Genetic analysis of products of conception. Should we abandon classic karyotyping methodology?

OBJECTIVE: To compare the results obtained by the classic and molecular methodology in the analysis of products of conception, the advantages and disadvantages of each method. METHODS: Retrospective non-randomized analysis of results obtained from product of conception samples submitted to genetic evaluation, from 2012 to 2017. The evaluations were performed using cytogenetics and/or chromosomal microarray analysis or arrays. RESULTS: Forty samples were analyzed using classic cytogenetics, of which 10% showed no cell growth, 50% had normal results and 40% had abnormalities. Of the 41 cases sent for array analysis it was not possible to obtain results in 7.3%, 39.5% were normal and 60.5% had abnormalities. There was no statistical difference among the results (p=0.89). Most abnormal results were seen till 9 weeks' gestation. The later abnormal miscarriage was seen at 28 weeks' gestation, with karyotype 46,XX,del(15)(q26.2-qter). The results are corroborated by the international literature. CONCLUSION: Classic cytogenetics and array techniques showed comparable results on the type of alteration observed. Array analysis is preferable to cell culture in delayed abortions, while cytogenetics is more able to show polyploidies. Both have the same growth failure rates when product of conception tissue is not properly collected.

Genetic analysis of products of conception. Should we abandon classic karyotyping methodology? / Análise genética dos produtos de concepção. Devemos abandonar a metodologia de cariotipagem clássica?

ABSTRACT Objective: To compare the results obtained by the classic and molecular methodology in the analysis of products of conception, the advantages and disadvantages of each method. Methods: Retrospective non-randomized analysis of results obtained from product of conception samples submitted to genetic evaluation, from 2012 to 2017. The evaluations were performed using cytogenetics and/or chromosomal microarray analysis or arrays. Results: Forty samples were analyzed using classic cytogenetics, of which 10% showed no cell growth, 50% had normal results and 40% had abnormalities. Of the 41 cases sent for array analysis it was not possible to obtain results in 7.3%, 39.5% were normal and 60.5% had abnormalities. There was no statistical difference among the results (p=0.89). Most abnormal results were seen till 9 weeks' gestation. The later abnormal miscarriage was seen at 28 weeks' gestation, with karyotype 46,XX,del(15)(q26.2-qter). The results are corroborated by the international literature. Conclusion: Classic cytogenetics and array techniques showed comparable results on the type of alteration observed. Array analysis is preferable to cell culture in delayed abortions, while cytogenetics is more able to show polyploidies. Both have the same growth failure rates when product of conception tissue is not properly collected.

RESUMO Objetivo: Comparar os resultados obtidos pela metodologia clássica e molecular na análise de produtos de concepção, além das vantagens e desvantagens de cada método. Métodos: Análise retrospectiva não randomizada dos resultados obtidos a partir de amostras de produto de concepção submetidas à avaliação genética, de 2012 a 2017. As análises foram realizadas por citogenética clássica e/ou análise cromossômica de microarray ou arrays. Resultados: Quarenta amostras foram analisadas por citogenética, das quais 10% não apresentaram crescimento celular, 50% apresentaram resultados normais, e 40% apresentaram anormalidades. Dos 41 casos encaminhados para análise por array, não foi possível obter resultados em 7,3%, 39,5% eram normais, e 60,5% apresentavam alterações. Não houve diferença estatística entre os resultados (p=0,89). A maioria dos resultados anormais foi observada até a nona semana de gestação. Uma perda fetal mais tardia foi observada na 28ª semana de gestação, com cariótipo 46,XX,del(15)(q26.2-qter). Os números observados corroboraram a literatura mundial. Conclusão: As técnicas de citogenética clássica e análise por array mostraram resultados comparáveis no tipo de alteração observada. O array é preferível à cultura de células em abortos tardios, enquanto a citogenética é mais capaz de mostrar poliploidias. Ambos têm as mesmas taxas de falha de crescimento quando o tecido do produto de concepção não é coletado adequadamente.

