Nicel Tasdemir

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.

Progression to impaired glucose tolerance or type 2 diabetes mellitus in polycystic ovary syndrome: a controlled follow-up study.

OBJECTIVE To investigate whether retesting with the oral glucose tolerance test (OGTT) is useful and necessary for all women with polycystic ovary syndrome (PCOS). DESIGN Follow-up study. SETTING Tertiary medical center. PATIENT(S) Eighty-four women with PCOS and 45 healthy controls. INTERVENTION(S) Peripheral venous blood sampling. MAIN OUTCOME MEASURE(S) We performed a 75-g 2-hour OGTT in women with normal glucose tolerance (NGT) and impaired glucose tolerance (IGT) at the time of the first test with and without PCOS. RESULT(S) The average follow-up period for women with PCOS was 2.6 years (range, 2-4.17 years). Seventy-eight of these women had NGT at baseline, 11.5% converted to IGT, with an annualized incidence rate of 4.5%. Of those women with IGT at baseline (n = 6), 33.3% converted to type 2 diabetes mellitus, with an annualized incidence rate of 10.4%. In the healthy subjects, the average follow-up period was 2.6 years (range, 2-4.08 years). Forty-two of these women had NGT at baseline, 2.3% converted to IGT, giving a progression of 0.9% per year. Among the three women with IGT at baseline, 33.3% reverted to NGT, and 66.6% had persistent IGT. CONCLUSION(S) Conversion rates from NGT to IGT or type 2 diabetes mellitus were accelerated in women with PCOS compared with healthy subjects. Women with PCOS should be tested regularly for early detection of abnormal glucose tolerance. In addition, the interval for periodic rescreening should be determined by further studies involving more women with PCOS.

Is subclinical hypothyroidism contributing dyslipidemia and insulin resistance in women with polycystic ovary syndrome

We aimed to analyze lipid parameters and determine the need for a 2-hour oral glucose tolerance test (OGTT) for the identification of IR and impaired glucose tolerance test (IGT) in subclinical hypothyroidism (SCH) women with and without polycystic ovary syndrome (PCOS). 20 patients with PCOS and SCH consisted of Group I and 39 patients with PCOS and normal thyroid function consisted of Group II and 53 healthy women with normal thyroid function consisted of Group III. Triglyceride levels were 143.26 ± 99.86 mg/dL in group 1 and 88.56 ± 37.56 mg/dL in group 2 and 83.71 ± 31.94 mg/dL in group 3 which were statistically significant. Total cholesterol, HDL- cholesterol, LDL-cholesterol were found similar between the groups. Fasting insulin levels were 12.45 ± 8.62 µU/mL in group 1 and 8.60 ± 5.35 µU/mL in group 2 and 7.04 ± 3.55 µU/mL in group 3 which were statistically significant (P = 0.027). HOMA-IR were 2.92 ± 2.34 in group 1 and 1.95 ± 1.52 in group 2 and 1.60 ± 0.86 in group 3 which were statistically significant (P = 0.046). This study showed that women with PCOS and subclinical hypothyroidism should be evaluated for dyslipidemia and Insulin resistance.

Assessment of impaired glucose tolerance prevalence with hemoglobin A1c and oral glucose tolerance test in 252 Turkish women with polycystic ovary syndrome: a prospective, controlled study

STUDY QUESTION What is the prevalence of abnormalities in glucose metabolism in patients with polycystic ovary syndrome (PCOS) and controls in a Turkish population? SUMMARY ANSWER The total prevalence of glucose abnormalities in PCOS patients was 16.3% [impaired glucose tolerance (IGT) 14.3%; type 2 diabetes mellitus (T2DM) 2%] and was higher than in healthy subjects (IGT 8.5%; T2DM 0%, respectively). WHAT IS KNOWN ALREADY One of the most common markers of chronic glycemia is hemoglobin Alc (HbA1c). However, little is known about whether the use of HbA1c results in diagnosis of more cases of glucose intolerance in the PCOS population than the oral glucose tolerance test (OGTT) alone. STUDY DESIGN, SIZE, DURATION This was a prospective study, including 252 women with PCOS and 117 control women without PCOS. PARTICIPANTS/MATERIALS, SETTING, METHODS The study was carried out in the gynecological outpatient department of Namik Kemal University Hospital, Turkey, between 2010 and 2012. Women with PCOS (n = 252) were diagnosed according to Rotterdam criteria. The control group included 117 women (aged 17-45 years) who were selected randomly. BMI of participants ranged between 15.6 and 47.9 kg/m(2). MAIN RESULTS AND THE ROLE OF CHANCE Patients with PCOS were comparable to controls in terms of age (24.8 versus 25.9 years, respectively) and had higher BMI (26.1 versus 24.9 kg/m(2), respectively). Of 252 patients with PCOS, 41 had glucose intolerance (IGT 14.3%; T2DM 2%) when compared with 10 of the 117 control patients (IGT 8.5%; T2DM 0%; odds ratios = 2.08; P = 0.045) during the OGTT. When an HbA1c value ≥ 5.6% was used to divide the total population, the prevalence of abnormal glucose metabolism was 7.9% in the patients with PCOS, below the value detected in the control patients (8.5%), which showed that 20 of 41 patients with abnormal glucose tolerance would not have been diagnosed, if the HbA1c alone had been used. When compared with the OGTT results, HbA1c provided 52.4% sensitivity, 74.4% specificity, 67.1% positive and 60.9% negative predictive values with a threshold value of 5.6% in abnormal glucose tolerance. The receiver operating characteristic analysis suggested a threshold value of 5.35% in HbA1c (75.6% sensitivity and 52.6% specificity) for the prediction of abnormal glucose tolerance. LIMITATIONS, REASONS FOR CAUTION This study did not involve weight-matched healthy subjects, which may cause a difference in prevalence of abnormal glucose metabolism between the groups, and the results are limited to an unselected population of patients who have the full PCOS phenotype. In addition, the incidence of T2DM among the first-degree relatives and 2-h insulin levels could not be reported in full. WIDER IMPLICATIONS OF THE FINDINGS Further investigation of the efficacy of HbA1c for the prediction of abnormal glucose tolerance should be undertaken in long-term prospective studies and in different geographic populations. At present, the only way to reliably detect abnormal glucose metabolism in Turkish women with PCOS appears to be using the OGTT. STUDY FUNDING/COMPETING INTEREST(S) No financial support. The authors have no competing interests to declare. TRIAL REGISTRATION NUMBER Not applicable.

