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Menstrual CycleSecular TrendsBMI and Metabolic AssociationsPuberty Timing

Age at menarche in the Canadian population: secular trends and relationship to adulthood BMI

Harris MA et al., 2008J Adolesc Health

Studies from around the world indicate a trend toward younger ages of menarche. The extent of this trend in the Canadian population is unknown, and the relationship to later-life health indicators has not yet been fully elucidated. The objective of this study is to estimate the trend in age at menarche (AAM) in the Canadian population and evaluate the relationship between AAM and adult body mass index (BMI). Our data source was a nationally representative survey (the Canadian Community Health Survey, 2.2), and analyses included 8080 women, aged 15 and older, who self-reported AAM. Height and weight were measured by the interviewers for the calculation of current BMI. We modeled the secular trend in AAM over time, and the relationship between current BMI and AAM. We found a statistically significant decline in AAM in successive age cohorts, indicating a 0.73-year (8.8-month) decrease in AAM between the oldest and youngest age cohorts in the sample. A 1-year increase in AAM was associated with a decrease in mean BMI of approximately 0.5 kg/m(2), after adjustment for covariates. A current age-AAM interaction term was nonsignificant, indicating that the relationship was stable throughout increasing temporal separation from puberty. The observed trend toward earlier menarche could be an indicator of a change in insulin-related metabolism, possibly mediated by behavioral and environmental variables. This study suggests that AAM may be an important clinical and public health indicator of susceptibility to overweight and obesity and attendant morbidity.

Bone HealthPerimenopause/MenopauseDiagnostics

Vertebral fracture status and the World Health Organization risk factors for predicting osteoporotic fracture risk

Peiqi Chen et al., 2008J Bone Miner Res

Vertebral fractures are the most common osteoporotic fracture, and patients with prevalent vertebral fractures have a greater risk of future fractures. However, radiographically determined vertebral fractures are not identified as a distinct risk factor in the World Health Organization (WHO) fracture risk assessment tool. The objective of this study was to evaluate and compare potential risk factors including morphometric spine fracture status and the WHO risk factors for predicting 5-yr fracture risk. We hypothesized that spine fracture status provides prognostic information in addition to consideration of the WHO risk factors alone. A randomly selected, population-based community cohort of 2761 noninstitutionalized men and women > or =50 yr of age living within 50 km of one of nine regional centers was enrolled in the Canadian Multicentre Osteoporosis Study (CaMOS), a prospective and longitudinal cohort study following subjects for 5 yr. Prevalent and incident spine fractures were identified from lateral spine radiographs. Incident nonvertebral fragility fractures were determined by an annual, mailed fracture questionnaire with validation, and nonvertebral fragility fracture was defined by investigators as a fracture with minimal trauma. A model considering the WHO risk factors plus spine fracture status provided greater prognostic information regarding future fracture risk than a model considering the WHO risk factors alone. In univariate analyses, age, BMD, and spine fracture status had the highest gradient of risk. A model considering these three risk factors captured almost all of the predictive information provided by a model considering spine fracture status plus the WHO risk factors and provided greater predictive information than a model considering the WHO risk factors alone. The use of spine fracture status along with age and BMD predicted future fracture risk with greater simplicity and higher prognostic accuracy than consideration of the risk factors included in the WHO tool.

Research

Human Fertilisation and Embryology Act 2008

United Kingdom Parliament, 2008

An Act to amend the Human Fertilisation and Embryology Act 1990 and the Surrogacy Arrangements Act 1985; to make provision about the persons who in certain circumstances are to be treated in law as the parents of a child; and for connected purposes. The 2008 Act updated the regulatory framework established in 1990 to reflect scientific and social developments. explicit provision for human admixed embryos (cytoplasmic hybrids) for research purposes; recognition of same-sex couples as legal parents following licensed treatment; replacement of the previous 'need for a father' welfare clause with 'supportive parenting'; tightened consent and withdrawal-of-consent provisions following the Evans judgment; expanded scope of pre-implantation genetic testing including saviour-sibling testing; statutory regulation of mitochondrial replacement (later activated via 2015 regulations); and enhanced parental order provisions for surrogacy. The 2008 Act maintained the HFEA's role as licensing authority and registry steward but reorganised offence definitions and licence conditions.

Fertility AwarenessMarquette MethodPregnancy Avoidance RatesElectronic Hormonal Monitoring

Efficacy of the Marquette Method of natural family planning

Fehring RJ et al., 2008MCN Am J Matern Child Nurs

To determine the effectiveness of the Marquette Method (MM) of natural family planning (NFP) as a method of avoiding pregnancy. This was a 12-month retrospective evaluation of the MM system of NFP. Two hundred and four women (mean age, 28.6 years) and their male partners (mean age, 30.3 years) who sought to learn a method for avoiding pregnancy with the MM from four clinical sites were taught to track their fertility by self-observation of cervical mucus, by use of an electronic monitor that measures urinary levels of estrone-3-glucuronide and luteinizing hormone, and by use of basal body temperature. All unintended pregnancies were evaluated by professional nurses as to whether they were intended or not. Pregnancy rates over 12 months of use were determined by survival analysis. There were a total of 12 unintended pregnancies, only 1 with correct use. The 12-month "correct use" pregnancy rate was 0.6 (i.e., 99.4% effective) and the "typical use" (total pregnancy rate) was 10.6 (i.e., 89.4% effective) per 100 users. When used correctly, the MM system of NFP is an effective means of avoiding pregnancy. The efficacy of the MM system includes proper preparation of the professional nurse NFP teachers.

Contraception/ComparisonBreast Cancer RiskBRCA Mutation CarriersCancer Risk

Effect of reproductive factors and oral contraceptives on breast cancer risk in BRCA1/2 mutation carriers and noncarriers: results from a population-based study

Lee E et al., 2008Cancer Epidemiol Biomarkers Prev

Multiparity and breast-feeding reduce breast cancer risk, whereas oral contraceptive use may slightly increase breast cancer risk in the general population. However, the effects of these factors in BRCA1 and BRCA2 mutation carriers are less clear. Case patients were 1,469 women from Los Angeles County ages 20 to 49 years with newly diagnosed breast cancer. Control subjects were 444 women without breast cancer, individually matched to a subset of cases on race, age, and neighborhood. BRCA1/2 genes were sequenced in the cases, and odds ratios of breast cancer associated with various reproductive and hormonal factors in BRCA1/2 mutation carriers and noncarriers were estimated using multivariable logistic regression. Ninety-four women had a deleterious BRCA1 or BRCA2 mutation. Number of full-term pregnancies was inversely associated with breast cancer risk regardless of BRCA1/2 mutation status. Longer breast-feeding duration was protective among noncarriers but not among mutation carriers; however, this apparent effect modification was not statistically significant (P = 0.23). Neither oral contraceptive use overall nor the use of low-dose oral contraceptives was associated with an increased risk of breast cancer in any subgroup. Our results suggest that parity protects against breast cancer in BRCA1/2 mutation carriers, whereas breast-feeding does not. Our data suggest no association between oral contraceptive use and breast cancer risk in BRCA1/2 mutation carriers. Further confirmation that currently available low-dose oral contraceptives do not increase breast cancer risk in carriers is important from a public health perspective given the high prevalence of oral contraceptive use in the United States.

