Yakup Kumtepe

Protective effects of amlodipine on ischemia-reperfusion injury of rat ovary: biochemical and histopathologic evaluation

OBJECTIVE To evaluate the effects of telmisartan as an antioxidant and for its tissue protective properties and to study the biochemical and histopathologic changes in experimental ischemia and ischemia/reperfusion injuries in rat ovaries. DESIGN Experimental study. SETTING Experimental surgery laboratory in a university department. ANIMAL(S) Forty-eight female adult rats. INTERVENTION(S) I: sham operation; II: bilateral ovarian ischemia; III: 3 h ischemia + 3 h reperfusion. IV and V: Rats were administered 10 and 20 mg/kg doses of telmisartan, respectively, before 0.5 h of ischemia, and then ovarian ischemia was applied; after 3 h of ischemia, the ovaries were removed. VI and VII: 3 h ovarian ischemia was applied; 2.5 h after the induction of ischemia, rats were administered the same doses of telmisartan; at the end of 3 h of ischemia, the ovaries were removed and a 3 h reperfusion followed. MAIN OUTCOME MEASURE(S) Superoxide dismutase, inducible nitric oxide synthase, and myeloperoxidase activity in rat ovarian tissue; and histopathologic changes in the ovarian tissue of the rats. RESULT(S) Ischemia and ischemia-reperfusion increased the inducible nitric oxide synthase and myeloperoxidase activity while decreasing the super oxide dismutase activity significantly in comparison with the sham group. Before ischemia and ischemia/reperfusion, telmisartan reversed the trend in inducible nitric oxide synthase activities and the level of myeloperoxidase. CONCLUSION(S) telmisartan is effective in reversing tissue damage induced by ischemia/reperfusion in ovaries.

Comparison of labor induction with misoprostol vs. oxytocin/prostaglandin E2 in term pregnancy

Objective: To compare the efficacy and safety of intravaginal and oral misoprostol vs. oxytocin/prostaglandin E2 (PGE2) gel for third trimester labor induction. Methods: Two hundred twenty‐four pregnant women were randomized to induction of labor either with misoprostol or oxytocin and PGE2 gel. Patients in the misoprostol group (n = 112) received 100 μg intravaginal misoprostol followed by 100 μg p.o. every 2 h. The oxytocin/PGE2 group consisted of 112 patients who underwent PGE2 cervical instillation 6 h before continuous oxytocin infusion. The perinatal, intrapartum and neonatal characteristics of both groups were determined. Results: Induction to active phase of labor was successfully achieved in 96 women (85.7%) in the misoprostol group vs. 86 women (76.8%) in the oxytocin/PGE2 group, but the drug initiation‐delivery interval was significantly shorter in the misoprostol group (9.2 ± 2.4 h) than in the oxytocin/PGE2 group (15.2 ± 3.2 h, P < 0.001). The incidence of adverse intrapartum outcomes was similar for both methods. Intravaginal misoprostol 100 μg followed by a single oral dose of 100 μg misoprostol safely produced labor and a vaginal delivery in 70% of patients. More than three tablets were required in only 10% of patients. There was a higher prevalence of cesarean section for failed induction in the oxytocin/PGE2 group than in the misoprostol group (13.4 vs. 6.3%, P < 0.001). The neonatal outcomes of both groups were also similar. Conclusion: Misoprostol is significantly more effective for labor induction than oxytocin/PGE2 gel. The maternal intrapartum and neonatal outcomes were the same for both induction regimens. From a clinical and perinatal perspective, misoprostol is an acceptable choice for labor induction.

Protective effects of erythropoietin on ischemia/reperfusion injury of rat ovary

OBJECTIVES To evaluate the effects of erythropoietin (EPO) as an antioxidant and tissue protective agent and study the biochemical and histopathological changes in experimental ischemia and ischemia/reperfusion (I/R) injury in rat ovaries. STUDY DESIGN 36 Adult female rats were used. The experimental groups were designed as Group 1: sham operation; Group 2: bilateral ovarian ischemia; and Group 3: 3 h period of ischemia followed by 3 h reperfusion. Group 4 rats were administered a 5000 IU dose of EPO, before 0.5 h of ischemia, and then bilateral ovarian ischemia was applied. After a 3 h period of ischemia, the bilateral ovaries were removed. In Group 5, a 3 h period of bilateral ovarian ischemia was applied. 2.5 h after the induction of ischemia, the rats were administered the same dose of EPO. At the end of a 3 h period of ischemia, 3h reperfusion was continued after the ovaries were removed. Group 6 underwent a sham operation after administration of 5000 IU/kg of EPO. After the experiments, superoxide dismutase (SOD), inducible nitric oxide synthase (iNOS), and myeloperoxidase (MPO) activity were determined, and histopathological changes were examined in all rat ovarian tissue. RESULTS Ischemia and ischemia/reperfusion increased the iNOS and MPO activity while decreasing the SOD activity significantly in comparison to the sham group. The 5000 IU/kg of EPO before ischemia and I/R reversed the trend in iNOS and MPO activities. The levels of SOD were decreased by the ischemia and I/R. The administration of EPO before ischemia and I/R treatments also reversed the trend in the SOD levels. In the ischemia/reperfusion plus EPO groups, though we observed minimal vascular dilation in the ovary stroma and some degenerative cell clusters, most of cellular structures did not show any pathological changes. CONCLUSIONS Administration of EPO is effective in reversing tissue damage induced by ischemia and/or ischemia/reperfusion in ovaries.

