Hormone replacement therapy and risk of breast cancer

To determine the effect of different types and formulations of hormone replacement therapy [HRT] on the risk of breast cancer in postmenopausal women at Mansoura University Hospitals. This study was conducted in Obstetrics and Gynaecology, General Surgery and Oncology and Nuclear Medicine Departments, Faculty of Medicine, Mansoura University from January 2005 to June 2008. The study group included 210 cases of postmenopausal women ranging in age from 50-70 years with breast cancer for whom surgical interventions were done according to the stage. The study group were matched with '0 cases representing control group. The rate of breast cancer was Increased with the use of opposed estrogens in oral form [adjusted relative risk "RR" 1.1; 95% confidence interval "CI" 1.31-1.42] and injectable [RR 1.1; 95% CI 0.86-1.20]. The rate of breast cancer was not increased among users of unopposed estrogens [RR 0.96; 95% CI 0.86-1.09] or of progestins only [RR 0.86; 95% CI 0.85-1.12]. Oral etstrogen-progestin combinations appear to be associated with an increased breast cancer risk while estrogens alone and progestins are not

role of serum vascular endothelial growth factor in the prediction of ovarian hyperstimulation syndrome in women with polycysic ovarian syndrome

Background: Ovarian hyperstimulation syndrome [OHSS] is an iatrogenic and potentially life-threatening complication of treatment with fertility drugs. Women with polycystic ovaries [PCO] and polycystic ovarian syndrome [PCOS] are at a particularly higher risk of developing OHSS. The traditional determinants viz, serum estradiol [E2] concentrations and the number of follicles on the day of human chorionic gonadotrophin [hCG] administration are not only increasingly recognized that they do not adequately define the risks for this syndrome but also do not accurately predict its occurrence. On the other hand, numerous reports now emphasized the role of vascular endothelial growth factor [VEGF] as an important mediator of the syndrome and that it provides a nonsteroidal index of the ovarian response to gonadotrophin simulation

Objective: The aim of this study was to examine the possible role of the circulating serum VEGF concentration pattern during ovarian stimulation as a method of predicting OHSS in women with PCOS and hence its possible real prevention. Design: A prospective designed study. Setting: Outpatient women's clinics, Departments of Obstetrics and Gynecology, Benha and Mansoura University Hospitals

Patients and Methods: A total of ninety-six women with anovulatory infertility due to PCOS were included in the study. All women underwent controlled ovarian stimulation and were followed-up for the development of OHSS. Cases who developed mild OHSS [n=6] were excluded from the study, while those who developed either moderate [n=6] or severe OHSS [n=2] were only included. Consequently, the remaining studied women [n=90] were divided into two groups: an "OHSS group" [moderate, n = 8] and a "non OHSS group" [n = 82]. Serum was collected from all patients in the early follicular phase before the initiation of the treatment, on the days of hCG injection and 48 hours after hCG injection and was assayed for VEGF concentration

Results: The serum VEGF concentration increased significantly in all the studied women during ovarian stimulation irrespective of whether OHSS developed or not. The rise was significantly higher on the day of hCG administration than in the early follicular phase at the beginning of ovarian stimulation in both groups [it increased from 156.3 +/- 45.2 to 257.4 +/- 108.6 pg/mL in women in whom OHSS developed and from 145.4 +/- 39.8 to 168.2 +/- 36.5 pg/mL in women in whom it did not] [P < 0.01].There was a further increment in the VEGF concentration 48 hours after hCG administration in both groups [up to 398.5 +/- 112.9 and 186.2 +/- 42.8 pg/mL respectively]. The levels of serum VEGF on both the day of hCG administration and 48 hours after hCG administration were significantly higher in women with OHSS than those without OHSS. A cut-off value of 240 pg/mL for serum VEGF concentration on the day of hCG administration offered a sensitivity of 76.8%, negative predictive value [NPV] of 82.2% and positive predictive value [PPV] of 73.4%. The rise in the serum VEGF concentration that occurred between the day of the beginning of cycle stimulation and the day of hCG administration [referred to as the "VEGF rise before hCG administration"] and that occurred between the day of hCG administration and 48 hours after hCG administration [referred to as the "VEGF rise after hCG administration"] were significantly higher in women in whom OHSS developed than in those without OHSS [P < 0.05]. Both were found to be good markers for the development of OHSS. The sensitivity, NPV and PPV for "VEGF rise after hCG administration" at a cut-off value of 100 pg/mL were 96.6%, 93.8% and 65.4% respectively in the prediction of OHSS. Similar values, although slightly lower were obtained for the "VEGF rise before hCG administration" at a cutoff value of 70pg/ mL [90.2%, 91.4% and 62.3% respectively]

Conclusion: The "VEGF rise after hCG administration" might offer a good single marker for prediction but not real prevention of the development of OHSS in PCOS women during ovarian simulation. Worthily "VEGF rise before hCG administration" might offer a similar good single marker for its prediction and also a real chance for its prevention at the same time both in in vitro fertilization [TVF] and non-IVF stimulated cycles. Prevention can be achieved by withholding hCG administration, canceling the cycle, lowering the dose of hCG or withholding hCG for a couple of days [coasting] and thus ultimately avoiding a life- threatening complication in such at risk group of women

Second trimester plasma homocysteine assay in prediction of pre-eclampsia

Homocysteine, the demethylated derivative of the essential amino acid, methionine, is regulated by several factors. Elevated levels during pregnancy are associated with an increased incidence of spontaneous abortion, intrauterine growth restriction, placental infarction and neural tube dejects. Pre-eclampsia was added to this list of homocysteine-related pregnancy complications. The aim of this study was to determine the value of second trimester plasma homocysteine levels in the prediction of pre-eclampsia. This prospective study included 168 healthy primigravidae with singleton gestation from those attended the antenatal care clinic at Mansoura and Benha University Hospitals. Blood samples were obtained at their antenatal visits between 16 - 20 weeks. Plasma homocysteine was measured by enzyme immunoassay. The participants were followed up clinically till delivery for subsequent development of preeclampsia. The mean [ +/- SD] homocysteine level at 18.4 +/- 2.0 weeks gestation in women who developed pre-eclampsia [Group I] was significantly higher than those who did not develop pre-eclampsia [Group II] [10.2 micromol/ L +/- 3.6 micromol /L versus 8.2 micromol / L +/- 1.6 micromol/L respectively: p < 0.001]. Those patients with plasma homocysteine level of> 12 micromol / L in early pregnancy had an increased risk for developing pre-eclampsia by almost two and half folds. Also, plasma homocysteine level showed significant negative correlation with serum folic acid. An elevated second trimester plasma homocysteine level is associated with increased risk for subsequent development of pre-eclampsia. Also, the significant negative correlation between plasma homocysteine and serum folic acid levels may offer a hope for the use of folic acid supplements to prevent the development of pre-eclampsia in high risk pregnancies