New candidate genes associated to endometriosis.

A previous GWAS study performed on Brazilian pooled samples indicated some SNPs (single nucleotide polymorphisms) differentially frequent in infertile patients with endometriosis and controls. Some of them were located in the genes whose biological function suggests that they could be associated with endometriosis pathogenesis; thus, the purpose here was to confirm GWAS findings in a larger group of cases and controls in order to associate the results with the pathogenesis of endometriosis. Then, a genetic association study comprising 394 infertile women with endometriosis and 650 fertile control women was conducted. TaqMan allelic discrimination assays were used to investigate the frequency of three SNPs in the genes KAZN (rs10928050), LAMA5 (rs2427284), and TAC3 (rs733629). The analysis revealed a significant association of KAZN rs10928050 (p = .015) and LAMA5 rs2427284 (p = .0059) SNPs with endometriosis-related infertility, while TAC3 rs733629 showed no difference between cases and controls. As a conclusion, it was possible to observe that individual genotyping of a larger sample of patients and controls confirmed the association among KAZN and LAMA5 with endometriosis-related infertility and revealed new candidate genes contributing to the condition.

Incidence of Y-chromosome microdeletions in children whose fathers underwent vasectomy reversal or in vitro fertilization with epididymal sperm aspiration: a case-control study / Incidência de microdeleções do cromossomo Y em filhos de pais que passaram por reversão de vasectomia ou fertilização in vitro com aspiração do epidídimo: um estudo caso-controle

ABSTRACT Objective To evaluate the incidence of Y-chromosome microdeletions in individuals born from vasectomized fathers who underwent vasectomy reversal or in vitro fertilization with sperm retrieval by epididymal aspiration (percutaneous epididymal sperm aspiration). Methods A case-control study comprising male children of couples in which the man had been previously vasectomized and chose vasectomy reversal (n=31) or in vitro fertilization with sperm retrieval by percutaneous epididymal sperm aspiration (n=30) to conceive new children, and a Control Group of male children of fertile men who had programmed vasectomies (n=60). Y-chromosome microdeletions research was performed by polymerase chain reaction on fathers and children, evaluating 20 regions of the chromosome. Results The results showed no Y-chromosome microdeletions in any of the studied subjects. The incidence of Y-chromosome microdeletions in individuals born from vasectomized fathers who underwent vasectomy reversal or in vitro fertilization with spermatozoa recovered by percutaneous epididymal sperm aspiration did not differ between the groups, and there was no difference between control subjects born from natural pregnancies or population incidence in fertile men. Conclusion We found no association considering microdeletions in the azoospermia factor region of the Y chromosome and assisted reproduction. We also found no correlation between these Y-chromosome microdeletions and vasectomies, which suggests that the assisted reproduction techniques do not increase the incidence of Y-chromosome microdeletions.

RESUMO Objetivo Avaliar a incidência de microdeleções do cromossomo Y em indivíduos nascidos de pais vasectomizados submetidos à reversão de vasectomia ou fertilização in vitro com recuperação de espermatozoides por aspiração do epidídimo (aspiração percutânea de espermatozoides do epidídimo). Métodos Estudo caso-controle que compreende crianças do sexo masculino de casais em que o homem havia sido previamente vasectomizado e escolheu reversão da vasectomia (n=31) ou fertilização in vitro com recuperação espermática por aspiração percutânea de espermatozoides do epidídimo (n=30) para obtenção de novos filhos, e um Grupo Controle de crianças do sexo masculino de homens férteis com vasectomia programada (n=60). A pesquisa de microdeleções do cromossomo Y foi realizada por reação em cadeia da polimerase nos pais e filhos, avaliando 20 regiões do cromossomo. Resultados O resultado não revelou microdeleções do cromossomo Y em qualquer indivíduo estudado. A incidência de microdeleções do cromossomo Y em indivíduos nascidos de pais vasectomizados que sofreram reversão de vasectomia ou fertilização in vitro com espermatozoides recuperados pela aspiração percutânea de espermatozoides do epidídimo não diferiu entre os grupos, e não houve nenhuma diferença entre indivíduos controle nascidos de gestações naturais ou incidência populacional em homens férteis. Conclusão Não foi encontrada nenhuma associação considerando microdeleções da região do fator de azoospermia no cromossomo Y e reprodução assistida. Não houve correlação entre microdeleções do cromossomo Y e vasectomia, o que sugere que as técnicas de reprodução assistida não aumentam a incidência de microdeleções do cromossomo Y.

