Correlation between thrombophilia and recurrent pregnancy loss in patients with polycystic ovary syndrome: a comparative study.

BACKGROUND: Patients with polycystic ovary syndrome (PCOS) have an increased prevalence of thrombophilia, leading to higher rates of pregnancy loss. The aim of this study was to determine the association between thrombophilia and recurrent pregnancy loss (RPL) in patients with and without PCOS. METHODS: In this comparative case-control study, we included 60 patients with RPL (≥3 consecutive pregnancy losses at <20 weeks of gestation) and PCOS (Group 1), 60 patients with PCOS and without RPL (Group 2), 60 patients with RPL and without PCOS (Group 3), and 60 healthy individuals (Group 4). These four study groups were compared regarding serum levels of testosterone, fasting insulin, homocysteine (Hcy), plasminogen activator inhibitor activity (PAI-Fx), protein C, protein S, antithrombin III, activated protein C ratio (APCR), factor V Leiden, prothrombin G20210A, and methylene tetrahydrofolate reductase gene mutations. RESULTS: Patients in Group 1 had significantly higher levels of testosterone (p = 0.026), dehydroepiandrosterone sulfate (p = 0.035), fasting insulin (p = 0.015), Hcy (p = 0.036), and PAI-Fx (p = 0.008) compared to Group 3. They also had higher proportions of APCR (p = 0.009) and a higher prevalence of factor V Leiden mutations compared to Group 3 (p = 0.001). However, there was no significant difference in protein C (p = 0.088), protein S (p = 0.514), or antithrombin III (p = 0.627) between the four study groups. CONCLUSION: Hyperinsulinemia, hyperandrogenemia, hypofibrinolysis, and hyperhomocysteinemia as well as APCR and factor V Leiden mutations are associated with RPL in patients with PCOS.

Elevation of HPV-18 and HPV-16 DNA in the plasma of patients with advanced cervical cancer.

OBJECTIVE: Cervical cancer (CC) is one of the main problems in women's health in which the pathologic role of the human papilloma virus, HPV, is undeniable. Molecular methods have shown viral DNA in affected tissues, related to the disease progression. PATIENTS AND METHODS: We here studied 100 patients with abnormal Pap test results. HPV DNA loads in the plasma samples were measured by quantitative real time PCR, using specific primers and probes for the E6 genes of HPV types 16, 18, 33 and 52. Another 50 women with no obvious malignancy were enrolled as controls. RESULTS: Pathological studies revealed 81 patients with CC and 19 with cervical intraepithelial neoplasia. Only 19 of the cancer patients (15 with squamous cell carcinomas and 4 with adenocarcinomas) had detectable genetic material of HPV-16 (N = 4) and HPV-18 (N = 15) in their plasma; genetic material of other types was absent. HPV DNA copies increased with advanced disease in both types. Significantly smaller amounts of HPV DNA of types 16 and/or 18 were detected in the plasma of 16% of the controls while other types were negative. CONCLUSION: The evidence of HPV DNA of high risk types in the plasma of women with CCs strongly emphasizes the necessity of more longitudinal comprehensive studies to determine its role as a possible biomarker in cervical cancer.

The value of transvaginal ultrasonography in the endometrial evaluation of breast cancer patients using tamoxifen.

OBJECTIVE: To estimate the value of transvaginal ultrasonography (TVU) in evaluating the endometrium in breast cancer patients on tamoxifen, and to investigate the relationship between TVU and histologic endometrial findings in these patients. SUBJECTS AND METHODS: 107 breast cancer patients taking tamoxifen were included in this study. TVU was performed twice for each patient: prior to starting tamoxifen therapy and 1 year after taking tamoxifen. An endometrial thickness of >or=5 mm was considered abnormal. Endometrial biopsy was performed at the same time the 2nd TVU was done. The patients were divided into 2 groups: symptomatic (group A) and asymptomatic (group B), based on whether or not there was abnormal vaginal bleeding. RESULTS: 31 patients (29%) were symptomatic, while the remaining 76 (71%) were asymptomatic. The endometrial thickness increased after 1 year of taking tamoxifen from 4.84+/-0.4 mm to 6.34+/-2.1 mm in group A and from 4.73+/-0.3 mm to 5.67+/-1.95 mm in group B (p>0.05). Endometrial biopsy revealed 77 (71.96%) atrophic endometria and 21 (19.62%) polyps. A comparison between the 2 groups showed a significant difference in patients with endometrial atrophy and atypical hyperplasia. Patients who had an endometrial thickness of >5 mm had a significantly higher prevalence of atypical hyperplasia (p=0.003) and polyps (p=0.041). The sensitivity, specificity, positive predictive and negative predictive values of TVU were 63.3, 28.57, 25.67 and 66.66%, respectively. CONCLUSION: Our study showed a discrepancy between TVU and endometrial biopsy findings, due to the specific histology of the endometrium in breast cancer patients using tamoxifen. Due to this discrepancy, TVU alone is not an effective screening test for endometrial pathology and its application alone might lead to an undesirably high frequency of invasive diagnostic procedures.

