The effects of different therapeutic modalities on cardiovascular risk factors in women with polycystic ovary syndrome: A randomized controlled study.

OBJECTIVE: This study was designed to evaluate the effects of 3 mg drospirenone/30 µg ethinyl estradiol (OC) alone or combined with 1700 mg metformin on metabolic risk factors. MATERIALS AND METHODS: In this randomized, prospective, controlled study, 87 non-obese (18-30 BMI) women of reproductive age (18-39) with polycystic ovary syndrome (PCOS) were assigned to control (n = 17), OC (n = 21), combination (n = 20) and metformin (n = 29) therapy groups. RESULTS: Adiponectin levels changed -28.27%, -20.37% and 35.78% after OC, combination and metformin therapies, respectively. High sensitive C-reactive protein levels (hsCRP) changed with OC, combination and metformin therapies by 102.32%, 3.2% and -7.14%, respectively. Plasminogen activator inhibitor-1 levels decreased 41.34% in the metformin group. Apolipoprotein-B levels changed in a manner similar to changes in hsCRP levels. The homeostatic model insulin resistance index changed significantly between the groups following treatment (p = 0.001). CONCLUSION: Six cycles of treatments with OC alone may cause metabolic variables to deteriorate in non-obese women with PCOS. The addition of metformin to OC may ameliorate some aspects of this effect.

The status of telomerase enzyme activity in benign and malignant gynaecologic pathologies.

BACKGROUND: Telomeres are essential for the function and stability of eukaryotic chromosomes. Telomerase consists of three subunits: human telomerase reverse transcriptase (hTERT), human telomerase RNA (hTR), and telomerase protein 1 (TP1). The hTERT subunit determines the activity of telomerase as an enzyme and is detected in most human tumors and regenerative cells. Telomerase activity is a useful cancer-cell detecting marker in some types of cancers. AIMS: The aim of this study was to assess of telomerase hTERT mRNA in gynaecological tumors for diagnosis of malignancy. STUDY DESIGN: Cross-sectional study. METHODS: A total of 55 gynaecologic tumor samples (35 ovarian, 13 endometrial, 6 cervical and 1 placental site trophoblastic tumor tissue) were obtained at the time of surgery. Quantification of hTERT mRNA was performed in a real-time reverse transcriptase polymerase chain reaction (RT-PCR) using the LightCycler TeloTAGGG hTERT Quantification Kit. RESULTS: It was histopathologically detected that 18 of the tissue samples were malignant and 37 of the samples were benign. 16 of the malignant tissue samples (88.9%) and 3 (8.1%) (endometrial tissue in proliferative phase, mucinous cyst adenoma and endometriosis) of the benign tissue samples were found to be hTERT positive. With the presence of these data, sensitivity and specificity of hTERT for the diagnosis of malignancy were calculated to be 88.9% and 91.9%, respectively. CONCLUSION: It was suggested that the measurement of telomerase activity in gynaecologic tumors, except for endometrial tissue in the reproductive phase, is a valuable method for pathological investigation.

Increasing the stimulation dose of rFHS in unexpected poor responders is not associated with better IVF outcome.

OBJECTIVES: The aim of this retrospective study is to determine whether increasing the stimulation dose of rFSH in unexpected poor responders is associated with better IVF outcome or not. METHODS: A total of forty eligible women who fulfilled our definition of poor responders (< or = 3 follicles, < 4 oocytes or E2 levels < or = 500 pg/ml on day of hCG administration) and who did not achieve an ongoing pregnancy in the first cycle and who returned for a second higher rFSH dose IVF cycle with a long-agonist protocol were included to the study. The first-low dose cycles and the second-high dose cycles were compared to each other. Each patient functioned as her own control. Main outcome measures of the study were daily and total dose of rFSH, duration of stimulation, number of follicles, number of oocytes retrieved, number of embryos and E2 level on day of hCG injection. RESULTS: The first-low dose cycles and the second-high dose cycles were comparable regarding patient characteristics. There were no significant differences in duration of stimulation, number of follicles, number of oocytes retrieved, number of embryos and E2 level on day of hCG injection between the first-low and second-high dose cycles. Daily and total dose of rFSH were significantly higher in the second-high dose cycles. Fewer cycles were cancelled during the second higher gonadotrophin dose after first unexpected poor response. CONCLUSIONS: Increasing the starting dose of gonadotrophin after an unexpected poor response in the first IVF cycle is not an effective approach. It may increase the oocyte retrieval rates and embryo transfer rates, but will not add any significant improvement in the number of oocytes retrieved and the number of transferable embryos. The only important benefit of increasing the dose was the low cancellation rate.

