Implication of FSHB rs10835638 variant in endometriosis in Brazilian women.

OBJECTIVE: The follicle-stimulating hormone subunit beta gene rs10835638 variant (c.-211G>T) may have detrimental effects on fertility and protective effects against endometriosis. A case-control analysis was performed, aiming to investigate the possible relationship between this variant and the development and/or progression of endometriosis. METHODS: This study included 326 women with endometriosis and 482 controls without endometriosis, both confirmed by inspection of the pelvic cavity during surgery. Genotyping was performed using a TaqMan real-time polymerase chain reaction assay. Genotype and allele frequencies and genetic models were compared between the groups. RESULTS: The genotype and allele frequencies of the rs10835638 variant did not differ between women with and those without endometriosis. Subdividing the endometriosis group into fertile and infertile groups did not result in a significant difference in these frequencies. However, the subgroup with minimal/mild endometriosis had a higher frequency of the GT genotype than the Control Group, regardless of fertility. The T allele was significantly more common in women with minimal/mild endometriosis than in the Control Group in the recessive model. CONCLUSION: The T allele is associated with the development of minimal/mild endometriosis in Brazilian women.

Live birth after single euploid frozen embryo transfer in a 39-year-old woman with high-grade mosaic Turner syndrome.

OBJECTIVE: To describe the reproductive and obstetric outcomes of an intracytoplasmic sperm injection cycle with preimplantation genetic testing for aneuploidy in an advanced reproductive-age woman with high-grade mosaic Turner syndrome. METHODS: Case report of a 39-year-old woman diagnosed with mosaic Turner Syndrome 45,X[90]/46,XX[10] karyotype who underwent in vitro fertilization treatment with blastocyst trophectoderm biopsy for preimplantation genetic testing using next-generation sequencing. RESULT(S): Two of the four blastocysts biopsied were euploid. The patient achieved ongoing pregnancy after the first single euploid frozen embryo transfer, followed by the birth of a healthy child. CONCLUSION: Autologous intracytoplasmic sperm injection cycles can be considered in a select group of advanced reproductive-age women diagnosed with high-grade mosaic Turner syndrome.

Involvement of SYCP2L and TDRD3 gene variants on ovarian reserve and reproductive outcomes: a cross-sectional study.

OBJECTIVE: Single nucleotide variants have been implicated in the response to fertility treatment and a pharmacogenomic approach may help to customize therapy based on patient genome. We aimed to evaluate the effect, individual and combined, of SYCP2L (rs2153157:G>A) and TDRD3 (rs4886238:G>A) variants on ovarian reserve, response to controlled ovarian stimulation (COS) and reproductive outcomes of women undergoing in vitro fertilization (IVF) treatment. METHODS: This cross-sectional study included 149 normoovulatory women undergoing IVF. Genotyping was performed using the TaqMan real-time polymerase chain reaction method. Clinical parameters and reproductive outcomes were compared according to the genotypes of the variants studied. RESULTS: Considering ovarian reserve, there were no significant differences among SYCP2L or TDRD3 genotypes in terms of FSH levels or AFC; however, AMH levels were significantly different in carriers of both variants. Regarding the SYCP2L rs2153157:G>A variant, lower AMH levels were observed in women carrying an AA genotype compared to women carrying a heterozygous genotype (p=0.01). Considering the TDRD3 rs4886238:G>A variant, women carrying an AA genotype presented higher AMH levels than carriers of GG and GA genotypes (p=0.025). Nevertheless, no difference was found regarding response to COS or reproductive outcomes. Considering the combined effect of the variants, women carrying the heterozygous genotype of both variants presented statistically increased AMH levels compared to SYCP2L rs2153157 AA genotype carriers and TDRD3 rs4886238 GG genotype carriers (p=0.042). CONCLUSIONS: Individually and combined, the SYCP2L rs2153157 and TDRD3 rs4886238 variants have an effect on AMH level.

Potential Epidemic Vulnerability and Socioepidemiological Profile of SARS-CoV2 in the Brazilian Northeast Region.