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.

Protection from cyclophosphamide-induced ovarian damage with bone marrow-derived mesenchymal stem cells during puberty

Abstract Objective: In female cancer survivors, the accelerated loss of primordial follicles may lead to premature ovarian failure. We investigated the protective effects of bone marrow derived mesenchymal stem cells (BMMSC) and gonadotropin releasing hormone analogue (GnRHa) against chemotherapeutic-induced ovarian toxicity in a rat model. Material and methods: Forty-eight Wistar albino female rats were divided into four groups. Group 1 was composed of rats that were given 200 mg/kg cyclophosphamide injection for each cycle (two cycles for each rat). Both cyclophosphamide and 0.4 µg GnRHa were administered to Group 2. Cyclophosphamide and 4 million/kg BMMSC were administered to Group 3. Cyclophosphamide, GnRHa, and BMMSC were administered to Group 4. Germ cell apoptosis, DNA fragmentation and primordial follicular count were investigated with Cleave Caspase-9 and TUNEL analysis. The presence of the SRY gene on the Y chromosome in the ovary of the recipient female rats was checked with PCR. Results: Immunohistochemical staining (IHS) of Caspase-9 and TUNEL was higher in Group 1 than in Group 3 (p < 0.05). Similarly, Group 4 had higher values than Group 3 (p < 0.05). The presence of the SRY gene was detected in Groups 3 and 4 with the PCR analysis. The mean primordal follicle count was lowest in Group 1 and the mean primordial follicle counts were higher in Groups 2 and 3 than in Group 1. The difference between Group 1 and Group 4 was not significant. Conclusion: BMMSC therapy was found to be protective from germ cell apoptosis and DNA damage when it was used with chemotherapy regimens including alkylating agents.

Protective effect of infliximab on ischemia/reperfusion injury in a rat ovary model: biochemical and histopathologic evaluation

OBJECTIVE The aim of this study was to investigate the effect of infliximab on experimentally induced ovarian ischemia/reperfusion injury (IRi). STUDY DESIGN A total of 42 female rats were equally divided into 6 experimental groups; group 1: sham operation, group 2: 3-h ischemia, group 3 and 4: 3-h ischemia, 3-h reperfusion, group 5 and 6: 3-h ischemia, 24h reperfusion. In group 4 and group 6, 30 min before reperfusion, infliximab was administered intraperitoneally at a dose of 5mg/kg. Bilateral ovaries were removed for histopathologic and biochemical analysis. Serum MDA (sMDA), tissue MDA (tMDA), serum NO (sNO), tissue NO (tNO) and serum catalase concentrations were analyzed. Tissue damage of ovarian tissue was scored by histological examination. RESULTS The infliximab administration significantly lowered the sNO, tNO and sMDA concentrations in group 4 compared to group 3 (p=0.041, p=0.025 and p=0.035, respectively). sNO, tNO and sMDA concentrations were also lower in group 6 when compared to group 5, but this differences were not significant (p>0.05). On the other hand, tMDA concentrations were lower in infliximab-applied groups when compared to ischemia/reperfusion groups (group 3 vs. 4 and 5 vs. 6) (p=0.045 and p=0.048, respectively). Moreover, histopathologic tissue damage scores in infliximab administration groups were significantly lower than in ischemia/reperfusion groups (p<0.001). CONCLUSION Infliximab attenuates I/R-induced ovarian tissue injury in rats subjected to ischemia/reperfusion.

