Ruşen Aytaç

Homocysteine concentrations in follicular fluid are associated with poor oocyte and embryo qualities in polycystic ovary syndrome patients undergoing assisted reproduction.

BACKGROUND A poor quality of oocytes and embryos and a low fertilization rate have been found in polycystic ovary syndrome (PCOS) patients. An inverse association between follicular fluid homocysteine (Hcy) levels and oocyte and embryo quality has also been demonstrated. We examined the relationship between follicular fluid Hcy concentrations and oocyte and embryo quality in PCOS patients undergoing assisted reproduction. METHODS Fifty-two PCOS patients were included in the study, and underwent GnRH agonist/recombinant FSH treatment. The Hcy, folate, vitamin B(12), malonyldialdehyde (MDA) and estradiol (E(2)) levels were measured in follicular fluid from single oocytes at time of retrieval. One follicle per ovary was sampled and 94 were analysed. Plasma hormones were also measured. Oocytes and embryos were graded (1-3) using standard approaches. RESULTS The concentrations of Hcy, E(2), vitamin B(12), folate and MDA in plasma were higher than in follicular fluid (all P < 0.001). Significant differences were observed in follicular Hcy levels between Grade 3 and Grade 2 oocytes (P < 0.001). Hcy levels were lower in Grade 1-2 embryos than that in Grade 3 embryos; follicular fluid vitamin B(12) levels were lower in patients showing high concentrations of follicular fluid Hcy (P < 0.01). The follicular fluid Hcy levels were negatively correlated with follicular fluid vitamin B(12) (r = -0.44), folate (r = -0.68) and fertilization rate (r = -0.85), and positively correlated with follicular fluid MDA (r = 0.51). CONCLUSIONS Concentrations of Hcy in follicular fluid on the dOPU may be a useful marker for fertilization rate, and oocyte and embryo quality in PCOS patients undergoing assisted reproduction.

Microdose gonadotropin-releasing hormone agonist flare-up protocol versus multiple dose gonadotropin-releasing hormone antagonist protocol in poor responders undergoing intracytoplasmic sperm injection–embryo transfer cycle

OBJECTIVE To compare the efficacy of microdose GnRH agonist (GnRH-a) flare-up and multiple dose GnRH antagonist protocols in patients who have a poor response to a long luteal GnRH-a protocol. DESIGN Prospective, randomized, clinical study. SETTING University hospital. PATIENT(S) Forty-two poor responder patients undergoing intracytoplasmic sperm injection (ICSI)-embryo transfer cycle. INTERVENTION(S) Twenty-one patients received microdose leuprolide acetate (LA) (50 microg twice daily) starting on the second day of withdrawal bleeding. The other 21 patients received 0.25 mg of cetrorelix daily when the leading follicle reached 14 mm in diameter. MAIN OUTCOME MEASURE(S) Serum E(2) levels, number of growing follicles and mature oocytes, embryo quality, dose of gonadotropin used, cancellation, fertilization, implantation rate and pregnancy rate (PR). RESULT(S) The mean serum E(2) concentration on the day of hCG administration was significantly higher in the microdose GnRH-a group than in the GnRH antagonist group (1,904 vs. 1,362 pg/mL). The clinical PRs per started cycle of microdose GnRH-a and GnRH antagonist groups were 14.2% and 9.5%, respectively. There were no statistically significant differences in the other ovulation induction characteristics, fertilization and implantation rates. CONCLUSION(S) Microdose GnRH-a flare-up protocol and multiple dose GnRH antagonist protocol seem to have similar efficacy in improving treatment outcomes of poor responder patients.

Tissue Trauma in Abdominal and Laparoscopic-Assisted Vaginal Hysterectomy

STUDY OBJECTIVE To compare the degree of tissue damage between abdominal and laparoscopic-assisted hysterectomy. DESIGN Prospective, randomized, controlled study (Canadian Task Force classification I). SETTING University hospital. PATIENTS Forty-six women. INTERVENTION Laparoscopic-assisted and abdominal hysterectomy. MEASUREMENTS AND MAIN RESULTS The degree of tissue injury caused by surgical trauma was assessed by measuring plasma levels of creatine phosphokinase (CPK), C-reactive protein (CRP), lactic dehydrogenase (LDH), and CA 125 in patients undergoing laparoscopic-assisted (n = 23) and abdominal hysterectomy (n = 23). Plasma levels of CPK-MB isoenzyme were measured in order to exclude the possibility of myocardial injury. Blood samples were taken preoperatively, and on the first and second postoperative days. There was no difference in demographic characteristics between the groups. One patient in the laparotomy group and two patients in the laparoscopy group were excluded from analysis due to bladder injury, postoperative thrombophlebitis, and conversion to laparotomy because of severe adhesions. The mean operation time was longer (105.5 +/- 23.1 minutes vs 77.3 +/- 18.7 minutes, p < .001), but the duration of hospital stay was shorter (2.7 +/- 0.8 days vs 4.3 +/- 1.4 days, p < .001) and analgesic requirement was lower in the laparoscopy group compared with the abdominal group. We observed significant postoperative increases in CRP and CPK in both groups on postoperative days 1 and 2, whereas the increase in LDH was significant only in the laparotomy group on postoperative day 2. There were no significant changes in CPK-MB and CA 125. Moreover, mean plasma levels of CRP and CPK were significantly higher in the laparotomy group on postoperative days 1 and 2 than in the laparoscopy group (p < .05). CONCLUSION Surgery is a significant cause of tissue injury that can be assessed by specific enzymes and proteins. We suggest that laparoscopic surgery causes less tissue damage as assessed by lower postoperative CRP and CPK values, and that less tissue trauma related with laparoscopic surgery may account for early mobilization and reduced analgesic requirement in these patients.

