Showing papers in "Obstetrical & Gynecological Survey in 2007"

A common allele on chromosome 9 associated with coronary heart disease

Abstract: Coronary heart disease (CHD), the commonest cause of death worldwide, is highly heritable, but the DNA sequence variations associated with elevated cardiovascular risk are largely unknown. The investigators planned a genome-wide associational study based on 100,000 single nucleotide polymorphisms and involving 3 sequential case-control comparisons made at a nominal significance threshold of P < 0.025. The study population included more than 23,000 participants from 4 Caucasian populations. Cases had severe, premature CHD starting before age 60 years and leading to coronary artery revascularization. Controls were healthy Caucasian men over age 65 and women over age 70 who lacked symptoms and a history of CHD. Individuals with diabetes or hypercholesterolemia were excluded. A 58-kilobase interval on chromosome 9p21 was consistently associated with CHD. The interval is near the CDKN2A and CDKN2B genes. It contains no annotated genes and is not associated with established CHD risk factors such as diabetes, plasma lipoproteins, or hypertension. Between 20% and 25% of Caucasians are homozygous for the risk allele, and they have an approximately 30%-40% increased risk of CHD. Mechanisms for the association between the risk allele and CHD remain incompletely understood. The allele might promote the development of atherosclerotic plaque, augment thrombogenesis, or increase the tendency of plaques to rupture. The association persisted after controlling for numerous possible confounding factors including age, gender, plasma lipid levels, blood pressure, diabetes, and plasma levels of C-reactive protein. The researchers believe that the effect of the risk allele on chromosome 9 on CHD is not mediated by established risk factors for cardiovascular disease. The present findings support the use of the whole-genome association approach for studying conditions as complex as CHD.

Explaining the decrease in U.S. deaths from coronary disease, 1980-2000

Abstract: Following a peak in deaths from coronary heart disease (CHD) in about 1968, age-adjusted rates have declined by half. Two factors may have made critical contributions: a substantial decrease in prevalence of major cardiovascular risk factors such as smoking, high cholesterol, and high blood pressure; and major breakthroughs in evidence-based treatments including coronary bypass graft surgery, coronary angioplasty, thrombolytic therapy, and stents. The investigators used a validated statistical model, IMPACT, in an attempt to identify those factors chiefly responsible for the impressive decline in CHD mortality. Data were available for U.S. adults 25 to 84 years of age covering the years 1980-2000. Between 1980 and 2000, the age-adjusted death rate for CHD fell from 543 to 267 deaths per 100,000 population among men, and from 263 to 134 per 100,000 population among women. The result was 341,745 fewer CHD deaths in 2000. The U.S. IMPACT model explained approximately 90% of the decline in CHD deaths. • About 47% of the decline in deaths from CHD was ascribed to treatments, including secondary preventive therapy following acute myocardial infarction (AMI) or revascularization (11%), initial treatments for AMI or unstable angina (10%), treatments for heart failure (9%), revascularization for chronic angina (5%), and other treatments (12%). • Approximately 44% of the decline in CHD deaths was attributed to changes in risk factors, including reductions in total cholesterol of 0.34 mmol/L; systolic blood pressure of 5.1 mm Hg; the prevalence of smoking by 11.7%; and physical inactivity by 5%. These reductions were, however, partly offset by increases in body mass index and the prevalence of diabetes. These effects accounted, respectively, for increases of 8% and 10% in CHD mortality. The proportional contributions of specific treatments and risk factor changes to the overall reduction in deaths from CHD in the year 2000 were relatively consistent. The contribution of treatments for AMI remained consistently smaller than that of secondary prevention or treatments for heart failure, regardless of whether best, minimum, or maximum estimates were compared. These findings suggest the need for comprehensive strategies to treat and prevent CHD. Efforts will be needed to maximize the coverage of effective treatments and to actively promote population-based prevention through reducing risk factors.

Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis

Abstract: Although bisphosphonates do inhibit bone resorption in postmenopausal women and lessen the risk of vertebral and hip fractures, as many as half of patients no longer adhere to prescribed oral treatment after 12 months. A single intravenous infusion of zoledronic acid reportedly decreases bone turnover and improves bone mineral density (BMD) for at least a year. In the HORIZON (Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly) Pivotal Fracture Trial, an international, randomized, double-blind, placebo-controlled study, postmenopausal women ranging in age from 65 to 89 years were assigned to receive either a 15-minute IV infusion of 5 mg of zoledronic acid or placebo at yearly intervals up to 24 months. All women received a daily supplement of 1000-1500 mg of calcium and 400-1200 IU of vitamin D. Participants had a bone mineral density (BMD) T score of -2.5 or less at the femoral neck or a score of -1.5 or less with 1 or more vertebral fractures. The efficacy analysis included 7736 patients, and the safety analysis, 7714 patients. The 3-year incidence of vertebral fracture was 10.9% in the placebo group and 3.3% in women given zoledronic acid, a 70% reduction (relative risk, 0.30; 95% confidence interval [CI], 0.24-0.38). Similar effects were noted after 1 and 2 years. Hip fractures were reduced 41% in actively treated women (hazard ratio, 0.59; 95% CI, 0.42-0.83). Nonvertebral fractures, all clinical fractures, and clinical vertebral fractures all were significantly less frequent in women given zoledronic acid-by 25%, 33%, and 77%, respectively. Actively treated women lost significantly less height than placebo recipients (-4.2 mm vs. -7.0 mm). BMD rose significantly at all measurement sites in the active treatment group compared to placebo recipients. Biochemical markers of bone turnover-including serum C-telopeptide of type I collagen, bone-specific alkaline phosphatase, and N-terminal propeptide of type I collagen-all decreased significantly with active treatment. Postdose symptoms were more frequent in actively treated women, but there were no significant group differences in numbers of deaths. Renal function was not compromised by zoledronic acid therapy. Serious atrial fibrillation was more frequent in actively treated women than in placebo patients (1.3% vs. 0.5%), as was the prevalence of inflammatory ocular disorders, mainly conjunctivitis. One patient in each group had potential osteonecrosis of the jaw. In this large-scale trial, once-a-year infusion of zoledronic acid was associated with a sustained decrease in vertebral, hip, and other fractures in postmenopausal women with osteoporosis over a 3-year period. Treatment was generally well tolerated and had a favorable safety profile.

