Homocysteine and C-reactive Protein Levels in Women with Polycystic Ovary Syndrome.

OBJECTIVES: Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in infertile women characterized by both reproductive and metabolic dysfunctions of different degrees. Furthermore, it has been associated with increased cardiovascular disease (CVD) risk and related long-term health sequela. The aim of this study is to evaluate serum homocysteine (Hcy) and C-reactive protein (CRP) levels in women with PCOS and to evaluate their relationship with clinical and laboratory parameters in women with PCOS. MATERIALS AND METHODS: The prospective single-center study included 45 women with PCOS (study group) and 41 control subjects. Demographic variables and Hcy, CRP, fasting blood glucose, insulin, follicle-stimulating hormone, luteinizing hormone, estradiol, total and free testosterone, dehydroepiandrosterone sulfate, thyroid-stimulating hormone levels, and lipid profiles of the subjects were recorded. homeostatic model assessment for insulin resistance (HOMA-IR) indexes were calculated. RESULTS: Fasting plasma glucose, insulin, HOMA-IR, free and total testosterone levels, and clinical hirsutism were significantly higher in the study group. There was no statistically significant difference in lipid profile between groups. Hcy and CRP levels were higher in the study group, which was not statistically significantly different (P > 0.05). CONCLUSION: Some of the parameters that are correlated with CVD risk were found to be higher in women with PCOS, although the difference for Hcy and CRP did not reach statistical significance. However, the current study reveals that the CVD risk associated with PCOS deserves more comprehensive prospective studies with long-term outcomes.

Adiponectin and leptin levels in normal weight women with polycystic ovary syndrome.

OBJECTIVES: Since polycystic ovarian syndrome (PCOS) is prevalent in reproductive women with obesity and insulin resistance, adipocytokines are often accused and investigated for pathophysiology. The aim of this study was to evaluate the adiponectin and leptin levels in normal-weight women with PCOS. METHODS: Forty women with PCOS and 40 age and body mass index (BMI) matched controls were included in the study. Adiponectin and leptin levels in addition to other biochemical parameters were measured. RESULTS: Leptin levels were statistically significantly higher in the study group compared to the control group (6.53 ± 2.670 vs 3.37 ± 2.002 ng/mL, p < 0.001 respectively). Although Adiponectin levels were lower in the study group compared to the control group (28.89 ± 16.124 µg/mL vs 31.05 ± 20.507, p = 0.714 respectively) the difference did not reach statistical significance. Leptin levels were positively correlated with fasting glucose, fasting insulin, free testosterone levels and homeostatic model assessment of insulin resistance (HOMA-IR) values. Adiponectin levels were negatively correlated with BMI. CONCLUSIONS: Adiponectin and leptin have been suggested to play a crucial role in the pathogenesis of PCOS. Different adipocytokine levels in the normal weight PCOS group compared to age and BMI matched controls support the idea that adipose tissue in this group of women has some distinctive features not only in high BMI subgroup but also in normal weight subgroup.

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.

Obesity and insulin resistance associated with lower plasma vitamin B12 in PCOS.

Polycystic ovary syndrome (PCOS) shares some or most components of metabolic cardiovascular syndrome, manifested by abdominal obesity, insulin resistance, dyslipidaemia and atherosclerosis. It has been previously demonstrated that folate and vitamin B(12) treatment improved insulin resistance in patients with metabolic syndrome. This study first investigated whether PCOS patients have lower or higher vitamin B(12), folate and homocysteine concentrations when compared with healthy, age and body mass index matched controls, and, then examined associations between vitamin B(12), folate, homocysteine and insulin resistance and obesity in PCOS patients. Homocysteine concentrations and homeostasis model assessment index were higher, whereas concentrations of vitamin B(12) were lower in PCOS patients with insulin resistance compared with those without insulin resistance. Serum vitamin B(12) concentrations were significantly lower in obese PCOS women in comparison with obese control women (P < 0.05). Fasting insulin, insulin resistance and homocysteine are independent determinants of serum vitamin B(12) concentrations in PCOS patients. Insulin resistance, obesity, and elevated homocysteine were associated with lower serum vitamin B(12) concentrations in PCOS patients.

Follicular-fluid anti-Mullerian hormone concentrations are predictive of assisted reproduction outcome in PCOS patients.

Serum anti-Mullerian hormone (AMH) concentrations constitute a sensitive marker for ovarian ageing. In addition, concentrations of AMH in the follicular fluid constitute a useful marker of embryo implantation in assisted reproduction cycles. The present study measured serum and follicular-fluid AMH concentrations on the day of oocyte retrieval. These data showed that clinical pregnancy rates (25.0, 34.1 and 42.1%, respectively, P < 0.001), embryo implantation rates (24.3, 35.0 and 44.4%, respectively, P < 0.001) and fertilization rates (59.2, 70.9 and 79.5%, respectively, P < 0.001) were markedly different among the low, moderate and high follicular-fluid AMH groups but not among the different serum AMH concentration groups. Follicular-fluid AMH concentrations were negatively correlated with follicular-fluid oestradiol concentrations. The results of this study suggest that follicular-fluid AMH concentration on the day of oocyte retrieval would appear to better reflect the reproductive outcome in PCOS patients undergoing assisted reproduction.

