Bülent Berker

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.

Comparative effects of atorvastatin and simvastatin on the plasma total homocysteine levels in women with polycystic ovary syndrome: a prospective randomized study.

OBJECTIVE To test the hypothesis that statins improve hyperhomocysteinemia in women with polycystic ovary syndrome (PCOS). DESIGN A prospective randomized study. SETTING University Hospital. PATIENT(S) Fifty-two women with PCOS and 52 women matched for age and body mass index as controls. INTERVENTION(S) Patients were randomly divided into two groups for treatment: group 1, atorvastatin, 20 mg daily (n = 26), and group 2, simvastatin, 20 mg daily (n = 26). Blood samples were obtained before and after treatment. MAIN OUTCOME MEASURE(S) Serum homocysteine levels. RESULT(S) After 12 weeks of treatment, serum homocysteine levels in group 1 had decreased from 14.3 +/- 2.9 to 10.6 +/- 1.7 micromol/L; in group 2, the levels decreased from 13.6 +/- 2.1 to 11.1 +/- 1.9 micromol/L. Both two groups, free testosterone and total testosterone declined statistically significantly (38.3% and 36.5%; and 40.6% and 46.0%, respectively). In group 1, vitamin B(12) increased from 362.1 +/- 107 to 478.7 +/- 267 pg/mL; in group 2, it increased from 391.3 +/- 107 to 466 +/- 211 pg/mL, but the change did not reach statistical significance. There was a considerable decline in the homeostatic model assessment index in group 1 (40.0% to 32.1%). CONCLUSION(S) Treatment with statins in women with PCOS leads to decreases in serum homocysteine levels.

The role of low-molecular-weight heparin in recurrent implantation failure: a prospective, quasi-randomized, controlled study.

Low-molecular-weight heparin did not provide any beneficial effect on pregnancy outcomes in patients with two or more implantation failures. Further trials are needed to confirm a trend in favor of low-molecular-weight heparin in the subgroup with women with three or more implantation failures.

Plasma interleukin-18 levels are increased in the polycystic ovary syndrome: relationship of carotid intima-media wall thickness and cardiovascular risk factors

OBJECTIVE To determine serum interleukin (IL)-18 levels and to find out whether IL-18 is associated with carotid intima-media wall thickness (IMT) and various cardiovascular risk factors in women with polycystic ovary syndrome (PCOS). DESIGN A prospective, controlled study. SETTING University hospital. PATIENT(S) Sixty women with PCOS and 60 healthy women were included this study. INTERVENTION(S) Serum levels IL-18, homocysteine (Hcy), C-reactive protein (CRP), IL-6, malonyldialdehyde (MDA), lipid and hormone profiles were measured. Carotid IMT was evaluated for both common carotid arteries. MAIN OUTCOME MEASURE(S) Serum IL-18, carotid IMT, Hcy, CRP, IL-6, MDA, and homeostasis model assessment of insulin resistance. RESULT(S) The evaluation, which was made without the obesity influence taken into consideration, revealed that patients with PCOS have increased serum IL-18 levels than that of the control group (214 +/- 102 vs. 170 +/- 78 pg/mL). The interaction between PCOS and obesity was seen to have statistical significance (F = 67.8). Body mass index (BMI), waist to-hip ratio, Hcy, and homeostasis model assessment of insulin resistance are independent determinants of plasma IL-18 in patients with PCOS. Elevated serum IL-18 levels were positively and significantly correlated with a greater carotid IMT. For Hcy and carotid IMT, the interaction between PCOS and obesity was found in a two-way ANOVA variation analysis (F = 48.5 and F = 81.5, respectively). CONCLUSION(S) Elevated serum IL-18 levels were associated with cardiovascular risk factors and carotid IMT in patients with PCOS.