American Cancer Society Guidelines for Breast Screening With MRI as an Adjunct to Mammography

Abstract: The American Cancer Society (ACS), in 2003, found that nonconventional screening measures such as magnetic resonance imaging (MRI) might be suitable for women at increased risk of breast cancer, but there was not enough evidence to warrant making recommendations. Since then, more information

A common variant on chromosome 9p21 affects the risk of myocardial infarction

Abstract: The investigators, recognizing that coronary artery disease (CAD), including acute myocardial infarction (MI), is the leading cause of death worldwide, carried out a genome-wide associational study on Icelandic patients with MI. Initially more than 300,000 single nucleotide polymorphisms (SNPs) were examined for any association with MI. Ultimately, the study enrolled 4587 cases and 12,769 controls. The strongest association with MI was noted with 3 correlated SNPs, all located within a 190-kb linkage disequilibrium block on chromosome 9p21. The association with MI was replicated in case-control sample sets of persons of European descent from 3 US cities. The identified variant was adjacent to the tumor suppressor genes CDKN2A and CDKN2B. It was associated with MI at a high level of significance (P = 1.2 × 10−20). The proteins encoded by these genes have a key role in regulating cell proliferation, cell senescence, and apoptosis—all important features of atherogenesis. Approximately 21% of individuals in the study population are homozygous for the variant, and it is estimated that their risk of having MI is 1.64-fold greater than for noncarriers. The risk is 2.02-fold greater for early-onset cases. The population-attributable risk was estimated as 21% for MI in general and 31% for early-onset cases. This is the first common variant found to consistently confer a substantial risk of MI, defined as an odds ratio exceeding 1.20, in multiple case-control groups of European descent. The variant poses a substantial risk from a public health viewpoint, but it explains only a small part of familial clustering of the disease and would not yield high linkage scores. The implication is that other susceptibility variants are as yet unidentified. In addition to MI, there is reason to believe that the present variant might increase the risk of CAD in general. Just how genetic variants influence the pathogenesis of MI remains to be clarified.

Maternal Mortality and Severe Morbidity Associated With Low-Risk Planned Cesarean Delivery Versus Planned Vaginal Delivery at Term

Abstract: Reported rates of elective primary cesarean delivery continue to increase markedly, prompting the present study comparing the risks of elective cesarean delivery with those of planned vaginal delivery. Participating were 46,766 healthy women at term who underwent planned cesarean delivery because of breech presentation, and 2,292,420 others having planned vaginal delivery. Overall rates of severe maternal morbidity were 27.3 per 1000 deliveries in the planned cesarean group and 9.0 per 1000 with planned vaginal delivery. Women in the planned cesarean group had increased postpartum risks of cardiac arrest, wound hematoma, hysterectomy, major puerperal infection, complications of anesthesia, venous thromboembolism, and hemorrhage necessitating hysterectomy. In addition, these women remained in hospital longer than those having planned vaginal delivery, but they had a lower risk of hemorrhage requiring blood transfusion. Absolute risk increases were low. There was no significant group difference in rates of in-hospital maternal death, and no mother died in hospital following planned cesarean delivery. Women having either spontaneous or instrumental vaginal delivery were less likely to become very ill or die than those having emergency cesarean delivery. The latter women had the highest in-hospital mortality rate (9.7 per 1000 deliveries) and also the highest rates of maternal morbidity-particularly from cardiac arrest, uterine rupture, hemorrhage requiring hysterectomy, hemorrhage requiring transfusion, and obstetrical shock. Women considering elective cesarean delivery should be aware that the risk of severe maternal morbidity is higher than with planned vaginal delivery. At the same time, absolute differences in morbidity risk were not marked in this study.

Systematic Review of Conservative Management of Postpartum Hemorrhage: What to Do When Medical Treatment Fails

Abstract: We performed a systematic review to identify all studies evaluating the success rates of treatment of major postpartum hemorrhage by uterine balloon tamponade, uterine compression sutures, pelvic devascularization, and arterial embolization. We included studies reporting on at least 5 cases. All searches were performed independently by 2 researchers and updated in June 2006. Failure of management was defined as the need to proceed to subsequent or repeat surgical or radiological therapy or hysterectomy, or death. As the search identified no randomized controlled trials, we proceeded to search for observational studies. This identified 396 publications, and after exclusions, 46 studies were included in the systematic review. The cumulative outcomes showed success rates of 90.7% (95% confidence interval [CI], 85.7%-94.0%) for arterial embolization, 84.0% (95% CI, 77.5%-88.8%) for balloon tamponade, 91.7% (95% CI, 84.9%-95.5%) for uterine compression sutures, and 84.6% (81.2%-87.5%) for iliac artery ligation or uterine devascularization (P = 0.06). At present there is no evidence to suggest that any one method is better for the management of severe postpartum hemorrhage. Randomized controlled trials of the various treatment options may be difficult to perform in practice. As balloon tamponade is the least invasive and most rapid approach, it would be logical to use this as the first step in the management.

