Systemic HCG treatment in patients with endometriosis: a new perspective for a painful disease.

BACKGROUND: Endometriosis is characterized by the presence of endometrium-like tissue outside the uterus. This condition causes painful periods, chronic pelvic pain, subfertility and a profound reduction in quality of life, especially during women's reproductive years. Currently available medical therapies offer comparatively little therapeutic benefit and are often burdened by considerable side effects. However, since clinical evidence shows that pregnancy leads to alleviation of endometriotic symptoms, we have for the first time examined the effect of human chorionic gonadotrophin (HCG) injections on symptoms such as dysmenorrhea and pelvic pain. PATIENTS AND METHODS: Thirty-one patients with histologically verified endometriosis refractory to therapy received 1 to 2 intramuscular injections of 1500 to 5000 IU HCG per week for a period of 3-12 months. A QoL questionnaire and the visual analog pain intensity scale (VAS) were used to evaluate quality of life and pain intensity, respectively, before and after three months of treatment. RESULTS: Three months of HCG therapy led to a highly significant reduction of endometriosis-related pain (p<0.001, Wilcoxon test) and to improvement of disease-related parameters such as sleeplessness (p<0.001), irritability (p<0.001), overall discomfort (p<0.001), depressive moods (p<0.001) and painful defecation (p=0.01). Dyspareunia and dysmenorrhea also clearly improved (both p<0.001), though HCG did not lead to significant reduction of dysuria (p=0.66). Prolonged therapy with HCG for up to 12 months (mean: 4.42 months) did not lead to reduction of the beneficial effect. CONCLUSIONS: HCG injections lead to significant and clinically relevant reduction in pain intensity and to greatly improved quality of life in women with therapy-refractory endometriosis. The remarkable clinical effect of parenteral HCG in our study will have to be confirmed in additional trials but clearly indicates an extremely promising new perspective in the treatment of endometriosis.

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.

Successful pregnancy resulting from in-vitro matured oocytes retrieved at laparoscopic surgery in a patient with polycystic ovary syndrome: case report.

Combined laparoscopic retrieval of immature oocytes and ovarian electrocautery represents a new management in patients with polycystic ovary syndrome (PCOS), one of the most prevalent endocrinopathies associated with anovulatory infertility. A 31-year-old para II presented with anovulatory, clomiphene-resistant PCOS, and a 6 year history of infertility. Conventional IVF treatment was abandoned in 1999 when she developed severe ovarian hyperstimulation syndrome (OHSS) following gonadotrophin stimulation. Sixteen oocytes were aspirated from both ovaries and collected in culture tubes containing a maturation medium. A total of three 2-cell embryos were transferred 48 h after ICSI. Two weeks after embryo transfer the urinary pregnancy test was positive and after another 2 weeks an ongoing singleton pregnancy with a fetal heartbeat was confirmed at transvaginal ultrasound examination. The combination of laparoscopy, in-vitro maturation and ICSI may open up new therapeutic strategies, even in patients without PCOS and regular menstrual cycles, undergoing laparoscopy for other causes of infertility such as tubal factors and endometriosis.

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.