Molecular mechanism for human sperm chemotaxis mediated by progesterone

Abstract: Sperm chemotaxis is a chemical guiding mechanism that may orient spermatozoa to the egg surface. A picomolar concentration gradient of Progesterone (P), the main steroidal component secreted by the cumulus cells that surround the egg, attracts human spermatozoa. In order to elucidate the molecular mechanism of sperm chemotaxis mediated by P, we combine the application of different strategies: pharmacological inhibition of signaling molecules, measurements of the concentrations of second messengers and activation of the chemotactic signaling. Our data implicate a number of classic signal transduction pathways in the response and provide a model for the sequence of events, where the tmAC-cAMP-PKA pathway is activated first, followed by protein tyrosine phosphorylation (equatorial band and flagellum) and calcium mobilization (through IP(3)R and SOC channels), whereas the sGC-cGMP-PKG cascade, is activated later. These events lead to sperm orientation towards the source of the chemoattractant. The finding proposes a molecular mechanism which contributes to the understanding of the signal transduction pathway that takes place in a physiological process as chemotaxis.


Chronic endometritis: a combined histopathologic and clinical review of cases  from 2002 to 2007

Matthew A. Smith

Southern Regional Area Health Education Centers

Miranda Smith

Department of Pathology, Southern Regional Area Health Education Center, Fayetteville, North Carolina, USA.

Abstract: Chronic plasmacytic endometritis (CPE) is an infectious or reactive process with multiple etiologies. The lesion is reportedly often associated with pelvic inflammatory disease and intermenstrual bleeding. However, the clinical significance of the diagnosis when found incidentally and whether particular pathologic findings are associated with clinically important CPE have not been evaluated. We reviewed 105 chronic endometritis cases that had been diagnosed earlier and 130 controls to examine the pathologic and clinical associations in a diverse population.A pathology database was searched for endometrial biopsies diagnosed as CPE, and 105 cases were found. Systematic randomized sampling identified 130 control cases (biopsies not diagnosed as CPE). Slides were carefully reviewed to assess 10 histopathologic features. Clinical records were reviewed for 15 clinical parameters. Analysis was performed using chi tests and SAS software.Few patients (3%) received antibiotics or further clinical intervention after the diagnosis of CPE was rendered. The clinical data trended toward fewer menstrual abnormalities as plasma cells increased. The intensity of inflammation showed no association with patient age or symptom duration. Evaluation of controls revealed 17 cases with missed diagnosis of CPE, representing an overall 16% underdiagnosis rate.In CPE, there are no specific clinical features that correlate with the intensity of pathologic findings; the most specific histologic feature is the presence of plasma cells, and it is predominantly identified in weakly proliferative endometrium. There is a clinically insignificant 16% pathologic underdiagnosis rate. In contrast to the findings of past studies, only a small percentage of patients had pelvic inflammatory disease (4%).

International Journal of Gynecological Pathology : Official Journal of the  International Society of Gynecological Pathologists


Health-related quality of life in Canadian adolescents and young adults: normative data using the SF-36

Wilma M Hopman, Claudie Berger, Lawrence Joseph, Tanveer Towheed, Jerilynn C Prior, Tassos Anastassiades, Suzette Poliquin, Wei Zhou, Jonathan D Adachi, David A Hanley, Emmanuel A Papadimitropoulos, Alan Tenenhouse

Abstract:
Objectives: Normative data for the SF-36 measure of health-related quality of life (HRQOL) exist for those over 25 years of age, based on data from the population-based Canadian Multicentre Osteoporosis Study (CaMos). CaMos recently recruited a sample of young Canadians aged between 16 and 24 years. The purpose of this study was to develop normative SF-36 data for this age group.

Methods: After direct standardization to the Canadian population, means, standard deviations (SD), 95% confidence intervals and percentage at floor and ceiling were produced for the eight domain and two summary scores of the SF-36. Domains are scored from 0 (poor) to 100 (excellent). Summary scores are standardized to a mean of 50, with scores over 50 representing better than average and below 50 poorer than average function. Separate analyses were completed for men and women, and for those 16-19 years and 20-24 years.

Results: The 1,001 community-based participants consisted of 474 men and 527 women from nine CaMos centres across Canada. Mean Physical Component Summary scores were 53.9 (SD = 6.9) and 53.3 (SD = 5.7) for young men and women, respectively. The equivalent Mental Component Summary scores were 49.3 (SD = 9.7) and 48.8 (SD = 8.9). In general, men scored somewhat higher than women, and younger (16-19 years) women scored higher than older (20-24 years) women, although the differences were small.

Conclusion: HRQOL is good in this cohort of young Canadians. Both men and women scored somewhat better on physically than mentally oriented domains. In general, Canadian scores were similar to those of the US, while a comparable Swedish sample scored higher than both countries on most domains. Results underscore the importance of taking country, age and gender into consideration when using normative data. Objectifs: Des données normatives sur la qualité de vie liée à la santé (QVLS) dans le questionnaire sur l’état de santé SF-36 existent déjà pour les personnes de plus de 25 ans grâce aux données représentatives de l’Étude canadienne multicentrique sur l’ostéoporose (CaMos). La CaMos a recruté récemment un échantillon de jeunes Canadiens âgés de 16 à 24 ans. Le but de notre étude était d’élaborer des données normatives SF-36 pour ce groupe d’âge. MÉTHODE: Après avoir effectué une standardisation directe à partir de la population canadienne, nous avons calculé les moyennes, les écarts-types (ET), les intervalles de confiance de 95% et le pourcentage minimum et maximum pour les huit domaines et les deux notes globales du SF-36. Les domaines sont notés de 0 (mauvais) à 100 (excellent). Les notes globales sont standardisées selon une moyenne de 50, les notes de plus de 50 indiquant des fonctions supérieures à la moyenne, et les notes de moins de 50, des fonctions inférieures à la moyenne. Nous avons analysé séparément les hommes des femmes, et le groupe des 16 à 19 ans de celui des 20 à 24 ans. RÉSULTATS: Les 1 001 participants sélectionnés dans la communauté comprenaient 474 hommes et 527 femmes des neuf centres CaMos du Canada. Les notes globales moyennes pour la composante santé physique étaient de 53,9 (ET=6,9) et de 53,3 (ET=5,7) pour les jeunes hommes et les jeunes femmes, respectivement. Les notes équivalentes pour la composante santé mentale étaient de 49,3 (ET=9,7) et de 48,8 (ET=8,9). En général, les hommes ont obtenu des notes un peu meilleures que celles des femmes, et les femmes plus jeunes (16 à 19 ans), de meilleures notes que leurs aînées (20 à 24 ans), mais ces différences étaient faibles.

Conclusion: La QVLS est bonne dans cette cohorte de jeunes Canadiens. Tant les hommes que les femmes ont obtenu des notes un peu meilleures pour la santé physique que pour la santé mentale. En général, les notes canadiennes étaient semblables à celles des États-Unis, mais un échantillon suédois comparable a obtenu des notes plus élevées que ces deux pays dans la plupart des domaines. Ces résultats soulignent l’importance de tenir compte du pays, de l’âge et du sexe lorsqu’on utilise des données normatives.


Fertility issues in women with diabetes

Fertility issues in women with diabetes

Abstract: Diabetes mellitus Type 1 and Type 2 should be considered in the differential diagnosis of menstrual abnormalities and infertility. The reproductive period of diabetic women may be reduced due to delayed menarche and premature menopause. During the reproductive years, diabetes has been associated with menstrual abnormalities, such as oligomenorrhea and secondary amenorrhea. It was found that better glycemic control and prevention of diabetic complications improves these irregularities and increases fertility rates close to those that are seen in the general population. Women with persistent menstrual abnormalities despite adequate treatment need to be approached by broader evaluation, which will include the examination of the hypothalamic-pituitary-ovarian axis and the hormonal status, presence of autoimmune thyroid disease and antiovarian autoantibodies, and hyperandrogenism.


Ovulation disturbances and mood across the menstrual cycles of healthy 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: We examined the cyclicity of negative mood relative to ovulation and ovulation disturbances in Menstrual Cycle Diary(c) data collected daily during a 1-year study of ovulation, exercise, and bone change. A validated quantitative basal temperature-based methodology was used to determine the onset of the luteal phase. 'Feeling depressed', 'feeling anxious', and 'feeling angry/frustrated' were scored on a scale of 0 (absent) to 4 (very intense). Mood scores were examined over two 15-day intervals centered on either ovulation/midpoint, or on the onset of flow. Data were available from 765 cycles of 62 healthy and initially ovulatory women with a mean age of 33.9 +/- 5.4 years. Of 739 cycles that could be classified, 532 (72%) were normally ovulatory, 185 (25%) were ovulatory with a short (<10 day) luteal phase, and 22 (3%) were anovulatory. Minor cyclic mood changes were present in both ovulatory and anovulatory menstrual cycles. In anovulatory cycles, mood tended to be more variable but less negative, with a time course that differed from that in ovulatory cycles. Mood scores did not differ based on luteal phase length or with hormone levels. Patterns and mechanisms of mood change in very symptomatic women appear to be essentially amplifications of normal experiences.

Journal of Psychosomatic Obstetrics and Gynaecology


Results of the live survey in Las Vegas, 2008, and the response of the AAGL

Journal of Minimally Invasive Gynecology


Maternal thyroid function during gestation is related to breech presentation at term

Sara Crawford

National Center for Chronic Disease Prevention and Health Promotion

Abstract:
OBJECTIVE: To study the relationship between suboptimal maternal thyroid function during gestation and breech presentation at term.

DESIGN: Prospective follow-up study during three trimesters of gestation.

PATIENTS: A total of 1058 Dutch Caucasian healthy pregnant women were prospectively followed from 12 weeks gestation until term (>or=37 weeks) delivery.

MEASUREMENTS: Maternal thyroid parameters [TSH, free T4 (FT4) and auto-antibodies to thyroid peroxidase] were assessed at 12, 24 and 36 weeks gestation as well as foetal presentation at term.

RESULTS: At term, 58 women (5.5%) presented in breech. Compared with women with foetuses in the cephalic position, those women who presented in breech at term had significantly higher TSH concentrations, but only at 36 weeks gestation (P = 0.007). No between group differences were obtained for FT4 level at any assessment. The prevalence of breech presentation in the subgroup of women with TSH >or= 2.5 mIU/l (90th percentile) at 36 weeks gestation was 11%, compared with 4.8% in the women with TSH < 2.50 mIU/l (P = 0.006). Women with TSH below the 5th percentile had no breech presentations. Breech position was significantly and independently related to high maternal TSH concentration (>or=2.5 mIU/l) at 36 weeks gestation (O.R.: 2.23, 95% CI: 1.14-4.39), but not at 12 and 24 weeks gestation.