Vascular endothelial growth factor (VEGF) and inducible nitric oxide synthase (iNOS) immunoreactivities in rat ovaries and uterine tubes after tubal ligation: a controlled immunohistochemical study

Objective To evaluate the effects of tubal ligation on ovarian and tubal tissues by means of immunohistochemical evaluation of two hypoxia related mediators: vascular endothelial growth factor (VEGF) and inducible nitric oxide synthase (iNOS). Design Fourteen Sprague-Dawley female rats were divided into two groups: a tubal ligation (Pomeroy technique) was carried out on rats in group 1 (n = 7) whereas those in group 2 served as controls (n = 7). Salpingo-oophorectomy was performed in group 1 during the second oestrous period following tubal ligation. Rats in group 2 were submitted to a salpingo-oophorectomy, as well. VEGF and iNOS immunoreactivities in ovarian and tubal tissues were evaluated by means of immunohistochemistry. Immunohistochemical scores and number of antral follicles were compared. Results In the ovary, VEGF immunoreactivity was significantly more intense in the granulosa (p = 0.002) and the theca cells (p = 0.001) of rats in group 1 but, in ovarian medulla (p = 0.259) and germinal epithelium (p = 0.209), it was not significantly different from that of rats in group 2. The iNOS immunoreactivity in ovarian granulosa cells (p = 0.073) and germinal epithelial cells (p = 0.805) did not differ between the two groups. The cytoplasmic VEGF (p = 0.001) and iNOS (p = 0.017) immunoreactivities in the uterine tube, were significantly more intense in group 1. However, VEGF immunoreactivity in the lamina propria of the uterine tube (p = 0.209) was of similar intensity in both groups. Conclusion Tubal ligation may lead to supraphysiological hypoxia as evidenced by increased VEGF and iNOS immunoreactivities in ovarian and tubal tissues.

Outcome of intrauterine pregnancies with intrauterine device in place and effects of device location on prognosis

OBJECTIVES This study aimed to compare the outcome of pregnancies with retained or removed intrauterine devices (IUDs) and the effect of IUD location on pregnancy outcome. STUDY DESIGN In a retrospective cohort study, we searched 27,578 records of women who had CuT380 IUD inserted, and 144 pregnancies with IUD were analyzed. IUDs were removed from 114 patients and retained for 30 patients. RESULTS The combined risk of adverse pregnancy outcomes (miscarriage, intrauterine fetal death, intrauterine growth retardation, preterm birth and preterm premature rupture of membranes) was 36.8% in the IUD-removed group and 63.3% in the IUD-retained group [p<.01; relative risk (RR)=2.0; 95% confidence interval (CI) 1.3-3.3]. Newborns of the IUD-retained women had significantly lower Apgar scores and significantly higher admission rate to the neonatal intensive care unit (p=.01; RR=10.8; 95% CI 1.04-111.6 and p<.01; RR=4.5; 95% CI 1.5-12.9, respectively). There were more miscarriages and adverse pregnancy outcome when the IUD was retained (16.9% vs. 66.7%) in patients with an IUD in low-lying position (p<.01; RR=3.9; 95% CI 1.8-8.6). CONCLUSION Women who conceived with an IUD in place and chose to continue the pregnancy without removing the IUD need close follow-up, as there appears to be higher risk of adverse pregnancy and neonatal outcome. Furthermore, when the IUD is retained in the low-lying position, there is increased risk of miscarriage and adverse pregnancy outcome compared to removal of the IUD. Future randomized controlled studies are needed to determine the outcome of pregnancies with retained or removed IUD. IMPLICATIONS In this study, we have evaluated the IUD location and its effect on pregnancy outcome in women with a retained or removed IUD. This study is the first to investigate the relationship between IUD location and pregnancy outcome in women who conceived with an IUD. We need evidence from a collaborative multicenter randomized trial to answer the question of whether the IUD should be removed in case of pregnancy.

The serum protein α2-Heremans-Schmid glycoprotein/fetuin-a concentration and carotid intima-media thickness in women with polycystic ovary syndrome.

OBJECTIVE To investigate fetuin-A concentrations and its association with metabolic and sonographic cardiovascular markers in women with polycystic ovary syndrome (PCOS) and healthy subjects. STUDY DESIGN Thirty-five women with PCOS and 37 healthy control women were matched for body mass index (BMI) and age. Serum fetuin-A concentrations, and reproductive and adrenal hormones were measured, and insulin resistance and carotid intima media thickness (CIMT) were evaluated in both groups. The correlations between cardiovascular risk factors, CIMT and fetuin-A concentrations were tested. RESULTS Mean fetuin-A concentrations were significantly elevated in the PCOS group compared with control subjects (101.2 ng/ml ± 33.55 vs. 82.5 ng/ml ± 32.65, P=0.019). CIMT was also higher in women with PCOS than in control subjects (0.51 ± 0.05 mm vs. 0.44 ± 0.05 mm, P<0.01). Serum lipid parameters were correlated to serum fetuin-A concentrations in the PCOS group, but no correlation was found between fetuin-A and CIMT (rPCOS=0.244, pPCOS=0.158; rcontrol=-0.002, pcontrol=0.988). CONCLUSION In this, the first study of fetuin-A concentrations in PCOS, the results showed that fetuin-A concentrations were increased in euglycemic patients with PCOS.