InfertilityMedical TreatmentAntioxidant TherapyOxidative Stress Management

N-acetyl cysteine for treatment of recurrent unexplained pregnancy loss

Amin AF et al., 2008Reprod Biomed Online

Pregnancy could be associated with a state of oxidative stress that could initiate and propagate a cascade of changes that may lead to pregnancy wastage. This process of oxidative stress may be suppressed by the antioxidant effect of N-acetyl cysteine (NAC). The current study aimed to evaluate the effect of NAC therapy in patients diagnosed with unexplained recurrent pregnancy loss (RPL). The study was a prospective controlled study performed in the Women's Health Centre, Assiut University, Egypt. A group of 80 patients with history of recurrent unexplained pregnancy loss were treated with NAC 0.6 g + folic acid 500 microg/day and compared with an aged-matched group of 86 patients treated with folic acid 500 microg/day alone. NAC + folic acid compared with folic acid alone caused a significantly increased rate of continuation of a living pregnancy up to and beyond 20 weeks [P < 0.002, relative risk (RR) 2.9, 95% confidence interval (CI) 1.5-5.6]. NAC + folic acid was associated with a significant increase in the take-home baby rate as compared with folic acid alone (P < 0.047, RR 1.98, 95% CI 1.3-4.0). In conclusion, NAC is a well-tolerated drug that could be a potentially effective treatment in patients with unexplained RPL.

Contraception/ComparisonCardiovascular EffectsArterial StiffnessHormonal Contraception Risk

Abstract 3002: Long Term Oral Contraceptive Use is an Independent Risk Factor for Arterial Stiffening

Rietzschel E et al., 2008Circulation

Oral contraceptives (OC) are among the most frequently used drugs in the world with approximately 100 million women worldwide taking OC. In contrast to the active controversy surrounding hormone replacement therapy, little attention has been focused on OC, a drug therapy taken by far more women for far longer time periods. We describe the population effects of current and long-term OC exposure on a prognostically well validated carotid-femoral pulse wave velocity (PWV). The Asklepios study is a representative sample (2524 apparently healthy M/F volunteers, aged 35–55 years, 1301 women) from the Belgian general population, free from overt cardiovascular disease. The subjects were extensively screened (biochemistry, lifestyle, cardiac and vascular echography, arterial tonometry). PWV was measured from flow patterns registered by Doppler echography in the femoral and carotid arteries. Of 1301 women (median age 45.7 y), 27.4% were actively taking OC. In contrast past use of OC is far more prevalent with 81% of women having taken OC for at least 1 year. The median duration of exposition in these women was 13 years. Age-adjusted PWV was higher 6.75 versus 6.55 m/s (difference 0.19 ± 0.09 m/s; p = 0.034). However, current OC users also had higher blood pressures (BP): systolic BP (+4.4 ± 0.9 mmHg; p < 0.001), diastolic BP (+2.3 ± 0.6 mmHg; p < 0.001). After adjustement for BP, the difference in PWV between current OC users and non-users 6.60 versus 6.62 m/s (difference 0.02 ± 0.09 m/s; p = 0.814). In contrast, duration of OC use is a significant determinant of PWV, even after adjustement for age, BP, lipid levels, body size, heart rate, drug therapy (lipid-lowering, antihypertensive), F = 6.1; p = 0.013. Per 10 years of OC exposure PWV increased by 0.1 m/s (0.02– 0.18; p = 0.013). Use of OC is associated with increased vascular stiffness in women. Current use is associated with increased PWV because OC’s increase blood pressure, long-term use (probably through structural remodelling of the vessels) is an independent determinant of PWV, increasing PWV by 0.10 m/s per 10 years exposure.

General OB/GYNInflammatory Bowel DiseasePopulation-Based Studies

Epidemiology of Crohn's disease in Québec, Canada

Lowe AM et al., 2008Inflamm Bowel Dis

Crohn's disease (CD) is an idiopathic inflammatory bowel disease (IBD). We aimed to determine the prevalence and incidence of CD in Québec and characterize the demographic and health-related factors associated with this disease. We identified CD cases in the provincial administrative databases for the years 1993-2002. The CD prevalence and incidence rates were estimated respectively for the periods 1993-2002 and 1998-2000. We validated the identified cases using clinically confirmed IBD cases. Predictor variables of CD were analyzed using the Poisson regression model to explain the variation in CD incidence rates across Québec. In all, 21,172 patients fulfilled the CD case definition for the period. The age and sex standardized average prevalence rate for 1993-2002 was 189.7 cases / 100,000 population and the age and sex standardized incidence rate of CD for the 1998-2000 period was 20.2 cases / 100,000 person-years. The female/male cases ratio among incident cases was 0.74 for the 0-14-year-old group, 1.30 for the 15-64-year-old group, and 1.77 for the cases older than 65 years old. After adjustment, independent predictors incidence of 5 reportable enteric diseases, proportion of individuals of Jewish ethnicity, and proportion of immigrant people. The identified predictors of CD explained 20% of the regional variance in the incidence rate of CD in the Québec population. Other factors such as genetic susceptibility to CD or the effect of an environmental cause should be taken into consideration in the models to explain the residual variance.

Bone HealthPerimenopause/Menopause

Association between change in BMD and fragility fracture in women and men

Claudie Berger et al., 2008J Bone Miner Res

Our objective was to estimate the relationship between longitudinal change in BMD and fragility fractures. We studied 3635 women and 1417 men 50-85 yr of age in the Canadian Multicentre Osteoporosis Study who had at least two BMD measurements (lumbar spine, femoral neck, total hip, and trochanter) within the first 5 yr of the study and fragility fractures (any, main, forearm/wrist, ribs, hip) within the first 7 yr. Multiple logistic regression was used to model the relationship between baseline BMD, BMD change, and fragility fractures. We found that, among nonusers of antiresorptives, independent of baseline BMD, a decrease of 0.01 g/cm(2)/yr in total hip BMD was associated with an increased risk of fragility fracture with ORs of 1.15 (95% CI: 1.01; 1.32) in women and 1.34 (95% CI: 1.02; 1.78) in men. The risk of fragility fractures in subgroups such as fast losers and those with osteopenia was better estimated by models that included BMD change than by models that included baseline BMD but excluded BMD change. Although the association between baseline BMD and fragility fractures was similar in users and nonusers of antiresorptives, the association was stronger in nonusers compared with users. These results show that BMD change in both men and women is an independent risk factor for fragility fractures and also predicts fracture risk in those with osteopenia. The results suggest that BMD change should be included with other variables in a comprehensive fracture prediction model to capture its contribution to osteoporotic fracture risk.

Research

Serious and deadly complications from pregnancy after endometrial ablation: two case reports and review of the literature

Laberge PY, 2008Journal de gynecologie, obstetrique et biologie de la reproduction

Endometrial ablation (EA) has been performed for the past two decades as an alternative to hysterectomy in women with dysfunctional-uterine bleeding unresponsive to medical treatment. However, unlike hysterectomy, this minimally invasive procedure is not an effective means of contraception. Pregnancy following EA has been reported, but the risks and complications related have not been emphasized. This is a report on two such cases and review of the literature, with a closer look at the frequent negative outcome. A 25-year-old woman underwent EA for dysfunctional-uterine bleeding unresponsive to medical treatment. She had no previous surgery, specifically she had no past myomectomy or caesarean section. She declined concomitant tubal ligation. She became pregnant five years later in early spring 2007 and sustained a large uterine rupture at 24 weeks and died in June 2007 secondary to massive internal bleeding at age 29. A 34-year-old woman with previous hysteroscopic EA became pregnant less than one year after surgery. At that time, she had refused concomitant tubal sterilization since her husband had a vasectomy. Unfortunately, the relationship ended soon after surgery and she had unprotected sexual intercourse with a new partner. Pregnancy termination was complicated by placenta increta, which required immediate abdominal hysterectomy. Pregnancy after EA is not a rare occurrence, regardless of which technique is used. Whether women choose to go on or terminate their pregnancy, this clinical situation can be associated with serious complications and even maternal death. Counselling about contraceptive options at the time of EA is paramount.

