Mesut Oktem

Black cohosh and fluoxetine in the treatment of postmenopausal symptoms : A prospective, randomized trial

The objective of this study was to evaluate the efficacy of fluoxetine and black cohosh in the treatment of women with postmenopausal symptoms. A total of 120 healthy women with menopausal symptoms were recruited to this prospective study with a follow-up period of 6 mo. They were randomly assigned to 1 of 2 groups and were treated with fluoxetine or black cohosh. After entry into the study, patients were examined at the first, second, third, and sixth months of the treatment period. The women kept diaries in which they reported the daily number and intensity of hot flushes and night sweats. In addition, at the beginning and end of the third month, they completed questionnaires consisting of a modified Kupperman Index, Beck’s Depression Scale, and a RAND-36 Quality-of-Life Questionnaire. Statistically significant differences were noted in the Kupperman Index and Beck’s Depression Scale at the end of the third month in both groups compared with baseline values. In the black cohosh group, the Kupperman Index decreased significantly compared with that in the fluoxetine group by the end of the third month. On the other hand, in the fluoxetine group, Beck’s Depression Scale decreased significantly compared with that in the black cohosh group. Monthly scores for hot flushes and night sweats decreased significantly in both groups; however, black cohosh reduced monthly scores for hot flushes and night sweats to a greater extent than did fluoxetine. At the end of the sixth month of treatment, black cohosh reduced the hot flush score by 85%, compared with a 62% result for fluoxetine. By the sixth month of the study, 40 women had discontinued the study—20 (33%) in the fluoxetine group and 20 (33%) in the black cohosh group. Compared with fluoxetine, black cohosh is more effective for treating hot flushes and night sweats. On the other hand, fluoxetine is more effective in improvements shown on Beck’s Depression Scale.

Prediction of preterm delivery among women with threatened preterm labor.

Background/Aims: To determine predictive values of fetal fibronectin and phosphorylated insulin-like growth factor binding protein-1 (phIGFBP-1) in cervicovaginal secretions and ultrasonographic measurement of cervical length for delivery <35 weeks in patients with uterine contractions. Methods: Our study included 51 women between 24 and 35 weeks’ gestation with uterine contractions and 90 controls. Cervicovaginal samples were analyzed for presence of fetal fibronectin and phIGFBP-1. Cervical length was measured by transvaginal sonography. Results: Preterm birth rate was 19.6% (10/51) in the study group. Negative predictive values of fetal fibronectin, phIGFBP-1 and ultrasonographic cervical length <20 mm, and <25 mm for delivery <35 weeks were 91.9, 92.3, 91.1, and 90.5%, respectively. Positive predictive values were 50, 58.3, 100 and 66.7%, respectively. When results of fetal fibronectin/phIGFBP-1 test and ultrasonographic cervical length <25 mm were combined, specificity and positive predictive values of each test for delivery within 7 days increased. Conclusion: Fetal fibronectin and phIGFBP-1 tests have approximately equivalent ability to predict delivery <35 weeks’ gestation. An ultrasonographic cervical length measurement >20 mm or a negative fetal fibronectin/phIGFBP-1 test obtained from patients with uterine contractions at 24–35 weeks’ gestation may avoid overdiagnosis.

Polycystic ovary syndrome is associated with elevated plasma soluble CD40 ligand, a marker of coronary artery disease

OBJECTIVE To determine the level of plasma soluble CD40 ligand (sCD40L) in patients with polycystic ovary syndrome (PCOS). DESIGN Prospective study. SETTING Baskent University School of Medicine in Turkey. PATIENT(S) Thirty-one patients with PCOS and 31 non-PCOS (control) patients. INTERVENTION(S) Determination of plasma sCD40L and homocysteine levels. MAIN OUTCOME MEASURE(S) Plasma sCD40L, fasting glucose, fasting insulin, homeostatic model assessment insulin resistance index (HOMA-IR), LH, FSH, E(2), total T, DHEAS, total cholesterol, high- and low-density lipoprotein cholesterol, triglyceride, homocysteine, and high-sensitivity C-reactive protein (hsCRP). RESULT(S) The mean serum fasting insulin and HOMA-IR levels were significantly higher in the PCOS group. The mean serum homocysteine level was significantly higher in the PCOS group. Despite a trend for higher high-sensitivity C-reactive protein levels in the PCOS group, the difference did not reach statistical significance. The mean plasma sCD40L level in the PCOS group was significantly higher than that in the control group (5.14 +/- 3.65 ng/mL vs. 3.45 +/- 2.64 ng/mL, respectively). CONCLUSION(S) Polycystic ovary syndrome is associated with elevated levels of sCD40L and homocysteine.

