Publications by authors named "Newton Sérgio de Carvalho"

36 Publications

Inside the pocket: Critical elements of HLA-mediated susceptibility to cervical precancerous lesions.

HLA 2021 Sep 10. Epub 2021 Sep 10.

Laboratory of Immunogenetics and Histocompatibility, Department of Genetics, Universidade Federal do Paraná (UFPR), Curitiba, Brazil.

Human papillomavirus (HPV) infection is a necessary cause for cervical cancer (CC), but it also depends on genetic factors, such as HLA polymorphism. However, few reports addressed the role of amino acids residues at the HLA peptide-binding cleft in HPV-related cervical disease. Therefore, we aimed to investigate the association between HLA-B, HLA-C, and HLA-DRB1 polymorphism and amino acid residues composing the pockets of the peptide-binding cleft of the respective polypeptide chains with cervical intraepithelial neoplasia (CIN II/III). HLA typing was performed by PCR-SSOP in 184 women with CIN II/III and 174 controls from South Brazil. Associations were estimated by multivariate logistic regression. FDR test was performed to correct the p-value for multiple comparisons. HLA-DRB1*13:01 was associated with protection against CIN II/III, while HLA-C*03:04 was associated with susceptibility. The amino acid residues isoleucine, tyrosine, and leucine at positions 95, 116, and 163 of HLA-C, respectively, were associated with CIN II/III susceptibility. In contrast, serine at positions 11 and 13 of HLA-DRB1 was associated with protection against the disease. Our results confirm previously reported associations between HLA and cervical diseases caused by HPV and suggest a role for amino acid residues at different positions of HLA-C and HLA-DRB1 in CIN II/III. This finding may be further explored to better understand the genetic risk and the influence of immune response to CC development.
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http://dx.doi.org/10.1111/tan.14429DOI Listing
September 2021

Association Between COVID-19 Pregnant Women Symptoms Severity and Placental Morphologic Features.

Front Immunol 2021 26;12:685919. Epub 2021 May 26.

Postgraduate Program of Health Sciences, School of Medicine, Pontifícia Universidade Católica do Paraná-PUCPR, Curitiba, Brazil.

Since the beginning of the pandemic, few papers describe the placenta's morphological and morphometrical features in SARS-CoV-2-positive pregnant women. Alterations, such as low placental weight, accelerated villous maturation, decidual vasculopathy, infarcts, thrombosis of fetal placental vessels, and chronic histiocytic intervillositis (CHI), have been described.

Objective: To analyze clinical data and the placental morphological and morphometric changes of pregnant women infected with SARS-CoV-2 (COVID-19 group) in comparison with the placentas of non-infected pregnant women, matched for maternal age and comorbidities, besides gestational age of delivery (Control group).

Method: The patients in the COVID-19 and the Control group were matched for maternal age, gestational age, and comorbidities. The morphological analysis of placentas was performed using Amsterdam Placental Workshop Group Consensus Statement. The quantitative morphometric evaluation included perimeter diameter and number of tertiary villi, number of sprouts and knots, evaluation of deposition of villous fibrin, and deposition of intra-villous collagen I and III by Sirius Red. Additionally, Hofbauer cells (HC) were counted within villi by immunohistochemistry with CD68 marker.

Results: Compared to controls, symptomatic women in the COVID-19 group were more likely to have at least one comorbidity, to evolve to preterm labor and infant death, and to have positive SARS-CoV-2 RNA testing in their concepts. Compared to controls, placentas in the COVID-19 group were more likely to show features of maternal and fetal vascular malperfusion. In the COVID-19 group, placentas of symptomatic women were more likely to show CHI. No significant results were found after morphometric analysis.

Conclusion: Pregnant women with symptomatic SARS-CoV-2 infection, particularly with the severe course, are more likely to exhibit an adverse fetal outcome, with slightly more frequent histopathologic findings of maternal and fetal vascular malperfusion, and CHI. The morphometric changes found in the placentas of the COVID-19 group do not seem to be different from those observed in the Control group, as far as maternal age, gestational age, and comorbidities are paired. Only the deposition of villous fibrin could be more accentuated in the COVID-19 group (p = 0.08 borderline). The number of HC/villous evaluated with CD68 immunohistochemistry did not show a difference between both groups.
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http://dx.doi.org/10.3389/fimmu.2021.685919DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187864PMC
July 2021

SARS-CoV-2 in asymptomatic pregnant women in South Brazil: RT-PCR and serological detection.

J Perinat Med 2021 Jul 10;49(6):717-722. Epub 2021 Jun 10.

Department of Obstetrics and Gynecology, Hospital de Clínicas, Universidade Federal do Paraná, Curitiba, Brazil.

Objectives: This study aims to detect the SARS-CoV-2 infection prevalence in asymptomatic pregnant women.

Methods: A group of 195 asymptomatic pregnant women who attended the prenatal care outclinic and to the obstetric emergency department was tested concomitantly for SARS-CoV-2 by RT-PCR and serological tests.

Results: The virus was detected by RT-PCR in two (1.02%) cases and 17 (8.71%) patients had antibodies detected by immunochromatographic tests.

Conclusions: Due to the high risk of this emerging infection in the health of pregnant women, fetuses and newborns, we suggest the universal screening of all pregnant women admitted to hospital through the combined method RT-PCR and serological.
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http://dx.doi.org/10.1515/jpm-2021-0173DOI Listing
July 2021

Brazilian Protocol for Sexually Transmitted Infections 2020: human papillomavirus (HPV) infection.

Rev Soc Bras Med Trop 2021 17;54(suppl 1):e2020790. Epub 2021 May 17.

Universidade Federal de Pelotas, Programa de Pós-Graduação em Epidemiologia, Pelotas, RS, Brasil.