Research

Japanese-style acupuncture for endometriosis-related pelvic pain in adolescents and young women: results of a randomized sham-controlled trial

Wayne PM et al., 2008Journal of pediatric and adolescent gynecology

To assess feasibility, and collect preliminary data for a subsequent randomized, sham-controlled trial to evaluate Japanese-style acupuncture for reducing chronic pelvic pain and improving health-related quality of life (HRQOL) in adolescents with endometriosis. Randomized, sham-controlled trial. Tertiary-referral hospital. Eighteen young women (13-22y) with laparoscopically-diagnosed endometriosis-related chronic pelvic pain. A Japanese style of acupuncture and a sham acupuncture control. Sixteen treatments were administered over 8 weeks. Protocol feasibility, recruitment numbers, pain not associated with menses or intercourse, and multiple HRQOL instruments including Endometriosis Health Profile, Pediatric Quality of Life, Perceived Stress, and Activity Limitation. Fourteen participants (out of 18 randomized) completed the study per protocol. Participants in the active acupuncture group (n = 9) experienced an average 4.8 (SD = 2.4) point reduction on a 11 point scale (62%) in pain after 4 weeks, which differed significantly from the control group's (n = 5) average reduction of 1.4 (SD = 2.1) points (P = 0.004). Reduction in pain in the active group persisted through a 6-month assessment; however, after 4 weeks, differences between the active and control group decreased and were not statistically significant. All HRQOL measures indicated greater improvements in the active acupuncture group compared to the control; however, the majority of these trends were not statistically significant. No serious adverse events were reported. Preliminary estimates indicate that Japanese-style acupuncture may be an effective, safe, and well-tolerated adjunct therapy for endometriosis-related pelvic pain in adolescents. A more definitive trial evaluating Japanese-style acupuncture in this population is both feasible and warranted.

Bone HealthPerimenopause/Menopause

The impact of incident fractures on health-related quality of life: 5 years of data from the Canadian Multicentre Osteoporosis Study

A Papaioannou et al., 2008Osteoporos Int

Using prospective data from the Canadian Multicentre Osteoporosis Study (CaMos), we compared health utilities index (HUI) scores after 5 years of follow-up among participants (50 years and older) with and without incident clinical fractures. Incident fractures had a negative impact on HUI scores over time. This study examined change in health-related quality of life (HRQL) in those with and without incident clinical fractures as measured by the HUI. The study cohort was 4,820 women and 1,783 men (50 years and older) from the CaMos. The HUI was administered at baseline and year 5. Participants were sub-divided into incident fracture groups (hip, rib, spine, forearm, pelvis, other) and were compared with those without these fractures. The effects of both time and fracture type on HUI scores were examined in multivariable regression analyses. Men and women with hip fractures, compared to those without, had lower HUI measures that ranged from -0.05 to -0.25. Both women and men with spine fractures had significant deficits on the pain attributes (-0.07 to -0.12). In women, self-care (-0.06), mobility and ambulation (-0.05) were also negatively impacted. Women with rib fractures had deficits similar to women with spine fractures, and these effects persisted over time. In men, rib fractures did not significantly affect HUI scores. Pelvic and forearm fractures did not substantially influence HUI scores. The HUI was a sensitive measure of HRQL change over time. These results will inform economic analyses evaluating osteoporosis therapies.

General OB/GYNTumor Aggressiveness Risk FactorsBreast Cancer RiskReproductive Risk Factors

Early age at first childbirth associated with advanced tumor grade in breast cancer

Veneroso C et al., 2008Cancer Detect Prev

Many studies have investigated risk factors for developing breast cancer, but few have explored whether these risk factors are associated with the aggressiveness of the tumor. This case-case study examined the relationship between risk factors for breast cancer and the histological grade of the tumor at diagnosis, an important indicator of breast cancer aggressiveness. We interviewed 215 breast cancer patients and obtained information on their demographics, reproductive history and hormone use. Grade of tumor was obtained from a review of the patients' pathological reports. The relationships between tumor aggressiveness (classified by tumor grade) and risk factors of interest were analyzed using multi-variable logistic regression. Maximum likelihood estimates of the odds ratio were obtained and 95% confidence intervals (CI) were calculated. In multivariable analyses we found that when comparing women who had their first child before age 20 with those who had their first child age 20 and older, women who had their first child before age 20 had approximately a 3.2 increased odds of having a higher-grade tumor (OR=3.20; 95% CI=1.20, 8.49). Long-term use of oral contraceptives, measured in years of oral contraceptive use, was also positively associated with a higher-grade tumor (OR=1.12; 95% CI=1.03-1.23). In addition we found that younger age at diagnosis was a strong predictor of a higher-grade tumor, with a 4% increased odds of having a higher-grade tumor for each year younger (OR=0.96; 95% CI=0.93-0.995). Early age at first birth, long-term use of oral contraceptives, and younger age at diagnosis were associated with advanced tumor grade.

Contraception/ComparisonBone Health EffectsContraceptive AssociationsSkeletal Outcomes

The effects of depot medroxyprogesterone acetate and intrauterine device use on fracture risk in Danish women

Vestergaard P et al., 2008Contraception

Depot medroxyprogesterone acetate (DMPA) use may be associated with an increased risk of fractures; however, nothing is known about the risk associated with intrauterine contraceptive device (IUD) use. Case-control study. All women with a fracture (n=64,548) in the year 2000 in Denmark served as cases. For each case, three age-matched controls were randomly drawn from the general population (n=193,641). Exposure was present or previous DMPA or IUD use (only IUD coated with hormones, not those coated solely with copper). Adjustments were made for confounders. DMPA use seemed to be associated with an increased risk of fractures [odds ratio (OR)=1.44, 95% confidence interval (CI): 1.01-2.06], while IUD use appeared to be associated with a decreased risk of fractures (OR=0.75, 95% CI: 0.64-0.87). DMPA use may cause an increased risk of fracture. However, the fact that use of DMPA is rare in Danish women and the lack of baseline data including smoking status and BMI does not allow causal inferences to be made. Likewise, the seemingly decreased risk of fractures with IUD use is probably not a pharmacological effect but rather the effect of residual confounding related to nonincluded confounders regarding lifestyle.

NaProTECHNOLOGYClinical OutcomesLive Birth RatesGeneral Practice Setting

Outcomes from treatment of infertility with natural procreative technology in an Irish general practice

Stanford JB et al., 2008J Am Board Fam Med

We evaluated outcomes in couples treated for infertility with natural procreative technology (NaProTechnology [corrected] NPT), a systematic medical approach for optimizing physiologic conditions for conception in vivo, from an Irish general practice. All couples receiving treatment from 2 NPT-trained family physicians between February 1998 and January 2002 were studied. The main outcome was live birth, and secondary outcomes included conceptions and multiple births. Crude proportions and adjusted life-table proportions were calculated per 100 couples. A total of 1239 couples had an initial consult for NPT, of which 1072 had been trying for at least a year to conceive and initiated treatment. The average female age was 35.8 years, the mean duration of attempting to conceive was 5.6 years, 24% had a prior birth, and 33% had previously attempted treatment with assisted reproductive technology (ART). All couples were taught to identify the fertile days of the menstrual cycle with the Creighton Model FertilityCare System, and most received additional medical treatment, including clomiphene (75%). In life-table analysis, the cumulative proportion of first live births for those completing up to 24 months of NPT treatment was 52.8 per 100 couples. The crude proportion was 25.5. Younger couples and couples without previous ART attempts had higher rates of live birth. Among live births, there were 4.6% twin births. NPT provided by trained general practitioners had live birth rates comparable to cohort studies of more invasive treatments, including ART. Further studies are warranted to compare NPT directly to other treatments.

