Sylvie Bérubé

Laparoscopic Surgery in Infertile Women with Minimal or Mild Endometriosis

Background Minimal or mild endometriosis is frequently diagnosed in infertile women. It is often treated by resection or ablation of the lesions, but whether this improves fertility has not been established. We carried out a randomized, controlled trial to determine whether laparoscopic surgery enhanced fecundity in infertile women with minimal or mild endometriosis. Methods We studied 341 infertile women 20 to 39 years of age with minimal or mild endometriosis. During diagnostic laparoscopy the women were randomly assigned to undergo resection or ablation of visible endometriosis or diagnostic laparoscopy only. They were followed for 36 weeks after the laparoscopy or, for those who became pregnant during that interval, for up to 20 weeks of pregnancy. Results Among the 172 women who had resection or ablation of endometriosis, 50 became pregnant and had pregnancies that continued for 20 weeks or longer, as compared with 29 of the 169 women in the diagnostic-laparoscopy group (cumulative probabilities, 30....BACKGROUND: Minimal or mild endometriosis is frequently diagnosed in infertile women. It is often treated by resection or ablation of the lesions, but whether this improves fertility has not been established. We carried out a randomized, controlled trial to determine whether laparoscopic surgery enhanced fecundity in infertile women with minimal or mild endometriosis. METHODS: We studied 341 infertile women 20 to 39 years of age with minimal or mild endometriosis. During diagnostic laparoscopy the women were randomly assigned to undergo resection or ablation of visible endometriosis or diagnostic laparoscopy only. They were followed for 36 weeks after the laparoscopy or, for those who became pregnant during that interval, for up to 20 weeks of pregnancy. RESULTS: Among the 172 women who had resection or ablation of endometriosis, 50 became pregnant and had pregnancies that continued for 20 weeks or longer, as compared with 29 of the 169 women in the diagnostic-laparoscopy group (cumulative probabilities, 30.7 percent and 17.7 percent, respectively; P=0.006 by the log-rank test). The corresponding rates of fecundity were 4.7 and 2.4 per 100 person-months (rate ratio, 1.9; 95 percent confidence interval, 1.2 to 3.1). Fetal losses occurred in 20.6 percent of all the recognized pregnancies in the laparoscopic-surgery group and in 21.6 percent of all those in the diagnostic-laparoscopy group (P=0.91). Four minor operative complications (intestinal contusion, slight tear of the tubal serosa, difficult pneumoperitoneum, and vascular trauma) were reported (three in the surgery group and one in the control group). CONCLUSIONS: Laparoscopic resection or ablation of minimal and mild endometriosis enhances fecundity in infertile women.

Genetic polymorphisms of the vitamin D binding protein and plasma concentrations of 25-hydroxyvitamin D in premenopausal women

BACKGROUND Vitamin D status, determined on the basis of 25-hydroxyvitamin D [25(OH)D] concentrations, is associated with the risk of several diseases. Vitamin D binding protein (DBP) is the major carrier of vitamin D and its metabolites, but the role of DBP single nucleotide polymorphisms (SNPs) on 25(OH)D concentrations is unclear. OBJECTIVE The objective was to evaluate the association of 2 DBP gene SNPs with 25(OH)D concentrations and explore whether such association varies according to the amount of vitamin D that needs to be transported. DESIGN This cross-sectional study included 741 premenopausal white women, mostly of French descent. Plasma 25(OH)D concentrations were measured by radioimmunoassay. DBP-1 (rs7041) and DBP-2 (rs4588) were genotyped with a Sequenom MassArray platform. Associations and interactions were modeled by using multivariate linear regression. RESULTS DBP-1 and DBP-2 SNPs were in strong linkage disequilibrium and were both associated with 25(OH)D concentrations. An additional copy of the rare allele of DBP-1 or DBP-2 was associated with lower 25(OH)D concentrations (beta = -3.29, P for trend = 0.0003; beta = -4.22, P for trend < 0.0001, respectively). These DBP polymorphisms explained as much of the variation in circulating 25(OH)D as did total vitamin D intake (r2 = 1.3% for DBP-1, r2 = 2.0% for DBP-2, and r2 < or = 1.2% for vitamin D intake). CONCLUSION Circulating 25(OH)D concentrations in premenopausal women are strongly related to DBP polymorphisms. Whether DBP rare allele carriers have a different risk of vitamin D-related diseases and whether such carriers can benefit more or less from dietary interventions, vitamin D supplementation, or sun exposure need to be clarified.

