing it into services may increase overall contraceptive prevalence. Conclusions: Introducing Standard Days Method into existing family planning has the potential of benefiting men and women in diverse settings and populations. This study illustrates the critical role of evidence in scaling up a health innovation.


Combined Estrogen-Progestogen Contraceptives (IARC Monograph Vol 100A)

International Agency for Research on Cancer


Surgical techniques for the management of male infertility

Abstract: Evaluation and surgical treatment of male infertility has evolved and expanded, now leading to more precise diagnoses and tailored treatments with diminished morbidity and greater success. Surgeries for male infertility are divided into four major categories: (i) diagnostic surgery; (ii) surgery to improve sperm production; (iii) surgery to improve sperm delivery; and (iv) surgery to retrieve sperm for use with in vitro fertilization and intracytoplasmic sperm injection (IVF-ICSI). While today we are more successful than ever in treating male infertility, pregnancy is still not always achieved likely due to factors that remain poorly understood. Clinicians treating infertility should advocate for couple-based therapy, and require that both partners have a thorough evaluation and an informed discussion before undergoing specific surgical therapies.


Medications used to treat nausea and vomiting of pregnancy and the risk of selected birth defects

Sonja A Rasmussen

Center for Surveillance, Epidemiology, and Laboratory Services

Abstract:
BACKGROUND: Nausea and vomiting of pregnancy (NVP) occurs in up to 80% of pregnant women, but its association with birth outcomes is not clear. Several medications are used for the treatment of NVP; however, data are limited on their possible associations with birth defects.

METHODS: Using data from the National Birth Defects Prevention Study (NBDPS)-a multi-site, population-based, case-control study-we examined whether NVP or its treatment was associated with the most common noncardiac defects in the NBDPS (nonsyndromic cleft lip with or without cleft palate [CL/P], cleft palate alone [CP], neural tube defects, and hypospadias) compared with randomly selected nonmalformed live births.

RESULTS: Among the 4524 cases and 5859 controls included in this study, 67.1% reported first-trimester NVP, and 15.4% of them reported using at least one agent for NVP. Nausea and vomiting of pregnancy was not associated with CP or neural tube defects, but modest risk reductions were observed for CL/P (adjusted odds ratio [aOR] = 0.87; 95% confidence interval [CI], 0.77-0.98) and hypospadias (aOR = 0.84; 95% CI, 0.72-0.98). Regarding treatments for NVP in the first trimester, the following adjusted associations were observed with an increased risk: proton pump inhibitors and hypospadias (aOR = 4.36; 95% CI, 1.21-15.81), steroids and hypospadias (aOR = 2.87; 95% CI, 1.03-7.97), and ondansetron and CP (aOR = 2.37; 95% CI, 1.18-4.76), whereas antacids were associated with a reduced risk for CL/P (aOR = 0.58; 95% CI, 0.38-0.89).

CONCLUSIONS: NVP was not observed to be associated with an increased risk of birth defects; however, possible risks related to three treatments (i.e., proton pump inhibitors, steroids and ondansetron), which could be chance findings, warrant further investigation.

Birth defects research. Part A, Clinical and molecular teratology


Pathogenesis and pathophysiology of endometriosis

Richard O Burney

Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Madigan Healthcare System, Tacoma, WA; Department of Clinical Investigation, Madigan Healthcare Syst...


NuvaRing (etonogestrel/ethinyl estradiol vaginal ring) FDA Prescribing Information


Current Medical Research(*) Summer-Fall 2011


IARC Monograph on Carcinogenic Hazards of Hormonal Contraceptives


Endometriosis and infertility: a review of the pathogenesis and treatment of endometriosis-associated infertility

Obstetrics and Gynecology Clinics of North America


Review on autoimmune reactions in female infertility: antibodies to follicle stimulating hormone

Abstract: Female fertility can be affected by diseases or dysfunctions of reproductive tract, neuroendocrine system, and immune system. Reproductive autoimmune failure can be associated with overall activation of immune system or with immune system reactions specifically directed against ovarian antigens. Majority of the antiovarian autoantibodies are directed against β-subunit of follicle stimulating hormone (anti-FSH). This paper summarizes a current clinical classification of female infertility in the context of general activation of autoimmunity and antiovarian autoimmunity by describing serum anti-FSH. The presence of naturally occurring anti-FSH in healthy women will be discussed. In addition, the putative impairment of ovarian folliculogenesis in case of increased production of those antibodies in infertile women will be characterized.


Ethnobiology and Ethnopharmacology of Lepidium meyenii (Maca), a Plant from the Peruvian Highlands

Abstract: Lepidium meyenii (maca) is a Peruvian plant of the Brassicaceae family cultivated for more than 2000 years, which grows exclusively in the central Andes between 4000 and 4500 m altitude. Maca is used as a food supplement and also for its medicinal properties described traditionally. Since the 90s of the XX century, an increasing interest in products from maca has been observed in many parts of the world. In the last decade, exportation of maca from Peru has increased from 1,415,000 USD in 2001 to USD 6,170,000 USD in 2010. Experimental scientific evidence showed that maca has nutritional, energizer, and fertility-enhancer properties, and it acts on sexual dysfunctions, osteoporosis, benign prostatic hyperplasia, memory and learning, and protects skin against ultraviolet radiation. Clinical trials showed efficacy of maca on sexual dysfunctions as well as increasing sperm count and motility. Maca is a plant with great potential as an adaptogen and appears to be promising as a nutraceutical in the prevention of several diseases.

Evidence-based complementary and alternative medicine : eCAM


CARTR 2012 Annual Report - 2011 Results from the Canadian ART Register

Abstract: Canadian ART Register (CARTR) annual report for 2011. In 2011, 31 of 32 Canadian ART clinics participated in CARTR. Voluntary professional society database operated by the Canadian Fertility and Andrology Society.