This article addresses human papillomavirus (HPV) infection, one of the topics covered by the Clinical Protocol and Therapeutic Guidelines for Comprehensive Care for People with Sexually Transmitted Infections, published by the Brazilian Ministry of Health. The Protocol and Guidelines have been developed based on scientific evidence and validated in discussions with specialists. This article presents epidemiological and clinical aspects and guidelines for health service managers and health workers about diagnosing and treating people with papillomavirus infection. This theme is a significant public health issue since it is the most prevalent sexually transmitted infection globally, capable of triggering the oncogenic process of cervical cancer and the possibility of anogenital warts. Important information is presented for gaining knowledge about HPV and action strategies for infection prevention and control, provision of quality care, and effective treatment of the disease. Infection by the human papillomavirus is the sexually transmitted infection of the highest contagion, superior to genital herpes and HIV.
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http://dx.doi.org/10.1590/0037-8682-790-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8210485PMC
May 2021

Brazilian Protocol for Sexually Transmitted Infections, 2020: infections causing vaginal discharge.

Rev Soc Bras Med Trop 2021 17;54(suppl 1):e2020593. Epub 2021 May 17.

Ministério da Saúde, Secretaria de Vigilância em Saúde, Brasília, DF, Brasil.

The topic of vaginal discharge is one of the chapters of the Clinical Protocol and Therapeutic Guidelines for Comprehensive Health Care for People with Sexually Transmitted Infections, published by the Brazilian Ministry of Health in 2020. The chapter has been developed based on scientific evidence and validated in discussions with specialists. This article presents epidemiological and clinical aspects associated with vaginal discharge conditions, as well as guidance to health service managers and health professionals. Screening, diagnosing, and treating these conditions, the main complaints among women seeking health services, caused by infectious or non-infectious factors, also are presented. Besides, information is presented on surveillance, prevention, and control actions to promote knowledge of the problem and provide quality care and effective treatment. In healthcare servicing cases of sexually transmitted infections, vaginal discharge is the main referred symptom, common among pregnant women.
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http://dx.doi.org/10.1590/0037-8682-593-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8210494PMC
May 2021

Brazilian Protocol for Sexually Transmitted Infections, 2020: infections that cause cervicitis.

Rev Soc Bras Med Trop 2021 17;54(suppl 1):e2020587. Epub 2021 May 17.

Universidade Federal do Paraná, Departamento de Tocoginecologia, Curitiba, PR, Brasil.

Infections that cause cervicitis are a topic presented in the "Clinical Protocol and Therapeutic Guidelines for Comprehensive Care for People with Sexually Transmitted Infections", published by the Brazilian Ministry of Health in 2020. The document was developed based on scientific evidence and validated in discussions with experts. This article presents epidemiological and clinical aspects of infections that cause cervicitis and recommendations on screening, diagnosis, and treatment of affected people and their sexual partnerships. Also, it discusses strategies for surveillance, prevention, and control of these infections for health professionals and health service managers involved in the programmatic and operational management of sexually transmitted infections. Expanding access to diagnostic tests and early treatment are crucial for controlling the spread of pathogens that cause cervicitis. Associated factors to cervicitis: sexually active women younger than 25 years old, new or multiple sexual partners, partners with STI, previous history or presence of other STI, and irregular use of condoms.
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http://dx.doi.org/10.1590/0037-8682-587-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8210491PMC
May 2021

Evaluation of the Seroprevalence of Infectious Diseases in 2,445 in vitro Fertilization Cycles.

Rev Bras Ginecol Obstet 2021 Mar 15;43(3):216-219. Epub 2021 Apr 15.

Universidade Federal do Paraná, Curitiba, PR, Brazil.

Objective:  To evaluate the seroprevalence of positive markers for syphilis, human immunodeficiency virus (HIV) I and II, human T cell lymphotropic virus (HTLV) I and II, and hepatitis B and C among women undergoing in vitro fertilization (IVF).

Methods:  We conducted a retrospective analysis among patients who underwent IVF, between January 2013 and February 2016, and who had complete screening records.

Results:  We analyzed 1,008 patients who underwent IVF, amounting to 2,445 cycles. Two patients (0.2%) tested positive for HIV I and II and none for HTLV I and II. Three patients (0.3%) had positive screening for syphilis, and two (0.2%) had positive hepatitis C antibody test (anti-HCV). A positive hepatitis B virus surface antigen (HbsAg) test was observed in 4 patients (0.4%), while 47 (4.7%) patients were positive for IgG antibody to hepatitis B core antigen (anti-HbC IgG), and only 1 (0.1%) was positive for IgM antibody to hepatitis B core antigen (anti-HbC IgM). The anti-HbS test was negative in 659 patients (65.3%). Only 34.7% of the patients had immunity against the Hepatitis B virus. Patients with an anti-HbS negative result were older than those with a hepatitis B test (anti-HbS) positive result (36.3 versus 34.9;  < 0.001).

Conclusion:  The present study showed lower infection rates than the Brazilian ones for the diseases studied in patients undergoing IVF. Only a few patients were immunized against hepatitis B.
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http://dx.doi.org/10.1055/s-0041-1725055DOI Listing
March 2021

[Brazilian Protocol for Sexually Transmitted Infections 2020: human papillomavirus (HPV) infection].

Epidemiol Serv Saude 2021 15;30(spe1):e2020790. Epub 2021 Mar 15.

Universidade Federal de Pelotas, Programa de Pós-Graduação em Epidemiologia, Pelotas, RS, Brasil.

This article addresses human papillomavirus (HPV) infection, this being one of the topics covered by the Clinical Protocol and Therapeutic Guidelines for Comprehensive Care for People with Sexually Transmitted Infections, published by the Brazilian Ministry of Health. The Protocol and Guidelines have been developed based on scientific evidence and validated in discussions with specialists. This article presents epidemiological and clinical aspects, as well as guidelines for health service managers and health workers about diagnosing and treating people with papillomavirus infection. This theme is an important public health problem, since it is the most prevalent sexually transmitted infection in the world, capable of triggering the oncogenic process of cervical cancer, as well as the possibility anogenital warts occurring. Important information is presented for gaining knowledge about HPV, as well as action strategies for infection prevention and control, provision of quality care and effective treatment of the disease.
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http://dx.doi.org/10.1590/S1679-4974202100014.esp1DOI Listing
March 2021

[Brazilian Protocol for Sexually Transmitted Infections 2020: infections causing vaginal discharge].