Longitudinal study of platelet size changes in gestation and predictive power of elevated MPV in development of pre-eclampsia.

OBJECTIVES: The aim of this cohort is to investigate whether any haematologic changes detectable by simple complete blood count (CBC) precede pre-eclampsia development and the diagnostic value of these markers in clinical practice for prediction of pre-eclampsia. METHODS: All pregnant women, in the first trimester, attending to GATA Haydarpasa Teaching Hospital Obstetric Outpatient Clinic for routine obstetric care were enrolled. Routine obstetric care consisted of monthly visits until 32nd week, bimonthly visits between 32nd and 36th week, and weekly thereafter. According to the study, protocol CBC was taken from women at each visit and recorded. After delivery, outcome data were obtained. RESULTS: A total of 1336 women were included into the statistical analysis and 107 (8%) of them developed pre-eclampsia. Parameters of CBC were similar between groups other than mean platelet volume (MPV) values. MPV values of pre-eclamptic women were significantly higher than normotensive counterparts from 24th gestational week up to gestational week at birth. In pre-eclamptic group, mean gestational age of diagnosis was 33.8 weeks and significant MPV increase was detected to precede the diagnosis by approximately 4.6 weeks (range 2.8-5.9 weeks). CONCLUSIONS: Our study provides evidence that MPV gradually increases in pregnant women affected by pre-eclampsia compared to women with normal pregnancies.

Second trimester amniotic fluid annexin A5 levels and subsequent development of intrauterine growth restriction.

OBJECTIVE: The purpose of this study was to investigate the levels of annexin A5 in second trimester amniotic fluid, and evaluate its correlation with subsequent development of intrauterine growth restriction (IUGR). METHOD: A total of 264 women undergoing mid-trimester amniocentesis between January 2007 and December 2007 were enrolled for the study. Amniocentesis was performed for routine indications. After delivery, outcome data were obtained. RESULTS: Maternal age, frequency of nulliparity, fetal sex and gestational week at amniocentesis were similar between groups. As expected, prevalence of smoking was higher in IUGR developing mothers. Significant positive correlations were present between annexin A5 levels and gestational age at amniocentesis (P = 0.02) and maternal age (P = 0.01). Linear regression analysis revealed that annexin A5 levels were positively correlated with patient's age. Smoking women had significantly lower annexin A5 levels in the mid-trimester amniotic fluid (9.9 +/- 2.3 and 10.7 +/- 1.3 ng/mL, P = 0.01). Logistic regression analysis demonstrated that after controlling for gestational age at amniocentesis, smoking, maternal age, and maternal hypertension, annexin A5 was not significantly associated with IUGR (P = 0.07). CONCLUSION: Amniotic fluid annexin A5 levels in the mid-trimester are not associated with IUGR at birth after controlling for maternal smoking and other confounders.

Comparison of the risk of malignancy index and self-constructed logistic regression models in preoperative evaluation of adnexal masses.

OBJECTIVE: The aim of this study was to evaluate women with adnexal masses in the preoperative period by creating 2 logistic regression models, 1 including sonographic morphologic characteristics and the other including both morphologic and color Doppler characteristics, to compare the diagnostic accuracy of these 2 models with the risk of malignancy index (RMI). METHODS: This prospective study included 38 malignant, 7 borderline, and 244 benign ovarian masses. The menopausal status, presence of septa, presence of papillary projections, location of the tumor, presence of ascites, presence of metastases, cancer antigen 125 level, tumor volume, septa thickness, and percentage of the solid component were included in the initial analysis. A second regression analysis was performed with the addition of Doppler parameters (location of blood flow and lowest resistive index) in the data set. Diagnostic performance of the 2 regression models and RMI were described and compared by generating receiver operating characteristic curves for each model. RESULTS: The area under the curve values for the morphologic model (model 1), Doppler model (model 2), and RMI were 0.907, 0.971, and 0.889, respectively. Significance levels of model 1 and the RMI were similar (P = .23), whereas model 2 had a significantly higher area under the curve compared with both model 1 (P = .037) and the RMI (P = .018). CONCLUSIONS: The addition of Doppler parameters in the regression model significantly increases the predictive performance. Nevertheless, in low-resource settings, the RMI remains the method of choice for distinguishing adnexal masses and referral to gynecologic oncology clinics.

