Caio Parente Barbosa

Analysis of FOXP3 polymorphisms in infertile women with and without endometriosis.

OBJECTIVE To evaluate FOXP3 polymorphisms (rs3761549, rs3761548, rs2232368, rs2232366, and rs2280883) in a group of infertile women with and without endometriosis and controls. DESIGN Case control study. SETTING Human Reproduction Outpatient Clinic of Faculdade de Medicina do ABC. PATIENT(S) The study groups were 177 infertile women with endometriosis, 71 women with idiopathic infertility, and 171 fertile women as controls. INTERVENTION(S) The FOXP3 polymorphisms were identified by TaqMan polymerase chain reaction (PCR). The results were analyzed statistically. MAIN OUTCOME MEASURE(S) Genotype distribution, allele frequency, and haplotype analysis of the FOXP3 polymorphisms. RESULT(S) Single-marker analysis revealed that FOXP3 rs3761549 was significantly associated with endometriosis. In the infertile group without endometriosis, single-marker analysis revealed statistical difference for rs2280883 and rs2232368 FOXP3 polymorphisms. No associations were found with rs3761548 and rs2232366 either for endometriosis-related infertility group or idiopathic infertility group. Haplotype analysis of five FOXP3 polymorphisms identified a haplotype CTTGA associated with endometriosis and ACTAG associated with idiopathic infertility. CONCLUSION(S) This is the first study to report an association between FOXP3 polymorphisms and endometriosis and/or infertility. These findings require replication in other populations but suggest that the FOXP3 polymorphisms can be associated with risk of idiopathic infertility (rs2280883 and rs2232368) and endometriosis (rs3761549) in Brazilian women.

Frequency of endometriotic lesions in peritoneum samples from asymptomatic fertile women and correlation with CA125 values

CONTEXT AND OBJECTIVE Serological testing for CA125 has been widely used to detect endometriosis and to monitor its progression. However, controversy still exists regarding the usefulness of the plasma CA125 assay for diagnosing endometriosis. Furthermore, some authors have described superficial endometriosis as a cyclical and normal phenomenon in womens lives, and have indicated that development and progression of this disease would only occur in some women as a result of immunological changes. This study aimed to determine the frequency of endometriosis and the correlation between serum CA125 levels and the presence of endometriotic lesions in the peritoneum of asymptomatic fertile patients. DESIGN AND SETTING Cross-sectional study at the Family Planning outpatient clinic of Faculdade de Medicina do ABC. METHODS Eighty asymptomatic fertile patients who underwent tubal sterilization surgery were studied. Blood and peritoneum samples were collected. CA125 levels were measured from blood samples, and peritoneum biopsies were studied using histopathological tests. RESULTS Histopathological evaluation of the peritoneum revealed that 16.25% of the patients had minimal or mild endometriosis. There was no statistically significant difference in CA125 levels between patients with and without endometriosis. CONCLUSION The presence of endometriotic lesions in the peritoneum of fertile patients supports the hypothesis that incidental findings of minimal or mild endometriosis may not be of clinical significance, and that the progression of the disease probably occurs as a result of immunological and genetic abnormalities. Serum CA125 levels did not show any diagnostic significance with regard to detecting the disease.

The possible role of genetic variants in autoimmune-related genes in the development of endometriosis

Numerous hypotheses have been put forward to explain the presence of ectopic endometrial tissue and stroma. The immune system participates in the homeostasis of the peritoneal cavity, and modifications in its functioning have been advanced to explain endometriosis and its consequences. Recently, the powerful anti-inflammatory effect of progesterone was recognized as a potential causal factor for endometriosis and could contribute to the autoimmune nature of endometriosis, as well as to more specific local and systemic changes. Autoimmune and inflammatory diseases are a diverse group of complex diseases characterized by loss of self-tolerance causing immune-mediated tissue destruction. Just as in autoimmune diseases, in endometriosis similar immunologic alterations occur, such as an increase in the number and cytotoxicity of macrophages, polyclonal increase in the activity of B lymphocytes, abnormalities in the functions and concentrations of B and T lymphocytes, and reduction in number or activity of natural killer cells. Furthermore, the presence of specific antiendometrial and antiovary antibodies was found both in endometriosis and infertility. Genetic factors play a role in the pathogenesis of endometriosis, and autoimmunity genes are therefore reasonable candidate genes for endometriosis and endometriosis-associated infertility. Single nucleotide polymorphisms are common in the human genome and affect the function of crucial components of the T-cell-antigen-receptor signaling pathways; they could have profound effects on the function of the immune system and thus on the development of autoimmune diseases. Here, we conducted a critical medical literature review about the possible role of genetic variants in autoimmune-related genes in the development of endometriosis.