Epidemiol Serv Saude 2021 15;30(spe1):e2020593. Epub 2021 Mar 15.

Ministério da Saúde, Secretaria de Vigilância em Saúde, Brasília, DF, Brasil.

The topic of vaginal discharge is one of the chapters of the Clinical Protocol and Therapeutic Guidelines for Comprehensive Care for People with Sexually Transmitted Infections, published by the Brazilian Ministry of Health in 2020. The chapter has been developed based on scientific evidence and validated in discussions with specialists. This article presents epidemiological and clinical aspects related to vaginal discharge conditions, as well as guidelines for health service managers and health professionals about screening, diagnosing and treating these conditions, which are one of the main complaints among women seeking health services, and which may be caused by infectious or non-infectious factors. In addition, information is presented on strategies for surveillance, prevention and control actions, in order to promote knowledge of the problem and provision of quality care and effective treatment.
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http://dx.doi.org/10.1590/S1679-4974202100007.esp1DOI Listing
March 2021

[Brazilian Protocol for Sexually Transmitted Infections 2020: infections that cause cervicitis].

Epidemiol Serv Saude 2021 15;30(spe1):e2020587. Epub 2021 Mar 15.

Universidade Federal do Paraná, Departamento de Tocoginecologia, Curitiba, PR, Brasil.

Infections that cause cervicitis are a topic presented in the "Clinical Protocol and Therapeutic Guidelines for Comprehensive Care for People with Sexually Transmitted Infections", published by the Brazilian Ministry of Health in 2020. The document was developed based on scientific evidence and validated in discussions with experts. This article presents epidemiological and clinical aspects of infections that cause cervicitis, as well as recommendations on screening, diagnosis and treatment of affected people and their sexual partnerships. In addition, it discusses strategies for surveillance, prevention and control of these infections for health professionals and health service managers involved in the programmatic and operational management of sexually transmitted infections. Expanding access to diagnostic tests and early treatment are crucial for controlling the spread of pathogens that cause cevicitis.
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http://dx.doi.org/10.1590/S1679-4974202100008.esp1DOI Listing
March 2021

MICA and KLRK1 genes and their impact in cervical intraepithelial neoplasia development in the southern Brazilian population.

Hum Immunol 2020 May 24;81(5):249-253. Epub 2020 Feb 24.

Department of Gynecology and Obstetrics, Infectious Diseases in Gynecology and Obstetrics Sector, Post Graduate Program of Gynecology and Obstetrics, Clinics Hospital of Federal University of Paraná (UFPR), Rua General Carneiro, 181, Alto da Glória, CEP 80060-900 Curitiba, Paraná, Brazil; Genetics Department of Federal University of Paranál, Biological Sciences Sector, Federal University of Paraná, Avenida Coronel Francisco H. dos Santos, 100. Centro Politécnico, Jardim das Américas, CEP 80050-540 Curitiba, Paraná, Brazil; Immunogenetics and Histocompatibility Laboratory (LIGH), Biological Sciences Sector, Federal University of Paraná, Avenida Coronel Francisco H. dos Santos, 100. Centro Politécnico, Jardim das Américas, CEP 80050-540 Curitiba, Paraná, Brazil.

Cervical carcinoma and cervical intraepithelial neoplasia (CIN) are associated with persistent infection by oncogenic subtypes of HPV (Human Papillomavirus). Factors linked to immunity, genetics and others like oral contraceptive use, sexual behavior, coinfections with other microorganisms and smoking seem to influence the mechanisms that determine regression or progression to CIN and cervical cancer. We investigated the effect of the MHC class I chain-related gene A (MICA) and Killer Cell Lectin Like receptor K1 (KLRK1) genes on cervical cancer and CIN lesions susceptibility in a group of 195 patients from southern Brazil. There were found a significantly higher number of ex-smokers in the control group (p = 0.005). There were more oral contraceptives (OC) users in the patient group. MICA*008:01/04 allele showed a significant difference between patient and control groups (p = 0.03; OR = 0.63, 95% CI 0.41-0.96), as well as MICA*018:01(p = 0.004, OR = 0.15, 95% CI 0.03-0.64) and MICA*002:01/020 (p = 0.01; OR = 0.60, 95% CI 0.40-0.88). We also analyzed cases and controls according to the MICA-129 genotypes (Met/Val). There was found a difference (p = 0.02) with the Met/Val genotype in a higher frequency in controls and Val/Val and Val/MICA del at a higher frequency in the patient group. For the KLRK1 gene there was no significant difference between groups.
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http://dx.doi.org/10.1016/j.humimm.2020.02.007DOI Listing
May 2020

Is there a role played by HLA-E, if any, in HPV immune evasion?

Scand J Immunol 2020 Mar 10;91(3):e12850. Epub 2019 Dec 10.

Departamento de Tocoginecologia, Hospital de Clínicas, Universidade Federal do Parana (UFPR), Curitiba, Brazil.

Cervical cancer incidence worldwide exceeds half a million new cases per year. The human papillomavirus (HPV) being the major causative agent of CC uses a variety of strategies to evade immune surveillance, where the immune status varies amongst individuals. This immune evasion altered by HPV is reflected in persistent infections, causing the evolution of cervical neoplasia. The role of the immune system in viral recognition and elimination is of extreme relevance in the development of CC. The interactions of the HLA-E ligand in the target cell along with CD94/NKG2 receptors, which are expressed predominantly, but not exclusively, on NK cells' surface, are responsible for activating or inhibiting cytotoxic activity according to their function. The engagement between HLA-E and CD94/NKG2 molecules is one of the fundamental surveillance mechanisms in patients with CIN I, II and III, where HLA-E expression increases significantly, especially in HPV 16 and 18 infections. Higher HLA-E expression was observed in most histopathological types of CC, and at the same time was correlated to best survival of the patient. This review aims to summarize and discuss the immunological role of HLA-E in the context of HPV infection and immune system evasion, and the oncogenic process of cervical cancer.
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http://dx.doi.org/10.1111/sji.12850DOI Listing
March 2020

Incidence rates and temporal trends of cervical cancer relating to opportunistic screening in two developed metropolitan regions of Brazil: a population-based cohort study.