Effect of PGD on implantation and ongoing pregnancy rates in cases with predominantly macrocephalic spermatozoa

Although its occurrence is rare, the presence of large headed or macrocephalic spermatozoa and increased chromosomal abnormality has recently been reported by several groups. Moreover, when intracytoplasmic sperm injection (ICSI) was performed with samples containing macrocephalic spermatozoa, lower fertilization and implantation rates result in poor clinical outcome. In order to evaluate the impact of preimplantation genetic diagnosis (PGD) on implantation and ongoing pregnancy rates in these couples, the results of 23 PGD cycles were compared with non-PGD cycles (n = 60) as well as cycles with absolute teratozoospermia (having zero normal morphology) with (n = 14) or without PGD (n = 66). Out of 82 embryos biopsied in the macrocephalic sperm group, abnormalities were detected in 46.4% of the embryos analysed. Most of the abnormalities were trisomies (37.0%) and complex aneuploidies (51.9%). A 33.3% pregnancy rate was achieved by selectively transferring euploid embryos after PGD with the statistically higher implantation rate of 25.0% compared with non-PGD cycles (IR: 12.3%, P < 0.01). Moreover, only one missed abortion (14.3%) was observed in the PGD group, whereas seven of the 15 pregnancies resulted in abortion in the non-PGD group (46.7%). Preliminary results indicate that patients should be counselled for increased chromosomal abnormality and a possible beneficial effect of eliminating chromosomally abnormal embryos with PGD on a bortion rates.

Assessment of DNA fragmentation and aneuploidy on poor quality human embryos

In human assisted reproduction, low embryo quality due to retarded growth and abnormal cellular morphology results in fewer embryos suitable for transfer. This study aimed to assess the extent of DNA fragmentation and aneuploidy in spare slow growing or arrested human embryos. In 19 assisted reproduction cycles, a total of 57 embryos unsuitable for embryo transfer were used for simultaneous apoptosis and aneuploidy assessment. Among them, 31 (54.3%) showed DNA fragmentation by terminal deoxynucleotidyl transferase-mediated dUDP nick-end labelling (TUNEL) analysis. Among 26 embryos that were negative for TUNEL, interpretable fluorescence in-situ hybridization (FISH) results were obtained for 25 embryos (96.2%). Sixteen embryos were detected to be chromosomally abnormal (64.0%); three were found to be chaotic, six had complex aneuploidy, six had complete monosomy and one was polyploid. The results show that a high level of DNA fragmentation and aneuploidy are common in embryos with slow growth and/or low quality. More detailed studies are needed to assess the effect of factors such as ovarian stimulation regimens and in-vitro culture conditions. Moreover, application of simultaneous TUNEL and FISH techniques can be informative regarding DNA integrity and aneuploidy.

Effect of acute and chronic administration of progesterone, estrogen, FSH and LH on oxidant and antioxidant parameters in rat gastric tissue

This study was conducted to investigate whether gastro-protective and gastro-toxic effects of acute and chronic administration of progesterone, estrogen, FSH and LH were related to oxidant and antioxidant parameters. Chronic administration of progesterone at a low dose (1mg/kg), which probably could not stimulate progesterone receptors (PRs), inhibited oxidative stress of FSH in gastric tissue by suppressing FSH. Progesterone (5mg/kg) may have been caused oxidative stress as reflected by PR stimulation. FSH may have decreased antioxidant parameters and increased oxidant parameters via PRs. Chronic administration of low dose of estrogen (1mg/kg) inhibited LH and but could not stimulate alpha-2 adrenergic receptors, which resulted in oxidative stress in gastric tissue. The higher dose of estrogen (5mg/kg), however, could stimulate alpha-2 receptors, exhibited antioxidant activity in acute and chronic administration. While antioxidant activity of estrogen and LH was blocked with yohimbine (an alpha-2 adrenergic receptor blocker), mifepristone prevented the oxidative stress of progesterone and FSH in gastric tissue. It is concluded that low doses of progesterone may inhibit FSH, whereas high doses of estrogen may stimulate alpha-2 receptors, suggesting that LH could have protective and antioxidant hormone effects.

