hMG addition affects the change in progesterone level during IVF stimulation and LBR: a retrospective cohort study.

BACKGROUND: Premature progesterone (P) rise during IVF stimulation reduces endometrial receptivity and is associated with lower pregnancy rates following embryo transfer (ET), which can influence provider recommendation for fresh or frozen ET. This study aimed to determine whether change in P level between in IVF baseline and trigger (𝚫P) is predictive of pregnancy outcome following fresh ET, and whether the ratio of gonadotropins influences P rise and, as a result, clinical pregnancy outcomes: clinical pregnancy rate (CPR) and live birth rates (LBR). METHODS: Retrospective cohort study at a single fertility center at an academic institution. The peak P level and 𝚫P were modeled in relation to prediction of CPR and LBR, and the ratios of hMG:rFSH were also modeled in relation to prediction of peak P level on day of trigger, 𝚫P, and CPR/LBR in a total of 291 patients undergoing fresh embryo transfer after controlled ovarian hyperstimulation-IVF (COH-IVF). RESULTS: 𝚫P correlates with CPR, with the most predictive range for success as 𝚫P 0.7-0.85 ng/mL (p = 0.005, 95% CI 0.635, 3.636; predicting CPR of 88.9%). The optimal range for peak P in regard to pregnancy outcome was 0.15-1.349 ng/mL (p = 0.01; 95% CI for coefficient in model 0.48-3.570). A multivariable logistic model for prediction of CPR and LBR using either peak or 𝚫P supported a stronger association between 𝚫P and CPR/LBR as compared to peak P. Furthermore, an hMG:rFSH ratio of > 0.6 was predictive of lowest peak P (p = 0.010, 95% CI 0.035, 0.256) and smallest 𝚫P (p = 0.012, 95% CI 0.030, 0.243) during COH-IVF cycles. Highest CPRs were observed within hMG:rFSH ratios of 0.3-0.4 [75.6% vs. 62.5% within and outside of the range, respectively, (p = 0.023, 95% CI 0.119, 1.618)]. Highest LBRs were seen within the range of 0.3-0.6 hMG:rFSH, [LBR of 55.4% vs. 41.4% (p = 0.010, 95% CI 0.176, 1.311)]. CONCLUSIONS: Our data supports use of 𝚫P to best predict pregnancy rates and therefore can improve clinical decision making as to when fresh ET is most appropriate. Furthermore, we found optimal gonadotropin ratios can be considered to minimize P rise and to optimize CPR/LBR, emphasizing the importance of luteinizing hormone (LH) activity in COH-IVF cycles.

A New Clock is Running for Multiple Myeloma: Circadian Clock Protein-Period 3 (PER-3) Polymorphism.

Circadian Clock Protein PERIOD 3 (PER-3) is situated on chromosome 1p36.23 and has a polymorphic domain that expresses 4 or 5 copies of the 54-bp tandem repeat sequence. PER-3 gene polymorphisms play a role in the dysregulation of the immune system. This study intended to investigate the distributions and clinical effectiveness of the PER-3 gene polymorphism in multiple myeloma (MM) patients. One hundred fifty patients diagnosed between January 2007-2009 and 100 healthy individuals were included in this study. All patients were suitable for autologous stem cell transplantation (ASCT) at first evaluation, and after 4 courses of VCD at least partial remission, ASCT was carried out. Later, LD was used as maintenance. Genotypes of PER-3 gene of patients and healthy controls were statistically compared before treatment. In addition, these genotypes' effects on overall and progression free survival (OS and PFS) were investigated. Median PFS in the 5R/5R genotype was found to be significantly longer, albeit low, at 86% (p = 0.046). In the statistical analysis performed between the 4R/4R genotype and others, the PFS of patients with 4R/4R was found to be significantly shorter at 40.4 months (p = 0.026). Patients with the 4R/4R genotype would have a risk of 2.049 times of a shorter PFS (p=0.009). With this first study investigating the effect of a circadian gene in MM, the net effect of PER-3 gene polymorphism on PFS was revealed, and it will be a guide for future studies.

Trehalose enhances osmotic tolerance and suppresses lysophosphatidylcholine-induced acrosome reaction in ram spermatozoon.

