Faruk Buyru

Indices of Oxidative Stress in Eutopic and Ectopic Endometria of Women with Endometriosis

This study was designed to determine the activities of superoxide dismutase and glutathione peroxidase and some of the lipid peroxidation indices (malondialdehyde and total sulfhydryl groups) in eutopic and ectopic endometria of patients with endometriosis. Ectopic endometrial tissues (ovarian cysts; n = 22) were obtained laparoscopically during the preovulatory period. Statistical analyses were made using the Wilcoxon signed-rank test. The levels of malondialdehyde and total sulfhydryl groups were similar in the eutopic and ectopic endometria, whereas the superoxide dismutase activity was found to be significantly higher in the latter (1,893 ± 780 vs. 3,512 ± 1,502 U/g protein; p = 0.002). Although the glutathione peroxidase activity was slightly lower in the ectopic than in the eutopic tissues, the difference was not found to be statistically significant. The malondialdehyde levels were positively correlated with the plasma 17β-estradiol concentrations in the ectopic endometria (r = 0.683, p = 0.001). No such correlation was seen in the eutopic tissue. It is suggested that various factors, such as cytokines released by activated macrophages in the peritoneal fluid and 17β-estradiol itself synthesized by the ovaries, may locally affect the oxidant status of ectopic endometria.

Role of inflammatory mediators in patients with recurrent pregnancy loss

OBJECTIVE To examine interleukin-12 (IL-12), IL-18, IFN-γ, intracellular adhesion molecule-1 (ICAM-1), leukemia inhibitory factor (LIF), and migration inhibitory factor (MIF) levels in precisely-timed blood and endometrial tissue samples from women with idiopathic recurrent pregnancy loss (RPL). DESIGN Case-control study. SETTING University hospital. PATIENT(S) Twenty-one women with RPL and 20 women with proven fertility (controls). INTERVENTION(S) Primary endometrial cells and blood samples during the midsecretory phase (days 19-23). MAIN OUTCOME MEASURE(S) Detection of IL-12, IL-18, IFN-γ, ICAM-1, LIF, and MIF via enzyme-linked immunosorbent assay in both blood and endometrial tissue samples. RESULT(S) The blood and tissue levels of IL-12, IL-18, and IFN-γ were statistically significantly higher, and the blood and tissue levels of LIF and MIF were statistically significantly lower in patients with RPL. Only the level of tissue ICAM-1 was higher in patients with RPL. There was a strong correlation between blood and tissue level measurements of IL-12, IL-18, LIF, and MIF. CONCLUSION(S) Our findings support the hypothesis that inflammatory processes may contribute to pregnancy loss, possibly through their role in implantation. We found that blood and tissue levels of IL-18, LIF, and MIF, and tissue levels of IL-12, IFN-γ, and ICAM-1 have statistically significant prognostic relevance.

Utility of c-erbB-2 expression in tissue and sera of ovarian cancer patients.

Abstract In this study, expression of the c-erbB-2 gene in tumors and healthy tissue of patients with ovarian cancer was investigated. Serum c-erbB-2 protein levels were also determined. Elevated serum values were observed in 45% of patients. c-erbB-2 protein levels in the tumors were significantly higher than in healthy tissue. Overexpression of the protein was observed in 60% of patients. However, no association was found behveen the clinical variables and tumor c-erbB-2 expression. This is the first study in the literature investigating the c-erbB-2 oncoprotein levels in the normal and tumor tissue. We conclude that the role of the c-erbB-2 gene in ovarian cancer warrants further studies.

A randomized, single-blind, prospective trial comparing three different gonadotropin doses with or without addition of letrozole during ovulation stimulation in patients with poor ovarian response

OBJECTIVE The aim of this randomized controlled trial (RCT) was to investigate whether IVF outcomes would differ between patients with POR who received three different gonadotropin doses with or without the addition of letrozole during ovulation stimulation. STUDY DESIGN Only those who fulfilled two of the three Bologna criteria were included to the study. 95 patients met the inclusion criteria and agreed to participate in the study. In the first group, 31 patients were treated with 450IU gonadotropins. In the second group, 31 patients were treated with 300IU gonadotropins. The third group comprised 33 patients and was treated with 150IU gonadotropins in combination with letrozole. RESULTS The results indicate that differences in doses of hMG and rFSH in patients with POR result in a similar number of retrieved MII and fertilized oocytes, similar fertilization rates, number of transferred embryos, implantation, cancelation, chemical, clinical, and ongoing pregnancy rates. CONCLUSIONS Increasing the dose of gonadotropins during ovulation stimulation is an intuitively appealing approach when the patient is a poor responder. However, increasing the dose does not necessarily improve the reproductive outcome. Using a mild stimulation with addition of letrozole was as effective as stimulation with higher doses of gonadotropins alone in this patient population.

