Influence of STAT4 gene polymorphisms in the pathogenesis of endometriosis.

The STAT4 gene is vital to signaling pathways in the immune response. Immunological alterations are involved in the pathogenesis of endometriosis, and STAT4 polymorphisms may be linked to disease development. This study's aim is to evaluate the possible association between four STAT4 polymorphisms (rs7601754/G > A, rs11889341/C > T, rs7574865/T > G, and rs7582694/C > G) and the pathogenesis of endometriosis in Brazilian women. This case-control study's sample comprised 238 women with endometriosis and 201 healthy, fertile women without endometriosis (which was surgically confirmed). Genotyping was performed using the TaqMan system with a real-time polymerase chain reaction; the genotype, allele, and haplotype frequencies were then compared between groups. A single-polymorphism analysis revealed that the TT genotype of the rs7574865/T > G polymorphism was significantly more frequent in women with minimal or mild endometriosis than in the controls (10% vs. 5%, p = 0.047). The CGAC, GTAT, and GTAC haplotypes were significantly more frequent in the women with endometriosis-related infertility (5.8%, 4.1%, and 2.9%, respectively) than in the controls (2.4%, 1.1%, and 0.8%, respectively; p = 0.020, p = 0.011, and p = 0.032, respectively), but the GGGC and CTAT haplotypes were significantly more prevalent in the control group (34.7% and 13.9%, respectively) than among the infertile group (26.2% and 9.1%, respectively). In addition, the CGAC haplotype was more frequently found in those with minimal or mild endometriosis (6.8%) than in the controls (2.4%, p = 0.009), and the GTAT haplotype was more commonly found in those with moderate or severe disease (3.6%) than in the controls (1.1%, p = 0.028). These findings suggest that STAT4 polymorphisms can influence the pathogenesis of endometriosis.

Kisspeptin/GPR54 System: What Do We Know About Its Role in Human Reproduction?

Kisspeptin is involved in the control of human reproduction bridging the gap between the sex steroid levels and feedback mechanisms that control the gonadotropin releasing hormone (GnRH) secretion; however, studies considering this peptide and infertility are limited. We conducted a review and critical assessment of available evidence considering kisspeptin structure, physiology, function in puberty and reproduction, its role in assisted reproduction treatments, kisspeptin dosage and the impact on KISS1 and GPR54 genes. Literature searches were conducted in PubMed using keywords related to: (i) kisspeptin or receptors, kisspeptin-1 (ii) reproduction or infertility or fertility (iii) gene and (iv) dosage or measurement or quantification or serum level, in human. Kisspeptin is a product of KISS1 gene that binds to a G-protein-coupled receptor (GPR54/KISS1R) stimulating the release of GnRH by hypothalamic neurons, leading to secretion of pituitary gonadotropins (LH and FSH) and sexual steroids, which in turn will act in the gonads to produce the gametes. Kisspeptin is being recognized as a crucial regulator of the onset of puberty, the regulation of sex hormone mediated secretion of gonadotropins, and the control of fertility. Inactivating and activating mutations in both KISS1 or GPR54 genes were associated with hypogonadotropic hypogonadism and precocious puberty. Despite this, studies considering kisspeptin and infertility are scarce. The understanding of the role of kisspeptin may lead to its use as a biomarker in infertility treatments and use in controlled ovarian hyperstimulation.

AMH and AMHR2 polymorphisms and AMH serum level can predict assisted reproduction outcomes: a cross-sectional study.