A potential novel treatment strategy: inhibition of angiogenesis and inflammation by resveratrol for regression of endometriosis in an experimental rat model

Abstract The aim of our study was to evaluate the effectiveness of resveratrol in experimentally induced endometrial implants in rats through inhibiting angiogenesis and inflammation. Endometrial implants were surgically induced in 24 female Wistar–Albino rats in the first surgery. After confirmation of endometriotic foci in the second surgery, the rats were divided into resveratrol (seven rats), leuprolide acetate (eight rats), and control (seven rats) groups and medicated for 21 d. In the third surgery, the measurements of mean areas and histopathological analysis of endometriotic lesions, VEGF, and MCP-1 measurements in blood and peritoneal fluid samples, and immunohistochemical staining were evaluated. After treatment, significant reductions in mean areas of implants (p < 0.01) and decreased mean histopathological scores of the implants (p < 0.05), mean VEGF-staining scores of endometriotic implants (p = 0.01), and peritoneal fluid levels of VEGF and MCP-1 (p < 0.01, for VEGF and p < 0.01, for MCP-1) were found in the resveratrol and leuprolide acetate groups. Serum VEGF (p = 0.05) and MCP-1 (p = 0.01) levels after treatment were also significantly lower in the resveratrol and leuprolide acetate groups. Resveratrol appears to be a potential novel therapeutic agent in the treatment of endometriosis through inhibiting angiogenesis and inflammation. Further studies are needed to determine the optimum effective dose in humans and to evaluate other effects on reproductive physiology.

Follicle-stimulating hormone receptor (FSHR) alternative skipping of exon 2 or 3 affects ovarian response to FSH.

Genes critical for fertility are highly conserved in mammals. Interspecies DNA sequence variation, resulting in amino acid substitutions and post-transcriptional modifications, including alternative splicing, are a result of evolution and speciation. The mammalian follicle-stimulating hormone receptor (FSHR) gene encodes distinct species-specific forms by alternative splicing. Skipping of exon 2 of the human FSHR was reported in women of North American origin and correlated with low response to ovarian stimulation with exogenous follicle-stimulating hormone (FSH). To determine whether this variant correlated with low response in women of different genetic backgrounds, we performed a blinded retrospective observational study in a Turkish cohort. Ovarian response was determined as low, intermediate or high according to retrieved oocyte numbers after classifying patients in four age groups (<35, 35-37, 38-40, >40). Cumulus cells collected from 96 women undergoing IVF/ICSI following controlled ovarian hyperstimulation revealed four alternatively spliced FSHR products in seven patients (8%): exon 2 deletion in four patients; exon 3 and exons 2 + 3 deletion in one patient each, and a retention of an intron 1 fragment in one patient. In all others (92%) splicing was intact. Alternative skipping of exons 2, 3 or 2 + 3 were exclusive to low responders and was independent of the use of agonist or antagonist. Interestingly, skipping of exon 3 occurs naturally in the ovaries of domestic cats--a good comparative model for human fertility. We tested the signaling potential of human and cat variants after transfection in HEK293 cells and FSH stimulation. None of the splicing variants initiated cAMP signaling despite high FSH doses, unlike full-length proteins. These data substantiate the occurrence of FSHR exon skipping in a subgroup of low responders and suggest that species-specific regulation of FSHR splicing plays diverse roles in mammalian ovarian function.

Impact of testicular histopathology as a predictor of sperm retrieval and pregnancy outcome in patients with nonobstructive azoospermia: correlation with clinical and hormonal factors

In this study, our objective was to evaluate the impact of testicular histopathology on the outcome of intracytoplasmic sperm injection (ICSI) cycles of patients with nonobstructive azoospermia and correlate with clinical and hormonal parameters. For this purpose, 271 patients with nonobstructive azospermia (NOA) who underwent testicular sperm extraction (TESE) for ICSI cycles were retrospectively evaluated for sperm retrieval, fertilisation, embryo cleavage, clinical pregnancy and live birth rates among different testicular histology groups. We also correlated hormonal and clinical factors with histological findings. Sperm retrieval and fertilisation rates (FR) were found to be significantly different among all testicular histological groups of NOA except for embryo cleavage, clinical pregnancy and live birth rates. Furthermore, serum follicle stimulating hormone (FSH) level was the most significant variable to predict sperm recovery on TESE. Separate analyses within each testicular histological group revealed that higher FSH was also associated with lower pregnancy rates in only maturation arrest group. In conclusion, testicular histology significantly influences sperm retrieval and FRs but not pregnancy and live birth rates in nonobstructive azoospermia. However, FSH is the best predictor of a successful TESE.

