Endometriosis in infertile women: an observational and comparative study of quality of life, anxiety, and depression.

BACKGROUND: A women's chances of getting pregnant decreases in cases of infertility, which may have several clinical etiologies. The prevalence of infertility is estimated as 10-15% worldwide. One of the causes of infertility is endometriosis, defined as the presence of an endometrial gland and/or stroma outside the uterus, inducing a chronic inflammatory reaction. Thus, infertility and endometriosis are diagnoses that significantly affect women's mental health. This study accessed and compared the levels of depression, anxiety, and quality of life in infertile women with and without endometriosis. METHODS: was an observational and cross-sectional study which included 201 infertile women, 81 of whom were also diagnosed with endometriosis. The STROBE Guidelines was used. The data were collected using validated scales: Hamilton D Questionnaire, Beck Depression Inventory, and Fertility Quality of Life Questionnaire; The data were collected at the Ideia Fertil Institute (Santo Andre, Brazil), between February 28 and June 8, 2019. RESULTS: the infertile women with endometriosis reported higher presence of depressive symptoms and a lower quality of life compared to women with infertility only. Similar presence of anxiety symptoms was observed regardless of being diagnosed with endometriosis. Women with infertility and endometriosis presented lower levels in quality-of-life domains when compared to women with infertility only - Mind and Body (58.33 × 79.17, p < 0.001), Relational (75 × 81.25, p = 0.009), Social (66.67 × 77.08, p = 0.001), Emotional (50.62 × 67.43, p < 0.001). CONCLUSION: the findings indicate the need for increased psychosocial support care for women suffering from infertility and endometriosis to assist them in maintaining and managing their own mental health and achieving their reproductive goals.

Oral health-related quality of life in patients aged 8 to 19 years with cleft lip and palate: a systematic review and meta-analysis.

BACKGROUND: Cleft lip and palate (CLP) is the most common facial birth defect worldwide and causes morphological, aesthetic, and functional problems with psychosocial implications for an individual's life and well-being. The present systematic review and meta-analysis assessed whether the treatment of CLP impacts the oral health-related quality of life (OHRQoL) in children and adolescents in comparison to healthy controls. METHODS: We searched MEDLINE/PubMed, EMBASE, and PsycINFO databases using terms related to CLP, and included articles until August 2023. Observational comparison studies that assessed OHRQoL in non-syndromic CLP patients aged 8-19 years with validated scales designed to such aim or scales capable to identify aspects related to oral health compared to healthy controls were included. We used the ROBINS-I tool for risk of bias assessment. A meta-analysis of continuous variables was performed using inverse variance for pooling estimates, Standardized Mean Difference (SMD) as a summary measure, with random effects model. Heterogeneity was estimated by the I2 statistics. Sensitivity analyses included subgrouping based on the scale, risk of bias and scale domains. Meta-regression was performed under a mixed-effects model considering the variables type of scale, scale domains and risk of bias. RESULTS: Fourteen studies were included comprising 1,185 patients with CLP and 1,558 healthy controls. The direction of the effect of OHRQoL favoured the healthy group (-0.92; 95% CI:-1,55;-0,10) and I2 = 95%. After removing three studies, I2 dropped to 80%. Meta-regression showed no influence on risk of bias (p = 0.2240) but influence of scale type (p = 0.0375) and scale domains (p < 0.001). The subgroup analysis indicated that the CPQ and COHIP scales presented very discrepant SMD values, despite pointing to the same effect direction. In contrast, the OHIP scale showed a non-significant difference between cases and controls, with estimates much lower than the other two scales. Results also suggest that OHRQoL associated with oral functionality and social well-being is more influential on outcomes than emotional well-being. CONCLUSION: The global OHRQoL is slightly worst in the CLP patients than control group. The difference between OHRQoL was mainly detected through OHIP. The most affected domains are functional, emotional and social. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022336956.

Prevention of HIV transmission with sperm washing within fertile serodiscordant couples undergoing non-stimulated intrauterine insemination.

