Immunosuppression in Human Decidua Against Natural Killer Cells
Daya S et al., 2010Am J Obstet Gynecol
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Estrogen therapy and risk of breast cancer in postmenopausal women: a case-control study and results of a multivariate analysis
Lumachi F et al., 2010Menopause
Several randomized trials and observational studies show that the use of hormone therapy (HT) increases the risk of breast cancer (BC). The aim of this study was to assess the effects of exposure to both HT and oral contraceptives (OCs) on BC risk in postmenopausal women, all residing in the same metropolitan area. Data regarding a series of 238 consecutive postmenopausal women with infiltrating ductal carcinoma (cases) and 255 randomly selected age-matched healthy women (controls) were reviewed. Odds ratios for no breast-feeding and HT and OC use were 1.82 (95% CI, 1.20-2.77), 2.49 (95% CI, 1.73-3.58), and 2.06 (95% CI 1.14-3.70), respectively. Four independent variables (years between menarche and menopause, breast-feeding, OC use, and HT use) were included in the final multivariate analysis using logistic regression. The cumulative odds ratio calculated from the observed versus predicted values, obtained using the logistic regression function, was 4.55 (95% CI, 2.13-9.71), whereas the cumulative risk of common exposure to both OCs and HT was 2.77 (95% CI, 1.44-5.32). The logistic model correctly classified 67.5% (95% CI, 63.2-71.5) of cases. The receiver operating characteristic (ROC) curve of the complete logistic function showed a fair area of accuracy (0.77; 95% CI, 0.72-0.81). Our results show that the risk of common exposure to both OCs and HT increases in women with other risk factors. However, several parameters traditionally considered in epidemiological studies do not have the same weight in each local community, suggesting the need to create different models to correctly select the high-risk population.
Relationship of omega-3 and omega-6 fatty acids with semen characteristics, and anti-oxidant status of seminal plasma: a comparison between fertile and infertile men
Safarinejad MR et al., 2010Clinical nutrition (Edinburgh, Scotland)
BACKGROUND & Fatty acid (FA) composition of the spermatozoa may be an important determinant of fertility. The aim was to evaluate polyunsaturated fatty acid (PUFA) composition of the blood plasma and spermatozoa in infertile men with idiopathic oligoasthenoteratozoospermia (OAT). Eighty-two infertile men with idiopathic OAT and seventy-eight fertile men defined according to semen concentration and proven fertility were enrolled in the study. The semen parameters were assessed according to World Health Organization criteria; three omega-3 fatty acids--alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and two omega-6 fatty acids--linoleic acid (LA) and arachidonic acid (AA) concentrations were measured in blood plasma and spermatozoa; and the seminal plasma enzymatic antioxidant levels of catalase, and superoxide dismutase (SOD) were also assessed. Proven fertile men had higher blood and spermatozoa levels of omega-3 FAs compared with the infertile patients. The ratio of serum omega-6/omega-3 fatty acids was significantly higher in infertile (14.8+/-4.3) patients compared to fertile controls (6.3+/-2.2) (P=0.001). Additionally, levels of AA were higher and the omega-3 index (EPA+DHA) was lower in infertile subjects than in fertile controls (all P values<0.05). Infertile DHA EPA (6.4+/-2.9 and 12.0+/-4.9, respectively) than fertile men (3.3+/-1.8 and 6.7+/-2.6, respectively) (both P=0.001). A strong negative correlation DHA EPA ratios and total sperm count (r=-0.62, P=0.001 and r=-0.64, P=0.001, respectively), sperm motility (r=-0.63, P=0.001 and r=-0.61, P=0.001, respectively), and sperm morphology (r=-0.61, P=0.001, and r=-0.59, P=0.002, respectively). Infertile men had lower concentrations of omega-3 FAs in spermatozoa than fertile men. These results suggest that research should be performed to assess the potential benefits of omega-3 FA supplementation as a therapeutic approach in infertile men with idiopathic OAT.