BACKGROUND: COVID-19 is a significant public health problem that can have a negative impact, especially in vulnerable regions. OBJECTIVE: This study aimed to provide evidence that could positively influence coping with COVID-19 based on the relationship between the potential epidemic vulnerability index (PEVI) and socioepidemiological variables. This could be used as a decision-making tool for the planning of preventive initiatives in regions with relevant vulnerability indices for the spread of SARS-CoV-2. METHODOLOGY: We performed a cross-sectional study, with the analysis of the population characteristics of COVID-19 cases associated with neighborhoods' PEVIs in the conurbation region of Crajubar, northeastern Brazil, through the mapping of socioeconomic-demographic factors and spatial autocorrelation. RESULTS: The PEVI distribution indicated low vulnerability in areas with high real estate and commercial value; as communities moved away from these areas, the vulnerability levels increased. As for the number of cases, three of the five neighborhoods with a high-high autocorrelation, and some other neighborhoods showed a bivariate spatial correlation with a low-low PEVI but also high-low with indicators that make up the PEVI, representing areas that could be protected by public health measures to prevent increases in COVID-19 cases. CONCLUSIONS: The impact of the PEVI revealed areas that could be targeted by public policies to decrease the occurrence of COVID-19.

History and legal aspects of bone marrow donor banks in Brazil

INTRODUCTION: Bone marrow transplants primarily depend on people who previously registered to be donors. From then on, the search for compatibility between donor and recipient begins. OBJECTIVE: To describe the historical landmarks and the legal apparatus of bone marrow donor banks in Brazil based on an integrative review. METHODS: LILACS database and PubMed and SciELO journals were used. The term bone marrow transplantation was the descriptor. Eligibility criteria were: articles with the theme of Bone Marrow Transplantation (BMT) and studies carried out on the national territory. RESULTS: A total of 88,855 articles were identified, among which 185 met the eligibility criteria. After they were thoroughly read, 14 articles were selected. The studies pointed out fragments that dealt with important historical landmarks for the establishment of bone marrow transplantation as a conventional treatment for oncohematological diseases. CONCLUSION: The use of BMT has a history of more than thirty years in Brazil. However, none of the articles identified specifically addresses the historical content of bone marrow transplantation.

Implication of FSHB rs10835638 variant in endometriosis in Brazilian women

ABSTRACT Objective The follicle-stimulating hormone subunit beta gene rs10835638 variant (c.-211G>T) may have detrimental effects on fertility and protective effects against endometriosis. A case-control analysis was performed, aiming to investigate the possible relationship between this variant and the development and/or progression of endometriosis. Methods This study included 326 women with endometriosis and 482 controls without endometriosis, both confirmed by inspection of the pelvic cavity during surgery. Genotyping was performed using a TaqMan real-time polymerase chain reaction assay. Genotype and allele frequencies and genetic models were compared between the groups. Results The genotype and allele frequencies of the rs10835638 variant did not differ between women with and those without endometriosis. Subdividing the endometriosis group into fertile and infertile groups did not result in a significant difference in these frequencies. However, the subgroup with minimal/mild endometriosis had a higher frequency of the GT genotype than the Control Group, regardless of fertility. The T allele was significantly more common in women with minimal/mild endometriosis than in the Control Group in the recessive model. Conclusion The T allele is associated with the development of minimal/mild endometriosis in Brazilian women.

Comparative metabolomic profiling of women undergoing in vitro fertilization procedures reveals potential infertility-related biomarkers in follicular fluid.

Infertility is a worldwide concern, affecting one in six couples throughout their reproductive period. Therefore, enhancing the clinical tools available to identify the causes of infertility may save time, money, and emotional distress for the involved parties. This study aims to annotate potential biomarkers in follicular fluid that are negatively affecting pregnancy outcomes in women suffering infertility-related diseases such as endometriosis, tuboperitoneal factor, uterine factor, and unexplained infertility, using a metabolomics approach through high-resolution mass spectrometry. Follicular fluid samples collected from women who have the abovementioned diseases and managed to become pregnant after in vitro fertilization procedures [control group (CT)] were metabolically compared with those from women who suffer from the same diseases and could not get pregnant after the same treatment [infertile group (IF)]. Mass spectrometry analysis indicated 10 statistically relevant differential metabolites in the IF group, including phosphatidic acids, phosphatidylethanolamines, phosphatidylcholines, phosphatidylinositol, glucosylceramides, and 1-hydroxyvitamin D3 3-D-glucopyranoside. These metabolites are associated with cell signaling, cell proliferation, inflammation, oncogenesis, and apoptosis, and linked to infertility problems. Our results indicate that understanding the IF's metabolic profile may result in a faster and more assertive female infertility diagnosis, lowering the costs, and increasing the probability of a positive pregnancy outcome.