BACKGROUND: In human assisted reproduction, the ovarian response to exogenous recombinant Follicle-stimulating Hormone (FSH) therapy is variable and difficult to predict. The standard protocol of ovarian hyperstimulation can result in satisfactory response; however, an unsatisfactory response necessitates FSH dose adjustment or results in ovarian hyperstimulation syndrome (OHSS). Polymorphisms in AMH and AMHR2 genes appear to affect hormone biological activities, thus affecting follicle recruitment and development, leading to infertility. We aimed to evaluate AMH and AMHR2 polymorphisms in infertile women, and correlate those findings with AMH, FSH and estradiol serum level response to controlled ovarian hyperstimulation (COH), as well as assisted reproduction outcomes. METHODS: A cross-sectional study comprising 186 infertile women that underwent one cycle of high complexity assisted reproductive treatment. Blood samples were collected and a TaqMan assay was used for AMH G146T/rs10407022 and AMHR2 A-482G/rs2002555, A10G/rs11170555, C1749G/rs2071558 and G4952A/rs3741664 genotyping, and FSH, estradiol and AMH levels were measured. The findings were correlated to human reproduction outcomes. RESULTS: AMH rs10407022 and AMHR2 rs2002555 polymorphisms were not associated with hormonal measurements, whereas AMHR2 rs11170555 and rs3741664 were positively associated with AMH, estradiol and FSH levels. The genotype distribution of AMH and AMHR2 genes according to Controlled Ovarian Hyperstimulation did not show a positive association. However, an association with AFC, degree of oocyte maturation (allele G of AMHR2 rs2071558) the number of embryos produced (alleles T and G of AMH rs10407022 and AMHR2 rs2002555, respectively) and frozen embryo (allele G of AMHR2 rs11170555) were found to be statistically associated. Considering COH, serum AMH and AFC were a positive predictor to OHSS. Regarding serum AMH and assisted reproduction outcomes, a positive correlation with all variables studied was found. Comparing AFC and AMH as predictors of human reproduction outcomes, the AFC was less effective than serum AMH. Considering pregnancy rates, no marker was positively associated. CONCLUSION: AMHR2 polymorphisms were associated with estradiol, AMH and FSH measurements, as well as number and quality of embryos, while AMH polymorphisms was associated with number of embryos produced. Serum AMH was correlated with nearly all variables analyzed in assisted reproductive treatment, demonstrating that it represents a better biomarker of OHSS and human reproduction outcomes compared to AMH and AMHR2 polymorphisms.

Analysis of vitamin D receptor gene (VDR) polymorphisms in Turner syndrome patients.

Individuals with Turner syndrome (TS) have increased risk for autoimmune diseases, especially thyroid abnormalities. The function of the vitamin D receptor (VDR) gene is influenced by several genetic polymorphisms which are associated with a susceptibility to a range of autoimmune diseases. Thus, we have hypothesized a possible relationship between thyroid abnormalities and VDR polymorphisms (ApaI/G1025-49T, TaqI/T1056C, FokI/T2C and BsmI G1024 + 283A) in TS patients. A case-control study was performed comprising 101 Brazilian women with TS and a control group consisting of 133 healthy fertile women without a history of autoimmune diseases. In TS group, 21.8% had Hashimoto's thyroiditis. Detection of VDR polymorphisms was performed using TaqMan system by real-time PCR. The χ(2) was used to compare allele and genotype frequencies between groups. Combined genotypes of VDR gene polymorphisms were assessed by the haplotype analysis. A p value <0.05 was considered statistically significant. Relatively similar VDR polymorphisms genotype and allelic frequencies in cases and controls were found, even when only considering the patients with thyroid abnormalities. Haplotype analysis showed that none of the VDR haplotypes were associated to thyroid diseases in TS patients. In conclusion, the results showed no association between VDR gene polymorphisms and thyroid abnormalities in Brazilian TS patients tested.

Folate metabolism abnormalities in infertile patients with endometriosis.