InfertilityDiagnostics

Diagnosis and treatment of unexplained infertility

Quaas A et al., 2008Rev Obstet Gynecol

Over the past decade, significant advances have occurred in the diagnosis and treatment of reproductive disorders. In this review, we discuss the routine testing performed to diagnose unexplained infertility. We also discuss additional testing, such as assessment of ovarian reserve, and the potential role of laparoscopy in the complete workup of unexplained infertility. Finally, we outline the available therapeutic options and discuss the efficacy and the cost-effectiveness of the existing treatment modalities. The optimal treatment strategy needs to be based on individual patient characteristics such as age, treatment efficacy, side-effect profile, and cost considerations.

Contraception/ComparisonFracture RiskYoung WomenCase-Control Study

Fracture risk in very young women using combined oral contraceptives

Vestergaard P et al., 2008Contraception

Little is known on fracture risk in young women using oral contraceptives. Case-control study (64,548 cases, 193,641 controls). Overall, no major association with risk of fracture was present. Only in a few age groups a limited increase (OR 1.1-1.5) was seen in those using low average doses (less than one tablet per day - i.e., intermittent use). Neither 20 nor >or=30 mcg per day of ethinylestradiol was associated with risk of fractures, while changing from 20 to >or=30 mcg per day or vice versa was associated with a limited increase in fracture risk (OR 1.1-1.4) in some age groups. In general, use of oral contraceptives in young women did not seem to be associated with an increased risk of fractures. The isolated increase seen in some strata with low average doses may be linked to factors associated with discontinuation of oral contraceptives rather than pharmacological effects.

Contraception/ComparisonInflammatory Bowel DiseaseMeta-AnalysisAutoimmune Risk

The risk of oral contraceptives in the etiology of inflammatory bowel disease: a meta-analysis

Cornish JA et al., 2008Am J Gastroenterol

Several environmental and genetic factors have been implicated to date in the development of Crohn's disease (CD) and ulcerative colitis (UC). The aim of this study was to provide a quantification of the risk of oral contraceptive pill (OCP) use in the etiology of inflammatory bowel disease. A literature search was performed to identify comparative studies reporting on the association of oral contraceptive use in the etiology of UC and CD between 1983 and 2007. A random-effect meta-analysis was used to compare the incidence of UC or CD between the patients exposed to the OCP and nonexposed patients. The results were adjusted for smoking. A total of 75,815 patients were reported on by 14 studies, with 36,797 exposed to OCP and 39,018 nonexposed women. The pooled relative risk (RR) for CD for women currently taking the OCP was 1.51 (95% confidence interval [CI] 1.17-1.96, P= 0.002), and 1.46 (95% CI 1.26-1.70, P < 0.001), adjusted for smoking. The RR for UC in women currently taking the OCP was 1.53 (95% CI 1.21-1.94, P= 0.001), and 1.28 (95% CI 1.06-1.54, P= 0.011), adjusted for smoking. The RR for CD increased with the length of exposure to OCP. Moreover, although the RR did not reduce once the OCP was stopped, it was no longer significant once the OCP was stopped (CI contains 1), both for CD and for UC. This study provides evidence of an association between the use of oral contraceptive agents and development of IBD, in particular CD. The study also suggests that the risk for patients who stop using the OCP reverts to that of the nonexposed population.

Ethics/PhilosophyIUD UseTreatment EthicsLevonorgestrel IUS

No justification for using IUD to treat menorrhagia

Raviele KM, 2008Linacre Q

This article questions the conclusions drawn by the author of "The Mirena® Levonorgestrel-releasing Intrauterine System and Its Application to A Moral Opinion" (Linacre Quarterly 75 [2008]: 60–70), i.e., that it is justified to use this intrauterine device to treat heavy periods of unknown etiology by the principle of double effect.

Ethics/PhilosophyReproductive MedicineConscience RightsHealthcare Provider Training

Protecting the right of informed conscience in reproductive medicine

Mirkes R, 2008J Med Philos

This essay sets down three directives for conscientiously objecting clinicians-physicians, particularly obstetrician/gynecologists, trained in NaProTechnology by the Pope Paul VI Institute and Creighton University School of Medicine and any medical professionals who share their natural law vision of reproductive health care-to protect their right to well-formed conscientious objection in reproductive medicine. understand the nature of a well-formed conscience and its rightful exercise. fulfill all reasonable American College of Obstetricians and Gynecologists' requirements for conscientious refusal. execute a political strategy to protect health-care conscience rights.

Research

Assisted reproductive technology may increase clinical mutation detection in male offspring

Feng C et al., 2008Fertility and Sterility

To investigate the risks of chromosome mutation after ART for couples with comparable genetic backgrounds. Prospective clinical observational study. In vitro fertilization center at a tertiary-care, university-affiliated teaching hospital.Patient(s)Ninety-seven male children whose fathers have normal spermatogenesis were recruited, including 19 babies conceived through IVF, 18 babies conceived through intracytoplasmic sperm injection (ICSI), and 60 naturally conceived babies, as well as the babies' fathers.Intervention(s)Collection of peripheral and umbilical cord blood samples.Main outcome measure(s)The Yq genetic status of the babies and fathers according to 13 Y-specific markers covering four azoospermia factor (AZF) subregions, the karyotype, and the neonatal examination.Result(s)We found that all children had a normal 46, XY karyotype, but de novo Y-chromosome microdeletions were identified in 1 (5.3%) of 19 IVF offspring and in 3 (16.7%) of 18 ICSI offspring. The incidence of de novo Y-chromosome microdeletion in male children conceived through ICSI or IVF was statistically significantly higher than that in those conceived naturally (10.8% vs. 0). In four babies with microdeletion, one was complicated, with hypospadias.Conclusion(s)Our results, for the first time, indicate that risks of gene mutation may increase in the ART offspring, even though their fathers have normal spermatogenesis and genetic background. Hence, intense attention should be placed on genetic safety in the ART children, and the benefits and risks of adopting ART should be balanced gingerly.

Bone HealthResearch Methodology

Geographic variation of bone mineral density and selected risk factors for prediction of incident fracture among Canadians 50 and older

Lisa Langsetmo et al., 2008Bone

Striking geographic variation in the incidence of osteoporotic fracture has been shown in national and international studies. The contributing risk factors for this variation are not fully understood. To determine the geographic variation of bone mineral density (BMD) values, prevalent low-trauma fracture, prior falls, and vertebral deformity and to determine how this variation is related to the geographic variation of incident low-trauma fracture. We studied incident fracture among 2484 men and 6093 women ages 50 and older from CaMos, a randomly-selected population-based longitudinal cohort recruited from within 50 kilometers of nine cities across Canada. Analyses included up to an eight-year follow-up. Estimates of fracture incidence are all age-standardized and given per 1000 person-years and CI denotes confidence interval. Among men, the lowest incidence of low-trauma fracture was 3.2 (95% CI: 1.1-7.5) in Quebec and the highest was 11.9 (95% CI: 7.1-18.6) in Calgary, compared with an overall incidence of 7.2 (95% CI: 5.8-8.7). Among women, the lowest incidence of low-trauma fracture was 11.5 (95% CI: 8.5-15.1) in Halifax and the highest was 18.5 (95% CI: 14.6-23.3) in Calgary, compared with an overall incidence of 15.3 (95% CI: 14.1-16.7). The regional variation in low-trauma fractures was similar to variation in hip fracture incidence among women (Pearson correlation, r=0.46 to 0.76) but not men (r=-0.06 to 0.05). We noted significant geographic variation in the prevalence of low BMD, as defined by BMD T-score< or =-2.5, however this variation was not directly related to low-trauma fractures or other risk factors. Furthermore, a model including age, BMD, falls, vertebral deformity, and prior clinical fracture was a good predictor of geographic variation of low-trauma fracture incidence in both men (r=0.66) and women (r=0.84). For both men and women, the burden of low-trauma fracture is not related to the prevalence of osteoporosis as defined by BMD, but is related to a more comprehensive assessment of fracture age, BMD, falls, prior fracture, and vertebral deformity.

