Koray Elter

Reply: Combating endometriosis by blocking proteasome and nuclear factor-κB pathways

BACKGROUNDnThe objective of this study is to investigate the effect of pyrrolidine dithiocarbamate [PDTC; a nuclear factor-kappaB (NF-kappaB) inhibitor] and bortezomib (Velcade; a proteasome inhibitor) on the development of experimental endometriotic implants in rats.nnnMETHODSnEndometriosis was surgically induced in 30 rats using the method of Vernon and Wilson. Three weeks later the viability and volume of the implants were recorded and classified. Afterwards, rats were put into three groups with equal numbers. The groups were labelled as the control, the PDTC and the bortezomib groups. Seven days after treatment, a third laparotomy was done and the volume of implants was measured again. The animals were then sacrificed, and the implants were stained with Ki67, proliferating cell nuclear antigen (PCNA), CD34, CD31 and Massons trichrome histochemical staining.nnnRESULTSnIn 80% of the implanted rats, vesicles at the suture region were observed, and the rats graded according to average vesicle diameter (D) as: Grade 1 (no vesicle, 20% of rats), Grade 2 (D < 2 mm, 33.3% of rats), Grade 3 (2 mm 4.5 mm, 26.7% of rats) and Grade 4 (D > 4.5 mm, 20% of rats). After treatment with PDTC or bortezomib, these percentages were decreased for Grades 3 and 4, and increased in Grade 1. The post-treatment implant volumes were decreased in the PDTC and bortezomib groups (P < 0.002 and P < 0.001), and slightly increased in the control group (P = 0.279). In the PDTC and bortezomib groups, CD34, CD31, PCNA and Ki67 expression levels were similar but were significantly reduced compared with the control group.nnnCONCLUSIONSnPDTC and bortezomib may represent a novel therapeutic strategy for treatment of endometriosis.

Screening for pre-eclampsia by using maternal serum inhibin A, activin A, human chorionic gonadotropin, unconjugated estriol, and alpha-fetoprotein levels and uterine artery Doppler in the second trimester of pregnancy.

Aims:u2002 To analyse the predictive power of maternal serum inhibin A, activin A, human chorionic gonadotropin (hCG), unconjugated estriol (uE3), alpha‐fetoprotein (AFP) levels and uterine artery Doppler in the second trimester of pregnancy in screening for pre‐eclampsia.

Exposure to low outdoor temperature in the midtrimester is associated with low birth weight

Background: Although seasonal variation of birth weight has been reported previously, contributing factors such as the meteorological factor and its specific period of exposure remain unclear.

Antral follicle assessment after down-regulation may be a useful tool for predicting pregnancy loss in in vitro fertilization pregnancies

Women with diminished ovarian reserve (OR) have a high rate of pregnancy loss. The relationship between hormonal OR tests and pregnancy loss has been studied previously, but, to our knowledge, that between the antral follicle count (AFC) and pregnancy loss has not. Therefore, we aimed to determine whether OR tests, including the AFC, can predict pregnancy loss in women achieving pregnancy by means of in vitro fertilization (IVF), and also to compare their predictive value. All women underwent a fresh cycle of intracytoplasmic sperm injection with a long protocol with mid-luteal start of the gonadotropin-releasing hormone analog, and antral follicles were counted on cycle day 3 following down-regulation. Pregnancy losses up to 12 gestational weeks (nu200a=u200a28) were compared with apparently healthy deliveries (nu200a=u200a34) in this retrospective analysis. Receiver operating characteristic analysis of consecutive pregnancies (nu200a=u200a71) was performed to analyze the optimum cut-off value for the significantly different OR tests. Women with a pregnancy loss had a lower AFC than those with healthy deliveries. Age and hormonal OR tests were comparable between groups. The optimum cut-off value for the AFC to predict pregnancy loss was 7.5. AFC may be a useful tool for predicting pregnancy loss in IVF pregnancies.

Intercycle variabilities of basal antral follicle count and ovarian volume in subfertile women and their relationship to reproductive aging: A prospective study

Background.u2003Reproducibility is an important issue when using tests for estimating ovarian reserve and counseling patients. However, little is known about the intercycle variabilities of basal antral follicle count and ovarian volume. In this prospective study, we analysed the intercycle variabilities of the antral follicle count and ovarian volume, and compared them with those of other basal ovarian reserve tests in subfertile patients. Method.u2003Fifty-two ovulatory and infertile women were followed for two consecutive spontaneous cycles. The antral follicle count, ovarian volume, serum follicle stimulating hormone and estradiol levels were determined on day 3 of both cycles. Limits of agreement between two measurements were determined. Results.u2003Limits of agreement were –u200a6.9 and 6.5 for the antral follicle count, and –u200a8.3 and 8.6 for the ovarian volume. These degrees of variation corresponded to a range of 1.30 and 1.45 times their means for the ovarian volume and antral follicle count, respectively. The variability in the antral follicle count was greater in women who were younger than 24.5 years than in those who were older. Conclusions.u2003Intercycle variabilities of the antral follicle count and ovarian volume were clinically significant. More variation was observed in the antral follicle count of young infertile patients. Therefore, a low antral follicle count in young, infertile, but ovulatory women should be cautiously interpreted. This may not reflect a low ovarian reserve, and these women may have a high antral follicle count in the next cycle.

