Implanon versus medroxyprogesterone acetate: effects on pain scores in patients with symptomatic endometriosis--a pilot study.

BACKGROUND: Implanon has been reported to be effective in the treatment of dysmenorrhea. We compared the therapeutic efficacies of depot medroxyprogesterone acetate (DMPA) and Implanon with regard to pain relief in women with endometriosis. STUDY DESIGN: In a clinical research center at a university hospital, 41 patients with dysmenorrhea, nonmenstrual pelvic pain and dyspareunia associated with histologically proven endometriosis were included in an open, prospective, randomized, controlled clinical trial. Twenty-one women were assigned by computer-generated randomization to receive Implanon, and 20 women to receive DMPA. As main outcome measures of this pilot study, we evaluated pain improvement quantified according to visual analog scale score, side effects, vaginal bleeding patterns, withdrawal rate and overall degree of satisfaction. RESULTS: During a follow-up period of 1 year, we ascertained a clear improvement in pain intensity for both treatment options. After 6 months, the average decrease in pain was 68% in the Implanon group and 53% in the DMPA group. The side-effects profile and the overall degree of satisfaction after study termination were comparable for both treatment options. CONCLUSION: Concerning pain relief, the therapeutic efficacy of the contraceptive implant Implanon is not inferior to that of DMPA in symptomatic endometriosis.

Interleukin-1 alpha but not interleukin-1 beta gene polymorphism is associated with polycystic ovary syndrome.

Interleukin-1 (IL1) is a multifunctional cytokine and IL1-mediated inflammatory processes have been proposed to influence the processes of ovulation, fertilization and implantation. All these parameters are also affected in women with polycystic ovary syndrome (PCOS). This study investigated the association of common polymorphisms of the interleukin-1 genes (IL1A and IL1B) with the occurrence and clinical characteristics of PCOS. We evaluated one polymorphism of the IL1alpha gene (IL1A C[-889]T) and two of the IL1beta gene (IL1B promoter C[-511]T and IL1B exon 5 position +3953) in 105 Caucasian women with PCOS and 102 healthy Caucasian controls by polymerase chain reaction. For the mutated IL1A allele, allele frequencies in women with PCOS and controls were 60% and 46%, respectively, versus 40% and 54%, respectively, for the wild type allele. Allele frequencies in women with PCOS and controls were 59% (54%) and 61% (41%), respectively, for the mutated IL1B promoter (mutated IL1B exon 5) and 41% (46%) and 39% (59%), respectively, for the wild type alleles. Presence of a polymorphism in the interleukin-1alpha but not the interleukin-1beta gene was found to correlate with the occurrence of PCOS (p=0.04; odds ratio 1.8). The serum level of FSH and subsequent LH/FSH ratio correlated with the polymorphism of IL1A within the PCOS group (p=0.005 and 0.01, respectively). We have shown that a common polymorphism of the interleukin-1alpha but not interleukin-1beta gene is associated with the presence of PCOS and with clinical parameters of women affected by this condition.

Impaired glucose tolerance is associated with changes in clinical and biochemical parameters in women with polycystic ovary syndrome.

BACKGROUND: To characterize the phenotype of women with polycystic ovary syndrome with and without impaired glucose tolerance by determining various polycystic ovary syndrome-associated clinical and laboratory parameters. METHODS: In a prospective clinical study, we evaluated a series of 102 Caucasian women with polycystic ovary syndrome. Women completed a detailed questionnaire and underwent a standardized oral glucose tolerance test. Various polycystic ovary syndrome-associated laboratory values such as hormonal and metabolic parameters were determined in these women and correlated to clinical data and the presence/absence of impaired glucose tolerance. Furthermore, the insulin resistance was calculated using the homeostasis model assessment index and correlated with clinical and biochemical parameters. RESULTS: Eighty-eight (86.3%) and 14 (13.7%) women were diagnosed as having non-impaired glucose tolerance and impaired glucose tolerance, respectively. Presence of impaired glucose tolerance was associated with an increased body mass index, increased body weight, elevated serum levels of bioavailable testosterone, insulin like growth factor-1, insulin, HbA1c, leucocytes, uric acid, alkaline phosphatase, hepatic C-reactive protein, and decreased serum levels of sex-hormone binding globulin. No association was ascertained with subfertility, hirsutism, and menstrual irregularities. We ascertained a positive correlation between the homeostasis model assessment index and body mass index, body weight, alkaline phosphatase, and hepatic C-reactive protein. CONCLUSIONS: Impaired glucose tolerance seems to be associated with a specific phenotype within polycystic ovary syndrome. This phenotype is more likely to present with biochemical parameters similar to an inflammatory reaction and a metabolic disorder.