Chronic endometritis is a frequent finding in women with recurrent implantation failure after in vitro fertilization
Johnston-MacAnanny EB et al., 2010Fertility and sterility
To determine the role of endometrial sampling for identification and treatment of chronic endometritis (CE) in patients undergoing IVF-ET who repeatedly failed to conceive despite the transfer of good-quality embryos. Retrospective chart review. University-based tertiary fertility center. PATIENT(S): Thirty-three patients with recurrent implantation failure (RIF) who underwent endometrial sampling and subsequent ET were analyzed based on immunohistochemically CE present on biopsy (group 1; n = 10) and CE absent on biopsy (group 2; n = 23). Patients with RIF undergoing IVF cycles during the same time period who did not have endometrial sampling were used as controls (group 3; n = 485). INTERVENTION(S): Endometrial sampling for CE and subsequent antibiotic treatment in affected patients followed by another IVF-ET cycle. RESULT(S): Chronic endometritis was identified in 30.3% of patients with RIF. Group 1 had lower implantation rates (11.5%) in the IVF cycle following treatment than did group 2 and group 3 (32.7% and 20.3%, respectively). Clinical pregnancy and ongoing pregnancy rates were similar across groups. CONCLUSION(S): Recurrent implantation failure warrants investigation of CE as a contributing factor. Women demonstrating CE on endometrial sampling have lower implantation rates in a subsequent IVF-ET cycle; however, there were no differences in subsequent clinical pregnancy or ongoing pregnancy rates after successful antibiotic treatment.
Dietary patterns in Canadian men and women ages 25 and older: relationship to demographics, body mass index, and bone mineral density
Lisa Langsetmo et al., 2010BMC Musculoskelet Disord
Previous research has shown that underlying dietary patterns are related to the risk of many different adverse health outcomes, but the relationship of these underlying patterns to skeletal fragility is not well understood. The objective of the study was to determine whether dietary patterns in men (ages 25-49, 50+) and women (pre-menopause, post-menopause) are related to femoral neck bone mineral density (BMD) independently of other lifestyle variables, and whether this relationship is mediated by body mass index. We performed an analysis of 1928 men and 4611 women participants in the Canadian Multicentre Osteoporosis Study, a randomly selected population-based longitudinal cohort. We determined dietary patterns based on the self-administered food frequency questionnaires in year 2 of the study (1997-99). Our primary outcome was BMD as measured by dual x-ray absorptiometry in year 5 of the study (2000-02). We identified two underlying dietary patterns using factor analysis and then derived factor scores. The first factor (nutrient dense) was most strongly associated with intake of fruits, vegetables, and whole grains. The second factor (energy dense) was most strongly associated with intake of soft drinks, potato chips and French fries, certain meats (hamburger, hot dog, lunch meat, bacon, and sausage), and certain desserts (doughnuts, chocolate, ice cream). The energy dense factor was associated with higher body mass index independent of other demographic and lifestyle factors, and body mass index was a strong independent predictor of BMD. Surprisingly, we did not find a similar positive association between diet and BMD. In fact, when adjusted for body mass index, each standard deviation increase in the energy dense score was associated with a BMD decrease of 0.009 (95% CI: 0.002, 0.016) g/cm(2) for men 50+ years old and 0.004 (95% CI: 0.000, 0.008) g/cm(2) for postmenopausal women. In contrast, for men 25-49 years old, each standard deviation increase in the nutrient dense score, adjusted for body mass index, was associated with a BMD increase of 0.012 (95% CI: 0.002, 0.022) g/cm(2). In summary, we found no consistent relationship between diet and BMD despite finding a positive association between a diet high in energy dense foods and higher body mass index and a strong correlation between body mass index and BMD. Our data suggest that some factor related to the energy dense dietary pattern may partially offset the advantages of higher body mass index with regard to bone health.
Variations in body mass index of users of depot-medroxyprogesterone acetate as a contraceptive
Pantoja M et al., 2010Contraception
Weight gain is a frequent reason for discontinuing the contraceptive with depot-medroxyprogesterone acetate (DMPA). This 3-year retrospective cohort study assessed body mass index (BMI; kg/m(2)) variations in 379 current or past DMPA users compared to TCu380A intrauterine device (IUD) users matched for age and BMI, categorized into G1 (normal weight), G2 (overweight) or G3 (obese) according to baseline BMI. Variations in weight and BMI were evaluated using analysis of variance. BMI increased progressively in all groups but significantly more in G1 and G2 DMPA users compared to nonusers and according to duration of use. In the G3 subgroup, weight trends were similar in the DMPA and IUD users. Normal and overweight women increased BMI with DMPA use; however, obese women did not increase weight. Weight increase in DMPA users could be associated with metabolic alterations related to duration of use in normal and overweight women and to alterations already present in obese women. Prospective studies are required to determine triggering factors. DMPA use or=30.
