Sevtap Kilic

The effect of anti-thyroid antibodies on endometrial volume, embryo grade and IVF outcome

Thyroid auto-immunity (TAI) has been implicated as the most common cause of hypothyroidism in general population, especially in women. Many studies revealed that increased infertility incidences with TAI. The aim of the present article was to evaluate the effect of thyroid auto-antibody (TAA) positivity on embryological parameters, IVF-outcome and endometrial volume (EnV) in infertile patients who were applied for routine artificial reproductive technologies (ART) programme. This study included prospective, sequential, cross-sectional analyses of parameters obtained from 69 patients with unexplained infertility. It was the first ART application of patients. Patients were homogenous for age, body mass index, basal hormone measurements and underwent same ovulation induction protocol. They were evaluated for thyroid hormone profile and TAAs and divided into three groups; TAA negative group (n = 31), TAA positive group (n = 23) and TAA positive and euthyroid with medication group (n = 15). There were no differences among groups for the number of Grade-1 and Grade-2 embryos, distribution of embryo-grades, number of oocytes retrieved and fertilised, biochemical pregnancy ratios (PR), EnV and miscarriage ratio. However, the clinical PR was significantly lower in the TAA positive group (p = 0.024). In conclusion, the embryo grades and EnV did not differ among groups. But the clinical PR differs and the anti-thyroid peroxides positivity, above the cut-off point, affects the clinical PR.

The relationship between obesity and fecundity.

OBJECTIVE Obesity is an important factor that might reduce fecundity. In order to determine the underlying physiological mechanisms and risk factors, the obesity-fecundity association is investigated in relation to parity, menstrual cycle regularity, smoking habits, and age. METHODS This was a retrospective cohort study of 22,840 women who gave birth between January 2006 and January 2007 in the Dr Zekai Tahir Burak Womens Health Research and Education Hospital. Age, parity, prepregnancy body mass index (BMI) values, time to pregnancy data related to smoking, and reproductive, medical, and gynecological history were obtained from the medical records. RESULTS Fecundity was reduced for overweight and obese women compared with optimal weight women, and this reduction was more evident for obese primiparous women. Fecundity remained reduced for overweight and obese women with normal menstrual cycles. Obese and overweight women were found to smoke significantly more than the optimal weight group. CONCLUSIONS Obesity was found to be associated with reduced fecundity for all weight-adjusted groups of women and persisted for women with regular cycles. Weight loss should be encouraged initially during the treatment of infertile overweight and obese women.

Metformin regresses endometriotic implants in rats by improving implant levels of superoxide dismutase, vascular endothelial growth factor, tissue inhibitor of metalloproteinase-2, and matrix metalloproteinase-9

OBJECTIVE We sought to test if metformin could regress endometriotic explants in rats. STUDY DESIGN After inducing endometriotic implants and randomization of female Wistar albino rats, they were given 25 and 50 mg/kg/day of oral metformin in group A (n = 9) and B (n = 8), respectively, for 28 days. Group C (n = 9) was given saline as placebo. RESULTS Mean volume, weight, and histologic score of implants in groups A (P < .01, P < .05, and P < .05, respectively) and B (P < .01, P < .05, and P < .05, respectively) were significantly lower than in group C. The activity of superoxide dismutase and tissue inhibitor of metalloproteinase-2 staining in groups A (P < .05 and P < .01, respectively) and B (P < .01 and P < .01, respectively) was significantly higher than in the control group. Moreover, there were more significant reductions in implant levels of vascular endothelial growth factor and matrix metalloproteinase-9 in groups A (both P < .001) and B (both P < .001) than in group C. CONCLUSION Metformin causes regression of endometriotic implants in rats.

The effect of levonorgestrel-releasing intrauterine device on menorrhagia in women taking anticoagulant medication after cardiac valve replacement

BACKGROUND This study was conducted to evaluate the effect of levonorgestrel-releasing intrauterine devices (LNG-IUDs) on menorrhagia in patients receiving anticoagulant therapy after cardiac valve replacement. STUDY DESIGN Forty women with menorrhagia who underwent cardiac valve replacement and were taking anticoagulant medication were enrolled in the study. The women were randomly divided into two groups: LNG-IUDs were inserted into 20 women in Group 1 over the first 3 days of menstrual bleeding, while the women in Group 2 were followed without any intervention. The activated partial thromboplastin time, prothrombin time, international normalized ratio, hematocrit level, hemoglobin level, ferritin level and pictorial bleeding assessments for the quantity of menstrual bleeding were recorded. RESULTS Three months after insertion of LNG-IUDs, the women in Group 1 had a significant decrease in blood loss and higher hemoglobin, hematocrit and ferritin values. No difference was detected for these parameters in the control group at the third and sixth months of the study. Coagulation parameters did not differ between the two groups. CONCLUSION LNG-IUDs can be considered as an effective non-surgical treatment for menorrhagia in women receiving anticoagulant therapy after cardiac valve replacement.

