Discrepancies in breast cancer's oncological outcomes between public and private institutions in the southeast region of Brazil: a retrospective cohort study.

Background: Brazil is a middle-income country with inequalities in its healthcare system. The disparities between public and private services affect the diagnosis and treatment of patients with breast cancer. The aim of this study is to assess whether disease-free survival (DFS) and overall survival (OS) are different in public and private specialized centers. Patient and methods: A retrospective cohort study with 1,545 breast cancer patients diagnosed from 2003 to 2011 at Barretos Cancer Hospital-BCH (public group, N = 1,408) and InORP Oncoclinicas (private group, N = 137) was conducted. A 1:1 propensity score matching (PSM) analysis was used to adjust the differences between the groups' characteristics (n = 137 in each group). Results: The median age at diagnosis was 54.4 years. Estimated DFS rates at 1, 5, and 10 years were 96.0%, 71.8%, and 59.6%, respectively, at BCH and 97.8%, 86.9%, and 78%, respectively, at InORP (HR: 2.09; 95% confidence interval [CI], 1.41-3.10; p < 0.0001). Estimated OS rates at 1, 5, and 10 years were 98.1%, 78.5%, and 65.4%, respectively, at BCH and 99.3%, 94.5%, and 91.9%, respectively, at InORP (HR: 3.84; 95% CI, 2.16-6.82; p < 0.0001). After adjustment by PSM, DFS and OS results in 1, 3, and 5 years remained worse in the public service compared to the private service. Conclusion: Patients treated in a public center have worse DFS and OS after a follow-up period of more than 5 years. These results were corroborated after carrying out the PSM.

Prevalence of sexually transmissible infections in adolescents treated in a family planning outpatient clinic for adolescents in the western Amazon.

Sexually transmitted infections (STIs) are among the most common public health problems worldwide, especially among adolescents and young adults, who account for almost 50% of all STI patients. Studies on the subject in the western Amazon are limited. This study aimed to evaluate the prevalence of STIs (chlamydia, gonorrhea, trichomoniasis, herpes simplex virus, syphilis, human immunodeficiency virus [HIV], hepatitis B, and hepatitis C) in adolescents treated at a family planning outpatient clinic in the western Amazon: Porto Velho, Rondônia, Brazil. A total of 196 adolescents were enrolled. During the gynecological examination, endocervical samples were collected to test for four STIs (chlamydia, gonorrhea, trichomoniasis, and herpes simplex virus), and blood samples were collected for the detection of HIV, syphilis, and hepatitis B and C. The mean age was 17.3 ± 1.5 years, the age at sexarche was 14.4 ± 1.6 years, and 54.6% of participants had their first sexual intercourse at 14 years or younger. Only 1.0% of the adolescents used condoms in all sexual relations, and 19.9% had casual partner(s) in the last year. In the evaluation of prevalence, we found that 32% of the adolescents had at least one STI, with the most prevalent being chlamydia (23%), followed by trichomoniasis (5.6%), herpes simplex (4.6%), and gonorrhea (3.1%). No positive cases of hepatitis B, hepatitis C, or HIV were detected, but 1% of the adolescents tested positive for syphilis. These indicators will support more effective health care strategies aimed at improving the quality of life of populations in this region of the western Amazon. In conclusion, our findings demonstrated high rates of STIs in the studied patients, reinforcing the need to expand epidemiological studies to implement more appropriate public policies and intervention strategies to prevent STIs in adolescents and other vulnerable populations in the western Amazon.

Associations among morphological parameters, clinical factors and euploid blastocyst formation.

OBJECTIVE: To evaluate the association among embryonic morphological parameters, clinical factors and euploid blastocyst formation. METHODS: This prospective cohort study included 422 blastocysts from 135 patients who had undergone preimplantation genetic analysis after intracytoplasmic sperm injection (ICSI). RESULTS: Of 422 blastocysts, 200 (47.4%) were euploid and 222 (52.6%) aneuploid. Women aged older than 38 years were more likely to develop aneuploid embryos (OR: 3.4, CI: 2.2-5.4, p<0.001). Poor ovarian reserve (OR: 3.3, p<0.001), increased male age (39.0 versus 40.7, p=0.019), and decrease in sperm percentage with normal morphology (2.5% vs. 1.9%, p=0.047) were associated with aneuploidy. Type C trophectoderm (TE) and type C inner cell mass were associated with a high risk of embryo aneuploidy, with OR of 4.1 (CI: 2.2-7.7, p<0.001) and 1.7 (CI: 1.01-3.0, p=0.048), respectively. Logistic regression analysis revealed maternal age and type C TE as the main risk factors for aneuploidy. Among combinations of factors, the best marker for the risk of aneuploidy was maternal age older than 38 years, combined with a type-C embryo with trophectoderm, which showed a positive predictive value of 88.6% and a specificity of 97.5%. CONCLUSIONS: Trophectoderm and type-C inner cell mass are the main embryo risk factors for aneuploidy, explaining approximately 71% and 60% of the risk, respectively. Among clinical factors, advanced maternal and paternal age (older than 38 and 36 years, respectively), antral follicles (<5), and a low percentage of sperm with normal morphology increased the risk of embryonic aneuploidy.