This study was aimed to investigate the influence of trehalose on osmotic tolerance and the ability of ram spermatozoon to undergo acrosome reaction induced by lysophosphatidylcholine (LPC). In experiment 1, the diluted ejaculates were exposed to anisosmotic fructose solutions (70, 500, 750 and 1000 mOsm l(-1) ) with or without 50 mm trehalose. The presence of trehalose in hyperosmotic conditions enhanced (P < 0.05) the percentage of live, live-intact and intact spermatozoa. Similarly, trehalose enhanced (P < 0.05) the live and live-intact spermatozoa during hypo-osmotic conditions. In experiment 2, the centrifuged ejaculates were diluted with TCG only or TCG containing either 50 or 100 mm trehalose. The acrosome reaction was induced by LPC. The percentage of acrosome-reacted spermatozoon was less (P < 0.05) in trehalose-supplemented groups compared to control. In experiment 3, the ejaculates were cryopreserved in an extender containing 0 mm (control), 50 mm or 100 mm trehalose. Supplementation of extender with trehalose, either 50 mm or 100 mm, enhanced the cryosurvival rate (P < 0.05) compared to the control. In conclusion, the presence of trehalose in anisosmotic conditions enhances the osmotic tolerance, cryosurvival rate of ram spermatozoon and suppresses their ability to undergo LPC and cryo-induced acrosome reaction.

Naringenin inhibits neointimal hyperplasia following arterial reconstruction with interpositional vein graft.

Vessels respond to injury by a healing process that includes the development of neointima. Stenosis secondary to neointima formation is the main cause of failure following arterial reconstructions. Vessel wall homeostasis is regulated by proinflammatory cytokines that affect smooth muscle cell proliferation, growth, migration, and death. We assessed the hypothesis that naringenin, a flavinoid possessing anti-inflammatory, antioxidant, and antiproliferative activities, reduces neointimal hyperplasia (NIH) following vascular injury.Arterial injury was created by interposition grafting of autologous right superficial epigastric vein graft into the right femoral artery (FA) in 48 male Sprague-Dawley rats. Following injury, the rats were divided into 4 groups (n = 12). Two groups were treated with naringenin (100 mg/kg intraperitoneal q daily) for 2 and 4 weeks each while 2 control groups received normal saline for the same durations. For Sham group (n = 10), the FA and vein were isolated without any additional procedure. Rats were killed at the end of treatment regimen in all groups, and FAs were harvested. Thickness of intima was measured in histologic sections, and levels of platelet derived growth factor (PDGF)-BB, TNFalpha, and Ki67 labeling index (Ki67 LI) were quantified in immunohistochemical analyses to assess the amount of NIH and mechanisms underlying its formation.Although there was no significant difference between the groups at 2 weeks, neointima thickness was lower in the naringenin treated group at 4 weeks (23.7 +/- 2.3 vs. 35.6 +/- 2.6 microm in control group; P < 0.001). The levels of PDGF-BB, and TNFalpha were lower in naringenin treated groups at both 2 weeks (PDGF-BB [0.21% +/- 0.03% versus 0.39% +/- 0.05% in control group, P < 0.001), TNFalpha (21.2% +/- 0.8% vs. 36.1% +/- 1.9% in control group, P < 0.001]) and 4 weeks (PDGF-BB [0.25% +/- 0.03% vs. 0.57% +/- 0.09% in control group, P < 0.001], TNFalpha [25.5% +/- 1.8% vs. 45.0% +/- 2.9% in control group, P < 0.001]). Ki67 LI was lower in naringenin treated groups at 2 weeks (13.9% +/- 2.8% vs. 18.7% +/- 3.7% in control group, P < 0.05), and at 4 weeks (17.5% +/- 2.6% vs. 31.1% +/- 4.7% in control group, P < 0.001), indicating a lower level of cellular proliferation.Naringenin reduces NIH following arterial reconstruction. This may be mediated by a decrease in PDGF-BB and TNFalpha levels and the resulting down-regulation of smooth muscle cells' migration and proliferation.

Inhibitory effects of desflurane and sevoflurane on oxytocin-induced contractions of isolated pregnant human myometrium.