Recombinant FSH increases live birth rates as compared to clomiphene citrate in intrauterine insemination cycles in couples with subfertility: a prospective randomized study

OBJECTIVE To compare the efficacy of intrauterine insemination (IUI) cycles undergoing ovarian hyperstimulation with recombinant FSH (rFSH) or clomiphene citrate (CC) in couples with unexplained and male subfertility. STUDY DESIGN Two hundred and nineteen subfertile couples were enrolled in this randomized prospective study. Patients were randomly assigned to receive 75IU rFSH or 100mg CC for two cycles. Cycles with more than four dominant follicles and/or serum E2 levels higher than 1500pg/ml were cancelled. Primary outcomes were live birth rates per patient and per cycle, secondary outcomes were clinical and multiple pregnancy rates. RESULTS One hundred and nine women received rFSH and 110 received CC. Both cumulative clinical pregnancy and live birth rates per patient were significantly higher in gonadotropin group (43.1% and 37.6%) as compared to CC group (28.2% and 20%) (p<0.05 and p<0.01, respectively). Live birth rate per cycle were significantly higher in gonadotropin group (24.3%) in comparison with CC group (13.8%) (p<0.05). However, clinical pregnancy rate per cycle was not different between groups (28.4% vs 20%) (p>0.05). There was no significant difference between gonadotropin and CC group groups in terms of multiple pregnancy rates (10.4% vs 12.5%, p>0.05). Continuous variables were compared with Students t test. Categorical variables were compared with Chi square test. CONCLUSION rFSH has significantly higher cumulative clinical pregnancy and live birth rates when compared to CC with similar multiple pregnancy rates in subfertile patients undergoing IUI.

Laparoscopic intracorporeal ultrasound guidance during hysteroscopic adhesiolysis

We introduce a case of hysteroscopic adhesiolysis by the guidance of laparoscopic intracorporeal ultrasound (LIU) in a patient complaining of amenorrhea and infertility found to have total intrauterine synechia. Adequate intrauterine adhesiolysis was performed by resectoscope with a wire loop, coordinating images of the endometrial cavity, uterine wall and the tip of the hysteroscope. She had regular menses after the operation and follow-up hysterosalpingogram at 3 months demonstrated satisfactory surgical results, with no evidence of intrauterine adhesions. To avoid the possibility of inadvertent uterine perforation, complex intrauterine procedures can be easily performed by the guidance of endoscopic ultrasonography.

Raloxifene has favourable effects on metabolic parameters but has no effect on left ventricular function in postmenopausal women

In this prospective randomized study, we investigated the effect of raloxifene on the echocardiographic parameters of left ventricular diastolic and systolic function and on blood levels of lipids, homocysteine, and lipoprotein (a) in postmenopausal osteoporotic patients and compared the results with those treated with risedronate. A total of 44 women were included in the study. Patients were randomized into two groups. Twenty-two patients received raloxifene 60 mg/day (group 1), and 22 patients received risedronate 5mg/day (group 2; the control group). All patients underwent quantitative two-dimensional pulsed wave Doppler and tissue Doppler echocardiography. Levels of fasting total-C, HDL-C, LDL-C, triglycerides, homocysteine, and lipoprotein (a) were measured. All echocardiographic and biochemical parameters were assessed at the beginning of the study and after the 6-month follow-up. Demographic characteristics and baseline metabolic and echocardiographic parameters were similar in the two groups. After 6 months of the therapy, serum levels of total-C, LDL-C, and homocysteine decreased significantly (P=.04, P=.02, P=.008, respectively) in the treated group when compared with the control group. All echocardiographic measurements except a wave from level of basal interventricular septum were similar in the two groups both before and after 6 month of therapy. In the control group, a wave from level of basal interventricular septum increased significantly (P=.019). In conclusions raloxifene may decrease serum levels of total-C, LDL-C, and homocysteine in postmenopausal osteoporotic patients and raloxifene therapy seems to have no significant effect on left ventricular systolic and diastolic function.

Laparoscopic Ultrasonography in the Management of Ovarian Cysts

Background: The aim of the study was to determine the role of laparoscopic ultrasonography in the management of ovarian cysts extirpated by means of endoscopic surgery. Methods: Laparoscopic ultrasonography was used during endoscopic surgery in 14 consecutive patients with an adnexal mass. The diagnostic accuracies of transvaginal and laparoscopic ultrasonography were compared according to the final pathological diagnosis. Estimations of the exact location of the ovarian mass by means of laparoscopic visualization and laparoscopic ultrasonography were compared. The presence of residual tumor tissue after cyst extirpation was monitored with laparoscopic ultrasonography. Results: Using laparoscopic ultrasound and transvaginal ultrasound the correct diagnosis was made in 12 of 14 (85.7%) and 9 of 14 (64.3%) patients, respectively (not significantly different). With laparoscopic visualization, the exact location of the ovarian tumor could be demonstrated in 57.1% (8/14) of the cases, while with laparoscopic ultrasonography precise visualization of the ovarian mass was achieved in all cases (not significantly different). Two patients were found to have residual tumor tissue in the ovary when laparoscopic ultrasonography was performed again after tumor extirpation. Conclusion: Laparoscopic ultrasonography seems to be useful in patients with an adnexal mass managed by endoscopic surgery, in terms of evaluating the internal characteristics and predicting the histological diagnosis of the ovarian cyst, deciding on the correct placement of the incision to prevent unnecessary trauma to the ovary, and evaluation of the ovary after cyst extirpation to expose any residual tumor tissue.