Incidence of Y-chromosome microdeletions in children whose fathers underwent vasectomy reversal or in vitro fertilization with epididymal sperm aspiration: a case-control study.

OBJECTIVE: To evaluate the incidence of Y-chromosome microdeletions in individuals born from vasectomized fathers who underwent vasectomy reversal or in vitro fertilization with sperm retrieval by epididymal aspiration (percutaneous epididymal sperm aspiration). METHODS: A case-control study comprising male children of couples in which the man had been previously vasectomized and chose vasectomy reversal (n=31) or in vitro fertilization with sperm retrieval by percutaneous epididymal sperm aspiration (n=30) to conceive new children, and a Control Group of male children of fertile men who had programmed vasectomies (n=60). Y-chromosome microdeletions research was performed by polymerase chain reaction on fathers and children, evaluating 20 regions of the chromosome. RESULTS: The results showed no Y-chromosome microdeletions in any of the studied subjects. The incidence of Y-chromosome microdeletions in individuals born from vasectomized fathers who underwent vasectomy reversal or in vitro fertilization with spermatozoa recovered by percutaneous epididymal sperm aspiration did not differ between the groups, and there was no difference between control subjects born from natural pregnancies or population incidence in fertile men. CONCLUSION: We found no association considering microdeletions in the azoospermia factor region of the Y chromosome and assisted reproduction. We also found no correlation between these Y-chromosome microdeletions and vasectomies, which suggests that the assisted reproduction techniques do not increase the incidence of Y-chromosome microdeletions. OBJETIVO: Avaliar a incidência de microdeleções do cromossomo Y em indivíduos nascidos de pais vasectomizados submetidos à reversão de vasectomia ou fertilização in vitro com recuperação de espermatozoides por aspiração do epidídimo (aspiração percutânea de espermatozoides do epidídimo). MÉTODOS: Estudo caso-controle que compreende crianças do sexo masculino de casais em que o homem havia sido previamente vasectomizado e escolheu reversão da vasectomia (n=31) ou fertilização in vitro com recuperação espermática por aspiração percutânea de espermatozoides do epidídimo (n=30) para obtenção de novos filhos, e um Grupo Controle de crianças do sexo masculino de homens férteis com vasectomia programada (n=60). A pesquisa de microdeleções do cromossomo Y foi realizada por reação em cadeia da polimerase nos pais e filhos, avaliando 20 regiões do cromossomo. RESULTADOS: O resultado não revelou microdeleções do cromossomo Y em qualquer indivíduo estudado. A incidência de microdeleções do cromossomo Y em indivíduos nascidos de pais vasectomizados que sofreram reversão de vasectomia ou fertilização in vitro com espermatozoides recuperados pela aspiração percutânea de espermatozoides do epidídimo não diferiu entre os grupos, e não houve nenhuma diferença entre indivíduos controle nascidos de gestações naturais ou incidência populacional em homens férteis. CONCLUSÃO: Não foi encontrada nenhuma associação considerando microdeleções da região do fator de azoospermia no cromossomo Y e reprodução assistida. Não houve correlação entre microdeleções do cromossomo Y e vasectomia, o que sugere que as técnicas de reprodução assistida não aumentam a incidência de microdeleções do cromossomo Y.

Evaluation of the frequency of G-765C polymorphism in the promoter region of the COX-2 gene and its correlation with the expression of this gene in the endometrium of women with endometriosis.