Sao Paulo Med J 2019;137(4):322-328. Epub 2019 Oct 31.

MD, PhD. Physician and Professor, Department of Obstetrics and Gynecology, School of Medical Sciences, Universidade Federal do Paraná (UFPR), Curitiba (PR), Brazil.

Background: Brazilian opportunistic screening programs for cervical cancer have limited impact. In the regions of two cities (Campinas and Curitiba) with high human development indices, consistent information from 96-97% of all cervical cancer cases managed within the public healthcare system is available.

Objective: To estimate the incidence rate (IR) and temporal trends in these regions, covering 2001-2012.

Design And Setting: A population-based cohort study was conducted under the assumption that all cervical cancer cases were managed in cancer referral center hospitals.

Methods: 3,364 records (1,646 from Campinas; 1,718 from Curitiba) were analyzed to provide estimates of IR, age-standardized IR (ASR) and cervical cancer trends (shown per 100,000 women/year). Longitudinal patterns were analyzed using linear regression and shown as annual percentage change (APC); P < 0.05 for significance.

Results: Annual IR and ASR estimates for cervical cancer ranged from 3.8 to 8.0 over 2001-2012, decreasing over more recent years, and were similar for the two regions. The age-specific IR was about 50% lower among women aged 45 years or older (IR-2001/IR-2012: Campinas = 14.8/8.0; Curitiba = 18.7/8.3; P < 0.001). There was an increasing APC trend in Campinas among women aged 15-24 years, and a decreasing IR trend for squamous-cell histology in both regions (P < 0.05).

Conclusion: Cervical cancer incidence estimates showed slowly decreasing trends in both regions, most evidently for women aged 45 years or older and for squamous-cell histology. These findings reflect the opportunistic nature of the population screening program, despite the comparatively high economic development level in the two regions.
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http://dx.doi.org/10.1590/1516-3180.2018.0306220719DOI Listing
March 2020

Mycoplasma genitalium, a stealth female reproductive tract.

Eur J Clin Microbiol Infect Dis 2020 Feb 14;39(2):229-234. Epub 2019 Sep 14.

Division of Immunology and Infectious Diseases, Department of Obstetrics and Gynecology, Weill Cornell Medicine, New York, NY, USA.

Mycoplasma genitalium was first isolated from the urethral swabs of two symptomatic men with urethritis in 1980. It is a sexually transmitted bacterium associated with a number of urogenital conditions in women like cervicitis, endometritis, pelvic inflammatory disease, infertility, and susceptibility to human immunodeficiency virus (HIV). However, M. genitalium may also act like a stealth pathogen at female reproductive tract, giving no symptoms. Its prevalence varies between different groups, with the average being 0.5-10% in the general population and 20-40% in women with sexually transmitted infections. The recommended treatment of this infection is azithromycin as a single 1-g dose. However, in recent years, macrolide resistance has increased which is significantly lowering the cure rate, being less than 50% in some studies. New treatment regimens need to be investigated due to increasing drug resistance. The discussion and suggestion of an algorithm for management of this infection is the highlight of this paper.
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http://dx.doi.org/10.1007/s10096-019-03707-8DOI Listing
February 2020

MASP-1 and MASP-2 Serum Levels Are Associated With Worse Prognostic in Cervical Cancer Progression.

Front Immunol 2018 23;9:2742. Epub 2018 Nov 23.

Department of Gynecology, Clinical Hospital, Federal University of Parana, Curitiba, Brazil.

MBL-associated serine proteases (MASP-1, MASP-2, MASP-3, MAp-44, and MAp-19) are key factors in the activation of the lectin pathway of complement. Serum levels of these components have been associated with recurrence and poor survival of some types of cancer, such as colorectal and ovarian cancer. In this investigation, we determined the serum levels of MASP-1, MASP-2, MASP-3, MAp-44, and MAp-19 in patients with cervical cancer and cervical intraepithelial neoplasia (CIN). A total of 351 women who underwent screening for cervical cancer or treatment at the Erasto Gaertner Cancer Hospital in Curitiba-Brazil, were enrolled in the study. Based on their latest cervical colposcopy-guided biopsy results, they were divided into four groups: CIN-I: = 52; CIN-II: = 73; CIN-III: = 141; and invasive cancer: = 78. All the serum protein levels were determined by time-resolved immunofluorometric assay (TRIFMA). Patients with invasive cancer presented significantly higher MASP-2, MASP-1, and MAp-19 serum levels than other groups ( < 0.0001; = 0.012; = 0.025 respectively). No statistically significant differences in MASP-3 and MAp-44 serum levels were found between the four studied groups. In addition, high MASP-2, MASP-1, and MAp-19 serum levels were significantly associated with poor survival in patients with invasive cancer and relapse ( = 0.002, = 0.0035 and = 0.025, respectively). High MASP-2, MASP-1, and MAp-19 serum levels were associated with cervical cancer progression and worse disease prognosis. These novel findings demonstrate the involvement of the serine proteases of the lectin pathway in the pathogenesis of cervical cancer and future investigations should clarify their role in the disease process.
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http://dx.doi.org/10.3389/fimmu.2018.02742DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6265985PMC
October 2019

MICA-129 A/G dimorphism, its relation to soluble mica plasma level and spontaneous preterm birth: A case-control study.

J Reprod Immunol 2018 09 10;129:9-14. Epub 2018 Jul 10.