Effect of thyroid function on assisted reproduction outcomes in euthyroid infertile women: A single center retrospective data analysis and a systematic review and meta-analysis.

Background: The influence of thyroid-stimulating hormone (TSH) on gestational outcomes have been studied and checked whether differing TSH levels are relevant on human reproduction outcomes. International guidelines recommend TSH values <2.5 mIU/L in women trying to conceive, since values above this level are related to a higher frequency of adverse reproductive outcomes. This study aimed to evaluate whether TSH values correlate with different gestational outcomes in euthyroid infertile women without autoimmune thyroid disease. Methods: A retrospective cohort study was conducted involving 256 women who underwent in vitro fertilization (IVF) treatment. The participants were divided into two groups: TSH 0.5-2.49 mIU/L (n=211) and TSH 2.5-4.5 mIU/L (n=45). The clinical data, hormonal profiles and reproductive outcomes were compared between groups. Additionally, a systematic review with meta-analysis following the PRISMA protocol was carried out in PubMed/MEDLINE, EMBASE, and SciELO, with no time or language restrictions, for articles comparing TSH groups named "low TSH" (<2,5 mIU/L) and "high TSH" (≥2.5 mIU/L). A meta-analysis of proportions was performed with pooled estimates expressed as relative risk (RR) of events and a random effects model. Results: Age, BMI, free thyroxine levels (FT4) hormonal profile and IVF outcomes were not different between groups, neither gestational outcomes (p=0.982). Also, no difference was observed when the TSH and FT4 levels were compared between patients with positive or negative gestational outcomes (p=0.27 and p=0.376). Regarding the systematic review with meta-analysis, 17 studies from 2006 to 2022 were included, and added by this original retrospective research comprising 13.247 women undergoing IVF. When comparing the proportions of clinical pregnancy between the TSH groups, no significant difference was found (RR 0.93, 95% CI 0.80-1.08), with high between studies heterogeneity (I²: 87%; τ2: 0.0544; p<0.01). The number of deliveries was not significantly different between groups, despite a trend towards higher frequency in the high-TSH group (RR 0.96, 95% CI 0.90-1.02). Conclusion: Variation in TSH levels within the normal range was not associated with pregnancy and delivery rates in women, without autoimmune thyroid disease, who underwent IVF treatment. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD 42022306967.

Impact of blood levels of progesterone on the day of ovulation onset on clinical, laboratory and reproductive parameters of young patients undergoing assisted reproduction: a cross-sectional study.

OBJECTIVE: To assess whether there is an association between the level of progesterone on the day of administration of human chorionic gonadotropin and clinical and laboratory characteristics, in addition to the results of in vitro fertilization of patients with a good prognosis. METHODS: A cross-sectional study comprising 103 women who underwent intracytoplasmic sperm injection treatment, between November 2009 and May 2015, aged ≤35 years, with no comorbidities, with fresh embryo transfer. Data were collected from patient medical records. RESULTS: There was a weak positive correlation between the level of progesterone on the day of human chorionic gonadotropin and the number of follicles larger than 14mm (ß=0.02, p=0.001), retrieved oocytes (ß=0.01, p=0.01) and oocytes in metaphase II (MII) (ß=0.02, p=0.02); that is, the increase in progesterone level has a slight association with increased values of these variables. Body mass index was inversely correlated with progesterone level on the day of human chorionic gonadotropin (ß=-0.01, p=0.02). No association was found between the level of progesterone on the day of human chorionic gonadotropin and the protocols used for controlled ovarian stimulation, quality of transferred embryos and the pregnancy rate. CONCLUSION: There is an association between the value of progesterone on the day of human chorionic gonadotropin administration with body mass index, number of follicles larger than 14mm, number of retrieved oocytes and oocytes in metaphase II. Unlike embryo quality and pregnancy rate, which do not have a statistically significant relation with this value in the population studied.

