Letrozole-associated controlled ovarian hyperstimulation in breast cancer patients versus conventional controlled ovarian hyperstimulation in infertile patients: assessment of oocyte quality related biomarkers.

BACKGROUND: Fertility preservation (FP) protocols in case of breast cancer (BC) include mature oocyte cryopreservation following letrozole associated controlled ovarian hyperstimulation (Let-COH). To date, the impact of Let-COH on the follicular microenvironment has been poorly investigated, although a high androgen/estrogen ratio was previously associated with low oocyte quality. METHODS: In this prospective study, follicular fluid (FF) steroid levels (estradiol, testosterone, progesterone) and cumulus cell (CC) gene expression related to oocyte quality (HAS2, PTGS2, GREM1) were compared between 23 BC patients undergoing Let-COH for FP and 24 infertile patients undergoing conventional COH without letrozole. All patients underwent an antagonist COH cycle, and ovulation was triggered with hCG or GnRHa in both groups. RESULTS: FF estradiol levels were significantly lower while testosterone levels were significantly higher in the study group compared to controls irrespective of the trigger method. However, estradiol levels increased significantly with GnRHa triggering compared to hCG in the study group (median = 194.5 (95.4-438) vs 64.4 (43.8-152.4) ng/ml, respectively, p < 0.001), but not in the control group (median = 335.5 (177.5-466.7) vs 354 (179-511) ng/ml, respectively). After hCG trigger, Cumulus cell (CC) gene expression was lower in the study group compared to the control group, and difference was significant for PTGS2. Conversely, CC gene expression of PTGS2 and GREM1 was significantly higher in the study group compared to controls when ovulation was triggered with GnRHa. CONCLUSIONS: Let-COH triggered with hCG may negatively impact oocyte quality. However, ovulation triggering with GnRHa may improve the oocyte microenvironment and cumulus cell genes expression in Let-COH, suggesting a positive impact on oocyte quality in breast cancer patients. TRIAL REGISTRATION: Clinicaltrials.gov - NCT02661932 , registered 25 January 2016, retrospectively registered.

Comparison of two assays measuring human chorionic gonadotrophin serum concentrations in pregnancy termination and trophoblastic or non-trophoblastic tumours.

BACKGROUND: Differences in human chorionic gonadotrophin (hCG) results provided by the commercial immunoassays reflect the heterogeneity of antibodies and the use of suboptimal standards. As a consequence, the principal forms of hCG and metabolites are differentially detected and the hCG tests are not suited for the same clinical applications. Conflicting results are available in the literature regarding which hCG variants are recognized by the Roche Elecsys hCG + ß test. The aim of our study was to compare the hCG concentrations provided by the Siemens Immulite 2000 test and the Roche test as well as to assess the concordance between both assays. METHODS: In this purpose, 152 samples obtained from women and 44 samples from men were analysed by both tests during the follow-up of pregnancy termination, gestational trophoblastic disease and malignancies. The intermediate precision of the Roche test was also investigated on a pool with a low hCG concentration. RESULTS AND CONCLUSIONS: The hCG concentrations measured with the Roche test were slightly lower compared with the Siemens assay; mean biases of -34.2% and -8% were respectively obtained for hCG values ≤100 UI/L and higher than 100 UI/L. The overall agreement between both assays was 96.1% for women and 97.7% for men. By using an upper reference limit of 3.2 UI/L for women and 1.6 UI/L for men, the Roche test demonstrated a respective concordance of 98.7% and 100%. This test also yielded an excellent precision with a coefficient of variation of 2.8% at a mean hCG concentration of 7 UI/L.

Marked 25-hydroxyvitamin D deficiency is associated with poor prognosis in patients with alcoholic liver disease.

BACKGROUND & AIMS: Vitamin D deficiency has been frequently reported in advanced liver disease. However, its influence on alcoholic liver disease (ALD) has been poorly elucidated. We investigated the association of vitamin D with clinical, biological, and histological parameters and survival in ALD patients. Furthermore, we explored the effect of vitamin D treatment on ALD patient peripheral blood mononuclear cells (PBMCs), and in a murine experimental model of ALD. METHODS: Serum levels of 25-hydroxyvitamin D [25(OH)D] were determined in 324 Caucasian ALD patients and 201 healthy controls. In vitro experiments on vitamin D pre-treated PBMCs evaluated TNFα production by ELISA in culture supernatants. Mice were submitted to an ethanol-fed diet and some of them were orally supplemented three times per week with 1,25(OH)2D. RESULTS: Severe deficiency in 25(OH)D (<10 ng/ml) was significantly associated with higher aspartate aminotransferase levels (p=1.00 × 10(-3)), increased hepatic venous pressure gradient (p=5.80 × 10(-6)), MELD (p=2.50 × 10(-4)), and Child-Pugh scores (p=8.50 × 10(-7)). Furthermore, in multivariable analysis, a low 25(OH)D concentration was associated with cirrhosis (OR=2.13, 95% CI=1.18-3.84, p=0.013) and mortality (HR=4.33, 95% CI=1.47-12.78, p=7.94 × 10(-3)) at one year. In addition, in vitro, 1,25(OH)2D pretreatment decreased TNFα production by stimulated PBMCs of ALD patients (p=3.00 × 10(-3)), while in vivo, it decreased hepatic TNFα expression in ethanol-fed mice (p=0.04). CONCLUSIONS: Low 25(OH)D levels are associated with increased liver damage and mortality in ALD. Our results suggest that vitamin D might be both a biomarker of severity and a potential therapeutic target in ALD.