Department of Gynecology and Obstetrics, Infectious diseases in Gynecology and Obstetrics Sector, Clinics Hospital of University of Paraná (UFPR), Post Graduate Program of Gynecology and Obstetrics, Rua General Carneiro, 181, Alto da Glória, CEP80060-900 Curitiba, Paraná, Brazil. Electronic address:

The aim of this case- control study was to investigate the association between preterm birth (PTB), MICA-129 A/G dimorphism and sMICA levels. Fifty pregnant women with singleton pregnancy and previous PTB, or clinic diagnostic of threatened preterm labor in the actual pregnancy, or cervical length less than 25 mm and 50 healthy pregnant women were enrolled. DNA was extracted for genotyping for MICA-129 A/G by real-time PCR and sMICA plasma level was quantified by sandwich ELISA assay. Clinical and socioeconomic characteristics, results of TaqMan® genotyping and ELISA quantification were compared between the groups using qui-square, Fisher´s exact or Mann-Whitney test. A binary logistic regression model was used to predict PTB. The correlation between MICA-129 A/G genotypes and sMICA levels was investigated. There were not statistically significant differences between MICA-129 A/G polymorphism and sMICA plasma level.There was found a correlation between MICA-129 val/val genotype and higher levels of sMICA (ρ: -0.342; p:0.001). The presence of MICA-129  val/val genotype may be influencing sMICA expression.
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http://dx.doi.org/10.1016/j.jri.2018.07.002DOI Listing
September 2018

Cervical Cancer Registered in Two Developed Regions from Brazil: Upper Limit of Reachable Results from Opportunistic Screening.

Rev Bras Ginecol Obstet 2018 Jun 20;40(6):347-353. Epub 2018 Jun 20.

Faculdade de Ciências Médicas, Universidade Federal do Paraná, Curitiba, Paraná, Brazil.

Objective:  The aim of this study was to assess the time trends and pattern of cervical cancer diagnosed in the period from 2001 to 2012 by means of an opportunistic screening program from two developed regions in Brazil.

Methods:  An observational study analyzing 3,364 cancer records ( = 1,646 from Campinas and  = 1,718 from Curitiba region) available in hospital-based cancer registries was done. An additional 1,836 records of CIN3/AIS from the region of Campinas was analyzed. The statistical analysis assessed the pooled data and the data by region considering the year of diagnosis, age-group, cancer stage, and histologic type. The Cochran-Armitage trend test was applied and  < 0.05 were considered significant.

Results:  The total annual cervical cancer registered from 2001 to 2012 showed a slight drop (273-244), with an age average of 49.5 y, 13 years over the average for CIN3/AIS (36.8 y). A total of 20.6% of the diagnoses (1.6% under 25 y) were done out of the official screening age-range. The biennial rate of diagnoses by age group for the region of Campinas showed an increase trend for the age groups under 25 y ( = 0.007) and 25 to 44 y ( = 0.003). Stage III was the most recorded for both regions, with an annual average of 43%, without any trend modification. There was an increasing trend for stage I diagnoses in the region of Campinas ( = 0.033). The proportion of glandular histologic types registered had an increased trend over time ( = 0.002), higher for the region of Campinas (21.1% versus 12.5% for the region of Curitiba).

Conclusion:  The number, pattern and trends of cervical cancer cases registered had mild and slow modifications and reflect the limited effectivity of the opportunistic screening program, even in developed places.
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http://dx.doi.org/10.1055/s-0038-1660841DOI Listing
June 2018

Women infected with HIV and the impact of associated sexually transmitted infections.

Int J Gynaecol Obstet 2018 Aug 2;142(2):143-147. Epub 2018 May 2.

Obstetrics and Gynecology Department, Sector of Infectious Diseases in Obstetrics and Gynecology, Clinical Hospital of the Federal University of Paraná, Curitiba, Paraná, Brazil.

Objective: To review the relationship between concomitant sexually transmitted infections in women infected with HIV.

Methods: PubMed and Scopus were searched for articles published in English and Portuguese between January 1, 1994, and December 31, 2015, using relevant keywords, including AIDS, HIV, female genital diseases, and sexually transmitted infections. Articles that associated sexually transmitted infections with HIV-infected women were selected for inclusion. Those that only investigated prevalence in pregnant women or focused on social or behavioral aspects were excluded.

Results: Of 108 identified articles, 24 were included. When correlated with HIV, genital herpes demonstrated an increased recurrence rate and increased replication rate for HIV in the mucosa. In HIV-positive women, syphilis can cause more genital ulcers. Bacterial vaginosis provides a pool of microorganisms that can increase the viral copy levels of genital HIV. Chlamydia, gonorrhea, and candidiasis may be more severe and complicated in women infected with HIV.

Conclusions: Screening of HIV-positive patients who could have other sexually transmitted infections is important to protect women and decrease the risk of transmission.
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http://dx.doi.org/10.1002/ijgo.12507DOI Listing
August 2018

Mannose-Binding Lectin Does Not Act as a Biomarker for the Progression of Preinvasive Lesions of Invasive Cervical Cancer.

Med Princ Pract 2017 7;26(6):530-534. Epub 2017 Nov 7.

Objective: To evaluate serum concentrations of mannose-binding lectin (MBL) in women presenting with different human papillomavirus (HPV)-associated cervical lesions.

Subjects And Methods: A total of 364 women, who underwent screening for cervical cancer or treatment at the Erasto Gaertner Cancer Hospital (HEG), Curitiba, Brazil, were enrolled in the study. Based on the latest cervical colposcopy-guided biopsy results, the women were divided into 4 groups: cervical intraepithelial neoplasia CIN-I (n = 54), CIN-II (n = 72), CIN-III (n = 145), and invasive cancer (n = 93). A time-resolved immunofluorometric assay was used to measure the MBL concentrations in serum. The statistical analysis was done using GraphPad Prism 6.0. Comparisons were performed by Kruskal-Wallis and Mann-Whitney tests and analyzed by χ2 test; continuous variables are presented as medians and categorical variables as frequencies.

Results: The median MBL concentrations in decreasing order were as follows: invasive cancer: 1,452 ng/mL, CIN-I: 1,324 ng/mL, CIN-II: 1,104 ng/mL, and CIN-III 1,098 ng/mL. However, no statistical significance was found among the 4 groups with HPV-associated lesions (p = 0.11). Equally, the MBL levels did not show a significant association between the age of the patients and the severity of the cervical lesions (p = 0.68). No statistical significance was found in the median values of MBL or in the status of MBL deficient (<100 ng/mL) and high producers (>1,000 ng/mL) among the women in each group (p = 0.77).