Serum antimüllerian hormone concentrations on day 3 of the in vitro fertilization stimulation cycle are predictive of the fertilization, implantation, and pregnancy in polycystic ovary syndrome patients undergoing assisted reproduction.

OBJECTIVE: To determine the possible relationship between serum antimüllerian hormone (AMH) concentrations on day 3 and controlled ovarian stimulation and reproductive outcomes in women with polycystic ovary syndrome. DESIGN: Prospective, clinical trial. SETTING: University hospital. PATIENT(S): Sixty women with PCOS. INTERVENTION(S): Serum concentrations of AMH measured on cycle day 3. MAIN OUTCOME MEASURE(S): Clinic pregnancy rate (CPR), implantation rate (IR), and fertilization rate (FR). RESULT(S): The CPR, IR, and FR were markedly different among the day-3 serum AMH groups (low, moderate, and high AMH groups). The CPR were 33.3, 46.1, and 60.0, respectively, in the low, moderate, and high serum AMH groups on day 3. The embryo IR were 18.6, 26.7, and 36.3, respectively. The FR were 54, 68, and 79, respectively. An AMH level≥3.01 ng/mL was shown to predict FR with a sensitivity of 86.4% and specificity of 75%. An AMH level≥3.2 ng/mL was shown to predict IR and CPR with sensitivity and specificity of 72.1% and 72.7%, and 75.6% and 77.3%, respectively. CONCLUSION(S): On day 3 of the in vitro fertilization stimulation cycle, serum concentrations of AMH can be used as a marker for ovarian response as well as reproductive outcome in assisted reproductive cycles of PCOS patients.

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 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.

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.

Oral contraceptive pretreatment does not improve outcome in microdose gonadotrophin-releasing hormone agonist protocol among poor responder intracytoplasmic sperm injection patients.

PURPOSE: To compare oral contraceptive (OC) pretreatment plus microdose GnRH-a in flare-up protocol and non-OC microdose GnRH-a in flare-up protocol among poor responder ICSI patients. METHODS: A retrospective analysis of poor responder ICSI patients. Patients were divided into two groups according to used microdose protocol. Precycle treatment with OC followed by follicular phase administration of 40 microg s.c. leuprolide acetate (LA) every 12 h beginning on after 2 day pill-free period and rFSH administration was begun on the third day of LA administration (OC-Group, n=26). Alternatively on day 2 after menses, patients were administered similar stimulation regime (non-OC Group, n=27). RESULTS: There were no significant differences between groups in the number of oocytes, peak estradiol levels, endometrial thickness, fertilization rates and embryo quality. Implantations and pregnancy rates per embryo transfer were similar. CONCLUSION: OC pretreatment plus microdose GnRHa in flare-up protocol does not offer advantages over non-OC microdose GnRHa in flare-up protocol among poor responder ICSI patients.

Does addition of low-dose aspirin and/or steroid as a standard treatment in nonselected intracytoplasmic sperm injection cycles improve in vitro fertilization success? A randomized, prospective, placebo-controlled study.

PURPOSE: To investigate the effects of short-term low-dose aspirin and/or steroid use on implantation and pregnancy rates in nonselected intracytoplasmic sperm injection (ICSI) cycles. METHODS: Two-hundred patients undergoing ICSI for their first cycle were enrolled in this study. Participants were then randomized into four groups on the embryo transfer day. Aspirin (100 mg/day) in group A, prednisolone (10 mg/day) in group B, aspirin along with prednisolone in group C were given while placebo was administrated to group D. RESULT: There were no statistically significant differences recorded in the demographic, ovulation induction cycle characteristics between groups. Mean transferred embryo number and mean top quality embryo number were similar among study groups. There were no statistical differences in implantation and pregnancy rates between study groups. CONCLUSION: Administration of low-dose aspirin and prednisolone alone or concomitant as a standard treatment have no positive effects on implantation and/or pregnancy rates.

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

BACKGROUND: Thromboembolism is a rare but extremely serious complication of ovarian hyperstimulation syndrome. CASE REPORT: We report a case of left internal jugular vein thrombosis, presenting as a late complication of moderate ovarian hyperstimulation syndrome. CONCLUSION: Prevention of vascular thrombosis should be a part of the treatment in the setting of assisted reproductive procedures complicated with ovarian hyperstimulation syndrome.