Effects of metformin plus simvastatin on polycystic ovary syndrome: a prospective, randomized, double-blind, placebo-controlled study.

OBJECTIVE: To evaluate the effect of a combination of simvastatin and metformin on biochemical parameters in women with polycystic ovary syndrome (PCOS). DESIGN: A prospective, randomized, double-blind, placebo-controlled study. SETTING: University hospital. PATIENT(S): Eighty-four women with PCOS randomly divided to two study groups. INTERVENTION(S): Patients were randomly assigned to receive metformin (500 mg three times a day) plus simvastatin (20 mg/day, n=42; group 1) or metformin (500 mg three times a day) plus placebo (once a day, n=42; group 2) for 12 weeks. Blood samples were obtained before and after treatment. MAIN OUTCOME MEASURE(S): Testosterone. RESULT(S): After 12 weeks of treatment, serum T levels decreased by 25.5% in group 1 and by 16.8% in group 2. There was a greater decrease of LH (45.5% vs. 6.7%) and a greater decline of the LH/FSH ratio (38.3% decreased vs. 4.4% increased) in the first group. In group 1 there was a greater decrease of total cholesterol (29.5% vs. 4.2%), low-density lipoprotein (LDL; 18.5% vs. 1.5%), and triglycerides (32% vs. 5.3%). High-density lipoprotein (HDL) increased in the first group by 14%, whereas it decreased by 1% in the second group. CONCLUSION(S): This report has demonstrated that the combination of metformin and simvastatin could lead to a better reduction of T and LH levels and thus reversing the LH:FSH ratio, lipid profile, and insulin resistance in patients with PCOS and may be an appropriate management option for patients with PCOS.

A randomized, controlled clinical trial comparing the effects of aromatase inhibitor (letrozole) and gonadotropin-releasing hormone agonist (triptorelin) on uterine leiomyoma volume and hormonal status.

OBJECTIVE: To examine and compare the efficacy and safety of GnRH agonist (GnRHa) vs. aromatase inhibitor in premenopausal women with leiomyomas. DESIGN: Multicenter, randomized, controlled clinical trial. SETTING: University hospitals. PATIENT(S): A total of 70 subjects with a single uterine myoma measuring >or=5 cm. Subjects were randomized into two groups with use of a random table. They were treated with aromatase inhibitor (group A) or GnRHa (group B). INTERVENTION(S): Group A received letrozole (2.5 mg/d) for 12 weeks. Group B received triptorelin (3.75 mg/mo) for 12 weeks. MAIN OUTCOME MEASURE(S): Measurement of myoma volume and E(2), FSH, LH, and T levels. RESULT(S): Total myoma volume decreased by 45.6% in group A and 33.2% in group B. Reductions in myoma volume in the two groups were statistically significant. There was no significant change in hormonal milieu in group A. The serum level of hormones significantly decreased in group B by the 12th week of treatment. CONCLUSION(S): Uterine myoma volume was successfully reduced by use of an aromatase inhibitor. Rapid onset of action and avoidance of initial gonadotropin flare with an aromatase inhibitor may be advantageous for short-term management of women with myomas of any size who are to be managed transiently and who wish to avoid surgical intervention, specifically women with unexplained infertility having uterine myoma.

Evaluation of sperm's chromatin quality with acridine orange test, chromomycin A3 and aniline blue staining in couples with unexplained recurrent abortion.

OBJECTIVE: To evaluate the sperm's chromatin quality in couples with spontaneous recurrent abortion. METHODS: Thirty couples with spontaneous recurrent abortion (case group) and 30 fertile couples (control group) referring to Zeinabieh Gynecology clinic of Shiraz were included. Semen samples were collected for each participant and were used for standard semen analysis and sperm nuclear maturity tests including Chromomycin A3 (CMA3), Aniline Blue (AB) staining and Acridine Orange (AO) test (by light microscopy). RESULT: Patients in case group had significantly higher percentage of CMA3 (p < 0.001) and AB (p < 0.001) positive spermatozoa compared to controls. However AO results did not differ significantly between groups (p = 0.656). Sperm morphology and progressive motility were negatively correlated with CMA3 (p = 0.001 and p = 0.043) and AB (p = 0.015 and p = 0.031) respectively. CONCLUSION: Evaluation of the sperm's quality via CMA3 and AB staining could be considered as one of the complementary tests of semen analysis for assessment of male factor in couples with spontaneous recurrent abortion.

Short-term metformin treatment for clomiphene citrate-resistant women with polycystic ovary syndrome.