CONCLUSIONS: Women with TSH levels above 2.5 mIU/l during end gestation are at risk for breech presentation, and as such for obstetric complications.


An internet-based prospective study of body size and time-to-pregnancy

Lauren A Wise

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

Kenneth J Rothman

Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA

Ellen M Mikkelsen

Department of Clinical Epidemiology Aarhus University Hospital Aarhus Denmark

Elizabeth E Hatch

Department of Epidemiology Boston University School of Public Health Boston MA USA

Abstract:
Background: Recent studies have shown that both female and male obesity may delay time-to-pregnancy (TTP). Little is known about central adiposity or weight gain and fecundability in women.

Methods: We examined the association between anthropometric factors and TTP among 1651 Danish women participating in an internet-based prospective cohort study of pregnancy planners (2007-2008). We categorized body mass index (BMI = kg/m(2)) as underweight (<20), normal weight (20-24), overweight (25-29), obese (30-34) and very obese (> or =35). We used discrete-time Cox regression to estimate fecundability ratios (FRs) and 95% confidence intervals (CI), controlling for potential confounders.

Results: We found longer TTPs for overweight (FR = 0.83, 95% CI = 0.70-1.00), obese (FR = 0.75, 95% CI = 0.58-0.97), and very obese (FR = 0.61, 95% CI = 0.42-0.88) women, compared with normal weight women. After further control for waist circumference, FRs for overweight, obese, and very obese women were 0.72 (95% CI = 0.58-0.90), 0.60 (95% CI = 0.42-0.85) and 0.48 (95% CI = 0.31-0.74), respectively. Underweight was associated with reduced fecundability among nulliparous women (FR = 0.82, 95% CI = 0.63-1.06) and increased fecundability among parous women (FR = 1.61, 95% CI = 1.08-2.39). Male BMI was not materially associated with TTP after control for female BMI. Compared with women who maintained a stable weight since age 17 (-5 to 4 kg), women who gained > or =15 kg had longer TTPs (FR = 0.72, 95% CI = 0.59-0.88) after adjustment for BMI at age 17. Associations of waist circumference and waist-to-hip ratio with TTP depended on adjustment for female BMI: null associations were observed before adjustment for BMI and weakly positive associations were observed after adjustment for BMI.

Conclusions: Our results confirm previous studies showing reduced fertility in overweight and obese women. The association between underweight and fecundability varied by parity.


Miscarriage rates after dehydroepiandrosterone (DHEA) supplementation in women with diminished ovarian reserve: a case control study

Abstract:
BACKGROUND: Dehydroepinadrosterone (DHEA) supplementation improves pregnancy chances in women with diminished ovarian reserve (DOR), by possibly reducing aneuploidy. Since a large majority of spontaneous miscarriages are associated with aneuploidy, one can speculate that DHEA supplementation may also reduce miscarriage rates.

METHODS: We retroactively compared, utilizing two independent statistical models, miscarriage rates in 73 DHEA supplemented pregnancies at two independent North American infertility centers, age-stratified, to miscarriages reported in a national U.S. in vitro fertilization (IVF) data base.

RESULTS: After DHEA supplementation the miscarriage rate at both centers was 15.1% (15.0% and 15.2%, respectively). For DHEA supplementation Mantel-Hänszel common odds ratio (and 95% confidence interval), stratified by age, was significantly lower, relative to odds of miscarriage in the general IVF control population [0.49 (0.25-0.94; p = 0.04)]. Miscarriage rates after DHEA were significantly lower at all ages but most pronounced above age 35 years.

DISCUSSION: Since DOR patients in the literature are reported to experience significantly higher miscarriage rates than average IVF patients, the here observed reduction in miscarriages after DHEA supplementation exceeds, however, all expectations. Miscarriage rates after DHEA not only were lower than in an average national IVF population but were comparable to rates reported in normally fertile populations. Low miscarriage rates, comparable to those of normal fertile women, are statistically impossible to achieve in DOR patients without assumption of a DHEA effect on embryo ploidy. Beyond further investigations in infertile populations, these data, therefore, also suggest the investigations of pre-conception DHEA supplementation in normal fertile populations above age 35 years.

Reproductive Biology and Endocrinology : RB&E


Oral contraceptive pill for primary dysmenorrhoea

Abstract: BACKGROUND: Dysmenorrhoea (painful menstrual cramps) is common. Combined OCPs are recommended in the management of primary dysmenorrhoea. OBJECTIVES: To determine the effectiveness and safety of combined oral contraceptive pills for the management of primary dysmenorrhoea. SEARCH STRATEGY: We conducted electronic searches for randomised controlled trials (RCTs) in the Cochrane Menstrual Disorders and Subfertility Group Register of controlled trials CENTRAL, CCTR, MEDLINE, EMBASE, and CINAHL (first conducted in 2001, updated on 5 November 2008). SELECTION CRITERIA: RCTs comparing all combined OCPs with other combined OCPs, placebo, no management, or management with nonsteroidal anti-inflammatories (NSAIDs) were considered. MAIN RESULTS: One study of low dose oestrogen and four studies of medium dose oestrogen combined OCPs compared with placebo, for a combined total of 497 women, reported pain improvement. For the outcome of pain relief across the different OCPs the pooled OR suggested benefit with OCPs compared to placebo (7 RCTs: Peto OR 2.01 [95% CI 1.32, 3.08]). The Chi-squared test for heterogeneity showed there is significant heterogeneity. A sensitivity analysis removing the studies with inadequate allocation concealment suggested significant benefit of treatment with the pooled OR of 2.99 (95% CI 1.76, 5.07). AUTHORS' CONCLUSIONS: There is limited evidence for pain improvement with the use of the OCP (both low and medium dose oestrogen) in women with dysmenorrhoea. There is no evidence of a difference between different OCP preparations.


Induced termination of pregnancy and low birthweight and preterm birth: a systematic review and meta-analyses

Knowledge Synthesis Group of Determinants of preterm/LBW births

Abstract:
BACKGROUND: History of induced termination of pregnancy (I-TOP) is suggested as a precursor for infant being born low birthweight (LBW), preterm (PT) or small for gestational age (SGA). Infection, mechanical trauma to the cervix leading to cervical incompetence and scarred tissue following curettage are suspected mechanisms.

OBJECTIVE: To systematically review the risk of an infant being born LBW/PT/SGA among women with history of I-TOP.

SEARCH STRATEGY: Medline, Embase, CINAHL and bibliographies of identified articles were searched for English language studies.

SELECTION CRITERIA: Studies reporting birth outcomes to mothers with or without history of induced abortion were included.

DATA COLLECTION: and analyses Two reviewers independently collected data and assessed the quality of the studies for biases in sample selection, exposure assessment, confounder adjustment, analytical, outcome assessments and attrition. Meta-analyses were performed using random effect model and odds ratio (OR), weighted mean difference and 95% confidence interval (CI) were calculated.

MAIN RESULTS: Thirty-seven studies of low-moderate risk of bias were included. A history of one I-TOP was associated with increased unadjusted odds of LBW (OR 1.35, 95% CI 1.20-1.52) and PT (OR 1.36, 95% CI 1.24-1.50), but not SGA (OR 0.87, 95% CI 0.69-1.09). A history of more than one I-TOP was associated with LBW (OR 1.72, 95% CI 1.45-2.04) and PT (OR 1.93, 95% CI 1.28-2.71). Meta-analyses of adjusted risk estimates confirmed these findings.

CONCLUSIONS: A previous I-TOP is associated with a significantly increased risk of LBW and PT but not SGA. The risk increased as the number of I-TOP increased.

BJOG : an international journal of obstetrics and gynaecology


Is preeclampsia an autoimmune disease?

Is preeclampsia an autoimmune disease?

Abstract: Preeclampsia is a life-threatening hypertensive disease of pregnancy. The condition is characterized by the presence of autoantibodies that activate the major angiotensin receptor, AT(1). Research conducted during the past decade has shown that these autoantibodies activate AT(1) receptors on a variety of cell types and provoke biological responses that are relevant to the pathophysiology of preeclampsia. The introduction of these autoantibodies into pregnant mice results in hypertension, proteinuria and a variety of other features of preeclampsia including small fetuses and placentas. These findings demonstrate the pathophysiological role of these autoantibodies in preeclampsia. The biological properties of these autoantibodies can be blocked by a 7-amino acid peptide that corresponds to a specific sequence associated with the second extracellular loop of the AT(1) receptor. The fact that autoantibodies from different individuals are directed to a common epitope provides obvious diagnostic and therapeutic opportunities. Research reviewed here raises the intriguing possibility that preeclampsia may be a pregnancy-induced autoimmune condition characterized by the presence of disease-causing angiotensin receptor activating autoantibodies.


Parity and subfertility effects of continuous oral contraceptive on fertility are important

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.


Breast cancer risk assessments comparing Gail and CARE models in African-American  women

Abstract: The Gail model has been used to predict invasive breast cancer risk in women using risk factors of age, age at menarche, age at first live birth, number of first-degree relatives with breast cancer, and number of previous benign breast biopsies. However, this model underestimates breast cancer risk in African-American women. The Contraceptive and Reproductive Experience (CARE) model has been developed to replace the Gail model in predicting breast cancer risk in African-American women. In a sample of 883 women who participated in the breast cancer screening program at Howard University Cancer Center, we compared the breast cancer risk estimates from the Gail model and the CARE model. The mean 5-year breast cancer risk was 0.88% (Range: 0.18-6.60%) for the Gail model and 1.29% (Range: 0.20-4.50%) for the CARE model. Using the usual cutoff-point of 1.67% or above for elevated risk, there is a significant difference in the proportion of women with elevated breast cancer risk between the Gail and the CARE models (McNemar's test, p < 0.0001). For both models, there was a significant mean risk difference between those with and without a family history of breast cancer (Wilcoxon rank-sum test, p < 0.0001). Our results confirm the need for validation of the Gail model in African-Americans and diversity in research. Although these findings are not perfect and perhaps not definitive, they are additive in the discussions during counseling and risk assessment in African-Americans. Furthermore, these findings will be complemented by new technologies such as genomics in refining our ability to assess risk.