A combination treatment of prednisone, aspirin, folate, and progesterone in women with idiopathic recurrent miscarriage: a matched-pair study.

OBJECTIVE: To compare a combination treatment of prednisone, aspirin, folate, and progesterone with no treatment in women with idiopathic recurrent miscarriage (IRM). DESIGN: Matched-pair study. SETTING: Academic research institution. SUBJECT(S): Women with a history of IRM, defined as three or more consecutive miscarriages before 20 weeks' gestation without associated anatomic, cytogenetic, hormonal, and infectious pathologies or antiphospholipid syndrome. INTERVENTION(S): Eighty of 210 eligible women consented to participate and were treated with prednisone (20 mg/d) and progesterone (20 mg/d) for the first 12 weeks of gestation, aspirin (100 mg/d) for 38 weeks of gestation, and folate (5 mg every second day) throughout their pregnancies. Fifty of 80 women became pregnant; they were compared with 52 women with IRM (matched for age and number of miscarriages), who became pregnant without treatment during the same observation period. MAIN OUTCOME MEASURE(S): Live birth rate, complications of pregnancy, such as preeclampsia, premature birth, and intrauterine growth restriction, and therapy-related side effects. RESULT(S): The overall live birth rates of the treatment and control groups were 77% (40 of 52) and 35% (18 of 52) (P=.04). The rates of first and second trimester miscarriage among the treatment and control groups were 19% (10 of 52) and 0 (0 of 52), and 63% (33 of 52) and 2% (1 of 52), respectively (P=.09 and P=1.0, respectively). The median gestational age at birth and median birth weight did not differ between the groups. We observed two and three cases of premature birth among the treatment and control groups, respectively (P=.3) and no cases of intrauterine growth restriction and Cushing's disease. Of 80 women who started treatment, one woman had an ectopic pregnancy and one woman terminated her pregnancy due to fetal chromosome aberration (trisomy 18). Three women stopped treatment due to nausea, depression, and tachycardia. CONCLUSION(S): A combination treatment of prednisone, aspirin, folate, and progesterone is associated with a higher live birth rate compared with no treatment in women with IRM.

A polymorphism of the interleukin 1 receptor antagonist is not associated with polycystic ovary syndrome in Caucasian women.

In a prospective case-control study we investigated the association of a common polymorphism of the interleukin 1 receptor antagonist gene (IL-1 RA) with the occurrence and the clinical characteristics of polycystic ovary syndrome (PCOS). Allele frequencies did not vary statistically significantly among women with PCOS and healthy controls or within the PCOS group with respect to their clinical characteristics.

The C46T polymorphism of the coagulation factor XII gene and idiopathic recurrent miscarriage.

Thrombophilia has been described to be involved in the pathogenesis of idiopathic recurrent miscarriage (IRM). We investigated the association between IRM and a C-->T polymorphism at nucleotide 46 in the 5'-untranslated region of the coagulation factor XII (FXII) gene. Two hundred and twelve women with a history of IRM and 149 healthy controls were tested by a mutagenically separated polymerase chain reaction assay (MS PCR). Allele and genotype frequencies were not significantly different between the study and the control groups. Our data suggest that the FXII gene is not a candidate gene for this condition.

Different steroids co-regulate long-term expansion versus terminal differentiation in primary human erythroid progenitors.