Recurrent idiopathic nonimmune hydrops fetalis: A case report.

A recurrent idiopathic nonimmune hydrops fetalis case in two subsequent pregnancies was observed in a woman with no child. In both pregnancies, all the detailed analysis, including a high level of ultrasonography, amniocentesis, serologic evaluation, routine blood work, hemoglobin electrophoresis, and glucose 6-phosphate/dehydrogenase level and postdelivery autopsy, was done, and after no clue of etiologic agent, pregnancy termination was applied for both. This case report illustrates the importance of recurrence of nonimmune hydrops fetalis in the absence of any etiology. Mostly, it is hard to establish an etiologic diagnosis for adequate management of subsequent pregnancies.

Pregnancy outcome following second-trimester amniocentesis: a case-control study.

The purpose of this study was to investigate whether second-trimester amniocentesis increases fetal loss rate. Two thousand sixty-eight women with singleton gestations who underwent mid-trimester amniocentesis at 15 to 22 weeks gestation and 2068 controls matched one-to-one for maternal age, parity, and the number of prior spontaneous abortions were studied prospectively in a case-control study design. The fetal loss rates and other adverse pregnancy outcomes were compared between the study and control groups using the Pearson chi2 test or Fisher exact test when appropriate. In the amniocentesis group, eight (0.4%) fetal losses occurred within 30 days of the procedure, and in the control group, six (0.3%) losses occurred within 30 days of the inclusion in the study; the difference was not statistically significant ( p = 0.59; OR, 1.34; 95% CI, 0.46 to 3.85). The total fetal loss rates including spontaneous abortions and intrauterine fetal deaths/stillbirths were 2.3 and 2% in the study and control groups, respectively, and the difference was not significant ( p = 0.59; OR, 1.12; 95% CI, 0.74 to 1.71). Amniotic fluid leakage occurred in only two (0.1%) of 2068 study patients. Transplacental needle passage was not associated with an increased risk of pregnancy loss compared with nontransplacental amniocentesis ( p = 0.92; OR, 0.96; 95% CI, 0.47 to 1.95). There was no statistically significant difference in fetal loss rate between women requiring two needle insertions to obtain amniotic fluid and those having only one insertion ( p = 1.00; OR, 0.75; 95% CI, 0.10 to 5.53). The rates of preterm deliveries, small for gestational age infants, preeclampsia/eclampsia, placental abruptions, and cesarean deliveries were also not significantly different between two groups (each p > 0.05). We conclude that second-trimester amniocentesis for prenatal diagnosis is a safe procedure that does not appear to increase fetal loss rate.

Aortic elastic properties in young pregnant women.

This study aimed to investigate the aortic elastic properties of young pregnant women by comparing them with those of age-matched healthy females. The study group consisted of 21 pregnant women at a mean age of 26 +/- 1 years; 22 healthy women at a mean age of 25 +/- 1 years constituted the control group. Doppler-color echocardiographic variables and serum estradiol (E2) levels were measured from both groups. The blood samples were obtained from the control group in the first week after menstrual bleeding. Diastolic and systolic blood pressure (DBP and SBP, respectively) were measured with a sphygmomanometer. Systolic and diastolic aortic diameters (AOS and AOD, respectively) were measured 3 cm proximal to the aortic valves. Aortic elastic properties were assessed according to the following formulas: 1, Aortic strain = (AOS - AOD)/AOD; 2, Aortic distensibility = 2 x (AOS - AOD)/(PP x AOD); 3, Aortic diameter change = AOS - AOD; 4, Aortic stiffness index = ln(SBP/DBP)/(AOS - AOD)/AOD. The results were expressed as mean +/- standard deviation and compared by t-test between groups. P < 0.05 was considered as statistically significant. All women in the study group were in their first pregnancy and second trimester. The height and weight were 160 +/- 5 vs 164 +/- 6 cm and 60 +/- 9 vs 54 +/- 3 kg in the study vs control groups, respectively (P < 0.05). The AOD was 26 +/- 3 vs 26 +/- 4 mm and AOS 29 +/- 3 vs 28 +/- 4 mm. Pulse pressure was 43 +/- 3 vs 45 +/- 8 mmHg in the study vs control groups, respectively (P > 0.05). The serum E2 level was significantly higher in pregnant women (21 300 +/- 2 300 pg/ml). Derived aortic elastic properties in pregnant women were also increased significantly (P < 0.0005). The indexes of aortic elastic properties are altered and aortic stiffness is decreased among young pregnant women. This may be due to the adaptation mechanisms including high estradiol levels detected in pregnancy.