Environmental factors in the development of chronic inflammation: a case-control  study on risk factors for Crohn's disease within New Zealand

Abstract: The role of environmental factors in the risk for Crohn's disease (CD), an inflammatory bowel disease (IBD), was investigated in a North Island-based New Zealand case-control cohort. A total of 315 CD patients and 536 controls were recruited through various sources to the Auckland CD Risk Factor Study. As well as demographic characteristics, the self-reported questionnaire included (1) smoking and drinking alcohol, (2) breastfeeding in infancy, (3) early life exposures to allergens and microbes, (4) health conditions lasting 6 months or longer and (5) taking antibiotics and any medications. There was strong evidence for familial associations of the disease, and minor effects of birth order and number of siblings. Being a smoker, especially over a long time period, and exposure to smoking during childhood and adolescence periods increased risk, whereas drinking alcohol at least once per week showed a slight protective effect. Long term use of the oral contraceptive pill increased the risk of developing CD, but breastfeeding and immunisation during infancy showed no significant association. Long term and debilitating illness (lasting 6 months or more), taking antibiotics prior to developing CD, or taking four or more antibiotics or any regular medication in a year during adolescence substantially increased the CD risk. Having a pet during childhood was a protective factor, but regularly feeding an animal was not sufficient to protect. Many of these significant factors are likely to impact on the colonic microflora and/or immune system. We conclude that, in addition to strong evidence for genetic associations, factors likely to impact on immune response or reduce early exposure to microbes provide a main risk factor for CD in this New Zealand population.


Dynamic model for multivariate markers of fecundability

David B Dunson

National Institute of Environmental Health Sciences

Abstract: Dynamic latent class models provide a flexible framework for studying biologic processes that evolve over time. Motivated by studies of markers of the fertile days of the menstrual cycle, we propose a discrete-time dynamic latent class framework, allowing change points to depend on time, fixed predictors, and random effects. Observed data consist of multivariate categorical indicators, which change dynamically in a flexible manner according to latent class status. Given the flexibility of the framework, which incorporates semi-parametric components using mixtures of betas, identifiability constraints are needed to define the latent classes. Such constraints are most appropriately based on the known biology of the process. The Bayesian method is developed particularly for analyzing mucus symptom data from a study of women using natural family planning.


Severity of interstitial cystitis symptoms and quality of life in female  patients

Chun-Pin Chang

Division of Public Health, Department of Family and Preventive Medicine, University of Utah School of Medicine, and Huntsman Cancer Institute, Salt Lake City, UT, United States of America.

Edward L Davis

Citrus Valley Medical Research, Inc., Glendora, California.

Abstract:
Objective: Interstitial cystitis (IC) is a visceral pain syndrome with a profound impact on quality of life (QOL). The main aims of the current study are as follows: (1) to determine possible factors that may increase the severity of symptoms and decrease QOL in women diagnosed with IC; (2) to study how symptom severity affects QOL adjusting for these factors; and (3) to investigate which symptom is most likely to impair IC patients' physical and mental QOL.

Methods: Forty-one women (age, 20-71 years) with moderate/severe IC enrolled in a clinical trial of intravesical pentosan polysulfate sodium in California (USA) were included in this cross-sectional analysis. Demographic and clinical characteristics were evaluated at baseline using the O'Leary-Sant Interstitial Cystitis Symptom Index (ICSI), pain assessment, urgency scale, voiding log for 24 h, and the Short Form-36 (SF-36).

Results: Being currently unmarried was associated with more severe symptoms. Being unemployed, currently unmarried, obese, never pregnant, and ever use of oral contraceptive were associated with a decrement in at least one QOL domain. Symptom severity was an independent predictor of worse QOL on three domains: bodily pain, general health, and mental health. Pain and nocturia were the only symptoms found to be associated with decline in overall physical quality of life. None of the symptoms had significant impact on the mental component summary of QOL.

Conclusions: Symptom severity and being currently unmarried were found to be associated with impairment in QOL in IC patients. Managing pain and nocturia may improve the patients' overall physical QOL.


Repeat low-trauma fractures occur frequently among men and women who have osteopenic BMD

Christopher S Kovacs

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

Jonathan D Adachi

McMaster University, Hamilton, ON, Canada

Abstract: Fracture risk assessment based solely on BMD has limitations. Additional risk factors include the presence of a previous low-trauma fracture. We sought to quantify the fracture burden attributable to first versus repeat fracture. We studied 2179 men and 5269 women, 50-90 yr of age, participating in the Canadian Multicentre Osteoporosis Study (CaMos). We included all low-trauma fractures that occurred over 8 yr of follow-up and classified these as either first or repeat clinical low-trauma fracture based on lifetime fracture history. Analyses were further stratified by sex, age, BMD risk categories (normal, osteopenia, osteoporosis), and vertebral deformity status. There were 128 fractures in men and 577 fractures in women. About 25% of fractures in men and 40% in women were repeat fractures. Just over one half of first fractures occurred in those with osteopenic BMD (58% in men, 54% in women). Just under one half of repeat fractures also occurred in those with osteopenic BMD (42% in men, 47% in women). The incidence of repeat fracture was, in most cases, nearly double, but sometimes nearly quadruple, the incidence of first fracture within a given BMD risk category in both men and women. Repeat fractures contribute substantially to overall fracture burden, and the contribution is independent of BMD. Furthermore, those with a combination of prior low-trauma fracture and another risk factor were at especially high risk of future fracture.


The venous thrombotic risk of oral contraceptives, effects of oestrogen dose and  progestogen type: results of the MEGA case-control study

Abstract:
Objective: To assess the thrombotic risk associated with oral contraceptive use with a focus on dose of oestrogen and type of progestogen of oral contraceptives available in the Netherlands.
Design: Population based case-control study.
Setting: Six participating anticoagulation clinics in the Netherlands (Amersfoort, Amsterdam, The Hague, Leiden, Rotterdam, and Utrecht).

Participants: Premenopausal women <50 years old who were not pregnant, not within four weeks postpartum, and not using a hormone excreting intrauterine device or depot contraceptive. Analysis included 1524 patients and 1760 controls.

MAIN OUTCOME MEASURES: First objectively diagnosed episodes of deep venous thrombosis of the leg or pulmonary embolism. Odds ratios calculated by cross-tabulation with a 95% confidence interval according to Woolf's method; adjusted odds ratios estimated by unconditional logistic regression, standard errors derived from the model.

Results: Currently available oral contraceptives increased the risk of venous thrombosis fivefold compared with non-use (odds ratio 5.0, 95% CI 4.2 to 5.8). The risk clearly differed by type of progestogen and dose of oestrogen. The use of oral contraceptives containing levonorgestrel was associated with an almost fourfold increased risk of venous thrombosis (odds ratio 3.6, 2.9 to 4.6) relative to non-users, whereas the risk of venous thrombosis compared with non-use was increased 5.6-fold for gestodene (5.6, 3.7 to 8.4), 7.3-fold for desogestrel (7.3, 5.3 to 10.0), 6.8-fold for cyproterone acetate (6.8, 4.7 to 10.0), and 6.3-fold for drospirenone (6.3, 2.9 to 13.7). The risk of venous thrombosis was positively associated with oestrogen dose. We confirmed a high risk of venous thrombosis during the first months of oral contraceptive use irrespective of the type of oral contraceptives.

Conclusions: Currently available oral contraceptives still have a major impact on thrombosis occurrence and many women do not use the safest brands with regard to risk of venous thrombosis.


Hormonal contraception and risk of venous thromboembolism: national follow-up  study

Abstract:
Objective: To assess the risk of venous thrombosis in current users of different types of hormonal contraception, focusing on regimen, oestrogen dose, type of progestogen, and route of administration.
Design: National cohort study.
Setting: Denmark, 1995-2005.

Participants: Danish women aged 15-49 with no history of cardiovascular or malignant disease.

Main Outcome Measures: Adjusted rate ratios for all first time deep venous thrombosis, portal thrombosis, thrombosis of caval vein, thrombosis of renal vein, unspecified deep vein thrombosis, and pulmonary embolism during the study period.

Results: 10.4 million woman years were recorded, 3.3 million woman years in receipt of oral contraceptives. In total, 4213 venous thrombotic events were observed, 2045 in current users of oral contraceptives. The overall absolute risk of venous thrombosis per 10 000 woman years in non-users of oral contraceptives was 3.01 and in current users was 6.29. Compared with non-users of combined oral contraceptives the rate ratio of venous thrombembolism in current users decreased with duration of use (<1 year 4.17, 95% confidence interval 3.73 to 4.66, 1-4 years 2.98, 2.73 to 3.26, and >4 years 2.76, 2.53 to 3.02; P<0.001) and with decreasing dose of oestrogen. Compared with oral contraceptives containing levonorgestrel and with the same dose of oestrogen and length of use, the rate ratio for oral contraceptives with norethisterone was 0.98 (0.71 to 1.37), with norgestimate 1.19 (0.96 to 1.47), with desogestrel 1.82 (1.49 to 2.22), with gestodene 1.86 (1.59 to 2.18), with drospirenone 1.64 (1.27 to 2.10), and with cyproterone 1.88 (1.47 to 2.42). Compared with non-users of oral contraceptives, the rate ratio for venous thromboembolism in users of progestogen only oral contraceptives with levonorgestrel or norethisterone was 0.59 (0.33 to 1.03) or with 75 mug desogestrel was 1.12 (0.36 to 3.49), and for hormone releasing intrauterine devices was 0.90 (0.64 to 1.26).

Conclusion: The risk of venous thrombosis in current users of combined oral contraceptives decreases with duration of use and decreasing oestrogen dose. For the same dose of oestrogen and the same length of use, oral contraceptives with desogestrel, gestodene, or drospirenone were associated with a significantly higher risk of venous thrombosis than oral contraceptives with levonorgestrel. Progestogen only pills and hormone releasing intrauterine devices were not associated with any increased risk of venous thrombosis.


Relation between fractures and mortality: results from the Canadian Multicentre Osteoporosis Study

Abstract:
Background: Fractures have largely been assessed by their impact on quality of life or health care costs. We conducted this study to evaluate the relation between fractures and mortality.

Methods: A total of 7753 randomly selected people (2187 men and 5566 women) aged 50 years and older from across Canada participated in a 5-year observational cohort study. Incident fractures were identified on the basis of validated self-report and were classified by type (vertebral, pelvic, forearm or wrist, rib, hip and "other"). We subdivided fracture groups by the year in which the fracture occurred during follow-up; those occurring in the fourth and fifth years were grouped together. We examined the relation between the time of the incident fracture and death.

Results: Compared with participants who had no fracture during follow-up, those who had a vertebral fracture in the second year were at increased risk of death (adjusted hazard ratio [HR] 2.7, 95% confidence interval [CI] 1.1-6.6); also at risk were those who had a hip fracture during the first year (adjusted HR 3.2, 95% CI 1.4-7.4). Among women, the risk of death was increased for those with a vertebral fracture during the first year (adjusted HR 3.7, 95% CI 1.1-12.8) or the second year of follow-up (adjusted HR 3.2, 95% CI 1.2-8.1). The risk of death was also increased among women with hip fracture during the first year of follow-up (adjusted HR 3.0, 95% CI 1.0-8.7).

