Serum and follicular fluid levels of soluble Fas and soluble Fas ligand in IVF cycles.

OBJECTIVE: To determine follicular fluid (FF) and serum levels of soluble Fas (sFas) and soluble Fas ligand (sFasL) in patients undergoing IVF cycles. STUDY DESIGN: A prospective comparative study among patients with endometriosis (n=12), infertility due to male factor (n=12) and poor responders (n=32) undergoing IVF cycles in Centrum IVF Clinic. Individual FF and serum samples were collected from patients during transvaginal ultrasonography-guided follicle aspiration. Patients were classified as poor responder patients undergoing IVF cycles with GnRHa, triptorelin and GnRH antagonist, cetrotide, patients with endometriosis and patients with infertility due to male factor. sFas, sFasL levels in both FF and serum samples and their correlations with clinical outcomes of IVF were measured in each study group. RESULTS: Serum and FF levels of sFas, sFasL were similar in the poor responder and male factor groups. There were no differences between the serum and FF levels of both sFas and sFasL among poor responder patients receiving either GnRH agonist or antagonist therapies. Serum levels of sFas were significantly lower in the endometriosis group compared to the male factor group. Serum and FF levels of sFas, sFasL were similar among patients with or without clinical pregnancy. CONCLUSION: sFas and sFasL are detected in both serum and follicular fluid samples from IVF cycles, their levels are similar between poor responder and male factor groups as well as between GnRH agonist and antagonist treatment groups. These soluble apoptotic factors may not be predictive for the outcomes of IVF. Decreased serum levels of sFas, suggests increased apoptosis in endometriosis.

Predictive value of glucose-insulin ratio in PCOS and profile of women who will benefit from metformin therapy: obese, lean, hyper or normoinsulinemic?

OBJECTIVE: The aim of the present study is to evaluate sub-groups of PCOS patients who will benefit from metformin therapy and to find out any predictors of ovulation in PCOS sub-groups. METHOD: In the current prospective-randomized, placebo-controlled, double-blind study, PCOS patients (n = 116) were divided into six main groups according to glucose to insulin ratio (G-I ratio mg/10(-4) U) and body mass index (BMI kg/m2) as: Group 1: normoinsulinemic (G-I ratio > or = 4.5 mg/10(-4) U), lean (BMI < 25) (n = 37); Group 2: normoinsulinemic, overweight (BMI: 25-29.9) (n = 19); Group 3: normoinsulinemic, obese (BMI > or = 30) (n = 18); Group 4: hyperinsulinemic (G-I ratio < 4.5 mg/10(-4) U), lean (n = 28); Group 5: hyperinsulinemic, overweight (n = 17); Group 6: hyperinsulinemic, obese (n = 20). Patients in each group were randomized onto placebo or metformin treatments (850 mg two to three times per day according to BMI). The rate of ovulation, biochemical profile, hormonal profile and clinical symptoms of hyperandrogenism were evaluated before and after 6 months of metformin and placebo treatments. RESULT(S): We observed a significant decrease in WHR following metformin therapy in the normoinsulinemic overweight sub-group (P < 0.05). The duration of the menstrual cycle significantly decreased in the normoinsulinemic obese sub-group on metformin therapy (P < 0.05). Metformin had a significant effect on hirsutism scores in hyperinsulinemic lean women (P < 0.05) and decreased DHEAS levels significantly in the lean hyperinsulinemic and normoinsulinemic groups (P < 0.05). Metformin had significant effects on ovulation in only lean hyperinsulinemic women (P < 0.05). CONCLUSIONS: Clinical outcomes of metformin therapy may be categorized on the basis of basal BMI and insulin levels in PCOS patients.

Body mass index is an independent risk factor for the development of endometrial polyps in patients undergoing in vitro fertilization.

OBJECTIVE: To determine the subgroup of patients in whom office hysteroscopy should be routinely performed before an in vitro fertilization (IVF) program. DESIGN: Retrospective cohort analysis. SETTING: Tertiary education and research hospital. PATIENT(S): Two hundred twenty-three patients who underwent a uterine evaluation by office hysteroscopy before the IVF and embryo transfer cycle. INTERVENTION(S): The office hysteroscopy was performed in the follicular phase of the menstrual cycle before the IVF cycle. MAIN OUTCOME MEASURE(S): The office findings: number of polyps, number of multiple polyps, and polyp size. RESULT(S): Patients with polycystic ovary syndrome (PCOS) had a higher number of endometrial polyps, but the difference was not statistically significant (28.9% vs. 18.3%). When comparing the patients according to BMI, patients with BMI >or=30 had a statistically significantly higher number of endometrial polyps versus BMI <30 (52% vs. 15%). On the other hand, obesity was positively correlated with the occurrence of polyps, size of the polyps, and occurrence of multiple number of polyps in the correlation analysis. In addition, logistic regression analysis using age, obesity, duration of infertility, and estradiol levels revealed that obesity was an independent prognostic factor for the development of endometrial polyps. CONCLUSION(S): Office hysteroscopy should be performed in patients with BMI >or=30 because obesity may act as an initiator for the pathogenesis of endometrial polyps.

Combining 2nd-trimester maternal serum homocysteine levels and uterine artery Doppler for prediction of preeclampsia and isolated intrauterine growth restriction.