The Prevalence of Different HPV Types in Turkish Women With a Normal Pap Smear

The age‐specific human papillomavirus (HPV) seroprevalence and HPV type distribution in women with normal cervical cytology were studied. Cervical smear samples obtained using liquid‐based smears from 582 clinically healthy women aged between 15 and 68 years from five centers from four different regions of Turkey, were studied between February 2010 and January 2011. Overall, 530 of the women with normal cytology were included and the samples were analyzed for the presence of HPV by AmpliTaq. Positive samples were typed further for 37 different HPV genotypes by a line blot assay. HPV was positive in 17.9% of the women. HPV prevalence was highest in the age group of 25–29 years (31.8%), and decreased with increasing age. HPV 16 was the most common type (3.6%) followed by type 6 (2.6%) and type 45 (2.2%). Types 11 and 18 were rare (0.6% and 0.4%, respectively). Among the risk factors, number of sexual partners and parity were positively correlated with HPV positivity. In the present study, a large number of sex partners and high parity increased the risk for HPV infection. The age‐specific distribution of HPV in women with normal Pap smears did not show a U‐shaped curve in contrast to European countries and the USA. J. Med. Virol. 84: 1242–1247, 2012.

The addition of gonadotrophin releasing hormone agonist to routine luteal phase support in intracytoplasmic sperm injection and embryo transfer cycles: a randomized clinical trial.

OBJECTIVES To determine the effects of addition of different dosages of gonadotrophin releasing hormone agonist (GnRH-a) to routine luteal phase support (LPS) on implantation and pregnancy rates. STUDY DESIGN Three hundred infertile couples who were treated by intracytoplasmic sperm injection and embryo transfer (ICSI-ET) following controlled ovarian stimulation (COS) with long luteal GnRH agonist protocol were enrolled. All women received 600 mg/day vaginal micronized progesterone plus 4 mg 17β estradiol for LPS starting from the day of oocyte retrieval. Patients (n=300) were randomized into three treatment groups. Group A (n=100) received leuprolide acetate 1 mg s.c. injection 3 days after ET in addition to routine LPS. Group B (n=100) received two sequential doses of leuprolide acetate 1 mg s.c. injections 3 and 6 days after ET in addition to routine LPS. Control group (n=100) received only the routine LPS. RESULTS A total of 279 patients completed the study. The groups were comparable in terms of baseline demographic parameters including age, duration of infertility and day 3 levels of FSH and estradiol. The cycle parameters of the groups were also comparable regarding the E2 level on day of hCG, number of retrieved oocytes, number of day 3 embryos, number of embryos transferred, and endometrial thickness on both days of OPU and ET. The implantation rates were similar in between the Groups A, B, and control group (20.7% and 25.8% vs. 13.3%, respectively; P=.099). The clinical pregnancy rates and miscarriage rates were similar in between the groups. The ongoing pregnancy rates were 27.4% in control group, 36% in Group A and 42.9% in Group B (P=.093). The OHSS rates were comparable in between the groups. The multiple pregnancy rates were significantly higher in Groups A and B than in control group (12% and 17.9% vs. 4.2%, respectively; P=.014). CONCLUSIONS The implantation, clinical pregnancy and ongoing pregnancy and multiple pregnancy rates seem to be increased with the addition of GnRH-a to routine luteal phase support.