BACKGROUND: In this study, we investigated the inhibitory effects of desflurane and sevoflurane on oxytocin-induced contractions of isolated human myometrium. METHODS: Following delivery of the infant and placenta, a small segment of myometrium was excised from the upper incisional surface of the lower uterine segment and 20 strips, randomly assigned into two groups (n = 10), were obtained from 20 non-laboring term parturients. The study protocol consisted of a 60-min period of spontaneous contractions, control recording with oxytocin 2 x 10(9) m (10-min period), washout interval of 10 min, volatile administration (three times per 15-min period) of 0.5, 1 and 2 minimum alveolar concentration (MAC), response to oxytocin (10-min period), a further washout interval (10-min period) and subsequent control recording with oxytocin without anesthetics. RESULTS: After oxytocin administration, the frequency and amplitude of contractions increased (P < 0.05) and the duration decreased (P < 0.05). The frequency and amplitude of contractions induced with oxytocin decreased significantly at 0.5, 1 and 2 MAC of desflurane and sevoflurane (P < 0.05). The amplitude of contractions was significantly different at 1 MAC between the two groups (P < 0.05). The duration of contractions at 2 MAC decreased in both groups (P < 0.05). CONCLUSIONS: Desflurane and sevoflurane at 0.5, 1 and 2 MAC inhibit the frequency and amplitude of myometrial contractions induced with oxytocin in a dose-dependent manner. However, desflurane inhibits the amplitude less than sevoflurane at 1 MAC. We suggest that 0.5 MAC of both agents and 1 MAC of desflurane may be safely used in the presence of oxytocin following delivery of the infant and placenta during Cesarean section without fear of uterine atony and hemorrhage.

Doppler ultrasound assessment and serum cancer antigen 125 in the diagnosis of ovarian tumors.

OBJECTIVE: To differentiate benign from malignant ovarian tumors based on sonographic detection of a solid component. METHOD: Sixty-three women with ovarian masses were evaluated preoperatively by gray scale and power/color Doppler ultrasonographic examination, with specific predefined criteria for the solid component. Sensitivity, specificity, and positive and negative predictive values were calculated and assessed against the histopathologic outcome. The contribution of cancer antigen (CA) 125 levels to the diagnostic accuracy was also assessed. RESULT: Sensitivity, specificity, and positive and negative predictive values were 100%, 95.2%, 91.3% and 100%, respectively, with two false-positive results. Had an elevated CA 125 level (>35 U/mL) been included in the malignancy criteria, the false-positive results would have been eliminated, giving an accuracy of 100%. CONCLUSION: Sonographic evaluation with predefined specific criteria for the detection of a solid tumor component is an accurate method of preoperative discrimination between benign and malignant ovarian tumors. A serum CA 125 assay may assist in eliminating false-positive results.

Effect of melatonin in the prevention of post-operative adhesion formation in a rat uterine horn adhesion model.

BACKGROUND: Our main aim was to investigate the effects of melatonin (ME), possibly the most powerful free-radical scavenger, on the prevention of i.p. adhesion formation in rat uterine horn. Our secondary aim was to determine whether different methods of administration of ME were beneficial. METHODS: Animals were randomly assigned into seven groups, each consisting of 13 rats. Measured serosal injury was created using a standard technique. While control and two sham groups were not given ME, two of the remaining four groups were given a single dose of 10 mg/kg (2 mg) of ME i.p. immediately after injury and 30 min prior to injury respectively. In the two other groups, ME treatment was continued daily for 5 days. All animals were killed 2 weeks after surgery and adhesions were determined and scored by a examiner blinded to the test. RESULTS: The extent, severity and total scores of adhesion were found to be significantly reduced in all of the ME treatment groups when compared with control and sham groups. There were no statistically significant differences between the treatment groups. CONCLUSIONS: This study showed that even single dose ME therapy was effective in the prevention of post- operative i.p. adhesion formation.

Human papillomavirus frequency of women at low risk of developing cervical cancer: a preliminary study from a Turkish university hospital.

PURPOSE: To investigate the frequency of human papillomavirus (HPV) infection among low-risk women for cervical cancer in our region. METHODS: In one year period, 230 consecutive women at low risk of developing cervical cancer were enrolled to the study. HPV DNA testing was performed by Hybrid Capture-I System (HC-I) and groups were constituted by HPV-positive and HPV-negative women. A comparison of the groups according to age, obstetric history and age at the beginning of sexual intercourse was made. Statistical analysis was performed. RESULTS: The frequency rate of HPV infection was demonstrated to be 6.1% (n = 14) in our study (5.9% in women < or = 45 years and 7.7% in women > 45 years). Age-dependent differences were not observed between groups. There was no significant difference between HPV-positive and negative women regarding obstetric characteristics and mean age at first intercourse. CONCLUSION: This study provided significant information on the frequency of HPV infection of low-risk women in our region. When considered with studies performed in other countries, our study may give some help on the natural history of HPV infection and cervical squamous lesions.

Differential diagnosis of intra-uterine device migrating to bladder using radiographic image of calculus formation and review of literature.

A 28-year-old woman in whom a copper-T 280-A intra-uterine device (IUD) had been placed 6 months previously, presented complaining of urinary system infection and lower abdominal pain. Intra-vesical migration of IUD was confirmed by radiography and cystoscopy. Since 1966, 17 other cases of calculus formation among 41 cases of intra-vesical migration have been reported.