Bone HealthPerimenopause/Menopause

Effectiveness of antiresorptives for the prevention of nonvertebral low-trauma fractures in a population-based cohort of women

L A Langsetmo et al., 2008Osteoporos Int

Observational studies are needed to quantify real-life effectiveness of antiresorptive therapy in the prevention of clinical fractures. Antiresorptive therapies were associated with an overall 32% reduction in low-trauma nonvertebral fracture risk among women 50 and older. Effectiveness may be lower among older women and those without risk factors. Randomized controlled trials have shown that antiresorptive therapies reduce the risk of fracture in selected populations, but further study is needed to quantify their real-life effectiveness. The study objective was to determine the association between antiresorptive use and low-trauma nonvertebral fracture in women 50 and older. The design was a retrospective nested case-control study (density-based sampling) within the Canadian Multicentre Osteoporosis Study. There were 5,979 eligible women with 453 cases and 1,304 matched controls. The current use of antiresorptives was associated with a decreased risk of fracture with OR = 0.68, 95% CI: 0.52-0.91; where OR is the adjusted odds ratio and CI is the confidence interval. Subgroup analysis yielded OR = 0.61, 95% CI: 0.42-0.89 for ages 50-74; OR = 0.76, 95% CI: 0.50-1.17 for ages 75+; OR = 0.58, 95% CI: 0.40-0.83 for those with a major risk factor; and OR = 0.92; 95% CI: 0.59-1.42 for those without a major risk factor. Major risk factors were prevalent low-trauma fracture, vertebral deformity (grade 2+), and BMD T-score < or = -2.5. Antiresorptive therapy is associated with a clinically important reduction in low-trauma nonvertebral fracture risk among community-dwelling women aged 50 and older. Antiresorptive therapy may be less effective for women 75 and older and women without major risk factors.

DiagnosticsMTHFR MutationsGenetic FactorsProspective Cohort

Influence of methylenetetrahydrofolate reductase gene polymorphisms on homocysteine concentrations after nitrous oxide anesthesia

Nagele P et al., 2008Anesthesiology

Mutations in the methylenetetrahydrofolate reductase (MTHFR) gene (677C>T, 1298A>C) cause elevated plasma homocysteine concentrations and have been linked to fatal outcomes after nitrous oxide anesthesia. This study tested the hypothesis that patients with common MTHFR 677C>T or 1298A>C mutations develop higher plasma homocysteine concentrations after nitrous oxide anesthesia than wild-type patients. In this prospective, observational cohort study with blinded, mendelian randomization, the authors included 140 healthy patients undergoing elective surgery. All patients received 66% nitrous oxide for at least 2 h. The main outcome variable, plasma total homocysteine, and folate, vitamin B12, and holotranscobalamin II were measured before, during, and after surgery. After completion of the study, all patients were tested for their MTHFR 677C>T or 1298A>C genotype. Patients with a homozygous MTHFR 677C>T or 1298A>C mutation (n = 25) developed higher plasma homocysteine concentrations (median [interquartile range], 14.9 [10.0-26.4] microm) than wild-type or heterozygous patients (9.3 [7.5-15.5] microm; n = 115). The change in homocysteine after nitrous oxide anesthesia was tripled in homozygous patients compared with wild-type (5.6 microm [+60%] vs. 1.8 microm [+22%]). Only homozygous patients reached average homocysteine levels considered abnormal (> 15 microm). Plasma 5-methyl-tetrahydrofolate concentrations increased uniformly by 20% after nitrous oxide anesthesia, indicating the inactivation of methionine synthase and subsequent folate trapping. Holotranscobalamin II concentrations remained unchanged, indicating no effect of nitrous oxide on vitamin B12 plasma concentrations. This study shows that patients with a homozygous MTHFR 677C>T or 1298A>C mutation are at a higher risk of developing abnormal plasma homocysteine concentrations after nitrous oxide anesthesia.

Menstrual CycleBody LiteracyReproductive Endocrinology

The menstrual cycle: a biological marker of general health in adolescents

Popat VB et al., 2008Ann N Y Acad Sci

Menstruation is the cyclic, orderly sloughing of the uterine lining on account of the interactions of hormones produced by the hypothalamus, pituitary, and ovaries. There is a tendency among parents and clinicians to view oligo-amenorrhea as a normal variant in the teen years. In fact, the 95th percentile for the time interval between cycles is 90 days. Thus, it is abnormal for an adolescent to be amenorrheic for greater than 3 months, even in the early gynecologic years. Identification of abnormal menstrual patterns throughout adolescence may permit early identification of potential health concerns for adulthood. Few problems in gynecologic endocrinology are as complex or challenging to the clinician as amenorrhea. However, thorough evaluation of menstrual cycle disorders in adolescence provides a window of opportunity for early diagnosis and treatment of conditions affecting the hypothalamic-pituitary-ovarian (HPO) axis. Here we discuss a systematic approach to the evaluation and treatment of amenorrhea in adolescents who do not have androgen excess. There is strong evidence that estrogen deficiency is a risk factor for later development of osteoporosis and hip fracture. Delay in the evaluation and treatment of disordered menses in some cases may contribute to reduced bone density. Both patients and clinicians need to view the ovary as an important endocrine organ that helps maintain health, especially bone health.

InfertilityReproductive EndocrinologyMenstrual Cycle

Effect of luteinized unruptured follicle cycles on clinical outcomes of frozen thawed embryo transfer in Chinese women

Wang L et al., 2008J Assist Reprod Genet

To determine the effect of luteinized unruptured follicle (LUF) cycles on frozen thawed embryo transfer (FET). A retrospective analysis comparing the clinical outcomes after FET among 144 cases of luteinized unruptured follicle (LUF) cycles and 866 cases of ovulation cycles. Reproductive medical center, Beijing China. Chinese infertile women who underwent FET. None. Clinical pregnancy rate (PR), implantation rate. The implantation rate, clinical pregnancy rate, on-going pregnancy rate and live birth rate in LUF group were 12.76% (49/384), 27.78% (40/144), 24.31% (35/144) and 19.44% (28/144), respectively, and in ovulation group, 14.74% (332/2251), 31.29% (271/866), 28.29% (245/866) and 22.23% (193/866), respectively (p > 0.05). LUF does not affect the clinical outcomes of FET. Patients of LUF should be included in FET treatment.