The value of the progesterone-to-estradiol ratio on the day of hCG administration in predicting ongoing pregnancy and live birth rates in normoresponders undergoing GnRH antagonist cycles

OBJECTIVE To investigate the relationship of the progesterone-to-estradiol (P/E2) ratio on the day of hCG administration with ongoing pregnancy rates in patients with normal ovarian reserve undergoing GnRH antagonist cycles. STUDY DESIGN Observational cohort study including 129 women with normal ovarian reserve undergoing the GnRH antagonist protocol at the IVF unit of Ankara University School of Medicine. Receiver operating characteristics (ROC) analysis was performed to determine cut-off values for the P/E2 ratio detrimental to IVF/ICSI-ET outcomes. The ongoing pregnancy rate was the primary outcome measure. Groups were compared using the independent-samples Students t-test, Mann Whitney and Chi-Square tests. Multivariate logistic regression analysis was used to study the association between the variables and the P/E2 ratio. RESULTS The optimal cut-off value for P/E2 ratio in GnRH antagonist cycles was 0.48; ongoing pregnancy rates and live birth rates were found to be significantly higher in patients with P/E2 ratios≤0.48 than those with>0.48 (50% vs 22.4%, p=0.001 and 38.5% vs 19.7%, p=0.02, respectively). In logistic regression analysis, the P/E2 ratio was found to be an independent predictor for pregnancy, but the sensitivity (69%), specificity (61%) and overall accuracy (67%) were low as a predictor test for cycle outcome. CONCLUSION Although a P/E2 ratio≤0.48 on the day of hCG administration was associated with significantly higher ongoing pregnancy and live birth rates, it has poor predictive value for cycle outcome in patients with normal ovarian reserve undergoing GnRH antagonist cycles.

Increased monocyte chemoattractant protein-1 levels indicating early vascular damage in lean young PCOS patients

Serum levels of monocyte chemoattractant protein-1 and C-reactive protein levels, as early signs of vascular damage and cardiovascular disease, were increased in young, lean patients with polycystic ovary syndrome. Serum monocyte chemoattractant protein-1 levels were positively correlated with serum LH, T, and C-reactive protein levels.

Comparison of the ultrashort gonadotropin-releasing hormone agonist-antagonist protocol with microdose flare -up protocol in poor responders: a preliminary study.

OBJECTIVE To determine the potential effect of the ultrashort gonadotropin-releasing hormone (GnRH) agonist/GnRH antagonist protocol versus the microdose GnRH agonist protocol in poor responders undergoing intracytoplasmic sperm injection (ICSI). MATERIAL AND METHODS The patients in the Agonist-Antagonist Group (n=41) were administered the ultrashort GnRH-agonist/ antagonist protocol, while the patients in the Microdose Group (n=41) were stimulated according to the microdose flare-up protocol. The mean number of mature oocytes retrieved was the primary outcome measure. Fertilization rate, implantation rate per embryo and clinical pregnancy rates were secondary outcome measures. RESULTS There was no differenc between the mean number of mature oocytes retrieved in the two groups. There were also no statistical differences between the two groups in terms of peak serum E2 level, canceled cycles, endometrial thickness on hCG day, number of 2 pronucleus and number of embryos transferred. However, the total gonadotropin consumption and duration of stimulation were significantly higher with the Agonist-Antagonist Group compared with the Microdose Group. The implantation and clinical pregnancy rates were similar between the two groups. CONCLUSION Despite the high dose of gonadotropin consumption and longer duration of stimulation with the ultrashort GnRH agonist/ antagonist protocol, it seems that the Agonist-Antagonist Protocol is not inferior to the microdose protocol in poor responders undergoing ICSI.

Infertility work-up: To what degree does laparoscopy change the management strategy based on hysterosalpingography findings?

The aim of this study was to assess the diagnostic accuracy of hysterosalpingography (HSG) on tubal patency (TP) and to determine whether performing laparoscopy (LS) can change the original management strategy based on HSG findings.

Diagnostic performance of p16 staining in atypical squamous cells ' cannot exclude high-grade squamous epithelial lesion ' in predicting high-grade cervical pathology

Abstract Atypical squamous cells ‘cannot exclude high-grade squamous epithelial lesion’ (ASC-H) cytology represents clear risk and has been a controversial issue in clinical practice. The objective of this study is to investigate the diagnostic performance of p16INK4A immunohistochemistry (IHC) among ASC-H Pap smears in predicting high-grade cervical intraepithelial lesions. Decolourisation and staining process with p16INK4A is applied to 27 ASC-H diagnosed conventional Pap smears, which were all managed with colposcopy-directed cervical biopsy priorly. Staining characteristics of ASC-H Pap smears were compared with histopathological data and sensitivity-specificity values of p16 triage to detect CIN2 + histopathology were determined. The sensitivity and specificity of positive p16INK4A immune staining to detect CIN2 + histopathology were as 87.5% and 68%, respectively. The positive predictive value of p16 triage is found as 53.8% and negative predictive value was as 92.8%. p16INK4A IHC seems applicable for conventional Pap smears and may provide an alternative triage option in ASC-H category.