Conclusion: In this study, there was no statistically significant difference in MBL serum levels among the groups with CIN. Hence MBL serum concentration appeared not to have influenced the progression of HPV-related preinvasive cervical lesions into invasive cancer.
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http://dx.doi.org/10.1159/000485037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5848474PMC
October 2018

Prevalence of Chlamydia trachomatis and Neisseria gonorrhea and associated factors among women living with Human Immunodeficiency Virus in Brazil: a multicenter study.

Braz J Infect Dis 2017 Jul - Aug;21(4):402-407. Epub 2017 May 18.

Universidade Federal do Paraná, Curitiba, PR, Brazil.

Background: Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC) cause infections in the female genital tract, increasing susceptibility to and infectiousness of HIV. The objectives of the present study were to determine the prevalence and associated factors of CT and GC infection among HIV-infected women in Brazil.

Methods: Cross-sectional study conducted from March to December 2015, including HIV-infected women attending referral centers in nine states of Brazil, aged 18-49 years, nonpregnant. An interview was conducted including socio-demographic, epidemiological and clinical characteristics. After the interview, gynecological examination was conducted to collect cervical cytology and vaginal secretion to C. trachomatis and N. gonorrhoeae tests through molecular biology.

Results: A total of 802 (89.1%) women participated. The prevalence of CT was 2.1% (17/802) and CG was 0.9% (7/802). The prevalence of a positive test for both CT and/or GC was 2.7%. The factors associated with positive CT/GC test in the multivariate logistic regression analysis were abnormal Papanicolau smear (OR 4.1; 95% CI: 1.54-11.09) and the presence of abnormal cervical discharge (OR 2.6; 95% CI: 1.02-6.71). Among 377 women who reported previous STI 245 (65.0%) reported using condom more frequently after being diagnosed. 62 (16.4%) discovered the STI after the partner told he was infected; 157 (41.6%) had STI symptoms and looked for care, and 158 (41.9%) discovered it in a routine consultation for another reason.

Conclusions: The control of STI represents a unique opportunity to improve reproductive health of women living with HIV. STI diagnosis can change their behavior and reduce the sexual transmission of HIV and bacterial STI.
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http://dx.doi.org/10.1016/j.bjid.2017.03.014DOI Listing
August 2017

Zika virus and pregnancy: An overview.

Am J Reprod Immunol 2017 02 3;77(2). Epub 2017 Jan 3.

Pontifical Catholic University of Parana, Curitiba, PR, Brazil.

In May 2015, the first episodes of Zika virus infection of the Latin America were confirmed in Brazil, where currently 196 976 cases were reported. The main route of transmission occurs by Aedes mosquitoes, and the most common symptoms are maculopapular rash, fever, conjunctivitis, polyarthralgia, and periarticular edema. However, the infection is asymptomatic in 80% of the cases. The congenital infection is characterized when the transmission to the fetus occurs during pregnancy, but the mechanisms of how the virus infects the placenta remain unclear. Anatomopathological findings were described in first- and third-trimester human placentas; however, the major affected tissue of the baby is the neural. Several clinical situations were listed in these fetuses, such as neurological, ophthalmological, auditory, and articular alterations. The World Health Organization proposed a new congenital syndrome caused by Zika virus. The virus has an important neurotropism and the main manifestation observed in the syndrome is microcephaly, which is usually severe and associated with other neurological injuries. The appearance of sudden rash in pregnant women determines immediate investigation through RT-PCR and serological analysis. Moreover, the prevention consists in using repellents and avoiding endemic areas, considering that the vaccine is still under development.
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http://dx.doi.org/10.1111/aji.12616DOI Listing
February 2017

Baby born too soon: an overview and the impact beyond the infection.

J Matern Fetal Neonatal Med 2017 May 2;30(10):1238-1242. Epub 2016 Aug 2.

a Department of Gynecology and Obstetrics - Infectious Diseases in Gynecology and Obstetrics Sector , Federal University of Paraná , Curitiba , Brazil.

Spontaneous preterm delivery, prematurity, and low birth weight due to prematurity account for a great part of neonatal morbidity and mortality. Inflammation may cause preterm labor, with the involvement of different mediators that produce diverse aspects of the inflammatory response. Although bacteria are considered to be the main trigger for intrauterine infection/inflammation, immunological factors also appear to be involved. Recently, molecular genetic studies have helped us better understand the underlying pathophysiologic processes. During mammalian pregnancy, maternal-fetal tolerance involves a number of immunosuppressive factors produced by placenta. Recently, placenta-derived exosomes have emerged as new immune regulators in the maternal immune tolerance. This review focuses on the specific immune parameters that become altered during human pregnancy, the identity and function of some immune modulators that have been best characterized to date, as well as a comprehensive evaluation of the pregnancy-associated mechanisms that downregulate proinflammatory immunity to a level sufficient to prevent the triggering of premature common pathway of labor and damage to developing organs.
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http://dx.doi.org/10.1080/14767058.2016.1209653DOI Listing
May 2017

Zika virus infection during pregnancy and microcephaly occurrence: a review of literature and Brazilian data.

Braz J Infect Dis 2016 May-Jun;20(3):282-9. Epub 2016 Apr 18.

Pontifícia Universidade Católica do Paraná (PUC-PR), Curitiba, PR, Brazil.

In November of 2015, the Ministry of Health of Brazil published an announcement confirming the relationship between Zika virus and the microcephaly outbreak in the Northeast, suggesting that infected pregnant women might have transmitted the virus to their fetuses. The objectives of this study were to conduct a literature review about Zika virus infection and microcephaly, evaluate national and international epidemiological data, as well as the current recommendations for the health teams. Zika virus is an arbovirus, whose main vector is the Aedes sp. The main symptoms of the infection are maculopapular rash, fever, non-purulent conjunctivitis, and arthralgia. Transmission of this pathogen occurs mainly by mosquito bite, but there are also reports via the placenta. Microcephaly is defined as a measure of occipto-frontal circumference being more than two standard deviations below the mean for age and gender. The presence of microcephaly demands evaluation of the patient, in order to diagnose the etiology. Health authorities issued protocols, reports and notes concerning the management of microcephaly caused by Zika virus, but there is still controversy about managing the cases. The Ministry of Health advises notifying any suspected or confirmed cases of children with microcephaly related to the pathogen, which is confirmed by a positive specific laboratory test for the virus. The first choice for imaging exam in children with this malformation is transfontanellar ultrasound. The most effective way to control this outbreak of microcephaly probably caused by this virus is to combat the vector. Since there is still uncertainty about the period of vulnerability of transmission via placenta, the use of repellents is crucial throughout pregnancy. More investigations studying the consequences of this viral infection on the body of newborns and in their development are required.
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http://dx.doi.org/10.1016/j.bjid.2016.02.006DOI Listing
March 2017

The role of P16ink4a and P53 immunostaining in predicting recurrence of HG-CIN after conization treatment.