Veerle Goossens

Abstract: 10. Assisted reproductive technology in Europe, 2008: results generated from European registers by ESHRE. Ferraretti AP(1), Goossens V, de Mouzon J, Bhattacharya S, Castilla JA, Korsak V, Kupka M, Nygren KG, Nyboe Andersen A; European IVF-monitoring (EIM); Consortium for European Society of Human Reproduction and Embryology (ESHRE). (1)ESHRE Central Office, Meerstraat 60, B-1852 Grimbergen, Belgium. annapia.ferraretti@sismer.it BACKGROUND: This 12th European IVF-monitoring (EIM) report presents the results of treatments involving assisted reproductive technology (ART) initiated in Europe during 2008. METHODS: From 36 countries (3 more compared with 2007), 1051 clinics reported 532 260 treatment cycles including: IVF (124 539), ICSI (280 552), frozen embryo replacements (FER, 97 120), egg donation (ED, 13 609), in vitro maturation (IVM, 562), preimplantation genetic diagnosis/screening (PGD/PGS, 2875) and frozen oocyte replacements (FOR, 4080). Overall, this represents a 7.9% increase in the activity since 2007, which is mainly related to an increase in cycles from almost all registers and only partially to the new countries entering EIM (Estonia, Kazakhstan, Moldova and Romania, 5480 cycles in total). European data on intrauterine insemination using husband/partner's (IUI-H) and donor (IUI-D) semen were reported from 27 and 21 countries, respectively. A total of 144 509 IUI-H (+1.5%) and 24 960 IUI-D (-4.3%) cycles were included. RESULTS: In 19 countries where all clinics reported to the ART register, a total of 350 143 ART cycles were performed in a population of 369.8 million, corresponding to 947 cycles per million inhabitants. For IVF, the clinical pregnancy rates per aspiration and per transfer were 28.5 and 32.5%, respectively, and for ICSI the corresponding rates were 28.7 and 31.9%. In FER cycles, the pregnancy rate per thawing was 19.3%. The delivery rate after IUI was 9.1% for IUI-H and 13.8% for IUI-D. In IVF and ICSI cycles, one, two, three and four or more embryos were transferred in 22.4, 53.2, 22.3 and 2.1%, respectively. The proportions of singleton, twin and triplet deliveries after IVF and ICSI (combined) were 78.3, 20.7 and 1.0%, respectively, resulting in a total multiple delivery rate of 21.7%, compared with 22.3% in 2007, 20.8% in 2006 and 21.8% in 2005. In FER cycles, the multiple delivery rate was 13.7% (13.4% twins and 0.3% triplets). In women undergoing IUI, twin and triplet deliveries occurred in 10.6% and 0.7% with IUI-H and in 9.4 and 0.3% with IUI-D, respectively. CONCLUSIONS: In comparison with previous years, there was an increase in the reported number of ART cycles in Europe. For the first time in 5 years, the pregnancy rates failed to show a year-on-year increase. Compared with 2007, the number of transfers of multiple embryos (3+) and a multiple delivery rate showed a marginal decline.


Assisted reproductive technology surveillance--United States, 2009

Dmitry M. Kissin

Division of Reproductive Health, National Center for Chronic Disease Prevention and Health Promotion, CDC

Abstract:
Sunderam S(1), Kissin DM, Flowers L, Anderson JE, Folger SG, Jamieson DJ,
Barfield WD; Centers for Disease Control and Prevention (CDC).

Morbidity and mortality weekly report. Surveillance summaries (Washington, D.C. : 2002)


Abstract: 17. Assisted reproductive technology in Europe, 2007: 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, Andersen AN; European IVF-Monitoring (EIM); Consortium for the European Society on Human Reproduction and Embryology (ESHRE). (1)ESHRE Central Office, Meerstraat 60, B-1852 Grimbergen, Belgium. jacques.demouzon@inserm.fr BACKGROUND: This 11th European IVF-monitoring report presents the results of assisted reproductive technology (ART) treatments initiated in Europe during 2007. METHODS: From 33 countries, 1029 clinics reported 493 184 treatment cycles: IVF (120 761), ICSI (256 642), frozen embryo replacement (91 145), egg donation (15 731), preimplantation genetic diagnosis/preimplantation genetic screening (4638), in vitro maturation (660) and frozen oocytes replacements (3607). Overall, this represents a 7.6% increase since 2006, mostly related to an increase in all registers. IUI using husband/partner's (IUI-H) and donor (IUI-D) semen was reported from 23 countries: 142 609 IUI-H (+6.2%) and 26 088 IUI-D (+7.2%). RESULTS: In 18 countries where all clinics reported, 376 971 ART cycles were performed in a population of 425.6 million (886 cycles per million). The clinical pregnancy rates per aspiration and per transfer were 29.1 and 32.8% for IVF, and 28.6 and 33.0% for ICSI. Delivery rate after IUI-H was 10.2% in women aged < 40 years. In IVF/ICSI cycles, 1, 2, 3 and ≥4 embryos were transferred in 21.4, 53.4, 22.7 and 2.5% of cycles, with no decline in the number of embryos per transfer since 2006. The proportion of multiple deliveries (22.3: 21.3% twin and 1.0% triplet), did not decrease compared with 2006 (20.8%) and 2005 (21.8%). In women < 40 years undergoing IUI-H, twin deliveries occurred in 11.7% and triplets in 0.5%. CONCLUSIONS: In comparison with previous years, the reported number of ART cycles in Europe increased in 2007; pregnancy rates increased marginally, but the earlier decline in the number of embryos transferred and multiple births did not continue.


Comparison of an interstitial cystitis/bladder pain syndrome clinical cohort with  symptomatic community women from the RAND Interstitial Cystitis Epidemiology  study

Abstract:
Purpose: The RAND Interstitial Cystitis Epidemiology survey estimated that 2.7% to 6.5% of United States women have urinary symptoms consistent with a diagnosis of interstitial cystitis/bladder pain syndrome. We describe the demographic and clinical characteristics of the symptomatic community based RAND Interstitial Cystitis Epidemiology cohort, and compare them with those of a clinically based interstitial cystitis/bladder pain syndrome cohort.

Materials and Methods: Subjects included 3,397 community women who met the criteria for the RAND Interstitial Cystitis Epidemiology high sensitivity case definition, and 277 women with an interstitial cystitis/bladder pain syndrome diagnosis recruited from specialist practices across the United States (clinical cohort). Questions focused on demographic information, symptom severity, quality of life indicators, concomitant diagnoses and treatment.

Results: Average symptom duration for both groups was approximately 14 years. Women in the clinical cohort reported worse baseline pain and maximum pain, although the absolute differences were small. Mean Interstitial Cystitis Symptom Index scores were approximately 11 for both groups, but mean Interstitial Cystitis Problem Index scores were 9.9 and 13.2 for the clinical cohort and the RAND Interstitial Cystitis Epidemiology cohort, respectively (p <0.001). The RAND Interstitial Cystitis Epidemiology subjects were more likely to be uninsured.