Maternal erythrocyte malondialdehyde level in preeclampsia prediction: a longitudinal study.

We aimed to determine the value of maternal erythrocyte malondialdehyde levels in the prediction of preeclampsia. 110 healthy women were included in this prospective study. Maternal erythrocyte malondialdehyde levels were measured at each trimester of pregnancy (10-14, 20-25 and 30-35 gestational weeks). On follow-up, patients were assigned to two groups as normotensive women and preeclamptic patients. Preeclampsia had developed in eight (8.9%) of the 90 pregnant women who completed the study. Preeclamptic patients were diagnosed between 36 and 39 gestational weeks (36.8 +/- 1.0 weeks). Malondialdehyde levels of preeclamptic patients increased significantly in the third trimester (p < 0.05), while there was no difference between values of malondialdehyde in the first and second trimester. Malondialdehyde levels were significantly higher in the patients who developed preeclampsia than in those who did not in the third trimester (p < 0.05). With the use of the receiver operating characteristics (ROC) 35.98 nmol malondialdehyde/gm hemoglobin was found to be a cut-off value predictive for the development of preeclampsia in the third trimester. However, cut-off values in the first and second trimesters could not be found. The sensitivity, specificity, positive and negative predictive values were 89, 75, 29 and 98%, respectively. Preeclampsia risk was found to increase nearly 24 times in values above 35.98 nmol malondialdehyde/ gm hemoglobin. Our results showed that maternal erythrocyte malondialdehyde could predict patients within a few weeks prior to onset of clinical symptoms of preeclampsia in the third trimester. There is no evidence of enhanced early lipid peroxidation in pregnancies with late onset preeclampsia.

Idiopathic calcinosis cutis of the vulva in an elderly woman. A case report.

BACKGROUND: Idiopathic calcinosis cutis of the vulva is a rare condition of unknown etiology. Only seven cases have been reported to date, and all of them were in children. We report the first case in an elderly woman. CASE: A 68-year-old woman presented with a labial lesion of unknown etiology. Excisional biopsy was performed, and histopathologic evaluation showed subepidermal calcification. Follow-up biochemical and hormonal analysis and screening tests for collagen vascular diseases revealed normal results. CONCLUSION: After diagnosis of calcinosis cutis, a laboratory workup to rule out abnormalities of calcium and phosphorus metabolism, malignant processes and collagen vascular diseases must be carried out. This approach in the evaluation of calcinosis cutis could lead to diagnosis of the underlying disease at an early stage.

Effects of pentoxifylline in the prevention of ovarian hyperstimulation syndrome in a rabbit model.

Tumor necrosis factor alpha (TNF-alpha) and other cytokines have been implicated in the pathogenesis of ovarian hyperstimulation syndrome (OHSS). Pentoxifylline, a methylxanthine derivative, was found to inhibit TNF-alpha synthesis. The aim of this study was to evaluate whether the use of pentoxifylline would prevent the occurrence of OHSS in a rabbit model. Thirteen rabbits were divided into two groups. The first group (n = 6) were given pentoxifylline 15 mg/kg intravenously and the second group (n = 7) were given physiological serum 15 mg/kg before ovulation induction. Ovarian hyperstimulation was induced in rabbits by 200 IU equine chorionic gonadotropin on day 1 and 100 IU human chorionic gonadotropin on day 3. Blood samples were analyzed for TNF-alpha on days 1, 3 and 5. All animals were autopsied on day 6 to evaluate the ovarian weight, ascites formation and histopathological changes. There was no difference between groups regarding weight gain, ascites formation and plasma TNF-alpha levels (p < 0.05). Ovarian weight and number of ovulations were significantly lower in the pentoxifylline group than the control group (p < 0.05). Pentoxifylline did not prevent ascites formation despite the observed decrease in ovarian weight and number of ovulations in OHSS in a rabbit model.

Androgen levels of preeclamptic patients in the third trimester of pregnancy and six weeks after delivery.