Background: Homocysteine levels can be impacted by enzymes variations. Aim: To correlate MTHFR, MTR and MTRR variants with homocysteine levels in the blood and follicular fluid and assisted reproduction results. Material & methods:MTHFR (rs2274976, rs1801131, rs1801133), MTR (rs1805087) and MTRR (rs1801394) genotyping was performed by TaqMan assays and compared with homocysteine levels, measured by ELISA, to oocytes retrieved and to the pregnancy status of women with endometriosis and controls. Results: The MTR G allele and GG genotype were more common in patients with endometriosis. They also showed lower levels of homocysteine and more clinical gestations. Epistasis analysis showed a model associated with gestational results, composed of MTHFR+MTR variants (CC+AG). Conclusion: The summation effect of variants in genes participating in folate metabolism was associated with pregnancy status in Brazilian women. MTR variants were more observed in endometriosis patients, as well as lower follicular Hcy levels and increased clinical pregnancy results.

What was the aim of the study? To correlate genetic variants to homocysteine levels in the blood and oocyte surrounding fluid, and the results of assisted reproduction techniques. How was the study done? A total of 152 women with endometriosis and controls with male infertility were evaluated. DNA was extracted from blood for genetic analysis, and homocysteine levels were measured from the blood and oocyte surrounding fluid. Genetic results were correlated to homocysteine levels, oocyte quality and pregnancy status. What were the results? A specific genetic marker occurred more in endometriosis patients. They also showed lower levels of homocysteine and a tendency to more clinical gestations than controls. What do the results of the study mean? Endometriosis patients showed specific genetic markers and different levels of homocysteine compared with controls. These results can be helpful to predict gestational results.

Plasminogen activator inhibitor-1 4G/5G polymorphism in infertile women with and without endometriosis.

OBJECTIVE: To evaluate PAI-1 genotypes in a group of infertile women with or without endometriosis and control subjects. DESIGN: Case-control study. SETTING: Human Reproduction Center of Medicina do ABC Faculty. POPULATION: One hundred and forty infertile women with endometriosis, 64 women with idiopathic infertility and 148 fertile women as control subjects. METHODS: The PAI-1 4G/5G polymorphism was identified by restriction fragment length polymorphism-polymerase chain reaction. MAIN OUTCOME MEASURES: Genotype distribution and allele frequency of the 4G/5G polymorphism of the PAI-1 gene. RESULTS: The frequencies of genotypes 4G/4G, 4G/5G and 5G/5G of the PAI-1 gene in the infertile women with endometriosis were 38.6, 37.1 and 24.3%, respectively, and in the control group 24.3, 33.8 and 41.9%, respectively (p=0.003). When the infertile women with endometriosis were divided according to their endometriosis stage, genotypes 4G/4G, 4G/5G and 5G/5G were identified, respectively, in 36.7, 32.9 and 30.4% of the patients with minimal/mild endometriosis (p=0.102) and in 41.0, 42.6 and 16.4% of the patients with moderate/severe endometriosis (p=0.001); in the women with idiopathic infertility, these genotypes were found at a frequency of 29.7, 34.3 and 36%, respectively (p=0.637). CONCLUSION: The data suggest that, in Brazilian women, the PAI-1 4G/5G polymorphism may be associated with a risk of endometriosis-associated infertility.

Chromosomal and molecular abnormalities in a group of Brazilian infertile men with severe oligozoospermia or non-obstructive azoospermia attending an infertility service.

PURPOSE: To determine the frequency of genetic alterations in a population of Brazilian infertile men with severe oligozoospermia or non-obstructive azoospermia. MATERIALS AND METHODS: Retrospective study of a group of 143 infertile men with severe oligozoospermia or non-obstructive azoospermia from the Andrology Outpatient Clinic of the Human Reproduction Service at the ABC School of Medicine. Of these patients, 100 had severe oligozoospermia, and 43 non-obstructive azoospermia. All patients underwent a genetic study which included karyotype analysis and Y-microdeletion investigation. RESULTS: Genetic abnormalities were found in 18.8% of the studied patients. Chromosomal abnormalities were found in 6.2% of the patients, being more prevalent in the azoospermia group (11.6%) than in the oligozoospermia group (4%). Chromosomal variants were found in 8.3%, and Y-chromosome microdeletions in 4.2% of patients. CONCLUSION: The high frequency of genetic alterations (18.8%) in our series justified performing a genetic investigation in a population with idiopathic infertility, as results may help determine the prognosis, as well as the choice of an assisted reproduction technique. Moreover, a genetic investigation could minimize the risk of transmitting genetic abnormalities to future generations such as genetic male infertility, mental retardation, genital ambiguity and/or birth defects.