Conclusions: The RAND Interstitial Cystitis Epidemiology community cohort was remarkably similar to an interstitial cystitis/bladder pain syndrome clinical cohort with respect to demographics, symptoms and quality of life measures. In contrast to other chronic pain conditions for which clinical cohorts typically report worse symptoms and functional status than population based samples, our data suggest that many measures of symptom severity and functional impact are similar, and sometimes worse, in the RAND Interstitial Cystitis Epidemiology cohort. These findings suggest that interstitial cystitis/bladder pain syndrome is significantly burdensome, and likely to be underdiagnosed and undertreated in the United States.


Should risk of bone fragility restrict weight control for other health reasons in postmenopausal women?--A ten year prospective study

Abstract:
Background: The aim of the present study was to investigate the health risks of excess body weight in the light of its protective effects on bone fragility.

Methods: Femoral neck and lumbar spine dual X-ray absorptiometry was performed for 1970 Finnish women with a mean baseline age of 58.8 years (range 53.1-65.7 years) in 1994 and 2004. Women were categorized according to baseline BMI into normal <25 kg/m2, overweight 25-29.9 kg/m(2) and obese ≥30 kg/m(2). Weight change (kg) was categorized into tertiles. Co-morbidities, not allowed to be present at baseline, was based on self-reports. Osteoporosis was defined as femoral neck or spinal (L2-L4) T-score <-2.5 SD at 10-year follow-up or <-2.0 SD+low trauma energy follow-up fracture. Uniand multivariate logistic regression models were used to estimate the 10-year risk of incident health disorders. Adjustment for age, number of diseases, alcohol intake and smoking was used in the multivariate models.

Results: Obesity (Ob) and overweight (Ow) were related with higher 10-year risk of hypertension (OR=2.6 (Ob)/OR=1.7 (Ow), p<0.001), coronary artery disease (OR=1.6, p<0.05/OR=1.2, p=NS), diabetes (OR=11.7/OR=5.3, p<0.001), osteoarthritis (OR=1.4, p<0.05/OR=1.1, p=NS), chronic back pain (OR=1.6, p=0.007/OR=1.2, p=NS) and poor self-rated health (OR=2.4, p<0.05/OR=1.5, p=NS) and lower risk of osteoporosis (OR=0.13/OR=0.28, p<0.001). Weight change of less than +1 kg was associated 1.8 and 2.6 times lower 10-year risk of having hypertension and breast cancer than weight change over 6.2 kg. Among obese women the absolute risk increase of hypertension was 17%, of diabetes 12%, and absolute risk reduction of osteoporosis 14% in comparison to BMI <25 kg/m(2).

Conclusions: Health related risks of high BMI outweigh its protective effects on bone. Weight gain increases the risk hypertension and breast cancer.


Knowledge, acceptability and use of the Billings natural family planning  method

Liza Yurie Teruya Uchimura

Pontifícia Universidade Católica do Paraná

Abstract: This is an observational quantitative and analytical study aimed at verifying the knowledge, acceptability and use of natural family planning (NFP) by patients in a university hospital from July to November, 2008. The data were collected using a structured questionnaire and analyzed with the softwares Excel and Statistica 8.0. Of the 113s women interviewed, 70 (62%) accepted the method and 1 (0.9%) used it routinely. Acceptance was higher among those who wished to become pregnant in the future compared to those who did not wish it. Acceptability was statistically significant (p = 0.0147) among the 28 (80%) non-contraceptive users compared to 42 (53.8%) who used some contraceptive method. Factors such as age, education, number of living children and religion were not statiscally associated with the acceptability of NFP. The Billings ovulation method has an adequate acceptability, but has a low actual use because of the lack of information by health professionals of its real effectiveness and applicability.


Hormonal contraception and the risk of HIV acquisition among women in South  Africa

Janneke H H M van de Wijgert

Department of Clinical Infection, Microbiology and Immunology, Institute of Infection and Global Health, University of Liverpool, Merseyside, United Kingdom.

Abstract:
Objectives: To evaluate the effect of hormonal contraception including combined oral contraceptives (COCs), and the injectable progestins depo-medroxyprogesterone acetate (DMPA) and norethisterone enanthate (Net-En) on the risk of HIV acquisition among women in South Africa. DESIGN/

Methods: We analyzed data from 5567 women aged 16-49 years participating in the Carraguard Phase 3 Efficacy Trial. Participants were interviewed about contraceptive use and sexual behaviors and underwent pelvic examinations and HIV testing quarterly. We used marginal structural Cox regression models to estimate the effect of hormonal contraception exposure on HIV acquisition risk among women overall and among young women (16-24 years) in particular.

Results: Two hundred and seventy participants became HIV-infected (3.7 per 100 woman-years); HIV incidence was 2.8, 4.6, 3.5 and 3.4 per 100 woman-years in the COC, DMPA, Net-En and nonhormonal contraceptive groups, respectively (P = 0.09). The adjusted hazard ratios (AHRs) were 0.84 [95% confidence interval (CI) 0.51-1.39], 1.28 (95% CI 0.92-1.78) and 0.92 (95% CI 0.64-1.32) among COC, DMPA and Net-En users, respectively, compared with the nonhormonal group controlling for covariates. Age modified the effect of hormonal contraception on HIV acquisition risk; among young women, the AHRs were 1.02 (95% CI 0.46-2.28) for COCs, 1.68 (95% CI 0.96-2.94) for DMPA and 1.36 (95% CI0.78-2.35) for Net-En users.

Conclusions: In this study conducted among South African women, hormonal contraception did not significantly increase the risk of HIV acquisition. However, the effect estimate does not rule out a moderate increase in HIV risk associated with DMPA use found in some other recent studies.


10. Cancers attributable to exposure to hormones in the UK in 2010

Abstract: The International Agency for Research on Cancer (IARC) Monographs on the carcinogenic risk to humans concluded that combined oral oestrogen–progestogen contraceptives are carcinogenic to humans (IARC, 2007). This evaluation was made on the basis of increased risks for cancer of the breast (among current and recent users only), cervix and liver (in populations that are at low risk for hepatitis B viral infection). There is also convincing evidence in humans that these agents confer a protective effect against cancer of the endometrium and ovary.


Effect of oral contraceptive therapy on homocysteine and C-reactive protein  levels in women: an observational study

Abstract:
Objective: Increased levels of homocysteine and C-reactive protein (CRP) are considered as independent risk factors for atherosclerosis. As the level of these factors is affected by sex hormones, a population-based assessment of their changes following oral contraceptive therapy is needed to avoid the side effects that might arise of these variations. To this aim, the present study was to investigate the effect of combined oral contraceptive (OCP) on CRP and homocysteine levels among young healthy women.