The purpose of this prospective non-randomized study was to study the effectiveness of semen washing followed by intrauterine insemination (IUI) in Human Immune Deficiency Virus (HIV)-discordant couples in which the male partner was infected, in preventing HIV transmission to uninfected partner and offspring. The study was performed in a private assisted reproductive center specialized in couples with infectious diseases and enrolled sixty-nine fertile couples in which male partner tested positive for HIV, seeking for reproductive treatment. Triple sperm washing followed by viral RNA purification and real-time polymerase chain reaction was performed prior to IUI intervention. HIV transmission to female partner and newborns, and clinical pregnancy rate were the main outcome measures. A total of 180 IUI treatment cycles were performed in 69 couples. There were 16 clinical pregnancies (clinical pregnancy rate/cycle 9.0%, clinical pregnancy rate/patient 23.2%), one of which resulted in miscarriage (6.3%). No seroconversion was detected in the 69 women treated with sperm washing followed by IUI or in any of the newborns (tested at birth and at 3 months of age). Sperm washing followed by IUI is a safe and effective treatment option for serodiscordant couples wishing to conceive and to prevent HIV virus transmission to the mothers and newborns.

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.

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.

Body fat distribution influences ART outcomes.

Body mass index (BMI) is the widely used method to evaluate obesity, but it cannot differentiate lean from fat mass neither mass distribution. Other methods have been proposed for this evaluation, as waist and hip circumferences (WC, HC) and ratio (WHR) and body fat analysis by bioimpedance (BF%), but they have not been applied to evaluate assisted reproduction (ART) outcomes. The present study aims at determining whether body composition and adipose tissue distribution are better than BMI on ART outcomes. Analysis was performed through five anthropometric measurements of 788 women submitted to controlled ovarian hyperstimulation and in vitro fertilization techniques. The increase of body fat, independently of the measurement method, was associated to worse reproductive results. However, a surprising finding was that eutrophic women with WC lower than 80 cm showed gestation rates two times superior (38.9% versus 14.3%) when compared to eutrophic women with WC larger than 80 cm (p = .002). Furthermore, obese women with WHR higher than 0.85 showed worse ART results, considering oocytes retrieved, mature oocytes and fertilization when compared to those with WHR lower than 0.85. As a conclusion, it was observed that the body fat distribution, especially WC, was more relevant than BMI to predict ART outcomes.

Do assisted reproduction outcomes differ according to aetiology of obstructive azoospermia?

Azoospermia is defined as absence of spermatozoa and may be secondary to blocked seminal ducts, known as obstructive azoospermia. Semen quality may be impaired due to factors such as sperm cell DNA fragmentation and presence of antisperm antibodies. The objective of this article was to investigate potential differences in outcomes of in vitro fertilisation and intracytoplasmic sperm injection between groups with different obstruction aetiology, as well as between the use of different techniques and sperm cells of different origins. Retrospective, multi-centre analysis of 621 first cycles was carried out between 2008 and 2015: Group I, congenital obstruction, 45 patients and Group 2, vasectomy, 576 patients. Sperm cell retrieval was achieved in all cases. Results were similar for Group I and II fertilisation rates, 70% versus 66.85% (p = .786); pregnancy rates, 42.5% versus 41.46% (p = .896); and live birth rates, 29.73% versus 17.69% (p = .071). According to sperm cell origin (579 epididymal vs. 42 testicular), pregnancy rates, 41.47% versus 43.9% (p = .760); and live birth rates, 18.3% versus 27.78% (p = .163) had no difference. Fertilisation, pregnancy and live birth rates did not differ according to obstruction aetiology. Outcomes did not differ between groups according to sperm cell origin.

Association between vitamin D plasma concentrations and VDR gene variants and the risk of premature birth.