Progesterone function in human endometrium: clinical perspectives
Young SL et al., 2010Semin Reprod Med
Progesterone is essential for endometrial receptivity and successful establishment of pregnancy. Either an insufficient progesterone concentration or an insufficient response to progesterone, therefore can lead to infertility and pregnancy loss. Assessment of the role that either progesterone insufficiency or inadequate progesterone response plays in human reproductive failure has been difficult to assess because serum progesterone concentrations fluctuate markedly, limiting the ability to characterize sufficiency of progesterone, and there are no highly reliable markers of endometrial function available. Recent evidence demonstrates exquisite sensitivity of normal endometrium to very low levels of progesterone stimulation, suggesting that progesterone insufficiency should not be a common cause of reproductive failure. Further evidence suggests that women with endometriosis, and possibly polycystic ovarian syndrome, have an altered progesterone response, which may explain some of the clinical features of these disorders and supports the hypothesis that progesterone resistance underlies some cases of human reproductive failure.
Use of oral contraceptives in pregnancy and major structural birth defects in offspring
Waller DK et al., 2010Epidemiology
Oral contraceptives (OCs) are the most commonly used reversible contraceptive method among US women. Although the majority of previous studies have reported no association between OC use during pregnancy and birth defects, some studies have reported increased occurrence of neural tube defects, limb reduction defects, and urinary tract anomalies. We assessed OC use among mothers who participated in the multisite, case-control, National Birth Defects Prevention Study. Mothers of 9986 infants with 32 types of birth defects and 4000 infants without birth defects were included. Maternal OC use during the first 3 months of pregnancy was associated with an increased odds ratio for 2 of 32 hypoplastic left heart syndrome (adjusted odds ratio = 2.3 [95% confidence interval = 1.3-4.3) and gastroschisis (1.8 [1.3-2.7]). Previous reports of associations between OC use and specific types of anomalies were not corroborated. Given that associations were assessed for 32 types of birth defects, our findings of 2 increased associations between OC use and gastroschisis and hypoplastic left heart syndrome should be interpreted as hypotheses until they can be evaluated further. Overall, our findings are consistent with the majority of previous studies that found women who use OCs during early pregnancy have no increased risk for most types of major congenital malformations.
Use of four biomarkers to evaluate the risk of breast cancer subtypes in the women's contraceptive and reproductive experiences study
Ma H et al., 2010Cancer Res
Epidemiologic studies suggest that some hormone-related risk factors in breast cancer differentially influence risk for disease subtypes classified by the status of the estrogen and progesterone receptors (ER/PR). However, it remains unclear whether human epidermal growth factor receptor 2 (HER2) or p53 expression status further differentiates these exposure-risk group associations. We evaluated the associations of oral contraceptive (OC) use and reproductive factors with incident invasive breast cancer subtypes among 1,197 population-based cases and 2,015 controls from the Los Angeles County or Detroit components of the Women's Contraceptive and Reproductive Experiences Study. Case-control comparisons by ER/PR/HER2/p53 status were conducted by multivariable polychotomous unconditional logistic regression methods. We found that OC use was not associated with any breast cancer subtype as defined by ER/PR/HER2/p53 status, except for a 2.9-fold increased risk of so-called triple-negative tumors (ER(-)/PR(-)/HER2(-)) among women of 45 to 64 years of age who started OC use before age 18. Parity was associated with a decreased risk of luminal A (ER(+) or PR(+), HER2(-)), luminal B (ER(+) or PR(+)/HER2(+)), and ER(-)/PR(-)/HER2(+) tumors. Age at first full-term pregnancy was positively associated with luminal A tumors among older women. Neither of these reproductive factors was associated with triple-negative tumors. Long duration of breast-feeding lowered the risk of triple-negative and luminal A tumors. p53 status did not define further differential risk patterns. Our findings offer evidence of differences in the hormone-related risk factors between triple-negative cancers and other ER/PR/HER2-defined subtypes of breast cancer.