Methods: We conducted an observational cross-sectional analysis of 90 healthy, non-obese women (mean age 25 years and body-mass index 22 kg/m2). Forty-five healthy women on OCP and 45 healthy controls were studied for CRP and homocysteine levels by enzyme-linked immunosorbent assay (ELISA). Unpaired t test and Chi-square test were used for comparison of variables between oral contraceptive users and non-oral contraceptive users.

Results: The results showed that the homocysteine (13.268±3.475 vs. 7.288±2.621 µmol/L) and CRP (5863.0±1349.5 vs. 1138.3±691.12 ng/ml) levels were significantly higher in women receiving OCP in comparison with the control group (p=0.027 and p<0.001, respectively).

Conclusion: The alteration in homocysteine and CRP levels could be attributed to the OCP suggesting that use of these pills should be reviewed in women with increased risk of atherosclerosis and other cardiovascular risk factors.

Anadolu Kardiyoloji Dergisi : AKD = the Anatolian Journal of Cardiology


Laparoendoscopic single-site surgery in gynecology

Obstetrics and Gynecology Clinics of North America


Monitoring of ovarian activity by measurement of urinary excretion rates of  estrone glucuronide and pregnanediol glucuronide using the Ovarian Monitor, Part  II: reliability of home testing

Pilar Vigil

Pontificia Universidad Católica de Chile

Catherine d'Arcangues

Special Programme of Research, Development, and Research Training in Human Reproduction, Geneva, Switzerland. darcanguesc@who.ch

Abstract:
Background: The UNDP/WHO/World Bank/Special Programme of Research, Development and Research Training in Human Reproduction (Geneva) set up a study to determine whether it is feasible for women to monitor their ovarian activity reliably by home testing. Daily self-monitoring of urinary hormone metabolites for menstrual cycle assessment was evaluated by comparison of results obtained with the Home Ovarian Monitor by untrained users both at home and in study centres.

Methods: Women collected daily data for urinary estrone glucuronide (E1G) and pregnanediol glucuronide (PdG) for two cycles, then the procedure was repeated in the women's local centre (in Chile, Australia or New Zealand) giving a total of 113 duplicate cycles. The tests were performed without the benefit of replicates or quality controls. The home and centre cycles were normalized and compared to identify assay errors, and the resulting home and centre menstrual cycle profiles were averaged.

Results: Reliable mean cycle profiles were obtained with the home and centre excretion rates agreeing to within 36 ± 21 nmol/24 h for E1G and 0.77 ± 0.28 µmol/24 h for baseline PdG values (1-5 µmol/24 h). The cycles had a mean length of 28.1 ± 3.1 days (n = 112; 5th and 95th percentiles: 24 and 35 days, respectively), a mean follicular phase of 14.8 ± 3.1 days (n = 107; 5th and 95th percentiles: 11 and 21 days) and a mean luteal phase length of 13.3 ± 1.5 days (n = 106; 5th and 95th percentiles: 11 and 17 days), calculated from the day of the LH peak.

Conclusions: The study confirmed that the Ovarian Monitor pre-coated assay tubes worked well even in the hands of lay users, without standard curves, quality controls or replicates. Point-of-care monitoring to give reliable fertility data is feasible.


Effect of hysterectomy with ovarian preservation on ovarian function

Abstract:
OBJECTIVE: To prospectively estimate the risk for earlier ovarian failure among women undergoing hysterectomy with ovarian preservation, as compared with women of similar age without hysterectomy.

METHODS: A prospective cohort study was conducted among women aged 30 to 47 years undergoing hysterectomy without bilateral oophorectomy (n=406) and women with intact uteri (n=465). Blood samples and questionnaire data were obtained at baseline and annually for up to 5 years. Hazard ratios (HR) for ovarian failure, defined as follicle-stimulating hormone levels 40 international units/L or higher, were calculated using Cox proportional hazards models.

RESULTS: Ovarian failure occurred among 60 of the women with hysterectomy and 46 of the women in the control group. Women undergoing hysterectomy were at nearly a twofold increased risk for ovarian failure as compared with women with intact uteri (HR 1.92, 95% confidence interval [CI] 1.29-2.86). The proportional hazards model further estimated that 14.8% of women with hysterectomies experienced ovarian failure after 4 years of follow-up compared with 8.0% of the women in the control group. Risk for ovarian failure was greater for women who had a unilateral oophorectomy along with their hysterectomy (HR 2.93, 95% CI 1.57-5.49), but also it was significantly increased for women who retained both ovaries (HR 1.74, 95% CI 1.14-2.65).

CONCLUSION: Increased risk of earlier ovarian failure is a possible consequence of premenopausal hysterectomy. Although it is unresolved whether it is the surgery itself or the underlying condition leading to hysterectomy that is the cause of earlier ovarian failure, physicians and patients should take into account this possible sequela when considering options for treatment of benign conditions of the uterus.

LEVEL OF EVIDENCE: II.


Physical activity, body mass index and bone mineral density-associations in a prospective population-based cohort of women and men: the Canadian Multicentre Osteoporosis Study (CaMos)

Christine L Hitchcock

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

Siri Forsmo

Norwegian University of Science and Technology

Jerilynn C Prior

Vancouver Hospital and Health Sciences Centre

Canadian Multicentre Osteoporosis Study Research Group

Abstract:
Background: Physical activity (PA) is an important modifiable risk factor for both bone mineral density (BMD) and body mass index (BMI). However, BMI is itself strongly predictive of BMD. Our aim was to determine the association between PA and BMD, with consideration of BMI as a potential mediating factor.

Methods: The Canadian Multicentre Osteoporosis Study (CaMos) is a population-based prospective cohort study of Canadian women and men. PA was determined from interviewer-administered questionnaires at baseline and Year 5 and summarized as daily energy expenditure in total metabolic equivalents of the task multiplied by minutes/day (MET*m/d). Height, weight, and total hip and lumbar spine BMD were measured at baseline and Year 5. General linear models assessed relationships between PA and BMD, both cross-sectionally (baseline PA with baseline BMD) and longitudinally (average PA and change in PA with change in BMD). BMI was considered as a mediating factor. Potential confounders included age, center, education, caffeine intake, alcohol exposure, smoking history, history of weight-cycling, age at menarche, past use of oral contraceptives, history of >3 months missed menstruation, menopausal status, and antiresorptive use, as relevant.