Comparison of hysterosalpingography and hysteroscopy in the evaluation of the uterine cavity in patients undergoing assisted reproductive techniques

OBJECTIVE To investigate the diagnostic value of hysterosalpingography (HSG) for intracavitary and structural uterine pathologies in comparison with hysteroscopy (HS) in patients undergoing intracytoplasmic sperm injection-embryo transfer and also to specify the patients who should be subjected to HS in the early stages of an infertility work-up. DESIGN Retrospective analysis. SETTING IVF unit of a university hospital. PATIENT(S) Three hundred fifty-nine consecutive women who underwent both HSG and HS for infertility investigation. INTERVENTION(S) HS and HSG. MAIN OUTCOME MEASURE(S) HS findings. RESULT(S) HSG shows a sensitivity of 21.56%, specificity of 83.76%, positive predictive value of 55.26%, and negative predictive value of 70.75%. Its false-negative rate is 78.43%, and its false-positive rate is 16.23%. Overall agreement between the two procedures is 68.9%. The risk of abnormal HS increases with advancing patient age and duration of infertility. Risk increments associated with patient age over 35 years and increasing number of previous assisted reproductive techniques (ART) persist even in the presence of a normal HSG. As expected, we encounter significantly less abnormal HS in the male factor infertility group. CONCLUSION(S) HS should be performed especially in patients older than 35 years of age and/or with a history of two or more previous ART trials even in the presence of a normal HSG. HSG shows unconvincing diagnostic value for intracavitary and structural uterine pathologies in infertility evaluation.

OVARIAN ECTOPIC PREGNANCY AFTER INTRACYTOPLASMIC SPERM INJECTION

A ruptured primary ovarian pregnancy occurred following ovulation induction, intracytoplasmic sperm injection (ICSI) and embryo transfer (ET). The exact mechanism of ovarian pregnancy after intracytoplasmic sperm injection is unclear, but, it is possible that there may be an association between blastocyst transfer and ovarian pregnancy in infertile patients who underwent ICSI, prolonged in vitro culture and fifth day embryo transfer at blastocyst stage.

Prognostic value of p53 accumulation in epithelial ovarian carcinomas

Abstract Aim: To evaluate the prognostic significance of p53 expression in epithelial ovarian carcinomas (EOC), and to look for correlations between p53 and other disease parameters. Material and methods: Immunohistochemical techniques were used to evaluate p53 expression in paraffin-embedded tissue specimens of 50 EOC cases. Results: p53 immunoreactivity was present in 33 of the 50 cases (66%). The expression of the p53 did not show any association with the tumor histologic type, grade or with the disease stage. However, p53 accumulation was significantly more prevalent among tumors with high mitotic index (p<0.01). Although median survival was low in the p53 negative cases, this biologic marker did not reveal as an independent prognostic factor in Cox’s regression analysis. Conclusion: Abnormalities of p53 expression which is an inducer of apoptosis occur commonly in EOC. Although we could not find it as an independent prognostic factor, p53 expression should be studied in larger series to reveal its accurate prognostic significance.

Serum levels of adenosine deaminase and pregnancy-related hormones in hyperemesis gravidarum.

Abstract Objectives: We investigated the correlation between pregnancy-related hormones and serum adenosine deaminase (indicator of cellular immunity) level in women with hyperemesis gravidarum. Materials and methods: Twenty patients with hyperemesis gravidarum and 20 normal pregnancies were included in this prospective, case-control study. Serum adenosine deaminase levels, hematological parameters (white blood cells, neutrophil, monocyte and lymphocyte counts) and hormone levels (prolactin, progesterone, thyroid stimulating hormone, human chorionic gonadotropin β subunit, estradiol (E2)) were measured in all women. Interrelations of blood cell counts and hormone levels with serum adenosine deaminase levels were also investigated. Results: Serum adenosine deaminase, human chorionic gonadotropin β subunit, thyroid stimulating hormone, E2, progesterone and prolactin levels, and lymphocyte and monocyte counts in women with hyperemesis gravidarum were significantly higher than in controls but white blood cells, neutrophil, T3 and T4 levels were not different. Serum adenosine deaminase level correlated with E2, progesterone, lymphocyte, and monocyte levels for all patients. Conclusion: Elevated serum adenosine deaminase in patients with hyperemesis gravidarum may relate to high levels of E2 and progesterone.

Internal jugular vein thrombosis as a late complication of ovarian hyperstimulation syndrome in an ICSI patient.

BackgroundThromboembolism is a rare but extremely serious complication of ovarian hyperstimulation syndrome.Case reportWe report a case of left internal jugular vein thrombosis, presenting as a late complication of moderate ovarian hyperstimulation syndrome.ConclusionPrevention of vascular thrombosis should be a part of the treatment in the setting of assisted reproductive procedures complicated with ovarian hyperstimulation syndrome.