[Retrospective studies of pregnancies after assisted medical reproduction from 2001-2009 and Central Hospital in Luxembourg (part 2)]
Arendt J et al., 2010Bulletin de la Societe des sciences medicales du Grand-Duche de Luxembourg
The first chapter analyses the ART methods of the Centre Hospitalier of Luxembourg, in the department of reproductive medicine between 2001 and 2009. The second chapter examines the techniques individually, their influence on pregnancy outcomes, the complications on offsprings and their health. The results coincide with literature in that risks are acceptable as long as good medical and biological conditions are maintained. Multiple pregnancies remain the most frequent complication, particularly once out of IVF. These are analysed separately as well as the pregnancies after egg and semen donation.
Effects of oral, vaginal, and transdermal hormonal contraception on serum levels of coenzyme q(10), vitamin e, and total antioxidant activity
Palan PR et al., 2010Obstetrics and gynecology international
The use of the transdermal contraceptive patch is associated with greater bioavailability of ethinyl estradiol (EE) compared with contraceptive vaginal ring or oral contraceptives (OC). We compared the influences of three contraceptive methods (OC, vaginal ring, and transdermal patch) on serum levels of coenzyme Q(10), alpha-tocopherol, gamma-tocopherol and total antioxidant capacity in premenopausal women. Blood samples from 30 premenopausal women who used hormonal contraception for at least 4 months were collected. Forty subjects who did not use any contraception were studied as control. Serum levels of coenzyme Q(10), alpha-tocopherol and gamma-tocopherol were measured by high-pressure liquid chromatography. Serum samples were also assayed for total antioxidant capacity (TAOC). Serum levels of coenzyme Q(10) and alpha-tocopherol were found to be significantly lower (P < .05) in all three contraceptive users compared with controls. Contraceptive patch users had the lowest levels of coenzyme Q(10) levels compared with normal subjects. Serum TAOC levels were significantly lower (P < .05) among the contraceptive user groups. Alterations in coenzyme Q(10) and alpha-tocopherol induced by hormonal contraception and the potential effect(s) of exogenous ovarian hormones should be taken into consideration in future antioxidant research.
The immune system in pregnancy: a unique complexity
Mor G et al., 2010American journal of reproductive immunology (New York, N.Y. : 1989)
Placental immune response and its tropism for specific viruses and pathogens affect the outcome of the pregnant woman's susceptibility to and severity of certain infectious diseases. The generalization of pregnancy as a condition of immune suppression or increased risk is misleading and prevents the determination of adequate guidelines for treating pregnant women during pandemics. There is a need to evaluate the interaction of each specific pathogen with the fetal/placental unit and its responses to design the adequate prophylaxis or therapy. The complexity of the immunology of pregnancy and the focus, for many years, on the concept of immunology of pregnancy as an organ transplantation have complicated the field and delayed the development of new guidelines with clinical implications that could help to answer these and other relevant questions. Our challenge as scientists and clinicians interested in the field of reproductive immunology is to evaluate many of the 'classical concepts' to define new approaches for a better understanding of the immunology of pregnancy that will benefit mothers and fetuses in different clinical scenarios.
Altered gene expression profiling in endometrium: evidence for progesterone resistance
Aghajanova L et al., 2010Seminars in reproductive medicine
Progesterone plays an important role in regulating multiple events in the uterus. It controls endometrial proliferation and differentiation, which are important for uterine function. Dysregulation of progesterone signaling leads to impaired physiological functions. Indeed, aberrant expression of progesterone-regulated genes in the endometrium has been implicated in several gynecologic disorders, including endometriosis, polycystic ovarian syndrome (PCOS), and endometrial hyperplasia. Although several investigators have analyzed eutopic endometrial expression of progesterone-target genes, the genesis and consequences of progesterone resistance remain unclear. We review evidence for progesterone resistance in endometrium of women with endometriosis, PCOS, and endometrial hyperplasia, and we identify possible mechanisms associated with reduced progesterone activity in endometrium of (some) women with these gynecologic disorders that have a significant impact on women's health and well-being.