OBJECTIVE: To evaluate the frequency of polymorphism G-765C (rs20417) of the COX-2 gene and the expression of this gene in the endometrium of women with endometriosis. STUDY DESIGN: This is a case-control study of 365 women with endometriosis (251 infertile and 114 fertile) submitted to laparoscopy/laparotomy with histological confirmation of endometriosis. The control group was composed of 522 fertile women without endometriosis. Of these, 37 patients from the endometriosis group and 47 from the control group were submitted to biopsy of the endometrium for analysis of the expression of the COX-2 gene. The genotypes were determined using analysis by High-Resolution Melt. Gene expression was measured by qRT-PCR with TaqMan methodology using the GAPDH gene as normalizer of the reactions. RESULTS: The distribution of the genotypes and alleles in the group of fertile women with moderate/severe endometriosis showed a statistically significant difference, demonstrating association of the ancestral allele, -765G, with increased risk of endometriosis (p = 0.028; OR 0.53; CI 0.32-0.90). The mean expression of the COX-2 gene (mRNA PTGS2) in the group of women with endometriosis was statistically higher compared to the control group (3.85 versus 2.84, p = 0.028). CONCLUSION: The present study identified that in Brazilian women the presence of the ancestral allele, -765G, of the COX-2 gene is associated with an increased risk for development of moderate/severe endometriosis associated with fertility, and that the eutopic endometrium of women with endometriosis showed increased expression of COX-2 when compared to the control group.

45,X karyotype in an infertile man: how is this possible?

The case was male, 32 years old, with a nonobstructive azoospermia diagnosis and an initial 45,X karyotype. We evaluated by classical cytogenetic methods, C and NOR banding, fluorescent in situ hybridization, and polymerase chain reaction investigations. After investigation, we found the following karyotype: 45,X,dic(Y;22)(q11.223;p11.2). This investigation contributes to our understanding of how chromosome rearrangements can influence fertility processes and how important it is to perform a cytogenetic analysis in infertility cases.

There is no relationship between Paraoxonase serum level activity in women with endometriosis and the stage of the disease: an observational study.

BACKGROUND: Endometriosis is a chronic condition whose pathophysiology is unknown, but there is evidence suggesting a link with oxidative stress. Paraoxonase is a serum enzyme which circulates associated with high-density lipoprotein (HDL). It acts protecting HDL and LDL of lipid peroxidation. We aimed to compare the serum levels of PON-1 activity in women with endometriosis in different stages of the disease (minimal/mild and moderate/severe). METHODS: 80 infertile women with endometriosis diagnosed by laparoscopy/laparotomy with histologic confirmation of the disease were divided according to the American Society for Reproductive Medicine classification in minimal/mild (n = 33) and moderate/severe (n = 47) cases. Paraoxonase activity and arilesterase activity were measured by spectrophotometry. Body mass index and fasting glucose levels were also determined. RESULTS: The paraoxonase activity were 191.29 ± 22.41 U/l in women with minimal/mild endometriosis and 224.85 ± 21.50 U/l in women with moderate/severe disease (P = 0.274). Considering arilesterase level, the results showed 89.82 ± 4.61 U/l in women with minimal/mild endometriosis and 90.78 ± 3.43 U/l in moderate/severe disease (P = 0.888). CONCLUSIONS: Evidence of lower paraoxonase activity in women with endometriosis was not found in this study. Besides, no difference was found considering minimal/mild or moderate/severe endometriosis.

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.

Prevalence of cases of Mycoplasma hominis, Mycoplasma genitalium, Ureaplasma urealyticum and Chlamydia trachomatis in women with no gynecologic complaints.