Results: The study included 2855 men and 6442 women. PA was inversely associated with BMI at baseline, and an increase in PA between baseline and Year 5 was associated with a decrease in BMI, with 0.41 (95% CI: 0.22, 0.60) kg/m(2) loss per 1000 MET*m/d increase (in men) and 0.40 (95% CI: 0.23, 0.57) kg/m(2) loss per 1000 MET*m/d increase (in women). BMI was strongly associated with BMD, both cross-sectionally and longitudinally. However, increased PA was associated with a small increase in total hip BMD, 0.004 (95% CI: 0.000-0.008) g/cm(2) per 1000 MET*m/d (in men) and 0.003 (95% CI: 0.000-0.007) g/cm(2) per 1000 MET*m/d (in women). Average PA was associated with an increase in lumbar spine BMD in women, but not in men; it was not associated with change in total hip BMD in either sex.

Conclusion: Increased PA is associated with an increase in BMD and a concomitant decrease in BMI. These findings suggest that population-level interventions to increase PA would favorably impact bone and other health outcomes.


Higher risk of venous thrombosis associated with drospirenone-containing oral  contraceptives: a population-based cohort study

Naomi Gronich

Rappaport Family Institute for Research in the Medical Sciences

Idit Lavi

Technion – Israel Institute of Technology

Abstract:
Background: Combined oral contraceptives are a common method of contraception, but they carry a risk of venous and arterial thrombosis. We assessed whether use of drospirenone was associated with an increase in thrombotic risk relative to third-generation combined oral contraceptives.

Methods: Using computerized records of the largest health care provider in Israel, we identified all women aged 12 to 50 years for whom combined oral contraceptives had been dispensed between Jan. 1, 2002, and Dec. 31, 2008. We followed the cohort until 2009. We used Poisson regression models to estimate the crude and adjusted rate ratios for risk factors for venous thrombotic events (specifically deep vein thrombosis and pulmonary embolism) and arterial thromboic events (specifically transient ischemic attack and cerebrovascular accident). We performed multivariable analyses to compare types of contraceptives, with adjustment for the various risk factors.

Results: We identified a total of 1017 (0.24%) venous and arterial thrombotic events among 431,223 use episodes during 819 749 woman-years of follow-up (6.33 venous events and 6.10 arterial events per 10,000 woman-years). In a multivariable model, use of drospirenone carried an increased risk of venous thrombotic events, relative to both third-generation combined oral contraceptives (rate ratio [RR] 1.43, 95% confidence interval [CI] 1.15-1.78) and second-generation combined oral contraceptives (RR 1.65, 95% CI 1.02-2.65). There was no increase in the risk of arterial thrombosis with drospirenone.

Interpretation: Use of drospirenone-containing oral contraceptives was associated with an increased risk of deep vein thrombosis and pulmonary embolism, but not transient ischemic attack or cerebrovascular attack, relative to secondand third-generation combined oral contraceptives.

CMAJ : Canadian Medical Association Journal = Journal De l'Association Medicale  Canadienne


The effects of ergot and non-ergot-derived dopamine agonists in an experimental mouse model of endometriosis

Abstract: Implantation of a retrogradely shed endometrium during menstruation requires an adequate blood supply, which allows the growth of endometriotic lesions. This suggests that the development of endometriosis can be impaired by inhibiting angiogenesis. The growth of endometriotic foci is impaired by commercial oncological antiangiogenic drugs used to block vascular endothelial growth factor (VEGF) signaling. The dopamine agonist cabergoline (Cb2) inhibits the growth of established endometriosis lesions by exerting antiangiogenic effects through VEGFR2 inactivation. However, the use of ergot-derived Cb2 is associated with an increased incidence of cardiac valve regurgitation. To evaluate the potential usage of non-ergot-derived dopamine agonists for the treatment of human endometriosis, we compared the efficacy of quinagolide with that of Cb2 in preventing angiogenesis and vascularization in a heterologous mouse model of endometriosis. Nude mice whose peritoneum had been implanted with eutopic human endometrial fragments were treated with vehicle, 50 μg/kg per day oral Cb2, or 50 or 200 μg/kg per day quinagolide during a 14-day period. At the end of the treatment period, the implants were excised in order to assess lesion size, cell proliferation, degree of vascularization, and angiogenic gene expression. Neoangiogenesis was inhibited and the size of active endometriotic lesions, cellular proliferation index, and angiogenic gene expression were significantly reduced by both dopamine agonists when compared with the placebo. Given that Cb2 and quinagolide were equally effective in inhibiting angiogenesis and reducing lesion size, these experiments provide the rationale for pilot studies to explore the use of non-ergot-derived dopamine agonists for the treatment of endometriosis in humans.


Contraceptive efficacy of emergency contraception with levonorgestrel given before or after ovulation

Abstract:
BACKGROUND: The contraceptive efficacy of emergency contraceptive pills containing levonorgestrel (LNG-EC) has been estimated in most previous studies by judging the day of ovulation from presumptive menstrual cycle data, thus providing poorly reliable estimates.

METHODS: In the present study, the efficacy of LNG-EC was determined in 393 cycles by dating ovulation on the basis of reliable hormonal and ovarian parameters validated by a database constructed in a separate study. In addition, the efficacy was determined separately for cycles in which LNG-EC was given before or after ovulation.

RESULTS: For the 148 women who had sexual intercourse during the fertile days, the overall accumulated probability of pregnancy was 24.7, while altogether 8 pregnancies were observed. Thus, the overall contraceptive efficacy of LNG-EC was 68%. Among the 103 women who took LNG-EC before ovulation (days -5 to -1), 16 pregnancies were expected and no pregnancy occurred (p<.0001). Among the 45 women who took LNG-EC on the day of ovulation (day 0) or thereafter, 8 pregnancies occurred and 8.7 were expected (p=1.00). These findings are incompatible with the inhibition of implantation by LNG-EC in women. The same cases were also analyzed using the presumptive menstrual cycle data, and important discrepancies were detected between the two methods.

CONCLUSION: The efficacy of LNG-EC has been overestimated in studies using presumptive menstrual cycle data. Our results confirm previous similar studies and demonstrate that LNG-EC does not prevent embryo implantation and therefore cannot be labeled as abortifacient.


The Blood-Testis Barrier and Its Implications for Male Contraception


Risk of venous thromboembolism from use of oral contraceptives containing  different progestogens and oestrogen doses: Danish cohort study, 2001-9

Abstract:
Objective: To assess the risk of venous thromboembolism from use of combined oral contraceptives according to progestogen type and oestrogen dose.
Design: National historical registry based cohort study.
Setting: Four registries in Denmark.

Participants: Non-pregnant Danish women aged 15-49 with no history of thrombotic disease and followed from January 2001 to December 2009.