Low dose naltrexone: side effects and efficacy in gastrointestinal disorders
Ploesser J et al., 2010International journal of pharmaceutical compounding
1. Int J Pharm Compd. 2010 Mar-Apr;14(2):171-3. side effects and efficacy in gastrointestinal disorders. Ploesser J(1), Weinstock LB, Thomas E. (1)St. Louis College of Pharmacy, St. Louis, Missouri. Use of low dose naltrexone has been advocated for a variety of medical problems. Only a few articles published in peer review effects of low dose naltrexone. The purpose of this frequency of adverse effects of low dose naltrexone treated for a variety of gastrointestinal disorders. to determine global efficacy in a retrospective survey. Patients (206) single gastroenterologist's clinical practice who were mailed a survey to evaluate the side effects and efficacy of naltrexone. Patients had either irritable bowel syndrome intestinal bacterial overgrowth, chronic idiopathic constipation, or inflammatory bowel disease. Patients with diarrhea were given 2.5 mg daily, constipation 2.5 mg twice daily, and inflammatory bowel disease 4.5 mg daily. In the patients who returned the survey, 47/121 (38.8%) had no side effects. 74/121 (61.2%) patients who had side effects, 58 complaints, and 32 had one or more gastrointestinal side effects. patients with side effects, 24/74 (32.4%) had short lived symptoms. naltrexone was terminated owing to side effects in 20/74 patients (27.0%). In 13 patients with idiopathic irritable bowel syndrome, 2 were markedly worse. In 85 patients with irritable bowel syndrome-small intestinal bacterial overgrowth, 15 were markedly improved, 32 were moderately worse, and 1 was markedly worse. In 12 patients with chronic constipation, 7 were markedly improved, 1 moderately improved, 1 was mildly improved, and 4 were unchanged. naltrexone frequently has side effects but in most is tolerable. be helpful for a member of patients with gastrointestinal disorders. 23965429
DIR Jahrbuch 2009 (Deutsches IVF-Register Annual Report 2009)
Deutsches IVF-Register e.V., 2010Deutsches IVF-Register Jahrbuch
Annual report (Jahrbuch) of the Deutsches IVF-Register (DIR) for treatment year 2009. DIR is the German national IVF/ICSI registry, founded 1982 — the oldest continuously operating ART registry. Voluntary professional-society database with high de-facto coverage of German fertility centres. Reports cycles, transfers, pregnancies and clinical outcomes by treatment type (IVF, ICSI, frozen embryo transfer, donor). German-language registry document. Used as a Phase B historical-archive source for the ART Registry Comparison study (cross-registry classification by reporting completeness on 7 framework dimensions).
CARTR 2010 Annual Report - 2009 Results from the Canadian ART Register
Canadian Fertility and Andrology Society, 2010CFAS
Canadian ART Register (CARTR) annual report for 2009. A total of 16,315 cycles was reported to CARTR. Voluntary professional society database operated by the Canadian Fertility and Andrology Society.
Retrospective Review: Outcomes from All Couples with 3 or More Recurrent Miscarriages Receiving Treatment from NaPro Fertility Clinic, Ireland 2010
Boyle PC et al., 2010
Couples presenting with 3 or more miscarriages fit the definition of recurrent miscarriage which affects 1% of those trying to conceive. Clinics based in Dublin and Galway use a multifactorial approach with NaProTechnology to evaluate and treat such couples. 355 couples with subfertility attended for 2+ consultations during 2010. 50 (14%) had 3+ miscarriages. Of 36 who conceived, 29 (80.6%) had live births, 4 (11.1%) miscarried, 2 (5.6%) had ectopic pregnancies. Average female age 37.5 years. Expected miscarriage rate for this population would be above 30-40%. A total miscarriage and ectopic rate of 16.7% per couple is encouraging. Women with recurrent miscarriage appear to have better than expected outcomes following a multifactorial NaPro treatment approach.