FMR1 alleles in women with idiopathic infertility / Alelos do gene FMR1 em mulheres com infertilidade idiopática

INTRODUCTION: The frequency of the premutation alleles of the FMR1 gene varies from 1:100 to 1:260 Israeli, Canadian, Finnish and American women, but it is unknown in Brazil. Premutation carriers may have reduced reproductive age and are at risk of transmitting the expanded allele to their offspring, and consequently fragile X syndrome. OBJECTIVE: To observe the distribution range of the FMR1 gene alleles in a population of women with idiopathic infertility, without symptoms of premature ovarian insufficiency. METHODS: The presence of premutation in FMR1 was assessed by conventional PCR, agarose, and acrylamide gel and analysis of fragments in capillary electrophoresis. Lymphocyte DNA obtained from 283 women undergoing infertility treatment was analyzed. RESULTS: 169 patients had the normal heterozygous allele (59.7%), 114 had the normal homozygous allele (40.6%) and no patient had the premutation. Premature ovarian insufficiency is seen in 20 to 30% of women with the permutated allele. Thus, the condition can be asymptomatic in a large part of the premutation carriers. Brazil has a diverse population and, therefore, the allele frequencies of many gene variants are unknown. Previous Brazilian studies have shown a low frequency of the premutation allele in different patient cohorts. Corroborating these articles, the results demonstrated that the frequency of the premutation allele is low in the infertile women population studied. CONCLUSION: Tracking the size of the FMR1 gene alleles allows the expansion of knowledge about the frequency of risk alleles associated with genetic diseases in the Brazilian population.

INTRODUÇÃO: A frequência dos alelos pré-mutados do gene FMR1 varia de 1:100 e 1:260 mulheres israelenses, canadenses, finlandesas e americanas, mas é desconhecida no Brasil. Portadoras da pré-mutação podem apresentar redução da idade reprodutiva e possuem risco de transmissão do alelo expandido para a prole, e consequentemente a Síndrome do X frágil. OBJETIVO: Observar a faixa de distribuição dos alelos do gene FMR1 em uma população de mulheres com infertilidade idiopática, sem sintomas de insuficiência ovariana prematura. MÉTODOS: A presença da pré-mutação em FMR1 foi avaliada por PCR convencional, gel de agarose e acrilamida e análise de fragmentos em eletroforese capilar. Analisou-se DNA de linfócitos obtidos de 283 mulheres em tratamento de infertilidade. RESULTADOS: Foi observado que 169 pacientes apresentam o alelo heterozigoto normal (59,7%), 114 apresentam o alelo homozigoto normal (40,6%) e nenhuma paciente apresentou a pré-mutação. A insuficiência ovariana prematura é observada em 20 a 30% das mulheres portadoras do alelo pré-mutado. Assim, a presença de um alelo pré-mutado pode ser assintomática em grande parte dos casos. O Brasil possui uma população diversificada e, portanto, as frequências alélicas de muitas variantes gênicas são desconhecidas. Estudos brasileiros anteriores mostraram uma baixa frequência do alelo pré-mutado em diferentes coortes de pacientes. Corroborando estes autores, os resultados demonstram que frequência do alelo pré-mutado é baixa na população de mulheres inférteis estudada. CONCLUSÃO: O rastreamento do tamanho dos alelos do gene FMR1 permite ampliar o conhecimento sobre a frequência dos alelos de risco para doenças genética na população brasileira.

Impact of blood levels of progesterone on the day of ovulation onset on clinical, laboratory and reproductive parameters of young patients undergoing assisted reproduction: a cross-sectional study

ABSTRACT Objective: To assess whether there is an association between the level of progesterone on the day of administration of human chorionic gonadotropin and clinical and laboratory characteristics, in addition to the results of in vitro fertilization of patients with a good prognosis. Methods: A cross-sectional study comprising 103 women who underwent intracytoplasmic sperm injection treatment, between November 2009 and May 2015, aged ≤35 years, with no comorbidities, with fresh embryo transfer. Data were collected from patient medical records. Results: There was a weak positive correlation between the level of progesterone on the day of human chorionic gonadotropin and the number of follicles larger than 14mm (ß=0.02, p=0.001), retrieved oocytes (ß=0.01, p=0.01) and oocytes in metaphase II (MII) (ß=0.02, p=0.02); that is, the increase in progesterone level has a slight association with increased values of these variables. Body mass index was inversely correlated with progesterone level on the day of human chorionic gonadotropin (ß=-0.01, p=0.02). No association was found between the level of progesterone on the day of human chorionic gonadotropin and the protocols used for controlled ovarian stimulation, quality of transferred embryos and the pregnancy rate. Conclusion: There is an association between the value of progesterone on the day of human chorionic gonadotropin administration with body mass index, number of follicles larger than 14mm, number of retrieved oocytes and oocytes in metaphase II. Unlike embryo quality and pregnancy rate, which do not have a statistically significant relation with this value in the population studied.