Outgrowth, long-term self-renewal, and terminal maturation of human erythroid progenitors derived from umbilical cord blood in serum-free medium can be modulated by steroid hormones. Homogeneous erythroid cultures, as characterized by flow cytometry and dependence on a specific mixture of physiologic proliferation factors, were obtained within 8 days from a starting population of mature and immature mononuclear cells. Due to previous results in mouse and chicken erythroblasts, the proliferation-promoting effect of glucocorticoids was not unexpected. Surprisingly, however, androgen had a positive effect on the sustained expansion of human female but not male erythroid progenitors. Under optimal conditions, sustained proliferation of erythroid progenitors resulted in a more than 10(9)-fold expansion within 60 days. Terminal erythroid maturation was significantly improved by adding human serum and thyroid hormone (3,5,3'-triiodothyronine [T3]) to the differentiation medium. This resulted in highly synchronous differentiation of the cells toward enucleated erythrocytes within 6 days, accompanied by massive size decrease and hemoglobin accumulation to levels comparable to those in peripheral blood erythrocytes. Thus, obviously, different ligand-activated nuclear hormone receptors massively influence the decision between self-renewal and terminal maturation in the human erythroid compartment.

Lack of association of TNFalpha gene polymorphisms and recurrent pregnancy loss in Caucasian women.

The tumor necrosis factor alpha (TNFalpha) gene plays an important role in immunology and inflammation. Variant alleles of TNFalpha are associated with altered RNA and serum protein levels in humans. Conflicting results have been obtained regarding the role of TNFalpha during pregnancy and recurrent pregnancy loss (RPL). This study investigated the relationship between RPL and two polymorphisms in the promoter of the TNFalpha gene (TNFalpha -308 and -863). Genotyping was performed in 168 RPL women and 212 ethnically matched healthy individuals. In addition, we performed analysis of TNFalpha serum protein levels. We demonstrate that neither the polymorphism -308 nor the polymorphism -863 of the TNFalpha gene is associated with RPL in Caucasian women. In addition, we did not find any association between TNFalpha serum levels and the occurrence of RPL in a subset of 36 RPL women and 36 healthy individuals. We conclude that TNFalpha polymorphisms and resting blood TNFalpha levels do not correlate with the propensity to recurrent pregnancy loss in Caucasian women.

Angiopoietin-2 polymorphism in women with idiopathic recurrent miscarriage.

OBJECTIVE: To investigate the relationship between idiopathic recurrent miscarriage and a polymorphism of the gene encoding for angiopoietin-2 (ANGPT2), an autochthonous modulator of angiogenesis during pregnancy. DESIGN: Prospective case control study. SETTING: Academic research institution. PATIENT(S): One hundred thirty-one women with a history of three or more consecutive pregnancy losses before 20 weeks' gestation, and 125 healthy, postmenopausal controls with at least two live births and no history of pregnancy loss. INTERVENTION(S): Peripheral venous puncture. MAIN OUTCOME MEASURE(S): Polymerase chain reaction and restriction fragment length polymorphism analysis were performed to identify the different ANGPT2 alleles. RESULT(S): No association between mutant (mt) allele and the occurrence of idiopathic recurrent miscarriage was found. Between women with primary and secondary idiopathic recurrent miscarriage, no statistically significant differences with respect to allele frequencies were observed. CONCLUSION(S): This is the first report on the ANGPT2 gene polymorphism in women with idiopathic recurrent miscarriage, demonstrating that the investigated polymorphism is not associated with idiopathic recurrent miscarriage in a white population.

Combined thrombophilic polymorphisms in women with idiopathic recurrent miscarriage.