Main Outcome Measures: Relative and absolute risks of first time venous thromboembolism.

Results: Within 8,010,290 women years of observation, 4307 first ever venous thromboembolic events were recorded and 4246 included, among which 2847 (67%) events were confirmed as certain. Compared with non-users of hormonal contraception, the relative risk of confirmed venous thromboembolism in users of oral contraceptives containing 30-40 µg ethinylestradiol with levonorgestrel was 2.9 (95% confidence interval 2.2 to 3.8), with desogestrel was 6.6 (5.6 to 7.8), with gestodene was 6.2 (5.6 to 7.0), and with drospirenone was 6.4 (5.4 to 7.5). With users of oral contraceptives with levonorgestrel as reference and after adjusting for length of use, the rate ratio of confirmed venous thromboembolism for users of oral contraceptives with desogestrel was 2.2 (1.7 to 3.0), with gestodene was 2.1 (1.6 to 2.8), and with drospirenone was 2.1 (1.6 to 2.8). The risk of confirmed venous thromboembolism was not increased with use of progestogen only pills or hormone releasing intrauterine devices. If oral contraceptives with desogestrel, gestodene, or drospirenone are anticipated to increase the risk of venous thromboembolism sixfold and those with levonorgestrel threefold, and the absolute risk of venous thromboembolism in current users of the former group is on average 10 per 10,000 women years, then 2000 women would need to shift from using oral contraceptives with desogestrel, gestodene, or drospirenone to those with levonorgestrel to prevent one event of venous thromboembolism in one year.

Conclusion: After adjustment for length of use, users of oral contraceptives with desogestrel, gestodene, or drospirenone were at least at twice the risk of venous thromboembolism compared with users of oral contraceptives with levonorgestrel.


Use of hormonal contraceptives and risk of HIV-1 transmission: a prospective cohort study

Partners in Prevention HSV/HIV Transmission Study Team

Abstract:
Background: Hormonal contraceptives are used widely but their effects on HIV-1 risk are unclear. We aimed to assess the association between hormonal contraceptive use and risk of HIV-1 acquisition by women and HIV-1 transmission from HIV-1-infected women to their male partners.

Methods: In this prospective study, we followed up 3790 heterosexual HIV-1-serodiscordant couples participating in two longitudinal studies of HIV-1 incidence in seven African countries. Among injectable and oral hormonal contraceptive users and non-users, we compared rates of HIV-1 acquisition by women and HIV-1 transmission from women to men. The primary outcome measure was HIV-1 seroconversion. We used Cox proportional hazards regression and marginal structural modelling to assess the effect of contraceptive use on HIV-1 risk.

Findings: Among 1314 couples in which the HIV-1-seronegative partner was female (median follow-up 18·0 [IQR 12·6-24·2] months), rates of HIV-1 acquisition were 6·61 per 100 person-years in women who used hormonal contraception and 3·78 per 100 person-years in those who did not (adjusted hazard ratio 1·98, 95% CI 1·06-3·68, p=0·03). Among 2476 couples in which the HIV-1-seronegative partner was male (median follow-up 18·7 [IQR 12·8-24·2] months), rates of HIV-1 transmission from women to men were 2·61 per 100 person-years in couples in which women used hormonal contraception and 1·51 per 100 person-years in couples in which women did not use hormonal contraception (adjusted hazard ratio 1·97, 95% CI 1·12-3·45, p=0·02). Marginal structural model analyses generated much the same results to the Cox proportional hazards regression.

Interpretation: Women should be counselled about potentially increased risk of HIV-1 acquisition and transmission with hormonal contraception, especially injectable methods, and about the importance of dual protection with condoms to decrease HIV-1 risk. Non-hormonal or low-dose hormonal contraceptive methods should be considered for women with or at-risk for HIV-1.

Funding: US National Institutes of Health and the Bill & Melinda Gates Foundation.


The costimulatory signal upregulation is associated with Th1 bias at the maternal-fetal interface in human miscarriage

Abstract: PROBLEM To evaluate whether the association of the costimulatory signal regulation with T helper 1/T helper 2 (Th1/Th2) bias at maternal-fetal interface in human pregnancy loss. METHOD OF STUDY The expression of CD80 and CD86 in decidual tissues and CD28 and cytotoxic T-lymphocyte antigen-4 (CTLA-4) in the decidual T cells was compared between normal early pregnancy and miscarriage by qPCR and Western blot. The cytokine production in decidual T cells was performed by flow cytometry. The correlation of costimulatory molecule expression with Th1/Th2 cytokines was analyzed. RESULTS The CD80 mRNA and protein expression showed no significant difference between normal pregnancy and miscarriage. An increase in the expression of CD28 and CD86 was accompanied by a decrease in the expression of CTLA-4 in miscarriage in comparison with the early pregnancy. The higher expression of interleukin (IL)-2 and interferon-γ (IFN-γ), and lower expression of IL-4 and IL-10 in the decidual T cells were present in miscarriage. A correlation analysis showed a significant positive correlation of CD86 and CD28 expression with the Th1 cytokine production (IL-2 and IFN-γ), a significant negative correlation of CTLA-4 expression with the Th1 cytokine production. CONCLUSION The upregualtion of costimulatory signals on T cells might form an abnormal immune microenvironment, a shift to Th1 responses, at maternal-fetal interface, which leads to human miscarriage.

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


Predicting fracture using 2D finite element modelling

Jonathan D Adachi

McMaster University, Hamilton, ON, Canada

Christopher S Kovacs

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

Jerilynn C Prior

Vancouver Hospital and Health Sciences Centre

Abstract: A decrease in bone density at the hip or spine has been shown to increase the risk of fracture. A limitation of the bone mineral density (BMD) measurement is that it provides only a measure of a bone sample's average density when projected onto a 2D surface. Effectively, what determines bone fracture is whether an applied load exceeds ultimate strength, with both bone tissue material properties (can be approximated through bone density), and geometry playing a role. The goal of this project was to use bone geometry and BMD obtained from radiographs and DXA measurements respectively to estimate fracture risk, using a two-dimensional finite element model (FEM) of the sagittal plane of lumbar vertebrae. The Canadian Multicentre Osteoporosis Study (CaMos) data was used for this study. There were 4194 men and women over the age of 50 years, with 786 having fractures. Each subject had BMD testing and radiographs of their lumbar vertebrae. A single two dimensional FEM of the first to fourth lumbar vertebra was automatically generated for each subject. Bone tissue stiffness was assigned based on the BMD of the individual vertebrae, and adjusted for patient age. Axial compression boundary conditions were applied with a force proportional to body mass. The resulting overall strain from the applied force was found. Men and women were analyzed separately. At baseline, the sensitivity of BMD to predict fragility fractures in women and men was 3.77% and 0.86%, while the sensitivity of FEM to predict fragility fractures for women and men was 10.8% and 11.3%. The FEM ROC curve demonstrated better performance compared to BMD. The relative risk of being considered at high fracture risk using FEM at baseline, was a better predictor of 5 year incident fragility fracture risk compared to BMD.