Interpretation: Vertebral and hip fractures are associated with an increased risk of death. Interventions that reduce the incidence of these fractures need to be implemented to improve survival.


Reprotoxicity of intrauterine insemination and in vitro fertilization-embryo transfer disposables and products: a 4-year survey

W Ombelet

Genk Institute for Fertility Technology, Department of Obstetrics and Gynaecology, Ziekenhuis Oost-Limburg, Schiepse Bos 6, 3600 Genk, Belgium. ; Faculty of Medicine and Life Sciences, Hasselt Univ...

Abstract: OBJECTIVE: To test consumables and other products used during oocyte collection, sperm preparation, IUI, embryo culture, and IVF-embryo transfer for their possible reprotoxic properties. DESIGN: A prospective 4-year survey of reprotoxicity testing of consumables and other products used in assisted reproductive technologies (ART). SETTING: Private infertility center in a university-affiliated teaching hospital. INTERVENTION(S): Thirty-six products of 72 different brands, including plastics, syringes, tubing, and surgical gloves were analyzed for their reprotoxicity in 350 human sperm survival tests (SpST). MAIN OUTCOME MEASURE(S): The SpST index: percentage progressive motility of test sample/percentage progressive motility of control sample after 24 and 96 hours. RESULT(S): Thirteen of 36 products were found to be reprotoxic: an SpST index <0.85 was noted 24 and 96 hours after exposure. These products included eight brands of unpowdered surgical gloves, two types of hysterometers and one type of tubing attached to the oocyte collection needle, one type of ovum pickup procedure needle, and one type of embryo transfer catheter. One type of condom used for ultrasound, one type of sterile Pasteur pipette and petri dish, as well as the cover of a specimen container, were reprotoxic. CONCLUSION(S): The SpST is an inexpensive, easy, and reliable method to identify potential reprotoxic products and consumables used in ART procedures. These data underline the importance of the inclusion of the SpST in a continuous quality control (QC) program of ART outcome.


Relevance of gastrointestinal symptoms in endometriosis

Abstract:
BACKGROUND: Endometriosis commonly presents with a range of symptoms none of which are particularly specific for the condition, often resulting in misdiagnosis or delay in diagnosis.

AIM: To investigate gastrointestinal symptoms in women with endometriosis and compare their frequency with that of the classical gynaecological symptoms.

METHODS: Systematic exploration of symptoms in a consecutive series of 355 women undergoing operative laparoscopy for suspected endometriosis.

RESULTS: Endometriosis was confirmed by histology in 290 women (84.5%). Bowel lesions were present in only 7.6%. Ninety per cent of women had gastrointestinal symptoms, of which bloating was the most common (82.8%), but 71.3% also had other bowel symptoms. All gastrointestinal symptoms were similarly predictive of histologically confirmed endometriosis. Seventy-six women (21.4%) had previously been diagnosed with irritable bowel syndrome and 79% of them had endometriosis confirmed.

CONCLUSION: Gastrointestinal symptoms are nearly as common as gynaecological symptoms in women with endometriosis and do not necessarily reflect bowel involvement.

The Australian & New Zealand journal of obstetrics & gynaecology


Managing the complications associated with assisted reproductive technologies

Abstract: Delaying conception has increased the demand on assisted reproduction. Currently, more than 1% of children are conceived through assisted reproductive technologies (ART) worldwide and this number is likely to continue increasing. Like any other medical intervention ART is associated with both short-term and long-term complications. The major short-term complications include ovarian hyperstimulation syndrome (OHSS) and multiple pregnancies. OHSS is difficult to predict, but meticulous preventive strategies and protocols are being developed that may limit it. Most of the morbidities in children born after ART are related to multiple pregnancies. New laboratory methodologies may allow the transfer of fewer embryos to maintain satisfactory live birth rates while reducing the risk of multiple pregnancies. In vitro fertilization may be associated with a slight increased risk for birth defects. Analysis of possible risks from these techniques is confounded by factors of underlying parental subfertility, fertility treatments and multiple births. The long-term sequelae remain largely undetermined. All outcomes of ART, including pregnancy rates and adverse complications, need to be compared with standard non-ART when deciding the appropriate course of treatment. The importance of counselling should never be ignored in any treatment decision.


The role of prolactin- and endometriosis-associated infertility

Abstract: This review will address the current understanding of the relationship between prolactin (PRL) and endometriosis-associated infertility. Although the exact mechanisms of action of hyperprolactinemia in patients with endometriosis-associated infertility have not been clearly established, this report reviews results from relevant studies in the literature. These include serum PRL levels in endometriosis-associated infertility, PRL receptors in ectopic endometriotic tissues, basal PRL levels after TSH and Danazol (isoxazolic derivative of the synthetic steroid 5alpha-ethinyl-testosterone) therapy, peritoneal fluid and nocturnal serum PRL levels in endometriosis, infertility, and luteal phase PRL concentrations in patients with endometriosis. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING Objectives: After completion of this article, the reader should be able to explain the relationship between prolactinand endometriosis-associated infertility, relate endometriosis with infertility, and summarize two ways in which prolactin and endometriosis may be linked in the pathophysiology of infertility.


Oral contraceptives and postmenopausal hormones and risk of contralateral breast  cancer among BRCA1 and BRCA2 mutation carriers and noncarriers: the WECARE Study

Leslie Bernstein

Centers for Disease Control and Prevention

Abstract: The potential effects of oral contraceptive (OC) and postmenopausal hormone (PMH) use are not well understood among BRCA1 or BRCA2 (BRCA1/2) deleterious mutation carriers with a history of breast cancer. We investigated the association between OC and PMH use and risk of contralateral breast cancer (CBC) in the WECARE (Women's Environment, Cancer, and Radiation Epidemiology) Study. The WECARE Study is a population-based case-control study of 705 women with asynchronous CBC and 1,398 women with unilateral breast cancer, including 181 BRCA1/2 mutation carriers. Risk-factor information was assessed by telephone interview. Mutation status was measured using denaturing high-performance liquid chromatography followed by direct sequencing in all participants. Outcomes, treatment, and tumor characteristics were abstracted from medical records. Ever use of OCs was not associated with risk among noncarriers (RR = 0.87; 95% CI = 0.66-1.15) or BRCA2 carriers (RR = 0.82; 95% CI = 0.21-3.13). BRCA1 carriers who used OCs had a nonsignificant greater risk than nonusers (RR = 2.38; 95% CI = 0.72-7.83). Total duration of OC use and at least 5 years of use before age 30 were associated with a nonsignificant increased risk among mutation carriers but not among noncarriers. Few women had ever used PMH and we found no significant associations between lifetime use and CBC risk among carriers and noncarriers. In conclusion, the association between OC/PMH use and risk of CBC does not differ significantly between carriers and noncarriers; however, because carriers have a higher baseline risk of second primaries, even a potential small increase in risk as a result of OC use may be clinically relevant.


Mitochondrial functions on oocytes and preimplantation embryos

Abstract: Oocyte quality has long been considered as a main limiting factor for in vitro fertilization (IVF). In the past decade, extensive observations demonstrated that the mitochondrion plays a vital role in the oocyte cytoplasm, for it can provide adenosine triphosphate (ATP) for fertilization and preimplantation embryo development and also act as stores of intracellular calcium and proapoptotic factors. During the oocyte maturation, mitochondria are characterized by distinct changes of their distribution pattern from being homogeneous to heterogeneous, which is correlated with the cumulus apoptosis. Oocyte quality decreases with the increasing maternal age. Recent studies have shown that low quality oocytes have some age-related dysfunctions, which include the decrease in mitochondrial membrane potential, increase of mitochondrial DNA (mtDNA) damages, chromosomal aneuploidies, the incidence of apoptosis, and changes in mitochondrial gene expression. All these dysfunctions may cause a high level of developmental retardation and arrest of preimplantation embryos. It has been suggested that these mitochondrial changes may arise from excessive reactive oxygen species (ROS) that is closely associated with the oxidative energy production or calcium overload, which may trigger permeability transition pore opening and subsequent apoptosis. Therefore, mitochondria can be seen as signs for oocyte quality evaluation, and it is possible that the oocyte quality can be improved by enhancing the physical function of mitochondria. Here we reviewed recent advances in mitochondrial functions on oocytes.

Journal of Zhejiang University. Science. B


Route of administration of contraceptives containing desogestrel/etonorgestrel and insulin sensitivity: a prospective randomized study

Abstract:
BACKGROUND: The study was conducted to investigate whether hormonal contraceptives administered via the oral and vaginal route exert a similar effect on insulin sensitivity (SI).

STUDY DESIGN: This is a prospective, randomized study performed in the University Hospital. Subjects were healthy lean young women, needing a hormonal contraceptive, randomly allocated to receive for 6 months (a) an oral contraceptive (OC) containing 30 mcg ethinylestradiol (EE)/150 mcg desogestrel (DSG) (high-estrogen group; n=12), (b) an OC containing 20 mcg EE/150 mcg DSG (low-estrogen group; n=12) and (c) a vaginal ring contraceptive releasing, per day, 15 mcg EE/120 mcg etonorgestrel, the active DSG metabolite (n=12). SI and glucose utilization independent of insulin (Sg) were evaluated by the minimal model method. Modifications of total, high-density lipoprotein (HDL) and low-density lipoprotein cholesterol and triglycerides were also evaluated.

RESULTS: Sg did not vary with any treatment. SI decreased during OCs (5.74+/-0.49 vs. 3.86+/-0.44; p=.0005), independently of the high/low-estrogen dose. SI did not decrease during vaginal ring use (4.64+/-1.03 vs. 5.25+/-1.36; p=.57; p=.019 vs. oral). Total cholesterol and HDL cholesterol increased (p=.02) during OCs, independently of the dose. Triglycerides increased during both oral (p=.01) and vaginal (p=.032) contraceptive use.

CONCLUSIONS: The present data indicate that in contrast to OC use, vaginal contraception with the ring does not deteriorate SI. The vaginal ring may represent an appropriate choice for long-term contraception in women at risk for developing diabetes mellitus or metabolic syndrome.


Melatonin and the ovary: physiological and pathophysiological implications

Abstract:
OBJECTIVE: To summarize the role of melatonin in the physiology and pathophysiology of the ovary.

DESIGN: Review of literature.

SETTING: University Health Science Center.

RESULT(S): Melatonin plays an essential role in the pathogenesis of many reproductive processes. Human preovulatory follicular fluid (FF) contains higher concentrations of melatonin than does plasma, and melatonin receptors are present in ovarian granulosa cells (GC). Melatonin has been shown to have direct effects on ovarian function. Reactive oxygen species and apoptosis are involved in a number of reproductive events including folliculogenesis, follicular atresia, ovulation, oocyte maturation, and corpus luteum (CL) formation. Melatonin and its metabolites are powerful antioxidants; the primitive and primary function of melatonin may be its actions as a receptor-independent free radical scavenger and a broad-spectrum antioxidant. A large amount of scientific evidence supports a local role of melatonin in the human reproductive processes. The indole also has potential roles in the pathophysiology of endometriosis, polycystic ovary syndrome (PCOS), and premature ovarian failure (POF).