Assisted reproductive technology in Europe, 2006: results generated from European registers by ESHRE
de Mouzon J et al., 2010Human reproduction (Oxford, England)
22. Assisted reproductive technology in Europe, 2006: results generated from European registers by ESHRE. de Mouzon J(1), Goossens V, Bhattacharya S, Castilla JA, Ferraretti AP, Korsak V, Kupka M, Nygren KG, Nyboe Andersen A; European IVF-monitoring (EIM) Consortium, for the European Society of Human Reproduction and Embryology (ESHRE). Glozheni O, Strohmer H, Bogaerts K, Kyurkchiev S, Pelekanos M, Rezabek K, Erb K, Gissler M, de Mouzon J, Shojaei T, Buhler K, Tarlatzis B, Kosztolanyi G, Bjorgvinsson H, Mocanu E, Scaravelli G, Lejins V, Gudleviciene Z, Lazarevski S, Simic TM, Lambalk C, Hazekamp JT, Kuczynski W, Calhaz-Jorge C. (1)ESHRE Central Office, Meerstraat 60, B-1852 Grimbergen, Belgium. jacques.demouzon@inserm.fr In this 10th European IVF-monitoring (EIM) report, the results of assisted reproductive techniques from treatments initiated in Europe during 2006 are presented. Data were mainly collected from existing national registers. From 32 countries, 998 clinics reported 458 759 IVF (117 318), ICSI (232 844), frozen embryo replacement (FER, 86 059), egg donation (ED, 12 685), preimplantation genetic diagnosis/screening (6561), in vitro maturation (247) and frozen oocytes replacements (3498). Overall this represents a 9.7% increase in activity since 2005, which is partly due to an increase in registers (seven more countries with complete coverage). European data on intrauterine insemination using husband/partner's (IUI-H) and donor (IUI-D) semen were reported from 22 countries. A total of 134 261 IUI-H and 24 339 IUI-D cycles were included. In 20 countries, where all clinics reported to the IVF register, a total of 359 110 assisted reproductive technology (ART) cycles were performed in a population of 422.5 million, corresponding to 850 cycles per million inhabitants. For IVF, the clinical pregnancy rates per aspiration and per transfer were 29.0 and 32.4%, respectively. For ICSI, the corresponding rates were 29.9 and 33.0%. After IUI-H the delivery rate was 9.2% in women below 40. After IVF and ICSI the distribution of transfer of one, two, three and four or more embryos was 22.1, 57.3, 19.0 and 1.6%, respectively. Compared with 2005, fewer embryos were replaced per transfer, but significant national differences in practice were apparent. The proportion of singleton, twin and triplet deliveries after IVF and ICSI combined was 79.2, 19.9 and 0.9%, respectively. This gives a total multiple delivery rates of 20.8% compared with 21.8% in 2005 and 22.7% in 2004. IUI-H in women below 40 years of age resulted in 10.6% twin and 0.6% triplet pregnancies. Compared with previous years, the reported number of ART cycles in Europe has increased, pregnancy rates have increased marginally, even though fewer embryos were transferred and the multiple delivery rates have declined.
ACOG Practice Bulletin No. 110: noncontraceptive uses of hormonal contraceptives
ACOG, 2009Obstet Gynecol
Patients are often unaware of the non-contraceptive benefits of hormonal contraception. and this represents an opportunity for counseling (2). A brief list of some common non-contraceptive benefits is provided in Box I. Most hormonal contraceptives combine progestin for its contraceptive effects and an estrogen to stabilize the endometrium and reduce unwanted spocane. Users progestin-only hormonal contraceptives avoid the sile citects associated with the use of contraceptives containing estrogen. Progestin-only contraceptives often can be used in women when estrogen is contraindicated; however, unpredictable spotting may be problematic for some patients. Over time, this unwanted bleeding generally subsides and progestin-only methods may provide highly effective long-term contraception. Since oral contraceptives containing 150 micrograms or mestranol were introduced in ryo0, the dose of estrogen current bills may. . .
Molecular mechanism for human sperm chemotaxis mediated by progesterone
Teves ME et al., 2009PLoS One
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 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
Smith M et al., 2009Int J Gynecol Pathol
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%).
Health-related quality of life in Canadian adolescents and young adults: normative data using the SF-36
Wilma M Hopman et al., 2009Can J Public Health
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. 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. 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. 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. 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. 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
Livshits A et al., 2009Women's health (London, England)
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
Harvey AT et al., 2009J Psychosom Obstet Gynaecol
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.
Results of the live survey in Las Vegas, 2008, and the response of the AAGL
Pasic RP et al., 2009J Minim Invasive Gynecol
Maternal thyroid function during gestation is related to breech presentation at term
Kuppens SM et al., 2009Clin Endocrinol (Oxf)
To study the relationship between suboptimal maternal thyroid function during gestation and breech presentation at term. Prospective follow-up study during three trimesters of gestation. A total of 1058 Dutch Caucasian healthy pregnant women were prospectively followed from 12 weeks gestation until term (>or=37 weeks) delivery. 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. 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. 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
Wise LA et al., 2009Hum Reprod
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. 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. 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 null associations were observed before adjustment for BMI and weakly positive associations were observed after adjustment for BMI. 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
Gleicher N et al., 2009Reprod Biol Endocrinol
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. 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. 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. 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.
