Association between cigarette smoking and ovarian reserve among women seeking fertility care.

INTRODUCTION: This study examined the association of smoking with ovarian reserve in a cross-sectional study of 207 women enrolled in the Louisville Tobacco Smoke Exposure, Genetic Susceptibility, and Infertility (LOUSSI) Study and assessed effect modification by NAT2 acetylator phenotype. METHODS: Information on current smoking status was collected using a structured questionnaire and confirmed by cotinine assay. Serum anti-Müllerian hormone (AMH) levels were used to assess ovarian reserve. Diminished ovarian reserve (DOR) was defined as AMH <1ng/mL. Single nucleotide polymorphisms in the NAT2 gene, which metabolizes toxins found in cigarette smoke, were analyzed to determine NAT2 acetylator status. Linear and logistic regression were used to determine the effects of smoking on ovarian reserve and evaluate effect modification by NAT2. Regression analyses were stratified by polycystic ovary syndrome (PCOS) status and adjusted for age. RESULTS: Current smoking status, either passive or active as measured by urinary cotinine assay, was not significantly associated with DOR. For dose-response assessed using self-report, the odds of DOR increased significantly for every additional cigarette currently smoked (Odds ratio, OR:1.08; 95% confidence interval, 95%CI:1.01-1.15); additionally, every 1 pack-year increase in lifetime exposure was associated with an increased odds of DOR among women without PCOS (OR: 1.08 95%CI: 0.99-1.18). These trends appear to be driven by the heavy or long-term smokers. Effect modification by NAT2 genotype was not established. CONCLUSION: A history of heavy smoking may indicate increased risk of diminished ovarian reserve.

Fumarate Hydratase Mutation in a Young Woman With Uterine Leiomyomas and a Family History of Renal Cell Cancer.

BACKGROUND: Heterozygous gene mutations in fumarate hydratase can result in a syndrome characterized by hereditary (cutaneous and uterine) leiomyomatosis and renal cell cancer. This disorder has been described in more than 200 families, but the prevalence of the disease is unknown. CASE: A 22 year-old woman of Bangladeshi lineage presented with menorrhagia and pelvic pain secondary to uterine leiomyomas and underwent an abdominal myomectomy. Because of a family history of renal cell cancer, she was tested for fumarate hydratase mutations and found to be a carrier. As a result of the risk of renal cell cancer associated with this mutation, an annual surveillance plan was initiated. CONCLUSION: Fumarate hydratase gene mutations should be considered in women presenting with leiomyomas and a family history of renal cancer.

GnRH decreases adiponectin expression in pituitary gonadotropes via the calcium and PKA pathways.

As endocrinologically active cells, adipocytes are capable of secreting various adipocytokines such as leptin, resistin, and adiponectin to impact metabolic function. Although adipocytes remain to be the primary site of synthesis and secretion, there is now growing evidence that supports the presence of adiponectin and its receptors within the hypothalamic-pituitary-gonadal axis, providing a possible link between obesity and abnormal reproductive physiology. It has been demonstrated that adiponectin may reduce gonadotropin-releasing hormone (GnRH) secretion from the hypothalamus as well as modulate gonadal steroid hormone production. Furthermore, prior data indicate that adiponectin may play a role in decreasing luteinizing hormone secretion from pituitary gonadotropes. We aimed to identify the hormonal regulators of adiponectin and its receptors, AdipoR1 and AdipoR2, in pituitary gonadotropes using immortalized gonadotropic LßT2 cells and primary rat pituitary cells. Our study shows significant alterations in adiponectin expression across the estrous cycle. In addition, we present a novel finding that GnRH suppresses pituitary adiponectin expression via the calcium and protein kinase A intracellular pathways in both cultured rat primary pituitary cells and the LßT2 gonadotrope cell line. The GnRH did not alter expression of the adiponectin receptors, AdipoR1 and AdipoR2, in cultured gonadotropes. Expression of the adiponectin receptors, AdipoR1 and AdipoR2, was not altered by GnRH in cell culture but in vivo or in vitro. Our data suggest that gonadotrope function may be modulated by GnRH-mediated changes in adiponectin expression.

Neonatal outcomes after demonstrated fetal lung maturity before 39 weeks of gestation.

OBJECTIVE: To compare outcomes among neonates delivered after documentation of fetal lung maturity before 39 weeks and those delivered at 39 or 40 weeks. METHODS: This was a retrospective cohort study of women with singleton pregnancy delivered at 36 0/7 to 38 6/7 weeks after positive fetal lung maturity testing (based on amniotic fluid lecithin to sphingomyelin ratio) or at 39 0/7 to 40 6/7 weeks (without maturity testing) at our center from 1999 to 2008. Women with fetuses with major congenital anomalies, cord prolapse, nonreassuring antepartum testing, placental abruption, or oligohydramnios were excluded. A primary composite neonatal outcome included death, adverse respiratory outcomes, hypoglycemia, treated hyperbilirubinemia, generalized seizures, necrotizing enterocolitis, hypoxic ischemic encephalopathy, periventricular leukomalacia, and suspected or proven sepsis. RESULTS: There were 459 neonates delivered at 36 to 38 weeks and 13,339 delivered at 39 to 40 weeks; mean birth weight was 3,107±548 g and 3,362±439 g, respectively. The risk of the composite adverse neonatal outcome was 6.1% for the 36- to 38-week group compared with 2.5% for the 39- to 40-week group (relative risk 2.4; confidence interval [CI] 1.7-3.5). After multivariable adjustment, early delivery remained significantly associated with an increased risk of the composite outcome (adjusted odds ratio [OR]1.7; CI 1.1-2.6) as well as several individual outcomes, including respiratory distress syndrome (adjusted OR 7.6; CI 2.2-26.6), treated hyperbilirubinemia (adjusted OR 11.2; CI 3.6-34), and hypoglycemia (adjusted OR 5.8; CI 2.4-14.3). CONCLUSION: Neonates delivered at 36 to 38 weeks after confirmed fetal lung maturity are at higher risk of adverse outcomes than those delivered at 39 to 40 weeks.

The effect of peritoneal dialysate on DXA bone densitometry results in patients with end-stage renal disease.

The bone mineral density of patients undergoing peritoneal dialysis (PD) is low compared to a healthy population. No studies have been conducted to investigate whether the presence of peritoneal dialysate affects dual-energy X-ray absorptiometry (DXA) results. We hypothesized that the presence of peritoneal dialysate would not affect the measurement of bone mineral density (BMD) or bone mineral content (BMC) in the spine. Thirty patients on PD had DXA scans of the lumbar spine and hip completed before and after the drainage of peritoneal dialysate. A paired t-test was used to compare the difference in area, BMC, and BMD before and after drainage of dialysate. A significant difference was found in the BMC of the spine before and after the drainage of dialyzate. We recommend that peritoneal dialyzate be removed prior to scanning patients on PD and that densitometry technologists should be observant about the presence of peritoneal dialysate.