What is the optimal goal of primary cytoreductive surgery for bulky stage IIIC epithelial ovarian carcinoma (EOC)

Abstract: What constitutes "optimal" cytoreduction for women operated on for ovarian cancer remains uncertain. A majority of studies have employed a cutoff of 1-2 cm to define optimal cytoreduction. Recent studies suggest that removing all gross disease promotes disease-free survival compared to the current Gynecologic Oncology Group threshold of 1 cm or less of residual disease. This prospective database analysis reviewed the records of 465 patients with stage IIIC epithelial ovarian carcinoma (EOC) who had cytoreductive surgery in the years 1989-2003. All participants had bulky abdominal tumor, and maximal cytoreduction was attempted if technically possible. The patients, whose median age was 60 years, were followed up for a median of 38 months. Nearly all the patients received at least 6 cycles of platinum-based systemic chemotherapy. Univariate analysis showed age at the time of surgery and the preoperative platelet count to be significant continuous variables. Categorical variables with prognostic significance included the presence of ascites, the site of the largest tumor mass, extensive upper abdominal cytoreduction, and the extent of residual disease. Multivariate analysis confirmed age, the presence or absence of ascites, and the diameter of residual disease as being significant factors. Median survival was 106 months when there was no gross residual disease, and declined steadily as the amount of residual disease increased. Median survival was 34 months when patients were left with more than 2 cm of residual disease. The major distinctions with regard to survival rate were between no gross residual disease, 1 cm or less of gross disease, and more than 1 cm of residual disease. A trend toward improved survival was noted in patients left with 0.5 cm or less of residual disease compared with those retaining 0.6-1 cm of disease (Fig. 1). The investigators conclude from these findings that removing all evidence of gross stage IIIC EOC prolongs survival and is an appropriate goal of primary cytoreductive surgery. If complete gross resection is not feasible, as little residual tumor as possible should be left behind. An incremental decrease in residual disease below 1 cm can incrementally enhance overall survival.

Bowel endometriosis: Presentation, diagnosis, and treatment

Abstract: Bowel endometriosis opens a new frontier for the gynecologist, as it forces the understanding of a new anatomy, a new physiology, and a new pathology. Although some women with bowel endometriosis may be asymptomatic, the majority of them develop a variety of gastrointestinal complains. No clear guid

The role of oxidative stress in spontaneous abortion and recurrent pregnancy loss: a systematic review.

Abstract: Human reproduction is not considered a highly efficient biological process. Before the end of the first trimester, 30%–50% of conceptions end in spontaneous abortion. Most losses occur at the time of implantation. 15%–20% of clinical pregnancies end in spontaneous abortions. Recurrent pregnancy loss is a frustrating clinical problem both for clinicians and patients. Recurrent pregnancy loss affects 0.5%–3% of women in the reproductive age group, and between 50%–60% of recurrent pregnancy losses are idiopathic. Oxidative stress-induced damage has been hypothesized to play a role in spontaneous abortion, idiopathic recurrent pregnancy loss, hydatidiform mole, defective embryogenesis, and drug-induced teratogenicity. Some studies implicate systemic and placental oxidative stress in the pathophysiology of abortion and recurrent pregnancy loss. Oxidant-induced endothelial damage, impaired placental vascularization and immune malfunction have all been proposed to play a role in the pathophysiology of idiopathic recurrent pregnancy loss. Oxidative stress-induced placental dysfunction may be a common cause of the multifactorial and polygenic etiologies of abortion, recurrent pregnancy loss, defective embryogenesis, hydatidiform mole, and drug-induced teratogenic effects. Oxidative stress-induced modification of phospholipids has been linked to the formation of antiphospholipid antibodies in the antiphospholipid syndrome. The objective of this review was to examine the association between oxidative stress, spontaneous abortion and recurrent pregnancy loss, based on the published literature. We conducted an extensive literature search utilizing the databases of Medline, CINAHL, and Cochrane from 1986 to 2005. The following keywords were used: oxidative stress, abortion, recurrent pregnancy loss, reactive oxygen species, antioxidants, fetal development, and embryopathies. We conducted an electronic search, as well as a manual search of cross-references. We have included all studies in the English language found in the literature focusing on oxidative stress and its association with abortions, recurrent pregnancy loss and drug-induced teratogenicity. The role of antioxidant vitamins for primary prevention of oxidative stress-induced pathologies needs to be investigated further. Target Audience: Obstetricians & Gynecologists, Family Physicians Learning Objectives: After completion of this article, the reader should be able to state that the causes of spontaneous and recurrent abortion are multifaceted, however, some of the causes may be preventable and also explain that the role of oxidative stress during pregnancy and adverse pregnancy outcomes has a basis in pathophysiology, although the role of oxidative stress and the treatment of oxidative stress during or before pregnancy remains speculative.