The role of survivin in the pathogenesis of endometriosis.

INTRODUCTION: Endometriosis is a common, estrogen-dependent condition, defined as the presence of endometrial-like tissue outside of the uterus, associated with often chronic and inflammatory reaction. The association of endometriosis with cancer is unclear, although endometriosis and cancer present some molecular similarities. Survinin, encoded by the BIRC5 gene, is a protein that controls cell division, inhibits apoptosis and promotes angiogenesis. Here we aimed to summarize and to discuss the main findings of studies that addressed the involvement of survivin in the pathogenesis of endometriosis. EVIDENCE ACQUISITION: We conducted a comprehensive retrieval from electronic databases, included the MEDLINE, EMBASE, with no restrictions to time span. We used the search terms endometriosis and survivin or BIRC5 and collected all relevant studies to explore the association between endometriosis and surviving expression. EVIDENCE SYNTHESIS: A total of 21 studies included in the systematic review, comprising sample collected from 1263 women with endometriosis. Results showed the involvement of more than 60 genes and proteins evaluated in eutopic, ectopic, endometrial and ovarian endometriosis, as well as in several gynecological conditions compared to healthy controls. CONCLUSIONS: The studies provided the basis for the involvement of survivin in the pathogenesis of the disease by several and independent pathways.

Expansion and herniation: evaluation of the best pregnancy rate predictor after quarter laser assisted hatching in frozen blastocyst transfers.

OBJECTIVE: To assess the recovery of thawed blastocysts submitted to quarter laser assisted hatching and examine potential correlations between the procedure and pregnancy rates. METHODS: This cross-sectional study included only single-blastocyst transfers performed from July 2017 to December 2018. A total of 765 blastocysts were thawed and immediately submitted to quarter laser assisted hatching in the zona pellucida; they were subsequently incubated for three hours until transfer time, at which time they were examined for collapse or expansion; expanded blastocysts were further evaluated for herniation. The Chi-square test was used in statistical analysis. RESULTS: 627 blastocysts expanded (81.9%) and yielded a pregnancy rate of 40% (251/627). 138 blastocysts collapsed after thawing (18.0%) and yielded a pregnancy rate of 25.4% (35/138) (p=0.001). Additional analysis of the subgroup of expanded blastocysts revealed that the 385 herniated blastocysts (61.4%) yielded a pregnancy rate of 43.9% (169/385). The remaining 242 non-herniated blastocysts (38.6%) yielded a pregnancy rate of 33.9% (82/242) (p=0.013). Statistical significance was attributed to events with a p<0.05. CONCLUSION: Quarter laser assisted hatching is a safe, valid, and relatively easy-to-use procedure for thawed blastocysts. Blastocysts that expanded and herniated after quarter laser assisted hatching presented statistically superior results.

ICSI in late matured oocytes, is it worth it? Study with laboratory, clinical and genetic evaluation results.