CONCLUSION(S): We summarize the current understanding of melatonin's essential functions in the human ovary. Melatonin could become an important medication for improving ovarian function and oocyte quality, and open new opportunities for the management of several ovarian diseases.


Mittelschmerz mimicking appendicitis

Mittelschmerz mimicking appendicitis

British journal of hospital medicine (London, England : 2005)


Detecting evidence of luteal activity by least-squares quantitative basal temperature analysis against urinary progesterone metabolites and the effect of wake-time variability

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: To assess computerised least-squares analysis of quantitative basal temperature (LS-BT) against urinary pregnanediol glucuronide (PdG) as an indirect measure of ovulation, and to evaluate the stability of LS-QBT to wake-time variation.

Study Design: Cross-sectional study of 40 healthy, normal-weight, regularly menstruating women aged 19-34. Participants recorded basal temperature and collected first void urine daily for one complete menstrual cycle. Evidence of luteal activity (ELA), an indirect ovulation indicator, was assessed using Kassam's PdG algorithm, which identifies a sustained 3-day PdG rise, and the LS-QBT algorithm, by determining whether the temperature curve is significantly biphasic. Cycles were classified as ELA(+) or ELA(-). We explored the need to pre-screen for wake-time variations by repeating the analysis using: (A) all recorded temperatures, (B) wake-time adjusted temperatures, (C) temperatures within 2h of average wake-time, and (D) expert reviewed temperatures.

Results: Relative to PdG, classification of cycles as ELA(+) was 35 of 36 for LS-QBT methods A and B, 33 of 34 (method C) and 30 of 31 (method D). Classification of cycles as ELA(-) was 1 of 4 (methods A and B) and 0 of 3 (methods C and D). Positive predictive value was 92% for methods A-C and 91% for method D. Negative predictive value was 50% for methods A and B and 0% for methods C and D. Overall accuracy was 90% for methods A and B, 89% for method C and 88% for method D. The day of a significant temperature increase by LS-QBT and the first day of a sustained PdG rise were correlated (r=0.803, 0.741, 0.651, 0.747 for methods A-D, respectively, all p<0.001).

Conclusion: LS-QBT showed excellent detection of ELA(+) cycles (sensitivity, positive predictive value) but poor detection of ELA(-) cycles (specificity, negative predictive value) relative to urinary PdG. Correlations between the methods and overall accuracy were good and similar for all analyses. Findings suggest that LS-QBT is robust to wake-time variability and that expert interpretation is unnecessary. This method shows promise for use as an epidemiological tool to document cyclic progesterone increase. Further validation relative to daily transvaginal ultrasound is required.


Direct-to-participant feedback and awareness of bone mineral density testing  results in a population-based sample of mid-aged Canadians

Abstract:
This population-based study of mid-aged Canadians assessed awareness of diagnosis by bone mineral density (BMD) following dual-energy X-ray absorptiometry (DXA) testing and compared the effects of feedback only to the physician with direct-to-participant feedback. Poor recall of osteoporosis results was observed irrespective of the feedback destination, but direct-to-participant feedback improved recall of borderline or normal results.
Introduction: BMD testing provides information about fracture risk. This study assessed whether awareness of results, in a random population sample of mid-aged Canadians, differed if results were provided to physicians only or directly to participants.

Methods: Prospective cohort study of 2,678 women and men aged 40-60 years from the Canadian Multicentre Osteoporosis Study. Participants completed hip and spine DXA and interviewer-administered questionnaires regarding demographics and osteoporosis risk factors. Lateral spine X-rays were conducted on those > or =50 years of age. All test results were reported to the participant, the family physician or both. Associations between BMD results, feedback destination and correct self-report results, 3 years later, were assessed using logistic regression while adjusting for potential confounders.

Results: Only 25% of men and 33% of women correctly reported their osteoporosis diagnoses. Direct-to-participant vs. physician-only reports did not improve recall of osteoporosis diagnosis but improved recall of borderline or normal BMD. Older (vs. younger) men and men with prevalent vertebral fractures demonstrated better recall of their osteoporosis diagnosis.

Conclusions: Recall of low BMD results was poor, despite direct-to-participant feedback and even in the presence of other osteoporosis risk factors. Direct-to-participant feedback may improve awareness of borderline or normal BMD results.

Osteoporosis International : a Journal Established As Result of Cooperation  Between the European Foundation for Osteoporosis and the National Osteoporosis  Foundation of the USA


Effects of intrapartum oxytocin administration and epidural analgesia on the concentration of plasma oxytocin and prolactin, in response to suckling during the second day postpartum

Abstract:
BACKGROUND: Oxytocin and prolactin stimulate milk ejection and milk production during breastfeeding. The aim of the present study was to make a detailed analysis of maternal release of oxytocin and prolactin in response to breastfeeding during the second day postpartum in mothers who had received oxytocin either intravenously for stimulation of labor or intramuscularly for prevention of postpartum hemorrhage and/or epidural analgesia or those who had received no such treatment in connection with birth.

METHODS: In a descriptive comparative study plasma oxytocin and prolactin concentrations were measured in response to suckling during the second day postpartum in women who had received intravenous intrapartum oxytocin (n = 8), intramuscular postpartum oxytocin (n = 13), or epidural analgesia, either with (n = 14) or without (n = 6) intrapartum oxytocin infusion, and women who received none of these interventions (n = 20). Hormone levels were analyzed by enzyme immunoassay.

RESULTS: All mothers showed a pulsatile oxytocin pattern during the first 10 minutes of breastfeeding. Women who had received epidural analgesia with oxytocin infusion had the lowest endogenous median oxytocin levels. The more oxytocin infusion the mothers had received during labor, the lower their endogenous oxytocin levels were during a breastfeeding during the second day postpartum. A significant rise of prolactin was observed after 20 minutes in all women, but after 10 minutes in mothers having received oxytocin infusion during labor. In all women, oxytocin variability and the rise of prolactin levels between 0 and 20 minutes correlated significantly with median oxytocin and prolactin levels.

CONCLUSION: Oxytocin, released in a pulsatile way, and prolactin were released by breastfeeding during the second day postpartum. Oxytocin infusion decreased endogenous oxytocin levels dose-dependently. Furthermore, oxytocin infusion facilitated the release of prolactin. Epidural analgesia in combination with oxytocin infusion influenced endogenous oxytocin levels negatively.

Breastfeeding medicine : the official journal of the Academy of Breastfeeding Medicine


Obesity in pregnancy: risks and management

Abstract: Maternal obesity is now considered one of the most commonly occurring risk factors seen in obstetric practice. Compared with women with a healthy pre-pregnancy weight, women with obesity are at increased risk of miscarriage, gestational diabetes, preeclampsia, venous thromboembolism, induced labour, caesarean section, anaesthetic complications and wound infections, and they are less likely to initiate or maintain breastfeeding. Babies of obese mothers are at increased risk of stillbirth, congenital anomalies, prematurity, macrosomia and neonatal death. Intrauterine exposure to obesity is also associated with an increased risk of developing obesity and metabolic disorders in childhood. This article reviews the prevalence of obesity in pregnancy and the associated maternal and fetal complications. Recommendations and suggestions for pre-conception, antenatal and postnatal care of women with obesity are presented, and current research in the UK and future research priorities are considered.


Risk factors according to estrogen receptor status of breast cancer patients in  Trivandrum, South India

Paolo Boffetta

Centre International de Recherche sur le Cancer

Anitha Mathews

Regional Cancer Center, Thiruvananthapuram

Abstract: Estrogen receptor (ER) status is an important biomarker in defining subtypes of breast cancer differing in antihormonal therapy response, risk factors and prognosis. However, little is known about association of ER status with various risk factors in the developing world. Our case-control study done in Kerala, India looked at the associations of ER status and risk factors of breast cancer. From 2002 to 2005, 1,208 cases and controls were selected at the Regional Cancer Center (RCC), Trivandrum, Kerala, India. Information was collected using a


Laparoscopic management of endometriosis: comprehensive review of best evidence

Abstract:
STUDY Objective: To provide a comprehensive review of the best evidence available in the laparoscopic management of endometriosis for pain and/or fertility and to provide practical recommendations based on this information.
Design: Review article of randomized controlled trials.

Patients: Women with endometriosis.

Methods: A systematic search was performed of the Cochrane Library and MEDLINE database for randomized controlled trials relating only to laparoscopic management of endometriosis. The information from 7 Cochrane review articles and 35 original randomized trials is presented in a clinically relevant question-and-answer format.

Conclusions: Awareness of endometriosis as a disease with substantial morbidity is vitally important. Laparoscopic treatment of endometriosis is beneficial for reducing pain and improving fertility. Laparoscopic presacral neurectomy, but not laparoscopic uterosacral nerve ablation, is a useful adjunct to conservative surgery for endometriosis in patients with a midline component of pain. Preoperative hormonal suppression with gonadotropin-receptor hormone analogue may be helpful in decreasing endometriosis disease scores. Postoperative hormonal suppression with either a gonadotropin-receptor hormone analogue or progestin (including the levonorgestrel intrauterine system) may be helpful in reducing pain and increasing time to recurrence of symptoms. Excisional cystectomy is the preferred method to treat endometrial cysts for both pain and fertility and may be aided by the use of mesna and initial circular excision. An absorbable adhesion barrier (Interceed), 4% icodextrin solution (Adept), and a viscoelastic gel (Oxiplex/AP, FzioMed, Inc., San Luis Obispd, CA; not available in the United States) are safe and effective products to help prevent adhesions in laparoscopic surgery to treat endometriosis.

Journal of Minimally Invasive Gynecology


Contemporary neonatal outcome following rupture of membranes prior to 25 weeks with prolonged oligohydramnios

Abstract:
BACKGROUND: Prolonged oligohydramnios following early preterm prelabour rupture of membranes (PPROM) is traditionally associated with high neonatal mortality and significant risk of pulmonary hypoplasia. However, recent evidence points to an apparent improvement in outcome.

AIMS: To document current neonatal outcomes following rupture of membranes prior to 25 weeks with severe persistent oligohydramnios and a latency to delivery of at least 14 days.

METHODS: A retrospective case note analysis over a 28-month period at Saint Luc University Hospital, Brussels.

