Endothelial cell-specific molecule 1 is regulated separately in follicular and serum compartments of PCOS patients: a pilot study.

OBJECTIVE: The aim of our study is to detect endothelial cell-specific molecule 1 (ESM-1) levels in the serum and follicular fluids (FF) of patients undergoing IVF/ICSI for PCOS. The presence of ESM-1 traffic between the serum and follicular compartment was analyzed. PATIENTS AND METHODS: A total of 50 patients, including 25 infertile patients diagnosed with PCOS according to the Revised Rotterdam criteria, and 25 patients in infertility follow-up for reasons other than PCOS, were included in the pilot study. Patients in the control group were required to have no clinical and laboratory findings of PCOS. Non-PCOS controls were selected from patients diagnosed with a male factor or unexplained infertility, and a homogeneous group was formed. Patients in PCOS and control groups were matched in terms of age and BMI. IVF/ICSI was started with antagonist protocol in both groups. Follicular fluids obtained on the day of egg collection were centrifuged, put into RNAlater, frozen, and stored until the day of analysis. Endothelial cell-specific Molecule 1 levels were measured in follicular fluid and serum samples of PCOS patients by enzyme-linked immunosorbent assay (ELISA) using the Human ESM-1 kit. RESULTS: Serum ESM-1 levels of the PCOS group were significantly lower than FF-ESM1 levels (668.6±189.2 vs. 979.0±233.9 ng/L, p<0.02). FF-ESM1 levels of the control group were significantly higher than serum ESM1 levels (639.3±206.4 ng/L vs. 503.2±102.4 ng/L, p<0.01). Serum ESM1 levels of the PCOS group were significantly higher than the control group (668.6±189.2 ng/L vs. 503.2±102.4 ng/L, p<0.01). Similarly, FF-ESM1 levels of the PCOS group were significantly higher than the control group (979.0±233.9 ng/L vs. 639.3±206.4 ng/L, p<0.01). There was no significant correlation between serum and FF-ESM1 levels. A positive and significant correlation was found between FF-ESM1 and serum LH levels in PCOS (r=0.655, p<0.02). Similarly, a positive and significant correlation was found between FF-ESM1 and serum testosterone levels in PCOS (r=0.470, p<0.03). Moreover, a positive and significant correlation was detected between FF-ESM-1, AFC, MII, and total oocyte counts in PCOS. CONCLUSIONS: Serum and FF-ESM-1 are regulated independently of each other in PCOS patients. ESM-1 may play a role in ovulatory dysfunction due to PCOS.

Fertility protective effect of taxifolin in cisplatin-induced ovarian damage.

OBJECTIVE: The aim of our study was to investigate the protective effect of taxifolin on ovarian damage and reproductive dysfunction created by cisplatin administration. MATERIALS AND METHODS: A total of 36 albino Wistar female adult rats were equally divided into 3 groups as cisplatin administered only (CIS), taxifolin+cisplatin (T+C) and healthy control group (HG). Taxifolin 50 mg/kg was administered orally by gavage in the T+C (n=12) group. In the HG (n=12) and CIS (n=12) groups, the same volume of distilled water as a solvent was orally administered. One hour after administration of taxifolin or distilled water, animals in the T+C and CIS groups were injected with cisplatin at a dose of 2.5 mg/kg intraperitoneally. This procedure was repeated once a day for 14 days. Six animals from each group were sacrificed on day 15, and their ovaries were removed for histopathological and biochemical analysis. Ovarian tissue malondialdehyde (MDA), total Glutathione (tGSH), Nuclear Factor-Kappa B (NF-kB), Tumor Necrosis Factor-α (TNF-α), Interleukin 1 beta (IL-1ß), and Interleukin-6 (IL-6) levels were measured. The remaining animals (n=6 in each group) were kept in the laboratory with mature male rats for two months to breed. RESULTS: CIS administration led to an increase in inflammatory molecules and membrane lipid peroxidation products, and decreased the synthesis of antioxidant molecules. Compared to the CIS group, the ovarian tissue MDA, NF-kB, TNF-α, IL-1ß and IL-6 levels were found to be significantly decreased in the T+C group (p<0.001 for all comparisons). On the other hand, the tGSH levels of the T+C group were significantly higher than the CIS group (p<0.001). Milder ovarian necrosis, fibrosis and follicle damage were detected in animals which were given taxifolin. Four out of the six rats (67%) treated with taxifolin gave birth within 27 days. CONCLUSIONS: We demonstrated, for the first time, that taxifolin ameliorates cisplatin-induced ovarian injury by decreasing MDA and proinflammatory cytokines and increasing the antioxidant enzyme. The fact that more than half of the animals receiving taxifolin became pregnant suggests that the cytoprotective effect of taxifolin is strong enough to preserve fertility.