Oral contraceptive pill for primary dysmenorrhoea
Wong CL et al., 2009Cochrane Database of Systematic Reviews
Dysmenorrhoea (painful menstrual cramps) is common. Combined OCPs are recommended in the management of primary dysmenorrhoea. To determine the effectiveness and safety of combined oral contraceptive pills for the management of primary dysmenorrhoea. 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). RCTs comparing all combined OCPs with other combined OCPs, placebo, no management, or management with nonsteroidal anti-inflammatories (NSAIDs) were considered. 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 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' 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
Shah PS et al., 2009BJOG : an international journal of obstetrics and gynaecology
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. To systematically review the risk of an infant being born LBW/PT/SGA among women with history of I-TOP. Medline, Embase, CINAHL and bibliographies of identified articles were searched for English language studies. Studies reporting birth outcomes to mothers with or without history of induced abortion were included. 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. 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. 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.
Is preeclampsia an autoimmune disease?
Xia Y et al., 2009Clinical immunology (Orlando, Fla.)
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
Hitchcock CL et al., 2009Fertil Steril
Breast cancer risk assessments comparing Gail and CARE models in African-American women
Adams-Campbell LL et al., 2009Breast J
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
Han DY et al., 2009Mutat Res
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
Cai B et al., 2009Biometrics
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
El Khoudary SR et al., 2009J Womens Health (Larchmt)
Interstitial cystitis (IC) is a visceral pain syndrome with a profound impact on quality of life (QOL). The main aims of the (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. 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). 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 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. 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
Langsetmo L et al., 2009J Bone Miner Res
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
van Hylckama Vlieg A et al., 2009BMJ
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. Population based case-control study. Six participating anticoagulation clinics in the Netherlands (Amersfoort, Amsterdam, The Hague, Leiden, Rotterdam, and Utrecht). 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. 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. 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. 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
Lidegaard Ø et al., 2009BMJ
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. National cohort study. Denmark, 1995-2005. Danish women aged 15-49 with no history of cardiovascular or malignant disease. 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. 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). 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
George Ioannidis et al., 2009CMAJ
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. 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. 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). 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
Nijs M et al., 2009Fertility and Sterility
To test consumables and other products used during oocyte collection, sperm preparation, IUI, embryo culture, and IVF-embryo transfer for their possible reprotoxic properties. A prospective 4-year survey of reprotoxicity testing of consumables and other products used in assisted reproductive technologies (ART). 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): percentage progressive motility of test sample/percentage progressive motility of control sample after 24 and 96 hours. RESULT(S): Thirteen of 36 products 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
Maroun P et al., 2009The Australian & New Zealand journal of obstetrics & gynaecology
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. To investigate gastrointestinal symptoms in women with endometriosis and compare their frequency with that of the classical gynaecological symptoms. Systematic exploration of symptoms in a consecutive series of 355 women undergoing operative laparoscopy for suspected endometriosis. 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. Gastrointestinal symptoms are nearly as common as gynaecological symptoms in women with endometriosis and do not necessarily reflect bowel involvement.
Managing the complications associated with assisted reproductive technologies
Patchava S et al., 2009Minerva ginecologica
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
Wang H et al., 2009Obstet Gynecol Surv
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. Obstetricians & Gynecologists, Family Physicians. 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
Figueiredo JC et al., 2009Breast Cancer Res Treat
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
Wang LY et al., 2009Journal of Zhejiang University. Science. B
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.
Route of administration of contraceptives containing desogestrel/etonorgestrel and insulin sensitivity: a prospective randomized study
Cagnacci A et al., 2009Contraception
The study was conducted to investigate whether hormonal contraceptives administered via the oral and vaginal route exert a similar effect on insulin sensitivity (SI). 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. 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. 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
Tamura H et al., 2009Fertility and sterility
To summarize the role of melatonin in the physiology and pathophysiology of the ovary. Review of literature. 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
Durai R et al., 2009British 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
Jennifer L Bedford et al., 2009Eur J Obstet Gynecol Reprod Biol
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. 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 (A) all recorded temperatures, (B) wake-time adjusted temperatures, (C) temperatures within 2h of average wake-time, and (D) expert reviewed temperatures. 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). 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.