Insulin-Like Growth Factor-I, IGF-Binding Protein-3, and Mammographic Breast Density

Some studies have suggested that insulin-like growth factor (IGF) pathway is related to premenopausal breast density, one of the strongest known breast cancer risk factors. This study was designed specifically to test the hypothesis that higher levels of IGF-I and lower levels of IGF-binding protein (IGFBP)-3 are associated with high mammographic breast density among premenopausal but not among postmenopausal women. A total of 783 premenopausal and 791 postmenopausal healthy women were recruited during screening mammography examinations. Blood samples were collected at the time of mammography, and plasma IGF-I and IGFBP-3 levels were measured by ELISA. Mammographic breast density was estimated using a computer-assisted method. Spearmans partial correlation coefficients (rs) were used to evaluate the associations. Adjusted mean breast density was assessed by joint levels of IGF-I and IGFBP-3 using generalized linear models. Among premenopausal women, high levels of IGF-I and low levels of IGFBP-3 were independently correlated with high breast density (rs = 0.083; P = 0.021 and rs = −0.124; P = 0.0005, respectively). Correlation of IGF-I with breast density was stronger among women in the lowest tertile of IGFBP-3 than among those in the highest tertile of IGFBP-3 (rs = 0.138; P = 0.027 and rs = −0.039; P = 0.530, respectively). In contrast, the correlation of IGFBP-3 with breast density was stronger among women in the highest tertile of IGF-I than among those in the lowest tertile of IGF-I (rs = −0.150; P = 0.016 and rs = −0.008; P = 0.904, respectively). Women in the combined top tertile of IGF-I and bottom tertile of IGFBP-3 had higher mean breast density than those in the combined bottom tertile of IGF-I and top tertile of IGFBP-3 (53.8% versus 40.9%; P = 0.014). No significant association was observed among postmenopausal women. Our findings confirm that IGF-I and IGFBP-3 are associated with breast density among premenopausal women. They provide additional support for the idea that, among premenopausal women, these growth factors may affect breast cancer risk, at least in part, through their influence on breast tissue morphology as reflected on mammogram.

Vitamin D and Calcium Intakes from Food or Supplements and Mammographic Breast Density

Background: A better understanding of factors that affect breast density, one of the strongest breast cancer risk indicators, may provide important clues about breast cancer etiology and prevention. This study evaluates the association of vitamin D and calcium, from food and/or supplements, to breast density in premenopausal and postmenopausal women separately. Methods: A total of 777 premenopausal and 783 post-menopausal women recruited at two radiology clinics in Quebec City, Canada, in 2001 to 2002, completed a food frequency questionnaire to assess vitamin D and calcium. Breast density from screening mammograms was assessed using a computer-assisted method. Associations between vitamin D or calcium and breast density were evaluated using linear regression models. Adjusted means in breast density were assessed according to the combined daily intakes of the two nutrients using generalized linear models. Results: In premenopausal women, total intakes of vitamin D and calcium were inversely related to breast density (β = −1.4; P = 0.004 for vitamin D; β = −0.8; P = 0.0004 for calcium). In multivariate linear regression, simultaneous increments in daily total intakes of 400 IU vitamin D and 1,000 mg calcium were associated with an 8.5% (95% confidence interval, 1.8-15.1) lower mean breast density. The negative association between dietary vitamin D intake and breast density tended to be stronger at higher levels of calcium intake and vice versa. Among postmenopausal women, intakes of vitamin D and calcium were not associated with breast density. Conclusion: These findings show that higher intakes of vitamin D and calcium from food and supplements are related to lower levels of breast density among premenopausal women. They suggest that increasing intakes of vitamin D and calcium may represent a safe and inexpensive strategy for breast cancer prevention.

Characteristics Related to the Prevalence of Minimal or Mild Endometriosis in Infertile Women

The objective of this case-control study is to identify factors associated with the prevalence of minimal or mild endometriosis among infertile women. Cases (N = 329) were women diagnosed by laparoscopy with minimal or mild endometriosis and without any other factors explaining their infertility. Controls (N = 262) were women in whom the infertility remained unexplained after a diagnostic laparoscopy. Selected characteristics were documented by means of a face-to-face interview before the laparoscopy. The prevalence of minimal or mild endometriosis was higher in women age 25 years or older, in those who reported menarche at the age of 13 years [prevalence odds ratio (POR) = 1.63; 95% confidence interval (CI) = 1.02–2.60] or older (POR = 1.73; 95% CI = 1.07–2.78), menstrual cycles of 27 days or less (POR = 1.63; 95% CI = 1.02–2.60), or caffeine intake of 300 mg per day or more (POR = 1.33; 95% CI = 0.91–1.94). The prevalence of minimal or mild endometriosis was inversely related to body mass index. Parous women were less likely to have endometriosis (POR = 0.61; 95% CI = 0.39–0.96) than were nulliparous women. Education, duration of infertility, and smoking status were not related to the presence of endometriosis. (Epidemiology 1998;9:504–510)