RESULTS: From 23 pregnancies that were complicated by PPROM prior to 25 weeks, 15 infants were born after 24 weeks with a latency of more than 14 days and persistent oligohydramnios. Nine infants (60%) had severe respiratory failure and clinical signs compatible with pulmonary hypoplasia. Seven of these infants (78%) responded to high frequency ventilation and inhaled nitric oxide therapy with good clinical outcome but two died from severe respiratory failure. Five infants showed no clinical signs of pulmonary hypoplasia and responded to conventional neonatal management. One of these infants died at 77 days of age of necrotising enterocolitis. One infant was not resuscitated and died within minutes of birth, following prior discussion with the perinatal team and the parents. Survivors in this high-risk group (73%) had low morbidity at the time of discharge.

SUMMARY: The favourable neonatal survival and morbidity figures are in keeping with recent published evidence. This study confirms improved outcome even amongst the highest risk infants with documented persistent oligohydramnios.


In vitro fertilization availability and utilization in the United States: a study of demographic, social, and economic factors

Abstract:
Objective: To characterize the demographic correlates of IVF availability and utilization.
Design: Demographic analysis of public data.
Setting: Each of the 50 states in the United States was used as a unit of analysis. PATIENT(S): Patients undergoing IVF, as demographically estimated. INTERVENTION(S): Publicly available data were collected through the Society for Assisted Reproductive Technology and the Centers for Disease Control. The US Census Bureau data were collected by using software available from the Centers for Disease Control. MAIN OUTCOME MEASURE(S): The number of physicians performing IVF and the number of IVF cycles per 100,000 reproductive-age women were used to estimate IVF availability and utilization. RESULT(S): In 2005, 1,031 providers performed 98,242 fresh IVF cycles in 430 centers. Overall availability was 2.5 IVF physicians per 100,000, and utilization was 236 IVF cycles per 100,000. Availability and utilization of IVF were highly correlated. Mean IVF availability and utilization were significantly higher in states with IVF insurance coverage. In adjusted analyses, IVF availability correlated positively with mandated insurance coverage, percentage of single persons, and median income. Utilization of IVF correlated with IVF availability, percentage urbanization, and percentage of individuals >or=25 years of age who had a bachelor's degree. CONCLUSION(S): Lower rates of IVF utilization in some states are correlated with a lack of insurance coverage and decreased availability of physicians providing this service.


Abnormal uterine bleeding: a focus on polycystic ovary syndrome

Abstract: Abnormal uterine bleeding imposes major medical, social and financial problems for women, their families and the health services. Abnormal uterine bleeding refers to the regularity, frequency, duration and volume of bleeding. Irregular menstrual bleeding is most common at the extremes of reproductive life, in the initial 12-18 months after menarche and 5-6 years before the menopause begins. In Australia, the estimated cost of investigating and managing heavy menstrual bleeding alone is approximately AUS $6 million per annum. This article addresses the common causes of irregular bleeding in preand peri-menopausal women and presents an investigational approach.


Cohort comparison of two fertility awareness methods of family planning

Abstract:
Objective: To determine if an electronic hormonal fertility monitor aided method (EHFM) of family planning is more effective than a cervical mucus only method (CMM) in helping couples to avoid pregnancy.

Study Design: Six hundred twenty-eight women were taught how to avoid pregnancy with either the EHFM (n=313) or the CMM (n = 315). Both methods involved standardized group teaching and individual follow-up. All pregnancies were reviewed and classified by health professionals. Correct use and total unintended pregnancy rates over 12 months of use were determined by survival analysis. Comparisons of unintended pregnancies between the 2 methods were made by use of the Fisher exact test.

Results: There were a total of 28 unintended pregnancies with the EFHM and 41 with the CMM. The 12-month correct use pregnancy rate of the monitor-aided method was 2.0%, and the total pregnancy rate was 12.0%. In comparison, the 12-month correct use pregnancy rate of the CMM was 3.0%, and the total pregnancy rate was 23.0%. There was a significant difference in total pregnancies between the 2 groups (p<0.05).

Conclusion: EFHM is more effective than CMM. Further research is needed to verify the results.


Comparison of text versus video for teaching laparoscopic knot tying in the  novice surgeon: a randomized, controlled trial

Abstract:
Background: Video seems advantageous over traditional text as an educational tool in conceptually-based procedures such as laparoscopy. However, this has never been tested directly.

Objective: The purpose of this study was to compare the use of text versus video as an educational tool for laparoscopic training, through a randomized controlled trial.

Study Design: Prospective, randomized, controlled clinical trial (Canadian Task Force classification I).

Methods: Eighty (n = 80) medical students, who had no experience with tying a laparoscopic intracorporeal knot, were randomly taught to do so by either reading a text with accompanying pictures (n = 40) or watching a short video with audio of comparable content (n = 40). The participants were allowed to review the material for as long as they needed to achieve understanding of the procedure. They were then asked to tie a laparoscopic square knot in a box trainer, with a limit time of 15 minutes. Time to review the educational material(s), time to tie the knot(s), numbers of attempts at the task (n), and numbers of those who expressed understanding of the task (n) were recorded.

Results: The number of participants who were able to complete the knot (n = 14 text v. n = 18 video, p = 0.49) and the average time needed for completion (479 s text v.494 s video, p = 0.38) were not statistically different in the two groups. However, time to review the material (407 s text v. 258 s video, p < 0.001), number of attempts at the task (15 text v. 5 video had n>2 attempts, p = 0.01), and number of those who expressed understanding when they could not complete the task (35% text v. 59% video, p = 0.047) were statistically different.

Conclusions: This is the first randomized trial evaluating video alone as an educational tool in laparoscopic training. It demonstrates that video is superior to text in achieving superior conceptual understanding, without improving operative times. Understanding through video instruction cannot make up for a lack of technical ability in novice surgeons.


Postoperative procedures for improving fertility following pelvic reproductive surgery

Abstract:
BACKGROUND: Hydrotubation with oil-soluble contrast media for unexplained infertility and adhesiolysis for infertility due to peritubal adhesions are primary procedures that are of recognised benefit. It is less clear whether postoperative procedures such as hydrotubation or second-look laparoscopy with adhesiolysis are beneficial following pelvic reproductive surgery.

OBJECTIVES: To assess the value of postoperative hydrotubation and second-look laparoscopy with adhesiolysis following female pelvic reproductive surgery.

SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group Specialised Register (August 2008), Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2007, Issue 2), MEDLINE (1966 to August 2008), EMBASE (1980 to August 2008), PsycINFO (1967 to August 2008), Current Contents (1993 to August 2008), Biological Abstracts (1969 to August 2008), CINAHL (1982 to August 2008) and reference lists of identified articles.

SELECTION CRITERIA: All randomised controlled trials in which a postoperative procedure was compared with a control group following pelvic reproductive surgery were considered for inclusion in the review.

DATA COLLECTION AND ANALYSIS: Five randomised controlled trials were identified and included in this updated review. An attempt was made to obtain further information from the authors of all five trials. All trials were assessed for quality. The studied outcomes were pregnancy, live birth, ectopic pregnancy and miscarriage rates, and the rates of tubal patency and procedure-related complications. Review authors extracted the data independently and the odds ratios (OR) were estimated for these dichotomous outcomes.

MAIN RESULTS: Five randomised controlled trials were identified and included in this review. The odds of pregnancy (OR 1.12, 95% confidence interval (CI) 0.57 to 2.21) and live birth (OR 0.61, 95% CI 0.24 to 1.59) were not significantly different with postoperative hydrotubation versus no hydrotubation. The odds of pregnancy (OR 0.96, 95% CI 0.44 to 2.07) or live birth (OR 0.67, 95% CI 0.19 to 2.32) were also not significantly different with second-look laparoscopy and adhesiolysis versus no second-look laparoscopy. Whether hydrotubation was early or late and whether hydrotubation fluid contained steroid or not had no significant impact on the odds of pregnancy or live birth. Late antibiotic hydrotubation increased the odds of at least one patent fallopian tube when compared with early hydrotubation in women (OR 7.72, 95% CI 2.50 to 8.93). The odds of infective morbidity significantly increased with early hydrotubation when compared with late non-antibiotic hydrotubation (OR 4.72, 95% CI 2.50 to 8.93). When comparing late hydrotubation following tubal stent removal with early hydrotubation in women who had no tubal stenting, there was no significant difference in pregnancy or live birth rates.

AUTHORS' CONCLUSIONS: There is insufficient evidence to support the routine practice of hydrotubation or second-look laparoscopy following female pelvic reproductive surgery. The studies on which this conclusion is based were either of poor quality or underpowered. These interventions should be performed in the context of a good quality, adequately powered randomised controlled trial. Postoperative hydrotubation with fluid containing antibiotic may offer benefit over hydrotubation fluid without antibiotic following tubal surgery. A randomised controlled trial of postoperative hydrotubation with antibiotic-containing fluid versus no hydrotubation for improving fertility following tubal surgery is justified.

The Cochrane database of systematic reviews


Risk factors with breast cancer among women in Delhi

Abstract:
Background: The incidence of breast cancer is on the rise in India, breast cancer is the second most common malignancy in Indian women.

Aim: The aim of this study was to find out the association of various risk factors with breast cancer among women in Delhi. SETTINGS AND Design: This was a case-control study in Lok Nayak Hospital, Delhi. METHODS AND MATERIAL: 332 women were studied. Subjects were women with breast cancer (N = 115) and age matched Control subjects (N-217) without breast cancer, attending Lok Nayak Hospital during 2006. Subjects were interviewed using a pretested questionnaire. The risk factors studied were: age, parity, socioeconomic status, marital status, breast feeding, menarche, menopause, family history. STATISTICAL ANALYSIS: Data was expressed in proportion. RESULTS AND

Conclusions: Age of the patient ranged from 25 to 80 years. In this study, 69 (60%) cases and 127 (58.5%) controls were illiterate, the mean duration sum of total breast feeding for all children was 6.58 years in cases and 7.4 years in controls (OR = 1.91; 95% CI, 1.17 - 3.13) (P P P< 0.05). There was a significant difference between breast cancer cases and controls in relation to place of residence, occupation, marital status, body mass index and breast feeding.


Side effects from the copper IUD: do they decrease over time?

Abstract:
Background: The copper intrauterine device (IUD) can cause side effects in some women; increased uterine bleeding and pain may cause early removal. Because of simplified reporting from previous research, little is known about how side effects might change over time.

Study Design: This is a secondary analysis of a prospective study of 1947 first-time copper IUD users. Over a 1-year period, we collected detailed information on side effects and looked for trends using generalized mixed-effects regression modeling.

Results: During menses, most bleeding and pain side effects were found to decrease over time (p<.05). During intermenstrual intervals, overall spotting and pain complaints remained unchanged, but the number of days with these problems increased (p<.05). Serious side effects that prompted either a clinic visit or IUD removal had varied patterns over time, depending on the type of problem.