Association of FSHR, LH, LHR, BMP15, GDF9, AMH, and AMHR polymorphisms with poor ovarian response in patients undergoing in vitro fertilization.

OBJECTIVE: This paper aimed to assess the correlation between LH, LHR, GDF9, FSHR, AMH, AMHR2, and BMP15 polymorphisms, which are related to follicular development, and decreased ovarian response in women undergoing controlled ovarian hyperstimulation (COH) for IVF. METHODS: This age-matched case-control study included three or four controls per woman undergoing COH. Controls were women with normal ovarian response (NOR) and cases were women with poor ovarian response (POR) in oocyte retrieval (three or fewer oocytes). DNA was extracted from peripheral blood and potential associations with gene polymorphisms related to follicular development (LH, LHR, GDF9, FSHR, AMH, AMHR2, and BMP15) were analyzed. RESULTS: Sixty-six patients were included, 52 in the NOR and 14 in the POR group. Two GDF9 polymorphisms were associated with follicular response after COH, one associated with POR - the presence of a mutant polymorphism in heterozygosis and homozygosis of the GDF9 398-39 (C to G) [23% NOR versus 68% POR (OR 4.01, CI 1.52-10.6, p=0.005)] - and another associated with protective response - the presence of normal homozygosis of GDF9 (C447T) [19.2% NOR versus 50% POR (OR 0.34, IC 0.14-0.84, p=0.019)]. No additional associations were found between the other analyzed polymorphisms and POR. CONCLUSIONS: This study found that GDF9 appears to play an important role in follicular development, whereas polymorphisms in its DNA chain may negatively affect ovarian reserve, such as 398-39 (C to G), or positively, as seen in C447T.

The usefulness of metaphase I oocytes in women who undergo controlled ovarian hyperstimulation for intracytoplasmic sperm injection.

OBJECTIVE: The aim of this study was to evaluate the fertilization and blastocyst formation rates of oocytes in metaphase I (MI) obtained from women who underwent controlled ovarian hyperstimulation (COH) for intracytoplasmic injection. METHODS: A prospective cohort study that included women from whom at least 1 MI and 1 MII oocyte were obtained after COH was performed. We collected 1,907 oocytes from 164 women (1291 MII, 352 MI and 258 prophase I or atretic). After oocyte classification, the MII and MI oocytes were incubated for 4 hours. RESULTS: After 4 hours, the rescue maturation rate was 57.2%; 205 MI oocytes matured to MII oocytes in vitro (rescued MI-MII group), and 153 remained in MI (arrested MI group). The normal fertilization rates were directly associated with oocyte maturation, with rates of 79.1%, 60.2%, and 31.9% in MII, MI-MII and MI oocytes, respectively (p<0.001). Group arrested MI had an odds ratio (OR) of 7.6 (CI 5.2 - 11.2, p<0.001) for abnormal fertilization compared with Group MII. The blastocyst formation rate was directly associated with oocyte maturation, at 36.4% for MII, 11.4% for MI-MII and 0.6% for MI. CONCLUSION: Oocytes collected at the MI stage after OCH that did not mature to MII after rescue maturation had a blastocyst formation rate of only 0.6%, while those in MII and MI-MII had rates of 36.4% and 11.4%, respectively. However, we found a pregnancy with the birth of a healthy baby from a blastocyst formed after intracytoplasmic sperm injection (ICSI) of an MI oocyte.

GDF9 polymorphisms: influence on ovarian response in women undergoing controlled ovarian hyperstimulation.

OBJECTIVE: The study looked into the possible influence of GDF9 polymorphisms on ovarian response in women with a normal ovarian reserve undergoing controlled ovarian hyperstimulation for in vitro fertilization (IVF). METHODS: This cross-sectional study included 67 women with normal ovarian reserve aged 30-39 years submitted to controlled ovarian hyperstimulation for IVF. We sequenced four polymorphisms in the GDF9 gene (C398G, C447T, G546A, and G646A) and analyzed their influence on follicular and oocyte outcomes. RESULTS: The mutant allele C398G decreased the total number of follicles >17mm (6.49 vs. 4.33, p=0.001), total number of follicles (10.11 vs. 7.33, p=0.032), number of MII oocytes retrieved, and serum progesterone levels on trigger day. The C447T polymorphism was associated with a greater number of follicles between 12 and 14 mm on the day of r-hCG, while the G546A polymorphism was associated with lower serum progesterone levels on trigger day. CONCLUSIONS: GDF9 gene polymorphisms C398G and C447T adversely affected ovarian response in women undergoing controlled ovarian hyperstimulation. These findings show that in addition to playing a role in the early stages of folliculogenesis, GDF9 polymorphisms have an important impact on the final stage of oocyte development.