Rev Col Bras Cir 2016 Feb;43(1):35-41

Departamento de Tocoginecologia, Universidade Federal do Paraná, Brasil.

Objective: Io evaluate the expression of p16INK4a and p53 biomarkers in conization specimens from patients with high grade cervical intraepithelial neoplasia (HG-CIN), correlating them with the ability to predict the recurrence.

Methods: we conducted a retrospective study of patients with HG-CIN in cervical biopsy treated with conization between January 1999 and January 2006 who had a minimum follow-up of 18 months. The expression of the p16 and p53 was assessed by tissue microarrays and correlated with disease recurrence. For analysis, we used the test of proportions (chi-square), considering value p<0.05, 95% CI and calculations of sensitivity, specificity and accuracy of these immunomarkers in predicting recurrence.

Results: the series comprised 83 patients aged between 16 and 86 years (35±11.7), divided into two groups: 30 with HG-CIN recurrence (study group) and 53 without recurrence (control group). Mean age, parity, smoking and conization technique were similar in both groups. The p53 expression was present in 43% of the study group and 57% of the control group, and the p16 was present in 43% of the study group and in 57% of the control group (p>0.05). p53 had a positive predictive value (PPV) of 42% and negative predictive value (NPV) of 73%, sensitivity 70%, specificity of 47% and accuracy of 59%. The p16, PPV 42%, NPV 72%, sensitivity 66%, specificity of 49% and accuracy of 56%.

Conclusion: immunohistochemistry expression of p53 and p16 showed low sensitivity and low specificity as predictors of HG-CIN recurrence after conization treatment.
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http://dx.doi.org/10.1590/0100-69912016001008DOI Listing
February 2016

Susceptibility and molecular characterization of Candida species from patients with vulvovaginitis.

Braz J Microbiol 2016 Apr-Jun;47(2):373-80. Epub 2016 Mar 2.

Graduate Program in Microbiology, Parasitology and Pathology, Department of Basic Pathology, Laboratory of Microbiology and Molecular Biology-LabMicro, Federal University of Paraná, Curitiba, Paraná, Brazil; Support and Diagnosis Unit, Mycology Laboratory, Federal University of Paraná, Brazil. Electronic address:

Vulvovaginal candidiasis affects women of reproductive age, which represents approximately 15-25% of vaginitis cases. The present study aimed to isolate and characterize yeast from the patients irrespective of the presentation of clinical symptoms. The isolates were subjected to in vitro susceptibility profile and characterization by molecular markers, which intended to assess the distribution of species. A total of 40 isolates were obtained and identified through the CHROMagar, API20aux and by ITS and D1/D2 regions sequencing of DNAr gene. Candida albicans strains were genotyped by the ABC system and the isolates were divided into two genotypic groups. The identity of the C. albicans, C. glabrata, C. guilliermondii, C. kefyr and Saccharomyces cerevisiae isolates was confirmed by the multilocus analysis. The strains of Candida, isolated from patients with complications, were found to be resistant to nystatin but sensitive to fluconazole, amphotericin B and ketoconazole, as observed by in vitro sensitivity profile. The isolates from asymptomatic patients, i.e., the colonized group, showed a dose-dependent sensitivity to the anti-fungal agents, fluconazole and amphotericin B. However, the isolates of C. albicans that belong to distinct genotypic groups showed the same in vitro susceptibility profile.
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http://dx.doi.org/10.1016/j.bjm.2016.01.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4874609PMC
December 2016

Uterus Didelphys with Obstructed Hemivagina and Ipsilateral Renal Agenesis (OHVIRA Syndrome).

JBRA Assist Reprod 2015 11 1;19(4):259-62. Epub 2015 Nov 1.

Gynecology and Obstetrics Department. Federal University of Paraná - Gynecology Endocrinology Sector, Curitiba, PR, Brazil.

This paper aimed to report a series of 19 cases of uterus didelphys associated with obstructed hemivagina and ipsilateral renal agenesis. This retrospective descriptive observational study included the medical records of 19 patients seen at the Endocrinology Gynecology Sector of the Obstetrics and Gynecology Department of the Federal University of Paraná, and focused on clinical data, complementary exams, patient management, and follow-up. From the 229 patients with genital anomalies seen between 1984 and 2009, 19 (8.3%) were diagnosed with uterus didelphys with vaginal septum and renal agenesis. The patients had a median age of ±16.3 years. Eight subjects (42.6 %) reported abdominal pain; two of them (0.1%) had pelvic masses and seven (36.8%) had dysmenorrhea. Blood retention was confirmed by ultrasound and/ or magnetic resonance imaging of the pelvis, which revealed the existence of a duplicated uterus of the didelphys type with a cystic mass containing old blood obliterating the hemivagina. Urinary tract examination revealed the existence of ipsilateral renal agenesis. Unusual manifestations such as associated infection and rupture of the vaginal septum during sexual intercourse were also reported. The prevalence of uterus didelphys associated with obstructed hemivagina and ipsilateral renal agenesis was 8.3% in a series of 229 genital anomalies. The observance of clinical features is essential for the early identification of the syndrome and the adequate management of the patients.
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http://dx.doi.org/10.5935/1518-0557.20150049DOI Listing
November 2015

Is there a role for cervicography in the detection of premalignant lesions of the uterine cervix?: a Brazilian experience.

J Low Genit Tract Dis 2012 Oct;16(4):387-93

Gynecology Department, Evangelic School of Medicine of Parana, Federal University of Parana, Parana, Brazil.