BACKGROUND: Premature birth is the main cause of mortality in children under 1 year, and vitamin D deficiency during gestation is associated with prematurity. The effects of vitamin D are mediated by its receptor, which is encoded by the VDR gene. VDR variants-such as single nucleotide variation (SNV)-are associated with increased risk of prematurity, but there are conflicting results. We evaluated serum vitamin D concentrations and the frequency of TaqI/A > G, BsmI/C > T, ApaI/C > A, and FokI/A > T VDR variants in mothers and preterm (PTN) and full-term (FTN) newborns. METHODS: We conducted a case-control study comprising 40 pairs of mothers and their PTNs (gestational age < 32 weeks and/or weight < 1500 g), and 92 pairs of mothers and FTNs as controls. Genotyping was performed by real-time PCR, and plasma vitamin D concentrations were measured by electrochemiluminescence. RESULTS: Vitamin D levels were significantly lower in PTN mothers. Genotypes TaqI/GG and BsmI/TT, and haplotypes AAG (TaqI/A-ApaI/A-FokI/G) and GCA (TaqI/G-ApaI/C-FokI/A) were significantly more frequent in PTN mothers, and genotypes TaqI/AG, ApaI/AA, and FokI/AG resulted in significantly lower vitamin D levels. Genotypes BsmI/TT and ApaI/AA were associated with vitamin D deficiency and 2.36 and 7.99 times greater likelihood of PTB, respectively. Vitamin D levels were also lower in PTNs, although it was not statistically significant. Genotypes BsmI/TT, ApaI/AA, and FokI/GG, and haplotype GAG (TaqI/G-ApaI/A-FokI/G) were significantly more frequent in PTNs. Those with FokI/GG genotypes had significantly lower vitamin D levels. CONCLUSIONS: VDR variants contribute to variations in vitamin D concentrations and the increased risk of prematurity.

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.

Access to public health services and integral care for women during the puerperal gravid period period in Ceará, Brazil.

BACKGROUND: Over time, the Brazilian health system, a growing country, has been developing to ensure good accessibility to health goods and services. This development is focusing on the principle of universality of access and completeness of health care. In this context, we aimed to evaluate the completeness of care and universality of access for women in their pregnancy and puerperal period in Ceará, Brazil. METHODS: A descriptive, cross-sectional study based on a quantitative approach, using information collected from the database of the regulation system of the state of Ceará and data from the Prenatal Monitoring System. The research population comprised of 1701 women who delivered a baby in an obstetric reference unit in the Health Macro-Region of Cariri, Ceará, Brazil from January to December 2015. RESULTS: There was a high rate of cesarean delivery (49.7%) and a high waiting time for access to high-risk delivery (32.6%) and neonatal intensive care unit (72.9%). There was also a low percentage (41.1%) of pregnant women undergoing an adequate number of prenatal consultations, dental care (20%), educational activities (15%), visits to the maternity ward (0.1%), laboratory tests of the third trimester (29.2%) and puerperal consultation (37.9%). CONCLUSIONS: It was concluded that the Maternal and Child Health Policy, especially the Rede Cegonha, which is still under development, does not ensure access and completeness of care for women during the prenatal, delivery, and puerperal periods, thus violating their reproductive rights. The results of this study allow a critical analysis by the academia and health managers in search of strategies to improve the services of Rede Cegonha in Brazil.

Association of BMP15 and GDF9 variants to premature ovarian insufficiency.