Causes of recurrent miscarriage after spontaneous pregnancy and after in vitro fertilization.

PROBLEM: We aimed to investigate the main causes of recurrent miscarriage (RM) in patients with losses after spontaneous gestation (SG) and after in vitro fertilization (IVF). METHOD OF STUDY: A prospective case-control study was conducted. The eligible patients were women who had experienced two or more consecutive abortions after <12 weeks' gestation, two consecutive losses after SG, or two consecutive losses after IVF. All patients were subjected to the following evaluations: karyotyping of the aborted material, alloimmune and autoimmune marker testing, and acquired and hereditary thrombophilia marker testing. RESULTS: In total, 58 patients were eligible: 32 patients with RM after SG and 26 patients with RM after IVF. The factors associated with RM were genetic (29%), immune (14%), thrombophilic (21%), and thrombophilic and immune (24%), and only 12% of the cases were idiopathic. Comparing the two study groups (SG and IVF), all studied factors were similar, except for a higher ANA positivity observed in the SG group (SG 30.4% vs IVF 5.3%, OR 8.6 (CI 1.1-21.1, P .048). CONCLUSION: Our study identified the possibly factors associated with recurrent miscarriage in 86% of the cases, and these factors appear to be similar in patients with recurrent miscarriage after spontaneous gestation and IVF. This study demonstrates that IVF with PGT-A with euploid embryo transfer could reduce abortions by up to 29%, but other factors need to be investigated even in patients undergoing in vitro fertilization.

Menopausal status is associated with a high risk for residual disease after cervical conization with positive margins.

BACKGROUND: We aimed to determine demographic and clinicopathological predictors for residual disease in women with cervical intraepithelial neoplasia (CIN 2/3) with endocervical cone margin involvement. METHODS AND FINDINGS: A cross-sectional study was conducted. The eligible patients were women who underwent hysterectomy as a treatment option after having a positive endocervical margin for CIN 2/3 in cervix conization specimens from 2000 to 2015. The patients were divided into two groups based on the persistence of CIN 2/3 and absence of CIN 2/3 in hysterectomy specimens. Demographic, clinical and histology information were collected in both groups. A total of 80 patients were eligible for the study; 37 (46.3%) had no persistence of CIN 2/3 and 43 (53.7%) had persistence of CIN 2/3 in the hysterectomy specimens. Demographic, clinical, and cone specimen characteristics, and a visible squamocolumnar junction and type of conization were analyzed as possible risk factors for the presence of residual lesions at hysterectomy, and none of these variables were associated with residual disease. Menopausal status was strongly associated with a high risk of persistent residual disease 81.2% (OR 4.9, CI 1.27-18.9), P = 0.014. In the multivariate analysis, only a menopausal status (P = 0.04) was associated with a high risk of persistent lesions. CONCLUSION: This analysis found that menopausal status exhibited an important association with persistent residual disease. Menopausal women with endocervical margin involvement exhibit a greater than 80% risk of persistent lesions.

Endometriosis-associated infertility: GDF-9, AMH, and AMHR2 genes polymorphisms.

PURPOSE: The purpose of this paper is to determine whether there is a correlation between polymorphisms in the growth differentiation factor-9 (GDF-9) gene and anti-Müllerian hormone (AMH) gene and its receptor, AMHR2, and endometriosis-associated infertility. METHODS: This is a case-control study to evaluate whether there is a correlation between polymorphisms in the GDF-9 gene (SNPs determined by direct sequencing), AMH gene, AMHR2 (both SNPs determined by genotyping using TaqMan Allelic Discrimination), and endometriosis-associated infertility. The study included 74 infertile women with endometriosis and 70 fertile women (tubal ligation) as a control group. RESULTS: Patient age and the mean FSH levels were similar between the infertile with endometriosis and fertile without endometriosis groups. The frequency of genotypes between the groups for GDF-9 gene polymorphisms did not show statistical significance, nor did the AMHR2 gene polymorphism. However, the AMH gene polymorphism did show statistical significance, relating the polymorphic allele with infertility in endometriosis. CONCLUSIONS: We demonstrate that an SNP in the AMH gene is associated with infertility in endometriosis, whereas several SNPs in the GDF-9 gene and the - 482A G SNP in the AMHR2 gene were found to be unrelated.

Recurrent miscarriage is associated with the dopamine receptor (DRD2) genotype.