Response to Antiretroviral Therapy After a Single, Peripartum Dose of Nevirapine

Abstract: A single dose of nevirapine for both the mother and newborn infant lowers the rate of mother-to-child transmission of HIV-1 by more than 40%. Nevertheless, large numbers of both women and infants become resistant to nevirapine when exposed to a single peripartum dose. This prospective observational study was done to assess virologic responses to nevirapine-based antiretroviral treatment in women and infants who had previously been randomly assigned to receive a single peripartum dose of nevirapine or placebo. The major end point for both mothers and infants was virologic failure at the 6-month follow-up visit after initiation of antiretroviral therapy. Of 218 women who began antiretroviral therapy, 112 had received a single dose of nevirapine, and 106, placebo. Rates of virologic failure 6 months after the start of antiretroviral treatment were 5% for placebo recipients and 18% for those given a single dose of nevirapine. Among 60 women who began antiretroviral treatment within 6 months of randomization, 42% of those given nevirapine but none of the placebo recipients were virologic failures. In contrast, no significant difference in failure rates were noted in women who began antiretroviral treatment 6 months or more postpartum. Among 30 infants placed on antiretroviral therapy, virologic failure after 6 months was significantly more frequent in those given a single dose of nevirapine than in placebo recipients (P < 0.001). On multivariate analysis stratified according to the timing of initial antiretroviral treatment, baseline counts of CD4 + cells and a single dose of nevirapine, but not the plasma level of HIV-1 RNA, were significantly associated with the time to virologic failure. Where possible, women who qualify for combination antiretroviral treatment on their own account should receive it. They not only are the women at highest risk of AIDS-related complications or death, but also are the likeliest to transmit infection to their infants. For women who do not yet qualify for antiretroviral treatment or where treatment is not available, prophylactic single dose of nevirapine-with or without other antiretroviral agents-remains an important way of preventing mother-to-child transmission of HIV-1 infection. Women exposed more remotely to a single dose of nevirapine have high rates of viral suppression when receiving nevirapine-based antiretroviral therapy.

Comparison of the Atkins, Zone, Ornish, and LEARN Diets for Change in Weight and Related Risk Factors Among Overweight Premenopausal Women. The A to Z Weight Loss Study: A Randomized Trial

Abstract: Recent trials indicate that low-carbohydrate, nonenergy-restricted diets are at least as effective as traditional low-fat, high-carbohydrate diets in promoting weight loss for up to a year. These trials were, however, limited in many respects. The A TO Z (Atkins, Traditional, Ornish, Zone We

Soluble endoglin and other circulating antiangiogenic factors in preeclampsia

Abstract: The circulating antiangiogenic protein soluble fms-like tyrosine kinase 1 (sFltl), also known as soluble vascular endothelial growth factor (VEGF) receptor 1, sequesters the proangiogenic proteins placental growth factor (PlGF) and VEGF. Its circulating level correlates with the severity of preclampsia and with the onset of hypertension or proteinuria. Increased expression of sFltl in pregnant rats creates a state resembling preeclampsia. Soluble endoglin, a coreceptor for transforming growth factors, is another antiangiogenic protein that acts with sFltl to produce a severe preeclampsia-like syndrome in pregnant rats. This nested case-control study, enrolling healthy nulliparous women taking part in the Calcium for Preeclampsia Prevention (CPEP) trial, was designed to show whether endoglin is associated with preeclampsia in humans. Seventy-two women having preeclampsia before 37 weeks' gestation were compared with four groups, each comprising 120 women, who had preeclampsia at term; had gestational hypertension; were normotensive but had an small-for-gestational-age infant; or were normotensive and delivered a normal-sized infant. Severe preeclampsia developed in 61% of women with preterm preeclampsia and 25% of those with preeclampsia at term (after 37 weeks' gestation). Symptomatic women with preterm preeclampsia had significantly higher serum levels of soluble endoglin than control women. Term preeclampsia also was associated with elevated circulating levels of endoglin. At 17-20 weeks' gestation, endoglin levels were significantly higher in women who later developed preterm preeclampsia than in control women. The same was the case at gestational weeks 25 through 28 for women who developed term preeclampsia. Elevated endoglin levels usually were accompanied by an increased sFltl:P1GF ratio. The risk of preeclampsia was greatest for women in the highest quartile of the control distributions for both biomarkers but not for either one alone. On multivariable analysis, large increases in the risk of preeclampsia with a small-for-gestational-age infant were associated with the highest quartile of soluble endoglin or sFltl:P1GF ratio. These findings, combined with those of experimental rodent studies, suggest that circulating soluble endoglin and spil-which cause endothelial dysfunction by different mechanisms-may contribute to the development of preeclampsia. Whether levels of these biomarkers will be useful in predicting the onset of clinical preeclampsia remains to be determined by longitudinal prospective studies.

Clomiphene, metformin, or both for infertility in the polycystic ovary syndrome

Abstract: Polycystic ovary syndrome (PCOS) may be the commonest cause of female infertility. In addition to anovulation, early pregnancy loss, and later complications of pregnancy, obesity-which is common in women with PCOS-has been implicated. Small-scale trials suggest that treatment with an insulin sensitizer such as metformin, alone or combined with clomiphene citrate, is at least equal to, and possibly superior to clomiphene alone as treatment for infertility. This randomized, placebo-controlled trial evaluated both of these agents, alone and combined, in 626 infertile women diagnosed as having PCOS. Extended-release metformin was given in a maximum dose of 1 gm daily, and clomiphene concurrently in a dose of 50 mg daily, starting on menstrual day 3. The dose of clomiphene was doubled if necessary. Treatment continued for up to six cycles over 30 weeks. Baseline variables were similar in all treatment groups. Rates of live birth were 22.5% in clomiphene-treated patients, 7.2% with metformin therapy, and 26.8% with combination therapy. The differences between the metformin group and the clomiphene and combined treatment groups were significant. Combined therapy was not significantly more effective than clomiphene alone. Similar results were obtained when adjusting for body mass index. Among secondary outcomes, ovulation rates were significantly higher with combined treatment than in either of the single-drug groups, but this did not translate into increased live births. Rates of conception and of live births per ovulatory cycle were significantly higher in the clomiphene and combined drug groups than with metformin alone. There were no multiple pregnancies in the metformin group. There were no notable group differences in rates of first-trimester pregnancy loss. Compared to metformin-treated women, those given clomiphene or combined therapy had significant increases in sex hormone-binding globulin levels and decreased free androgen indices. Serious adverse events-mostly pregnancy complications-were most frequent in the clomiphene and combined treatment groups. Gastrointestinal side effects were more frequent, and vasomotor and ovulatory symptoms less frequent, in the metformin group than in the clomiphene group. These findings fail to support the view that extended-release metformin, alone or combined with clomiphene citrate, improves live birth rates in previously infertile women with PCOS. Clomiphene alone seems preferable as first-line treatment for these patients despite a risk of multiple births. Combining the two drugs does not further increase the chances of a live birth.