Familial mediterranean fever-related nephrotic syndrome and successful full-term pregnancy.

Familial Mediterranean fever (FMF) is a systemic disease with an autosomal recessive inheritance. The most serious complication of FMF is renal amyloidosis. Pregnancy may adversely affect renal function in FMF patients with amyloidosis and nephrotic syndrome. A 20-year-old woman with FMF related nephrotic syndrome became pregnant while receiving colchicine therapy. Colchicine treatment was continued during pregnancy with close observation. She gave birth to a 2400 g healthy female newborn at the 38th week of gestation. Pregnancy and neonatal outcome were uneventful. It is advisable to continue colchicine treatment during conception and pregnancy in FMF patients with amyloid related nephrotic syndrome. Colchicine treatment with bed rest, protein reinforcement, acetylsalicylic acid administration and close follow-up may improve the outcome of pregnancy in FMF patients.

The effect of hormone therapy on plasma homocysteine levels: a randomized clinical trial.

OBJECTIVE: An elevated plasma homocysteine level is a risk factor for cardiovascular diseases. Hormone therapy (HT) may reduce fasting plasma homocysteine levels. We studied 80 postmenopausal women to determine the effect of medroxyprogesterone acetate (MPA) combined with conjugated equine estrogens (CEE) on fasting plasma homocysteine levels. DESIGN: In a randomized, double blind, prospective, placebo-controlled study, we randomly assigned 80 healthy postmenopausal women between CEE 0.625 mg/d combined with MPA 2.5 mg/d (n = 20), CEE 0.625 mg/d combined with MPA 5 mg/d (n = 20), unopposed CEE 0.625 mg/d (n = 20), and placebo (n = 20) all given for a duration of 6 months. Fasting plasma homocysteine levels were measured before and at the end of the treatment. RESULTS: Before treatment, plasma homocysteine concentrations were similar in all groups. After 6 months of unopposed CEE, the mean fasting plasma homocysteine levels decreased by 19.02% when compared with baseline levels (P < 0.05). The mean fasting plasma homocysteine concentrations decreased by 17.63% and 19.56% from baseline in both the CEE plus MPA 2.5 mg/d and CEE plus MPA 5 mg/d groups, respectively (P < 0.05 for each group). In contrast, plasma homocysteine levels increased by 11.66% in the placebo group. The homocysteine lowering effect did not differ significantly among the three groups of women receiving unopposed CEE alone and CEE plus MPA at two different doses. CONCLUSION: Six months of estrogen therapy (ET) and combined estrogen-progestogen therapy (EPT) significantly lower fasting plasma homocysteine levels in healthy postmenopausal women with equal efficacy.

Differential RNA expression and polyribosome loading of alternative transcripts of the Akap4 gene in murine spermatids.