OBJECTIVE: To compare laboratory results of embryo development from late matured oocytes in relation to mature oocytes in D+0. METHODS: We carried out a cross-sectional study during the period from January to December 2018, in which we collected data through medical records analysis. 913 oocytes were collected and divided into 3 groups: group 1 - 643 MII oocytes; group 2 - 119 MI oocytes and; group 3 - 151 PI oocytes. These studied oocytes were from different maternal ages and infertility factors. The analyzed variables were fertilization rate, embryo cleavage, top quality embryos on the third day of development, blastocyst stage, top quality blastocysts, euploid blastocysts, top quality blastocysts and gestation. We documented the data, and performed the statistical analysis using the chi-square test (p<0.05). RESULTS: All MII oocytes were injected (643); 103/119 MI oocytes and 88/151 PI oocytes that matured late in D + 1, were also injected. The fertilization rate of the three groups did not present statistical difference. The oocytes of group 1 had a statistically proven better prognosis than oocytes from groups 2 and 3 when compared, respectively, embryo cleavage (p=0.000), top quality embryos on the third day of development (p=0.000) and blastocyst formation rate (p=0.004). In the LMO group, there were no euploid embryos and, therefore, there no embryo transfer. CONCLUSION: Although late matured oocytes have made blastocyst formation possible, even if in low rates, there were no viable embryos for transfer.

Prevalence of preeclampsia and eclampsia in adolescent pregnancy: A systematic review and meta-analysis of 291,247 adolescents worldwide since 1969.

OBJECTIVE: Hypertensive disorders are among the main causes of maternal and perinatal morbidity and mortality, and the findings regarding the occurrence of preeclampsia (PE) and eclampsia (E) in adolescent pregnancy are conflicting. We performed a systematic review and meta-analysis aimed to determining the prevalence of PE and E in adolescent pregnancy considering socioeconomic and temporal characteristics. STUDY DESIGN: MEDLINE, EMBASE and SciELO databases, with no time span restrictions. Studies that reported the occurrence of PE and E in adolescent pregnancy. Study selection, data extraction and bias assessment were performed by three independent investigators. Meta-analysis techniques comprised random-effects model and double-arcsine transformation; χ1 and I2 tests were used to assess heterogeneity. Meta-regression used Hunter-Schmidt model; publication bias were assessed by funnel and Baujat plots. RESULTS: Seventy studies were included, ranging from 1969 to 2019 and comprising 30 countries and 291,247 adolescents. The overall prevalence rate of PE/E was 6.7 % (95 % CI = 5.8-7.6). Subgroup analysis revealed association of PE/E (P = 0.050) and E (P = 0.0113) with country income, and the highest prevalences were found in low-and medium-income country groups (11.5 %, 95 % CI=7.8-15.8 and 10.6 %, 95 % CI=6.05-16.2). Association of PE with publication year (P = 0.0022) was also found with an observable reduction in prevalence rate across the years. CONCLUSIONS: The findings seem to confirm that socioeconomic and demographic characteristics play a role for the risk of PE/E in adolescent pregnancy. Although the occurrence of PE has declined worldwide, the problem has broader dimensions beyond health issues.

Cancer fertility preservation: a report from a Brazilian social program.

OBJECTIVE: To present clinical and laboratory data of a Brazilian social program for cancer fertility preservation. METHODS: We carried out a descriptive observational study between July 2011 and December 2018. 246 patients were included from a social program in a private assisted reproduction clinic in Santo André/Brazil for oocyte cryopreservation before starting oncological treatment. RESULTS: 246 cancer patients resorted to fertility preservation before initiating cancer treatment. These were diagnosed with 27 different types of cancer, and the breast type is the most prevalent. 2528 MII oocytes (mean of 10.3 oocytes per patient) were vitrified. Four patients thawed their oocytes to submit in vitro fertilization, three had embryos transferred and one achieved pregnancy. CONCLUSION: Preservation of fertility offers patients, especially at reproductive age, a viable way to perform their cancer treatment without compromising future gestation. It is important that professionals duly counsel oncological patients so, if they wish, they can have the possibility to guarantee her fertility preserved.

Psychological stress levels in women with endometriosis: systematic review and meta-analysis of observational studies.