PURPOSE: To identify genetic variation associated to premature ovarian insufficiency (POI). METHODS: A total of 74 women with POI (group POI), 45 women with increased FSH levels (group high FSH), and 88 controls (non-POI) were studied. Genotyping of BMP15:c.-9C>G (rs3810682), BMP15:c.328+905A>G (rs3897937), and BMP15:c.852C>T (rs17003221); and GDF9:c.134-694G>A (rs4705974), GDF9:c.-31-951G>A (rs11748063), GDF9:c.-152G>C (rs30177), and GDF9:g.1073C>T (rs803224) was performed by the TaqMan methodology. Chi-square and Fisher's exact tests were performed to evaluate the distribution of genotypes, alleles, odds ratio, and the Hardy-Weinberg equilibrium of each variation. Haplotype analysis was performed for each gene considering the case and control groups. Bonferroni's correction was applied to chi-square and Fisher's exact test data, and p values < 0.007 for genotypes and alleles and < 0.006 for haplotypes were considered significant. RESULTS: It was observed a statistically significant difference in genotype distribution of BMP15:c.852C>T between group POI and controls (p < 0.001). TT and TC genotypes were more frequently observed in group POI. Genotype distribution in case group POI, however, was not in the Hardy-Weinberg equilibrium, due to the increased number of heterozygotes in the sample. Concerning GDF9, no association was found among the studied genetic variants and POI or high FSH groups. CONCLUSION: It is concluded from the present study that the genotypes CT and TT from BMP15:c.852C>T variation may be risk factors for the development of POI.

The role of Kisspeptin levels in polycystic ovary syndrome: a systematic review and meta-analysis.

PURPOSE: Polycystic ovarian syndrome (PCOS) is a complex and not fully elucidated pathology. This prevalent endocrinopathy affects patients in reproductive age, impacts on estrogen-dependent diseases, as well as in infertility. In this context, Kisspeptin (KP) may be considered a potential biomarker for PCOS diagnosis and follow-up. Here, we aimed to verify the levels of KP in obese and non-obese patients with PCOS, their relationship with other hormones, in comparison to healthy controls. METHODS: A systematic review and meta-analysis were performed according to the PRISMA guidelines. We searched MEDLINE, EMBASE, PsycINFO, Global Health, The Cochrane Library, Health Technology Assessment Database, and Web of Science for eligible studies. A random effects model meta-analysis of standardized mean difference (SMD) was conducted and the I2 was used to assess heterogeneity. Meta-regression was conducted through mixed-effects model. RESULTS: A total of 12 studies were included, comprising 660 PCOS patients and 600 controls. The KP levels were lower in the control group (0.76: 0.17-1.35; 95% CI). In the subgroup analyses, patients were divided in non-overweight/obese (BMI < 25) and overweight/obese (BMI ≥ 25) groups. The meta-regression revealed a difference between the obese and non-obese groups (z = 2.81; p = 0.0050). CONCLUSIONS: PCOS patients showed higher KP levels than control, and obese non-PCOS patients also showed altered KP levels. All studies had poor descriptions of sample collection, pre-analytical and analytical procedures, which is critical considering structural characteristics of the KP molecule.

Factors associated with reporting delays and severity of childhood sexual abuse in São Paulo, Brazil.

Negative health outcome and its relationship with length and severity of Childhood Sexual Abuse is well established in the literature. Until recently, this literature consisted disproportionately of studies of adults recalling past events. For guidelines for the treatment of childhood survivors, research focused on child victims may be more relevant. We aim to characterize factors related to long-term and severe sexual abuse among children in São Paulo, Brazil. We conducted a cross-sectional study of children up to the age of ten, referred to a specialty program on sexual abuse between 2004 and 2013. Length and severity of the abuse were tested for associations with variables related to the abuse using a Chi-square test, followed by the Poisson regression with robust variance for prevalence ratio. Most children experienced abuse were reliant on relatives or friends for housing (45%). The time between abuse and reporting was longer when the perpetrator lived in the same household as the child and when abuse was reported by a relative or friend. Abuse was more frequent among female children, but longer and more severe in males. A lack of independent housing, parents' education and social stigma facilitated childhood sexual abuse by delaying reporting among our sample.

Regulation of access to the hospital care network for children in Ceará, Brazil.