SurgeryPreoperative AssessmentAdhesion DetectionComplication Prevention

Preoperative periumbilical ultrasound-guided saline infusion (PUGSI) as a tool in predicting obliterating subumbilical adhesions in laparoscopy

Cho J et al., 2008Fertil Steril

To report the novel technique of periumbilical ultrasound-guided saline infusion (PUGSI). Prospective study of two noninvasive diagnostic tests to detect obliterating subumbilical adhesions. Tertiary care center. PATIENT(S): One hundred fifty patients were included in the study. Patients without risk factors for adhesions were used as a control group (n = 38), whereas the study group had risk factors for intra-abdominal adhesions (n = 112). INTERVENTION(S): Preoperative examination with the visceral slide and the PUGSI. MAIN OUTCOME MEASURE(S): The presence of obliterating subumbilical adhesions in the high-risk patient and the ability of the PUGSI to detect them preoperatively. RESULT(S): There were no obliterating umbilical adhesions in the control group. The prevalence of obliterating umbilical adhesions in the risk group was 3.6%. The visceral slide test had an accuracy of 96.4%, a sensitivity of 50%, and a specificity of 98.1%, with a negative predictive value of 98.1% and a positive predictive value of 50%. The PUGSI test was able to detect all cases of obliterating subumbilical adhesions, demonstrating sensitivity and specificity of 100%. CONCLUSION(S): The PUGSI test has excellent negative and positive predictive values and is useful in determining patients who have obliterating subumbilical adhesions. Use of both tests preoperatively appears to be helpful in identifying patients at risk for visceral injury during laparoscopic surgery.

Bone HealthPerimenopause/Menopause Open Access

Change in bone mineral density as a function of age in women and men and association with the use of antiresorptive agents

Berger C et al., 2008CMAJ

Measurement of bone mineral density is the most common method of diagnosing and assessing osteoporosis. We sought to estimate the average rate of change in bone mineral density as a function of age among Canadians aged 25-85, stratified by sex and use of antiresorptive agents. We examined a longitudinal cohort of 9423 participants. We measured the bone mineral density in the lumbar spine, total hip and femoral neck at baseline in 1995-1997, and at 3-year (participants aged 40-60 years only) and 5-year follow-up visits. We used the measurements to compute individual rates of change. Bone loss in all 3 skeletal sites began among women at age 40-44. Bone loss was particularly rapid in the total hip and was greatest among women aged 50-54 who were transitioning from premenopause to postmenopause, with a change from baseline of -6.8% (95% confidence interval [CI] -7.5% to -4.9%) over 5 years. The rate of decline, particularly in the total hip, increased again among women older than 70 years. Bone loss in all 3 skeletal sites began at an earlier age (25-39) among men than among women. The rate of decline of bone density in the total hip was nearly constant among men 35 and older and then increased among men older than 65. Use of antiresorptive agents was associated with attenuated bone loss in both sexes among participants aged 50-79. The period of accelerated loss of bone mineral density in the hip bones occurring among women and men older than 65 may be an important contributor to the increased incidence of hip fracture among patients in that age group. The extent of bone loss that we observed in both sexes indicates that, in the absence of additional risk factors or therapy, repeat testing of bone mineral density to diagnose osteoporosis could be delayed to every 5 years.

General OB/GYNInterstitial CystitisUTI DetectionCase-Control Study

Urinary tract infection and inflammation at onset of interstitial cystitis/painful bladder syndrome

Warren JW et al., 2008Urology

Interstitial cystitis/painful bladder syndrome (IC/PBS) is a chronic disease primarily in women that is of low incidence and unknown etiology and manifests as bladder pain and urinary symptoms. Acute urinary tract infection (UTI) is of high incidence in women, presents as dysuria and urinary symptoms, and is caused by uropathogenic bacteria. We hypothesized that UTI is present at the onset of IC/PBS in some women. For a case-control study seeking risk factors for IC/PBS, women with IC/PBS symptoms of 12 months or less were recruited and evaluated by interview and medical record review. The date of symptom onset was identified by a six-step process. Three evidence-based methods using culture, urinalysis, and symptoms were used separately and in combination to diagnose UTI at IC/PBS onset. Of 1177 screened women, 314 with recent-onset IC/PBS, including numerous confirming characteristics, were enrolled in the study; 98% of the requested medical records were obtained and reviewed. Evidence of a UTI at the onset of IC/PBS was found in 18% to 36% of women. Common UTI features not used in its diagnosis (short interval to medical care, hematuria, antibiotic treatment, and improvement after antibiotics) were significantly more common in those with onset UTI than in those without. These retrospective data suggest that a proportion, probably a minority, of women at IC/PBS onset had evidence of UTI or inflammation. Our results indicate that UTI is present at the onset of IC/PBS in some women and might reveal clues to IC/PBS pathogenesis.

AndrologyAcrosome ReactionEstradiol Effects on SpermHormonal Interactions

Physiological action of oestradiol on the acrosome reaction in human spermatozoa

Vigil P et al., 2008Andrologia

The acrosome is a secretory vesicle located in the sperm head. The acrosome reaction consists in the fusion of the sperm plasma membrane with the external acrosomal membrane. It has been observed that this reaction does not take place in spermatozoa incubated in cervical mucus, hydrogel that contains high concentrations of oestradiol in the peri-ovulatory period. The objective of the present study was to analyse the influence of oestradiol on the acrosome reaction in human spermatozoa to evaluate the possible inhibitory effect of this hormone. Spermatozoa were incubated in progesterone (10.1 nmol l(-1)); oestradiol plus progesterone (oestradiol at 840 pmol l(-1) and progesterone at 10.1 nmol l(-1)), oestradiol (840 pmol l(-1)) and control (without steroidal hormones) for 30 min, 60 min, 240 min and 24 h. The acrosome reaction was evaluated by stain with Hoechst 33258 and fluorescein isothiocyanate-conjugated Pisum sativum agglutinin lectin. Progesterone-incubated spermatozoa showed the highest percentage of acrosome reaction (P < 0.05). Spermatozoa incubated with oestradiol and oestradiol plus progesterone showed the lowest percentage of acrosome reaction. The present study demonstrates the inhibitory role of oestradiol on the acrosome reaction, stimulated by progesterone in human spermatozoa under physiological conditions.

Contraception/ComparisonGeneral OB/GYN Open Access

Cervical dysplasia and cancer and the use of hormonal contraceptives in Jamaican women

McFarlane-Anderson N et al., 2008BMC Womens Health

This study was conducted to determine whether use of hormonal contraceptives is associated with cervical dysplasia and cancer in a population where there is widespread use of hormonal contraception and the rates of cervical cancer remain high at 27.5/100,000. A case-control study was conducted among women visiting the colposcopy and gynaelogical clinics at a tertiary referral hospital. Two hundred and thirty six cases CIN I (72), II (59), III (54), cancer (51) and 102 controls, consented and were interviewed on use of contraceptives using a structured questionnaire. Logistic regression was used to determine odds ratios (ORs) and 95% confidence intervals (CIs) associated with use of hormonal contraception in cases and controls and in low and high risk cases. Recruitment was carried out from 2001-2002. Contraceptives oral contraceptives - 35%, injections (depot medroxy progesterone acetate (Depo-provera) - 10%, Intrauterine devices - 2%, combinations of these and tubal ligation - 30%. 23% reported use of 'other' methods, barrier contraceptives or no form of contraception. Barrier contraceptive use was not significantly different between cases and controls. Current and/or past exposure to hormonal contraceptives (HC) by use of the pill or injection, alone or in combination with other methods was significantly higher in the cases. In multivariate analysis with age and number of sexual partners as co-variates, use of hormonal contraception was associated both with disease, [OR, 1.92 (CI 1.11, 3.34; p = 0.02] and severity of the disease [OR, 2.22 (CI 1.05, 4.66) p = 0.036]. When parity and alcohol consumption were added to the model, hormonal contraception was no longer significant. The significant association with high risk disease was retained when the model was controlled for age and number of sexual partners. Depo-provera use (with age and number of sexual partners as covariates) was also associated with disease [OR, 2.43 (CI 1.39, 4.57), p = 0.006] and severity of disease [OR 2.51 (1.11, 5.64) p = 0.027]. With parity and alcohol added to this model, depo-provera use retained significance. Exposure to HC > 4 years conferred more risk for disease and severity of disease. Hormonal contraception did confer some risk of dysplasia and women using HC should therefore be encouraged to do regular Pap smear screening.