Inflammatory-metabolic parameters in obese and nonobese normoandrogenemic polycystic ovary syndrome during metformin and oral contraceptive treatment

Our aim was to evaluate the optimal treatment strategy addressing cardiovascular risk in obese and nonobese patients with polycystic ovary syndrome (PCOS). We planned a prospectıve randomized clinical study. Normoandrogenemic and oligoamenorrheic women with PCOS and impaired glucose tolerance (n = 96) were enrolled in the study. Six months of treatment with metformin HCL or oral contraceptive pills (OCPs) were given to the patients. Group 1 were obese and receiving metformin. Group 2 were obese and receiving OCPs. Group 3 were nonobese and receiving metformin, and Group 4 were nonobese receiving OCPs. ADMA, homocysteine, high sensitive C-reactive protein (hs-CRP) and homeostasis model assessment estimate of insulin resistance (HOMA-IR) were investigated. ADMA, homocysteine, hs-CRP and HOMA-IR were similar in obese and nonobese groups before the treatment. After 6 months of treatment, a significant decrease was observed in ADMA, homocysteine and HOMA-IR levels in Groups 1 and 3. An increase in ADMA and hs-CRP levels was observed in Groups 2 and 4. In this study, metformin treatment leads to improvement in hormonal and metabolic parameters and decreases ADMA and homocysteine levels possibly independent of BMI. However, the use of oral contraceptives in obese and nonobese patients with PCOS with impaired glucose tolerance increases ADMA and hs-CRP levels and creates an increase in the metabolic risk.

Effect of bevacizumab on postoperative adhesion formation in a rat uterine horn adhesion model and the correlation with vascular endothelial growth factor and Ki-67 immunopositivity

We investigated whether adhesion formation is prevented by the inhibition of angiogenesis in a rat uterine horn adhesion model. A single-dose of bevacizumab was effective in preventing postoperative intraperitoneal adhesion formation among 30 Wistar albino rats that underwent serosal injury by use of a standard technique after laparotomy with intraperitoneal bevacizumab.

Regression of endometrial autografts in a rat model of endometriosis treated with etanercept

OBJECTIVE To determine the efficacy of anti-tumor necrosis factor therapy (etanercept) for treating endometriosis in the rat endometriosis model. STUDY DESIGN A randomized, placebo-controlled, blinded study using rat endometriosis model. After the peritoneal implantation of endometrial tissue, twenty-eight Wistar female rats were randomized to two equal intervention groups: the control group and the etanercept-treated group. After measuring implant volume, pretreatment blood and peritoneal fluid samples were obtained. A vehicle treatment of 2 mL saline to the rats in control group and 0. 4 mg/kg etanercept SC once weekly were administered in the etanercept-treated group. After four weeks treatment period, the volumes and histopathological properties of the implants were evaluated. A scoring system was used to evaluate preservation of epithelia. Endometrial explants were evaluated immunohistochemically for tumor necrosis factor receptor type 2 (TNFR2). A scoring system was used to evaluate expression grade of TNFR2. RESULTS There was not a significant difference in spherical volume between control (131.0 (60.3-501.2)) and treatment groups (72.8 (31.2-149.6)) (p>0.025). There was a significant change in between the volumes of implants before and after treatment in etanercept group (p<0.05). At the end of the treatment significant differences among the groups were found in histopathological and immunohistochemical parameters (p<0.05) also histologic scores and HSCORES were decreased in the treatment group significantly (p<0.05). CONCLUSION These results indicate that etanercept was found to effectively reduce the development of endometriosis in this experimental rat model.