Regulation is a state management tool to ensure that networked health services and goods comply with the principles of universality of access and integrality of care in the Unified Health System. To describe the regulatory actions of access to children's health services in the hospital setting, a descriptive, documentary study was performed to address data on the regulation of access to hospital health-care points for children from January to October 2015. The sample consisted of 2485 hospitalization procedures and regulated transfers in children between 0 and 15 years old living in the Juazeiro do Norte Health Region in the State of Ceará. The children's health-care network in the referenced region includes 8 hospitals that together provide care for 105 163 children in the surgical, emergency, and intensive care areas. These hospitals have a total of 176 beds, of which 118 are pediatric clinics, 7 are surgical pediatric units, and 51 are neonatal and intensive care units. In the medical clinics, 2279 children were hospitalized for local admissions, and 206 (8.9%) were transferred to intensive care units. Most children were under 1 year old (43.6%). The regulation of access to the hospitals' health-care network seems to guarantee local and regional access to 6 municipalities in the region. However, a high waiting time for intensive care beds was observed.

Sexual satisfaction among involuntarily childless women: A cross-cultural study in Italy and Brazil.

Infertility has been negatively associated with sexual satisfaction. This study aimed to estimate the relation of infertility to sexual satisfaction from a cross-cultural perspective, comparing Italian and Brazilian women. Between June 2012 and January 2013, 528 women seeking assisted reproduction technology (ART) treatment in Italy (39%) or Brazil (61%) completed self-reports of sexual satisfaction (ISS) and infertility-related stress in the marital domain (IRS). IRS was the same across countries. ISS differed, with 34.31% of the Italians and 43.52% of the Brazilians being sexually dissatisfied at a clinical level (ISS score >30). Multiple logistic regression models showed that being sexually dissatisfied at a clinical level was associated with lower education and higher IRS among Italian women, regardless of having a diagnosed cause of infertility. It was instead associated with higher IRS only among the Brazilian women who had a diagnosed cause of infertility. These findings suggest that, regardless of nationality, sexual satisfaction and infertility-related stress need to be addressed in the treatment of infertile women turning to ART. However, as factors associated with these dimensions vary across countries, interventions to promote sexual satisfaction among infertile women should be adapted to their specific socio-cultural context.

Potential of RASSF1A promoter methylation as biomarker for endometrial cancer: A systematic review and meta-analysis.

BACKGROUND: An epigenetic approach to explaining endometrial carcinogenesis necessitates good understanding of Ras association domain family 1 isoform A (RASSF1A) promoter methylation data from primary studies. AIMS: Differential magnitude of reported associations between RASSF1A promoter methylation and endometrial cancer (EC) prompted a meta-analysis to obtain more precise estimates. METHODS: Literature search yielded eight included articles. We calculated pooled odds ratios (OR) and 95% confidence intervals and subgrouped the data by race. Sources of heterogeneity were investigated with outlier analysis. RESULTS: The pooled ORs indicated increased risk, mostly significant. The overall effect (OR 11.46) was reflected in the European outcome (OR 15.07). However, both findings were heterogeneous (I2=57-70%) which when subjected to outlier treatment, erased heterogeneity (I2=0%) and retained significance (OR 9.85-12.66). Significance of these pre- and post-outlier outcomes were pegged at P≤0.0001. Only the Asian pre-outlier (OR 6.85) and heterogeneous (I2=82%) outcome was not significant (P=0.12) but when subjected to outlier treatment, erased heterogeneity (I2=0%) and generated significance (OR 23.74, P≤0.0001). CONCLUSIONS: Consistent increased risk associations underpinned by significance and robustness render RASSF1A with good biomarker potential for EC.

Copy number variation analysis reveals additional variants contributing to endometriosis development.

PURPOSE: Endometriosis is a gynecological disease influenced by multiple genetic and environmental factors. The aim of the current study was to use SNP-array technology to identify genomic aberrations that may possibly contribute to the development of endometriosis. METHODS: We performed an SNP-array genotyping of pooled DNA samples from both patients (n = 100) and controls (n = 50). Copy number variation (CNV) calling and association analyses were performed using PennCNV software. MLPA and TaqMan Copy-Number assays were used for validation of CNVs discovered. RESULTS: We detected 49 CNV loci that were present in patients with endometriosis and absent in the control group. After validation procedures, we confirmed six CNV loci in the subtelomeric regions, including 1p36.33, 16p13.3, 19p13.3, and 20p13, representing gains, while 17q25.3 and 20q13.33 showed losses. Among the intrachromosomal regions, our results revealed duplication at 19q13.1 within the FCGBP gene (p = 0.007). CONCLUSIONS: We identified CNVs previously associated with endometriosis, together with six suggestive novel loci possibly involved in this disease. The intergenic locus on chromosome 19q13.1 shows strong association with endometriosis and is under further functional investigation.