Plasma Concentrations of Selected Organobromine Compounds and Polychlorinated Biphenyls in Postmenopausal Women of Quebec, Canada

Background Brominated flame retardants, especially polybrominated diphenyl ethers (PBDEs), have been widely used in North America, but little is known about the level of exposure of human populations to these compounds. Objectives We set out to assess the internal exposure of postmenopausal Canadian women to selected organobromine compounds and to investigate factors associated with this exposure. Methods We measured concentrations of four PBDEs, one polybrominated biphenyl, and for comparative purposes, 41 polychlorinated biphenyl (PCB) congeners in plasma samples from 110 healthy postmenopausal women who were recruited at a mammography clinic in 2003–2004. Results PBDE-47 was the major PBDE congener, with a mean (geometric) concentration of 8.1 ng/g lipids and extreme values reaching 1,780 ng/g. By comparison, the mean concentration of the major PCB congener (PCB-153) was 41.7 ng/g and the highest value was 177 ng/g. PBDEs 47, 99, and 100 were strongly intercorrelated, but weaker correlations were noted with PBDE-153. As the sum of PBDEs (∑PBDEs) increased, the relative contribution of PBDE-47 to the ∑PBDEs increased, whereas that of PBDE-153 decreased. PBDE-153 was the only brominated compound correlated to PCB-153. PBDE levels were not linked to any sociodemographic, anthropometric, reproductive, or lifestyle variables documented in the present study. Age and body mass index gain since the age of 18 years were significant predictors of PCB-153 plasma levels. Conclusion Our results suggest that exposure to PBDE-47 likely occurs through direct contact with the penta-PBDE formulation, whereas exposure to PBDE-153 may originate in part from the food chain.

Fecundity of Infertile Women with Minimal or Mild Endometriosis And Women with Unexplained Infertility

OBJECTIVE To assess whether infertile women with minimal or mild endometriosis have lower fecundity than women with unexplained infertility. DESIGN Prospective cohort study. SETTING Twenty-three infertility clinics across Canada. PATIENT(S) Three hundred thirty-one infertile women aged 20-39 years. INTERVENTION(S) Diagnostic laparoscopy for infertility. Infertile women with minimal or mild endometriosis (n = 168) were compared with women with unexplained infertility (n = 263). Both groups were managed expectantly. The women were followed up for 36 weeks after the laparoscopy or, for those who became pregnant, for up to 20 weeks of the pregnancy. MAIN OUTCOME MEASURE(S) Fecundity refers to the probability of becoming pregnant in the first 36 weeks after laparoscopy and carrying the pregnancy for > or = 20 weeks. The fecundity rate is the number of pregnancies per 100 person-months. RESULT(S) Fecundity was 18.2% in infertile women with minimal or mild endometriosis and 23.7% in women without endometriosis (log-rank test). The fecundity rate was 2.52 per 100 person-months in women with endometriosis and 3.48 per 100 person-months in women with unexplained infertility. The crude and adjusted fecundity rate ratios were 0.72 and 0.83 (95% confidence interval = 0.53-1.32), respectively. CONCLUSION(S) The fecundity of infertile women with minimal or mild endometriosis is not significantly lower than that of women with unexplained infertility.

Job strain and pregnancy-induced hypertension.

This paper presents the results of applying the case-specular method to two earlier studies of wire codes and childhood cancers (DA Savitz et al, Am J Epidemiol 1988;128:21-38, and SJ London et al, Am J Epidemiol 1991;9:923-937). The method compares the wire codes of case residences with the wire codes of specular residences constructed by switching the location of the case residence across the center of the street. The method was designed to discriminate between the magnetic field hypothesis, which postulates that childhood cancer is affected by magnetic fields and that wire codes are a proxy for magnetic fields, and the neighborhood hypothesis, which postulates that childhood cancer is affected by some characteristics of the neighborhood other than magnetic fields and that wire codes are a proxy for those characteristics. Although the results from the two applications of the method have limited precision, they support the results originally reported (odds ratios of around 2 for very high current configuration residences and childhood cancers) and do not support suggestions that the associations are due to confounding by socio-economic and neighborhood factors. The results leave open the question of whether or not control selection bias could have influenced the original associations, because there was no convincing evidence that the control-specular matrices were symmetric.In a case-control study we assessed whether exposure to high job strain during the first 20 weeks of pregnancy increases the risk of preeclampsia and gestational hypertension. Cases (128 with preeclampsia and 201 with gestational hypertension) and controls (N = 401) were primiparous women who had a paid occupation for at least 1 week during the first 20 weeks of their pregnancy and who delivered between 1984 and 1986 in 10 hospitals of Quebec, Canada. Based on their job title, we assigned women scores of psychological demand and decision latitude derived from the National Population Health Survey and classified these women as exposed to high (high demand, low latitude) versus low (low demand, high latitude) job strain. Women exposed to high job strain were more likely to develop preeclampsia [adjusted odds ratio (aOR) = 2.1; 95% confidence interval (CI) = 1.1-4.1] than women exposed to low job strain. The risk was quite similar for women exposed to a full-time, high strain job (> or =35 hours per week) (aOR = 2.0) than in a part-time, high strain job (aOR = 1.8). High job strain increased the risk of gestational hypertension slightly (aOR = 1.3; 95% CI = 0.8-2.2). These results indicate that women exposed to high job strain are at higher risk of developing preeclampsia and, to a lesser extent, gestational hypertension.