Conclusion: Side effects from the copper IUD can be troubling for both user and clinician. Some problems improve over time, while others do not. This information may be helpful in counseling women who are considering IUD use and current users who are contemplating IUD removal due to side effects.


Risk factors for triple-negative breast cancer in women under the age of 45  years

Abstract: Little is known about the etiologic profile of triple-negative breast cancer (negative for estrogen receptor/progesterone receptor/human epidermal growth factor), a breast cancer subtype associated with high mortality and inadequate therapeutic options. We undertook this study to assess the risk for triple-negative breast cancer among women 45 years of age and younger in relation to demographic/lifestyle factors, reproductive history, and oral contraceptive use. Study participants were ascertained in two previous population-based, case-control studies. Eligible cases included all primary invasive breast cancers among women ages 20 to 45 years in the Seattle-Puget Sound area, diagnosed between January 1983 and December 1992, for whom complete data was obtained for estrogen receptor, progesterone receptor, and human epidermal growth factor status (n = 897; including n = 187 triple-negative breast cancer cases). Controls were age matched and ascertained via random digit dialing. Oral contraceptive use > or =1 year was associated with a 2.5-fold increased risk for triple-negative breast cancer (95% confidence interval, 1.4-4.3) and no significantly increased risk for non-triple-negative breast cancer (P(heterogeneity) = 0.008). Furthermore, the risk among oral contraceptive users conferred by longer oral contraceptive duration and by more recent use was significantly greater for triple-negative breast cancer than non-triple-negative breast cancer (P(heterogeneity) = 0.02 and 0.01, respectively). Among women < or =40 years, the relative risk for triple-negative breast cancer associated with oral contraceptive use > or =1 year was 4.2 (95% confidence interval, 1.9-9.3), whereas there was no significantly increased risk with oral contraceptive use for non-triple-negative breast cancer among women < or =40 years, nor for triple-negative breast cancer or non-triple-negative breast cancer among women 41 to 45 years of age. In conclusion, significant heterogeneity exists for the association of oral contraceptive use and breast cancer risk between triple-negative breast cancer and non-triple-negative breast cancer among young women, lending support to a distinct etiology.

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


Combined oral contraceptive use and the risk of systemic lupus erythematosus

Abstract:
Objective: To assess whether the risk of incident systemic lupus erythematosus (SLE) is associated with the use of combined oral contraceptives (COCs), because studies of the link between exogenous hormonal exposure and the risk of SLE have produced conflicting results.

Methods: We conducted a population-based nested case-control study among women ages 18-45 years, using the UK's General Practice Research Database. All incident cases of SLE from 1994-2004 (n = 786) were identified in the database and matched with up to 10 controls (n = 7,817) among women without SLE at the time of the case's diagnosis.

Results: The adjusted rate ratio (RR) of incident SLE associated with any use of COC was 1.19 (95% confidence interval [95% CI] 0.98-1.45), whereas with current use it was 1.54 (95% CI 1.15-2.07). The rate was particularly increased in current users who had only recently started COC use (RR 2.52, 95% CI 1.14-5.57) compared with longer-term current users (RR 1.45, 95% CI 1.06-1.99). The risk appeared to be particularly elevated with current exposure to firstor second-generation contraceptives (RR 1.65, 95% CI 1.20-2.26), and increasing with the dose of ethinyl estradiol (RR 1.42, 1.63, and 2.92 for < or =30 microg, 31-49 microg, and 50 microg, respectively).

Conclusion: The use of COCs is associated with an increased risk of SLE. This risk is particularly elevated in women who recently started contraceptive use, suggesting an acute effect in a small subgroup of susceptible women.


Epigenetics and environmental chemicals

Epigenetics and environmental chemicals

Abstract:
PURPOSE OF REVIEW: Epigenetics investigates heritable changes in gene expression occurring without changes in DNA sequence. Several epigenetic mechanisms, including DNA methylation, histone modifications, and microRNA expression, can change genome function under exogenous influence. Here, we review current evidence indicating that epigenetic alterations mediate toxicity from environmental chemicals.

RECENT FINDINGS: In-vitro, animal, and human investigations have identified several classes of environmental chemicals that modify epigenetic marks, including metals (cadmium, arsenic, nickel, chromium, and methylmercury), peroxisome proliferators (trichloroethylene, dichloroacetic acid, and TCA), air pollutants (particulate matter, black carbon, and benzene), and endocrine-disrupting/reproductive toxicants (diethylstilbestrol, bisphenol A, persistent organic pollutants, and dioxin). Most studies conducted so far have been centered on DNA methylation, whereas only a few investigations have studied environmental chemicals in relation to histone modifications and microRNA.

SUMMARY: For several exposures, it has been proved that chemicals can alter epigenetic marks, and that the same or similar epigenetic alterations can be found in patients with the disease of concern or in diseased tissues. Future prospective investigations are needed to determine whether exposed individuals develop epigenetic alterations over time and, in turn, which such alterations increase the risk of disease. Also, further research is needed to determine whether environmental epigenetic changes are transmitted transgenerationally.


Point of failure as a predictor of in vitro fertilization treatment discontinuation

Abstract: Among 2,245 women, those who experienced a chemical pregnancy that failed to progress to a clinically recognized pregnancy or a spontaneous abortion on their first IVF cycle were more likely to discontinue IVF treatment than those whose first cycle ended before embryo transfer or who did not have a positive pregnancy test after transfer. However, among women who did continue to a second IVF cycle, those who had at least a chemical pregnancy on the first cycle were more likely to have a live birth on the second attempt than those women who had failed before conception in the first cycle (34% success rate compared with 21%, respectively).


Cumulative pregnancy probabilities among couples with subfertility: effects of varying treatments

Abstract:
OBJECTIVE: To model the cumulative probability of pregnancy among couples with subfertility without a definitive diagnosis, according to different treatment strategies.

DESIGN: A beta distribution of fecundity was fitted that reproduced the cumulative probability of pregnancy in prospective studies of natural fertility, and this distribution was applied to simulated cohorts starting with one million couples each. Probabilities of pregnancy were generated for each cycle of each couple.

SETTING: Simulation study.

PATIENT(S): Hypothetic subfertile population.

INTERVENTION(S): After 2 or 4 years of attempting pregnancy and diagnostic evaluation to exclude anovulation, tubal obstruction, and severe male factor, simulated treatments were applied to the remaining nonpregnant couples, with treatment effects based on published literature.

MAIN OUTCOME MEASURE(S): Simulated cumulative probability of pregnancy.

RESULT(S): Initially, the cumulative probability of pregnancy was highest for early treatment with IVF, but over time, conservative treatment or frequent intercourse approached the same cumulative probability.

CONCLUSION(S): In couples without clear indications for IVF, the main benefit of early IVF may be to shorten time to pregnancy, a benefit that must be weighed against costs and potential adverse outcomes. Couples should be encouraged to maintain regular intercourse to maximize chances of pregnancy, even after unsuccessful treatment attempts.


Triple-negative breast cancers are increased in black women regardless of age or  body mass index

Abstract:
Introduction: We investigated clinical and pathologic features of breast cancers (BC) in an unselected series of patients diagnosed in a tertiary care hospital serving a diverse population. We focused on triple-negative (Tneg) tumours (oestrogen receptor (ER), progesterone receptor (PR) and HER2 negative), which are associated with poor prognosis.

Methods: We identified female patients with invasive BC diagnosed between 1998 and 2006, with data available on tumor grade, stage, ER, PR and HER2 status, and patient age, body mass index (BMI) and self-identified racial/ethnic group. We determined associations between patient and tumour characteristics using contingency tables and multivariate logistic regression.

Results: 415 cases were identified. Patients were racially and ethnically diverse (born in 44 countries, 36% white, 43% black, 10% Hispanic and 11% other). 47% were obese (BMI > 30 kg/m2). 72% of tumours were ER+ and/or PR+, 20% were Tneg and 13% were HER2+. The odds of having a Tneg tumour were 3-fold higher (95% CI 1.6, 5.5; p = 0.0001) in black compared with white women. Tneg tumours were equally common in black women diagnosed before and after age 50 (31% vs 29%; p = NS), and who were obese and non-obese (29% vs 31%; p = NS). Considering all patients, as BMI increased, the proportion of Tneg tumours decreased (p = 0.08).

Conclusions: Black women of diverse background have 3-fold more Tneg tumours than non-black women, regardless of age and BMI. Other factors must determine tumour subtype. The higher prevalence of Tneg tumours in black women in all age and weight categories likely contributes to black women's unfavorable breast cancer prognosis.


Fertility awareness-based methods: another option for family planning

Abstract: Modern fertility awareness-based methods (FABMs) of family planning have been offered as alternative methods of family planning. Billings Ovulation Method, the Creighton Model, and the Symptothermal Method are the more widely used FABMs and can be more narrowly defined as natural family planning. The first 2 methods are based on the examination of cervical secretions to assess fertility. The Symptothermal Method combines characteristics of cervical secretions, basal body temperature, and historical cycle data to determine fertility. FABMs also include the more recently developed Standard Days Method and TwoDays Method. All are distinct from the more traditional rhythm and basal body temperature methods alone. Although these older methods are not highly effective, modern FABMs have typical-use unintended pregnancy rates of 1% to 3% in both industrialized and nonindustrialized nations. Studies suggest that in the United States physician knowledge of FABMs is frequently incomplete. We review the available evidence about the effectiveness for preventing unintended pregnancy, prognostic social demographics of users of the methods, and social outcomes related to FABMs, all of which suggest that family physicians can offer modern FABMs as effective means of family planning. We also provide suggestions about useful educational and instructional resources for family physicians and their patients.

Journal of the American Board of Family Medicine : JABFM


Defining the proliferative phase endometrial defect

Abstract:
OBJECTIVE: To evaluate proliferative phase endometrial development in a heterogeneous infertility population.

DESIGN: Retrospective study.

SETTING: University-based infertility practice.

PATIENT(S): Two hundred forty-six treatment cycles.

INTERVENTION(S): Clomiphene citrate or FSH ovarian stimulation, followed by IUI or IVF.

MAIN OUTCOME MEASURE(S): Endometrial thickness according to transvaginal ultrasonography; clinical pregnancy rate.

RESULT(S): Endometrial growth began from a nadir of approximately 4.5 mm on cycle day 4 and increased linearly to a plateau of approximately 10 mm on cycle day 9. This same pattern was observed in all cycles, regardless of pregnancy, drug, or underlying diagnosis. Follicle-stimulating hormone-stimulated cycles showed a significantly increased endometrial thickness compared with clomiphene citrate cycles (10.1 vs. 8.3 mm). Maximum endometrial thickness achieved showed a correlation with age, body mass index, and maximum E(2) level. Subjects who carried a primary diagnosis of polycystic ovary syndrome, endometriosis, or recurrent pregnancy loss all achieved a significantly lower peak endometrial thickness than control subjects. There was a trend toward increased endometrial thickness in cycles resulting in pregnancy compared with those not (10.1 vs. 9.6 mm, respectively).