Comparison of GnRH agonists and antagonists in normoresponder IVF/ICSI in Turkish female patients

PurposeTo evaluate the results of gonadotropin-releasing hormone agonist (GnRHa) and gonadotropin-releasing hormone antagonist (GnRHant) use in two demographically matched groups of normoresponder in-vitro fertilisation or intracytoplasmic sperm injection (IVF/ICSI) patients in a prospective study.MethodsWe randomised 93 patients undergoing IVF/ICSI between May 2005 and August 2006. Patients with IVF indications were included except for those with polycystic ovary syndrome or azoospermia, women older than 38 years and those with follicle-stimulating hormone (FSH) ≥10 IU/ml. Patients were stimulated with standard 225 IU recombinant FSH. In Group I (n=45) a daily dose of GnRHant cetrorelix acetate 0.25 mg was administered when follicles reached a diameter of ≥14 mm. Group II (n=48) patients were desensitised with the GnRHa, leuprolide acetate, in a long protocol. Human chorionic gonadotropin (hCG) was administered when at least three follicles of 18 mm in diameter were observed. Oocyte retrieval was scheduled 36 hours following hCG administration and embryos were transferred on day 3 after oocyte retrieval.ResultsThe two groups were homogenous for age, infertility duration, basal FSH and serum oestradiol (E2) (P=0.537, P=0.911, P=0.103 and P=0.733, respectively). In Group II (the GnRHa group) more antral follicles (P<0.001), a longer induction duration (P=0.017) and higher peak E2 levels (P<0.001) were observed. No differences were observed in the number of oocytes retrieved (P=0.749), embryos achieved and transferred (P=0.677), or fertilisation rates (P=0.839) between the two groups. There was no statistically significant difference between groups in clinical pregnancy rates, cycle cancellation and ovarian hyperstimulation (P=0.437, P=0.109 and P=0.415, respectively).ConclusionGnRHant and GnRHa provide comparable results in normoresponder patients, while GnRHant allows a greater flexibility in their treatment.

Relationship between Preterm Labor and Thrombophilic Gene Polymorphism: A Prospective Sequential Cohort Study

Objective: Premature labor is still the leading cause of infant mortality and morbidity worldwide. Multiple etiological factors including genetics and environment are held responsible for preterm birth. However, scientific data regarding the link between premature birth and genetics are limited. Subjects and Methods: In this study, we included 50 women who had premature labor (group 1) but did not have any known risks for a premature delivery such as uterine anomaly, polyhydramnios, hypertension, and diabetes mellitus, and another 50 healthy women who had term labor as control (group 2). We compared these two patient groups for MTHFR C677T, MTHFR C1298T, prothrombin 20210A, factor V and ACE polymorphisms. Results: We could not detect a statistical significance between groups for polymorphisms in MTHFR C677T, MTHFR C1298T, prothrombin 20210A, factor V and ACE polymorphisms. Conclusion: We investigated the relationship between premature and term labor and thrombophilic gene polymorphism. However, we found no associations with premature or term labor with the parameters included.

Environmental tobacco smoke exposure during intrauterine period promotes granulosa cell apoptosis: a prospective, randomized study

Objective: To evaluate the intrauterine effect of cigarette smoke on cell death and DNA damage in follicular cells of fetal ovarian tissue. Methods: A prospective, randomized study was conducted with 25 female wistar-albino rats. The rats were randomized to be exposed either to cigarette smoke or to room air, initiating from proestrous period and during pregnancy. Newborn female rats were categorized as Group 1 (n = 24) that had been exposed to cigarette smoke during intrauterine life and Group 2 (n = 7) that had been exposed to room air during intrauterine life. Bilateral ooferectomies were performed on the 2nd week of their life. TUNEL (in-situ Terminal Deoxynucleotidyl-Transferase Mediated dUTP-Nick-End Labeling) immunofluorescent staining and immunohistochemical analyses with caspase-3 were used for detection of DNA damage and apoptosis. Primary outcomes were apoptotic index and immunohistochemical scores (HSCORE). Secondary outcomes were ovarian follicle counts and birth weights of newborn rats. Results: There was a significant increase of HSCORE and apoptotic index in Group 1. Increased immunofluorescent staining; evaluating DNA damage, with TUNEL method was observed in granulosa cells in Group 1. Conclusions: Intrauterine exposure to cigarette smoke diminishes ovarian reserve of female offspring, raising the concern about the generational impact of maternal smoking on ovarian function in the human.