Conservative management of abnormally invasive placentation.

Abstract: Due to the growing number of cesarean deliveries, the frequency of abnormally invasive placentation is increasing. The optimal management of this condition remains unclear. This article reviews the efficacy and safety of conservative management of abnormally invasive placentation. We performed a MEDLINE and Embase search and reviewed all articles on conservative management of abnormally invasive placentation published from 1985 through 2006. Over the past 20 years, 48 reports have described outcomes of 60 women who were treated conservatively for abnormally invasive placentation. Twenty-six women were managed without any additional interventions. In most of these patients (19/26), the placenta had been partially removed. In 4 of these 26, conservative therapy failed. Twenty-two women received adjuvant methotrexate. In most of these women (19/22), the entire placenta was left in situ. In 5, therapy failed. Twelve women were managed with arterial embolization. In most of these (9/12), the diagnosis was made antepartum and the placenta was completely left in situ. In 3, therapy failed. Overall, 11 women experienced infection (11/60), 21 women experienced vaginal bleeding (21/60), and 4 suffered disseminated intravascular coagulopathy (4/60). Spontaneous loss of placental tissue was noted in 16 women. Subsequent pregnancies were reported in 8 women. Conservative management of abnormally invasive placentation can be effective and fertility can be preserved. It should only be considered in highly selected cases when blood loss is minimal and there is desire for fertility preservation. Whether adjuvant methotrexate or selective arterial embolization is beneficial is uncertain. Undetectable hCG values do not seem to guarantee complete resorption of retained placental tissue.

Salpingo -oophorectomy and the risk of ovarian, fallopian tube, and peritoneal cancers in women with a BRCA1 or BRCA2 mutation

Abstract: Women with adverse mutations in the BRCA1 or BRCA2 gene are at an increased lifetime risk of ovarian cancer, and these mutations also increase vulnerability to cancers of the fallopian tube and peritoneum. Risk levels were examined in a prospective study based on data from an international registry comprising 32 centers in Canada, the United States, Europe, and Israel. The 1828 women identified as carrying a BRCA1 or BRCA2 mutation were followed up for a mean of 3.5 years. Participants had a mean age at entry of 47 years. Approximately three-fourths of the women carried a BRCA1 mutation and about one-fourth, a BRCA2 mutation; eight individuals carried both. Nearly one-third of women in the study (30.4%) had undergone bilateral salpingo-oophorectomy before entering the study, and another 38.5% had an oophorectomy during follow-up. Fifty incident cancers were discovered during follow-up. Thirty-two of these cancers developed in women with intact ovaries. Eleven cancers were identified at the time of prophylactic oophorectomy, and 7 others after this procedure. The cumulative incidence of peritoneal cancer was estimated at 4.3% two decades after oophorectomy. The overall adjusted reduction in cancer risk associated with bilateral oophorectomy was 80%, with a multivariate hazard ratio of 0.2 and a 95% confidence interval of 0.07-0.58 (Fig. 1). The risk of ovarian, tubal, and primary peritoneal cancers in women with intact ovaries was highest for those 60-70 years of age who carried the BRCA1 mutation. Based on estimated incidence rates for women having both ovaries intact, the estimated penetrance of ovarian cancer was 62% up to age 75 years for carriers of the BRCA1 mutation, and 18% up to age 75 for those carrying the BRCA2 mutation. The investigators conclude that the risk of ovarian, tubal, and peritoneal cancer is lowered by 80% for carriers of the BRCA1 or BRCA2 mutation who undergo prophylactic oophorectomy. The findings support prophylactic surgery as a very effective risk reduction measure. Both the ovaries and the fallopian tubes should be removed. The residual risk of peritoneal cancer is not high enough to recommend against prophylactic surgery.

Large maternal weight loss from obesity surgery prevents transmission of obesity to children who were followed for 2 to 18 years

Abstract: Anti-obesity surgery can be life saving for morbidly obese women. However, it can result in malnutrition which could adversely affect subsequent pregnancy outcomes. Biliopancreatic diversion (BPD), which entails partial gastric resection and shunting of bile and pancreatic secretions to the distal small bowel, probably has the greatest potential to cause malnutrition. This study evaluated the health status of children born to obese women before or after they had BPD surgery. There were 172 children 2 to 18 years of age born to 113 obese women after they had BPD and lost substantial weight (the AMS group, born after maternal surgery; average body mass index [BMI], 31 kg/m 2 ), and 45 same-aged siblings who were born before maternal surgery (BMS group; average BMI of 48 kg/m 2 ). Follow-up at a tertiary referral center exceeded 88%; the mean duration of follow-up was 6 years. Conventional BPD with distal gastrectomy was performed on 23 mothers, while 90 underwent BPD with pylorus sparing, "duodenal switch" and sleeve gastrectomy. In the BMS group, 57% of children were overweight or obese and 36% were normal weight; in the AMS group, the numbers were 35% and 60%, respectively. The prevalence of childhood obesity (BMI >95th percentile for age, equivalent to a BMI of 30 to 34.9 kg/m 2 ) and severe obesity (BMI ≥35 kg/m 2 ) were 52% and 45% lower, respectively, in the children of BMS mothers, although a statistically significant reduction in obesity occurred only in boys, whose z score decreased from 1.4 BMS to 0.57 AMS (corrected for birth order). The prevalence of underweight (BMI <5th percentile for age) was the same in both groups. Gestational weight gain in the AMS group averaged 7 kg. In both boys and girls 6 to 18 years of age who were born to mothers in the AMS group, overweight was about as prevalent as in the general population. The preoperative maternal BMI predicted overweight and obesity in offspring after adjusting for age, parity, birth order, and gender. Neither low birth weight nor being small for gestational age correlated with future overweight or obesity. Questionnaire responses suggested that children born to women in the AMS group had progressed normally in the intellectual and social domains.