Association between reproductive factors and breast cancer in an urban set up at  central India: a case-control study

KM Lodha

Biochemistry, Gandhi Medical College, Bhopal, India

Abstract:
Background: Epigenetic changes, geography and environmental factors do surpass the genetic factors in the development of breast cancer. This study investigates the association of reproductive factors with the breast cancer in this context.

Objective: To detect the association of reproductive risk factors with breast cancer in an urban set up at central India.

Study Design: Matched paired community-based case-control study.

Materials and Methods: The study was conducted for a period of a year from October 2008 to August 2009 in Bhopal (MP). Demographic data and reproductive risk factor related information were collected using structured questionnaire. Data analysis was done by Epi-info and SPSS 16.

Results: History of using oral contraceptive pills (OR = 3.02, 95% CI: 1.28-7.11), history of not having breastfeeding (OR = 3.62, 95% CI: 1.29-10.16) and family history of breast cancer (OR = 3.98, 95%CI: 1.06-14.826) were associated significantly with the occurrence of breast cancer in multivariate analysis.

Conclusions: The findings of the present study suggests that positive family history of breast cancer and history of using OCP may be the epigenetic factors promoting the occurrence of breast cancer while breastfeeding reduces the possibility of acquiring breast cancer.


Persistent organic pollutants and endometriosis: Importance of biologic media for defining exposure - the endo study

Germaine M Buck Louis

Eunice Kennedy Shriver National Institute of Child Health and Human Development

Patrick J Parsons

University at Albany, State University of New York

Abstract:
Background and
Aims: Persistent organic pollutants (POPs) have been associated with endometriosis, though with equivocal results possibly reflecting choice of biospecimen. We sought to assess this ...


Renaissance of surgical recanalization for proximal fallopian tubal occlusion:  falloposcopic tuboplasty as a promising therapeutic option in tubal infertility

Abstract:
STUDY Objective: To assess the clinical effectiveness of falloposcopic tuboplasty in tubal infertility.
Design: Retrospective cohort study (Canadian Task Force classification II-3).
Setting: Infertility clinic.

Patients: Three hundred forty-five infertile patients (≥2y) with a diagnosis of proximal tubal occlusion, either bilateral or unilateral, between January 2005 and January 2011.

Intervention: Falloposcopic tuboplasty. MEASUREMENTS AND

MAIN Results: Medical records for 345 patients with a diagnosis of proximal tubal occlusion were reviewed. Of the 345 patients, 304 underwent falloposcopic tuboplasty, with successful recanalization achieved in 248 patients (81.6%). Ninety-one of the 304 patients (29.9%) became pregnant. Of these, 18 patients (19.8%) miscarried, and 4 (4.4%) had ectopic pregnancies in the recanalized tube. At 1-, 3-, 6-, and 9-month follow-up, the cumulative probability of conception was 23.1%, 50.6%, 73.6%, and 82.4%, respectively. Related complications included postsurgical infection (0.3%), perforation of the fallopian tube (1.3%), and accidental breakage of the catheter (4.9%) or the falloposcope (1.3%).

Conclusions: Falloposcopic tuboplasty is safe and effective for treatment of tubal infertility. The pregnancy rate after falloposcopic tuboplasty is comparable to that after in vitro fertilization, which suggests that it can be an alternative to in vitro fertilization in women with tubal infertility.

Journal of Minimally Invasive Gynecology


Fluid Retention over the Menstrual Cycle: 1-Year Data from the Prospective  Ovulation Cohort

Christine L Hitchcock

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

Abstract: We report menstrual and mid-cycle patterns of self-reported "fluid retention" in 765 menstrual cycles in 62 healthy women. Self-reported "fluid retention," commonly described as bloating, is one element of the clinical assessment and diagnosis of premenstrual symptoms. These daily diary data were collected as part of an observational prospective one-year study of bone changes in healthy women of differing exercise characteristics. Ovulation was documented by quantitative basal temperature analysis, and serum estradiol and progesterone levels were available from initial and final cycles. Fluid retention scores (on a 0-4 scale) peaked on the first day of menstrual flow (mean ± SE : 0.9 ± 0.1), were lowest during the mid-follicular period, and gradually increased from 0.22 ± 0.05 to 0.50 ± 0.09 over the 11 days surrounding ovulation. Mid-cycle, but not premenstrual, fluid scores tended to be lower in anovulatory cycles (ANOVA P = 0.065), and scores were higher around menstruation than at midcycle (P < 0.0001). Neither estradiol nor progesterone levels were significantly associated with fluid retention scores. The peak day of average fluid retention was the first day of flow. There were no significant differences in women's self-perceived fluid retention between ovulatory and anovulatory cycles.


Hormonal contraception and mental health: results of a population-based study

E Toffol

Finnish Institute for Health and Welfare

Abstract:
Background: The effects of oral contraceptives (OCs) on mental health are not clear, and no study has been focused on the effects of the levonorgestrel-releasing intrauterine system (LNG-IUS) on mental health. The aim of this study was to analyse the association between the use of OCs and the LNG-IUS and psychological well-being and psychopathology.

Methods: The associations between the current use of OCs and the LNG-IUS, and their duration versus mood symptoms [Beck Depression Inventory (BDI)], psychological well-being [(General Health Questionnaire-12 (GHQ-12)] and recent psychiatric diagnoses [(Composite International Diagnostic Interview (CIDI)] were examined among women who participated in the Finnish-population-based Health 2000 study. Analyses were performed on the 30to 54-year-old sample (n = 2310); some of the analyses were extended to include the younger age group (18to 54-year-old sample; n = 3223).

Results: Overall, hormonal contraception was well tolerated with few significant effects on psychological well-being. The length of OC use was inversely associated with some BDI items ('dissatisfaction, irritability, lost interest in people, earlier waking and lost interest in sex'), and directly associated with 'worries about one's health' (BDI) and with a current diagnosis of 'alcohol dependence' (CIDI). The current use of the LNG-IUS was inversely associated with 'earlier waking' (BDI) and with 'impaired concentration' (GHQ), while the length of LNG-IUS use was inversely associated with 'strain' (GHQ).