Vitamin D deficiency and hyperparathyroidism in relation to ethnicity: a cross-sectional survey in healthy adults.

BACKGROUND: The study of vitamin D status at population level gained relevance since vitamin D deficiency was recently suggested to trigger chronic disease. AIM OF THE STUDY: We aimed to describe vitamin D status, its association with bone and mineral metabolism and risk factors for deficiency in adults over 40 years in Belgium. METHODS: We conducted a cross-sectional survey in a stratified random sample of 401 subjects aged between 40 and 60 years living in Brussels, and drawn from 4 different ethnic backgrounds: autochthonous Belgian, Moroccan, Turkish and Congolese. 25-Hydroxyvitamin D (25OHD), parathyroid hormone (PTH), osteocalcin, C-telopeptide and bone mineral density was measured. RESULTS: Three-hundred and six subjects (77%) showed 25OHD concentrations below 50 nmol/l,135 (34%) below 25 nmol/l and 18 (5%) below 12.5 nmol/l. The proportion of subjects with vitamin D deficiency was four times greater amongst those of Moroccan or Turkish descent compared with those of Congolese or Belgian descent. Moroccan subjects showed a significant higher PTH and bone marker concentrations compared to Belgian. Ethnicity, season and sex were independently associated with vitamin D deficiency in multivariate analysis. CONCLUSION: The prevalence of vitamin D deficiency is very high amongst the adult population of Brussels but immigrants are at greater risk. Given the established link between population health and adequate vitamin D status, a policy of vitamin D supplementation should be considered in these risk groups.

Acrylamide does not induce tumorigenesis or major defects in mice in vivo.

Chronic administration of acrylamide has been shown to induce thyroid tumors in rat. In vitro acrylamide also causes DNA damage, as demonstrated by the comet assay, in various types of cells including human thyroid cells and lymphocytes, as well as rat thyroid cell lines. In this work, mice were administered acrylamide in their drinking water in doses comparable with those used in rats, i.e., around 3-4 mg/kg per day for mice treated 2, 6, and 8 months. Some of the mice were also treated with thyroxine (T(4)) to depress the activity of the thyroid. Others were treated with methimazole that inhibits thyroid hormone synthesis and consequently secretion and thus induces TSH secretion and thyroid activation. These moderate treatments were shown to have their known effect on the thyroid (e.g. thyroid hormone and thyrotropin serum levels, thyroid gland morphology...). Besides, T(4) induced an important polydipsia and degenerative hypertrophy of adrenal medulla. Acrylamide exerted various discrete effects and at high doses caused peripheral neuropathy, as demonstrated by hind-leg paralysis. However, it did not induce thyroid tumorigenesis. These results show that the thyroid tumorigenic effects of acrylamide are not observed in another rodent species, the mouse, and suggest the necessity of an epidemiological study in human to conclude on a public health policy.

Relationship among maternal serum endocrinology, placental karyotype, and intervillous circulation in early pregnancy failure.

OBJECTIVE: To evaluate the relationship among maternal serum endocrinology, placental karyotype, and intervillous blood flow in missed miscarriage. DESIGN: Cross-sectional study of maternal serum, transvaginal ultrasound/Doppler, and placental cytogenetic and immunohistochemical investigations. SETTING: Tertiary care academic hospital. PATIENT(S): One hundred fifty-two women with missed miscarriage between 7 and 13 weeks of gestation. INTERVENTION(S): Ultrasound features, placental intervillous circulation findings on color Doppler imaging, and maternal serum level of alpha-fetoprotein (AFP), beta-hCG, E(2), P, and inhibin A were compared retrospectively with placenta karyotype and hCG immunochemistry. MAIN OUTCOME MEASURES: Data were analyzed according to karyotype results, presence or absence of an intervillous circulation, and delay between fetal demise and evacuation. RESULT(S): The presence of intervillous blood flow and serum concentrations of the different hormones were independent of placental karyotype. Serum beta-hCG and P were significantly higher in cases with intervillous blood flow. No difference in immunostaining for beta-hCG was found between placental tissues from normal pregnancies and missed miscarriages, but significantly higher villous beta-hCG content was found on Western blotting in miscarriage with a recent fetal demise. CONCLUSION(S): The excessive entry of maternal blood inside the placenta in the early stage of most miscarriages is unrelated to conceptus karyotype, and hCG features may reflect a temporary attempt of the trophoblast to stabilize after the initial oxidative insult.