AIM: To evaluate the efficacy of a combined 2nd-trimester maternal serum homocysteine and uterine artery Doppler screening at 20 weeks of gestation for complications of pregnancy: preeclampsia, isolated intrauterine growth restriction (IUGR), placental abruption, and stillbirths. METHODS: Consecutive singleton pregnancies without previous risk factors who had homocysteine measured as part of a serum-screening program for trisomy 21 had uterine artery Doppler performed. Sensitivity, specificity, positive and negative predictive values, odds ratio, and positive and negative likelihood ratios for the subsequent development of preeclampsia, isolated IUGR, placental abruption, stillbirth, and preterm delivery were calculated for the following methods (1) homocysteine cut-off level 6.3 micromol/l (95th centile); (2) on Doppler ultrasound bilateral notches with a mean resistance index (RI) >0.55 (50th centile), all unilateral notches with a mean RI >0.65 (80th centile), and absence of notches with a mean RI >0.7 (95th centile), and (3) Doppler ultrasound notch evaluation (bilateral, unilateral, absence as in method 2) combined with the homocysteine cut-off level of 6.3 micromol/l. RESULTS: By using a logistic regression model, methods 1 and 2 predicted preeclampsia (p < 0.001), isolated IUGR (p < 0.01), and "any complication" (p < 0.01). The sensitivity for prediction of preeclampsia using the combined method (3) was 61.3% for a false-positive rate of 2%, better than that for isolated IUGR (54%) below the 5th centile and "any complication" (56%). CONCLUSION: This prospective study confirms the potential of a combined method of elevated homocysteine and uterine artery Doppler screening for preeclampsia, isolated IUGR, and any obstetric complication.

Mood scores in relation to hormone replacement therapies during menopause: a prospective randomized trial.

There is lack of studies in literature about the long-term effects of hormone replacement therapies and cholesterol levels on mood scores in menopause. In the present study we have investigated whether serum lipid levels affect mood scores in menopause and evaluated the long-term effects of the combined hormone replacement regimens (HRT) on depressive symptoms in postmenopausal women. In this prospective-randomized, placebo-controlled, double-blind study, 286 women in menopause were divided into four groups according to therapeutic regimens they received; 1) Conjugated equine estrogen (CEE) of 0.625 mg plus medroxyprogesterone acetate (MPA) of 2.5 mg (n = 79), 2) CEE (0.625 mg) plus MPA of 5 mg (n = 77), 3) tibolone of 2.5 mg (a selective tissue estrogenic activity regulator) (n = 76), and 4) Calcium (Ca) of 1,000 mg (n = 54). Beck Depression Inventory (BDI), and serum levels of lipoprotein lipids were assessed before and after 12-months of treatment with oral continuous HRT and Ca supplementation. BDI scores in the study groups were not correlated with lipid profiles. We compared two subgroups of patients with initial BDI scores 0-14 (normal mood scores) in order to asses for the possible relation between the lipid profile and mood. Following treatment, first subgroup had increased scores to 15-30 (mildly depressed women, n = 27) and the second subgroup preserved BDI scores of 0-14 (normal mood scores, n = 23). Serum levels of total cholesterol, high-density lipoprotein, low-density lipoprotein and body mass index were found to be similar between these two groups. BDI scores decreased significantly in all HRT groups after 12 months of treatment, compared to Ca group (p < 0.05). We did not observe any correlation between BDI scores and lipid profiles before and following continuous HRT or Ca supplementation. Continuous combined hormone replacement regimens, CEE + MPA and tibolone, have superior long-term effects on mood scores in menopause and should be considered during the decision process for use of HRT due to menopausal symptoms.

Serum and follicular fluid levels of soluble Fas, soluble Fas ligand and apoptosis of luteinized granulosa cells in PCOS patients undergoing IVF.

BACKGROUND: There are limited data about the levels of soluble apoptotic factors and their modulation with therapeutic regimens in IVF cycles. The aim of the current study was to determine follicular fluid, and serum levels of soluble Fas (sFas) and soluble Fas ligand (sFasL) in PCOS patients undergoing IVF/ICSI cycles; also to investigate the effects of metformin on these factors and on apoptosis of luteinized granulosa cells. METHODS: We investigated the serum and follicular fluid levels of sFas and sFasL in patients with PCOS (n = 28) and compared them with those of the patients with infertility due to male factor (n = 12) undergoing IVF cycles. Effects of metformin therapy on these parameters and apoptosis of luteinized granulosa cells were also investigated among the patients with PCOS. RESULTS: Serum levels of sFas were significantly lower in the PCOS group compared to those in women with infertility due to male factor. Metformin therapy in PCOS patients preceding IVF cycles increased serum levels of sFas and decreased follicular fluid levels of sFasL compared to those on placebo. Follicular fluid from PCOS patients demonstrated luteinized granulosa cell DNA fragmentation in agarose gel, whereas a similar pattern was not observed among PCOS patients undergoing metformin therapy. CONCLUSION: Decreased serum levels of sFas and luteinized granulosa cell DNA fragmentation is observed in patients with PCOS undergoing IVF cycles. Metformin therapy preceding IVF demonstrates an antiapoptotic effect with increased serum levels of sFas, decreased follicular fluid levels of sFasL and prevention of luteinized granulosa cell DNA fragmentation.

Empty follicle syndrome in two sisters with three cycles: case report.

Empty follicle syndrome (EFS) is characterized by a lack of retrieved oocytes in the presence of multiple follicle development, in both natural and stimulated cycles. The aim of the present case report is to point out the possibility of genetic factors that could be responsible for some occurrences of EFS. Two sisters with moderate deafness underwent controlled ovarian hyperstimulation and IVF/ICSI cycles at the same centre. During all three cycles there were normal follicular development, estradiol levels and bio-available hCG plasma levels, but no oocytes and cumulus-corona complexes were retrieved, despite second hCG injections. These cases may represent an inherited condition of EFS with hearing loss with genetic factors affecting both the aetiology of EFS and the hearing loss.