INTRODUCTION: Endometriosis is defined as the presence of endometrial-like tissue outside the uterus, associated with chronic and inflammatory reaction. Symptoms range from dysmenorrhea, dyspareunia, chronic pelvic pain, unexplained infertility to asymptomatic. The patients' quality of life is affected by anxiety, depression and stress. We aimed to verify the prevalence and levels of psychological stress among women with endometriosis. EVIDENCE ACQUISITION: The systematic review followed the PRISMA statement and the MOOSE guideline. Databases searched were MEDLINE, EMBASE, PsychNET and SciELO. The risk of bias was assessed with a modified Newcastle-Ottawa Scale. The meta-analysis of proportions used inverse variance method for pooling and random-effects model. For the stress levels we used the restricted maximum likelihood estimator for summary effects. Heterogeneity was assessed through I2 and Q statistics. Publication bias was assessed through funnel plots. Meta-regression adopted a mixed-effects model, considering patient age, endometriosis staging, stress assessment tool and data collection as categorical moderators. EVIDENCE SYNTHESIS: We included 15 studies encompassing 4,619 women with endometriosis. The overall prevalence of mild/high stress was 68% (95%CI:57%-79%), I2=98% and τ2=0.0228. The mean level of stress was 41.78% (95%CI =34.05%-49.51%), I2=99.9% and τ2=83.35. Meta-regression showed relationship with endometriosis staging. CONCLUSIONS: This is the first meta-analysis exploring the association between endometriosis and psychological stress. The interdisciplinary management of the disease should expand the mental health support in this patient care, beyond pain management. Finally, the attitude of the medical team acknowledging the patients' psychological stress may positively affect their treatment.

The impact of high progesterone levels on the day of HCG administration in assisted human reproduction treatments.

OBJECTIVE: Progesterone is a steroid hormone that acts on the endometrium. It is known for producing physical and mood-related side effects. Few studies have looked into how progesterone levels affect embryo development and quality. This study aimed to find a cutoff level for serum progesterone on the day of HCG administration from which embryo quality is impaired. METHODS: The study included 145 cycles, from which 885 oocytes and 613 embryos were obtained. All patients had their serum progesterone levels measured on the day of HCG administration. Data sets were collected from patient medical records. The chi-square test was used to assess qualitative variables and the Mann-Whitney test to evaluate quantitative variables. RESULTS: Statistical analysis revealed that serum progesterone levels and reproductive variables were not significantly associated. In regards to oocyte maturity, however, when progesterone levels were greater than 1.3 ng/mL the probability of oocytes being immature increased by 12.7%. The fragmentation rate of embryos categorized as "top quality" in D3 increased proportionately to increases in progesterone levels (12.23%). CONCLUSION: High progesterone levels appeared to be correlated with increased embryo fragmentation rates, but high serum levels of the hormone on the day of HCG administration had no impact on reproductive variables and were not associated with impaired embryo development.

Can trophectoderm morphology act as a predictor for euploidy?

OBJECTIVE: Euploid embryo transfers yield better implantation rates. In Brazil, morphological evaluation is performed to select the best embryos, since genetic analysis is still an expensive procedure. This study aimed to evaluate whether there is an association between trophectoderm morphology and ploidy status. METHODS: The study included 113 blastocysts formed in D5/D6 from 58 in vitro fertilization cycles held from January/2016 to May/2017. All patients with indication for PGD/PGS were included in the study. The mean age of the female patients was 37.04±5.65years. Biopsied blastocysts were categorized for morphology. Cells were sent for genetic analysis using the CGH array, SNP array or NGS techniques. Statistical analysis was performed using the chi square test, and statistical significance was assigned to differences with p≤0.05. RESULTS: Chromosome analysis revealed that 44 (38.9%) blastocysts were euploid. Blastocysts with trophectoderm grades A, B, and C had euploidy rates of 71.43%, 60% and 19.67%, respectively (p≤0.05). CONCLUSION: Although the best trophectoderm morphology grades had higher euploidy rates, this indicator alone is not enough to warrant embryo genetic viability.

Causes of endometriosis and prevalent infertility in patients undergoing laparoscopy without achieving pregnancy.