Evaluation of embryo transfer time (day 2 vs day 3) after imposed single embryo transfer legislation: When to transfer?

To determine whether the timing of embryo transfer (day 2 or day 3) affects pregnancy outcome in IVF patients, receiving single or double embryo transfer, 380 patients were included in this retrospective study. All patients underwent GnRH antagonist protocol. When stratified by number of transferred embryos, single embryo transfer (SET) patients undergoing a day 2 embryo transfer (ET) had similar biochemical pregnancy (25% vs 20.4%; p > 0.05) and clinical pregnancy (16.6% vs 14.6%; p > 0.05) rates to SET patients that were undergoing a day 3 ET. A similar observation was again noted in double embryo transfer (DET) patients undergoing a day 2 ET, with similar biochemical pregnancy (35% vs 29.8%; p > 0.05) and clinical pregnancy (25% vs 15.5%; p > 0.05) rates to DET patients undergoing a day 3 ET. Women, despite age, number of transferred embryos and ET timing, have similar reproductive outcomes. Shortening or lengthening the duration of in vitro culture provides no obvious benefit.

The Presence of Endometrioma Does Not Impair Time-Lapse Morphokinetic Parameters and Quality of Embryos: A Study On Sibling Oocytes.

Objective: To see whether the oocytes retrieved from an ovary with an endometrioma would develop into embryos with aberrant timings of cleavage as assessed using time-lapse monitoring (TLM) and poorer morphologic quality compared with sibling oocytes from the contralateral ovary with no endometrioma in the same patient after intracytoplasmic sperm injection. Methods: This was an observational prospective study at an in vitro fertilization (IVF) center of a private hospital. It included analysis and comparison of 128 embryos (69 embryos developed from the ovary with endometrioma and 59 embryos from the contralateral ovary without endometrioma serving as controls from a total of 20 women with infertility). Morphology of the embryo was assessed twice (days 3 and 5), again by capturing images with the TLM system. Morphokinetic parameters of embryos and clinical pregnancy rates were recorded separately from ovaries with and without endometrioma and were the primary outcomes of the study. Secondary outcomes included number of retrieved oocytes, number of metaphase II (MII) oocytes, fertilization rates, and conventional morphological classification of embryos. Results: There were no differences in terms of the following time-lapse morphokinetic parameters of embryos. The mean numbers of oocytes and MII oocytes collected from the ovary with the endometrioma were similar to those collected from the contralateral ovary without endometrioma. Fertilization rates and the percentage of embryos with top morphologic quality were also similar. Conclusions: According to the morphokinetic parameters, this study further strengthens the notion that removal of endometriomas before IVF is not a necessity in terms of better oocyte quality and development.

Apoptosis through regulation of Bcl-2, Bax and Mcl-1 expressions in endometriotic cyst lesions and the endometrium of women with moderate to severe endometriosis.

The aim of the study was to evaluate apoptosis through regulation of Bcl-2, Bax and Mcl-1 proteins by comparing their expressions in endometriotic cyst lesions and the endometrium of the patients with moderate to severe endometriosis. This is a cross-sectional study of 30 women in reproductive age with a clinical or sonographic suspicion of endometrioma, who underwent laparoscopy. Bcl-2 expression was positive both in cystic endometriotic lesions and endometrium, and its expression was significantly reduced in the cystic endometriotic lesions (p < 0.0001). There was a significant difference in Bcl-2 expression between cystic endometriotic stromal cells and endometrial stromal cells (p < 0.0001). Bax expression was positive both in cystic endometriotic lesions and endometrium, and its expression was significantly lower in the endometrium (p < 0.0001). There was a significant difference in Bax expression between cystic endometriotic stromal cells and endometrial stromal cells (p = 0.03). Mcl-1 expression was positive both in cystic endometriotic lesions and endometrium, and its expression was significantly lower in the cystic endometriotic lesions (p = 0.003). Apoptosis may play a role in the pathophysiology of endometriosis by potentially contributing to the survival of regurgitating endometrial cells in the peritoneal cavity.

Reproductive Outcomes of Hysteroscopic Septoplasty Techniques.