The purpose of this research is to compare the prevalence of dopamine receptor D2 polymorphisms in women with recurrent miscarriage (RM) and healthy patients. Fifty-four women were enrolled in this case-control study. We performed DNA extraction of peripheral blood, followed by polymerase chain reaction to confirm single-strand polymorphisms and to sequence two polymorphisms: polymorphism 1 (rs6275) and polymorphism 2 (rs6277) in exon 7 of the dopamine receptor D2 (DRD2). The frequency of DRD2 polymorphism 2 (rs6277) was increased in the subjects with RM. An analysis of the DRD2 genotypes demonstrated an odds ratio of 2.37 (1.05-5.36, 95% confidence interval) for the polymorphism 2 (rs6277) in RM. The mean of the serum prolactin level was higher in the patients with RM (12.5 ng/ml) than in healthy women (8.1 ng/ml) p = 0.03. An excess homozygosity of the DRD2 polymorphism suggests a genetic predisposition to RMs, which could result in a mild serum prolactin increase. Thus, because of the potential role of prolactin in reproductive regulation, this polymorphism could play an important role in early pregnancy implantation and pregnancy maintenance.

Dopamine receptor D2 genotype (3438) is associated with moderate/severe endometriosis in infertile women in Brazil.

OBJECTIVE: To compare the prevalence of dopamine receptor D2 polymorphisms in patients with peritoneal endometriosis and in healthy control subjects. DESIGN: Case-control study. SETTING: University hospital. PATIENT(S): One hundred seven women aged ≥18 years who were enrolled when seeking care for infertility caused by peritoneal endometriosis or for tubal ligation. INTERVENTION(S): We performed DNA extraction of peripheral blood, followed by polymerase chain reaction to confirm single-strand polymorphisms and to sequence two polymorphisms. MAIN OUTCOME MEASURE(S): We sequenced two polymorphisms in exon 7 of the dopamine receptor D2 (DRD2) gene. Polymorphism 1 occurs in nucleotide 3420 (cytosine to thymine, 313 histidine), and polymorphism 2 occurs in nucleotide 3438 (cytosine to thymine, 319 proline). RESULT(S): The frequency of the DRD2 polymorphism 2 was increased in subjects with peritoneal moderate/severe endometriosis. Analysis of the DRD2 genotypes demonstrates an odds ratio of 2.98 (95% confidence interval 1.47-6.04) for polymorphism 2 in peritoneal moderate/severe endometriosis. CONCLUSION(S): Our results revealed that an excess of DRD2 polymorphism 2 was found in exon 7 in women with peritoneal moderate/severe endometriosis. The presence of polymorphism 2 could cause a defect in a post-receptor signaling mechanism, resulting in a mild increase in serum prolactin levels. Thus, the potential angiogenic role of prolactin may play a role in the implantation of ectopic endometriosis tissue.

T helper (Th)1, Th2, and Th17 interleukin pathways in infertile patients with minimal/mild endometriosis.

In the present study, interleukin (IL)-10, IL-12, IL-17, and IL-23 levels were measured in serum and peritoneal fluid of women with minimal or mild endometriosis and compared with levels in controls without endometriosis. Higher IL-23 levels were encountered in the peritoneal fluid of women with endometriosis, suggesting a possible role of this cytokine in these women's infertility.

There is no complete linkage between the polymorphisms N680S and T307A of the follicular stimulating hormone receptor gene in fertile women.

PURPOSE: We conducted a cross-sectional study to evaluate the linkage of FSHR T307A and N680S in a group of fertile women. METHODS: Peripheral blood was obtained from 51 fertile women. DNA extraction and isolation were performed. For the detection of the T307A polymorphism a set of primers (5_-TCTGAGCTTCATCCAATTTGCA-3_and 5_-GGGAAAGAGGGCA GCTGCAA-3) was used and then the product was further amplified by a second PCR-RFLP using another set of primers (5_-CAAATCTATTTTAAGGCAAGAAGTTGATTATATGCCTCAG-3_and 5_-GTAGATTCCAATGCAGA GATCA-3). For the N680S polymorphism the primers (5_-TTTGTGGTCATCTGTGGCTGC-3_ and 5_-CAAAGGCAAGGACTGAATT ATC ATT-3_) were used. Statistical analysis for the association between the polymorphisms was performed by the Spearman test. RESULTS: We calculated the association between the homozygosis at codon 307 and at codon 680 both for T/T-S/S and A/A-N/N. A significant association between the genotypic results at codon 680 with those at codon 307 was found (r = 0.6363, P = 0.001). However, a complete linkage between these two polymorphisms was rejected as there were 12 patients with discordant results from the expected A-N/T-S at codons 307 and 680, respectively. CONCLUSION: The current data demonstrated an association but failed to demonstrate a complete linkage between these two polymorphisms.