BACKGROUND: Endometriosis is a disease with an unknown pathogenesis that can lead to infertility. Endometrial polyps, fibroids, and polycystic ovarian syndrome (PCOS) have relatively high frequency and are causes of infertility. We hypothesized a possible relationship between the presence of polyps, fibroids, and PCOS in infertile women with endometriosis who underwent laparoscopy and did not get pregnant, compared to women in the control group. METHODS: This study was a cross-sectional study of 1243 infertile patients (621 with endometriosis and 622 controls). Endometriosis, Body Mass Index (BMI), infertility duration, age, and smoking habits were analyzed in relation to the presence of endometrial polyps, fibroids, and PCOS. RESULTS: Polyps, 1.8 (95% CI 1.3-2.5); fibroids, 2.5 (95% CI 1.5-4.1); and PCOS, 1.0 (95% CI 0.6-1.6 were observed in the endometriosis group. A total of 285 patients (45.9%) were classified presenting endometriosis grades I and II, and 336 patients (54.1%) with grades III and IV. Our findings showed a significant association between the presence of fibroids in 129 women with endometriosis (20.8%), and in 69 (53.9%) with endometriosis grades III and IV (P=0:04). Among the 31 PCOS patients, 24 (77.4%) showed grades I and II (P<0.001). CONCLUSIONS: Endometriosis and infertility are associated with the presence of polyps and fibroids. Furthermore, associations between the presence of fibroids with endometriosis grades III and IV, and presence of PCOS with grades I and II were observed.

Aberrant telomerase expression in the endometrium of infertile women with deep endometriosis.

BACKGROUND AND AIMS: Considering the complex cellular and molecular mechanisms involved in endometriosis formation and progression and the similarities concerning the association of endometriosis with tumorigenesis and metastasis, we hypothesized a possible relationship between telomerase and the development/progression of endometriosis. The present study aimed to evaluate the expression of telomerase in the endometrium and peritoneal endometriotic lesions from women with endometriosis and controls. METHODS: A case-control study was performed comprising 25 infertile women with endometriosis and 44 fertile women without endometriosis as controls. Samples of endometrium and endometriotic peritoneal lesions of the same patient were harvested in the late luteal phase of the cycle. The expression of hTERT and GAPDH genes was measured by mRNA using qRT-PCR based on TaqMan methodology. Student t test was used to compare the values between the groups; p >0.05 was accepted as statistically significant. RESULTS: The mean expression of hTERT in the endometriosis group was significantly high when compared to the control group (1.24 ± 4.67 vs. 0.31 ± 1.10, p = 0.026). When the expression of hTERT was compared in relation to disease stage, the group of moderate/severe endometriosis showed increased expression in relation to control group (2.59 ± 7.35 vs. 0.31 ± 1.10, p = 0.026). Regarding endometriotic peritoneal lesions, only one 1/25 expressed hTERT mRNA. This patient had deep endometriosis. CONCLUSIONS: There was an association between the expression of telomerase (hTERT mRNA) and the genesis and progression of endometriosis.

Complex small supernumerary marker chromosome with a 15q/16p duplication: clinical implications.

BACKGROUND: Complex small supernumerary marker chromosomes (sSMCs) consist of chromosomal material derived from more than one chromosome and have been implicated in reproductive problems such as recurrent pregnancy loss. They may also be associated with congenital abnormalities in the offspring of carriers. Due to its genomic architecture, chromosome 15 is frequently associated with rearrangements and the formation of sSMCs. Recently, several different CNVs have been described at 16p11.2, suggesting that this region is prone to rearrangements. RESULTS: We detected the concomitant occurrence of partial trisomy 15q and 16p, due to a complex sSMC, in a 6-year-old girl with clinical phenotypic. The karyotype was analyzed by G and C banding, NOR staining, FISH and SNP array and defined as 47,XX,+der(15)t(15;16)(q13;p13.2)mat. The array assay revealed an unexpected complex sSMC containing material from chromosomes 15 and 16, due to an inherited maternal translocation (passed along over several generations). The patient's phenotype included microsomia, intellectual disability, speech delay, hearing impairment, dysphagia and other minor alterations. DISCUSSION: This is the first report on the concomitant occurrence of partial trisomy 15q and 16p. The wide range of phenotypes associated with complex sSMCs represents a challenge for genotype-phenotype correlation studies, accurate clinical assessment of patients and genetic counseling.