Objective: This study aimed to compare cervical cancer screening by cervicography with screening by Pap test.

Materials And Methods: This was a comparative multicenter study of cervical cytology and cervicography. The cervicography (slides of the cervix) was taken after the Pap test was completed. In total, samples were collected from 1176 patients. Colposcopy with biopsy was considered the gold standard for the final diagnosis of lesions observed by the Pap test and cervicography. Statistical analysis was performed using the binomial test.

Results: In cases in which the Pap test was negative for cervical lesions, diagnosis by cervicography was positive in 15 cases of cervical intraepithelial neoplasia 1 (CIN 1) (p = .00052), in 1 case of CIN 2, in 1 case of CIN 3, and in 1 case of cancer. However, cervicography produced 3 false-positive results (p < .0001).

Conclusions: Cervicography may be used as a complementary screening method to the Pap test for cervical cancer.
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http://dx.doi.org/10.1097/LGT.0b013e31824454beDOI Listing
October 2012

[Prevalence of Chlamydia trachomatis and Neisseria gonorrhoea infections in sexual actives young women at a southern Brazilian city].

Rev Bras Ginecol Obstet 2011 Nov;33(11):328-33

Acadêmica de Pós-graduação Mestrado em Clínica Médica da Universidade Federal do Paraná – UFPR – Curitiba (PR), Brasil.

Purpose: to determine the prevalence of Chlamydia and gonorrhea in a sample of women from Curitiba.

Methods: this was a cross-sectional study with a sample of sexually active non-pregnant women aged between 16 and 23 years-old, with an intact uterus, with up to four sexual partners, without evidence of fever or purulent cervicitis, submitted to pelvic examination and PCR-based urine- testing for Chlamydia and gonorrhea. Exclusion criteria included: vaccination for HPV, vaccination history for the past 21 days, previous abnormal cytology, history of genital warts, splenectomy, immune disorders, and use of immunosuppressive drugs. An interview regarding sociodemographic and obstetric data and gynecological risk behavior for sexual transmitted diseases was applied. For statistical analysis, we used the χ(2) or Fisher's exact test to assess the association between variables.

Results: the prevalence of Chlamydia and gonorrhea infection in the study group was 10.7 and 1.5%, respectively, and the rate of coinfection was 0.9%. No correlation was found between the age range of the volunteers, the onset of sexual activity, the number of sexual partners and of new sexual partners in the last six months, and the presence of Chlamydia or gonorrhea. In women who had vaginal discharge or ectropion, the prevalence of Chlamydia infection was two times higher than in those without such signs.

Conclusions: the results of this study were similar to national studies using PCR in urine samples for the detection of Chlamydia and gonorrhea in samples of non-pregnant women of the same age groups and with the same background. Since the volunteers with more than four sexual partners and those who had purulent endocervicitis were excluded, it is believed that the prevalence of Chlamydia and gonorrhea infection could have been greater in this population.
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November 2011

HPV infection and intraepithelial lesions from the anal region: how to diagnose?

Braz J Infect Dis 2011 Sep-Oct;15(5):473-7

Gynecology and Obstetrics Sector, Department of ObGyn, Hospital de Clínicas, Universidade Federal do Paraná, Curitiba, PR, Brazil.

In the last years, the prevalence of HPV infection in the anal region has increased, especially in some groups like homosexual and HIV-positive people. Since this infection can be associated with the development of squamous anal cancer due to its progression from HPV infection to anal intraepithelial neoplasia (AIN) and finally to cancer, the screening and evaluation of these conditions are important. Anal cytology and high resolution anoscopy are good methods that are available and can be used. Although useful, these methods should be performed correctly and not indiscriminately in all patients. Patients for whom anal cytology screening is recommended are: HIV-infected patients, homosexuals, women who present with high-grade vulvar squamous intraepithelial neoplasia, vulvar cancer or cervical cancer. An abnormal anal cytology should be further evaluated with high resolution anoscopy.
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http://dx.doi.org/10.1016/s1413-8670(11)70230-6DOI Listing
September 2012

[Echographic characteristics of the corpus luteum in early pregnancy: morphology and vascularization].

Rev Bras Ginecol Obstet 2010 Nov;32(11):549-55

Médico Plantonista e Ecografista da Maternidade do Hospital de Clínicas da Universidade Federal do Paraná – UFPR Curitiba (PR), Brasil.

Purpose: the purpose of this research was to evaluate the morphological aspects and vasculature of the corpus luteum (CL) based on ultrasound parameters during early pregnancy and to assess their relationship with early pregnancy loss.

Methods: this was a prospective cohort study of 90 pregnant patients between 6 and 8 weeks plus 6 days weeks of gestation. We included women at low risk, without acute or chronic systemic disease and with spontaneous conception.

Exclusion Criteria: use of drugs or smoking, drugs inducing ovulation, history of more than one abortion, no heartbeat visible in the embryo and impossibility of visualization of the corpus luteum. The size, volume, morphological aspects, resistive index, and peak systolic velocity of the corpus luteum were measured by transvaginal sonography.

Results: ninety patients were included in the study. Maternal age ranged from 15 to 41 years (mean 28.6 ± 5.8 years). The corpus luteum could be visualized in 87 patients (96.7%), 79 patients had normal pregnancies (90.1%), whereas spontaneous losses occurred in 8 cases (9.9%). In a comparison of the survivors and losses, there was no difference in mean CL diameter (21.8 versus 20.0 mm; p=0.108, Mann-Whitney test), mean CL volume (4.2 versus 3.0 cm³; p=0.076, Mann-Whitney test), mean resistive index (0.55 versus 0,58; p=0.220, Mann-Whitney test), peak systolic velocity (15 versus 15 cm/s; p=0.757, Mann-Whitney test). There was a positive relation between maternal age and resistive index.

Conclusions: no apparent correlation was found between the morphological and vascular aspects of the corpus luteum in early normal pregnancies and first-trimester pregnancy losses.
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http://dx.doi.org/10.1590/s0100-72032010001100006DOI Listing
November 2010
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