BACKGROUND: The aim of this study was to measure the circulating levels of androgens in the third trimester of pregnancy and six weeks after delivery and to discuss androgen contribution in the pathogenesis of preeclampsia. METHODS: Twenty-two preeclamptic and 20 normotensive women completed this prospective study. Blood samples were drawn in the third trimester (28-32 gestational weeks) and six weeks after delivery. Serum total testosterone (T), free testosterone (fT) dehydroepiandrosterone sulfate (DHEAS), androstenodione (A), sex hormone binding globulin (SHBG) and estradiol (E2) levels were measured. The statistical analyses of the data were performed by using Wilcoxon Rank test within the groups, Student unpaired t test and Chi-square test between the groups with the SPSS program. RESULTS: T and fT levels were found to be significantly higher (p<0.05) in preeclamptic women in the third trimester compared to the values of normotensive controls. However, there were significant decreases (p<0.05) in T and fT levels six weeks after delivery, reaching values not significantly different from normotensive subjects (p>0.05). Furthermore, SHBG, DHEAS, A and E2 levels were not significantly different (p>0.05) between the groups in the third trimester or six weeks after delivery. CONCLUSION: We conclude that higher blood androgen levels measured in preeclamptic patients may be implicated in the pathogenesis of preeclampsia.

Activated protein C resistance in Turkish women with severe preeclampsia.

The purpose of this study was to investigate the occurrence rate of APC resistance (APC-R) with severe preeclampsia in Turkish women. Thirty-two consecutive women having severe preeclampsia were included in the study. Thirty-two healthy pregnant women served as the control group. APC-R assays were performed in the third trimester of pregnancy, and 3 and 9 months after delivery. APC-R was demonstrated in the third trimester, 3 months and 9 months after delivery in 27 (84.4%), 23 (71.9%) and 5 (15.6%) of 32 preeclamptic patients, respectively. APC-R rates were significantly higher in preeclamptic group than in normal pregnant women in the third trimester of pregnancy (p < 0.05). Decreased mean APC activity and also increased APC-R rate was still persisting in preeclamptic group for 3 months after delivery. Nine months after delivery, the mean APC activity and also APC-R rates approached to the normal pregnant women; however, there was a significant difference between both groups (p < 0.05). Our results indicate that acquired APC-R may be a contributory factor in the pathogenesis of preeclampsia.

Continuous versus cyclical transdermal oestrogen replacement therapy in postmenopausal women: effects on lipoprotein(a) and nitric oxide levels.

The purpose of our study was to compare the effects of cyclical versus continuous transdermal oestrogen replacement therapy on lipoprotein (a) (Lp(a)) and nitric oxide levels. The patients were randomly assigned into two groups. The first group received transdermal 17-beta oestradiol 50 microg/day for 21 days and the second group the same treatment on a continuous basis. Medroxyprogesterone acetate (10 mg/day orally) was added between the 14th and 25th days to each group. Lipoprotein (a) and nitric oxide levels were measured before the study and after six months. These values were compared using the Wilcoxon rank test within the groups and the unpaired t-test between the groups. Lipoprotein (a) levels decreased significantly in each group at the sixth month (p < 0.05). When compared between the groups, the decrease of lipoprotein (a) levels in the second group was more prominent at the sixth month (p < 0.05). Nitric oxide levels increased in each group after six months (p < 0.05). No difference in nitric oxide levels was observed between the groups before and after the therapy (p > 0.05). Continuous transdermal estradiol had a better effect on lipoprotein (a) levels than cyclical therapy The seven day pause in the 21-day administration did not affect nitric oxide levels negatively after six months.

Long-term effects of continuous oral and transdermal estrogen replacement therapy on sex hormone binding globulin and free testosterone levels.

OBJECTIVE: To determine the long-term effects of estrogen replacement therapy on sex hormone binding globuline (SHBG) and free testosterone (fT) levels in surgical postmenopausal women. STUDY DESIGN: Forty patients with surgical menopause were enrolled in this prospective study. The women were randomly divided into two groups. The first group received oral therapy (continuous conjugated equine estrogens (CEE) - 0.625mg per day) and the second group received transdermal therapy (patches delivering continuous 17beta-estradiol (E2)--0.05mg per day). Serum SHBG and fT levels were determined at baseline and after first and second years of treatment. Two-way repeated measures analysis of variance with Bonferroni adjusted post-hoc test and unpaired-t-test were performed for statistical analysis with SPSS program. RESULTS: Serum SHBG levels increased significantly with oral CEE after first year of treatment (P<0.05) and remained at this level for the next year. Transdermal therapy did not affect SHBG levels after first and second years (P<0.05). Serum fT levels did not change significantly in either group at the end of the first or second years (P<0.05) although there was a significant difference between the groups after 2 years (P<0.05). CONCLUSION: Oral conjugated estrogens increased SHBG levels during therapy. This effect may balance the increased estrogen and androgen stimulation on breast tissue and may be more beneficial to the cardiovascular system in postmenopausal women.