Variants in endothelial nitric oxide synthase (eNOS) gene in idiopathic infertile Brazilian men.

PURPOSE: In recent years, considerable concern has been expressed about the deleterious effects of reactive oxygen species (ROS) on sperm function, because ROS at high levels is potentially detrimental to sperm function and quality. Nitric oxide (NO) is a powerful anti-oxidant present in seminal plasma. The aim of the study was to analyze the distribution of the of endothelial nitric oxide synthase (eNOS) gene (T-786C, G894T, e 4a/b) polymorphisms in idiopathic infertile Brazilian men and evaluate the possible role of these polymorphisms in sperm count. METHODS: A case-control study was performed comprising 208 infertile men [n=74 with non-obstructive azoospermia and n=134 with severe oligozoospermia] and 201 fertile men as controls. Genotyping of eNOS polymorphisms was performed by real time (T-786C and G894T) and conventional PCR (4a/b). The results were analyzed statistically and a p-value<0.05 was considered significant. RESULTS: According to the sperm count, relatively similar eNOS polymorphism genotypes and allele frequencies were found among the groups. Combined genotypes of the eNOS polymorphisms did not identify a haplotype associated with idiopathic infertility, even when the patients were separated in non-obstructive azoospermia or severe oligozoospermia. CONCLUSION: In conclusion, the findings demonstrate that, in Brazilian population studied, genetic variations, T-786C, G894T, and e 4a/b, of the eNOS gene are not associated with male infertility.

TYK2 rs34536443 polymorphism is associated with a decreased susceptibility to endometriosis-related infertility.

INTRODUCTION: Tyrosine kinase 2 gene (TYK2) is part of the janus kinase (JAK) that binds to the type I interferon-α receptor (IFNAR) on the cell surface of IFN-producing cells, and have crucial importance in the etiology of autoimmune and inflammatory diseases. Many polymorphisms of the TYK2 gene have been identified, and recently, a number of case-control studies were conducted to investigate the association of these polymorphisms with autoimmune and inflammatory diseases, with conflicting results. Based on these observations, we hypothesized that the TYK2 polymorphisms (rs34536443, rs2304256, rs280523, rs12720270 and rs12720356) might be involved in the pathogenesis of endometriosis and/or infertility. METHODS: Genetic association study comprising 275 infertile women with endometriosis, 92 women with idiopathic infertility and 307 fertile women as controls. TYK2 polymorphisms were identified by TaqMan PCR. Genotype distribution, allele frequency and haplotype analysis of the TYK2 polymorphisms were performed. A p-value <0.05 was considered significant. RESULTS: Single-marker analysis revealed that TYK2 rs34536443 was significantly associated with protection against endometriosis-related infertility, especially in moderate/severe disease (p = 0.002; OR = 0.24, 95% IC = 0.09-0.62). No difference was found considering the infertile group without endometriosis. No associations were found considering rs2304256, rs280523, rs12720270 and rs12720356 either for endometriosis-related infertility group or idiopathic infertility group. Haplotype analysis of five TYK2 polymorphisms identified a haplotype "CTATG" associated with protection against endometriosis-related infertility, especially in moderate/severe disease (p = 0.027). CONCLUSION: This is the first study to report an association between TYK2 polymorphisms and endometriosis and/or infertility. These findings require replication in other populations but suggest the TYK2 rs34536443 polymorphisms and "CTATG" haplotype can be associated with a decreased susceptibility to endometriosis-related infertility in Brazilian women.