Comparing the effects of endometrial injury with hysteroscopy or Pipelle cannula on fertility outcome.

OBJECTIVE: To compare the effects of mechanical endometrial injury performed with hysteroscopy or Pipelle cannula on fertility outcome in patients with implantation failure. PATIENTS AND METHODS: Sixty patients with a history of two or more failed ICSI despite the transfer of high-quality embryos were equally divided into three groups: Group A - injury with hysteroscopy (n=20), Group B - injury with Pipelle cannula (n=20), Group C - no injury (n=20). Patients in group A underwent endometrial injury with monopolar needle forceps between days 10-12 of the proliferative phase in the preceding cycle before ovarian stimulation. Patients in group B underwent endometrial injury with Pipelle cannula between days 22-24 of the mid-luteal phase in the preceding cycle. Patients in group C had no injuries. Beta-hCG, clinical pregnancy, live birth and miscarriage rates were analyzed among the groups. RESULTS: There were no significant differences in terms of positive pregnancy test, clinical pregnancy and live birth rates between hysteroscopy and Pipelle groups. Compared to the control group, both clinical pregnancy and live birth rates were found to be significantly higher in patients who underwent endometrial injury with hysteroscopy or Pipelle cannula. Miscarriage rates in the control group were significantly higher than those in the Pipella or hysteroscopic injury. CONCLUSIONS: Endometrial injuries performed in the follicular phase with hysteroscopic monopolar forceps or in the secretory phase with Pipelle cannula increase pregnancy and live birth.

Endometrial polyps prevent embryo implantation via creatine and lactate pathways.

OBJECTIVE: This study was planned to investigate the concentration of basic endometrial metabolites such as endometrial choline (Cho), creatine (Cr) and lactate in subfertile women diagnosed with endometrial polyps. PATIENTS AND METHODS: Twenty patients with endometrial polyps detected in routine infertility evaluation and 20 fertile control patients with at least two children were included in the study. The endometrium of the patients in both groups was subjected to spectroscopy at mid-luteal phase and Cho, Cr, and lactate signals were recorded as a ppm. RESULTS: Compared to the fertile group, a decrease in Cr signal and an increase in lactate signal were detected in patients with endometrial polyp. Cho densities of both groups were found to be similar. The Cho peak of patients with endometrial polyp was 3.01 ± 1.22 ppm, while the Cho peak of the control patients was 2.90 ± 1.13 ppm. The Cr peak of patients with endometrial polyp was 1.36 ± 0.33 ppm, while the Cr peak of the control patients was 1.99 ± 0.02 ppm. The lactate peak of patients with endometrial polyp was 0.87± 0.10 ppm, while the lactate peak of the control patients was 0.54 ± 0.32 ppm. CONCLUSIONS: Decreased Cr and increased lactate signals may be evidence of impaired receptivity in subfertile patients with endometrial polyps.

Calcium gluconate infusion is not as effective as dopamine agonists in preventing ovarian hyperstimulation syndrome.

OBJECTIVE: The aim of the study was to compare the effectiveness of calcium gluconate and cabergoline therapy in the prevention of ovarian hyperstimulation syndrome (OHSS). PATIENTS AND METHODS: Eight hundred and forty-five women who underwent GnRH antagonist protocol and at high risk for developing OHSS were divided into two groups, those given cabergoline (n=435) or calcium gluconate (n=410). In cabergoline group, 0.5 mg of cabergoline was administered once daily p.o. starting on the day of ovulation trigger and continued until the following 8 days. In calcium gluconate group, intravenous calcium gluconate was administered daily for four days starting on the day of oocyte pickup (OPU). 10 ml of 10% calcium gluconate solution was dissolved in 200 ml of physiological saline and administered by intravenous route within 40 minutes. Infusion was started within the first 30 minutes following the OPU and continued on the 1st, 2nd and 3rd days after OPU. RESULTS: Mild OHSS was developed in 367 (89%) patients receiving calcium gluconate infusion, while 251 patients (57%) in the cabergoline group developed mild OHSS. The frequency of mild OHSS in the calcium group was significantly higher than the cabergoline group (p<.001). Moderate OHSS was observed in 32 people (7.8%) in the calcium gluconate group, while it was observed in 184 people in the cabergoline group (42.3%). Calcium gluconate infusion significantly reduced the development of moderate OHSS compared to cabergoline therapy (p<.001). Severe OHSS developed in 11 patients (2.7%) in the calcium gluconate group, while severe OHSS did not develop in those given cabergoline (0%, p<.001). Clinical pregnancy, live birth and abortion rates were similar in the two groups. When logistic regression analysis was performed, a significant correlation was found between age, BMI, AMH, the number of antral follicle count, OHSS history, paracentesis, progesterone on the day of hCG, 2 PN zygotes, and HbA1c levels and the development of OHSS. No correlation was found between the use of metformin or cetrotide and the development of OHSS. CONCLUSIONS: Calcium gluconate treatment is not effective in the prevention of OHSS.