Dopamine agonists and the risk of cardiac-valve regurgitation

Abstract: Dopamine agonists, which are first-line drugs for treating Parkinson's disease and also are used to treat restless legs syndrome, reportedly may be associated with fibrotic heart valve disease. Pergolide has been implicated, but there is reason to believe that not all dopamine agonists pose a risk. Unlike other drugs of this class, pergolide and cabergoline are strong agonists of the 5-hydroxytryptamine 2B receptor expressed on heart valves. The investigators used data from the United Kingdom General Practice Research Database to form a population-based cohort of 11,417 individuals 40 to 80 years of age who, in the years 1988-2005, were prescribed anti-Parkinsonian drugs. In a nested case-control analysis, each patient with newly diagnosed cardiac valve regurgitation was matched with up to 25 control subjects for age, gender, and year of entry into the cohort. In addition to pergolide and cabergoline, patients variably received the dopamine agonists bromocriptine, lisuride, pramipexole, and ropinirole. Incidence-rate ratios for heart valve regurgitation were estimated by conditional logistic regression analysis. Patients in the study cohort had a mean age at entry of 69 years and were followed for an average of 4.2 years. Thirty-one case patients had newly diagnosed cardiac valve regurgitation. Six each were currently receiving pergolide and cabergoline, whereas the remaining 19 had not received any dopamine agonist within the previous year. The incidence-rate ratio associated with the current use of pergolide was 7.1, with a 95% confidence interval of 2.3-22.3. The respective figures for cabergoline were 4.9 and 1.5-15.6. There was no indication that the risk of valve regurgitation was increased by the current use of other dopamine agonists. A particularly close association was evident when daily doses exceeded 3 mg of either pergolide or cabergoline, and the risk also was increased when either of these drugs was used for 6 months or longer. The only other significant risk factor was current use of amantadine. When adjusting for body mass index, smoking status, and the presence or absence of coronary heart disease, hypertension, diabetes, Parkinson's disease, restless legs syndrome, and hyperprolactinemia, incidence-rate ratios for pergolide and cabergoline were 6.0 and 6.9, respectively. The respective excess risk figures were 33 and 21 additional case patients for every 10,000 persons exposed per year. In this large-scale cohort study, current use of either pergolide or cabergoline was associated with a considerably increased risk of newly diagnosed heart valve regurgitation. No such association was found for other dopamine agonists, The increase in risk may actually have been underestimated because not all patients were monitored echocardiographically.

In vitro fertilization with preimplantation genetic screening

Abstract: Both in vitro fertilization (IVF) and preimplantation genetic screening are being increasingly used, the latter for women of advanced maternal age. Observational studies show that, when screening is added to IVF, implantation rates increase but rates of ongoing pregnancies do not. Some researchers believe that preimplantation genetic screening of cleavage-stage embryos for aneuploidies may make IVF more effective. The present multicenter, randomized, double blind, controlled trial compared 3 cycles of IVF with embryo selection based either on preimplantation genetic screening or on the morphologic features of the embryo. Of the 408 participants, all women ranging in age from 35 through 41 years, 206 were assigned to preimplantation genetic screening. Screening accompanied 434 of 836 cycles of IVF. Screening began 3 days after follicular aspiration by biopsying a single blastomere on all embryos having 4 or more blastomeres. Compared with control women, those having preimplantation genetic screening had a significantly lower rate of ongoing pregnancy (25% vs. 37%). The rate ratio was 0.69, with a 95% confidence interval (CI) of 0.51-0.93. Biochemical and clinical pregnancy rates also were significantly lower in the screened group, but there was no significant difference in rates of miscarriage. Women assigned to genetic screening had a significantly lower rate of live births than control subjects (24% vs. 35%). The rate ratio was 0.68, with a 95% CI of 0.50-0.92. Not only did preimplantation genetic screening fail to increase rates of ongoing pregnancy and live births following IVF in this population of older women, but observed rates were lower than in control (unscreened) women. At present, preimplantation genetic screening should not be routinely performed in women of advanced maternal age who undergo IVF. It is not clear whether different results would be obtained in women with indications for genetic screening other than advanced maternal age.

Treatment of Periodontal Disease and the Risk of Preterm Birth

Abstract: Background Maternal periodontal disease has been associated with an increased risk of preterm birth and low birth weight. We studied the effect of nonsurgical periodontal treatment on preterm birth. Methods We randomly assigned women between 13 and 17 weeks of gestation to undergo scaling and root planing either before 21 weeks (413 patients in the treatment group) or after delivery (410 patients in the control group). Patients in the treatment group also underwent monthly tooth polishing and received instruction in oral hygiene. The gestational age at the end of pregnancy was the prespecified primary outcome. Secondary outcomes were birth weight and the proportion of infants who were small for gestational age. Results In the follow-up analysis, preterm birth (before 37 weeks of gestation) occurred in 49 of 407 women (12.0%) in the treatment group (resulting in 44 live births) and in 52 of 405 women (12.8%) in the control group (resulting in 38 live births). Although periodontal treatment improved periodo...