Purpose: To evaluate the prevalence of Mycoplasma hominis, Mycoplasma genitalium, Ureaplasma urealyticum, Chlamydia trachomatis, Trichomonas vaginalis and Neisseria gonorrhoeae in women with no gynecologic complaints screened in the Human Reproduction outpatient clinic of Faculdade de Medicina of ABC, Brazil. Methods: A total of 106 women without gynecologic complaints and in reproductive age were evaluated. DNA was extracted from cells of the genitourinary tract with bacteria for the detection of six types of bacteria by polymerase chain reaction. Results: We found that 11.3 % of women had infection with M. hominis and 2.83 % for C. trachomatis. The other bacteria investigated occurred in 2.83 % of women. The percentage of infections identified was 15 %. Conclusion: The data showed a low percentage of women with genitourinary tract bacteria without symptoms. However, these infections can be sexually transmitted, and relate to infertility and other serious illnesses. The identification and treatment of infection in asymptomatic woman can avoid transmission and future genitourinary trait complications.

Combination of polymorphisms in luteinizing hormone ß, estrogen receptor ß and progesterone receptor and susceptibility to infertility and endometriosis.

OBJECTIVES: To determine whether the combination of PR (PROGINS), ERß G+1730A and/or LHß G1502A polymorphisms in infertile women with and without endometriosis and in a control group increases the risk of infertility and/or endometriosis. STUDY DESIGN: Case-control study including 201 infertile women with endometriosis, 80 infertile women without endometriosis and 206 fertile women as control group. PROGINS was identified by PCR (polymerase chain reaction) and ERß G+1730A and LHß G1502A were identified by PCR-RFLP (restriction fragment length polymorphism). RESULTS: A statistically significant difference was found for the combination of LHß+ERß polymorphisms among infertile patients with endometriosis and control group (p=0.003, OR=2.468), among infertile patients with endometriosis I/II and control group (p=0.002, OR=3.081), among infertile patients with endometriosis III/IV and control group (p=0.035, OR=2.136) and for the combination of LHß+PROGINS polymorphisms among infertile patients with endometriosis I/II and control group (p=0.014, OR=3.081). However, the odds of developing endometriosis are not enhanced in the presence of the two polymorphisms, being similar to the odds when only LH polymorphism is present. CONCLUSIONS: Individually, the presence of LHß G1502A and ERß G+1730A polymorphisms is associated with infertility and endometriosis associated infertility. However, when two polymorphisms are present in the same individual it does not appear to increase the chance of developing endometriosis or infertility.

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.

Polymorphism of the estrogen receptor ß gene is related to infertility and infertility-associated endometriosis.

OBJECTIVE: To determine the frequency of the estrogen receptor b gene (ERß) +1730 G/A polymorphism in infertile women with and without endometriosis and controls. SUBJECTS AND METHODS: Case-control study that included 136 women with endometriosis, 69 women without endometriosis and 209 fertile women as controls. The ERß gene + 1730 G/A polymorphism was identified by RFLP-PCR (Restriction Fragment Length Polymorphism - Polymerase Chain Reaction). RESULTS: Genotypes GG, GA and AA of the ERß gene presented frequencies of 60.3%, 38.2% and 1.5%, respectively, in the women with endometriosis (p < 0.0022). Of the infertile women without endometriosis, 63.8% presented the normal homozygous genotype GG, 30.4% the GA heterozygous genotype, and 5.8% the homozygous mutated genotype AA (p < 0.0275). In the control group, 77.5% presented the normal homozygous genotype GG, 21.1% the heterozygous genotype GA, and 1.4% the homozygous mutated genotype AA. CONCLUSION: The data suggest that the estrogen receptor ß gene (ERß) +1730 G/A polymorphism can be associated with risk of infertility and endometriosis-associated infertility.

Polymorphism of the estrogen receptor β gene is related to infertility and infertility-associated endometriosis / O polimorfismo do gene do receptor β de estrógeno está relacionado com infertilidade e endometriose associada à infertilidade