Background and Objectives: Since little is known regarding the correlation between different techniques used during hysteroscopic septoplasty and reproductives outcomes, we amied to evaluate the results of two different techniques of hysteroscopic septoplasty (HS). Methods: Data were retrospectively reviewed on 49 patients who underwent HS for symptomatic septate uterus from January 1, 2010, through April 30, 2014. The patients were divided into 2 groups based on the HS technique used. Group I consisted of 27 patients who underwent HS by monopolar hook cautery with the operating hysteroscope. Group II consisted of 22 patients who had the procedure performed with scissors and guided by an office hysteroscope. All the procedures in the both groups were performed in the operating room under general anesthesia. Pregnancy outcomes within the first year after HS for both groups were evaluated. Results: Reproductive outcomes were obtained from 44 patients who attempted to conceive after HS within the first year. In the 25 patients in group I, 23 had pregnancies, of which 15 (65.2%) continued to term, 3 (13%) ended in a preterm live birth, and 5 (21.7%) ended in loss of pregnancy (abortion). In the 19 patients in group II, there were 17 pregnancies, of which 11 (64.7%) continued to term, 2 (11.7%) ended in a preterm live birth, and 4 (23.5%) ended in first- or second-trimester abortion. The overall live-birth rate was 78.2% in group I and 76.4% in group II (P = .85). Conclusions: Our data show that the rates of pregnancy that reach term and overall rates of live births are similar between the 2 HS techniques. Additional studies are needed to evaluate the impact of the techniques on reproductive outcomes.

Comparison of ovulation induction protocols after endometrioma resection.

Background and Objectives: The aim of this study was to compare the in vitro fertilization (IVF) outcomes of long gonadotropin-releasing hormone agonist (GnRH-a) and GnRH-antagonist (GnRH-ant) protocols in endometriosis patients who have undergone laparoscopic endometrioma resection surgery. To our knowledge, there is no study in the current literature that compares the effectiveness of long GnRH-a and GnRH-ant protocols in management of IVF cycles in endometriosis patients who underwent laparoscopic endometrioma resection surgery. Methods: Eighty-six patients with stage III to IV endometriosis who had undergone laparoscopic resection surgery for endometrioma were divided into 2 groups: those who had ovarian stimulation with a long GnRH-a protocol (n = 44), and those who had ovarian stimulation with a GnRH-ant protocol (n = 42). Results: The number of follicles on human chorionic gonadotropin injection day, duration of hyperstimulation, number of retrieved metaphase II oocytes, and total number of grade 1 embryos were statically significantly higher in the long GnRH-a protocol. There were no significant differences in positive β-human chorionic gonadotropin pregnancy rates (25% vs 21.4%; P = .269) and ongoing pregnancy rates per patient (20.5% vs 19.1%; P = .302) between the 2 protocols. Conclusions: Long GnRH-a and GnRH-ant protocols both present similar IVF outcomes in patients with endometriosis who have undergone laparoscopic endometrioma resection surgery. A long GnRH-a protocol may lead to a higher number of embryos that can be cryopreserved, providing the possibility of additional embryo transfers without having to go through the process of ovarian stimulation again.

Effects of Irisin and Exercise on Metabolic Parameters and Reproductive Hormone Levels in High-Fat Diet-Induced Obese Female Mice:

It has been documented that exogenously administered irisin (1010 fibronectin-type III domain-containing 5 [FNDC5]), which is a new polypeptide hormone, induces the browning of subcutaneous fat and thermogenesis. In this study, effects of physical activity and exogenous administration of irisin were investigated on parameters related with reproduction and metabolism in the high-fat diet-induced obesity model of the female C57BL/6J mice. Sixty mice were gathered at age approximately 5 to 6weeks and were divided into 3 groups. Control group remained sedentary. Irisin group remained also sedentary but intravenously received 1010 FNDC5-expressing adenovirus after 20 weeks. Exercise group performed treadmill after 6 weeks. All mice were sacrificed 22 to 23 weeks after the start of the study. There was a significantly greater Δ weight in the controls compared with the irisin and exercise groups (P < .05). Glucose and insulin levels were significantly higher in the controls (P < .05). The serum irisin level was significantly higher in the exercise group (P < .05). Serum luteinizing hormone levels were significantly increased in the irisin group (P < .05). Serum anti-Müllerian hormone levels were significantly higher in irisin and exercise groups (P < .05). There were significant negative correlations between serum irisin levels and Δ weight and homeostatic model assessment of insulin resistance (r = −0.327, r = −0.297, respectively; P < .05 for both). The numbers of primordial follicles per ovary were similar (P > .05), whereas primary and secondary follicles per ovary were higher in the irisin and exercise groups compared with controls (P < .05). Pharmacologic introduction of irisin may improve metabolic factors such as insulin sensitivity and obesity by promoting weight loss and consequently improving the reproductive potential.