Progesterone and the Risk of Preterm Birth among Women With a Short Cervix

Abstract: Spontaneous delivery before 34 weeks of gestation was less frequent in the progesterone group than in the placebo group (19.2% vs. 34.4%; relative risk, 0.56; 95% confidence interval [CI], 0.36 to 0.86). Progesterone was associated with a nonsignificant reduction in neonatal morbidity (8.1% vs. 13.8%; relative risk, 0.59; 95% CI, 0.26 to 1.25; P = 0.17). There were no serious adverse events associated with the use of progesterone.

Kisspeptin-54 Stimulates the Hypothalamic-pituitary Gonadal Axis in Human Males

Abstract: Kisspeptin is a 54-amino acid peptide that activates the G protein-coupled receptor GPR54. This system appears to be an important regulator of reproduction. Mutation of GPR54 is associated with failed reproductive function. Studies in rodents and primates indicate that the endogenous neuropeptide agonist for GPR54, kisspeptin, strongly stimulates the hypothalamic-pituitary-gonadal axis. This double-blind, placebo-controlled, crossover study examined the effects of elevated circulating levels of kisspeptin on testosterone and gonadotropin concentrations in six males who received 90-minute intravenous infusions of 4 pmol/kg/minute of kisspeptin-54 and physiological saline in random order. Increasing infusion rates of kisspeptin-54 led to a dose-dependent rise in mean plasma kisspeptin immunoreactivity (IR). A dose-dependent increase in luteinizing hormone (LH) levels also was documented. Mean levels of follicle-stimulating hormone (FSH) also increased over time as kisspeptin-54 was infused, and there was a trend toward increased plasma testosterone levels. The increases in FSH and testosterone, however, were not dose-dependent. Elevations in circulating levels of LH, FSH, and testosterone were significant compared with responses to saline infusion. Infusion of kisspeptin-54 had no effect on the release of inhibin B or on sexual arousal scores. The course of kisspeptin-IR after reaching a plateau level followed first-order kinetics with a plasma half-life of 27 minutes, a mean metabolic clearance rate of 3.2 m/kg/minute, and a volume of distribution of 128 ml/kg. Systemic administration of kisspeptin-54 acutely increases circulating levels of gonadotropins and testosterone in human males. This potentially provides a novel means of manipulating the hypothalamic-pituitary-gonadal axis in patients with reproductive disorders.

Colonoscopic withdrawal times and adenoma detection during screening colonoscopy

Abstract: Colonoscopy is increasingly used to screen for colorectal neoplasms and to remove benign adenomatous polyps before they become cancerous. This study, conducted at a large community-based gastroenterology practice, examined the proposal that endoscopists who take more time to examine the colorectal mucosa-prolonging withdrawal of the scope-detect more neoplasms. Twelve experienced gastroenterologists performed a total of 7882 colonoscopies during a 15-month period; 2053 of them were screening exams in persons having their first colonoscopy. Detection rates were compared for practitioners whose colonoscopic withdrawal times were less than 6 minutes and 6 minutes or longer. Experts believe that at least 6 minutes are needed to adequately inspect the colon and rectum. Nearly one in four of those examined (23.5%) were found to have adenomatous polyps. The mean withdrawal time was 6.3 minutes when no polyps were removed and 10.6 minutes when polyps were removed. Withdrawal times correlated closely with lesion detection rates, whether or not polyps or masses were manipulated. In cases where polyps were removed, withdrawal times correlated inversely with polyp size, and longer withdrawal times correlated positively with the removal of polyps less than 5 mm in diameter. Endoscopists taking 6 minutes or longer to withdraw the colonoscope had significantly higher rates of detection of all adenomas, advanced adenomas, and hyperplastic lesions. Those with relatively long withdrawal times detected nearly 4-fold more adenomas than endoscopists with relatively short withdrawal times. The rates of detection of advanced neoplasms were 6.4% and 2.6%, respectively, and of all neoplasms, 28.3% and 11.8%. The findings in this observational study are preliminary and therefore should be cautiously interpreted. Nevertheless, they may inform future attempts to find ways of preventing colorectal cancer.

Puerperal pyrexia: a review. Part I.

Abstract: Puerperal pyrexia and sepsis are among the leading causes of preventable maternal morbidity and mortality not only in developing countries but in developed countries as well. Most postpartum infections take place after hospital discharge, which is usually 24 hours after delivery. In the absence of p

Rupture of the primigravid uterus: a review of the literature.

Abstract: Uterine rupture is a catastrophic obstetric complication, associated with high rates of perinatal morbidity and mortality The most common risk factor is previous uterine surgery, and most cases of uterine rupture occur in women with a previous cesarean delivery Traditionally, the primigravid uteru

A review of idiopathic hydramnios and pregnancy outcomes.

Abstract: Idiopathic hydramnios is defined as hydramnios that is not associated with congenital anomalies of the central nervous system or gastrointestinal tract, maternal diabetes, isoimmunizaton, fetal infection (CMV or toxoplasmosis), placental tumors, or multiple gestations. Hydramnios is diagnosed when t

Use of selective serotonin-reuptake inhibitors in pregnancy and the risk of birth defects