The efficacy of first-trimester PAPP-A and free βhCG levels for predicting adverse pregnancy outcome

Abstract Objective: To determine whether first-trimester measurements of maternal serum PAPP-A and free βhCG levels were associated with adverse pregnancy outcomes. Study Design: First trimester maternal serum free βhCG and PAPP-A were measured in 490 singleton pregnancies. Pregnancies were followed by the fetal-maternal unit, and predictive efficacy of these markers for small for gestational age (SGA) babies, gestational diabetes mellitus and hypertensive disorders were analyzed by cut-off values determined by using a ROC analysis, and also, by using the fifth percentile as the cut-off value. Results: The sensitivities for PAPP-A in predicting pregnancies with a SGA baby and those complicated by a hypertensive disorder were 49% and 73%, respectively, when optimal cut-off values were used. Specificities were 76% and 65%, respectively. Serum free βhCG had no predictive value for individual pregnancy outcomes. Conclusion: Efficacy of first trimester maternal serum markers in predicting adverse pregnancy outcome is low. Even after optimization of cut-off values, these markers do not appear to be clinically acceptable as an effective tool for screening for adverse pregnancy outcomes.

Effect of tibolone treatment on intima- media thickness and the resistive indices of the carotid arteries

OBJECTIVEnTo assess the effect of tibolone treatment on the intima-media thickness (IMT) of the common carotid artery (CCA) and the resistive indices (RIs) of the CCA and internal (ICA) and external (ECA) carotid and the vertebral arteries (VAs) in postmenopausal women as sonographic markers of atherosclerosis.nnnDESIGNnA prospective study.nnnSETTINGnUniversity hospital.nnnPATIENT(S)nTwenty postmenopausal women who had no cardiovascular disease.nnnINTERVENTION(S)nNoninvasive measurements of the IMT of the CCA and the RI of the CCA, ICA, ECA, and VA were made with ultrasound at baseline and after 12 weeks of tibolone treatment.nnnMAIN OUTCOME MEASURE(S)nIMT of the CCA and RI of the CCA, ICA, ECA, and VA.nnnRESULT(S)nThree months of tibolone treatment decreased the IMT of the CCA (mean +/- SD) from 0.70 +/- 0.22 mm (95% confidence interval [CI], 0.60-0.80) to 0.47 +/- 0.17 mm (95% CI, 0.39-0.55) by 28%. Resistive indices of the CCA, ICA, and VA also decreased significantly.nnnCONCLUSION(S)nThe present study showed that tibolone treatment decreases both the IMT of the CCA and RI of the CCA, ICA, and VA, which appears to be related to its anti-atherosclerotic effect. Nevertheless, the clinical implications of these findings are yet to be investigated.

Should we consider performing oral glucose tolerance tests more frequently in postmenopausal women for optimal screening of impaired glucose tolerance

ObjectiveTo investigate an optimal screening protocol for impaired glucose tolerance (IGT) and type II or non-insulin-dependent diabetes mellitus (DM) by using fasting plasma glucose (FPG) and oral glucose tolerance test (OGTT) in postmenopausal women. DesignOne hundred consecutive postmenopausal women were screened with FPG determination, and then all underwent an OGTT. Basal serum lipid and insulin levels of these women were also determined. Insulin sensitivity was determined by using the homeostasis model assessment. Receiver operating characteristic analysis was performed to determine the efficacy of these variables in detecting women with IGT and DM, and optimal cutoff values were determined. ResultsFPG with a cutoff value of 98 mg/dL had the best combination of sensitivity (71%) and specificity (76%) for the detection of IGT and DM. Combined FPG and body mass index screening (with the optimal cutoff value of 26.5 kg/m2) improved the sensitivity to 96% but decreased the specificity to 47%. This combined screening protocol detected 94% of the women with IGT and all diabetic women. ConclusionsGiven that IGT and DM are common among postmenopausal women and DM can be prevented by nonpharmacologic interventions in women with IGT, OGTT may be used more frequently among these women. Our data indicate that for optimal screening of non-insulin-dependent DM and IGT, OGTT should be considered in postmenopausal women, especially when risk factors in addition to age are present. This model may detect most of the women with IGT and almost all diabetic women.

Postomenopozal sürenin lipid ve lipoprotein seviyeleri üzerindeki etkisi

Objective: To investigate the effect of years since menopause, independent of age, on lipid and lipoprotein levels. Materials and Methods: Records of 80 post menopausal women, who were admitted to the Menopause Outpatient Clinic of the Marmara University Hospital between January - October 2003, were retrospectively analyzed. The participants were first divided into two groups according to their age; younger group consisted of those, who were between 41 and 51 years of age (n=36), and older group consisted of those, who were

Does birthweight affect the mode of delivery

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