Associations of Polymorphisms in Anti-Müllerian Hormone (AMH Ile49Ser) and its Type II Receptor (AMHRII -482 A>G) on Reproductive Outcomes and Polycystic Ovary Syndrome: a Systematic Review and Meta-Analysis.

BACKGROUND/AIMS: Reported associations of reproductive outcomes (RO) and polycystic ovary syndrome (PCOS) with genotypes of the Ile49Ser and -482A>G polymorphisms in the Anti-Müllerian hormone (AMH) gene and its type II receptor (AMHRII), respectively, have conflicting results. METHODS: PubMed, Google Scholar and Science Direct databases were searched for studies that investigated Ile49Ser and -482A>G in RO and PCOS. Using the metaanalytic approach, we estimated risk (odds ratio [OR] with 95% confidence intervals) using standard genetic models. RESULTS: All calculated summary effects were non-significant. Overall associations of Ile49Ser and -482A>G with RO were absent (OR 0.95-0.99, P = 0.76-0.96) but implied increased risk in PCOS (OR 1.07-1.17, P = 0.49-0.55). Where heterogeneity of the pooled ORs were present, its sources were explored using the Galbraith plot. Detection and omission of the outlying studies in both polymorphisms not only erased heterogeneity of the recalculated pooled outcomes but also changed direction of association, where null effects turned to increased risk (Ile49Ser in RO) and increased risk became reduced risk (-482A>G in PCOS). Implications of the Ile49Ser and -482A>G, effects pointed to protection for Caucasians (OR 0.64-0.89, P = 0.36-0.73) in RO and increased risk in PCOS (OR 1.19-1.45, P = 0.28-0.65). Asian effects in RO and PCOS were variable (OR 0.97-1.24, P = 0.58-0.91). CONCLUSIONS: In summary, we found no evidence of significant associations of Ile49Ser and -482A>G with RO and PCOS, although contrasting Ile49Ser effects were implied among Caucasians between RO (up to 0.36% reduced risk) and PCOS (up to 1.5-fold increased risk).

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.

Are FSHR polymorphisms risk factors to premature ovarian insufficiency?

Premature ovarian insufficiency (POI) is an ovarian dysfunction characterized by increased FSH levels and amenorrhea before 40 years old. In recent years, the search for genetic causes of POI intensified and studies have been published relating the presence of mutations and polymorphisms in genes associated with development, recruitment and oocyte atresia. The aim of this study was to evaluate the presence of FSHR polymorphisms in our population and contribute with the elucidation of POI etiology. To achieve it, we have studied 100 patients with POI (G1), 60 patients with border line levels of FSH (G2) and 123 controls with regular menopause onset. Cytogenetic analysis of patients' samples and genotyping of Asn680Ser and Ala307Thr polymorphisms were performed in cases and controls. Cytogenetic analysis showed that 92% of G1 patients had normal karyotype, 4% presented polymorphic variants, 3% presented mosaic karyotype involving X chromosome. In G2, 91.6% had normal karyotype results, 3.2% displayed polymorphic variants, and 3.3% presented a mosaic karyotype involving X chromosome. Statistical comparison showed that the polymorphic allele of Ala307Thr polymorphism is more frequent in patients than in controls (G1: p < 0.001 and G2: p = 0.0259). This association has not been previously reported. We concluded that Ala307Thr polymorphism in FSHR can be potentially associated to POI development and can be considered as a screening marker in patients with ovarian failure signals.