CONCLUSION(S): Endometrial development follows a predictable pattern, with a plateau in growth at cycle day 9. Diseases associated with infertility manifest a proliferative phase defect that can be recognized clinically.


Metabolic and hormonal effects of myo-inositol in women with polycystic ovary syndrome: a double-blind trial

Abstract: To investigate the effects of treatment with Myo-inositol (an insulin sensitizing drug), on circulating insulin, glucose tolerance, ovulation and serum androgens concentrations in women with the Polycystic Ovary Syndrome (PCOS). Forty-two women with PCOS were treated in a double-blind trial with Myo-inositol plus folic acid or folic acid alone as placebo. In the group treated with Myo-inositol the serum total testosterone decreased from 99.5 +/- 7 to 34.8 +/- 4.3 ng/dl (placebo group: from 116.8 +/- 15 to 109 +/- 7.5 ng/dl; P = 0.003), and serum free testosterone from 0.85 +/- 0.1 to 0.24 +/- 0.33 ng/dl (placebo group: from 0.89 +/- 0.12 to 0.85 +/- 0.13 ng/dl; P = 0.01). Plasma triglycerides decreased from 195 +/- 20 to 95 +/- 17 mg/dl (placebo group: from 166 +/- 21 to 148 +/- 19 mg/dl; P = 0.001). Systolic blood pressure decreased from 131 +/- 2 to 127 +/- 2 mmHg (placebo group: from 128 +/- 1 to 130 +/-1 mmHg; P = 0.002). Diastolic blood pressure decreased from 88 +/- 1 to 82 +/- 3 mmHg (placebo group: from 86 +/- 1 to 90 +/- 1 mmHg; P = 0.001). The area under the plasma insulin curve after oral administration of glucose decreased from 8.54 +/- 1.149 to 5.535 +/- 1.792 microU/ml/min (placebo group: from 8.903 +/- 1.276 to 9.1 +/- 1.162 microU/ml/min; P = 0.03). The index of composite whole body insulin sensitivity (ISI comp) increased from 2.80 +/- 0.35 to 5.05 +/- 0.59 mg(-2)/dl(-2) (placebo group: from 3.23 +/- 0.48 to 2.81 +/- 0.54 mg(-2)/dl(-2); P < 0.002). 16 out of 23 women of Myo-inositol group ovulated (4 out of 19 in placebo group). Treatment of PCOS patients with Myo-inositol provided a decreasing of circulating insulin and serum total testosterone as well as an improvement in metabolic factors.

European review for medical and pharmacological sciences


Vocal cues of ovulation in human females

Abstract: Recent research has documented a variety of ovulatory cues in humans, and in many nonhuman species, the vocal channel provides cues of reproductive state. We collected two sets of vocal samples from 69 normally ovulating women: one set during the follicular (high-fertility) phase of the cycle and one set during the luteal (low-fertility) phase, with ovulation confirmed by luteinizing hormone tests. In these samples we measured fundamental frequency (pitch), formant dispersion, jitter, shimmer, harmonics-to-noise ratio and speech rate. When speaking a simple introductory sentence, women's pitch increased during high- as compared with low-fertility, and this difference was the greatest for women whose voices were recorded on the two highest fertility days within the fertile window (the 2 days just before ovulation). This pattern did not occur when the same women produced vowels. The high- versus low-fertility difference in pitch was associated with the approach of ovulation and not menstrual onset, thus representing, to our knowledge, the first research to show a specific cyclic fertility cue in the human voice. We interpret this finding as evidence of a fertility-related enhancement of femininity consistent with other research documenting attractiveness-related changes associated with ovulation.


Endometrial growth and uterine blood flow: a pilot study for improving endometrial thickness in the patients with a thin endometrium

Abstract:
OBJECTIVE: To examine whether thin endometria can be improved by increasing uterine radial artery (uRA) blood flow.

DESIGN: A prospective observational study.

SETTING: University hospital and city general hospital.

PATIENT(S): Sixty-one patients with a thin endometrium (endometrial thickness [EM] <8 mm) and high radial artery-resistance index of uRA (RA-RI >or=0.81).

INTERVENTION(S): Vitamin E (600 mg/day, n = 25), l-arginine (6 g/day, n = 9), or sildenafil citrate (100 mg/day, intravaginally, n = 12) was given.

MAIN OUTCOME MEASURE(S): EM and RA-RI were assessed by transvaginal color-pulsed Doppler ultrasound.

RESULT(S): Vitamin E improved RA-RI in 18 (72%) out of 25 patients and EM in 13 (52%) out of 25 patients. L-arginine improved RA-RI in eight (89%) out of nine patients and EM in six (67%) patients. Sildenafil citrate improved RA-RI and EM in 11 (92%) out of 12 patients. In the control group (n = 10), who received no medication to increase uRA-blood flow, only one (10%) patient improved in RA-RI and EM. The effect of vitamin E was histologically examined in the endometrium (n = 5). Vitamin E improved the glandular epithelial growth, development of blood vessels, and vascular endothelial growth factor protein expression in the endometrium.

CONCLUSION(S): Vitamin E, l-arginine, or sildenafil citrate treatment improves RA-RI and EM and may be useful for the patients with a thin endometrium.


Comparison of effects of ginger, mefenamic acid, and ibuprofen on pain in women with primary dysmenorrhea

Abstract:
OBJECTIVES: To compare the effects of ginger, mefenamic acid, and ibuprofen on pain in women with primary dysmenorrhea.

METHODS: This was a double-blind comparative clinical trial conducted from September 2006 to February 2007. Participants were 150 students (18 years old and over) with primary dysmenorrhea from the dormitories of two medical universities who were alternately divided into three equal groups. Students in the ginger group took 250 mg capsules of ginger rhizome powder four times a day for three days from the start of their menstrual period. Members of the other groups received 250 mg mefenamic acid or 400 mg ibuprofen capsules, respectively, on the same protocol. A verbal multidimensional scoring system was used for assessing the severity of primary dysmenorrhea. Severity of disease, pain relief, and satisfaction with the treatment were compared between the groups after one menstruation.

RESULTS: There were not significant differences between groups in baseline characteristics, p > 0.05. At the end of treatment, severity of dysmenorrhea decreased in all groups and no differences were found between the groups in severity of dysmenorrhea, pain relief, or satisfaction with the treatment, p > 0.05. No severe side effects occurred.

CONCLUSION: Ginger was as effective as mefenamic acid and ibuprofen in relieving pain in women with primary dysmenorrhea. Further studies regarding the effects of ginger on other symptoms associated with dysmenorrhea and efficacy and safety of various doses and treatment durations of ginger are warranted.

Journal of alternative and complementary medicine (New York, N.Y.)


Efficacy and Efficiency in Natural Family Planning Services

Abstract: Relatively few Catholic couples in the United States use modern methods of natural family planning (NFP). So too, few Catholic physicians and health professionals prescribe the use of NFP methods for their patients. Reasons for low use of NFP methods include their perceived low efficacy; the complexity of learning, using, and teaching these methods; and the prolonged (and often unnecessary) required abstinence. Newer and simplified methods of NFP have been developed by physicians and scientists that are less complex and use modern technologies of detecting fertility and communicating instructions. Catholic physicians and scientists need to continue to answer the call by the Holy Fathers (from Pius XII to Benedict XVI) to develop secure and scientifically sound methods of NFP.


Assisted reproductive technology and major structural birth defects in the United States

Abstract:
Background: With >1% of US births occurring following use of assisted reproductive technology (ART), it is critical to examine whether ART is associated with birth defects.

Methods: We analyzed data from the National Birth Defects Prevention Study, a population-based, multicenter, case-control study of birth defects. We included mothers of fetuses or live-born infants with a major birth defect (case infants) and mothers who had live-born infants who did not have a major birth defect (control infants), delivered during the period October 1997-December 2003. We compared mothers who reported ART use (IVF or ICSI) with those who had unassisted conceptions. Multiple logistic regression was used to adjust for the following confounders: maternal race/ethnicity, maternal age, smoking and parity; we stratified by plurality.

Results: ART was reported by 1.1% of all control mothers, and by 4.5% of control mothers 35 years or older. Among singleton births, ART was associated with septal heart defects (adjusted odds ratio [aOR] = 2.1, 95% confidence intervals [CI] 1.1-4.0), cleft lip with or without cleft palate (aOR = 2.4, 95% CI 1.2-5.1), esophageal atresia (aOR = 4.5, 95% CI 1.9-10.5) and anorectal atresia (aOR = 3.7, 95% CI 1.5-9.1). Among multiple births, ART was not significantly associated with any of the birth defects studied.

Conclusions: These findings suggest that some birth defects occur more often among infants conceived with ART. Although the mechanism is not clear, couples considering ART should be informed of all potential risks and benefits.


Cumulative live-birth rates after in vitro fertilization

Abstract: BACKGROUND: Outcomes of in vitro fertilization (IVF) treatment are traditionally reported as pregnancies per IVF cycle. However, a couple's primary concern is the chance of a live birth over an entire treatment course. METHODS: We estimated cumulative live-birth rates among patients undergoing their first fresh-embryo, nondonor IVF cycle between 2000 and 2005 at one large center. Couples were followed until either discontinuation of treatment or delivery of a live-born infant. Analyses were stratified according to maternal age and performed with the use of both optimistic and conservative methods. Optimistic methods assumed that patients who did not return for subsequent IVF cycles would have the same chance of a pregnancy resulting in a live birth as patients who continued treatment; conservative methods assumed no live births among patients who did not return. RESULTS: Among 6164 patients undergoing 14,248 cycles, the cumulative live-birth rate after 6 cycles was 72% (95% confidence interval [CI], 70 to 74) with the optimistic analysis and 51% (95% CI, 49 to 52) with the conservative analysis. Among patients who were younger than 35 years of age, the corresponding rates after six cycles were 86% (95% CI, 83 to 88) and 65% (95% CI, 64 to 67). Among patients who were 40 years of age or older, the corresponding rates were 42% (95% CI, 37 to 47) and 23% (95% CI, 21 to 25). The cumulative live-birth rate decreased with increasing age, and the age-stratified curves (< 35 vs. > or = 40 years) were significantly different from one another (P<0.001). CONCLUSIONS: Our results indicate that IVF may largely overcome infertility in younger women, but it does not reverse the age-dependent decline in fertility.