Conclusions: The influence of hormonal birth control on mental health is modest and mainly favourable. The length of current OC use seems to have some beneficial effects on mood although the longer the duration of use, the greater the association with a diagnosis of alcohol dependence. Knowledge of the use of hormonal contraception might be of value when assessing psychopathology in women. The cross-sectional design, with partly retrospective data collection, precludes any causal conclusions.


Clinical, endocrine and metabolic effects of metformin vs N-acetyl-cysteine in women with polycystic ovary syndrome

Abstract:
OBJECTIVE: To evaluate the clinical, endocrine and metabolic effects of metformin and N-acetyl-cysteine (NAC) in patients with polycystic ovary syndrome (PCOS).

STUDY DESIGN: In this prospective trial, 100 women with PCOS were randomly divided to receive metformin (500 mg p.o. three times daily) or NAC (600 mg p.o. three times daily) for 24 weeks. Hyperandrogenism, lipid profiles, hirsutism scores, menstrual irregularity, insulin sensitivity and tumour necrosis factor-α (TNF-α) levels were measured at baseline and after the treatment period.

RESULTS: Both treatments resulted in a significant decrease in body mass index, hirsutism score, fasting insulin, HOMA index, free testosterone and menstrual irregularity compared with baseline values, and both treatments had equal efficacy. NAC led to a significant decrease in both total cholesterol and low-density lipoprotein levels, whereas metformin only led to a decrease in total cholesterol level. Although TNF-α levels increased following treatment for both groups, the difference from baseline was not significant.

CONCLUSIONS: Metformin and NAC appear to have comparable effects on hyperandrogenism, hyperinsulinaemia and menstrual irregularity in women with PCOS. The effects of metformin and NAC on insulin sensitivity are not associated with TNF-α.

European Journal of Obstetrics, Gynecology, and Reproductive Biology


Sex hormone-binding globulin, oligomenorrhea, polycystic ovary syndrome, and childhood insulin at age 14 years predict metabolic syndrome and class III obesity at age 24 years

Abstract:
OBJECTIVE: We hypothesized that oligomenorrhea (menstrual cyclicity ≥42 days), hyperandrogenism, low levels of sex hormone-binding globulin (SHBG), childhood insulin, and metabolic syndrome (MetS) at age 14 years would predict MetS and class III obesity (body mass index ≥40 kg/m(2)) at age 24 years.

STUDY DESIGN: In this prospective study of schoolgirls, at age 14 years, the girls were categorized as regularly cycling (n = 375), oligomenorrheic (n = 18), or oligomenorrhea plus biochemical hyperandrogenism (polycystic ovary syndrome [PCOS]; n = 12), together designated PCOS.

RESULTS: Significant explanatory variables for MetS at age 24 years included childhood insulin, MetS, and PCOS category (all positive) and SHBG (negative) at age 14 years. Using categorical data, top decile of childhood insulin, MetS at age 14, bottom decile of SHBG, and PCOS category were significant positive predictors for MetS at age 24. SHBG (negative), black race (positive), and oligomenorrhea (positive) were significant explanatory variables for class III obesity at age 24. Using categorical data, black race, MetS at age 14, bottom decile of SHBG, PCOS category, and top decile of childhood insulin were positive explanatory variables for class III obesity at age 24 years.

CONCLUSIONS: Oligomenorrhea, PCOS (a subcohort of oligomenorrhea), hyperandrogenism, low SHBG, MetS, and childhood insulin at age 14 years may represent a critical, reversible pathway for the development of MetS and class III obesity in young adulthood.


The effect of myoinositol supplementation on insulin resistance in patients with gestational diabetes

Rosario D'Anna

Department of Obstetrics and Gynecology, University of Messina, Italy.

Abstract:
AIM: To test the hypothesis that myoinositol supplementation will improve insulin sensitivity as measured by markers of insulin resistance such as homeostasis model assessment of insulin resistance and adiponectin in women with gestational diabetes.

METHODS: The trial was carried out in diet-treated patients with gestational diabetes diagnosed in our department between April 2008 and September 2009. Subjects were randomly assigned to receive either myoinositol supplementation (4 g daily) plus folic acid (400 μg daily)-the study group-or folic acid only (400 μg daily)-the control group. Both groups received the same diet prescription. Homeostasis model assessment of insulin resistance and adiponectin were assayed while fasting at the time of the diagnostic oral glucose tolerance test and after 8 weeks of treatment.

RESULTS: There were 69 evaluable patients, 24 in the study group and 45 in the control group. Fasting glucose and insulin, and consequently homeostasis model assessment of insulin resistance, decreased in both groups (50% in the study group vs. 29% in the control group), but the decline in the study group was significantly greater than that in the control group (P = 0.0001). Adiponectin increased in the myoinositol group while it decreased in the control group (P = 0.009).

CONCLUSION: Myoinositol improves insulin resistance in patients with gestational diabetes.

Diabetic medicine : a journal of the British Diabetic Association


Obstetric hemorrhage

Obstetric hemorrhage

Abstract: An obstetric hemorrhage may occur before or after delivery, but more than 80% of cases occur postpartum. Worldwide, a massive obstetric hemorrhage, resulting from the failure of normal obstetrical, surgical and/or systemic hemostasis, is responsible for 25% of the estimated 358,000 maternal deaths each year. Most women will not have identifiable risk factors. Nonetheless, primary prevention of a postpartum hemorrhage (PPH) begins with an assessment of identifiable risk factors. Women identified as being at high risk of a PPH should be delivered in a center with access to adequately trained staff and an onsite blood bank. A critical feature of a massive hemorrhage in obstetrics is the development of disseminated intravascular coagulation (DIC), which, in contrast to DIC that develops with hemorrhage from surgery or trauma, is frequently an early feature. Data from clinical trials to guide management of transfusion in PPH are lacking. There are likely to be similarities in the management of transfusion in severe PPH to that of major bleeding in other clinical situations, but the pathophysiological processes that contribute to a massive PPH may necessitate different transfusion strategies such as the ratio of red blood cells to plasma components, in particular fibrinogen. Caution should be exercised when considering the appropriate place for recombinant activated factor VII (rFVIIa) in the management of a major PPH. An early hysterectomy is recommended for severe bleeding as a result of placenta accreta or uterine rupture. However, in women with uterine atony who have ongoing bleeding in spite of an adequate transfusion, it may be reasonable to consider a trial of rFVIIa before a hysterectomy.

Journal of thrombosis and haemostasis : JTH