The effect of leptin and resveratrol on JAK/STAT pathways and Sirt-1 gene expression in the renal tissue of ischemia/reperfusion induced rats.

OBJECTIVE: Our study aimed to investigate the possible modifying effects of leptin and combined use of resveratrol on rat renal I/R injury and their relationship on signal pathways and apoptosis-related mechanisms. BACKGROUND: Renal ischemia-reperfusion (I/R) injury is an important cause of acute renal failure. METHODS: Male Sprague Dawley rats were divided into 5 groups: Control, I/R, I/R+leptin, I/R+resveratrol and I/R+leptin+resveratrol. Leptin (10 µg/kg BW) was administered (i.p.) 30 min prior to I/R. Resveratrol was administered by gavage at 20 mg/kg BW per d for 12 d prior to I/R. The left renal artery was exposed to 1 h of ischemia and 1 h of reperfusion. RESULTS: Resveratrol treatment alone increased TNF-α, TNF-α R1, NF-κB, SIRT-1, STAT1 and STAT3 mRNA levels and decreased caspase 3 protein levels. Leptin treatment alone significantly decreased the caspase 3 protein levels. The combined use of resveratrol and leptin significantly increased STAT3, and caspase 3 mRNA levels, and decreased the caspase 3 protein levels. Apoptosis was significantly decreased especially in the leptin and leptin+resveratrol groups. CONCLUSION: The present study suggest that a combined use of resveratrol and leptin has preventive and regulatory effects on renal I/R injury; the mechanism involves decreasing apoptosis, likely by altering the JAK/STAT pathway and SIRT1 expression (Fig. 8, Ref. 24).

Effects of ceranib-2 on cell survival and TNF-alpha in colon cancer cell line.

OBJECTIVE: The aim of this study was to investigate the effects of a novel anti-cancer drug, ceranib-2, which targets the acid ceramidase, in human colon cancer cell line. MATERIALS AND METHODS: The cell lines were treated with 50 µM of ceranib-2. Relative mRNA expression of TNF-alpha, TNF-R1 and ASAH were assessed by quantitative RT-PCR. RESULTS: Ceranib-2 reduced cell viability in a dose-dependent manner and the apoptotic values of cells following treatment with the dose of 50 µM were reduced significantly both at 24 h and 48 h compared to the control cells (p < 0.001). TNF-alpha receptor 1 (TNF-R1) mRNA levels were reduced significantly in the cell lines treated with both 25 µM and 50 µM of ceranib-2 for 24 h compared to the control cells (p < 0.05), whereas the difference between the treatment and the control cell lines diminished at 48 h. The human acid ceramidase gene (ASAH) mRNA levels were significantly higher in the cell lines treated with 50 µM of ceranib-2 for 48 h than in the other cell lines (p < 0.001). CONCLUSION: The study shows that ceranib-2 increased apoptosis by inducing ASAH expression and reduced TNF-R1 expression in human colon cancer cell lines in a dose and time-dependent manner (Fig. 3, Ref. 17).

Comparison of GnRH antagonist and agonist mini-dose long protocols in infertile cases undergoing controlled ovarian hyperstimulation.

AIM: The purpose of the present study was to determine if there is a difference between multi-dose gonadotropin releasing hormone (GnRH) antagonist protocol and long GnRH agonist protocol. MATERIALS AND METHODS: This retrospective study compared the data pertaining to patients chosen as per predetermined acceptance criteria, 113 of whom were administered multi-dose antagonist protocol for controlled ovarian hyperstimulation (COH) while 133 were administered long agonist protocol for COH at Suleymaniye Teaching Hospital of Obstetrics and Gynecology. RESULTS: While cancellation rate was found to be significantly higher in antagonist group (17.7% vs 11.28%), the number of follicles > 14 mm and > 16 mm, E2 level, and the number of retrieved oocytes on the day of hCG trigger were significantly lower in the same group. However, there was no difference between fertilization rates and embryonic development rates. The pregnancy rates per transfer and per cycle were found to be 40.9% and 31.7%, respectively; in the antagonist group they were lower, though not significantly, when compared to agonist group (44.1% and 39.1%, respectively). Ongoing pregnancy rates were found to be similar between the groups. CONCLUSION: GnRH antagonist treatment protocol has a level of efficacy similar to agonist treatment protocol in terms of pregnancy results for all groups.