Effect of acupuncture on symptoms of anxiety in women undergoing in vitro fertilisation: a prospective randomised controlled study

Purpose To determine if acupuncture improves symptoms of anxiety in infertile women undergoing in vitro fertilisation (IVF) treatment. Methods A randomised clinical trial was performed in 43 patients undergoing IVF. The patients were randomised into two groups: test group (n=22) and control group (n=21). The anxiety level of each patient was analysed before and after treatment using the Hamilton Anxiety Rating Scale (HAS). Treatment sessions consisted of four weekly sessions. In the test group, needles were inserted at points HT7, PC6, CV17, GV20 and Yintang. In the control group, needles were inserted in areas near but not corresponding to acupuncture points. Results The mean HAS score after the 4-week experimental period was significantly lower in the test group than in the control group (19.4±3.2 vs 24.4±4.2; p=0.0008). Conclusions The results indicate that acupuncture can reduce anxiety symptoms observed by the reduction of psychological parameters of women undergoing IVF. Further evidence should be sought as to whether acupuncture might be a complementary option for patients undergoing IVF.

OC-125 immunostaining in endometriotic lesion samples.

PurposeTo determine the presence of OC-125 staining in endometriotic lesions and to verify whether there is an association with endometriosis stage.MethodsThirteen patients from the Family Planning programs (group I) and 53 patients from the Chronic Pelvic Pain outpatient clinic (group II) were studied. Endometriotic lesions were excised from areas of endometriosis incidence and studied by histopathological assay and by immunohistochemistry for OC-125 staining.ResultsThe histopathological study disclosed that all patients from group I had minimal/mild endometriosis. In group II, 39.6% had minimal/mild endometriosis, and 60.4% had moderate/severe endometriosis. OC-125 staining was negative in all samples from group I. In group II, OC-125 staining was positive in 52.4% patients with minimal/mild endometriosis and in 81.2% with moderate/severe endometriosis.ConclusionThe data suggest that the OC-125 antibody is probably related to endometriosis activity and, consequently, to the progression and severity of the illness.

Methylenetetrahydrofolate reductase polymorphisms are related to male infertility in Brazilian men.

OBJECTIVE The objective of this study was to analyze the distribution of the methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms in idiopathic infertile Brazilian patients with nonobstructive azoospermia (NOA) or severe oligozoospermia and fertile Brazilian men as controls to explore the possible association of these polymorphisms and male infertility. METHODS A case-control study was carried out, including 156 idiopathic infertile Brazilian patients with NOA (n=49) or severe oligozoospermia (n=107) and 233 fertile men as controls. Polymorphisms C677T and A1298C were studied by quantitative polymerase chain reaction and the results were statistically analyzed. RESULTS The frequency of genotypes MTHFR 677CC, 677CT, and 677TT in idiopathic infertile men with NOA were 55.1%, 30.6%, and 14.3% (p=0.0305); 50.6%, 42.0%, and 7.5% (p=0.0006) regarding the severe oligozoospermic men; and 71.7%, 53.0%, and 5.6% in the control group. As for polymorphism A1298C, regarding the NOA group, the frequencies of the 1298AA, 1298AC, and 1298CC genotypes were 53.0%, 28.6%, and 18.4% (p=0.0132); 42.0%, 44.9%, and 13.1% (p=0.0188) among the severe oligozoospermic group; and 55.8%, 38.2%, and 6.0% (14/233) in the control group. CONCLUSION The data suggest that MTHFR C677T and A1298C could be important genetic factors predisposing to infertility in Brazilian infertile men.

Avaliação dos fatores relacionados à ocorrência da incontinência urinária feminina

OBJETIVO: Avaliar os fatores de risco relacionados a ocorrencia da incontinencia urinaria feminina. METODOS: Estudo caso-controle que incluiu 253 mulheres (102 incontinentes e 151 continentes) convidadas a responder a um questionario epidemiologico sobre possiveis fatores de risco para a incontinencia urinaria como: idade, estado hormonal, raca, Indice de Massa Corporal, paridade, tipos de partos (normais, forcipes ou cesarianas), peso do maior recem-nascido, utilizacao de episiotomia e ou analgesia durante o parto, historia de histerectomia, pratica de atividade fisica, tabagismo, diabetes mellitus, constipacao intestinal, historia de asma bronquica e ou doenca pulmonar obstrutiva cronica, uso de diureticos e ou antidepressivos. RESULTADOS: Foram encontrados, apos a aplicacao do modelo de regressao logistica binaria, como fatores de risco para a ocorrencia de incontinencia urinaria: a idade [OR = 1,07 (IC 1,03 - 1,1)], o parto normal [OR = 1,5 (IC 1,1 - 12,0)], o parto forcipe [OR = 35,0 (IC 3,7 - 327)] e o peso do maior recem-nascido [OR = 1,001 (IC 1 - 1,002)]. Alem disso, identificamos como fator de protecao a cesariana [OR = 0,39 (IC 0,23 - 0,65)]. CONCLUSAO: Os fatores de risco independentes para a ocorrencia da incontinencia urinaria foram idade, parto normal, parto forcipe e peso do maior recem-nascido e, como fator de protecao, a cesariana.