Effects of FSHR and FSHB Variants on Hormonal Profile and Reproductive Outcomes of Infertile Women With Endometriosis.

Background: Single nucleotide variants (SNVs) FSHB:c.-211G>T, FSHR:c.919G>A, and FSHR:c.2039G>A were reported to be associated with the variability in FSH and LH levels, and in vitro fertilization (IVF) outcomes. In this study, we aimed to evaluate the effects of FSHB:c.-211G>T, FSHR:c.919G>A, and FSHR:c.2039G>A variants, alone and combined, on the hormonal profile and reproduction outcomes of women with endometriosis. Methods: A cross-sectional study was performed comprising 213 infertile Brazilian women with endometriosis who underwent IVF treatment. Genotyping was performed using TaqMan real-time PCR. Variables were compared according to the genotypes of each variant and genetic models, and the combined effects of the SNVs were evaluated using the multifactorial dimensionality reduction method. Results: FSHB:c.-211G>T affected LH levels in women with overall endometriosis and minimal/mild disease. FSHR:c.919G>A affected FSH levels in women with overall endometriosis and the number of oocytes retrieved in those with moderate/severe endometriosis. Moreover, the FSHR:c.2039G>A affected FSH levels in women with overall endometriosis, LH levels and total amount of rFSH in those with minimal/mild disease, and number of follicles and number of oocytes retrieved in those with moderate/severe endometriosis. No effect on hormone profile or reproductive outcomes was observed when the genotypes were combined. Conclusions: Variants of the FSHB and FSHR genes separately interfered with the hormonal profiles and IVF outcomes of women with endometriosis.

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.

Are ovarian reserve tests reliable in predicting ovarian response? Results from a prospective, cross-sectional, single-center analysis.

OBJETIVE: Several biomarkers of ovarian reserve have been proposed as possible predictors of the response to controlled ovarian stimulation (COS). We aimed to evaluate age, FSH, AMH, antral follicle count (AFC), and ovarian response prediction index (ORPI), as potential predictors of response to COS. METHODS: Cross-sectional study enrolling of 188 infertile women who underwent the first cycle of IVF/ICSI. AFC was evaluated; serum FSH and AMH levels were measured by ELISA. ORPI was calculated as AMH x AFC/patient´s age. RESULTS: As expected, hypo-responder group had less retrieved oocytes, MII, and embryos compared to the good responders. The hyper-response patients were younger, with lower FSH, increased AMH, AFC, and ORPI values. Regarding the assessment of the predictive capacity of ovarian reserve tests, none of them individually or combined showed a good predictive capacity for hypo-response. With respect to the hyper-responder group, individually AMH was the best predictor, while in the multivariable model, ORPI demonstrated the best predictive capacity. Furthermore, patients with serum AMH < 2.09 ng/mL (p25) had fewer AFC than patients with higher AMH values. CONCLUSIONS: Our findings suggest that none of the ovarian reserve tests showed a good predictive capacity for hypo-response, while the ORPI was the strongest predictor of hyper-response in normovulatory infertile women.

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.

Paraoxonase single nucleotide variants show associations with polycystic ovary syndrome: a meta-analysis.