Research

Outcomes following prolonged preterm premature rupture of the membranes

Everest NJ et al., 2008Archives of disease in childhood. Fetal and neonatal edition

Rupture of the membranes in the second trimester is reported to be associated with high rates of pregnancy loss, neonatal mortality and morbidity. This article describes the outcomes of liveborn infants delivered following a prolonged period of membrane rupture occurring before 24 weeks' gestation. Over a 5-year period, consecutive pregnancies complicated by spontaneous rupture of the membranes before 24 weeks' gestation were identified. Evaluation of short-term outcomes before discharge of liveborn infants delivered, in a tertiary referral centre, following prolonged rupture of membranes of duration greater than 2 weeks. Of 98 pregnancies identified with rupture of the membranes before 24 weeks' gestation, 40 (41%) women progressed to deliver a liveborn infant following a latent period of at least 14 days. Although most liveborn infants required neonatal intensive care including mechanical ventilation (n = 38; 78%), the survival rate to hospital discharge was 70% (n = 28). Airleak occurred in 7 (25%) survivors and 8 (67%) deaths. Among the survivors, 12 (43%) required supplemental oxygen at 36 weeks' postmenstrual age and no infant had grade 3 or 4 intraventricular haemorrhage. One infant had a postmortem diagnosis of pulmonary hypoplasia and nine others had clinical features consistent with this diagnosis. Low liquor volume was not uniformly associated with a poor outcome. With full contemporary neonatal intensive care, the outcome for liveborn infants in the present cohort delivered following membrane rupture occurring before 24 weeks' gestation, of at least 14 days duration, was better than previously reported.

Reproductive EndocrinologyEpilepsy and Reproductive HormonesInadequate Luteal PhaseCatamenial Epilepsy

Reproductive hormonal changes and catamenial pattern in adolescent females with epilepsy

El-Khayat HA et al., 2008Epilepsia

We aimed to evaluate the effect of epilepsy on the reproductive hormones levels among female patients, and to investigate the frequency of catamenial pattern of seizures. A total of 42 female patients with epilepsy and 21 healthy females (control group) were included. Subjects were at least 2 years postmenarche with regular cycles. Symptoms of premenstrual syndrome (PMS) were assessed using calendar of premenstrual experience scoring. Patients were evaluated for catamenial pattern of seizures. Levels of FSH, LH, estradiol (E), and progesterone (P) were assessed for all subjects in the three phases of the cycles. Pelvi-abdominal ultrasound was performed near time of ovulation, to follow up size of mature follicle. Symptoms of PMS were not different in patients and controls, or in patients with and those without catamenial tendency. In both perimenstrual (M) and midluteal phases, FSH and P levels were lower and E/P ratio higher in patients group. There was a catamenial pattern of seizures in 31% of patients (53.8% M C(1); 46.15% inadequate luteal phase C(3)pattern). Patients with C(3)pattern showed lower P levels in the midluteal phase compared to patients with noncatamenial pattern, to those with C(1)pattern or to controls. Patients with C(1)pattern had lower P levels than controls in the M phase. There was evident disruption in the reproductive hormones in female patients with epilepsy with lower FSH and P levels and higher E/P ratio. A total of 31% of patients showed catamenial pattern of seizures (C(1)and C(3)patterns) that was significantly related to P withdrawal.

InfertilityAndrologyEthics/Philosophy

Intracytoplasmic sperm injection (ICSI)--what are the risks?

Alukal JP et al., 2008Urol Clin North Am

In vitro fertilization used in combination with intracytoplasmic sperm injection allows otherwise sterile couples to become parents. Despite recent studies on the safety of these technologies, there is still only an incomplete picture of the risks associated with the usage of these assisted reproductive techniques to offspring. The risk of multiple gestations continues to be of major concern because of its association with low birth weight, preterm delivery, and increased perinatal mortality. This article outlines the risks associated with in vitro fertilization/intracytoplasmic sperm injection as a well-defined treatment for couples with severe male factor infertility.

Reproductive EndocrinologyInflammatory MechanismsLuteinized Unruptured FollicleG-CSF in Reproduction

Granulocyte colony-stimulating factor (G-CSF) in the mechanism of human ovulation and its clinical usefulness

Makinoda S et al., 2008Curr Med Chem

In 1980, Espey proposed a famous hypothesis that mammalian ovulation is comparable to an inflammatory reaction and many researches have proved the validity of his hypothesis in the last three decades. For example, interleukin (IL)-1beta, IL-6, tumor necrosis factor (TNF)- alpha, granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage colony-stimulating factor (M-CSF) and other inflammatory cytokines presence was proven in the preovulatory follicle. Since granulocyte is the major leukocyte and it plays a very important role during inflammation, the importance of granulocyte and its related cytokine, granulocyte colony-stimulating factor (G-CSF) in the mechanism of human ovulation is easily predictable. G-CSF is one of the hemopoietic cytokines and it has strong positive effects on granulocytes. G-CSF increases the number of granulocytes and it improves the function of granulocytes. In this review, the participation of leukocytes in the ovulation mechanism is demonstrated first. Second, the participation of G-CSF is shown in comparison with the above mentioned cytokines. Finally, since G-CSF has been used for more than 20 years as a medicine without severe side effects in the field of oncology, the clinical application of G-CSF for the treatment of an ovulation disorder, luteinized unruptured follicle (LUF), will be discussed.

Reproductive EndocrinologyDHEA TreatmentAndrogen SupplementationHormonal Interventions

Premature ovarian failure and dehydroepiandrosterone

Mamas L et al., 2008Fertil Steril

In the light of similarities between premenstrual syndrome and toxaemia, and the fact that treatment of the former with progesterone not only relieved the symptoms (Greene and Dalton, 1953) but also prevented the development of edema, hypertension, and albumin

Research

Chronic endometritis: correlation among hysteroscopic, histologic, and bacteriologic findings in a prospective trial with 2190 consecutive office hysteroscopies

Cicinelli E et al., 2008Fertility and sterility

To evaluate the type and etiopathogenic role of infectious agents detected in endometrial cultures obtained from women with chronic endometritis (CE). Prospective controlled study. University hospital. PATIENT(S): 2190 women undergoing hysteroscopy for different indications. INTERVENTION(S): Vaginal and endometrial samples were collected from 438 women with a CE diagnosis at hysteroscopy and 100 women with no signs of CE (controls). MAIN OUTCOME MEASURE(S): Histology and cultures for common bacteria, Neisseria gonorrhoeae and Mycoplasma, and molecular biology testing for Chlamydia were performed. RESULT(S): We compared results of vaginal and intrauterine cultures obtained from women with and without CE. Histologic results were positive in 388 of these cases (88.6%), and at least one microorganism was found in 320 endometrial samples (73.1%). In the control group, histologic results and endometrial culture were positive in only 6% and 5% of cases, respectively. The most frequent infectious agents detected at the endometrial level were common bacteria (58% of cases). Ureaplasma urealyticum was detected in 10% and Chlamydia in only 2.7% of positive endometrial cultures. In only 143 (32.6%) cases were the same infectious agent isolated in endometrial and vaginal cultures. CONCLUSION(S): More than 70% of CE cases resulted from nongonococcal, nonchlamydial infections. Common bacteria and Mycoplasma were the most frequent etiologic agents. Vaginal cultures have low concordance with endometrial cultures.