Prevalence of the polymorphism MTHFR A1298C and not MTHFR C677T is related to chromosomal aneuploidy in Brazilian Turner Syndrome patients

BACKGROUND Dysfunctions in the folate metabolism can result in DNA hypomethylation and abnormal chromosome segregation. Two common polymorphisms of this enzyme (C677T and A1298C) reduce its activity, but when associated with aneuploidy studies the results are conflicting. The objective of the present study is to analyze the MTHFR gene polymorphisms in women with Turner Syndrome and in a control group, correlating the findings to the chromosomal aneuploidy. METHODS The study comprised 140 patients with Turner Syndrome, of which 36 with chromosome mosaicism and 104 non-mosaics, and a control group of 209 fertile and healthy women without a history of any offspring with aneuploidy. Polymorphisms C677T and A1298C were studied by RFLP-PCR and the results were statistically analyzed. RESULTS The frequency of genotypes MTHFR 677CC, 677CT and 677TT in the patients with Turner Syndrome and chromosome mosaicism was, respectively, 58.3%, 38.9% and 2.8%. Among the patients with non-mosaic Turner Syndrome, 47.1% presented genotype 677CC, 45.2% genotype 677CT, and 7.7% genotype 677TT. Among the 209 individuals of the control group, genotypes 677CC, 677CT and 677TT were found at the following frequencies: 48.3%, 42.1% and 9.6%, respectively. As for polymorphism A1298C, the patients with Turner Syndrome and chromosome mosaicism presented genotypes 1298AA, 1298AC and 1298CC at the following frequencies: 58.3%, 27.8% and 13.9%, respectively. Among the non-mosaic Turner Syndrome patients, genotype 1298AA was found in 36.5%, genotype 1298AC in 39.4%, and genotype 1298CC in 22.1%. In the control group, genotypes 1298AA, 1298AC and 1298CC were present at the following frequencies: 52.6%, 40.7% and 6.7%, respectively. CONCLUSION No correlation was observed between the MTHFR gene polymorphism 677 and chromosomal aneuploidy in the Turner Syndrome patients. However, the MTHFR gene polymorphism at position 1298, mainly genotype 1298CC that reduces the enzyme efficiency, was more frequent in the group of Turner Syndrome patients, suggesting its involvement in mechanisms related to chromosomal imbalances.

Influence of acupuncture on the outcomes of in vitro fertilisation when embryo implantation has failed: a prospective randomised controlled clinical trial

Objective To evaluate the effectiveness of acupuncture and moxibustion as an adjuvant treatment in women undergoing in vitro fertilisation (IVF) when embryo implantation has failed. Methods A prospective, randomised controlled clinical trial was conducted with 84 infertile patients who had had at least two unsuccessful attempts of IVF. The patients were randomised in three groups: control (n=28), sham (n=28) and acupuncture (n=28). The sample size was calculated by assuming a pregnancy rate of 10% when embryo implantation had failed. The pregnancy rates of the current IVF cycle were evaluated by measurement of blood β human chorionic gonadotrophin (βhCG) and subsequent transvaginal ultrasound. Acupuncture was performed on the first and seventh day of ovulation induction, on the day before ovarian puncture and on the day after embryo transfer. In the acupuncture group, patients were treated with moxibustion at nine acupuncture points (BL18, BL22, BL23, BL52, CV3, CV4, CV5, CV7, GV4) and needling at 12 points. In the sham group needles were inserted in eight areas that did not correspond to known acupuncture points. Results The clinical pregnancy rate in the acupuncture group was significantly higher than that in the control and sham groups (35.7% vs 7.1% vs 10.7%; p=0.0169). Conclusions In this study, acupuncture and moxibustion increased pregnancy rates when used as an adjuvant treatment in women undergoing IVF, when embryo implantation had failed.

Analysis of vitamin D receptor gene polymorphisms in women with and without endometriosis.

An aberrant immunologic mechanism has been suggested to be involved in the pathogenesis of endometriosis. Genetic alterations in the vitamin D receptor gene (VDR) may lead to important defects in gene activation that principally affect immune function. We have hypothesized a possible relationship between endometriosis and/or infertility and the VDR polymorphisms (ApaI, TaqI, FokI, and BmsI). The study was a case-control study including 132 women with endometriosis-related infertility, 62 women with idiopathic infertility, and 133 controls. VDR polymorphisms were studied by restriction fragment length polymorphism. We found relatively similar VDR polymorphism genotype frequencies in cases and controls. When patients with minimal/mild and moderate/severe endometriosis were studied separately, no difference was found. When we compared infertile groups with and without endometriosis there was no statistically significant difference. The data suggest that VDR polymorphisms did not play an important role in the pathogenesis of endometriosis and/or infertility in the Brazilian women studied.