BACKGROUND: Etiology of polycystic ovary syndrome (PCOS) is attributed to genetic and environmental factors. One environmental factor is oxidative stress. Paraoxonase 1 (PON1) is an antioxidant high-density lipoprotein-associated enzyme encoded by the PON1 gene. The PON1 gene has been implicated in the risk for PCOS, the influence of which appears to come from single nucleotide variants (SNVs) at multiple genetic loci. However, association study reports have been inconsistent which compels a meta-analysis to obtain more precise estimates. METHODS: From 12 publications, extracted genotype data were used in two genetic procedures. First, linkage disequilibrium (LD) was used to group eight PON SNVs into three: LD1, LD2 and LD3. Second, frequencies of the variant (var), wild-type (wt) and heterozygous (het) genotypes were used for genetic modeling (allele-genotype for LD1 and standard for LD2 and LD3). Risk associations were expressed in terms of pooled odds ratios (ORs), 95% confidence intervals (CIs) and Pa-values. Evidence was considered strong when significance was high (Pa < 0.0001) and heterogeneity absent (I2 = 0%). Pooled effects were subjected to modifier (power), subgroup (Asian/Caucasian), outlier, sensitivity and publication bias treatments. Multiple comparisons were Bonferroni-corrected. RESULTS: This meta-analysis generated 11 significant outcomes, five in LD1, six in LD2 and none in LD3. All six LD2 outcomes did not survive the Bonferroni-correction but two of the five in LD1 did. These two core LD1 findings conferred greater odds of PCOS to the var allele in the highly significant (Pa < 0.0001) overall (OR 1.44, 95% CI 1.24-1.67) and Asian (OR 1.41, 95% CI 1.20-1.65) outcomes. Of these two core outcomes, the Asian effect was homogeneous (I2 = 0%) but not the overall (I2 = 29%). CONCLUSIONS: Of the eight PON SNVs examined, two (rs854560 and rs662) were associated with PCOS risk. These 1.4-fold increased risk effects rendered Asians susceptible to PCOS. High statistical power, high significance, zero to low-level heterogeneity, robustness and lack of bias in the core outcomes underpinned the strong evidence for association.

Novel variants in POLH and TREM2 genes associated with a complex phenotype of xeroderma pigmentosum variant type and early-onset dementia.

BACKGROUND: Xeroderma pigmentosum (XP) is a rare, genetically heterogeneous, autosomal recessive disorder caused by defects in the genes involved in repairing DNA damaged by ultraviolet radiation. These defects lead to a propensity to develop skin cancer at early ages as a hallmark, and progressive neurological degeneration can be observed in around 25% of patients. Eight clinically heterogeneous groups have been identified so far (XPA to XPG and XPV). Xeroderma pigmentosum variant type (XPV) is associated with pathogenic variants in POLH on chromosome 6, and no neurological dysfunction has been seen in these cases. However, on the same chromosome, it has been shown that TREM2 is associated with some types of dementia, particularly in patients with a behavioral variant frontotemporal phenotype. METHODS: Gene mutational analysis was performed by whole-exome sequencing. RESULTS: We report a case of a Caucasian woman with XP that developed behavioral and cognitive impairment at age 37. Whole-exome sequencing identified novel homozygous variants in POLH c.638C>G (p.Ser213*) and TREM2 c.154C>T (p.Arg52Cys), classifying the patient as XPV and suggesting that her frontotemporal dementia phenotype could be related to the variant in TREM2. CONCLUSION: This paper describes a rare case of a patient with two novel variants in the same chromosome associated with XPV and early-onset dementia.

BIRC5/Survivin Expression as a Non-Invasive Biomarker of Endometriosis.

The etiology of endometriosis is highly complex, and although it is a benign disease, it has several biological behaviors similar to malignant lesions, including cell invasion, neo-angiogenesis, and decreased apoptosis. Survivin is a protein encoded by the BIRC5 gene that plays a role in cell division by inhibiting apoptosis and regulating the process of mitosis in embryonic and cancer cells. Therefore, we aimed to evaluate the expression of BIRC5 in samples of peripheral blood of women with and without endometriosis. This study comprised of 40 women with endometriosis and 10 healthy women as controls. Peripheral blood samples were collected in the three phases of the menstrual cycle (follicular, ovulatory, and luteal). The expression of the BIRC5 gene was evaluated by RT-qPCR using the TaqMan methodology. The BIRC5 expression was significantly higher in all phases of the menstrual cycle in women with endometriosis, regardless of the disease stage. The accuracy of BIRC5 expression in the peripheral blood for the diagnosis endometriosis presented AUC of 0.887 (p < 0.001), with 97.2% of sensitivity and specificity of 65.5% considering the overall endometriosis group. Regarding the minimal/mild endometriosis group, the AUC presented a value of 0.925 (p < 0.001), with 100% of sensitivity and 79.3% of specificity, whereas in the moderate/severe endometriosis group the AUC was 0.868 (p < 0.001), with a sensitivity of 95.8% and specificity of 65.5%. These findings suggest that the expression of BIRC5 may be a potential noninvasive biomarker for the diagnosis of endometriosis.