OBJECTIVE: To determine the frequency of the estrogen receptor b gene (ERβ) +1730 G/A polymorphism in infertile women with and without endometriosis and controls. SUBJECTS AND METHODS: Case-control study that included 136 women with endometriosis, 69 women without endometriosis and 209 fertile women as controls. The ERβ gene + 1730 G/A polymorphism was identified by RFLP-PCR (Restriction Fragment Length Polymorphism - Polymerase Chain Reaction). RESULTS: Genotypes GG, GA and AA of the ERβ gene presented frequencies of 60.3 percent, 38.2 percent and 1.5 percent, respectively, in the women with endometriosis (p < 0.0022). Of the infertile women without endometriosis, 63.8 percent presented the normal homozygous genotype GG, 30.4 percent the GA heterozygous genotype, and 5.8 percent the homozygous mutated genotype AA (p < 0.0275). In the control group, 77.5 percent presented the normal homozygous genotype GG, 21.1 percent the heterozygous genotype GA, and 1.4 percent the homozygous mutated genotype AA. CONCLUSION: The data suggest that the estrogen receptor β gene (ERβ) +1730 G/A polymorphism can be associated with risk of infertility and endometriosis-associated infertility.

OBJETIVO: Determinar a frequência do polimorfismo +1730 G/A do gene do receptor beta de estrógeno (ERβ) em mulheres inférteis com e sem endometriose e controles. SUJEITOS E MÉTODOS: Estudo caso-controle que incluiu 136 mulheres com endometriose, 69 mulheres sem endometriose e 209 mulheres férteis como controles. O polimorfismo ERβ + 1730 G/A foi identificado por RFLP-PCR (Restriction Fragment Length Polymorphism - Polymerase Chain Reaction). RESULTADOS: Os genótipos GG, GA e AA do polimorfismo ERβ + 1730 G/A apresentaram frequência de 60,3 por cento, 38,2 por cento e 1,5 por cento, respectivamente, nas mulheres com endometriose (p = 0,0022). Das mulheres inférteis sem endometriose, 63,8 por cento apresentaram o genótipo homozigoto normal GG, 30,4 por cento o genótipo heterozigoto GA e 5,8 por cento o genótipo homozigoto mutado AA (p = 0,0275). No grupo controle, os genótipos GG, GA e AA apresentaram frequência de 77,5 por cento, 21,1 por cento e 1,4 por cento. CONCLUSÃO: Os dados sugerem que o polimorfismo ERβ +1730G/ pode estar associado ao risco de infertilidade e infertilidade associada à endometriose.

The progins progesterone receptor gene polymorphism is not related to endometriosis-associated infertility or to idiopathic infertility.

OBJECTIVE: This study aimed to determine the frequency of the PROGINS polymorphism in women with endometriosis-associated infertility, in infertile women without endometriosis and in controls. INTRODUCTION: The human progesterone receptor gene has two isoforms that modulate the biological action of progesterone: isoform A, which is capable of inhibiting the activation of the estrogen receptors, and isoform B, which has the capacity to activate the estrogen receptors. Several polymorphisms have been described for this gene, among which one stands out: a polymorphism named PROGINS, which has been speculated to be related to the genesis of endometriosis by several studies with conflicting results. METHODS: This was a prospective study that included 148 patients with endometriosis-associated infertility, 50 idiopathic infertile patients and 179 fertile women as controls. The PROGINS polymorphism was studied by PCR. RESULTS: Genotypes P1P1, P1P2 and P2P2 (P2 representing the PROGINS polymorphism) of the progesterone receptor gene presented frequencies of 93.9%, 5.4% and 0.7%, respectively, in the women with endometriosis-associated infertility (p=0.2101, OR=0.51, 95% CI=0.24-1.09); 94.4%, 4.2% and 1.4%, respectively, in the patients with minimal/mild endometriosis (p=0.2725, OR=0.53, 95% CI=0.20-1.43); 93.5%, 6.5% and 0%, respectively, among the patients with moderate/severe endometriosis (p=0.3679, OR=0.49, 95% CI=0.18-1.31); 86.0%, 14.0% and 0%, respectively, in idiopathic infertile women (p=0.8146, OR=1.10, 95% CI=0.46-2.63); and 88.3%, 10.6% and 1.1%, respectively, in the control group. CONCLUSION: The data suggest that PROGINS is not related either to endometriosis-associated infertility or to idiopathic infertility in the population studied.