Embryo development characteristics in Robertsonian and reciprocal translocations: a comparison of results with non-translocation cases

The effect of translocations on embryo development was evaluated and results were compared in terms of embryo development with those of embryos obtained from standard intracytoplasmic sperm injection (ICSI) cycles. In 23 translocation carriers with 34 cycles, fertilization, pronuclear morphology scoring (PMS), developmental arrest, cleavage and blastocyst formation were evaluated and compared with embryos obtained from non-translocation cases undergoing ICSI (n = 98 cycles). In 28 cycles, preimplantation genetic diagnosis (PGD) was performed on prezygotes (first and second polar body biopsy for female carriers; n = 3) or on embryos having seven or more blastomeres (blastomere biopsy; n = 25). In six cycles for four couples, probes for translocated chromosomes were not available, so PGD could not be performed. Overall, in translocation cases, a lower fertilization rate, a higher rate of retarded embryo development, and a lower rate of blastocyst formation were observed compared with embryos of non-translocation cases. Fluorescence in-situ hybridization (FISH) analysis showed a 70.9% abnormality rate for reciprocal translocations and 55.0% for Robertsonian translocations respectively. In cases with Robertsonian and reciprocal translocation carriers, the probability of poor embryo development, which may be a result of high segregation abnormalities, may negatively affect the outcome of assisted reproductive techniques. This poor prognosis should also be considered when genetic counselling for translocation is given.

Antioxidant Potential and Transferrin, Ceruloplasmin, and Lipid Peroxidation Levels in Women with Preeclampsia

Background The aim of this study was to evaluate lipid peroxidation and antioxidant function in patients with preeclampsia and in normotensive pregnant women and to assess an association with the severity of the disease. Methods Twenty-one patients with mild preeclampsia, 15 patients with severe preeclampsia, and 19 normotensive pregnant women were included in the study. Plasma antioxidant potential (AOP) status, ceruloplasmin (Cp) and transferrin (Trf) levels as antioxidants, and malondialdehyde (MDA) levels as an indicator of lipid peroxidation were measured. Results Whereas the AOP and Trf levels of the severe and mild preeclampsia groups were found to be reduced, the MDA and Cp levels were increased compared with those of the normotensive pregnant group. There were statistically significant negative correlations between AOP and MDA in all groups. No differences were observed between the groups with severe and mild preeclampsia with respect to these analytes. Conclusion Our findings suggest that lipid peroxidation may be an important factor in the pathogenesis of preeclampsia and that plasma antioxidants and oxidants are altered in preeclampsia. However, these findings may not be useful in distinguishing women with severe and mild preeclampsia.

A genetic survey of 1935 Turkish men with severe male factor infertility

Male factor infertility is the sole reason in approximately 25% of couples who suffer from infertility. Genetic factors such as numerical and structural chromosomal abnormalities and microdeletions of the Y chromosome might be the cause of poor semen parameters. The results of karyotype analyses and Y-chromosome microdeletions of 1935 patients with severe male factor infertility, which is the largest series from Turkey, were assessed retrospectively. The frequency of cytogenetic abnormalities among 1214 patients with non-obstructive azoospermia (NOA) and 721 patients with severe oligoasthenoteratozoospermia (OAT) were 16.40 and 5.83% respectively. The overall incidence of Y-chromosome microdeletion was 7.70%. The incidence of Y chromosome microdeletion in patients with NOA and OAT was 9.51 and 1.86% respectively. The abnormality rate increased with the severity of infertility. Some patients (n = 22) were carriers of both chromosomal abnormalities and Y-chromosome microdeletions. Results suggest the need for genetic screening and proper genetic counselling before initiation of assisted reproduction treatment.

Serum levels of insulin, IGF‐1, and IGFBP‐1 in pre‐eclampsia and eclampsia

Objectives: To investigate whether the serum concentrations of insulin, insulin‐like growth factor‐1 (IGF‐1), and insulin‐like growth factor binding protein‐1 (IGFBP‐1) were altered in women with mild pre‐eclampsia, severe pre‐eclampsia, and eclampsia. Methods: In this prospective study, we investigated 20 mild pre‐eclamptic, 20 severe pre‐eclamptic, and 20 eclamptic patients in the third trimester. The control group consisted of 20 healthy pregnant women. Serum levels of insulin, IGF‐1, and IGFBP‐1 were measured. Results: In patients with eclampsia, serum levels of IGF‐1 were lower, and IGFBP‐1 were higher, respectively, than control and other study groups (P<0.001) The values of IGF‐1 in mild pre‐eclampsia and severe pre‐eclampsia were lower compared with control groups (both P<0.01), but there were no differences between mild and severe pre‐eclampsia. The serum levels of IGFBP‐1 in severe pre‐eclampsia were higher compared with control groups (P<0.01), but there was no statistical difference between mild pre‐eclampsia and other groups. Conclusions: IGF‐1 was lower, and IGFBP‐1 was higher in pre‐eclamptic and eclamptic patients than controls, these alterations were related to the severity of pre‐eclampsia.