OBJECTIVE: To evaluate the effect of a short-course pretreatment with metformin on hyperandrogenism, insulin resistance, cervical scores, and pregnancy rates in women with clomiphene citrate (CC)-resistant polycystic ovary syndrome (PCOS). METHODS: Thirty-seven women with CC-resistant PCOS were randomly assigned to be pretreated with 500 mg of metformin or placebo 3 times per day for 2 cycles, and 100 mg of CC was given on days 5 through 9 of the second cycle in both groups. Luteinizing hormone (LH), follicle stimulating hormone (FSH), dehydroepiandrostendione sulfate (DHEAS), total testosterone (T), glucose, and insulin levels were measured at baseline and after the first cycle, as well as body mass index (BMI), cervical score, and pregnancy rate. RESULTS: After 1 cycle, BMI, total T level, and percentage of participants with insulin resistance were significantly decreased in the metformin group, without any significant decrease in LH, FSH, and DHEAS levels; and in the second cycle, CC treatment resulted in a higher ovulation rate and a thicker endometrium in the metformin group. The pregnancy rate and cervical scores were also higher in that group. CONCLUSION: The short-course pretreatment with metformin decreased hyperandrogenism and insulin resistance and improved cervical sores, ovulation rate, and pregnancy rate among women with CC-resistant PCOS.

Effect of folic acid in women with and without insulin resistance who have hyperhomocysteinemic polycystic ovary syndrome.

OBJECTIVE: To study the effect of folic acid on homocysteine (Hcy) levels in women with insulin resistance and polycystic ovary syndrome (PCOS) in a prospective clinical trial. METHOD: Of 210 women with PCOS, 70 were hyperhomocysteinemic; and of these, 32 were insulin resistant and 38 were not. The 70 women were treated with folic acid for 3 months. Baseline and serum levels of Hcy and insulin were measured in both groups. RESULTS: In both groups Hcy concentrations were significantly decreased following folic acid supplementation. The mean+/-SD levels before and after treatment were 14.03+/-1.5 micromol/L and 12.53+/-1.72 micromol/L in group 1 (P<0.001), and they were 12.07+/-0.87 micromol/L and 8.83+/-0.78 micromol/L in group 2 (P<0.001). CONCLUSION: The Hcy levels of hyperhomocysteinemic women with PCOS were reduced after 3 months of folic acid supplementation, and the rate of reduction was higher among women without insulin resistance. No change was found in fasting insulin levels.

Second trimester cardiac output and its predictive value for preeclampsia.

OBJECTIVE: To predict women at risk of preeclampsia in the second trimester by the assessment of maternal cardiac output (CO). METHODS: Between October 2001 to November 2003, we carried out a cross-sectional, prospective, hospital-base study in Shiraz University of Medical Sciences, Shiraz, Iran. Cardiac output was measured in 102 normotensive women at gestational age 19-25 weeks by Doppler echocardiography. Patients with CO >7.4 L/min were considered high risk group (Group 1) and those with CO < or =7.4 L/min were in Group II. They were followed-up until delivery and the incidence of preeclampsia was determined in both groups. RESULTS: Twenty percent (6/30) of patient in Group 1, and 1.4% of patients in group II developed preeclampsia (p < 0.003). A cut off point of 7.34% L/min was chosen for prediction of preeclampsia that showed 85.7% sensitivity, 74.2% specificity with a negative predictive value of 98% and positive predictive value of 20%. CONCLUSION: Cardiac out put is significantly elevated in preclinical state of preeclampsia. Echocardiography is a non-invasive method to evaluate the maternal homodynamic during the second trimester and can help to identify high-risk patient before the development of preeclampsia, thereby it may improve the outcome of pregnancy.

Abortifacient effect of Prangos ferulacia on pregnant rats.

PURPOSE: Prangos ferulacea grows in southern Iran and used in Iranian herbal medicine for gastrointestinal disorders, but it seems it has an abortifacient effect on pregnant women. To verify its potential as an abortifacient agent, we administered the leaves of this plant to pregnant rats. MATERIAL AND METHODS: Hydroalcoholic and aqueous extract of the leaves was administered orally at different doses to 60 rats on the first 18 days of pregnancy. Group 1 (G1) was considered as control group and was given only water. Groups 2-5 (G2-G5) received 25, 50, 100 mg/g per day and Groups 6-8 (G6-G8) received 300, 500 and 1000 mg/g per day, respectively. On Day 18 of pregnancy, they were killed and laparotomized. The uterine horns of each group were opened to see whether they contained any live and degenerated/dead fetuses. We used Student's t-test to analyze the data (p < or = .05 was considered significant). RESULTS: Of the total 504 fetuses in the studied groups, 13 fetuses (2.57%) were aborted. The abortion rate in the control group was 2 (1.94%) of 103 fetuses; the abortion rate was higher in the treated groups but not statistically significant. There was no relationship between the dose and type of extract and abortion rate in all studied groups. CONCLUSION: This study shows that the aqueous or hydroalcoholic extract of P. ferulacea is ineffective on the rate of abortion of pregnant rats. Future studies should be performed with higher doses to test the efficacy of this agent on other animals.

Laparoscopic management of hepatic endometriosis: report of two cases and review of the literature.

Hepatic endometriosis is rare. Only 15 cases have been reported in the literature. All 15 were treated by laparotomy. We report two additional cases of hepatic endometriosis managed for the first time laparoscopically. Endometriosis is a progressive disease especially in women of reproductive age. One of the differential diagnoses of liver endometriosis is malignancy. Currently, there are no reports in the literature regarding complications arising from the progression of hepatic endometriosis. However, this lack of evidence does not deny its existence.