Genetic Polymorphisms Involved in Insulin-like Growth Factor (IGF) Pathway in Relation to Mammographic Breast Density and IGF Levels

The insulin-like growth factor (IGF) pathway is believed to play a role in carcinogenesis of the mammary gland. Single nucleotide polymorphisms (SNPs) of IGF-I, IGF-binding protein-3 (IGFBP-3), IGF receptor 1, insulin receptor substrate 1, and phosphoinositide-3-kinase, catalytic, β polypeptide genes, which are members of the IGF pathway, have been associated with risk of common cancers, breast density, and/or IGF levels but results remain inconclusive. Thus, we evaluated the association of 11 targeted IGF pathway SNPs with circulating IGF levels and mammographic breast density. Among 741 white premenopausal women, blood samples were collected at time of screening mammography, and plasma IGF-I and IGFBP-3 levels were measured by ELISA. Percent and absolute breast density were estimated using a computer-assisted method. Multivariate linear models were used to examine the associations. Women carrying increasing number of copies of the rare allele of IGF-I rs1520220 and rs6220 SNPs had increased percent breast density (Ptrend = 0.04 and 0.06, respectively). Carriers of increasing number of copies of the rare allele of phosphoinositide-3-kinase, catalytic, β polypeptide rs361072 SNP had decreased percent (Ptrend = 0.04) and absolute (Ptrend = 0.02) breast density. An association of insulin receptor substrate 1 rs1801278 SNP with absolute density (Ptrend = 0.03) was also observed. All four IGFBP-3 SNPs (including rs2854744) were associated with IGF-I and IGFBP-3 levels. This study shows that several components of the IGF pathway are associated with breast density or IGF levels. Our findings provide additional support for the idea that several components of the IGF pathway may affect breast cancer risk and that this effect on breast cancer development may be mediated, at least in part, through its influence on the morphogenesis of breast tissue. (Cancer Epidemiol Biomarkers Prev 2008;17(4):880–8)

Influence of Insulin-like Growth Factors on the Strength of the Relation of Vitamin D and Calcium Intakes to Mammographic Breast Density

Diets with higher vitamin D and calcium contents were found associated with lower mammographic breast density and breast cancer risk in premenopausal women. Because laboratory studies suggest that the actions of vitamin D, calcium, insulin-like growth factor (IGF)-I, and IGF-binding protein-3 (IGFBP-3) on human breast cancer cells are interrelated, we examined whether IGF-I and IGFBP-3 levels could affect the strength of the association of vitamin D and calcium intakes with breast density. Among 771 premenopausal women, breast density was measured by a computer-assisted method, vitamin D and calcium intakes by a food frequency questionnaire, and levels of plasma IGF-I and IGFBP-3 by ELISA methods. Multivariate linear regression models were used to examine the associations and the interactions. The negative associations of vitamin D or calcium intakes with breast density were stronger among women with IGF-I levels above the median (beta = -2.8, P = 0.002 and beta = -2.5, P = 0.002, respectively) compared with those with IGF-I levels below or equal to the median (beta = -0.8, P = 0.38 and beta = -1.1, P = 0.21; P(interaction) = 0.09 and 0.16, respectively). Similar results were observed within levels of IGFBP-3 (P(interaction) = 0.06 and 0.03, respectively). This is the first study to report that the negative relation of vitamin D and calcium intakes with breast density may be seen primarily among women with high IGF-I or high IGFBP-3 levels. Our findings suggest that the IGF axis should be taken into account when the effects of vitamin D and calcium on breast density (and perhaps breast cancer risk) are examined at least among premenopausal women.