Abstract: Estimates of the lifetime risk of major depression in women range from 10% to 25%, peaking during the reproductive years. Today, selective serotonin-reuptake inhibitors (SSRIs) are the most commonly used type of antidepressant medication. Recent studies suggest that taking these drugs while pregnant may be associated with birth defects in general and with congenital heart defects in particular. The investigators have analyzed data from 9622 case infants having major birth defects and 4092 control infants who were born in the years 1997 to 2002 and enrolled in the National Birth Defects Prevention Study. Both cases and controls were chosen through birth defects surveillance systems in 8 states. The mothers took part in a standardized phone interview dealing with exposure to potential risk factors, including medications, before and during pregnancy. Exposure was defined as taking any SSRI from 1 month before to 3 months after conception. Combining cases and control subjects, 3% of study participants reported having used a SSRI at some time before or during pregnancy, and 2.3% during the designated 4-month interval. No significant association was found between the maternal use of SSRIs during early pregnancy and congenital heart defects. There were, however, 3 conditions associated with maternal use of SSRIs. They included anencephaly (adjusted odds ratio [OR], 2.4; 95% confidence interval [CI], 1.1-5.1); craniosynostosis (OR, 2.5; 95% CI, 1.5-4.0); and omphalocele (OR, 2.8; 95% CI, 1.3-5.7). None of the mothers of case infants having defects associated with SSRI use were found to have been exposed at the same time to medications known to have teratogenic effects. This study failed to establish any association between the maternal use of SSRIs during early pregnancy and an elevated risk of congenital heart defects-or of several other classes of birth defects. Three associations were observed, but the absolute risks were small in view of the baseline risk of birth defects inherent in all pregnancies. At the same time, maternal stress and depression during pregnancy have been implicated in adverse reproductive outcomes, and discontinuing antidepressant therapy in pregnant women who are seriously depressed may negatively affect both the mother and infant.

Human embryonic stem cell lines derived from single blastomeres

Abstract: At present it is necessary to destroy embryos ex utero to obtain human embryonic stem (hES) cells, but a study in mice suggests that ES cells might be generated using a single-cell biopsy technique similar to that used for preimplantation genetic diagnosis (PGD). This will not interfere with the developmental potential of the embryo. Overnight growth of a single blastomere could yield cells that may be used for both genetic testing and stem cell production without altering the clinical outcome. The investigators carried out ten experiments which, collectively, showed that hES cells can be derived from single blastomeres. Starting with unused embryos produced by in vitro fertilization, 19 ES-cell-like outgrowths and two stable hES cell lines were obtained. A majority of isolated blastomeres divided at least once, and about half formed vesicles or clumps that produced outgrowths within 2 days. The cells remained able to form derivatives of all three embryonic germ layers (primitive endoderm, mesoderm, ectoderm) in vitro and also in teratomas. Among the outcomes observed over several days were three that are typical when ES cells are derived from human embryos. Cells resembling trophectoderm dominated some cultures. Secondly, cells that initially resembled ES cells differentiated within cultures. Finally, ES-cell-like cells continued to proliferate without differentiating. Some hES cell lines proliferated without differentiating for longer than 8 months. Both karyotypes and the expression of markers of pluripotency were normal. The ability to create new stem cell lines without destroying embryos addresses the ethical concerns shared by many interested individuals. Potentially, matched tissues can be generated for children and siblings born from transferred PGD embryos. Further studies will be needed to learn whether blastomere-derived hES cell lines resemble conventional hES cell lines in their ability to form functional differentiated cell types. The investigators recommend that, until safety issues are resolved, this procedure be used only in the context of PGD.

Gestational diabetes : A review of the current literature and guidelines

Abstract: Despite large numbers of original research studies spanning 4 decades there is still no consensus on the subject of gestational diabetes. Should all pregnant women be screened or only those with risk factors? Or is it safe not to screen at all? Which screening test and which diagnostic test are the

Vitamins and perinatal outcomes among HIV-negative women in Tanzania

Abstract: The mother's micronutrient status is a key determinant of fetal growth and survival. While iron and folate supplements now are provided to pregnant women in many developing countries, the dietary intake of other micronutrients often is inadequate. Multivitamin supplements have significantly lowered rates of fetal death, preterm birth, and low birth weight in HIV-positive Tanzanian women. The present, similarly designed trial was done to learn whether supplements are equally effective in HIV-negative women. The double-blind trial enrolled 8468 women at 12-27 weeks' gestational age, all of whom received supplemental iron and folic acid prenatally. Participants received either a multivitamin supplement or placebo daily up to 6 weeks after delivery. The supplement included 20 mg of vitamin B 1 , 20 mg of vitamin B 2 , 25 mg of vitamin B 6 , 100 mg of niacin, 50 μg of vitamin B 12 , 500 mg of vitamin C, 30 mg of vitamin E, and 0.8 mg of folic acid. These doses were, on average, at least twice the recommended dietary allowance (RDA) and, in several instances, 6-10 times the RDA. Vitamin A and zinc were omitted. A total of 8137 women gave birth to a live infant and were eligible for analyses of birth weight and prematurity. Women in the supplement and placebo groups had similar baseline characteristics. The interval from randomization to 6 weeks postpartum averaged 5.6 months. Compliance during this interval averaged 80% and did not differ significantly between the two study groups. Low birth weight (less than 2500 g) was significantly less common in the multivitamin group than in placebo recipients; the relative risk (RR) was 0.82, with a 95% confidence interval (CI) of 0.70-0.95. Mean birth weight was modestly but significantly higher in the multivitamin group. Supplementation had no significant effects on the risk of either preterm birth (before 37 weeks' gestation) or fetal death. The risk of a small-for-gestational-age infant was reduced 23% in the multivitamin group. The RR of cesarean delivery in the multivitamin group compared to the placebo group was 1.15 (95% CI, 0.99-1.33). Supplementation did not significantly influence the risk of maternal death. Maternal anemia was less frequent in women given supplements, and they had significantly higher hemoglobin levels. The low cost of vitamin supplements and their positive effects on the risk of low birth weight and a small-for-gestational-age infant recommend their use by all pregnant women. Prenatal vitamin supplementation could prove to be a very cost-effective means of improving birth outcomes in developing countries.