OC-125 immunostaining in endometriotic lesion samples.

PURPOSE: To determine the presence of OC-125 staining in endometriotic lesions and to verify whether there is an association with endometriosis stage. METHODS: Thirteen 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. RESULTS: The 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. CONCLUSION: The data suggest that the OC-125 antibody is probably related to endometriosis activity and, consequently, to the progression and severity of the illness.

The progins progesterone receptor gene polymorphism is not related to endometriosis-associated infertility or to idiopathic infertility

OBJECTIVE: This study aimed to determine the frequency of the PROGINS polymorphism in women with endometriosis-associated infertility, in infertile women without endometriosis and in controls. INTRODUCTION: The human progesterone receptor gene has two isoforms that modulate the biological action of progesterone: isoform A, which is capable of inhibiting the activation of the estrogen receptors, and isoform B, which has the capacity to activate the estrogen receptors. Several polymorphisms have been described for this gene, among which one stands out: a polymorphism named PROGINS, which has been speculated to be related to the genesis of endometriosis by several studies with conflicting results. METHODS: This was a prospective study that included 148 patients with endometriosis-associated infertility, 50 idiopathic infertile patients and 179 fertile women as controls. The PROGINS polymorphism was studied by PCR. RESULTS: Genotypes P1P1, P1P2 and P2P2 (P2 representing the PROGINS polymorphism) of the progesterone receptor gene presented frequencies of 93.9 percent, 5.4 percent and 0.7 percent, respectively, in the women with endometriosis-associated infertility (p=0.2101, OR=0.51, 95 percent CI=0.24-1.09); 94.4 percent, 4.2 percent and 1.4 percent, respectively, in the patients with minimal/mild endometriosis (p=0.2725, OR=0.53, 95 percent CI=0.20-1.43); 93.5 percent, 6.5 percent and 0 percent, respectively, among the patients with moderate/severe endometriosis (p=0.3679, OR=0.49, 95 percent CI=0.18-1.31); 86.0 percent, 14.0 percent and 0 percent, respectively, in idiopathic infertile women (p=0.8146, OR=1.10, 95 percent CI=0.46-2.63); and 88.3 percent, 10.6 percent and 1.1 percent, respectively, in the control group. CONCLUSION: The data suggest that PROGINS is not related either to endometriosis-associated infertility or to idiopathic infertility in the population studied.

+1730 G/A polymorphism of the estrogen receptor beta gene (ERbeta) may be an important genetic factor predisposing to endometriosis.

OBJECTIVE: To determine the frequency of the estrogen receptor gene (ERbeta) +1730 G/A polymorphism in Brazilian women with endometriosis. DESIGN: Case-control study. SETTING: Endometriosis Outpatient Clinic and Family Planning Outpatient Clinic of ABC Faculty of Medicine. POPULATION: A total of 108 patients with endometriosis and a control group consisting of 210 fertile women. METHODS: The ERbeta gene +1730 G/A polymorphism was identified by restriction fragment length polymorphism-polymerase chain reaction. MAIN OUTCOME MEASURE(S): Genotype distribution and allele frequency of the +1730 G/A polymorphism in the ERbeta gene. RESULTS: Genotypes GG, GA and AA of the ERbeta gene presented frequencies of 50.9%, 47.2% and 1.9%, respectively, in the women with endometriosis. Among the patients with stage I/II endometriosis, 47% presented the normal homozygous genotype GG; 51% had a GA heterozygous genotype and 2% had a homozygous mutated genotype AA. Among the patients with stage III/IV endometriosis, genotypes GG, GA and AA were present in 54.3%, 44% and 1.7%, respectively. In the control group, 74.3% presented the normal homozygous genotype GG, 24.3% the heterozygous genotype GA and 1.4% the homozygous mutated genotype AA. CONCLUSION: The data suggest that the ERbeta gene +1730 G/A polymorphism can be associated with the risk of endometriosis development, regardless of the stage of the disease.