Research

Consensus on infertility treatment related to polycystic ovary syndrome

Thessaloniki ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group, 2008Fertility and Sterility

The treatment of infertile women with polycystic ovary syndrome (PCOS) is surrounded by many controversies. On the basis of the currently available evidence, a group of experts reached a consensus regarding the therapeutic challenges raised in these women. Before any intervention is initiated, preconceptional counseling should be provided emphasizing the importance of lifestyle, especially weight reduction and exercise in overweight women, smoking, and alcohol consumption. The recommended first-line treatment for ovulation induction remains the anti-estrogen clomiphene citrate (CC). Recommended second-line intervention, should CC fail to result in pregnancy, is either exogenous gonadotropins or laparoscopic ovarian surgery (LOS). The use of exogenous gonadotropins is associated with increased chances for multiple pregnancy, and, therefore, intense monitoring of ovarian response is required. Laparoscopic ovarian surgery alone is usually effective in less than 50% of women, and additional ovulation induction medication is required under those circumstances. Overall, ovulation induction (representing the CC-gonadotropin paradigm) is reported to be highly effective with a cumulative singleton live-birth rate of 72%. Recommended third-line treatment is in vitro fertilization (IVF). More patient-tailored approaches should be developed for ovulation induction based on initial screening characteristics of women with PCOS. Such approaches may result in deviation from the above mentioned first-line, second-line, or third-line ovulation strategies in well-defined subsets of patients. Metformin use in PCOS should be restricted to women with glucose intolerance. Based on recent data available in the literature, the routine use of this drug in ovulation induction is not recommended. Insufficient evidence is currently available to recommend the clinical use of aromatase inhibitors for routine ovulation induction. Even singleton pregnancies in PCOS are associated with increased health risk for both the mother and the fetus.

Fertility AwarenessProgram ImplementationTypical Use EffectivenessCommunity-Based Providers

Being strategic about contraceptive introduction: the experience of the Standard Days Method

Gribble JN et al., 2008Contraception

Many national and institutional family planning policies explicitly include fertility awareness-based methods among the method options that should be made available, but these methods are often not offered for a variety of reasons. After testing the efficacy of the Standard Days Method (SDM), which is a fertility awareness-based method that identifies Days 8-19 of the menstrual cycle as fertile for women with cycles lasting between 26 and 32 days, pilot studies were conducted to introduce it into programs. Through 14 pilot studies around the world, ministries of health, family planning associations and community development organizations introduced the SDM. Follow-up interviews with users and other data collection methodologies were used to track user characteristics and experiences. Supervision data and simulated clients assessed the effects on service delivery. The SDM appeals to a broad range of women throughout the world. Clients report using abstinence or condoms to manage the fertile days. Both men and women report high levels of satisfaction with the method. The cross-study first-year failure rate of 14.1 pregnancies per 100 woman-years of use is similar to typical-use rates found in the SDM efficacy trial. The results of the pilot studies offer guidance for scaling up service delivery of the SDM. Condom counseling can help many users manage the fertile window effectively. Because out-of-range cycles can lead to method failure, users must understand the importance of tracking cycle length and be willing to switch to another method when the SDM is contraindicated. Community providers can offer the method; within clinical settings, SDM counseling typically takes no more time than allowed in most program norms. Training providers to address alcohol use and gender-based violence improves SDM method use and contributes to better quality of care.

Fertility AwarenessFertile Window EstimationVariability and DurationE3G and LH Detection

Variability in the hormonally estimated fertile phase of the menstrual cycle

Fehring RJ et al., 2008Fertil Steril

The purpose of this study was to determine the variability in length of the fertile phase of the menstrual cycle with 140 participants who produced 1,060 cycles with an electronic hormonal fertility monitor. The length of the fertile phase, as defined by the first day with a threshold level of urinary E3G and ending with a second day above a threshold of LH, varied from <1 to >7 days, with the most frequent length being 3 days.

AndrologyMetabolic SyndromeObesity and Hormonal DysfunctionSystemic Disease Impact

The metabolic syndrome and male infertility

Kasturi SS et al., 2008J Androl

Metabolic syndrome (MetS) is highly prevalent, affecting more than 47 million US residents. This condition is also multifaceted, potentially leading to significant disturbance of numerous physiologic processes. This review article evaluates the literature regarding metabolic syndrome and male reproductive health. Links between obesity, dyslipidemia, hypertension, and insulin resistance are each examined with regard to their associated detrimental effects on male fertility. At the end of this manuscript, we propose a new MetS/male infertility paradigm. Additional studies specifically addressing the components of MetS and their impact on male reproduction will enhance our understanding of the underlying pathophysiology. These studies may also help clarify the role for therapeutic intervention.

Bone HealthISCD GuidelinesPerimenopausal BMD ScreeningTechnical Standards

Dual-Energy X-Ray Absorptiometry Technical issues: the 2007 ISCD Official Positions

Christine Simonelli et al., 2008J Clin Densitom

At the 2007 Position Development Conference, the Dual-Energy X-ray Absorptiometry Technical Task Force investigated three major areas of bone density testing. Although bone mineral density (BMD) testing in men had previously been reviewed at the 2005 Position Development Conference, we reviewed the most recent data in men to develop appropriate indications for bone density testing in men. We continue to recommend screening at age 70 and discuss the clinical risk factors that may be an appropriate indication for earlier BMD testing. Menopausal transition (perimenopause) was considered an important time to consider BMD evaluation because bone loss may be significant prior to menopause. However, because fracture risk is inherently low in women of this age without other risk factors, screening BMD testing is not appropriate. We discuss the risk factors that are strong indicators of fracture risk that may be increased during the menopause transition. The presence of these risk factors are appropriate indications for BMD testing with applicability of WHO diagnostic categorization. The issue of establishing a high threshold for BMD was investigated thoroughly and the current literature was reviewed. Despite the fact there is agreement that all BMD values greater than T-score -1.0 are not normal, it was felt that because of the paucity of sensitivity data and confounding factors such as high body mass index, an upper threshold could not be established or recommended at this time. This was felt to be an important area for further research.

Research

DIR Jahrbuch 2007 (Deutsches IVF-Register Annual Report 2007)

Deutsches IVF-Register e.V., 2008Deutsches IVF-Register Jahrbuch

Annual report (Jahrbuch) of the Deutsches IVF-Register (DIR) for treatment year 2007. 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).

Research

Effect of cell phone usage on semen analysis in men attending infertility clinic: an observational study

Agarwal A et al., 2008Fertility and sterility

To investigate the effect of cell phone use on various markers of semen quality. Observational study. Infertility clinic. PATIENT(S): Three hundred sixty-one men undergoing infertility evaluation were divided into no use; <2 h/day; 2-4 h/day; >4 h/day. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Sperm parameters (volume, liquefaction time, pH, viscosity, sperm count, motility, viability, and morphology). RESULT(S): The comparisons of mean sperm count, motility, viability, and normal morphology among four different cell phone user groups were statistically significant. Mean sperm motility, viability, and normal morphology were significantly different in cell phone user groups within two sperm count groups. The laboratory values of the above four sperm parameters decreased in all four cell phone user groups as the duration of daily exposure to cell phones increased. CONCLUSION(S): Use of cell phones decrease the semen quality in men by decreasing the sperm count, motility, viability, and normal morphology. The decrease in sperm parameters was dependent on the duration of daily exposure to cell phones and independent of the initial semen quality.