OBJECTIVE: To identify associations or interrelations between carriage of the methylenetetrahydrofolate reductase (MTHFR) C677T, the MTHFR A1298C, the factor V Leiden G1691A, the factor II prothrombin G20210A, the human platelet antigen (HPA) 1 C12548T, and the apolipoprotein (APO) B R3500Q polymorphisms and idiopathic recurrent miscarriage (IRM). DESIGN: Prospective case control study. SETTING: Academic research institution. PATIENT(S): One hundred forty-five women with a history of three or more consecutive pregnancy losses before 20 weeks gestation and 101 healthy postmenopausal women with at least two live births and no history of pregnancy loss. INTERVENTION(S): Peripheral venous punctures. MAIN OUTCOME MEASURE(S): Multiplex polymerase chain reaction was performed to identify the different alleles of six candidate genetic risk factors for IRM (MTHFR C677T, MTHFR A1298C, factor V Leiden G1691A, factor II prothrombin G20210A, HPA 1 C12548T, and the APO B R3500Q). RESULT(S): Allele and genotype frequencies of all polymorphisms were not significantly different between the study and the control groups. Also, no significant associations occurred between combinations of polymorphisms and the occurrence of IRM. CONCLUSION(S): Our data fall short of showing any significant association between single polymorphisms of the MTHFR, the Factor V Leiden, the Factor II Prothrombin, the HPA 1 and APO B genes or combinations of these polymorphisms and the occurrence of IRM.

The C677T polymorphism of the methylenetetrahydrofolate reductase gene and idiopathic recurrent miscarriage.

OBJECTIVE: To investigate the association between the C677T polymorphism of the 5,10-methylenetetrahydrofolate reductase gene (MTHFR), serum homocysteine levels, and idiopathic recurrent miscarriage in a Middle-European white population. METHODS: In a case control study, we investigated 133 women with a history of three or more consecutive pregnancy losses before 20 weeks' gestation and 74 healthy controls with at least two live births and no history of pregnancy loss. A DNA extraction and polymerase chain reaction followed by restriction fragment length polymorphism analysis were used to genotype women for the presence of the MTHFR C677T polymorphism. Serum homocysteine levels were assessed by a fluorescence polarization immunoassay. RESULTS: The MTHFR allele frequencies in women with idiopathic recurrent miscarriage and controls were 34.6% and 21.6%, respectively, for the T allele (mutant) and 65.4% and 78.4%, respectively, for the C allele (wild type) (P =.007, odds ratio 1.9, 95% confidence interval 1.2, 3.1). The MTHFR genotype frequencies in women with idiopathic recurrent miscarriage and controls were: 17.3% (T/T), 34.6% (C/T), 48.1% (C/C) and 5.4% (T/T), 32.4% (C/T), 62.2% (C/C), respectively (P =.03, odds ratio 3.7, 95% confidence interval 1.2, 11.8 [T/T versus C/T and C/C]). Serum concentrations of homocysteine were significantly higher in carriers of a MTHFR mutant allele compared with women with no mutant allele (mean 7.4 +/- 2.4 micromol/L [T/T + C/T] versus 6.5 +/- 2.6 micromol/L [C/C], P =.05). CONCLUSION: Carriage of the mutant allele of the MTHFR C677T polymorphism is associated with elevated serum levels of homocysteine and idiopathic recurrent miscarriage.

Polymorphisms of the angiotensinogen gene, the endothelial nitric oxide synthase gene, and the interleukin-1beta gene promoter in women with idiopathic recurrent miscarriage.

Interleukin (IL)-1beta, angiotensinogen (Agt), and endothelium-derived nitric oxide synthase (eNOS) are thought to be involved in idiopathic recurrent miscarriage (IRM). We investigated the correlation between IRM and common polymorphisms in Agt, Nos3 and IL-1beta genes: one polymorphism in the promoter region of the IL-1beta gene, one in exon 2 of the Agt gene, and one in exon 7 of the Nos3 gene. A total of 130 women with a history of IRM and 67 healthy control women were included in the study. Genotyping for the C/T transition at position -511 in the promoter region of IL1B, for the single base M235T polymorphism of Agt, and for the missense Glu298Asp variant of Nos3 was performed using PCR, an allele-specific oligonucleotide hybridization assay, and pyrosequencing, respectively. Allele and genotype frequencies of all polymorphisms were similar among women with IRM and controls. Between women with primary and secondary recurrent miscarriages, no statistically significant differences between allele and genotype frequencies were observed. Despite promising experimental data, our data fall short of showing any significant association between a variant of the promoter region of IL1B, the M235T polymorphism of Agt, and the Glu298Asp missense variant of Nos3 and the occurrence of IRM.