An X chromosome-linked gene, Akap4, is expressed only during spermiogenesis and encodes the major fibrous sheath protein of the mouse sperm flagellum. All sperm contain the AKAP4 protein even though only X chromosome-bearing spermatids express the gene, indicating that the Akap4 mRNA and/or protein must be shared among the conjoined spermatids via the intercellular bridges. There are two mouse Akap4 cDNA clones, Akap82 and Fsc1, which represent mRNAs that arise by alternative processing of a single gene. Although Akap82 and Fsc1 encode identical mature proteins, they differ in their 5' UTRs. We hypothesized that the expression pattern of these two mRNAs might be relevant to the issue of mRNA and/or protein transport into adjacent spermatids. Expression of both transcripts began in round spermatids, but the amount of the Akap82 transcript in condensing spermatids increased twofold relative to Fsc1. Significantly, only the Akap82 transcript was found on polyribosomes and translated in spermatids. These results indicate that the Akap82 transcript and/or its protein must be shared among the conjoined X and Y chromosome-bearing spermatids. Although Fsc1 was not polysomal, both the Akap82 and Fsc1 transcripts were deadenylated during spermiogenesis, suggesting that deadenylation is not always correlated with loading of mRNAs onto polyribosomes in germ cells. The distinct 5' UTR sequences in Akap82 and Fsc1 did not differ in their ability to regulate translation of reporter constructs either in vivo or in vitro. Antisense RNA transcripts complementary to both the Akap82 and Fsc1 mRNAs were present, suggesting that translatability may be regulated by these RNAs.

Calreticulin on the mouse egg surface mediates transmembrane signaling linked to cell cycle resumption.

Calreticulin, a protein best known as an endoplasmic reticulum chaperone, also is found on the extracellular plasma membrane surface of many cell types where it serves as a mediator of adhesion and as a regulator of the immune response. In this report, we demonstrate that calreticulin is present on the extracellular surface of the mouse egg plasma membrane and is increased in the perivitelline space after egg activation. The extracellular calreticulin appears to be secreted by vesicles in the egg cortex that are distinct from cortical granules. An anticalreticulin antibody binds to extracellular calreticulin on live eggs and inhibits sperm-egg binding but not fusion. In addition, engagement of cell surface calreticulin by incubation of mouse eggs in the presence of anticalreticulin antibodies results in alterations in the localization of cortical actin and the resumption of meiosis as indicated by alterations in chromatin configuration, decreases in cdc2/cyclin B1 and MAP kinase activities, and pronuclear formation. These events occur in the absence of any observable alterations in intercellular calcium. These data demonstrate that calreticulin functionally interacts with the egg cytoskeleton and can mediate transmembrane signaling linked to cell cycle resumption. These studies suggest a role for calreticulin as a lectin that may be involved in signal transduction events during or after sperm-egg interactions at fertilization.

Requirements for glucose beyond sperm capacitation during in vitro fertilization in the mouse.

In both the mouse and the human, it is a point of controversy whether glucose is necessary for in vitro fertilization. Some of this controversy has resulted from a failure to distinguish between requirements for glucose during sperm capacitation versus requirements during the multistage process of fertilization. Using the mouse as a model, we performed a series of experiments designed to identify specific processes that might require glucose. We observed a positive correlation between increasing glucose concentrations during capacitation and fertilization, and increasing fertilization of zona pellucida (ZP)-intact eggs. These data supported a requirement for glucose in the fertilization medium even when sperm were first capacitated in the presence of 5.5 mM glucose. This glucose requirement was observed for both ZP-intact and ZP-free eggs. During ZP-free in vitro fertilization, some binding and fusion between the plasma membrane of the sperm and egg occurred in the absence of glucose and at concentrations less than 1 mM, suggesting that this substrate is not absolutely required. However, glucose concentrations of 1 mM or higher greatly facilitated both binding and fusion under these conditions. These subtle distinctions suggest that during ZP-free in vitro fertilization, 1 mM glucose represents a threshold level that facilitates binding and fusion. Taken as a whole, the data suggest requirements for glucose during both capacitation and fertilization under normal physiologic conditions.

24-year-old female with amenorhea: bilateral primary ovarian Burkitt lymphoma.

OBJECTIVES: Burkitt's lymphoma (BL) occurs mostly in children. Isolated bilateral ovarian involvement presenting with amenorrhea is extremely rare in young adults. CASE: A 24-year-old female presented with secondary amenorrhea. Bilateral adnexal masses were identified on physical examination and abdominal computed tomography (CT). She underwent total abdominal histerectomy and bilateral salpingoophorectomy. Histopathologic evaluation yielded a diagnosis of BL of ovaries. Combined chemotherapy was administered. After complete remission an autologous bone marrow transplantation (ABMT) was performed. She died 35 days after ABMT. CONCLUSIONS: Although rare, BL should be kept in mind when isolated ovarian tumors are detected in young patients.